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WO2008067710A1 - Substituted cyclohexane compounds, preparation methods and medicine uses thereof - Google Patents

Substituted cyclohexane compounds, preparation methods and medicine uses thereof Download PDF

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Publication number
WO2008067710A1
WO2008067710A1 PCT/CN2007/002769 CN2007002769W WO2008067710A1 WO 2008067710 A1 WO2008067710 A1 WO 2008067710A1 CN 2007002769 W CN2007002769 W CN 2007002769W WO 2008067710 A1 WO2008067710 A1 WO 2008067710A1
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group
substituted
halogen atom
alkoxy
amide
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Chinese (zh)
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Mingwei Wang
Qing Liu
Na Li
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Shanghai Institute of Materia Medica of CAS
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Shanghai Institute of Materia Medica of CAS
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P3/00—Drugs for disorders of the metabolism
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C233/63—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to a compound having a substituted cyclohexanyl structure, a preparation method thereof and a modulator of Glucagon like peptide-1 receptor (GLP-1R) in prevention and/or treatment
  • GLP-1R Glucagon like peptide-1 receptor
  • Medical use of metabolic disorders including but not limited to diabetes, insulin resistance and obesity, etc.
  • cardiovascular diseases including but not limited to diabetes, insulin resistance and obesity, etc.
  • neurodegenerative diseases such as Alzheimer's disease.
  • Diabetes is a group of clinical syndromes caused by the interaction of genetic and environmental factors. It is mainly divided into type 1 and type 2. The basic pathophysiology of type 1 diabetes is absolute insulin secretion, and clinical treatment is mainly supplemented with insulin. It is also known as insulin-dependent diabetes. Type 2 diabetes accounts for more than 95% of the diseased population.
  • Insulin resistance is a key factor in the development and progression of type 2 diabetes.
  • Therapeutic drugs for type 2 diabetes include sulfonylureas, biguanides, other insulin sensitizers, and ancillary measures.
  • the potassium ion channel When the sulfonylurea-type hypoglycemic agent binds to the receptor of the pancreatic ⁇ -cell membrane, the potassium ion channel is closed, and the potassium ion efflux is blocked, resulting in depolarization of the cell membrane, causing the Ca 2+ channel to open, causing extracellular calcium influx, intracellular. When the calcium ion concentration is increased, the release of insulin is triggered.
  • the biguanide hypoglycemic agent can suppress appetite, increase the binding of insulin to the receptor, promote the anaerobic glycolysis of glucose, inhibit tissue respiration, and inhibit hepatic gluconeogenesis. Mainly there are metformin, phenformin and butyl bismuth.
  • hypoglycemic agents mainly include Thiazolidinediones (such as troglitazone, rosiglitazone, pioglitazone, etc.), ⁇ 3-adrenergic receptor modulators, glucagon receptor antagonists, Fatty acid metabolism interfering drugs, a-glycosidase inhibitors (such as acarbose, voglibose, miglitol, etc.) and aldose reductase inhibitors.
  • Thiazolidinediones such as troglitazone, rosiglitazone, pioglitazone, etc.
  • ⁇ 3-adrenergic receptor modulators such as glucagon receptor antagonists
  • Fatty acid metabolism interfering drugs such as acarbose, voglibose, miglitol, etc.
  • aldose reductase inhibitors such as acarbose, voglibose, miglitol, etc.
  • GLP-1R Glucagon like peptide-1 receptor
  • GPCR G protein-coupled receptor
  • GLP-1 promotes the differentiation of embryonic stem cells into cell-like cells with insulin secretion (J Endocrinol. 2005, 186: 343-52). GLP-1 acts on the central body to promote Cell survival reduces apoptosis, reduces neurotoxicity of amyloid peptides, inhibits the progression of neurodegenerative diseases, and promotes learning and memory, so GLP-1 has recently been proposed for the treatment of Alzheimer's disease (Ann NY Acad Sci) , 2004, 1035: 290-315; Nat Med, 2003, 9: 1173-1179; Curr Alzheimer Res, 2005, 2: 377-385; J Pharmacol Exp Ther, 2002, 302: 881-888). In addition, GLP-1 also plays an important role in the cardiovascular system.
  • GLP-1R has the effect of lowering blood pressure and dilating blood vessels.
  • Acute injection of GLP-1 can improve left ventricular systolic function in cardiac hypertrophy experiments. It also reduces myocardial cell damage in the presence of myocardial ischemia and reperfusion (X Hypertens, 2003, 21: 1125 - 1135; Am J Physiol Endocrinol Metab, 2004, 287: E1209 - E1215; Circulation, 2004, 110: 955 - 961 ; Diabetes, 2005, 54 : 146 - 151). Due to the above-mentioned clear physiological effects, since the discovery of this target in the mid-1980s, the search for small molecule agonists of GLP-1R has been a research hotspot of many new drug development institutions in the world.
  • GLP-1 drugs such as the GLP-1 derivative developed by Danovo Nordisk, Denmark (trade name Liraglutide; entering Phase III clinical trials) and Amylin Pharmaceuticals and Eli Lilly and Company
  • GLP-1 analogue Exendin-4 trade name Exenatide; was approved for listing in April last year, this year's sales are expected to exceed $1 billion.
  • GLP-1 and its peptide analogs there have been no reports of successful development of non-peptide small molecule GLP-1R agonists. Due to the inconvenient oral administration of peptide drugs, the search for non-peptide GLP-1R modulators and the development of new anti-diabetic drugs with independent intellectual property rights are the common concerns of many new drug research institutions.
  • Another object of the present invention is to provide a process for producing a compound represented by any one of the following formulae I to VI;
  • a further object of the present invention is to provide a pharmaceutical composition containing a compound represented by any one of the following Formulae I to VI;
  • a further object of the present invention is to provide a compound represented by any one of the following Formulae I to VI as a glucagon-like peptide-1 receptor modulator for preventing and/or treating metabolic disorders (including but not limited to diabetes, Medical uses such as insulin resistance and obesity, cardiovascular disease and neurodegenerative diseases such as Alzheimer's disease.
  • metabolic disorders including but not limited to diabetes, Medical uses such as insulin resistance and obesity, cardiovascular disease and neurodegenerative diseases such as Alzheimer's disease.
  • the present invention provides a glucagon-like peptide-1 receptor modulator, which increases the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases ( Members of the drug such as Alzheimer's disease.
  • the present invention relates to a compound represented by any one of the following formulae I to VI, or a pharmaceutically acceptable salt thereof:
  • X, ⁇ , Z are (C) n and n is 0-2, oxygen, sulfur or nitrogen.
  • R t , R 2 , R 3 , R 4 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkane; hydroxy; nitro; carboxy; aldehyde; oxiran; Amine group; amide group; carboxamide group; fluorenyl group; alkylthio group; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted a pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group.
  • R 5 , R 6 , R 7 are each independently any of the following substituents: gas; alkane; cycloalkane; anthracene; amine; amine alkyl; amide; carboxamide; alkylthio; Or an unsubstituted aryl group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group.
  • the above formula compound is characterized by -
  • X, Y, ⁇ are (CH 2 ) n , n is 0-2, oxygen, sulfur or nitrogen, Rpremise R 2 , R 3 are each independently: Wherein any of the following substituents is H; d- (alkyl group; an alkyl group containing any one, two or three substituted d- groups including a halogen atom, d-(alkoxy group or hydroxyl group) a C 2 -alkenyl group; any one, two or three substituted C 2 _C e 1 ⁇ 2 alkenyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a C 2 -C 6 alkynyl group; Any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, C "C 6 alkoxy group or a hydroxyl group; a C 3 _C e cycloalkyl group; Any one, two or three substituted C 3 -
  • R 6 , R 7 are: Wherein is any one of the following substituents: H ; a group of d-C 6 ; an alkyl group containing any one, two or three substituted dC 6 including a halogen atom, an alkoxy group or a hydroxyl group.
  • a substituted pyranyl group containing a halogen atom, d- (: 4 alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, B Any one, two or three substituted thienyl groups including a thio group; containing an alkyl group including a halogen atom, dC 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted pyrrolyl groups, fluorenyl, methylthio, ethylthio; (c r , decanoyl; containing a halogen atom, (alkoxy group of Cs or hydroxyl group) Any one, two or three substituted c, - c e de
  • R w , Ru are each independently a substituent of any of the following: H ; alkyl of dC 6 ; any one, two or three substituted Cs including a halogen atom, an alkoxy group of d- or a hydroxyl group "C 6 thiol; C 2 - ( 6 alkenyl; any one, two or three substituted C 2 - (: 6 alkenyl group) including a halogen atom, an alkoxy group or a hydroxyl group; C 2 - (: 6 alkynyl; any one, two or three substituted C 2 - ( 6 alkynyl group; C 3 - C 6 containing an alkoxy group including a halogen atom, dC e or a hydroxyl group; Any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom, an alkoxy group
  • R 12 is any one of the following substituents: H; C" (alkyl group of 6 ; any one, two or three substituted alkyl groups including a halogen atom, a c alkoxy group or a hydroxyl group) C 2 - (: 6 alkenyl; any one, two or three substituted c 2 -c alkenyl groups including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; c 2 - c 6 An alkynyl group; any one, two or three substituted c 2 -c 6 alkynyl groups including a halogen atom, an alkoxy group of dC e or a hydroxyl group; a c 3 - c 6 cyclodecyl group; Any one, two or three substituted c 3 - c 6 cycloalkyl groups of a halogen atom, c "
  • R 6 and R 7 are: Wherein R 13 and R w are each independently a substituent of any one of the following: H; ( ⁇ -(: 6 fen); any one or two containing an alkoxy group including a halogen atom, d-Cs or a hydroxyl group; Or a three-substituted C "C 6 alkyl group; a C 2 - C 6 alkenyl group; any one, two or three substituted groups including a halogen atom, a dC 6 decyloxy group or a hydroxyl group ( 2 - ( 6 alkenyl; C 2 - ( 6 alkynyl; any one, two or three substituted C 2 - C 6 containing a halogen atom, C "C 6 of a hospitaloxy group or a hydroxyl group"Alkynyl; C 3 -C 6 cycloalkyl; any one, two or three substituted C 3 -C 6 cyclodecyl groups containing
  • R 15 and R 16 each independently are any one of the following substituents: H; d- ( 6 alkyl; any one or two containing a halogen atom, C "C 6 alkoxy group or a hydroxyl group” or a three-substituted alkyl group of d-Ce; a C 2 -C 6 alkenyl group; Any one, two or three substituted ( 2- ( 6 alkenyl; C 2 -C e alkynyl) containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; containing a halogen atom, CrC Any one, two or three substituted c 2 - c 6 block groups of 6 alkoxy groups or hydroxyl groups; c 3 -c 6 cycloalkyl groups; containing alkane including a prime atom, c "c 6 Any one, two or three substituted
  • R 7 are: Wherein is any one of the following substituents: H; a fluorenyl group of Cr C 6 ; any one, two or three substituted d-C B 1 ⁇ 2 containing a halogen atom, a decyloxy group or a hydroxyl group of d- ⁇ embankment group; C 2 - C e alkylene group; containing optionally include halogen, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents of C 2 - C 6 alkenyl; C 2 - (: 6 alkynyl group; contain any alkoxy or hydroxy include halogen atoms, the inner one, two or three substituents of C 2 -C e alkynyl group; C 3 - C 6 cycloalkyl group of embankment ; contain any halogen atoms include, d-Ce alkoxy or hydroxy the embankment, including one, two or three substituents of (3 -
  • two or three substituted furanyl groups containing a halogen atom, a halogen group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, Any one, two or three substituted pyranyl groups including an ethylthio group; an alkyl group including a halogen atom, CrG, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carbon amide any group, a mercapto group, methylthio, ethylthio, including one, two or three substituents thienyl; comprising pigment containing atoms, C "(alkyl, nitro, carboxyl, aldehyde, alkoxy 4 Base, amine group,
  • R 5 , , R 7 are: Wherein, each independently is any one of the following substituents: H; a fluorenyl group of d-C 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group - an alkyl group of C 6 ; an alkenyl group of C 2 - G; an alkenyl group containing any one, two or three substituted C 2 - C 6 groups including a halogen atom, a decyloxy group of -Ce or a hydroxyl group; C 2 - (6 alkynyl; comprising any one, two or three substituents of C 2 include a halogen atom, an alkoxy group or a hydroxyl dC including the e - (6 alkynyl; C 3 -C 6 of cycloalkyl; comprising any one, two or three of the substituents include C 3 prime atoms
  • R 12 is any one of the following substituents: H; d-(alkyl; any one, two or three substituted Cr C including a halogen atom, d- (a alkoxy group or a hydroxyl group) e alkyl; ⁇ - ⁇ alkenyl; include halogen atom-containing, ( ⁇ - alkoxy or hydroxy arbitrary (6, including one, two or three substituents of C 2 - (6 alkenyl; C 2 - (alkynyl; any one, two or three substituted C 2 -C 3 alkynyl groups including a halogen atom, an alkoxy group of d-C 6 or a hydroxyl group; C 3 - C e cyclic alkyl with; containing optionally include halogen atoms, C "C 6 alkoxy or hydroxy, including one, two or three substituents of C 3 - C 6 cycloalkyl group emb
  • R 5 , R 6 , R 7 are: Wherein R 13 and R 14 are each independently a substituent of any of the following: H; an alkyl group of d-C 6 ; any one, two or three containing a halogen atom, a hydroxyl group of d- or a hydroxyl group.
  • 3 ⁇ 4 comprise any pigment containing atoms, a hydroxyl group or a -Ce the embankment, including one, two or three substituents of C 2 -C 6 Alkynyl; C 3 -C 6 cycloalkanoyl; any one, two or three substituted C 3 - ( 6 ring) containing an alkoxy group including a halogen atom, C, -C 6 or a hydroxyl group Alkanoyl; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrole benzoyl; ) ⁇ (C) n , n is 0-2 , 0; S or NH; (C3 ⁇ 4) possibly, n is 0-2, 0; S or NH.
  • R 2 , R 3 are each independently : Wherein Rn is any one of the following substituents: 3 ⁇ 4; C"(fluorenyl); any one, two or three substituted (C 6 fluorenyl group containing a halogen atom, a fluorenyloxy group or a hydroxyl group) ; C 2 - C 6 alkenyl group; a halogen atom-containing include any, (the embankment of Ce alkoxy or hydroxy, including one, two or three substituents of C 2 _C 6 alkenyl; C 2 - (alkynyl Any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, a Cr alkoxy group or a hydroxyl group; a C 3 - C 6 cycloalkyl group; containing a halogen atom, Any one, two or three substituted C 3 -C 6 cycloalkyl groups such as alkoxy or hydroxy groups
  • n is 0-2, 0; S or Lan time;
  • R 5 , R 6 and R 7 are: Wherein is any one of the following substituents: H; d-C e fluorenyl; any one, two or three substituted C" (including 6 ) containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce Alkyl; C 2 -C 6 alkenyl; containing halogen Atom, an optionally c "c embankment 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - (: 6 alkenyl; C 2 - (6 alkynyl; include a halogen atom-containing, CrC Any one, two or three substituted C 2 -C 6 alkynyl groups including an alkoxy group or a hydroxyl group of e ; a C 3 -C 6 cyclodecyl group; a fluorene containing a halogen atom, C "C e " any of a group or a
  • R 5 , R 6 , R 7 are:
  • each of Ru independently is any one of the following substituents: H; C" (alkyl group of 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group) C 6 alkyl; C 2 - (: 6 alkenyl; any one, two or three substituted ( 2- ( 6 olefin) containing a halogen atom, d- alkoxy group or a hydroxyl group) group; (2 alkynyl group; comprises contain any halogen atom, C "C e alkoxy or hydroxy group including one, two or three substituents of C 2 - C 6 alkynyl group; C 3 -C e a cycloalkyl group; any one, two or three substituted C 3 -C 6 cycloalkyl groups including a sulfhydryl group or a hydroxy group including a aryl group; d-Ce;
  • R 12 is any of the following substituents: H ; a fluorenyl group of CrC e ; an alkoxy group containing a halogen atom, -Cs Any one, two or three substituted d-(: 6 fluorenyl groups; C 2 - ( 6 alkenyl group; containing a halogen atom, an alkoxy group or a hydroxyl group, etc.)
  • One, two or three substituted C 2 - (: 6 alkenyl; C 2 - ( 6 alkynyl; containing any one or two including a halogen atom, an alkoxy group or a hydroxyl group three substituted C 2 -C 6 alkynyl group of; C 3 - C e cycloalkyl; contain any halogen atoms include, CrC e alkoxy or hydroxy group including one, two or three substituents of ( 3 -C
  • R 5 , R 6 , R 7 are: .
  • R 13 and R 14 are each independently a substituent of any of the following: H; a fluorenyl group of d-C 6 ; any one, two or three groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; Substituted d-(alkyl; C 2 - 0>alkenyl; any one, two or three substituted C 2 - including a halogen atom, C, -C 6 alkoxy group or hydroxyl group (6 alkenyl; C 2 -C 6 alkynyl group; a halogen atom-containing optionally include, dC 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - C s alkynyl; a C 3 -C 6 cycloalkyl group; any one, two or three substituted C 3 -C 6 cycloalkyl groups including a halogen atom, a decyloxy
  • R 18 and R w are each independently a substituent of any of the following: H; an alkyl group of d-C 6 ; any one, two or three substitutions including a halogen atom, an alkoxy group of dc or a hydroxyl group; D-( 6 alkyl; C 2 -C fi alkenyl; any one, two or three substituted C 2 - C 6 dry groups containing a halogen atom, an alkoxy group or a hydroxyl group C 2 - ( 6 alkynyl; any one, two or three substituted C 2 _C e alkynyl group including a halogen atom, a decyloxy group or a hydroxyl group of d C 6 ; C 3 - C e a cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom, an alkyl group of d-C 6 ; any one, two
  • a substituted fluorenyl group containing a halogen atom, d-(indenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group, methylthio group, ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, a fluorenyl group of a Cr C 4 group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, C t - C 4 , a nitro group, a carboxyl group, an alde
  • R 5 , R 6 and R 7 are: Wherein R 9 is any one of the following substituents: H; an alkyl group of Cr ( ⁇ ; an arbitrary one, two or three substituted Cs including a halogen atom, a C: ( 6 alkoxy group or a hydroxyl group) An alkyl group of t -C 6 ; 0 2 -(: 6 alkenyl; any one, two or three substituted C 2 - (alkenes) including a halogen atom, a decyloxy group or a hydroxyl group of d- groups; C 2 - (6 alkynyl; contain any include halogen atoms, hydroxyl group, or embankment Cr C 6 inner one, two or three substituents of C 2 -C e alkynyl group; C 3 - a C 6 cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom
  • R 7 is -
  • R w each independently is any one of the following substituents: H ; a fluorenyl group of dC 6 ; any one, two or three substituted groups including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group Alkyl; C 2 - (: 6 alkenyl; any one, two or three substituted C 2 - (alkenyl; C 2 - containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group) (6 alkynyl group; includes any containing halogen atoms, C "C 6 alkoxy or hydroxy, including one, two, or Three substituted C 2 - (6 alkynyl group; c 3 - c fi embankment cycloalkyl group; one, two or three substituents include a halogen atom contain any, c "c embankment 6 alkoxy or hydroxy, including the c 3 - c e cycl
  • Substituted furanyl containing any of a halogen atom, a dc 4 graft, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and the like.
  • substituents pyranyl include halogen atom-containing, ( ⁇ - (alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto 4 Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, c "c 4 sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group Base, amide group, carboxamide group, sulfhydryl group, methylthio group, ethyl sulphide Including any one, two or three substituents pyrrolyl; d_c 6 alkanoyl; includes any halogen atom-containing, c "c embankment 6 alkoxy or hydroxy, including one, two or three substituents of c"C
  • ⁇ is any of the following substituents: H; C "C fl alkyl; any one, two or three substituted Cs including a halogen atom, (; - (; 6 alkoxy or hydroxy group) "C 6 alkyl with; C 2 - C 6 alkenyl group; a halogen atom-containing include, CrC 6 alkoxy or hydroxy embankment, including any one, two or three substituents of C 2 -C 6 alkenyl group; An alkynyl group of C 2 - C B ; an alkynyl group containing any one, two or three substituted C 2 _C B groups including a halogen atom, an alkoxy group or a hydroxyl group of -Ce; a ring of C 3 - C 6 alkyl; include halogen atom-containing, C "C 6 alkoxy or hydroxy embankment, including any one, two or three substituents: H; C "C fl alkyl; any one
  • R 13 and R 14 are each independently a substituent of any of the following: H; an alkyl group of dC 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of CrC 6 or a hydroxyl group; (; 6 alkyl; C 2 -C 6 alkenyl group; includes any containing halogen atoms, C alkoxy or hydroxy group including one, two or three substituents of C 2 - C 6 alkenyl group; C 2 -C e alkynyl; any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, an alkoxy group of C "C e or a hydroxyl group; C 3 - C e a cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups
  • such a compound or a physiologically acceptable salt thereof is provided in the form of a pharmaceutical composition, either alone or in combination with a pharmaceutically acceptable carrier or excipient.
  • the present invention also provides a medicament comprising the above compound for preventing and/or treating metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases ('such as Alzheimer' s disease) and so on.
  • the invention relates to a method of preventing and/or treating metabolic disorders, including but not limited to diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease.
  • the method comprises administering to a subject in need or willingness to receive treatment or prevention a compound having a fair amount of a glucagon-like peptide-1 receptor or a pharmaceutically acceptable salt thereof for preventing or Treat the above diseases or symptoms.
  • the above metabolic disorders including but not limited to diabetes, insulin resistance and obesity
  • cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease
  • X, ⁇ , Z are (CH 2 ) n , and n is 0 - 2, oxygen, sulfur or nitrogen.
  • R 2 , R 3 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkane; hydroxy; nitro; carboxy; aldehyde; alkoxy; amine; amine sulfhydryl; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • R 5 , R 6 , R 7 are each independently any one of the following substituents: hydrogen; alkane; cycloalkane; alkoxy; amine; amine alkyl; amide; carboxamide; alkylthio; Unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • the present invention relates to a combination preparation comprising a compound having a selective modulation of a glucagon-like peptide-1 receptor, particularly a function of activating the receptor, or a pharmaceutically acceptable salt thereof Or alone or in combination with a pharmaceutically acceptable carrier or excipient.
  • This compound has the structure of the following formula -
  • X, ⁇ , Z are ((3 ⁇ 4) thread, n is 0-2, oxygen, sulfur or nitrogen.
  • RR 2 , R 3 , R 4 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkyl; light base; nitro; carboxy; aldehyde; methoxy; amine; Amide; carboxamide; mercapto; alkylthio; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; Substituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • Ra, R 7 are each independently any one of the following substituents: hydrogen; anthracene; a cyclic alkane; an alkoxy group; an amine group; an amine group; an amide group; a carboxamide group; an alkylthio group; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • the present invention provides a kit comprising the above combined preparation.
  • the present invention still further provides the use of the above-described combination preparation for the prevention and/or treatment of a disorder (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer' s disease), etc., to achieve selective stimulation of the glucagon-like peptide-1 receptor, improve the patient's symptoms and quality of life.
  • a disorder including but not limited to diabetes, insulin resistance and obesity
  • cardiovascular diseases and neurodegenerative diseases such as Alzheimer' s disease
  • neurodegenerative diseases such as Alzheimer' s disease
  • metabolic disorder refers to a related symptom and/or disease caused by metabolic disorders such as sugar, fat or protein caused by various causes.
  • diabetes refers to a multi-pathogenic metabolic disease characterized by chronic hyperglycemia accompanied by disorders of sugar, fat and protein metabolism caused by insulin secretion and/or dysfunction.
  • the metabolic disorders in the body are not well controlled, leading to chronic complications of tissues such as the eyes, kidneys, nerves, blood vessels and heart, resulting in blindness, gangrene in the lower limbs, Uremic, stroke or myocardial infarction, even life-threatening.
  • insulin resistance refers to a decrease in the sensitivity of tissues surrounding the body to insulin, and target tissues such as muscles and fats are resistant to insulin-induced glucose uptake. Insulin resistance is prevalent in type 2 diabetes, accounting for more than 90%, and is one of the main factors in the development of type 2 diabetes.
  • obesity refers to an excess of body fat, a male weighing more than 25% of the ideal body weight, or a woman weighing more than 30% of the ideal body weight. Genetic factors, hypothalamic disease, endocrine disorders, overeating and too little activity are all causes of obesity.
  • AD Alzheimer's Disease
  • AD Alzheimer's dementia
  • cardiovascular disease includes heart disease, pulmonary heart disease, hypertension, and hyperlipidemia. With “onset The rate is high, the mortality rate is high, the disability rate is high, the recurrence rate is high, and the “complication is more”.
  • an "effective amount" of a compound for treating a particular condition refers to an amount sufficient to ameliorate or to some extent alleviate the symptoms associated with the disease.
  • This dose can be administered in a single dose or in accordance with a therapeutic regimen. This dose cures the disease, but is typically administered to improve the condition. Repeated administration to improve symptoms may be desirable.
  • pharmaceutically acceptable salts, esters or other derivatives include any salt, ester or derivative which is readily prepared by those skilled in the art using known methods.
  • the compounds thus derived and produced can be administered to animals and humans without toxic effects.
  • the compound is either pharmaceutically active or a prodrug.
  • treatment means that the disease and symptoms are improved in any way, or other beneficial changes. Treatment also includes the use of the compounds of the invention in medicine.
  • administration of a particular pharmaceutical composition to "improve" the symptoms of a particular disease means any reduction, whether permanent, temporary, prolonged, transient, can be attributed to or associated with the pharmaceutical composition. Relevant application.
  • substantially pure means sufficiently uniform that no impurities can be detected by standard analytical methods used by those skilled in the art to evaluate purity, such as thin layer chromatography (TLC), gel electrophoresis, and High performance liquid chromatography (HPLC). Or sufficiently pure also means that even further purification does not alter the physicochemical properties detectable by the substance, such as enzymatic activity and biological activity.
  • Methods for producing substantially chemically pure compounds for purification are well known to those skilled in the art. However, a substantially chemically pure compound can be a stereoisomer or a mixture of isomers. In this case, further purification may increase the specific activity of the compound.
  • prodrug refers to a compound that is administered in vivo and which can be metabolized or converted into a biologically, pharmaceutically or therapeutically active form.
  • the pharmaceutically active compound will be modified to reproduce the active compound by metabolic processes.
  • Prodrugs can be designed to alter their metabolic stability, or to transport precursors of properties, to mask their side effects or toxicity, to improve the taste of the drug, or to alter other properties.
  • substantially is the same or uniform or similar, and the understanding of the relevant art by those skilled in the art may vary in the context and is generally at least 70%, preferably at least 80°/. , preferably at least 90%, optimally at least 95% identical.
  • composition refers to any mixture. It may be a solution, suspension, liquid, powder, ointment, aqueous, non-aqueous or any combination thereof.
  • object as used herein includes humans and animals, for example, dogs, cats, cows, pigs, rodents, and the like. Experienced practitioners should understand that the subject is suitable and willing to treat and prevent diabetes and its complications.
  • the present invention provides a modulator of glucagon-like peptide-1 receptor function, which increases the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases.
  • a member of a drug such as a sexually transmitted disease (such as Alzheimer's disease).
  • the present invention relates to a compound represented by any one of the following formulae I to VI, or a pharmaceutically acceptable salt thereof:
  • X, ⁇ , Z are (C3 ⁇ 4) n , n is 0-2, oxygen, sulfur or nitrogen.
  • R 1 R 2 each independently is any one of the following substituents: hydrogen; halogen; alkane; cycloalkane; hydroxy; nitro; carboxy; aldehyde; alkoxy; amine; aminyl; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • R 5, 3 ⁇ 4, R 7 are each independently any of the following substituents: hydrogen; hydrocarbon embankment; cyclic hydrocarbon embankment; alkoxy; amino; alkyl with an amine; amide group; carboxamide group; burning thio; substituted Or an unsubstituted aryl group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group.
  • the compound of the present invention may be a specific stereoisomer, such as the R- or S-configuration, or a mixture thereof, for example, a racemic mixture.
  • Compounds contemplated herein include all classes of pharmaceutically active compounds, or solutions or mixtures thereof. Also included are hydration types thereof, such as aqueous solutions, hydrolysates or ionized products of these compounds; and these compounds may contain varying amounts of bound water molecules.
  • the compounds of the invention may be prepared or synthesized according to any suitable method. Preferably, the compound is prepared by the synthetic procedure cited in Section F below.
  • the compound or a pharmaceutically acceptable salt thereof is provided in the form of a pharmaceutical composition, either alone or in combination with a pharmaceutically acceptable carrier or excipient.
  • the compounds of the invention may be prepared in the form of their pharmaceutically acceptable salts with any suitable acid.
  • suitable acid for example, inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.; organic acids such as formic acid, acetic acid, propionic acid, benzoic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, citric acid, etc.;
  • a sulfonic acid such as methanesulfonic acid or ethylsulfonic acid; an arylsulfonic acid such as benzenesulfonic acid or p-toluenesulfonic acid can be used.
  • the present invention relates to methods for preventing and/or treating metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease.
  • the method comprises administering to a subject in need or willingness to receive treatment or prevention an effective amount of a compound that selectively agonizes the glucagon-like peptide-1 receptor or a pharmaceutically acceptable salt thereof for treating or preventing the above-mentioned diseases. Or symptoms.
  • the above disease is treated or prevented by administering an effective amount of a compound represented by any one of the following formulas I to VI or a pharmaceutically acceptable salt thereof:
  • X, Y, and ⁇ are (CH, ⁇ is 0-2, oxygen, sulfur or nitrogen, respectively).
  • RR 2 , R 3 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkane; light base; nitro; carboxyl; aldehyde; alkoxy; amine; Amido; carboxamide; sulfhydryl; sulfhydryl; ether; a thioether; a substituted or unsubstituted aryl group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrole group; base.
  • R 7 are each independently a substituent of any of the following: hydrogen; anthracene; a cycloalkyl; an oxirane; an amine; an amine alkyl; an amide; a carboxamide; an alkylthio; a substituted or unsubstituted Aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • Any subject can be controlled by this method, preferably a mammal, more preferably a human.
  • the method can be used to control metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease).
  • a preferred disease or condition is any disease or condition caused or accompanied by insulin secretion and/or dysfunction.
  • metabolic disorders including but not limited to diabetes, insulin resistance and obesity
  • it can be used alone or in combination with other diabetes treatments including insulin sensitizers that are marketed or will be marketed.
  • insulin sensitizers that are marketed or will be marketed.
  • Inventive compound Any suitable metabolic disorder (including but not limited to diabetes, insulin resistance, and obesity) therapeutic agents can be used in combination with the compounds of the present invention.
  • typical insulin sensitizers include rosiglitazone and pioglitazone.
  • the above insulin sensitizer is not administered when the compound of the invention is used. More preferably, the compound of the present invention is used to treat or prevent a disease or symptom caused by the use of the above-mentioned diabetes therapeutic agents (including insulin sensitizers) which have been marketed or will be marketed to produce drug resistance or side effects.
  • the above-mentioned diabetes therapeutic agents including insulin sensitizers
  • diabetes therapeutics including insulin sensitizers
  • it can be administered alone or in combination with other suitable diabetes therapeutics, including insulin sensitizers, by any suitable method.
  • it can be administered by intracavitary injection, subcutaneous injection, intravenous injection, intramuscular injection, intradermal injection, orally or topically with the compound of the present invention, or with a pharmaceutically acceptable salt thereof.
  • the method further comprises performing a diagnosis and prognosis assessment of the disease or condition of the subject to whom it is administered.
  • Any suitable method can be used to diagnose and assess the associated disease or condition and its prognosis.
  • Diagnosis and prognosis can be based on detecting and/or identifying any or all of the in vivo substances, such as glycated hemoglobin, enzymes, anti-pro-, antibodies, nucleic acids or other pathological and clinical markers, and related symptoms.
  • a diagnostic or prognostic method disclosed in International Patent No. WO 01/44815 and U.S. Patent No. 5,571,674 can be used.
  • the invention also relates to a combination formulation comprising a compound that selectively modulates glucagon-like peptide-1 receptor function, or a pharmaceutically acceptable salt thereof, and one or more Therapeutic drugs for metabolic disorders include insulin sensitizers.
  • such a combination comprises a compound of the present invention or a pharmaceutically acceptable salt thereof and one or more therapeutic agents for metabolic disorders including an insulin sensitizer, which is represented by any one of the following formulas I to VI -
  • X, ⁇ , Z are (CH 2 ) coherent, n is 0-2, oxygen, sulfur or nitrogen.
  • R l 7 R 2 , R 3 , R 4 are each independently one of the following substituents: hydrogen; dentate; alkane; cycloalkane light; hydroxy; nitro; carboxy; acid group; alkoxy group; Amine alkyl; amide group; carboxamide; fluorenyl; alkylthio; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; Or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • R 5 , Re, R 7 are each independently any of the following substituents: hydrogen; alkane; cycloalkane; alkoxy; amine; amine alkyl; amide; carboxamide; alkylthio; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.
  • Any suitable therapeutic agent for diabetes including insulin sensitizers, can be used in the combination formulations of the invention.
  • one or more of the above-mentioned diabetes therapeutic agents including insulin sensitizers may be included in the combined preparation of the present invention.
  • a method of treating or preventing a disease or condition caused or accompanied by insulin secretion and/or dysfunction comprising administering an effective amount to a subject in need and willing to receive treatment or prevention The above combined preparation, or a pharmaceutically acceptable salt thereof, thereby treating or preventing the above diseases or symptoms.
  • kits comprising a compound of the present invention or a pharmaceutically acceptable salt thereof, and the use of the above compound or a pharmaceutically acceptable salt thereof for controlling secretion and/or secretion by insulin Instructions for the use of a disease or condition caused by or associated with a dysfunction.
  • kits comprising the combination of the above, and treatment with the combination Or instructions for the prevention of a disease or condition caused or accompanied by insulin secretion and/or dysfunction.
  • the compounds of the invention are formulated for any suitable route of administration, for example, intraluminal, subcutaneous, intravenous, intramuscular, intradermal Injection, oral or topical.
  • the method can be administered by injection in a single dose in an ampoule, or in a multi-dose container with an added buffer.
  • the formulations may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles.
  • the formulations may contain formulating agents such as suspending, stabilizing and/or dispersing agents.
  • the active ingredient may be in a powder form with a suitable vehicle, sterile non-pyrogenic water or other solvent before use.
  • the topical medicament of the present invention may be a foam, a gel, an ointment, an ointment, a transdermal patch, or a paste.
  • compositions and methods for administration that may be used in the present invention include, but are not limited to, U.S. Patents 5,736,154, 6,197, 801 Bl, 5,741,511, 5, 886, 039 5, 941, 868, 6, 258, 374B1 and 5, 686, 102.
  • the size of the dose to be treated or prevented will vary depending on the severity of the condition and the route of administration.
  • the dose and frequency of administration will vary with age, weight, health status, and individual patient response.
  • Dosage forms include tablets, troches, soy capsules, dispersing agents, suspending agents, solutions, capsules, films and the like.
  • the compound of the present invention may be in accordance with a general pharmaceutical mixing technique with a pharmaceutical carrier or excipient such as ⁇ -cyclodextrin and 2-hydroxypropyl- ⁇ -cyclodextrin. Finely mixed.
  • a pharmaceutical carrier or excipient such as ⁇ -cyclodextrin and 2-hydroxypropyl- ⁇ -cyclodextrin. Finely mixed.
  • a special carrier, a local or parenteral route, can be used depending on the needs of the administration.
  • parenteral dosage forms such as compositions for intravenous injection or infusion
  • similar pharmaceutical vehicles can be employed, water, glycols, oils, buffers, sugars, preservatives, liposomes, etc., which are well known to those skilled in the art. .
  • parenteral compositions include, but are not limited to, 5% w/v dextrose, physiological saline or other solutions.
  • the total dose of the compound of the present invention, alone or in combination with other preparations, can be administered in vial vials in a volume of from about 1 ml to about 2000 ml. The amount of diluent will vary depending on the total dose administered.
  • the invention also provides a kit for achieving a therapeutic regimen.
  • the kit comprises an effective amount of a compound of the invention in a pharmaceutically acceptable form, alone or in combination with other agents, in one or more containers.
  • the preferred pharmaceutical form is in combination with sterile saline, dextrose solution, buffer solution, or other pharmaceutically acceptable sterile liquid.
  • the composition may be frozen or dried; in this case, the kit optionally further comprises a pharmaceutically acceptable solution, preferably a sterile solution, in a container to reconstitute the complex A solution for injection purposes is formed.
  • Typical pharmaceutically acceptable solutions are physiological saline and dextrose solutions.
  • the kit of the invention further comprises a composition for injection, preferably in sterile form A needle or syringe and/or a packed alcohol pad. Instructions for use by a doctor or patient may optionally be included.
  • the ketone (0. 67 eq) of COOH was dissolved in an appropriate amount of diethyl ether and water, and cooled in an ice salt bath.
  • Sodium cyanide (1. 67 eq) was added and stirred vigorously. When most of the sodium cyanide is dissolved and the temperature of the reaction solution falls below 5 °C, an appropriate amount of concentrated hydrochloric acid is slowly added dropwise to maintain the reaction temperature between 5 ° C and 10 ° C. After the completion of the dropwise addition, the ice bath was removed while vigorously stirring for 2 hours. After standing, the ether layer was separated, and the aqueous layer was poured into a reaction flask, and water was added to dissolve the salt.
  • the aqueous layer was extracted with diethyl ether. EtOAc was evaporated. The residue was poured into concentrated hydrochloric acid and saturated with hydrogen chloride gas and stood overnight. Then, take part of the hydrogen chloride gas with air, and then slowly add 50% sodium hydroxide solution to adjust to alkaline. The mixture was cooled in an ice-bath, and stirred with mechanical stirring, sodium hydroxide solid (0. 6 eq.), and steam distilled until no excess of ammonia and ketone. Dilute with water and extract with ether (discard). The aqueous layer was acidified with concentrated hydrochloric acid, cooled, and filtered to give an hydroxy acid.
  • A-hydroxy acid (0, 69 eq) was added to the acid chloride (0.66 eq), and the reaction was heated in a water bath. The crystallized was cooled to obtain a product. Under nitrogen, take LDA (1.2mra 0 l) in an appropriate amount of tetrahydrofuran, cool to 50 ⁇ , slowly add carboxylic acid (0.5 mmol), continue to stir for 30 minutes, continue at 50 °C Stir for 2 hours. Cool to a 10 (TC, drop nitro-substituted olefin (1.5 awake 0 1) with a liquid nitrogen/methanol bath, react for 5 hours, and slowly raise the temperature of the reaction solution to 0-10 ° C. Add the appropriate amount. 17% dilute hydrochloric acid, stirring in an ice bath overnight. Add water, dichloromethane extract, wash with water and saturated brine, and dry.
  • FIG. 1 Reporter gene method to detect the agonistic effects of compounds on GLP-1R.
  • the GLP-1 concentration gradient is 10, 1, 0.1.
  • FIG. 1 Reporter gene assay for the antagonism of exendin 9-39 on GLP-1.
  • concentration of GLP-1 was chosen to be 0.05 nM, and the concentration gradient of exendi- 39 was 10000, 1000, 100, 10, 1, 0. 1, 0 nM, and the activity of exendir 39 was set to 100%.
  • exendin ⁇ reported dose-dependently induced by inhibition of gene expression of GLP- 1, which IC 5. The value was 68. 22 nM, indicating that its biological activity is mediated by GLP-1R.
  • FIG. 4 Receptor competitive binding assay method to detect the affinity of GLP-1 for receptors.
  • the GLP-1 concentration gradient is 1000, 200, 40, 8, 1. 6, 0. 32, 0. 064, 0 nM.
  • GLP-1 can specifically bind to GLP-1R in a competitive manner with 125 1 standard GLP-1, and its IC 50 value is 0. 66 nMo
  • HP1100 HPLC system with binary gradient pump, online vacuum degasser, autosampler, column oven and photodiode array detector The column was ZORBAX SB-C18 (2.11 x 150 mm, 3. 5 ⁇ ), the mobile phase was acetonitrile/water, the flow rate was 0.2 ml/min, and the detection wavelength was 254 nm.
  • the melting point was measured by an IA6304 melting point apparatus; NMR was measured by Varian Mercury-300 and Varian Mercury Plus 400 nuclear magnetic resonance spectrometer (solvent CDC1 3 , CD 3 0D or DMS0-d 6 ); ESI-MS by AB Mariner mass spectrometer The EI was measured by a Finnigan MAT95 mass spectrometer.
  • the materials used in the synthesis are commercially available products unless otherwise specified.
  • the temperature should be between 5 ° C and 10 °.
  • the ice bath was removed while vigorously stirring for 2 hours.
  • the ethyl ether layer was separated, and the aqueous layer was poured into a reaction flask, and water was added to dissolve the salt.
  • the aqueous layer was extracted with diethyl ether.
  • the residue was poured into concentrated hydrochloric acid and saturated with hydrogen chloride gas and stood overnight. Then use the air to remove some of the hydrogen chloride gas, and then slowly add 50% sodium hydroxide solution to adjust to alkaline. Cool in an ice bath, mechanically stir, add sodium hydroxide solid (0.6 eq), steam distilled until free of ammonia and ketone. Dilute with water and extract with ether (discard).
  • GLP-1R is a G protein-coupled receptor.
  • GLP-1R binds to an agonist, the G ⁇ subunit of the G protein is activated. Stimulation of adenylate cyclase leads to an increase in intracellular cAMP levels. Since the cAMP response element exists in the promoter region of the proinsulin gene, cAMP binds to the response element to initiate transcription of the pre-insulin gene, thereby stimulating insulin expression and secretion (Diabetes, 2000, Vol. 49: 1156-1164).
  • HEK 293 human embryonic kidney cell strain stably transfected with a GLP-1R receptor gene expression vector and a luciferase reporter gene expression vector regulated by a cAMP response element was used to detect its response to a test compound (Cell). Biology, 1992, Vol. 89: 8641-8645; Proc. Natl. Acad. Sci. USA 1987, Vol. 84: 3434-3438). A sample that induces expression of a luciferase reporter gene when screened for a compound is considered to have GLP-1R agonistic activity.
  • DMEM medium (GIBC0 company)
  • HEK293/GLP1R+Luc cells were inserted into 96-well culture plates at 20,000/100 ⁇ /well, and cultured overnight at 37 ° C in DMEM medium containing 10% fetal calf serum and 500 ⁇ ⁇ / ⁇ 1 G418.
  • the GLP-1 standard was diluted to a concentration gradient and then added to the above 96-well microplate at 1 ⁇ /well. Incubate for 6 hours at 37 ° C under 5% CO 2 . Luciferase activity was measured by the Steady-GloTM Luciferase Assay System Kit, and the Victor 2 reader was used for reading.
  • DMEM medium (GIBC0 company)
  • HEK293/GLP1R+Luc cells were inserted into 96-well culture plates at 20,000/100 ⁇ /well, and cultured overnight at 37 ° C in DMEM medium containing 10% fetal calf serum and 500 ⁇ ⁇ / ⁇ 1 G418.
  • the Exendir 39 was diluted to a certain concentration gradient, and then added to the above 96-well microplate at 1 ⁇ M/well, incubated at 37 ° C, 5% CO 2 for 10 minutes, and then added 0. 05 nMGLP-1 Incubate for 6 hours at 37 ° C under 5% CO 2 .
  • Luciferase activity was measured by the Steady-GloTM Luciferase Assay System Kit, and the Victor 2 reader was used for reading.
  • the reporter gene detection method is a method for indirectly determining the level of intracellular CAMP concentration. To confirm that the active compound does increase intracellular cAMP concentration, functional verification is performed directly using the cAMP assay kit.
  • HEK 293 cells were incubated at 20,000 cells/lOOul/well in 96-well culture plates, cultured overnight at 37 ° C, GLP-1 was serially diluted with dimethyl sulfoxide, and added to the above 96-well microplates at 1 ⁇ l/well. Incubate for 15 min at 37 ° C, 5% CO 2 . Intracellular cAMP levels were measured by cAMP-Screen DirectTM Systerm kit instructions.
  • GLP-1 dose-dependently induced cAMP in cells (Table 3, FIG. 3), which EC 5.
  • the value was 0. 079 nM, suggesting that it acts as a GLP-1R agonist and plays a role in GLP-1R signaling.
  • HEK 293/GLP1R+Luc cell line self-built by National New Drug Screening Center
  • Labeled compound 125 1 labeled GLP-1 (Amersham Biosciences)
  • HEK 293/GLP1R+Luc cells in 10 5 logarithmic growth phase were incubated with 125 1 GLP-1 positive peptide (final concentration 40 M) for 4 hours at 25 ° C in 200 ⁇ l test buffer.
  • the cells were washed three times with a washing solution using a cell harvester. Scintillation fluid was added and each well reading was read on a Microbata counter.
  • GLP-1 specifically binds to receptors that compete with 125 1 GLP-1 (Table 4, Figure 4), its IC S .
  • the value is 0. 66 nM.

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Abstract

Substituted cyclohexane compounds represented by any one of formula I-VI. The preparation method of these compounds and uses thereof as glucagons like peptide-1 receptor(GLP-1R) regulators for preventing and/or treatment of metabolic disorders, which include but not limit to diabetes, insulin-resistance and obesity etc., cardiovascular diseases and neurodegenerative diseases such as Alzheimer's diseases.

Description

一类具有取代环己垸结构的化合物、 及其制备方法和医学用途 技术领域  Compounds with substituted cyclohexanium structure, preparation method thereof and medical use thereof

本发明涉及一类具有取代环己垸结构的化合物、 及其制备方法和其作为胰髙血糖样肽 一 1受体（Glucagon like peptide- 1 receptor, GLP-1R) 调节剂在预防和 /或治疗代谢紊 乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症等）、 心血管疾病、 神经退行性 疾病 (如 Alzheimer' s病)等的医学用途。  The present invention relates to a compound having a substituted cyclohexanyl structure, a preparation method thereof and a modulator of Glucagon like peptide-1 receptor (GLP-1R) in prevention and/or treatment Medical use of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity, etc.), cardiovascular diseases, neurodegenerative diseases (such as Alzheimer's disease).

背景技术  Background technique

'糖代谢紊乱， 特别是糖尿病， 已成为现代社会严重威胁人类健康与生命的主要疾病。 据预测， 全世界糖尿病患者正以每年 6%的速度递增， 到 2006年末已有 3. 2亿患者（我国 为 6000万人， 占居第二位）。 糖尿病是一组由遗传和环境因素相互作用而引起的临床综合 症， 主要分为 1型和 2型， 其中 1型糖尿病的基本病理生理为绝对性胰岛素分泌不足， 临 床治疗以补充胰岛素为主， 故又称为胰岛素依赖型糖尿病。 2型糖尿病占患病群体的 95% 以上， 临床研究发现绝大多数 2型糖尿病患者可合成正常甚至过量的胰岛素， 但因靶细胞 对胰岛素的敏感性降低 （也称 "胰岛素抵抗" ）， 导致胰岛素相对不足， 又称为非胰岛素 依赖型糖尿病。 胰岛素抵抗是 2型糖尿病发生和发展过程中的关键因素。 2型糖尿病的治 疗药物包括磺脲类、双胍类、其他胰岛素增敏剂及辅助措施等。磺脲类降糖药物与胰腺 β 细胞膜的受体结合后， 关闭钾离子通道， 阻断钾离子外流， 导致细胞膜去极化， 促使 Ca2+ 通道开放， 造成胞外钙离子内流， 胞内钙离子浓度增加后， 触发胰岛素的释放。 按其问世 先后分为两代， 第一代如甲苯磺丙脲， 第二代包括格列本脲（优降糖)、 格列齐特 （达美 康)， 格列吡嗪 （美吡哒）和格列喹酮 （糖适平） 等。 双胍类降糖药物能抑制食欲， 增加 胰岛素与受体的结合， 促进细胞对葡萄糖的无氧酵解， 抑制组织呼吸， 抑制肝糖元异生。 主要有二甲双胍、 苯乙双胍和丁双胍等。 其他降糖药主要包括噻唑烷二酮类 (Thiazolidinediones ) 药物 （例如曲格列酮、 罗格列酮、 吡格列酮等）、 β 3-肾上腺素 受体调节剂、 胰高血糖素受体拮抗剂、 脂肪酸代谢干扰药、 a -糖苷酶抑制药 （例如阿卡 波糖、 伏格列波糖、 米格列醇等） 以及醛糖还原酶抑制剂等。 'Glucose metabolism disorders, especially diabetes, have become the main diseases that threaten human health and life in modern society. It is predicted that diabetes patients worldwide are increasing at a rate of 6% per year. By the end of 2006, there were 320 million patients (60 million in China, ranking second). Diabetes is a group of clinical syndromes caused by the interaction of genetic and environmental factors. It is mainly divided into type 1 and type 2. The basic pathophysiology of type 1 diabetes is absolute insulin secretion, and clinical treatment is mainly supplemented with insulin. It is also known as insulin-dependent diabetes. Type 2 diabetes accounts for more than 95% of the diseased population. Clinical studies have found that most patients with type 2 diabetes can synthesize normal or even excess insulin, but the sensitivity of target cells to insulin is reduced (also known as "insulin resistance"), resulting in Relatively insufficient insulin, also known as non-insulin dependent diabetes. Insulin resistance is a key factor in the development and progression of type 2 diabetes. Therapeutic drugs for type 2 diabetes include sulfonylureas, biguanides, other insulin sensitizers, and ancillary measures. When the sulfonylurea-type hypoglycemic agent binds to the receptor of the pancreatic β-cell membrane, the potassium ion channel is closed, and the potassium ion efflux is blocked, resulting in depolarization of the cell membrane, causing the Ca 2+ channel to open, causing extracellular calcium influx, intracellular. When the calcium ion concentration is increased, the release of insulin is triggered. According to its advent, it was divided into two generations, the first generation such as toluene propyl propyl urea, the second generation including glibenclamide (glibenclamide), gliclazide (Damecon), glipizide (mepyrazin) ) and gliclazide (sugar flat) and so on. The biguanide hypoglycemic agent can suppress appetite, increase the binding of insulin to the receptor, promote the anaerobic glycolysis of glucose, inhibit tissue respiration, and inhibit hepatic gluconeogenesis. Mainly there are metformin, phenformin and butyl bismuth. Other hypoglycemic agents mainly include Thiazolidinediones (such as troglitazone, rosiglitazone, pioglitazone, etc.), β 3-adrenergic receptor modulators, glucagon receptor antagonists, Fatty acid metabolism interfering drugs, a-glycosidase inhibitors (such as acarbose, voglibose, miglitol, etc.) and aldose reductase inhibitors.

胰高血糖素样肽- 1受体 （Glucagon like peptide-1 receptor, GLP-1R)属于 B类型 的 G蛋白偶联受体 (G protein-coupled receptor, GPCR)。 当机体摄入营养物质时， 肠 内分泌细胞释放的肠肽激素一胰高血糖素样肽- 1 (Glucagon like peptide-1 , GLP- 1 )， 通过与 GLP- 1R高度特异性地结合使其活化， 刺激胰岛素分泌， 抑制胰髙血糖素的产生， 使餐后血糖降低并维持在恒定水平。 生理条件下， GLP-1 刺激胰岛素分泌的作用依赖于血 糖浓度， 不会因持续分泌而发生低血糖。 GLP- 1还具有促进 β细胞的增殖和分化， 以及神 经调节功能， 延迟胃排空， 降低食欲。 在体外， GLP-1 能促进胚胎干细胞分化为具有胰岛 素分泌功能的类 细胞（J Endocrinol. 2005， 186 : 343-52) 。 GLP-1作用于中枢能促进 细胞存活而减少凋亡， 降低 -淀粉样肽的神经毒， 抑制神经退行性病变的进程 及促进 学习和记忆， 所以最近有人提出将 GLP- 1用于 Alzheimer' s病的治疗 (Ann N Y Acad Sci, 2004, 1035 : 290-315 ; Nat Med, 2003, 9 : 1173—1179 ; Curr Alzheimer Res, 2005, 2 : 377 - 385 ; J Pharmacol Exp Ther, 2002, 302 : 881 - 888)。 另外， GLP- 1在心血管系统中也有重要作 用。 它具有降低血压和扩张血管的作用， 急性注射 GLP-1能在心肌肥大实验中改善左心室 的收缩功能。 它还能在心肌缺血后再灌注的情况下减轻心肌细胞的损伤 （X Hypertens, 2003， 21 : 1125 - 1135 ; Am J Physiol Endocrinol Metab, 2004, 287 :E1209 - E1215 ; Circulation, 2004, 110 : 955 - 961 ; Diabetes, 2005, 54 : 146 - 151)。 由于上述明确的生 理效应， 自 80年代中期发现该靶点以来， 寻找 GLP- 1R的小分子激动剂乃是国际许多新药 开发机构的研究热点。 Glucagon like peptide-1 receptor (GLP-1R) belongs to type B G protein-coupled receptor (GPCR). When the body ingests nutrients, the gutagonal peptide-1 (GLP-1) released by the enteroendocrine cells is activated by highly specific binding to GLP-1R. It stimulates insulin secretion, inhibits the production of glucagon, and lowers postprandial blood glucose and maintains it at a constant level. Under physiological conditions, the effect of GLP-1 on insulin secretion is dependent on blood glucose concentration, and hypoglycemia does not occur due to sustained secretion. GLP-1 also promotes the proliferation and differentiation of beta cells, as well as neuromodulation, delays gastric emptying, and reduces appetite. In vitro, GLP-1 promotes the differentiation of embryonic stem cells into cell-like cells with insulin secretion (J Endocrinol. 2005, 186: 343-52). GLP-1 acts on the central body to promote Cell survival reduces apoptosis, reduces neurotoxicity of amyloid peptides, inhibits the progression of neurodegenerative diseases, and promotes learning and memory, so GLP-1 has recently been proposed for the treatment of Alzheimer's disease (Ann NY Acad Sci) , 2004, 1035: 290-315; Nat Med, 2003, 9: 1173-1179; Curr Alzheimer Res, 2005, 2: 377-385; J Pharmacol Exp Ther, 2002, 302: 881-888). In addition, GLP-1 also plays an important role in the cardiovascular system. It has the effect of lowering blood pressure and dilating blood vessels. Acute injection of GLP-1 can improve left ventricular systolic function in cardiac hypertrophy experiments. It also reduces myocardial cell damage in the presence of myocardial ischemia and reperfusion (X Hypertens, 2003, 21: 1125 - 1135; Am J Physiol Endocrinol Metab, 2004, 287: E1209 - E1215; Circulation, 2004, 110: 955 - 961 ; Diabetes, 2005, 54 : 146 - 151). Due to the above-mentioned clear physiological effects, since the discovery of this target in the mid-1980s, the search for small molecule agonists of GLP-1R has been a research hotspot of many new drug development institutions in the world.

多家国际著名跨国医药公司均在开发 GLP-1类创新药物， 如丹麦 Novo Nordisk公司 开发的 GLP- 1衍生物（商品名为 Liraglutide; 进入三期临床试验）和美国 Amylin医药公 司和礼来公司联合开发的 GLP- 1类似物 Exendin- 4 (商品名 Exenatide; 已于去年 4月份 批准上市， 今年销售额预计超出 10亿美元)。 目前除了 GLP- 1及其多肽类似物外， 尚无任 何有关非肽类小分子 GLP-1R激动剂获得成功开发的报道。 由于多肽药物不便口服， 寻找 非肽类 GLP-1R调节剂， 开发具有自主知识产权的新型抗糖尿病药物是目前许多新药研究 机构所共同关注的方向。  A number of internationally renowned multinational pharmaceutical companies are developing innovative GLP-1 drugs, such as the GLP-1 derivative developed by Danovo Nordisk, Denmark (trade name Liraglutide; entering Phase III clinical trials) and Amylin Pharmaceuticals and Eli Lilly and Company The joint development of the GLP-1 analogue Exendin-4 (trade name Exenatide; was approved for listing in April last year, this year's sales are expected to exceed $1 billion). In addition to GLP-1 and its peptide analogs, there have been no reports of successful development of non-peptide small molecule GLP-1R agonists. Due to the inconvenient oral administration of peptide drugs, the search for non-peptide GLP-1R modulators and the development of new anti-diabetic drugs with independent intellectual property rights are the common concerns of many new drug research institutions.

发明内容  Summary of the invention

本发明的目的在于提供一类由以下通式 I至 VI任意一个表示的化合物及其药学上可 以接受的盐；  It is an object of the present invention to provide a class of compounds represented by any one of the following formulae I to VI and pharmaceutically acceptable salts thereof;

本发明的另一目的在于提供一种制备由以下通式 I至 VI任意一个表示的化合物的方 法；  Another object of the present invention is to provide a process for producing a compound represented by any one of the following formulae I to VI;

本发明的又一目的在于提供一种含有由以下通式 I至 VI任意一个表示的化合物的药 物组合物；  A further object of the present invention is to provide a pharmaceutical composition containing a compound represented by any one of the following Formulae I to VI;

本发明的再一目的在于提供由以下通式 I至 VI任意一个表示的化合物作为胰高血糖 样肽- 1 受体调节剂在预防和 /或治疗代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵 抗和肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病） 等的医学用途。  A further object of the present invention is to provide a compound represented by any one of the following Formulae I to VI as a glucagon-like peptide-1 receptor modulator for preventing and/or treating metabolic disorders (including but not limited to diabetes, Medical uses such as insulin resistance and obesity, cardiovascular disease and neurodegenerative diseases such as Alzheimer's disease.

本发明提供胰高血糖样肽一 1受体调节剂， 增加了预防和 /或治疗代谢紊乱性疾病（包 括但不局限于糖尿病、 胰岛素抵抗和肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病） 等药物的成员。 本发明涉及由以下通式 I至 VI任意一个表示的化合物， 或其药物学上可接受的盐：

Figure imgf000006_0001
The present invention provides a glucagon-like peptide-1 receptor modulator, which increases the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases ( Members of the drug such as Alzheimer's disease. The present invention relates to a compound represented by any one of the following formulae I to VI, or a pharmaceutically acceptable salt thereof:
Figure imgf000006_0001

III

Figure imgf000006_0002
III
Figure imgf000006_0002

IV V VI 及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂化 物或其金属配合物。  IV V VI and all its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

其中 X， Υ, Z分别为（C ) n， n为 0-2， 氧， 硫或氮。 Wherein X, Υ, Z are (C) n and n is 0-2, oxygen, sulfur or nitrogen.

其中 Rt， R2， R3， R4各自独立地为下列任意一种取代基： 氢； 卤素； 烷径； 环烷烃； 羟 基； 硝基； 羧基； 醛基； 垸氧基； 胺基； 胺垸基； 酰胺基； 碳酰胺基； 巯基； 烷硫基； 醚; 硫醚； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。 Wherein R t , R 2 , R 3 , R 4 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkane; hydroxy; nitro; carboxy; aldehyde; oxiran; Amine group; amide group; carboxamide group; fluorenyl group; alkylthio group; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted a pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group.

R5， R6, R7各自独立地为下列任意一种取代基： 氣； 烷弪； 环烷烃； 垸氧基； 胺基； 胺 烷基； 酰胺基； 碳酰胺基； 烷硫基； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代 或未取代的呋喃基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡 咯基。 R 5 , R 6 , R 7 are each independently any of the following substituents: gas; alkane; cycloalkane; anthracene; amine; amine alkyl; amide; carboxamide; alkylthio; Or an unsubstituted aryl group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group.

优选地， 上述通式化合物的特征在于- Preferably, the above formula compound is characterized by -

X， Y， Ζ分别是 (CH2) n， n为 0-2， 氧， 硫或氮， R„ R2， R3， 分别各自独立为:

Figure imgf000006_0003
其中 为下列任意一种取代基为 H; d- ( 的烧基； 含有包括卤素原子、 d- ( 的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d- 的烷基； C2- 的烯基； 含有包括卤素 原子、 d-C^的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2_Ce ½烯基； C2- C6的 炔基;含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3_Ce的环烷基； 含有包括卤素原子、 d- 的垸氧基或羟基在内的任意一个、 两个 或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、 -(4的垸基、硝基、羧基、 醛基、垸氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 c「c4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- ( 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d-c4的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 c「 G的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括 素原子、 C「 ( 4的烷基、硝基、 羧基、 酸基、烷氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； c「 c6的垸酰基； 含 有包括卤素原子、 - 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 CrC6的烷 酰基； C2- 的烯酰基； 含有包括卤素原子、 Cr^的垸氧基或羟基在内的任意一个、 两个或 者三个取代的 C2_C6的烯酰基； C2-Ce的炔酰基； 含有包括卤素原子、 d- C6的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- Cfi的炔酰基； C3- C6的环烷酰基； 含有包括卤素 原子、 CrC6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3 C6的环烷酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 吡喃甲酰基； 为（(¾)„， n为 0-2， 0； S或者 NH时; X, Y, Ζ are (CH 2 ) n , n is 0-2, oxygen, sulfur or nitrogen, R„ R 2 , R 3 are each independently:
Figure imgf000006_0003
Wherein any of the following substituents is H; d- (alkyl group; an alkyl group containing any one, two or three substituted d- groups including a halogen atom, d-(alkoxy group or hydroxyl group) a C 2 -alkenyl group; any one, two or three substituted C 2 _C e 1⁄2 alkenyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a C 2 -C 6 alkynyl group; Any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, C "C 6 alkoxy group or a hydroxyl group; a C 3 _C e cycloalkyl group; Any one, two or three substituted C 3 -C 6 cycloalkyl groups of an atom, d- alkoxy group or a hydroxyl group; aryl; benzyl; furyl; pyranyl; thienyl; pyrrole Pyridyl; Containing any one or two including a halogen atom, -( 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) Or three substituted aryl groups; containing a halogen atom, c "c 4 alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, Any one, two or three substituted pyridyl groups including an ethylthio group; containing a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carbon Any one, two or three substituted furanyl groups including an amide group, a decyl group, a methylthio group, an ethylthio group; a thiol group including a halogen atom, dc 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group Any one, two or three substituted pyranyl groups, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, c "G", and a nitrate Base, carboxyl group, aldehyde group, decyloxy group, amine group, amide group Any carbon amide group, a mercapto group, methylthio, ethylthio, including one, two or three substituents thienyl; comprising pigment containing atoms, C "(an alkyl group, a nitro group, a carboxyl group, an acid group 4, Any one, two or three substituted pyrrolyl groups including an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; c" a decanoyl group of c 6 ; Any one, two or three substituted CrC 6 alkanoyl groups of an atom, a decyloxy group or a hydroxyl group; a C 2 - enoyl group; a halogen atom or a hydroxyl group including a halogen atom, Cr^ any one, two or three substituents of C 2 _C 6 alkenyl group of; C 2 -C e alkynyl group; an alkoxy or hydroxy optionally having a halogen atom include, d- C 6 inner one, two Or three substituted C 2 -C fi alkynyl; C 3 -C 6 cycloalkanoyl; any one, two or three substitutions including a halogen atom, a decyloxy group of CrC 6 or a hydroxyl group the cycloalkyl group of C 3 C 6; adamantyl embankment formyl, substituted adamantane formyl; aryl Group; a benzyl group; furoyl; formyl pyran; thenoyl; pyrroyl; formyl pyran; when S or NH; is ((¾) ", n is 0-2, 0;

， R6， R7分别为：

Figure imgf000007_0001
其中 为下列任意一种取代基： H; d- C6的院基； 含有包括卤素原子、 -^的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d-C6的烷基； 02-( 6的烯基； 含有包括卤素 原子、 C「C6的垸氧基或径基在内的任意一个、 两个或者三个取代的 C2- ( 6的烯基； C2- C6的 炔基；含有包括卤素原子、 C Ce的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C3 的炔基； C3- C6的环垸基； 含有包括卤素原子、 - 的烷氧基或羟基在内的任意一个、两个 或者三个取代的(：3- C6的环烷基； 芳基； 苄基；呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、 -C^烷基、硝基、羧基、 醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 -( 4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- (：4的垸基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- 的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d- (：4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括卤素原子、 d-C4的烷基、硝基、羧基、 醛基、烷氧基、 胺基、酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； （ cr,的垸酰基； 含 有包括卤素原子、 （ Cs的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c,- ce的垸 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或 者三个取代的 c2- c6的烯酰基； c2- c6的炔酰基； 含有包括卤素原子、 - 的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 c2- c6的炔酰基； c3- c6的环烷酰基； 含有包括卤素 原子、 （ Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c3-ce的环垸酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2) n， n为 0-2， 0； S或者 NH时； , R 6 , R 7 are:
Figure imgf000007_0001
Wherein is any one of the following substituents: H ; a group of d-C 6 ; an alkyl group containing any one, two or three substituted dC 6 including a halogen atom, an alkoxy group or a hydroxyl group. 0 2 -( 6 alkenyl; any one, two or three substituted C 2 - ( 6 alkenyl; C 2 containing a halogen atom, C "C 6 oxime or a diatom group" - an alkynyl group of C 6 ; any one, two or three substituted C 2 -C 3 alkynyl groups including a halogen atom, an alkoxy group of C Ce or a hydroxyl group; a ring of C 3 - C 6 Any one, two or three substituted (including 3 - C 6 cycloalkyl groups; aryl; benzyl; furyl; pyranyl) containing a halogen atom, an alkoxy group or a hydroxyl group ; thienyl; pyrrolyl; pyridyl; containing halogen atom, -C^alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, B any of a group including two or three aryl group substituents; containing a halogen atom include, - (4 alkyl, nitro, carboxyl, aldehyde Any alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two, three or substituted pyridyl; include a halogen atom-containing, d- (: 4 of Any one, two or three substituted furanyl groups including a mercapto group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one or two containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Or three a substituted pyranyl group; containing a halogen atom, d- (: 4 alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, B Any one, two or three substituted thienyl groups including a thio group; containing an alkyl group including a halogen atom, dC 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted pyrrolyl groups, fluorenyl, methylthio, ethylthio; (c r , decanoyl; containing a halogen atom, (alkoxy group of Cs or hydroxyl group) Any one, two or three substituted c, - c e decanoyl; C 2 - C e enoyl; any one or two containing a halogen atom, an alkoxy group of d-Ce or a hydroxyl group Or three substituted c 2 - c 6 enoyl groups; c 2 - c 6 alkynyl groups; any one, two or three substituted c 2 groups including a halogen atom, an alkoxy group or a hydroxyl group - c 6 alkynyl group; c 3 - C 6 cycloalkyl group; a halogen atom-containing comprises, (Ce of Alkoxy or hydroxy, including any one, two or three substituents of c 3 -c e embankment cycloalkyl group; formyl embankment adamantyl, substituted adamantane formyl; aryl group; a benzyl group; furoyl; pyran Formyl; thiophene; pyrrolyl; (CH 2 ) n , n is 0-2, 0; S or NH;

或者 R5， ， R" R8， R9， 。分别为：

Figure imgf000008_0001
其中 Rw， Ru各自独立为下列任意一种取代基： H; d-C6的烷基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C「C6的垸基； C2- (6的烯基； 含有包括卤素原子、 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- (：6的 烯基； C2- (：6的炔基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2- ( 6的炔基； C3- C6的环烷基； 含有包括卤素原子、 Ce的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- 04的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括 素原子、 C「 C4的烷基、硝基、 羧基、 醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 CrC^烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、（^-(]4的垸基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 (]4的烷基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- (：4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d-C6的烷酰基； 含有包括卤素原子、 CrCe的烷氧基或羟基在内的任意一个、两个或者三个 取代的 d- CB的垸酰基； C2- Ce的烯酰基； 含有包括卤素原子、 -(：6的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2- Cs的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 CrCe 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3-C6的环垸酰基； 含有包括卤素原子、 Cr-Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- ( 的 环垸酰基； 金刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为 (C¾)„， n为 0-2， 0； S或者 NH时; 为（CH2) n， n为 0-2, 0； S或者 NH时; Or R 5 , , R" R 8 , R 9 , respectively:
Figure imgf000008_0001
Wherein R w , Ru are each independently a substituent of any of the following: H ; alkyl of dC 6 ; any one, two or three substituted Cs including a halogen atom, an alkoxy group of d- or a hydroxyl group "C 6 thiol; C 2 - ( 6 alkenyl; any one, two or three substituted C 2 - (: 6 alkenyl group) including a halogen atom, an alkoxy group or a hydroxyl group; C 2 - (: 6 alkynyl; any one, two or three substituted C 2 - ( 6 alkynyl group; C 3 - C 6 containing an alkoxy group including a halogen atom, dC e or a hydroxyl group; Any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom, an alkoxy group of Ce or a hydroxyl group; an aryl group; a benzyl group; a furyl group; a thiol group; a pyrenyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a halogen atom, d- 4 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group Any one, two or three substituted aryl groups including a thio group or an ethylthio group; containing a arginine atom, C "C 4 Any one, two or three substituted pyridyl groups such as an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Containing any one or two including a halogen atom, a CrC alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Or a three-substituted furyl group; containing a halogen atom, a sulfhydryl group of (^-( 4 ), a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group Any one, two or three substituted pyranyl groups including an ethylthio group; containing an alkyl group including a halogen atom, ( 4 ), a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group Any one, two or three substituted thienyl groups including a carboxamide group, a fluorenyl group, a methylthio group and an ethylthio group; containing a halogen atom, d- (: 4 fluorenyl group, nitro group, carboxyl group, aldehyde) Base, alkoxy group, amine group, amide group, carboxamide group, sulfhydryl group, A Group, ethylthio, including any one, two or three substituents pyrrolyl; dC 6 alkanoyl; contain any halogen atom includes, CrC e alkoxy or hydroxy group including, two or three a substituted decanoyl group of d-C B ; an enoyl group of C 2 - C e ; containing a halogen atom, a hydroxyl group such as 6 or a hydroxyl group Any one, two or three substituted C 2 - C s enoyl groups; C 2 - C 6 alkynyl groups; any one, two or three containing a halogen atom, a decyloxy group or a hydroxyl group of a CrCe Substituted C 2 -C 6 alkynyl; C 3 -C 6 cyclodecanoyl; any one, two or three substituted C containing a halogen atom, an alkoxy group of Cr-Ce or a hydroxyl group 3 - (cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (C3⁄4) „, n is 0-2, 0; S or NH; (CH 2 ) n , n is 0-2, 0; S or NH;

或者 R5， R6, R7分别为-

Figure imgf000009_0001
其中 R12为下列任意一种取代基： H; C「 ( 6的烷基； 含有包括卤素原子、 c「 的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 的烷基； C2- (：6的烯基； 含有包括卤素 原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c2-c 烯基； c2- c6的 炔基;含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、两个或者三个取代的 c2-c6 的炔基； c3- c6的环垸基； 含有包括卤素原子、 c「c6的烷氧基或羟基在内的任意一个、两个 或者三个取代 c3- c6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 （^- 的烷基、硝基、羧基、 醛基、垸氧基、 胺基、酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-c^垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d-c4的垸基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- ( 的烷基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d- c4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、 烷基、 硝基、羧基、醛基、烷氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d-Ce的烷酰基； 含 有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的烷 酰基； c2- Cs的烯酰基； 含有包括卤素原子、（ CB的烷氧基或羟基在内的任意一个、两个或 者三个取代的 C2- C6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 d- ce的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 c2- c6的炔酰基； c3- c6的环垸酰基； 含有包括卤素 原子、 d- 的浣氧基或轻基在内的任意一个、 两个或者三个取代的 c3- c6的环烷截基； 金 刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2) n， n为 0-2， 0； S或者 NH时; Or R 5 , R 6 , R 7 are -
Figure imgf000009_0001
Wherein R 12 is any one of the following substituents: H; C" (alkyl group of 6 ; any one, two or three substituted alkyl groups including a halogen atom, a c alkoxy group or a hydroxyl group) C 2 - (: 6 alkenyl; any one, two or three substituted c 2 -c alkenyl groups including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; c 2 - c 6 An alkynyl group; any one, two or three substituted c 2 -c 6 alkynyl groups including a halogen atom, an alkoxy group of dC e or a hydroxyl group; a c 3 - c 6 cyclodecyl group; Any one, two or three substituted c 3 - c 6 cycloalkyl groups of a halogen atom, c "c 6 alkoxy group or a hydroxyl group; an aryl group; a benzyl group; a furyl group; a pyranyl group; a thienyl group; ; pyrrolyl; pyridyl; containing halogen atom, (^-alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted aryl groups; including halogen atom, dc^ fluorenyl group, nitro group, carboxyl group, aldehyde Any, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two, three or substituted pyridyl; include a halogen atom-containing, dc embankment 4 Any one, two or three substituted furyl groups including a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group; Any one or two of a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) Or a three-substituted pyranyl group; a fluorenyl group including a halogen atom, d-c 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, Any one, two or three substituted thienyl groups including an ethylthio group; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group Any one or two of methylthio or ethylthio Three or substituted pyrrolyl; d-Ce alkanoyl; contain any halogen atom includes, a hydroxyl group or a dC embankment 6 of the inner one, two or three substituents of dC 6 alkanoyl; C An enoyl group of 2 - C s ; an enoyl group containing any one, two or three substituted C 2 - C 6 groups including a halogen atom, (C B alkoxy group or hydroxyl group); C 2 - C 6 An alkynyl group; a acetylenedoyl group having any one, two or three substituted c 2 - c 6 groups including a halogen atom, an alkoxy group of d- c e or a hydroxyl group; a c 3 - c 6 cyclodecanoyl group; Any one, two or three substituted c 3 - c 6 cycloalkane groups containing a halogen atom, a decyloxy group or a light group of d-; an adamantyl formyl group, a substituted adamantyl form group; Acyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH 2 ) n , n is 0-2, 0; S or NH;

或者 ， R6， R7分别为：

Figure imgf000010_0001
其中 R13， Rw各自独立为下列任意一种取代基： H; (^-(：6的院基； 含有包括卤素原子、 d-Cs的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C「 C6的烷基； C2- C6的烯基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的（2-( 6的 烯基； C2- ( 6的炔基； 含有包括卤素原子、 C「C6的院氧基或羟基在内的任意一个、两个或者 三个取代的 C2- C6的炔基； C3-C6的环烷基； 含有包括卤素原子、 d- Ce的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3-C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- ( 的垸基、 硝基、 羧基、 醛基、 '烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括 素原子、 C「 的烷基、 硝基、 羧基、 醛基、烷氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d-C4 垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- C4的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 d- 的垸基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 Cr" C4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d-C6的烷酰基； 含有包括卤素原子、 CrCe的垸氧基或羟基在内的任意一个、两个或者三个 取代的 d- Ce的烷酰基； C2- C6的烯酰基； 含有包括卤素原子、 d- C6的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2- Cs的烯酰基； C2_C6的炔酰基； 含有包括卤素原子、 CrC6 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3- C6的环垸酰基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的 环垸酰基； 金刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； n为 0-2， 0； S或者 NH时; X2为（CH2) n， n为 0-2, 0； S或者 NH时。 Or, R 6 and R 7 are:
Figure imgf000010_0001
Wherein R 13 and R w are each independently a substituent of any one of the following: H; (^-(: 6 fen); any one or two containing an alkoxy group including a halogen atom, d-Cs or a hydroxyl group; Or a three-substituted C "C 6 alkyl group; a C 2 - C 6 alkenyl group; any one, two or three substituted groups including a halogen atom, a dC 6 decyloxy group or a hydroxyl group ( 2 - ( 6 alkenyl; C 2 - ( 6 alkynyl; any one, two or three substituted C 2 - C 6 containing a halogen atom, C "C 6 of a hospitaloxy group or a hydroxyl group"Alkynyl; C 3 -C 6 cycloalkyl; any one, two or three substituted C 3 -C 6 cyclodecyl groups containing a halogen atom, a decyloxy group or a hydroxyl group of d-C e Aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, d-(indenyl, nitro, carboxyl, aldehyde, 'alkoxy, amine Any one, two or three substituted aryl groups, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substituted alkyl, nitro, carboxy, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio group a pyridyl group; containing any one of a halogen atom, a dC 4 fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group, two or three substituents furanyl; containing a halogen atom include, d- C 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio Any one, two or three substituted pyranyl groups including an ethylthio group; a mercapto group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, Any one, two or three substituted thienyl groups including a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a thiol group including a halogen atom, Cr"C 4 , a nitro group, a carboxyl group, an aldehyde group, Alkoxy, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted pyrrolyl groups such as a methylthio group or an ethylthio group; an alkanoyl group of dC 6 ; or any one or two containing a halogen atom or a hydroxyl group including a CrC e Or an alkanoyl group of three substituted d-C e ; an alkenoyl group of C 2 - C 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of d-C 6 or a hydroxyl group; C 2 - C s alkylene group; C 2 _C 6 alkynyl group; a halogen atom-containing optionally include, CrC alkoxy or hydroxy embankment 6 of the inner one, two or three substituents of C 2 - C 6 alkynyl of Acyl; C 3 -C 6 cyclodecanoyl; any one, two or three substituted C 3 -C 6 cyclodecanoyl groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; adamantane Formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; n is 0-2, 0; S or NH; X 2 is (CH 2 ) n , n is 0-2, 0; S or NH.

当 R R2， R3， 分别各自独立为:

Figure imgf000010_0002
其中 R15， R16各自独立为下列任意一种取代基： H; d- ( 6的烷基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d-Ce的烷基； C2- C6的烯基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 （2-( 6的 烯基； C2- Ce 炔基； 含有包括卤素原子、 CrC6的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 c2- c6的块基； c3-c6的环烷基； 含有包括 素原子、 c「 c6的烷氧基或羟基在内 的任意一个、两个或者三个取代的 c3- ce的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 啶基； 含有包括 素原子、 d- c4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 C「 ( 的烷基、 硝基、 羧基、 醛基、垸氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 -(:4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- ( 4的垸基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的吡喃基； 含有包括卤素原子、 d- c4的焼基、硝基、羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括 素原子、 C「 (；4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d- C6的垸酰基； 含有包括卤素原子、 CrC6的烷氧基或羟基在内的任意一个、 两个或者三个 取代的 Cr C6的烷酰基； C2- C6的烯酰基； 含有包括卤素原子、 CrC^烷氧基或羟基在内的 任意一个、两个或者三个取代的 c2- c6的烯酰基； c2- cs的炔酰基； 含有包括卤素原子、 的浣氧基或羟基在内的任意一个、 两个或者三个取代的 c2- c6的炔酰基； c3- c6的环烷酰基； 含有包括卤素原子、 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 -(]6的 环烷酰基； 金刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； X,为（CH ， n为 0-2， 0； S或者 NH时； X2为 (C¾) n， n为 0-2, 0; S或者 NH时； When RR 2 , R 3 , respectively, are independent:
Figure imgf000010_0002
Wherein R 15 and R 16 each independently are any one of the following substituents: H; d- ( 6 alkyl; any one or two containing a halogen atom, C "C 6 alkoxy group or a hydroxyl group" or a three-substituted alkyl group of d-Ce; a C 2 -C 6 alkenyl group; Any one, two or three substituted ( 2- ( 6 alkenyl; C 2 -C e alkynyl) containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; containing a halogen atom, CrC Any one, two or three substituted c 2 - c 6 block groups of 6 alkoxy groups or hydroxyl groups; c 3 -c 6 cycloalkyl groups; containing alkane including a prime atom, c "c 6 Any one, two or three substituted c 3 - c e cyclodecyl groups such as oxy or hydroxy; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridine; includes atoms of any element, d- c 4 embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two Or three substituted aryl groups; containing a halogen atom, C" (alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, B Any one, two or three substituted pyridyl groups including a thio group; containing an alkyl group including a halogen atom, -(: 4 , Any one, two or three substituted furanyl groups including a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two of an atom, d-( 4 thiol, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio or a three-substituted pyranyl group; a fluorenyl group including a halogen atom, d-c 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, and a thio, including any one, two or three substituents thienyl; comprising pigment containing atoms, C "(; 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, Any one, two or three substituted pyrrolyl groups such as a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group; a decanoyl group of d-C 6 ; an alkoxy group or a hydroxyl group including a halogen atom, CrC 6 Any one, two or three substituted Cr C 6 alkanoyl groups a C 2 -C 6 alkenoyl group; an enoyl group having any one, two or three substituted c 2 - c 6 groups including a halogen atom, a CrC alkoxy group or a hydroxyl group; c 2 - c s Any one, two or three substituted c 2 - c 6 alkynyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a c 3 - c 6 cycloalkanoyl group; Any one, two or three substituted -() 6 cycloalkanoyl groups of an atom, an alkoxy group or a hydroxyl group; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl ; pyranoyl; thiophene; pyrroyl; X, (CH, n is 0-2, 0; S or NH; X 2 is (C3⁄4) n , n is 0-2, 0; S Or NH;

， ， R7分别为：

Figure imgf000011_0001
其中 为下列任意一种取代基： H; Cr C6的垸基； 含有包括卤素原子、 d- ^的焼氧基 或羟基在内的任意一个、 两个或者三个取代的 d- CB ½垸基； C2- Ce 烯基； 含有包括卤素 原子、 C「C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的烯基； C2- (：6的 炔基;含有包括卤素原子、 的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-Ce 的炔基； C3- C6的环垸基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个 或者三个取代的( 3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、 d- C4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括 素原子、 ^- 的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 c4的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr ^的烧基、硝基、羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 CrG的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的噻吩基; 含有包括 素原子、 C「 ( 4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d- C6的垸酰基； 含 有包括卤素原子、 Cr 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的烷 酰基； C2- C6的烯酰基； 含有包括卤素原子、 C,- C6的烷氧基或羟基在内的任意一个、 两个或 者三个取代的 C2- C6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 C「 C6的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3- Ce的环垸酰基； 含有包括卤素 原子、 （ C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环烷酰基； 金 刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2)„， n为 0-2， 0； S或者 NH时; , , R 7 are:
Figure imgf000011_0001
Wherein is any one of the following substituents: H; a fluorenyl group of Cr C 6 ; any one, two or three substituted d-C B 1⁄2 containing a halogen atom, a decyloxy group or a hydroxyl group of d-^ embankment group; C 2 - C e alkylene group; containing optionally include halogen, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents of C 2 - C 6 alkenyl; C 2 - (: 6 alkynyl group; contain any alkoxy or hydroxy include halogen atoms, the inner one, two or three substituents of C 2 -C e alkynyl group; C 3 - C 6 cycloalkyl group of embankment ; contain any halogen atoms include, d-Ce alkoxy or hydroxy the embankment, including one, two or three substituents of (3 - C 6 cycloalkyl group embankment; aryl group; a benzyl group; furanyl; pyranyl ; thienyl; pyrrolyl; pyridyl; containing an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl group Any one, two or three substituted aryl groups, including an ethylthio group; Any one, two or three substituted alkyl, nitro, carboxy, aldehyde, decyloxy, amino, amido, carboxamido, fluorenyl, methylthio, ethylthio Pyridyl; containing any of a halogen atom, an alkyl group of c 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, or the like. , two or three substituted furanyl groups; containing a halogen atom, a halogen group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, Any one, two or three substituted pyranyl groups including an ethylthio group; an alkyl group including a halogen atom, CrG, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carbon amide any group, a mercapto group, methylthio, ethylthio, including one, two or three substituents thienyl; comprising pigment containing atoms, C "(alkyl, nitro, carboxyl, aldehyde, alkoxy 4 Base, amine group, amide group, carboxamide group, sulfhydryl group, Any thio, ethylthio, including one, two or three substituents pyrrolyl; d- C 6 acyl group of the embankment; contain any halogen atoms include, Cr or the embankment group including a hydroxyl, two Or a three-substituted alkanoyl group of d-C 6 ; a C 2 - C 6 alkenoyl group; any one, two or three substitutions including an alkoxy group including a halogen atom, C, -C 6 or a hydroxyl group; the C 2 - C 6 alkenyl group; C 2 - C 6 alkynyl group; a halogen atom includes contain any C, C 'C 6 alkoxy or hydroxy embankment inner one, two or three substituents of 2 - -; C 6 alkynyl group of group C e embankment ring C 3; includes optionally containing a halogen atom, (C6 alkoxy group or a hydroxyl group, including one, two or three substituents of C 3 - C 6 cycloalkyl of Acyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH 2 ), n is 0-2, 0 ; S or NH;

或者 R5， ， R7分别为：

Figure imgf000012_0001
其中^， 各自独立为下列任意一种取代基： H; d- C6的垸基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的垸基； C2- G的烯基； 含有包括卤素原子、 -Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的 烯基； C2- ( 6的炔基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2- ( 6的炔基； C3-C6的环烷基； 含有包括 素原子、 C,-C6的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括 素原子、 d- 4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-C ^烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 CrC4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr (：4的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 -(：4的烷基、硝基、羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- (：4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基; d-Ca的焼酰基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个 取代的 c「c6的垸酰基； C2- C6的烯酰基； 含有包括卤素原子、 d- 0；6的烷氧基或羟基在内的 任意一个、两个或者三个取代的 c2- Ce的烯酰基； C2-Ce的炔酰基； 含有包括卤素原子、 d_C6 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c2- c6的炔酰基； c3- c6的环垸酰基; 含有包括卤素原子、 C,- C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3-Ce的 环烷酰基； 金刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； Xi ¾ (CH2)„, n为 0 - 2， 0； S或者 NH时； ¾为 (CH ， n为 0-2， 0； S或者 NH时； Or R 5 , , R 7 are:
Figure imgf000012_0001
Wherein, each independently is any one of the following substituents: H; a fluorenyl group of d-C 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group - an alkyl group of C 6 ; an alkenyl group of C 2 - G; an alkenyl group containing any one, two or three substituted C 2 - C 6 groups including a halogen atom, a decyloxy group of -Ce or a hydroxyl group; C 2 - (6 alkynyl; comprising any one, two or three substituents of C 2 include a halogen atom, an alkoxy group or a hydroxyl dC including the e - (6 alkynyl; C 3 -C 6 of cycloalkyl; comprising any one, two or three of the substituents include C 3 prime atoms, C, -C 6 alkoxy or hydroxy embankment including - C 6 cycloalkyl group of embankment; aryl group; a benzyl group; furan a pyranyl group; a pyrenyl group; a pyrrolyl group; a pyridyl group; a fluorenyl group including a sulfonyl group, a d- 4 group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group Any one, two or three substituted aryl groups including a methylthio group and an ethylthio group; containing a halogen atom, dC^alkyl group, and a nitrate Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; any C r C alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio 4 including one, two or three Substituted furanyl; containing a halogen atom, Cr (: 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted pyranyl groups; containing a halogen atom, -(: 4 alkyl group, nitro group, carboxyl group, aldehyde group, Any one, two or three substituted thienyl groups including a methoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- (: 4 ) Any one, two or three substituted pyrrolyl groups including an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a decanoyl group of d-Ca; any one, two or three substituted c"c 6 decanoyl groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; a C 2 - C 6 enoyl group; Any one, two or three substituted c 2 - C e enoyl groups including a halogen atom, an alkoxy group of d- 0; 6 or a hydroxyl group; a C 2 -C e alkynyl group; Any one, two or three substituted c 2 - c 6 alkynyl groups of an atom, d_C 6 decyloxy or hydroxy; c 3 - c 6 cyclodecanoyl; containing a halogen atom, C, - any hydroxy group or a C 6 embankment inner one, two or three substituents of C 3 -Ce cycloalkyl group; Adamantane formyl, substituted adamantyl embankment formyl; aryl group; a benzyl group; furoyl; pyran formyl; thenoyl; pyrroyl; Xi ¾ (CH 2) " , n is 0 - 2, 0; When S or NH; 3⁄4 is (CH, n is 0-2, 0; S or NH;

或者 R5， Rs， R7分别为：

Figure imgf000013_0001
其中 R12为下列任意一种取代基： H; d- ( 的烷基； 含有包括卤素原子、 d- (^的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 Cr Ce的烷基； ^-^的烯基； 含有包括卤素 原子、 （^-( 6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 6的烯基； C2- ( 的 炔基;含有包括卤素原子、 d- C6的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C3 的炔基； C3- Ce的环垸基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、 两个 或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、 Cr 的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-C4 浣基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr ^的烷基、硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括 素原子、 C「( ,的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的噻吩基； 含有包括卤素原子、 Ct-C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； Cr Ce的垸酰基； 含 有包括卤素原子、 CrCe的垸氧基或羟基在内的任意一个、 两个或者三个取代的 （ - Ce的烷 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、两个或 者三个取代的 c2- c6的烯酰基;. c2-ce的炔酰基； 含有包括卤素原子、 d- (：6的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 c2-ce的炔酰基； c3- c6的环烷酰基； 含有包括卤素 原子、 Cr 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- Ce的环垸酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（C ) n， n为 0-2， 0； S或者 NH时； Or R 5 , R s , R 7 are:
Figure imgf000013_0001
Wherein R 12 is any one of the following substituents: H; d-(alkyl; any one, two or three substituted Cr C including a halogen atom, d- (a alkoxy group or a hydroxyl group) e alkyl; ^ - ^ alkenyl; include halogen atom-containing, (^ - alkoxy or hydroxy arbitrary (6, including one, two or three substituents of C 2 - (6 alkenyl; C 2 - (alkynyl; any one, two or three substituted C 2 -C 3 alkynyl groups including a halogen atom, an alkoxy group of d-C 6 or a hydroxyl group; C 3 - C e cyclic alkyl with; containing optionally include halogen atoms, C "C 6 alkoxy or hydroxy, including one, two or three substituents of C 3 - C 6 cycloalkyl group embankment; aryl group; a benzyl group; furan a pyranyl group; a pyrenyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a halogen atom, Cr, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group any thio, ethylthio, including one, two or three aryl group substituents; containing a halogen atom include, dC 4 Huan, nitro, carboxy Any one, two or three substituted pyridyl groups including an aldehyde group, an oxime group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and a halogen atom, d- Any one, two or three substituted furanyl groups such as an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group. Any one or two containing a halogen atom, an alkyl group of a Cr ^ group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Or a three-substituted pyranyl group; containing a sulfonyl group, C", fluorenyl, nitro, carboxy, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio Any one, two or three substituted thienyl groups including an ethylthio group; an alkyl group including a halogen atom, C t -C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group Base, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituents pyrrolyl; Cr C e of the embankment acyl; one, two or three substituents include a halogen atom contain any, CrC e the embankment or a hydroxyl group, including the (- C e alkanoyl; C 2 - C e alkylene group; containing optionally include halogen atoms, C "C 6 alkoxy or hydroxy, including one, two or a three-substituted c 2 - c 6 alkenoyl group; a c 2 -c e alkynyl group; containing any one, two or three including a halogen atom, d- (: 6 decyloxy group or hydroxyl group) a substituted c 2 -c e acetylenic group; c 3 - c 6 cycloalkanoyl; any one, two or three substituted C 3 - including a halogen atom, an alkoxy group of Cr or a hydroxyl group Cyclodecanoyl group of C e ; adamantyl, substituted adamantyl form; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrrolyl; (C) n , n is 0 -2, 0; S or NH;

或者 R5， R6， R7分别为：

Figure imgf000014_0001
其中 R13， R14各自独立为下列任意一种取代基： H; d- C6的烷基； 含有包括卤素原子、 d- 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的垸基； C2- (；6的烯基； 含有包括卤素原子、 CrCe的烷氧基或羟基在内的任意一个、 两个或者三个取代的（2-(：6的 烯基； C2- C6的炔基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、两个或者 三个取代的 C2- (6的炔基； C3- C6的环烷基； 含有包括卤素原子、 C,- C6的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3-C6的环垸基； 芳基； 苄基； 呋喃基；吡喃基； 噻吩基; 吡咯基； 吡啶基； 含有包括卤素原子、 d- ( 4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d (4的烷基、硝基、羧基、醛基、垸氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d - C4的垸基、 硝基、 羧基、 醒基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d-C4 浣基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 C「C4的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- (4的烧基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d-Ce的垸酰基； 含有包括卤素原子、 Cr 的烷氧基或羟基在内的任意一个、两个或者三个 取代的 C「 Cs的垸酰基； C2- Cs的烯酰基； 含有包括卤素原子、 Cr (6的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2- C6的烯酰基； C2- Ce的炔酰基； 含有包括! ¾素原子、 -Ce 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2-C6的炔酰基； C3-C6的环烷酰基; 含有包括卤素原子、 C,- C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- ( 6的 环烷酰基； 金刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰¾; )^ (C ) n， n为 0-2， 0； S或者 NH时; 为（C¾)„， n为 0-2， 0； S或者 NH时。 R2， R3， 分别各自独立为:
Figure imgf000015_0001
其中 Rn为下列任意一种取代基： ¾； C「 ( 的垸基； 含有包括卤素原子、 ^ 的垸氧基 或羟基在内的任意一个、 两个或者三个取代的（ C6的垸基； C2- C6的烯基； 含有包括卤素 原子、 （ Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2_C6 烯基； C2- ( 的 炔基;含有包括卤素原子、 Cr^的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2_C6 的炔基； C3- C6的环烷基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、两个 或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括 素原子、 C「 (：4的垸基、硝基、羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 (^-(：4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d-C4的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- (^的垸基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的批喃基； 含有包括 素原子、 （^-( 的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括 素原子、 d- C4的垸基、 硝基、 羧基、 醛基、垸氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d- C6的烧酰基； 含 有包括卤素原子、 C「C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- Ce的烷 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 Ct- Ce的垸氧基或羟基在内的任意一个、 两个或 者三个取代的 C2- C6的烯酰基； C2- Ce的炔酰基； 含有包括卤素原子'、 CrC6的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- Cs的炔酰基； C3- C6的环烷酰基； 含有包括卤素 原子、 C「CS的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环烷酰基； 金 刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（ )„， n为 0-2， 0； S或者蘭时； Or R 5 , R 6 , R 7 are:
Figure imgf000014_0001
Wherein R 13 and R 14 are each independently a substituent of any of the following: H; an alkyl group of d-C 6 ; any one, two or three containing a halogen atom, a hydroxyl group of d- or a hydroxyl group. Substituted d-C 6 fluorenyl; C 2 - (; 6 alkenyl; any one, two or three substituted ( 2 - (including a halogen atom, an alkoxy group of CrC e or a hydroxyl group) :; - C 2 C 6 alkynyl group; a C 6 alkenyl group containing optionally include halogen atoms, C "C 6 alkoxy or hydroxy, including one, two or three substituents of 2 - (6 alkynyl a C 3 -C 6 cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups containing a halogen atom, a C,-C 6 decyloxy group or a hydroxyl group; ; an aryl group; a benzyl group; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, D- (4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amino Any one, two or three substituted aryl groups, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Promoter, any one of D (alkyl, nitro, carboxyl, aldehyde, alkoxy embankment, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including 4, two or three a substituted pyridyl group; a fluorenyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, a awake group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted furanyl groups; containing a halogen atom, dC 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, Any one, two or three substituted pyranyl groups including a methylthio group and an ethylthio group; containing an alkyl group including a halogen atom, C "C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group groups, amide groups, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include a halogen atom-containing, d- (4 burning group, a nitro group, Carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl Any one, two or three substituted pyrrolyl groups such as a methylthio group or an ethylthio group; a decanoyl group of dC e ; or one or two containing an alkoxy group including a halogen atom, Cr, or a hydroxyl group; Or a three-substituted C"C s decanoyl group; a C 2 - C s enoyl group; a C containing any one, two or three substituents including a halogen atom, a Cr ( 6 decyloxy group or a hydroxyl group) alkenyl group of C 6 - 2; C 2 - C e alkynyl group;! ¾ comprise any pigment containing atoms, a hydroxyl group or a -Ce the embankment, including one, two or three substituents of C 2 -C 6 Alkynyl; C 3 -C 6 cycloalkanoyl; any one, two or three substituted C 3 - ( 6 ring) containing an alkoxy group including a halogen atom, C, -C 6 or a hydroxyl group Alkanoyl; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrole benzoyl; )^(C) n , n is 0-2 , 0; S or NH; (C3⁄4) „, n is 0-2, 0; S or NH. R 2 , R 3 , are each independently :
Figure imgf000015_0001
Wherein Rn is any one of the following substituents: 3⁄4; C"(fluorenyl); any one, two or three substituted (C 6 fluorenyl group containing a halogen atom, a fluorenyloxy group or a hydroxyl group) ; C 2 - C 6 alkenyl group; a halogen atom-containing include any, (the embankment of Ce alkoxy or hydroxy, including one, two or three substituents of C 2 _C 6 alkenyl; C 2 - (alkynyl Any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, a Cr alkoxy group or a hydroxyl group; a C 3 - C 6 cycloalkyl group; containing a halogen atom, Any one, two or three substituted C 3 -C 6 cycloalkyl groups such as alkoxy or hydroxy groups of dC e ; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; Pyridyl; containing a sulfonyl group, C" ( 4 : fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) Any one, two or three substituted aryl groups; containing a halogen atom, (^-(: 4 thiol, nitro, carboxy) Any one, two or three substituted pyridyl groups including an alkyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; 4 is any alkyl, nitro, carboxyl, aldehyde, alkoxy embankment, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents furan Any one containing a halogen atom, d-(^, sulfonyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio One, two or three substituted carboxy groups; containing a sulfhydryl group, (^-(alkyl, nitro, carboxyl, aldehyde, oxirane, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; a mercapto group including a sulfonate atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group Any of an amide group, a carboxamide group, a thiol group, a methylthio group or an ethylthio group D- containing optionally include a halogen atom, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents; and one, two or three substituents pyrrolyl; d- C 6 acyl burning C e alkanoyl; C 2 - C e alkylene group; include a halogen atom-containing, C t - any alkoxy or hydroxy C e embankment inner one, two or three substituents of C 2 - C 6 of Alkenoyl; C 2 -C e alkynyl; acetylene group containing any one, two or three substituted C 2 - C s including a halogen atom ', CrC 6 alkoxy group or a hydroxyl group; C 3 - a C 6 cycloalkyl group; contain any include halogen atoms, hydroxy group or a C embankment "C S inner one, two or three substituents of C. 3 - C 6 cycloalkyl group; a formyl adamantane , substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (), n is 0-2, 0; S or Lan time;

R5， R6, R7分别为：

Figure imgf000015_0002
其中 为下列任意一种取代基： H; d- Ce 垸基； 含有包括卤素原子、 d- Ce的垸氧基 或羟基在内的任意一个、 两个或者三个取代的 C「 ( 6的浣基； C2-C6的烯基； 含有包括卤素 原子、 c「c6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- (：6的烯基； C2- (6的 炔基;含有包括卤素原子、 CrCe的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3- C6的环垸基； 含有包括卤素原子、 C「Ce的垸氧基或羟基在内的任意一个、 两个 或者三个取代的( 3- C6的环烷基； 芳基；苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- ( 的烷基、硝基、羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 的浣基、 硝基、 羧基、 醒基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 C「 ( 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 ( 4的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括 素原子、 C「 C4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、 d- C4的烷基、硝基、羧基、醛基、烷氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； C「 C6的烷酰基； 含 有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 CrCe的烷 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、 两个或 者三个取代的 C2 C6的烯酰基； C2- Ce的炔酷基； 含有包括卤素原子、 d- (：6的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2 C6的炔酰基； C3- Ce的环垸酰基； 含有包括卤素 原子、 d-c6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c3- 的环烷酰基； 金 刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； ¾为（C ) n， η为 0-2， 0； S或者 ΝΗ时； R 5 , R 6 and R 7 are:
Figure imgf000015_0002
Wherein is any one of the following substituents: H; d-C e fluorenyl; any one, two or three substituted C" (including 6 ) containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce Alkyl; C 2 -C 6 alkenyl; containing halogen Atom, an optionally c "c embankment 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - (: 6 alkenyl; C 2 - (6 alkynyl; include a halogen atom-containing, CrC Any one, two or three substituted C 2 -C 6 alkynyl groups including an alkoxy group or a hydroxyl group of e ; a C 3 -C 6 cyclodecyl group; a fluorene containing a halogen atom, C "C e " any of a group or a hydroxy group including, two or three substituents of (3 - C 6 cycloalkyl; and aryl; benzyl; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridinyl; comprising Any one or two including a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) Or a three-substituted aryl group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, a awake group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methyl group, an ethyl group, and an ethyl group Any one, two or three substituted pyridyl groups; containing a halogen atom, C" (alkyl, nitro, carboxy , Any aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents furanyl; containing a halogen atom include, (4 Any one, two or three substituted pyrans of thiol, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio group; comprising pigment containing atoms, C "4 alkyl with C, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including any One, two or three substituted thienyl groups; containing an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group Any one, two or three substituted pyrrolyl groups such as a thio group or an ethylthio group; C"C 6 alkanoyl group; any one or two containing a halogen atom or a hydroxyl group including a halogen atom, dC e Or alkanoyl group of three or more substituted CrC e ; alkenoyl group of C 2 -C e ; Any one, two or three substituted C 2 C 6 enoyl groups including a halogen atom, C "C 6 alkoxy group or a hydroxyl group; C 2 - C e alkynyl group; containing a halogen atom , d- (: any 6 alkoxy or hydroxy, including one, two or three substituents of C 2 C 6 alkynyl group of; C 3 - C e embankment cycloalkyl group; a halogen atom-containing include, DC 6 Any one, two or three substituted c 3 -cycloalkanoyl groups such as alkoxy or hydroxy; adamantyl formyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyran Formyl; thiophene; pyrrolyl; 3⁄4 is (C) n , η is 0-2, 0; S or ΝΗ;

或者 R5， R6， R7分别为：

Figure imgf000016_0001
Or R 5 , R 6 , R 7 are:
Figure imgf000016_0001

其中^， Ru各自独立为下列任意一种取代基： H; C「 ( 6的烷基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C6的烷基； C2- (：6的烯基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或者三个取代的（2-(：6的 烯基； （2 的炔基； 含有包括卤素原子、 C「Ce的烷氧基或羟基在内的任意一个、两个或者 三个取代的 C2- C6的炔基； C3-Ce的环烷基； 含有包括 素原子、 d-Ce的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环烷基； 芳基；苄基；呋喃基；吡喃基； 噻吩基; 吡咯基； 吡啶基； 含有包括 素原子、 C「 (：4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 ( 4的垸基、硝基、羧基、 醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d-c的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的吡喃基； 含有包括卤素原子、 d- ^的垸基、硝基、羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 c「 c4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d-C6的烷酰基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个 取代的 C「 C6的烷酰基； C2-C6的烯酰基； 含有包括卤素原子、 Cr 的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2- C6的烯酰基； C2- Cfi的炔酰基； 含有包括卤素原子、 C「C6 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3-C6的环烷酰基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c3-c6的 环烷酰基； 金刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； ¾为（(¾)„， n为 0-2， 0； S或者 NH时； 为（CH ， n为 0-2, 0； S或者 NH时； Wherein, each of Ru, independently is any one of the following substituents: H; C" (alkyl group of 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group) C 6 alkyl; C 2 - (: 6 alkenyl; any one, two or three substituted ( 2- ( 6 olefin) containing a halogen atom, d- alkoxy group or a hydroxyl group) group; (2 alkynyl group; comprises contain any halogen atom, C "C e alkoxy or hydroxy group including one, two or three substituents of C 2 - C 6 alkynyl group; C 3 -C e a cycloalkyl group; any one, two or three substituted C 3 -C 6 cycloalkyl groups including a sulfhydryl group or a hydroxy group including a aryl group; d-Ce; aryl; benzyl; furanyl ; pyranyl; thienyl; pyrrolyl; pyridyl; containing a purine atom, C " ( 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, any mercapto, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, (4 embankment , Nitro, carboxyl, aldehyde, alkoxy, amine, amide group, carbonamide group, Any one, two or three substituted pyridyl groups including a mercapto group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, dc, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, Any one, two or three substituted furanyl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, a nitro group, a carboxyl group, an aldehyde group, and an anthracene group; Any one, two or three substituted pyranyl groups including an oxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a fluorenyl group containing a halogen atom, d-^ Any one, two or three substituted thienyl groups, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two of a halogen atom, c "c 4 thiol group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group" three or substituted pyrrolyl; dC 6 alkyl Group; a halogen atom content including; containing optionally include a halogen atom, an alkoxy group or a hydroxyl dC 6, including one, two or three substituents of C "C 6 alkanoyl; C 2 -C 6 alkenyl group of Any one, two or three substituted C 2 -C 6 enoyl groups such as a decyloxy group or a hydroxyl group of Cr; a C 2 -C fi alkynyl group; an alkoxy group containing a halogen atom, C "C 6 " Any one, two or three substituted C 2 -C 6 alkynyl groups, including a hydroxyl group or a hydroxyl group; a C 3 -C 6 cycloalkanoyl group; an alkoxy group or a hydroxyl group including a halogen atom, d- Any one, two or three substituted c 3 -c 6 cycloalkanoyl; adamantyl formyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene ; pyrroyl group; 3⁄4 is ((3⁄4)„, n is 0-2, 0; S or NH; (CH, n is 0-2, 0; S or NH;

或者 R5， R6， 分别为: L!^^^T X入 2 RK12 其中 R12为下列任意一种取代基： H; CrCe的垸基； 含有包括卤素原子、 -Cs的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d- (：6的垸基； C2- ( 6的烯基； 含有包括卤素 原子、 - 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- (：6的烯基； C2 - ( 6的 炔基；含有包括卤素原子、 ( - 的烧氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3- Ce的环烷基； 含有包括卤素原子、 CrCe的烷氧基或羟基在内的任意一个、 两个 或者三个取代的（3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 - 的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- 的垸基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、（^^的垸基、硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 .乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括 素原子、 d_C4 ½垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的噻吩基; 含有包括卤素原子、 (：4的烷基、 硝基、羧基、醛基、烷氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； CrC6的垸酰基； 含 有包括卤素原子、 Cr 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d-Ce的烷 酰基； C2- C6的烯酰基； 含有包括卤素原子、 d- Cfi的垸氧基或羟基在内的任意一个、 两个或 者三个取代的 C2-Ce的烯酰基； C2- Ce的炔酰基； 含有包括卤素原子、 -(6的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3_C6的环垸酰基； 含有包括卤素 原子、 -Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- Ce的环烷酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； ¾为 ¾)„， n为 0-2， 0； S或者 NH时； Or R 5 , R 6 , respectively: L!^^^TX into 2 R K 12 wherein R 12 is any of the following substituents: H ; a fluorenyl group of CrC e ; an alkoxy group containing a halogen atom, -Cs Any one, two or three substituted d-(: 6 fluorenyl groups; C 2 - ( 6 alkenyl group; containing a halogen atom, an alkoxy group or a hydroxyl group, etc.) One, two or three substituted C 2 - (: 6 alkenyl; C 2 - ( 6 alkynyl; containing any one or two including a halogen atom, an alkoxy group or a hydroxyl group three substituted C 2 -C 6 alkynyl group of; C 3 - C e cycloalkyl; contain any halogen atoms include, CrC e alkoxy or hydroxy group including one, two or three substituents of ( 3 -C 6 cycloalkyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing alkyl group including halogen atom, d-C 4 , nitro group, carboxyl group, aldehyde Any one, two or three substituted aryl groups including a base, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one or two containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Or a three-substituted pyridyl group; a thiol group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted furanyl groups; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, Any one, two or three substituted pyranyl groups including a fluorenyl group, a methylthio group, an ethylthio group; a aryl group, a d-C 4 1⁄2 fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, Any one, two or three substituted thienyl groups, including an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Containing any one or two including a halogen atom, (alkyl group of 4 , nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) Or a substituted triazole group; a decanoyl group of C r C 6 ; an alkanoyl group having any one, two or three substituted d-Ce including a halogen atom, an alkoxy group of Cr or a hydroxyl group; 2 - C 6 alkenoyl; any one, two or three substituted C 2 -C e alkenoyl group including a halogen atom, a d-C fi decyloxy group or a hydroxyl group; C 2 - C e alkynyl group; contains include halogen atoms, - or a hydroxyl group, any embankment (6, including one, two or three substituents of C 2 - C 6 alkynyl group; the ring acyl embankment of C 3 _C 6; comprising Any one, two or three substituted C 3 -C e cycloalkanoyl groups including a halogen atom, an alkoxy group of -Ce or a hydroxy group; adamantyl, substituted adamantyl formyl; aroyl; benzyl Acyl; furoyl; pyranoyl; thiophene; pyrrolyl; 3⁄4 is 3⁄4) , N-0-2, 0; S, or NH;

或者 R5， R6, R7分别为： .

Figure imgf000018_0001
Or R 5 , R 6 , R 7 are: .
Figure imgf000018_0001

其中 R13， R14各自独立为下列任意一种取代基： H; d- C6的垸基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- ( 的烷基； C2- 0>的烯基； 含有包括卤素原子、 C,- C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 6的 烯基； C2-C6的炔基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2- Cs的炔基； C3- C6的环垸基； 含有包括卤素原子、 d-Cs的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环烷基； 芳基；苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 （^-(：4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲疏基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 ( 4的烷基、硝基、羧基、醛基、垸氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d - C4的烷基、 硝基、 羧基、 醛基、 焼氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 0>的烷基、硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 —个、两个或者三个取代的吡喃基； 含有包括卤素原子、 d- C4的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- ( 4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d- C6的烷酰基； 含有包括卤素原子、 CrC6的烷氧基或羟基在内的任意一个、两个或者三个 取代的 C,-C6的烷酰基； C2-C6的烯酰基； 含有包括卤素原子、 - 的綜氧基或羟基在内的 任意一个、两个或者三个取代的 C2- C6的烯酰基； C2- C6的块酰基； 含有包括 素原子、 C「C6 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c2-c6的炔酰基； c3- c6的环垸酰基; 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c3- ^的 环烷酰基； 金刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（。 )„， n为 0- 2, 0； S或者 NH时； 为（C¾)。， n为 0-2, 0； S或者腿时。 Wherein R 13 and R 14 are each independently a substituent of any of the following: H; a fluorenyl group of d-C 6 ; any one, two or three groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; Substituted d-(alkyl; C 2 - 0>alkenyl; any one, two or three substituted C 2 - including a halogen atom, C, -C 6 alkoxy group or hydroxyl group (6 alkenyl; C 2 -C 6 alkynyl group; a halogen atom-containing optionally include, dC 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - C s alkynyl; a C 3 -C 6 cycloalkyl group; any one, two or three substituted C 3 -C 6 cycloalkyl groups including a halogen atom, a decyloxy group or a hydroxyl group of d-Cs; an aryl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (^-(: 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide) Any one, two or three substituted aryl groups including a carbamide group, a carbhydryl group, a thiol group, an ethylthio group, and an ethylthio group; (4 any alkyl, nitro, carboxyl, aldehyde, alkoxy embankment, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents of Pyridyl; containing an alkyl group including a halogen atom, d - C 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted furanyl groups; containing an alkyl group including a halogen atom, 0>, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl sulfide Any one, two or three substituted pyranyl groups including a thiol group; an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group Any one, two or three substituted thienyl groups, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d-( 4 alkyl group, nitro group, carboxyl group) , aldehyde group, alkoxy group, amine group, amide group, carboxamide group, sulfhydryl group, Any thio, ethylthio, including one, two or three substituents pyrrolyl; d- C 6 alkanoyl; contain any halogen atoms include, CrC alkoxy or hydroxy 6 including a two a substituted or three C, -C 6 alkanoyl; C 2 -C 6 alkenyl group; a halogen atom-containing include, - any mechanized or hydroxyl group including one, two or three substituents of C 6 alkenoyl C - 2; C 2 - C 6 acyl group of blocks; includes any pigment containing C atoms, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents of 2 -c 6 Alkynyl; c 3 - c 6 cyclodecanoyl; any one, two or three substituted c 3 - ^ containing a halogen atom, a decyloxy group or a hydroxyl group of dC 6 Cycloalkanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (.) „, n is 0-2, 0; S or NH; (C3⁄4)., n is 0-2, 0; S or leg.

当 R R2， R3， 分别各自独立为:

Figure imgf000019_0001
其中 R18， Rw各自独立为下列任意一种取代基： H; d- C6的烷基； 含有包括卤素原子、 d-c 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d- ( 6的烷基； C2- Cfi的烯基； 含有包括卤素原子、 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的 燥基； C2- ( 6的炔基； 含有包括卤素原子、 d C6的垸氧基或羟基在内的任意一个、 两个或者 三个取代的 C2_Ce 炔基； C3- Ce的环烷基； 含有包括卤素原子、 d- C6的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环垸基；芳基；苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- 的烷基、.硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d- (^的垸基、硝基、羧基、醛基、 烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d-C4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的咲喃基； 含有包括卤素原子、 d- ( 的垸基、 硝 基、 羧基、 醛基、 浣氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 Cr C4的垸基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 Ct- C4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d- 的烷酰基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、两个或者三个 取代的 d- 的垸酰基； C2-C3的烯酰基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的 任意一个、两个或者三个取代的 C2-C6的烯酰基； C2-C6的炔酰基； 含有包括卤素原子、 CrC6 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2-C6的炔酰基； C3- C6的环垸酰基； 含有包括卤素原子、 Cr 的烧氧基或羟基在内的任意一个、 两个或者三个取代的 C3- ( 6的 环烷酰基； 金刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（CH2)„， n为 0-2， 0； S或者 NH时; 为（CH2) n， n为 0-2, 0; S或者 NH时， When RR 2 , R 3 , respectively, are independent:
Figure imgf000019_0001
Wherein R 18 and R w are each independently a substituent of any of the following: H; an alkyl group of d-C 6 ; any one, two or three substitutions including a halogen atom, an alkoxy group of dc or a hydroxyl group; D-( 6 alkyl; C 2 -C fi alkenyl; any one, two or three substituted C 2 - C 6 dry groups containing a halogen atom, an alkoxy group or a hydroxyl group C 2 - ( 6 alkynyl; any one, two or three substituted C 2 _C e alkynyl group including a halogen atom, a decyloxy group or a hydroxyl group of d C 6 ; C 3 - C e a cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom, an alkoxy group of d-C 6 or a hydroxyl group; an aryl group; a benzyl group; a furyl group ; pyranyl; thienyl; pyrrolyl; pyridyl; containing an alkyl group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, Any one, two or three substituted aryl groups including a methylthio group and an ethylthio group; containing a halogen atom, d- (^ Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one, two or three of a halogen atom, an alkyl group of dC 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. a substituted fluorenyl group; containing a halogen atom, d-(indenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group, methylthio group, ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, a fluorenyl group of a Cr C 4 group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, C t - C 4 , a nitro group, a carboxyl group, an aldehyde group, an anthracene group Base, amine group, amide group, carboxamide group, sulfhydryl group, methylthio group Ethylthio, including any one, two or three substituents pyrrolyl; D- alkanoyl; containing optionally include a halogen atom, a hydroxyl group or a dC embankment 6 of the inner one, two or three substituents D-decanoyl; C 2 -C 3 enoyl; any one, two or three substituted C 2 -C 6 olefins including a halogen atom, an alkoxy group of d-Ce or a hydroxyl group Acyl; C 2 -C 6 alkynyl; any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, an alkoxy group of CrC 6 or a hydroxyl group; C 3 - C embankment 6 cycloalkyl group; a halogen atom-containing optionally include, Cr burn or hydroxy group including one, two or three substituents of C 3 - cycloalkyl group (6; adamantane formyl, substituted adamantyl carboxylic embankment Acyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH 2 ), n is 0-2, 0; S or NH; (CH 2 ) n , n is 0-2, 0; S or NH,

R5， R6, R7分别为：

Figure imgf000020_0001
其中 R9为下列任意一种取代基： H; Cr (^的烷基； 含有包括卤素原子、 C「 (：6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 Ct- C6的烷基； 02-(：6的烯基； 含有包括卤素 原子、 d- 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 的烯基； C2- ( 6的 炔基;含有包括卤素原子、 Cr C6的垸氧基或羟基在内的任意一个、两个或者三个取代的 C2-Ce 的炔基； C3- C6的环烷基； 含有包括卤素原子、 CrC6的垸氧基或羟基在内的任意一个、两个 或者三个取代 C3-C6的环垸基； 芳基；苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、（^-^的烷基、硝基、羧基、 醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-〇4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、（,_( 4的垸基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d C4的垸基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d- (^的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括 素原子、 d- ( 4的烷基、硝基、羧基、醛基、垸氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； C6的垸酰基； 含 有包括卤素原子、 d 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的垸 酰基； C2-C6的烯酰基； 含有包括卤素原子、 CrC6的烷氧基或羟基在内的任意一个、 两个或 者三个取代的 C2- C6的烯酰基； C2-C3的炔酰基； 含有包括卤素原子、 烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2-C6的炔酰基； C3- Ce的环烷酰基； 含有包括卤素 原子、 - 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- Ce的环垸酰基； 金 刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（C ) n， n为 0-2， 0； S或者 NH时； R 5 , R 6 and R 7 are:
Figure imgf000020_0001
Wherein R 9 is any one of the following substituents: H; an alkyl group of Cr (^; an arbitrary one, two or three substituted Cs including a halogen atom, a C: ( 6 alkoxy group or a hydroxyl group) An alkyl group of t -C 6 ; 0 2 -(: 6 alkenyl; any one, two or three substituted C 2 - (alkenes) including a halogen atom, a decyloxy group or a hydroxyl group of d- groups; C 2 - (6 alkynyl; contain any include halogen atoms, hydroxyl group, or embankment Cr C 6 inner one, two or three substituents of C 2 -C e alkynyl group; C 3 - a C 6 cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom, a decyloxy group or a hydroxyl group of CrC 6 ; an aryl group; a benzyl group; a furyl group ; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, (^-^ alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, fluorenyl) , methylthio, ethylthio, including any one, two or three aryl group substituents; containing a halogen atom include, d-4 alkyl square, a nitro group Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; , _ ( 4 thiol, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio, any one, two or three Substituted furanyl; containing a halogen atom including a halogen atom, d C 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, d-(^, alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, Any one, two or three substituted thienyl groups including a mercapto group, a methylthio group, an ethylthio group; a di-( 4 alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, Amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituents pyrrolyl group; a C 6 acyl embankment; includes any halogen atom-containing, d is a hydroxyl group or embankment, including one, two or three substituents embankment 6 of d- C acyl; C 2 -C 6 alkenyl group; a halogen atom-containing optionally include, CrC 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - C 6 alkenyl group of; C 2 -C An alkynyl group of 3 ; a C 2 -C 6 alkynyl group containing a halogen atom, an alkoxy group or a hydroxyl group; a C 3 -C e cycloalkanoyl group; Any one, two or three substituted C 3 -C e cyclodecanoyl groups including an atom, an alkoxy group or a hydroxyl group; an adamantyl formyl group, a substituted adamantyl form group; an aroyl group; a benzyl group; Formyl; pyranoyl; thiophene; pyrrolyl; (C) n , n is 0-2, 0; S or NH;

或者 ， ， R7分别为-

Figure imgf000020_0002
Or, R 7 is -
Figure imgf000020_0002

其中 Rw， 各自独立为下列任意一种取代基： H; d-C6的垸基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 - 的烷基； C2- (：6的烯基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 的 烯基； C2- ( 6的炔基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2- ( 6的炔基； c3- cfi的环垸基； 含有包括卤素原子、 c「 c6的垸氧基或羟基在内 的任意一个、两个或者三个取代的 c3- ce的环烷基；芳基；苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 c「 c4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、

Figure imgf000021_0001
硝基、羧基、醛基、 垸氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 -^的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d-c4 嫁基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、（^-( 4的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 c「c4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d_C6的烷酰基； 含有包括卤素原子、 c「c6的垸氧基或羟基在内的任意一个、两个或者三个 取代的 c「 C6的烷酰基； C2- C6的烯酰基； 含有包括 素原子、 C「 ( 6的烷氧基或羟基在内的 任意一个、两个或者三个取代的 c2- ce的烯酰基； c2- ce的炔酰基； 含有包括卤素原子、 c -c6 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3-Ce的环垸酰基； 含有包括卤素原子、 CrC6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- (6的 环垸酰基； 金刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（(¾)„， n为 0-2， 0； S或者腿时； 为（(¾)„， n为 0-2， 0; S或者 NH时; Wherein R w , each independently is any one of the following substituents: H ; a fluorenyl group of dC 6 ; any one, two or three substituted groups including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group Alkyl; C 2 - (: 6 alkenyl; any one, two or three substituted C 2 - (alkenyl; C 2 - containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group) (6 alkynyl group; includes any containing halogen atoms, C "C 6 alkoxy or hydroxy, including one, two, or Three substituted C 2 - (6 alkynyl group; c 3 - c fi embankment cycloalkyl group; one, two or three substituents include a halogen atom contain any, c "c embankment 6 alkoxy or hydroxy, including the c 3 - c e cycloalkyl; aryl; benzyl; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, c "c 4 alkyl with, a nitro group, a carboxyl group Any one, two or three substituted aryl groups, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group;
Figure imgf000021_0001
Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three of an atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Substituted furanyl; containing any of a halogen atom, a dc 4 graft, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and the like. one, two or three of the substituents pyranyl; include halogen atom-containing, (^ - (alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto 4 Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, c "c 4 sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group Base, amide group, carboxamide group, sulfhydryl group, methylthio group, ethyl sulphide Including any one, two or three substituents pyrrolyl; d_c 6 alkanoyl; includes any halogen atom-containing, c "c embankment 6 alkoxy or hydroxy, including one, two or three substituents of c"C 6 alkanoyl; C 2 -C 6 alkenoyl; containing any one, two or three substituted c 2 - c e including a prime atom, C " (alkoxy or hydroxy group of 6 ) Alkenyl group; c 2 - c e alkynyl group; any one, two or three substituted C 2 -C 6 alkynyl group containing a halogen atom, a c-C 6 alkoxy group or a hydroxyl group; a C 3 -Ce cyclodecanoyl group; any one, two or three substituted C 3 - ( 6 -cyclodecanoyl groups; adamantyl group, including a halogen atom, a decyloxy group of CrC 6 or a hydroxyl group; Substituting adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; ((3⁄4) „, n is 0-2, 0; S or leg; ((3⁄4)„, n is 0-2, 0; S or NH;

或者 R5， R6， ！^分别为-

Figure imgf000021_0002
其中^为下列任意一种取代基： H; C「Cfl 烷基； 含有包括卤素原子、（；-(；6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 C「C6的垸基； C2- C6的烯基； 含有包括卤素 原子、 CrC6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2-C6 烯基； C2- CB的 炔基;含有包括卤素原子、 -Ce的烧氧基或羟基在内的任意一个、两个或者三个取代的 C2_CB 的炔基； C3- C6的环烷基； 含有包括卤素原子、 C「C6的垸氧基或羟基在内的任意一个、两个 或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 C4的烷基、硝基、羧基、醛基、院氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- ( 4的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- (：4的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 c,- c4 烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、 Cr ( 4的垸基、硝基、羧基、醛基、垸氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d-c 的烷酰基； 含 有包括卤素原子、 （ Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的垸 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或 者三个取代的 C2- C6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 C「 (：6的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3-Ce的环烷酰基； 含有包括卤素 原子、 Cr 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环烷酰基； 金 刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； X^ (CH2) n， η为 0-2， 0； S或者 ΝΗ时; Or R 5 , R 6 , ! ^ separately -
Figure imgf000021_0002
Wherein ^ is any of the following substituents: H; C "C fl alkyl; any one, two or three substituted Cs including a halogen atom, (; - (; 6 alkoxy or hydroxy group) "C 6 alkyl with; C 2 - C 6 alkenyl group; a halogen atom-containing include, CrC 6 alkoxy or hydroxy embankment, including any one, two or three substituents of C 2 -C 6 alkenyl group; An alkynyl group of C 2 - C B ; an alkynyl group containing any one, two or three substituted C 2 _C B groups including a halogen atom, an alkoxy group or a hydroxyl group of -Ce; a ring of C 3 - C 6 alkyl; include halogen atom-containing, C "C 6 alkoxy or hydroxy embankment, including any one, two or three substituents of C 3 - C 6 cycloalkyl group; an aryl group; a benzyl group; furanyl; Pyranyl; thienyl; pyrrolyl; pyridyl; containing alkyl group including a halogen atom, C 4 , nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide Any one, two or three substituted aryl groups including a thiol group; an alkyl group including a halogen atom, dC 4 , a nitro group, a carboxyl group Any one, two or three substituted pyridyl groups, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- ( 4 alkyl, nitrate Any one, two or three substituted furanyl groups including a carboxy group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two of d-(: 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio or a three-substituted pyranyl group; including a halogen atom, c, -c 4 alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, and ethyl group Any one, two or three substituted thienyl groups including a thio group; containing a halogen atom, Cr ( 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carbon amide) Any one, two or three substituted pyrrolyl groups including a thiol group, a thiol group, a methylthio group, an ethylthio group; an alkanoyl group of dc; containing any one including a halogen atom, a decyloxy group or a hydroxyl group of Ce , two or three substituted d-C 6 decanoyl groups; C 2 - C e Any one, two or three substituted C 2 -C 6 alkenoyl groups including a halogen atom, an alkoxy group or a hydroxyl group of d-; a C 2 -C 6 alkynyl group; a halogen atom, C "(: any embankment 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - C 6 alkynyl group; a cycloalkyl group of C 3 -C e; include a halogen atom-containing Any one, two or three substituted C 3 -C 6 cycloalkanoyl groups, alkoxy or Cr, alkanoyl formyl, substituted adamantyl; aroyl; benzoyl; furan Acyl; pyranoyl; thiophene; pyrrolyl; X^(CH 2 ) n , η is 0-2, 0; S or hydrazine;

或者 R5， R6, R7， ， ， ¾。分别为：

Figure imgf000022_0001
其中 R13， R14各自独立为下列任意一种取代基： H; d-C6的烷基； 含有包括卤素原子、 CrC6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 (；6的烷基； C2-C6的烯基； 含有包括卤素原子、 C 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的 烯基； C2- Ce 炔基； 含有包括卤素原子、 C「Ce的烷氧基或羟基在内的任意一个、两个或者 三个取代的 C2-C6的炔基； C3- Ce的环烷基； 含有包括卤素原子、 Ct-Ce的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3-C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d- 的烷基、硝基、羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基 ·,含有包括卤素原子、 CrC4的烷基、 硝基、 羧基、 醛基、 焼氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- C4的院基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基；含有包括卤素原子、 (：4的垸基、硝基、羧基、醛基、 焼氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 ί基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； c「 c6的烷酰基； 含有包括卤素原子、 c「ce的烷氧基或羟基在内的任意一个、两个或者三个 取代的 d- c6的烷酰基； c2-ce的烯酰基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的 任意一个、两个或者三个取代的 c2- c6的烯酰基； c2- c6的炔酰基； 含有包括卤素原子、 C -Ce 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c2- c6的炔酰基； c3- c6的环垸酰基; 含有包括卤素原子、 -( 6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 （3-( 6的 环垸酰基； 金刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为(。 )„， n为 0-2， 0； S或者 NH时； 为 (C )„， n为 0-2， 0； S或者 NH时。 Or R 5 , R 6 , R 7 , , , 3⁄4. They are:
Figure imgf000022_0001
Wherein R 13 and R 14 are each independently a substituent of any of the following: H; an alkyl group of dC 6 ; any one, two or three substituted groups including a halogen atom, a decyloxy group of CrC 6 or a hydroxyl group; (; 6 alkyl; C 2 -C 6 alkenyl group; includes any containing halogen atoms, C alkoxy or hydroxy group including one, two or three substituents of C 2 - C 6 alkenyl group; C 2 -C e alkynyl; any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, an alkoxy group of C "C e or a hydroxyl group; C 3 - C e a cycloalkyl group; any one, two or three substituted C 3 -C 6 cyclodecyl groups containing a halogen atom, an alkoxy group of C t -C e or a hydroxyl group; an aryl group; a benzyl group; Furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted aryl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- Any one, two or three substituted pyridyl groups including an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Any one or two containing a halogen atom, an alkyl group of CrC 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Or three substituted furanyl groups; containing a halogen atom, d-C 4 , a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methyl group, Any one, two or three substituted pyranyl groups including an ethylthio group; containing a halogen atom, (: 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, Any one, two or three substituted thienyl groups including a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, Alkoxy group, amine group, Any one, two or three substituted pyrrolyl groups such as an amide group, a carboxamide group, a yl group, a methylthio group, an ethylthio group; c" an alkanoyl group of c 6 ; containing a halogen atom, c "c e Any one, two or three substituted d-c 6 alkanoyl groups such as alkoxy or hydroxy; c 2 -c e acyl; containing a halogen atom, d- alkoxy or hydroxy group Any one, two or three substituted c 2 - c 6 alkenoyl groups; c 2 - c 6 alkynyl group; any one containing a halogen atom, a C-Ce alkoxy group or a hydroxyl group; Two or three substituted c 2 - c 6 alkynyl groups; c 3 - c 6 cyclodecanoyl groups; containing any one, two or three including a halogen atom, - ( 6 decyloxy group or hydroxyl group) Substituted ( 3- ( 6 -cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; „, n is 0-2, 0; S or NH; (C)„, n is 0-2, 0; S or NH.

另外优选地，该类化合物或其在 物学上可接受的盐是以药物组合物的形式，或单独， 或与药物学上可接受的载体或赋形剂联合提供。 本发明还提供了包括上述化合物的药物， 用于预防和 /或治疗代谢紊乱性疾病（包括但不局限于糖尿病、 胰岛素抵抗和肥胖症)、 心 血管疾病和神经退行性疾病 （'如 Alzheimer' s病）等。  Further preferably, such a compound or a physiologically acceptable salt thereof is provided in the form of a pharmaceutical composition, either alone or in combination with a pharmaceutically acceptable carrier or excipient. The present invention also provides a medicament comprising the above compound for preventing and/or treating metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases ('such as Alzheimer' s disease) and so on.

再一方面， 本发明涉及预防和 /或治疗代谢紊乱性疾病 （包括但不局限于糖尿病、 胰 岛素抵抗和肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病）等的方法。 该 方法包括对需要或愿意接受治疗或预防的对象， 给予有交女量的、 选择性地调节胰髙血糖素 样肽一 1受体的化合物或其药物学上可接受的盐， 以预防或治疗上述疾病或症状。优选地， 上述代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症)、 心血管疾病和神 经退行性疾病 （如 Alzheimer' s病）等通过给予有效量的由以下通式 I至 VI任意一个表 示的化合物或其药物学上可接受的盐来预防或治疗：  In a further aspect, the invention relates to a method of preventing and/or treating metabolic disorders, including but not limited to diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease. The method comprises administering to a subject in need or willingness to receive treatment or prevention a compound having a fair amount of a glucagon-like peptide-1 receptor or a pharmaceutically acceptable salt thereof for preventing or Treat the above diseases or symptoms. Preferably, the above metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease), etc., by administering an effective amount of the following Formula I to Any of the compounds VI or a pharmaceutically acceptable salt thereof for prevention or treatment:

Figure imgf000023_0001
Figure imgf000023_0001

III III

Figure imgf000023_0002
Figure imgf000023_0002

VI VI

IV V 及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂化 物或其金属配合物。 IV V And all of its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

其中 X， Υ, Z分别为（CH2) n， n为 0 - 2， 氧， 硫或氮。 Wherein X, Υ, Z are (CH 2 ) n , and n is 0 - 2, oxygen, sulfur or nitrogen.

其中 R2， R3， 各自独立地为下列任意一种取代基： 氢； 卤素； 烷弪； 环烷烃； 羟 基； 硝基； 羧基； 醛基； 烷氧基； 胺基； 胺垸基； 酰胺基； 碳酰胺基； 巯基； 垸硫基； 醚; 硫醚； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。 Wherein R 2 , R 3 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkane; hydroxy; nitro; carboxy; aldehyde; alkoxy; amine; amine sulfhydryl; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R5， R6， R7各自独立地为下列任意一种取代基： 氢； 烷烃； 环烷烃； 烷氧基； 胺基； 胺 烷基； 酰胺基； 碳酰胺基； 烷硫基； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代 或未取代的呋喃基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡 咯基。 R 5 , R 6 , R 7 are each independently any one of the following substituents: hydrogen; alkane; cycloalkane; alkoxy; amine; amine alkyl; amide; carboxamide; alkylthio; Unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

另一方面， 本发明涉及联合制剂， 该联合制剂包括一种具有选择性调节胰高血糖素样 肽一 1 受体， 尤其是激活该受体功能的化合物， 或其药物学上可接受的盐， 或单独， 或与 药物学上可接受的载体或赋形剂组合存在。 该化合物具有以下通式的结构-  In another aspect, the present invention relates to a combination preparation comprising a compound having a selective modulation of a glucagon-like peptide-1 receptor, particularly a function of activating the receptor, or a pharmaceutically acceptable salt thereof Or alone or in combination with a pharmaceutically acceptable carrier or excipient. This compound has the structure of the following formula -

Figure imgf000024_0001
Figure imgf000024_0001

III III

Figure imgf000024_0002
Figure imgf000024_0002

IV V VI  IV V VI

及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂化 物或其金属配合物。 And all of its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

其中 X， Υ, Z分别为 ((¾)„， n为 0-2， 氧， 硫或氮。  Where X, Υ, Z are ((3⁄4)„, n is 0-2, oxygen, sulfur or nitrogen.

其中 R R2， R3， R4各自独立地为下列任意一种取代基： 氢； 卤素； 烷烃； 环垸烃； 轻 基； 硝基； 羧基； 醛基； 垸氧基； 胺基； 胺烷基； 酰胺基； 碳酰胺基； 巯基； 烷硫基； 醚; 硫醚； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。 Wherein RR 2 , R 3 , R 4 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkyl; light base; nitro; carboxy; aldehyde; methoxy; amine; Amide; carboxamide; mercapto; alkylthio; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; Substituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

， Ra, R7各自独立地为下列任意一种取代基： 氢； 垸烃； 环垸烃； 烷氧基； 胺基； 胺 垸基； 酰胺基； 碳酰胺基； 烷硫基； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代 或未取代的呋喃基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡 咯基。 , Ra, R 7 are each independently any one of the following substituents: hydrogen; anthracene; a cyclic alkane; an alkoxy group; an amine group; an amine group; an amide group; a carboxamide group; an alkylthio group; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

本发明提供了包括上述联合制剂的药盒。 本发明还进一步提供了应用上述联合制剂用 于预防和 /或治疗代 i射紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症)、 心血 管疾病和神经退行性疾病 （如 Alzheimer' s病）等， 达到选择性地激动胰高血糖素样肽一 1受体的药效， 改善患者的症状和生命质量。  The present invention provides a kit comprising the above combined preparation. The present invention still further provides the use of the above-described combination preparation for the prevention and/or treatment of a disorder (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer' s disease), etc., to achieve selective stimulation of the glucagon-like peptide-1 receptor, improve the patient's symptoms and quality of life.

为了阐明发明内容且不受其局限， 对发明分成以下几个小节进行详细描述。  In order to clarify the contents of the invention and not to be limited thereto, the invention will be described in detail in the following subsections.

A定义  A definition

除非另有定义， 本发明所用的技术和科学上的术语， 与本发明所属领域的通用技术的 一般理解具有相同意义。 本处提到的来源于基因库和其他数据库的所有专利， 申请， 公布 的申请和其他出版物和序列被全面收入引用作为参考。 如果本节阐明的定义与本专利参用 的来源于基因库和其他数据库的所有专利， 申请， 公布的申请和其他出版物和序列被收入 和引用的定义阐述相反， 或不一致时， 以本节阐明的定义为准。  The technical and scientific terms used in the present invention have the same meaning as the general understanding of the general art in the field to which the invention pertains, unless otherwise defined. All patents, applications, published applications and other publications and sequences derived from the Gene Bank and other databases referred to herein are referenced in full revenue. If the definitions set forth in this section are inconsistent with, or inconsistent with, all patents, applications, published applications, and other publications and sequences derived from the Gene Bank and other databases referenced in this patent, or inconsistent, The definition of clarification shall prevail.

本文所用， "一"或 "一个"指 "至少一个" 或 "一个或多个"。  As used herein, "a" or "an" refers to "at least one" or "one or more."

本文所用， "代谢紊乱性疾病"系指由各种原因造成的糖、 脂肪或蛋白质等代谢失调 而引起的相关症状和 /或疾病。  As used herein, "metabolic disorder" refers to a related symptom and/or disease caused by metabolic disorders such as sugar, fat or protein caused by various causes.

本文所用， "糖尿病"指一种多病因的代谢性疾病， 特点是慢性高血糖， 伴随因胰岛 素分泌及 /或作用缺陷引起的糖、 脂肪和蛋白质代谢紊乱。 随着糖尿病得病时间的延长， 身体内的代谢紊乱如得不到很好地控制， 可导致眼、 肾、 神经、 血管和心脏等组织等器官 的慢性并发症， 以致最终发生失明、 下肢坏疽、 尿毒症、 脑中风或心肌梗死， 甚至危及生 命。  As used herein, "diabetes" refers to a multi-pathogenic metabolic disease characterized by chronic hyperglycemia accompanied by disorders of sugar, fat and protein metabolism caused by insulin secretion and/or dysfunction. As the time of diabetes is prolonged, the metabolic disorders in the body are not well controlled, leading to chronic complications of tissues such as the eyes, kidneys, nerves, blood vessels and heart, resulting in blindness, gangrene in the lower limbs, Uremic, stroke or myocardial infarction, even life-threatening.

本文所用， "胰岛素抵抗"是指体内周围组织对胰岛素的敏感性降低， 肌肉、 脂肪等 靶组织对胰岛素促进葡萄糖摄取的作用发生了抵抗。胰岛素抵抗普遍存在于 2型糖尿病中， 几乎占 90%以上， 是 2型糖尿病的发病主要因素之一。  As used herein, "insulin resistance" refers to a decrease in the sensitivity of tissues surrounding the body to insulin, and target tissues such as muscles and fats are resistant to insulin-induced glucose uptake. Insulin resistance is prevalent in type 2 diabetes, accounting for more than 90%, and is one of the main factors in the development of type 2 diabetes.

本文所用， "肥胖症"是指体内脂肪的量过多， 男人体重超过理想体重的 25%或女人 体重超过理想体重的 30%的现象。 遗传因素、 下丘脑病患、 内分泌紊乱、 饮食过量和活动 太少都是产生肥胖症的原因。  As used herein, "obesity" refers to an excess of body fat, a male weighing more than 25% of the ideal body weight, or a woman weighing more than 30% of the ideal body weight. Genetic factors, hypothalamic disease, endocrine disorders, overeating and too little activity are all causes of obesity.

本文所用， "阿尔茨海默病（Alzheimer' s Disease, AD, 又称早老性痴呆 Alzheimer' s dementia)是一种神经系统的进行性蜕变性疾病， 临床上表现为智力水平的慢性削弱及记 忆的慢性丢失。  As used herein, "Alzheimer's Disease (AD), also known as Alzheimer's dementia) is a progressive degeneration of the nervous system, clinically characterized by chronic impairment of intelligence and memory. Chronic loss.

本文所用， "心血管疾病"包括心脏病、 肺心病、 高血压和高脂血症等。 具有 "发病 率高， 死亡率高， 致残率高， 复发率高" 以及 "并发症多"的特点。 As used herein, "cardiovascular disease" includes heart disease, pulmonary heart disease, hypertension, and hyperlipidemia. With "onset The rate is high, the mortality rate is high, the disability rate is high, the recurrence rate is high, and the "complication is more".

本文所用的用于治疗某一特定疾病的化合物的 "有效量" 指足够改善或在某种程度 上减轻与此病相伴的症状的量。 这一剂量可以单一剂量给药， 也可按照治疗方案给药。 这 一剂量可治愈疾病， 但典型的是为了改善该症状而给药。 为改善症状重复给药可能是需要 的。  As used herein, an "effective amount" of a compound for treating a particular condition refers to an amount sufficient to ameliorate or to some extent alleviate the symptoms associated with the disease. This dose can be administered in a single dose or in accordance with a therapeutic regimen. This dose cures the disease, but is typically administered to improve the condition. Repeated administration to improve symptoms may be desirable.

本文所用， "药物学上可接受的盐、 酯或其他衍生物" 包括领域技术人员用已知方 法易于制备的任何盐， 酯或衍生物。 这样衍生和生成的化合物可对动物和人给药， 不具有 毒性作用。 该化合物或是具有药物活性， 或是药物前体。  As used herein, "pharmaceutically acceptable salts, esters or other derivatives" include any salt, ester or derivative which is readily prepared by those skilled in the art using known methods. The compounds thus derived and produced can be administered to animals and humans without toxic effects. The compound is either pharmaceutically active or a prodrug.

本文所用， "治疗"指疾病和症状用任何方式得以改善， 或其他有益的改变。 治疗也 包括本发明化合物在药物上的应用。  As used herein, "treatment" means that the disease and symptoms are improved in any way, or other beneficial changes. Treatment also includes the use of the compounds of the invention in medicine.

本文所用， 给予某一特定药物组合物 "改善" 某一特定疾病的症状是指任何减轻， 无论永久的， 临时的， 长时期的， 短暂的， 都能归因于或与该药物组合物的施用有关。  As used herein, administration of a particular pharmaceutical composition to "improve" the symptoms of a particular disease means any reduction, whether permanent, temporary, prolonged, transient, can be attributed to or associated with the pharmaceutical composition. Relevant application.

本文所用， "基本上纯" 是指足够均匀， 通过本领域技术人员为评价纯度使用的标 准分析方法探测不出杂质， 所述标准分析方法有如薄层层析法（TLC)， 凝胶电泳和高效液 相色谱法 （HPLC)。 或者足够纯也指即使进一步纯化也不能改变该物质可探测到的理化特 性， 例如酶活性和生物活性。 用于纯化化合物制得基本上化学纯的方法， 是本领域技术人 员所公知的。 然而基本上化学纯的化合物可以是立体异构体或同分异构体的混合物。 在这 种情况下， 进一步纯化也许会增加化合物的比活性。  As used herein, "substantially pure" means sufficiently uniform that no impurities can be detected by standard analytical methods used by those skilled in the art to evaluate purity, such as thin layer chromatography (TLC), gel electrophoresis, and High performance liquid chromatography (HPLC). Or sufficiently pure also means that even further purification does not alter the physicochemical properties detectable by the substance, such as enzymatic activity and biological activity. Methods for producing substantially chemically pure compounds for purification are well known to those skilled in the art. However, a substantially chemically pure compound can be a stereoisomer or a mixture of isomers. In this case, further purification may increase the specific activity of the compound.

本文所用， "药物前体"是指一种体内给药的化合物， 该化合物可被代谢， 或转化为 生物学上、 药物学上或治疗学上的活性形式。 为了制造药物前体， 药物活性化合物将被修 饰， 使该活性化合物通过代谢过程再产生。 药物前体可被设计成改变其代谢稳定性， 或运 输特性的前体， 以掩盖其副作用或毒性， 改良药物的味觉， 或改变其他特性。 凭借药代动 力学及药物体内代谢的知识， 一旦药物学上活性化合物为已知， 本领域技术人员就可以设 计出该化合物的药物前体。 [_参 Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, 1985, pages 388-392]。  As used herein, "prodrug" refers to a compound that is administered in vivo and which can be metabolized or converted into a biologically, pharmaceutically or therapeutically active form. To produce a prodrug, the pharmaceutically active compound will be modified to reproduce the active compound by metabolic processes. Prodrugs can be designed to alter their metabolic stability, or to transport precursors of properties, to mask their side effects or toxicity, to improve the taste of the drug, or to alter other properties. By virtue of pharmacokinetics and knowledge of the metabolism of the drug in the body, once the pharmaceutically active compound is known, one skilled in the art can design a prodrug of the compound. [_See Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, 1985, pages 388-392].

术语 "基本上"相同或均匀或相似， 按照本领域技术人员对相关技术的理解可在上下 文中有所改变， 并且一般为至少 70%， 优选为至少 80°/。， 更优为至少 90%, 最优为至少 95% 相同。  The term "substantially" is the same or uniform or similar, and the understanding of the relevant art by those skilled in the art may vary in the context and is generally at least 70%, preferably at least 80°/. , preferably at least 90%, optimally at least 95% identical.

这里所用的 "组合物"指任何混合物。 可以是溶液、 混悬液、 液体、 粉末、 油膏、 水 性的、 非水性的或它们的任何组合。  As used herein, "composition" refers to any mixture. It may be a solution, suspension, liquid, powder, ointment, aqueous, non-aqueous or any combination thereof.

这里所用的 "联合"指两种或多种之间的任何联合。  As used herein, "union" refers to any association between two or more.

这里使用的术语 "对象"包括人和动物， 例如， 狗， 猫， 牛， 猪， 啮齿动物等。 有经 验的实施者应可理解对象为适于并愿意对糖尿病及其并发症进行治疗和预防。  The term "object" as used herein includes humans and animals, for example, dogs, cats, cows, pigs, rodents, and the like. Experienced practitioners should understand that the subject is suitable and willing to treat and prevent diabetes and its complications.

这里使用的任何保护性基团， 氨基酸和其他化合物的缩写， 与它们通用的、 公认的缩 写或 IUPAC- IUB委员会颁布生化命名一致， 除非特别说明。 B胰高血糖素样肽一 1受体调节剂 Any of the protective groups, abbreviations of amino acids and other compounds used herein, are consistent with their general, recognized abbreviations or the biochemical nomenclature issued by the IUPAC-IUB Commission, unless otherwise stated. B glucagon-like peptide-1 receptor modulator

本发明提供胰高血糖素样肽一 1受体功能的调节剂，增加了预防和 /或治疗代谢紊乱性 疾病（包括但不局限于糖尿病、胰岛素抵抗和肥胖症)、心血管疾病和神经退行性疾病（如 Alzheimer' s病） 等药物的成员。 本发明涉及由以下通式 I至 VI任意一个表示的化合物， 或其药物学上可接受的盐：  The present invention provides a modulator of glucagon-like peptide-1 receptor function, which increases the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases. A member of a drug such as a sexually transmitted disease (such as Alzheimer's disease). The present invention relates to a compound represented by any one of the following formulae I to VI, or a pharmaceutically acceptable salt thereof:

Figure imgf000027_0001
Figure imgf000027_0001

III

Figure imgf000027_0002
III
Figure imgf000027_0002

及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂化 物或其金属配合物。  And all of its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

其中， X， Υ, Z分别为（C¾) n， n为 0-2， 氧， 硫或氮。 Where X, Υ, Z are (C3⁄4) n , n is 0-2, oxygen, sulfur or nitrogen.

其中 R1 R2， ， 各自独立地为下列任意一种取代基： 氢； 卤素； 烷烃； 环烷烃； 羟 基； 硝基； 羧基； 醛基； 烷氧基； 胺基； 胺垸基； 酰胺基； 碳酰胺基； 巯基； 浣硫基； 醚; 硫醚； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。 Wherein R 1 R 2 , , each independently is any one of the following substituents: hydrogen; halogen; alkane; cycloalkane; hydroxy; nitro; carboxy; aldehyde; alkoxy; amine; aminyl; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R5， ¾, R7各自独立地为下列任意一种取代基： 氢； 垸烃； 环垸烃； 烷氧基； 胺基； 胺 垸基； 酰胺基； 碳酰胺基； 烧硫基； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代 或未取代的呋喃基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡 咯基。 R 5, ¾, R 7 are each independently any of the following substituents: hydrogen; hydrocarbon embankment; cyclic hydrocarbon embankment; alkoxy; amino; alkyl with an amine; amide group; carboxamide group; burning thio; substituted Or an unsubstituted aryl group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group.

本发明的化合物可以是一个特定的立体异构体， 例如 R-或 S-构型， 或它们的混合物， 例如， 外消旋混合物。 这里考虑的化合物包括所有具有药物活性的化合物种类， 或其溶液 或混合物。 还包括其水合类型， 例如这些化合物的水溶液， 水解产物或电离产物； 并且这 些化合物可含有不同数量的结合水分子。 本发明的化合物可按照任何合适的方法来制备或合成。 优选地， 用以下面 F节中引证 的合成法制备该化合物。 The compound of the present invention may be a specific stereoisomer, such as the R- or S-configuration, or a mixture thereof, for example, a racemic mixture. Compounds contemplated herein include all classes of pharmaceutically active compounds, or solutions or mixtures thereof. Also included are hydration types thereof, such as aqueous solutions, hydrolysates or ionized products of these compounds; and these compounds may contain varying amounts of bound water molecules. The compounds of the invention may be prepared or synthesized according to any suitable method. Preferably, the compound is prepared by the synthetic procedure cited in Section F below.

另外优选地，该化合物或其药物学上可接受的盐以药物组合物的形式提供，或者单独， 或者与一种药物学上可接受的载体或赋形剂结合。  Further preferably, the compound or a pharmaceutically acceptable salt thereof is provided in the form of a pharmaceutical composition, either alone or in combination with a pharmaceutically acceptable carrier or excipient.

本发明的化合物可用任何合适的酸以其药物学上可接受的盐的形式来制备。 例如， 无 机酸如盐酸、 氢溴酸、 硝酸、 硫酸、 磷酸等； 有机酸诸如甲酸、 乙酸、 丙酸、 苯甲酸、 马 来酸、 富马酸、 琥珀酸、 酒石酸、 柠檬酸等； 烷基磺酸如甲基磺酸、 乙基磺酸等； 芳基磺 酸如苯磺酸、 对甲苯磺酸等均可使用。  The compounds of the invention may be prepared in the form of their pharmaceutically acceptable salts with any suitable acid. For example, inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.; organic acids such as formic acid, acetic acid, propionic acid, benzoic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, citric acid, etc.; A sulfonic acid such as methanesulfonic acid or ethylsulfonic acid; an arylsulfonic acid such as benzenesulfonic acid or p-toluenesulfonic acid can be used.

C治疗和预防方法  C treatment and prevention methods

本发明涉及用于预防和 /或治疗代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素 ί氏 抗和肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病）等的方法。 该方法包 括对需要或愿意接受治疗或预防的对象， 给予有效量的、 选择性地激动胰高血糖素样肽一 1受体的化合物或其药物学上可接受的盐来治疗或预防上述疾病或症状。  The present invention relates to methods for preventing and/or treating metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease. The method comprises administering to a subject in need or willingness to receive treatment or prevention an effective amount of a compound that selectively agonizes the glucagon-like peptide-1 receptor or a pharmaceutically acceptable salt thereof for treating or preventing the above-mentioned diseases. Or symptoms.

优选地， 上述疾病通过给予有效量的由以下通式 I至 VI任意一个表示的化合物或其 药物学上可接受的盐来治疗或预防：  Preferably, the above disease is treated or prevented by administering an effective amount of a compound represented by any one of the following formulas I to VI or a pharmaceutically acceptable salt thereof:

Figure imgf000028_0001
Figure imgf000028_0001

III III

Figure imgf000028_0002
Figure imgf000028_0002

I IV V V  I IV V V

及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂 化物或其金属配合物。 And all of its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

其中， X， Y， Ζ分别为（CH ， η为 0-2， 氧， 硫或氮。  Wherein, X, Y, and Ζ are (CH, η is 0-2, oxygen, sulfur or nitrogen, respectively).

其中 R R2， R3, 各自独立地为下列任意一种取代基： 氢； 卤素； 烷弪； 环烷烃； 轻 基； 硝基； 羧基； 醛基； 烷氧基； 胺基； 胺烷基； 酰胺基； 碳酰胺基； 巯基； 焼硫基； 醚; 硫醚； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。Wherein RR 2 , R 3 are each independently one of the following substituents: hydrogen; halogen; alkane; cycloalkane; light base; nitro; carboxyl; aldehyde; alkoxy; amine; Amido; carboxamide; sulfhydryl; sulfhydryl; ether; a thioether; a substituted or unsubstituted aryl group; a substituted or unsubstituted pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrole group; base.

; ， R7各自独立地为下列任意一种取代基： 氢； 垸烃； 环垸烃； 垸氧基； 胺基； 胺 烷基； 酰胺基； 碳酰胺基； 烷硫基； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代 或未取代的呋喃基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡 咯基。 And R 7 are each independently a substituent of any of the following: hydrogen; anthracene; a cycloalkyl; an oxirane; an amine; an amine alkyl; an amide; a carboxamide; an alkylthio; a substituted or unsubstituted Aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

可以用本方法防治任何对象， 优选哺乳动物， 更优选人。  Any subject can be controlled by this method, preferably a mammal, more preferably a human.

本方法可用来防治代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病）等。 优选的疾病或症状是任何由胰岛 素分泌和 /或功能障碍引起或伴随的疾病或症状。  The method can be used to control metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease). A preferred disease or condition is any disease or condition caused or accompanied by insulin secretion and/or dysfunction.

在预防和 /或治疗代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症） 时， 可单独使用或与其他巳经上市或将要上市的糖尿病治疗药物包括胰岛素增敏剂联合使 用本发明的化合物。 任何合适的代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和 肥胖症） 治疗药物均可与本发明的化合物联合使用。 其中， 典型的胰岛素增敏剂包括罗格 列酮和吡格列酮等。  In the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), it can be used alone or in combination with other diabetes treatments including insulin sensitizers that are marketed or will be marketed. Inventive compound. Any suitable metabolic disorder (including but not limited to diabetes, insulin resistance, and obesity) therapeutic agents can be used in combination with the compounds of the present invention. Among them, typical insulin sensitizers include rosiglitazone and pioglitazone.

在本发明的优选实施方案中， 使用本发明化合物时不给予上述胰岛素增敏剂。 更优选 地， 用本发明的化合物治疗或预防因使用上述已经上市或将要上市的糖尿病治疗药物 （包 括胰岛素增敏剂）而产生抗药性或毒副反应所引起的疾病或症状。  In a preferred embodiment of the invention, the above insulin sensitizer is not administered when the compound of the invention is used. More preferably, the compound of the present invention is used to treat or prevent a disease or symptom caused by the use of the above-mentioned diabetes therapeutic agents (including insulin sensitizers) which have been marketed or will be marketed to produce drug resistance or side effects.

可以通过任何合适的方法单独以 发明的化合物给药， 或与其他合适的糖尿病治疗药 物包括胰岛素增敏剂联合使用。 例如， 可以通过腔内注射， 皮下注射， 静脉内注射， 肌内 注射，真皮内注射， 口服或局部以本发明的化合物给药， 或以其药物学上可接受的盐给药。  It can be administered alone or in combination with other suitable diabetes therapeutics, including insulin sensitizers, by any suitable method. For example, it can be administered by intracavitary injection, subcutaneous injection, intravenous injection, intramuscular injection, intradermal injection, orally or topically with the compound of the present invention, or with a pharmaceutically acceptable salt thereof.

在具体实施方案中， 本方法进一步包括对给药对象的疾病或症状进行诊断和预后评 估。 可以使用任何适合的方法用于诊断和评估相关疾病或症状及其预后。 诊断和预后可以 基于检测和 /或鉴定任何或所有的体内物质， 例如糖化血红蛋白、 酶、 抗'原、 抗体、 核酸 或其他病理性和临床标记物等以及相关症状。 例如， 可以使用国际专利 W0 01/44815和美 国专利 5， 571， 674揭示的诊断或预后方法。  In a specific embodiment, the method further comprises performing a diagnosis and prognosis assessment of the disease or condition of the subject to whom it is administered. Any suitable method can be used to diagnose and assess the associated disease or condition and its prognosis. Diagnosis and prognosis can be based on detecting and/or identifying any or all of the in vivo substances, such as glycated hemoglobin, enzymes, anti-pro-, antibodies, nucleic acids or other pathological and clinical markers, and related symptoms. For example, a diagnostic or prognostic method disclosed in International Patent No. WO 01/44815 and U.S. Patent No. 5,571,674 can be used.

D联合制剂， 药盒和联合用药的方法  D combined preparation, kit and method of combination

另一方面， 本发明也涉及联合制剂， 这种联合包括一种选择性调节胰高血糖素样肽一 1受体功能的化合物， 或其药物学上可接受的盐， 和一种或多种代谢紊乱性疾病治疗药物 包括胰岛素增敏剂。  In another aspect, the invention also relates to a combination formulation comprising a compound that selectively modulates glucagon-like peptide-1 receptor function, or a pharmaceutically acceptable salt thereof, and one or more Therapeutic drugs for metabolic disorders include insulin sensitizers.

优选地， 这种联合用药包括本发明化合物或其药物学上可接受的盐和一种或多种代谢 紊乱性疾病治疗药物包括胰岛素增敏剂， 该化合物由以下通式 I至 VI任意一个表示-

Figure imgf000030_0001
Preferably, such a combination comprises a compound of the present invention or a pharmaceutically acceptable salt thereof and one or more therapeutic agents for metabolic disorders including an insulin sensitizer, which is represented by any one of the following formulas I to VI -
Figure imgf000030_0001

III  III

Figure imgf000030_0002
及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂化 物或其金属配合物。
Figure imgf000030_0002
And all of its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

其中 X， Υ, Z分别为（CH2)„， n为 0-2， 氧， 硫或氮。 Wherein X, Υ, Z are (CH 2 ) „, n is 0-2, oxygen, sulfur or nitrogen.

其中 Rl 7 R2， R3， R4各自独立地为下列任意一种取代基： 氢； 齒素； 烷烃； 环烷轻； 羟 基； 硝基； 羧基； 酸基； 烷氧基； 胺基； 胺烷基； 酰胺基； 碳酰胺基； 琉基； 烷硫基； 醚; 硫醚； 取代或未取代的芳基； .取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。 Wherein R l 7 R 2 , R 3 , R 4 are each independently one of the following substituents: hydrogen; dentate; alkane; cycloalkane light; hydroxy; nitro; carboxy; acid group; alkoxy group; Amine alkyl; amide group; carboxamide; fluorenyl; alkylthio; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; Or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R5， Re, R7各自独立地为下列任意一种取代基： 氢； 烷烃； 环烷烃； 烷氧基； 胺基； 胺 烷基； 酰胺基； 碳酰胺基； 烷硫基； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代 或未取代的呋喃基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡 咯基。 R 5 , Re, R 7 are each independently any of the following substituents: hydrogen; alkane; cycloalkane; alkoxy; amine; amine alkyl; amide; carboxamide; alkylthio; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

在本发明的联合制剂中可以使用任何合适的糖尿病治疗药物包括胰岛素增敏剂。 在一 个特定实施方案中， 用于本发明联合制剂中可以包括上述糖尿病治疗药物包括胰岛素增敏 剂中的一种或多种。  Any suitable therapeutic agent for diabetes, including insulin sensitizers, can be used in the combination formulations of the invention. In a specific embodiment, one or more of the above-mentioned diabetes therapeutic agents including insulin sensitizers may be included in the combined preparation of the present invention.

在另一个特定实施方案中， 提供了一种治疗或预防由胰岛素分泌和 /或功能障碍引起 或伴随的疾病或症状的方法， 该方法包括对需要和愿意接受治疗或预防的对象给予有效量 的上述联合制剂， 或其药物学上可接受的盐， 从而治疗或预防上述疾病或症状。  In another specific embodiment, a method of treating or preventing a disease or condition caused or accompanied by insulin secretion and/or dysfunction is provided, the method comprising administering an effective amount to a subject in need and willing to receive treatment or prevention The above combined preparation, or a pharmaceutically acceptable salt thereof, thereby treating or preventing the above diseases or symptoms.

在另一个特定实施方案中， 提供了一个药盒， 其中包括本发明的化合物或其药物学上 可接受的盐以及使用上述化合物或其药物学上可接受的盐来防治由胰岛素分泌和 /或功能 紊乱引起或伴随的疾病或症状的使用说明。  In another specific embodiment, there is provided a kit comprising a compound of the present invention or a pharmaceutically acceptable salt thereof, and the use of the above compound or a pharmaceutically acceptable salt thereof for controlling secretion and/or secretion by insulin Instructions for the use of a disease or condition caused by or associated with a dysfunction.

在再一个实施方案中， 提供了一个药盒， 包括上述联合制剂及使用所述联合制剂治疗 或预防由胰岛素分泌和 /或功能紊乱引起或伴随的疾病或症状的使用说明。 In still another embodiment, a kit is provided, comprising the combination of the above, and treatment with the combination Or instructions for the prevention of a disease or condition caused or accompanied by insulin secretion and/or dysfunction.

E配方和剂量  E formula and dosage

根据本发明， 本发明的化合物， 单独或与其它药剂， 载体或赋形剂联合， 为任何合适 的给药途径制定制剂， 例如腔内注射、 皮下注射、 静脉内注射、 肌内注射、 真皮内注射、 口服或局部用药。 本方法可以使用注射给药制剂， 以单剂量的形式在安瓿， 或多剂量容器 中与添加的缓冲剂注射给药。 制剂可采取以下形式如混悬液、 溶液或在油性或水性媒介中 的乳液。 制剂可以含有配方试剂如混悬剂、 稳定剂和 /或分散剂。 此外， 使用前， 活性成 分可以粉末形式与合适的载体， 无菌无热源水或其他溶剂构成剂型。 本发明的局部用药可 采用泡沫， 凝胶， 软膏， 油膏， 转皮膜片， 或膏状物。  According to the invention, the compounds of the invention, alone or in combination with other agents, carriers or excipients, are formulated for any suitable route of administration, for example, intraluminal, subcutaneous, intravenous, intramuscular, intradermal Injection, oral or topical. The method can be administered by injection in a single dose in an ampoule, or in a multi-dose container with an added buffer. The formulations may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles. The formulations may contain formulating agents such as suspending, stabilizing and/or dispersing agents. In addition, the active ingredient may be in a powder form with a suitable vehicle, sterile non-pyrogenic water or other solvent before use. The topical medicament of the present invention may be a foam, a gel, an ointment, an ointment, a transdermal patch, or a paste.

本发明中可以使用的用于给药的药用组合物和方法包括， 但不局限于， 美国专利 5, 736, 154、 6, 197， 801 Bl、 5， 741, 511、 5, 886, 039、 5， 941, 868、 6， 258， 374B1和 5， 686, 102 所阐述的内容。  Pharmaceutical compositions and methods for administration that may be used in the present invention include, but are not limited to, U.S. Patents 5,736,154, 6,197, 801 Bl, 5,741,511, 5, 886, 039 5, 941, 868, 6, 258, 374B1 and 5, 686, 102.

治疗或预防的剂量大小会因病情的严重性和给药途径而有所变化。 剂量和用药频度会 因年龄、 体重、 健康状况和病人个体反应不同而不同。  The size of the dose to be treated or prevented will vary depending on the severity of the condition and the route of administration. The dose and frequency of administration will vary with age, weight, health status, and individual patient response.

需要指出的是 （诊治医生也应知道)， 根据毒性和副反应， 必须采取必要措施终止、 中断或降低治疗剂量。 相反， 如果临床反应不明显 （排除毒性和副反应)， 医生应适当调 整治疗方案， 提高剂量。  It should be pointed out that (the doctor should also know), according to toxicity and side effects, necessary measures must be taken to terminate, interrupt or reduce the therapeutic dose. Conversely, if the clinical response is not obvious (excluding toxicity and side effects), the doctor should adjust the treatment plan to increase the dose.

任何合适的给药途径均可被采用。剂型包括片剂， 锭剂， 豆状胶囊， 分散剂，悬浮剂， 溶液， 胶囊， 膜片及类似物等。  Any suitable route of administration can be employed. Dosage forms include tablets, troches, soy capsules, dispersing agents, suspending agents, solutions, capsules, films and the like.

在实际应用中， 本发明的化合物， 单独或与其他制剂联合， 可以按照一般药物学混合 技术与药物载体或赋形剂， 例如 β—环糊精和 2—羟基一丙基一 β—环糊精紧密混和。 根 据投药的需要， 可采用通用载体、 局部或非肠道途径的特殊载体。 制备非肠道剂型， 例如 静脉内注射或灌输的组合物， 可采用类似的药物媒质， 本领域技术人员所公知的水， 乙二 醇，油，缓冲剂，糖，防腐剂，脂质体等。这种非肠道组合物的例子包括，但不限制于 5%W/V 的右旋糖， 生理盐水或其他溶液。本发明的化合物的总剂量，单独或和其他制剂联合给药， 可用小瓶静脉注射液给药， 体积大约从 1毫升到 2000毫升。 根据给药的总剂量， 稀释液 量也会不同。  In a practical application, the compound of the present invention, alone or in combination with other preparations, may be in accordance with a general pharmaceutical mixing technique with a pharmaceutical carrier or excipient such as β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Finely mixed. A special carrier, a local or parenteral route, can be used depending on the needs of the administration. For the preparation of parenteral dosage forms, such as compositions for intravenous injection or infusion, similar pharmaceutical vehicles can be employed, water, glycols, oils, buffers, sugars, preservatives, liposomes, etc., which are well known to those skilled in the art. . Examples of such parenteral compositions include, but are not limited to, 5% w/v dextrose, physiological saline or other solutions. The total dose of the compound of the present invention, alone or in combination with other preparations, can be administered in vial vials in a volume of from about 1 ml to about 2000 ml. The amount of diluent will vary depending on the total dose administered.

本发明还提供了实现治疗方案的药盒。 该药盒将有效剂量的本发明化合物以药物学上 可接受的形式单独或与其他试剂联合， 包含在一个或多个容器中。 优选的药物形式是与无 菌盐水， 右旋糖溶液， 缓沖溶液， 或其他药物学上可接受的无菌液体合用。 或者， 组合物 可被冻千或干燥； 在这种情况下， 药盒任选地进一步将一种药物学上可接受的溶液， 优选 无菌的溶液包含在一个容器中， 以重新组成复合物形成用于注射目的的溶液。 典型的药物 学上可接受的溶液是生理盐水和右旋糖溶液。  The invention also provides a kit for achieving a therapeutic regimen. The kit comprises an effective amount of a compound of the invention in a pharmaceutically acceptable form, alone or in combination with other agents, in one or more containers. The preferred pharmaceutical form is in combination with sterile saline, dextrose solution, buffer solution, or other pharmaceutically acceptable sterile liquid. Alternatively, the composition may be frozen or dried; in this case, the kit optionally further comprises a pharmaceutically acceptable solution, preferably a sterile solution, in a container to reconstitute the complex A solution for injection purposes is formed. Typical pharmaceutically acceptable solutions are physiological saline and dextrose solutions.

在另一个实施方案中， 本发明的药盒进一步包含用于注射组合物的优选以无菌形式包 装的针或针筒和 /或包装的酒精垫。 可任选地包括供医生或患者使用的说明书。 In another embodiment, the kit of the invention further comprises a composition for injection, preferably in sterile form A needle or syringe and/or a packed alcohol pad. Instructions for use by a doctor or patient may optionally be included.

F制备方法  F preparation method

^NH2 ^ 、 NH2 .HCI ^ 、 < ^ NH 2 ^, NH 2 .HCI ^, <

CN ^COOH A COOH

Figure imgf000032_0001
取氰化钠 （leq)溶于适量的水中， 加入氯化铵 （l. leq)， 室温下搅拌， 当氯化铵完 全溶解后， 加入上述酮 （leq) 的甲醇溶液。 反应温度迅速上升， 继续搅拌 2小时。 加水 稀释， 用苯提取。 苯层用水洗， 用 6N盐酸提取氨基腈。 CN ^COOH A COOH
Figure imgf000032_0001
Sodium cyanide (leq) was dissolved in an appropriate amount of water, ammonium chloride (l. leq) was added, and the mixture was stirred at room temperature. After the ammonium chloride was completely dissolved, a methanol solution of the above ketone (leq) was added. The reaction temperature rose rapidly and stirring was continued for 2 hours. Dilute with water and extract with benzene. The benzene layer was washed with water, and the aminonitrile was extracted with 6N hydrochloric acid.

合并酸液， 回流 2小时， 加水稀释。 减压蒸馏， 去除酮和其他的挥发性物质。  The combined acid solutions were refluxed for 2 hours and diluted with water. Distillation under reduced pressure to remove ketones and other volatile materials.

加氨水调节 ra至弱碱性， 冷却至室温。 有黄色的晶体出现。 过滤， 滤饼用少量的水 洗， 然后用乙醚和 95%的热乙醇洗。 干燥得到氨基酸。 （，  Add ammonia to adjust ra to weakly alkaline and cool to room temperature. There are yellow crystals appearing. After filtration, the filter cake was washed with a small amount of water and then washed with diethyl ether and 95% hot ethanol. Dry to give amino acids. (,

取上述氨基酸（leq) 溶于氢氧化钠溶液（1. 25eq)， 冷却至 30°C以下， 同时滴加酰 氯（l. leq)和氢氧化钠溶液（2eq)， 始终维持反应液呈弱碱性。 滴加结束后继续搅拌 0. 5 小时。 加浓盐酸调节 PH至酸性， 冷却， 过滤得到粗品。 用乙醇重结晶得到产物。

Figure imgf000032_0002
The above amino acid (leq) was dissolved in sodium hydroxide solution (1.25 eq), cooled to below 30 ° C, while adding acid chloride (l. leq) and sodium hydroxide solution (2 eq), always maintaining the reaction solution as a weak base Sex. 5小时。 After the end of the addition of stirring was continued for 0.5 hours. Concentrated hydrochloric acid was added to adjust the pH to acidity, cooled, and filtered to give a crude material. Recrystallization from ethanol gave the product.
Figure imgf000032_0002

、5-7  5-7

0  0

COOH 取酮 （0. 67eq)溶于适量的乙醚和水中， 冰盐浴冷却。 加入氰化钠 （1. 67eq)， 剧烈 搅拌。当大部分的氰化钠全部溶解后且反应液温度降至 5°C以下， 慢慢滴加适量的浓盐酸， 维持反应温度在 5°C到 10°C之间。 滴加结束后， 移去冰浴， 同时剧烈搅拌 2小时。 静置， 分离乙醚层， 将水层倒入反应瓶中， 加水溶解盐。 水层再用乙醚提取， 合并乙醚层， 蒸去 乙醚。 将残余物倒入浓盐酸中， 并用氯化氢气体饱和， 放置过夜。 然后先用空气带走部分 氯化氢气体， 再慢慢滴加 50%氢氧化钠溶液调节至碱性。冰浴冷却， 用机械搅拌， 加入氢 氧化钠固体 （0. 6eq)， 水蒸汽蒸馏直至无多余的氨和酮。 加水稀释， 乙醚提取 （弃去）。 水层用浓盐酸酸化， 冷却， 过滤得到 α—羟基酸。  The ketone (0. 67 eq) of COOH was dissolved in an appropriate amount of diethyl ether and water, and cooled in an ice salt bath. Sodium cyanide (1. 67 eq) was added and stirred vigorously. When most of the sodium cyanide is dissolved and the temperature of the reaction solution falls below 5 °C, an appropriate amount of concentrated hydrochloric acid is slowly added dropwise to maintain the reaction temperature between 5 ° C and 10 ° C. After the completion of the dropwise addition, the ice bath was removed while vigorously stirring for 2 hours. After standing, the ether layer was separated, and the aqueous layer was poured into a reaction flask, and water was added to dissolve the salt. The aqueous layer was extracted with diethyl ether. EtOAc was evaporated. The residue was poured into concentrated hydrochloric acid and saturated with hydrogen chloride gas and stood overnight. Then, take part of the hydrogen chloride gas with air, and then slowly add 50% sodium hydroxide solution to adjust to alkaline. The mixture was cooled in an ice-bath, and stirred with mechanical stirring, sodium hydroxide solid (0. 6 eq.), and steam distilled until no excess of ammonia and ketone. Dilute with water and extract with ether (discard). The aqueous layer was acidified with concentrated hydrochloric acid, cooled, and filtered to give an hydroxy acid.

取 α—羟基酸 （0, 69eq)加入酰氯（0. 69eq)， 水浴加热反应。 冷却析晶， 得产物。

Figure imgf000033_0001
在氮气保护下， 取 LDA ( 1. 2mra0l )溶于适量的四氢呋喃中， 冷却至一50Ό， 慢慢滴加 羧酸 (0. 5mmol ), 维持该 度继续搅拌 30分钟， 50°C继续搅拌 2小时。 用液氮 /甲醇浴冷 却至一 10(TC， 滴加硝基取代的烯烃（1. 5醒01)， 反应 5个小时， 反应液温度慢慢升至 0 一 10°C。 加入适量的 17%稀盐酸， 冰浴中搅拌过夜。 加水， 二氯甲垸提取， 依次用水和饱 和食盐水洗涤， 干燥。 蒸去溶剂上柱分离。 A-hydroxy acid (0, 69 eq) was added to the acid chloride (0.66 eq), and the reaction was heated in a water bath. The crystallized was cooled to obtain a product.
Figure imgf000033_0001
Under nitrogen, take LDA (1.2mra 0 l) in an appropriate amount of tetrahydrofuran, cool to 50 Ό, slowly add carboxylic acid (0.5 mmol), continue to stir for 30 minutes, continue at 50 °C Stir for 2 hours. Cool to a 10 (TC, drop nitro-substituted olefin (1.5 awake 0 1) with a liquid nitrogen/methanol bath, react for 5 hours, and slowly raise the temperature of the reaction solution to 0-10 ° C. Add the appropriate amount. 17% dilute hydrochloric acid, stirring in an ice bath overnight. Add water, dichloromethane extract, wash with water and saturated brine, and dry.

附图说明  DRAWINGS

图 1. 报告基因方法检测化合物对 GLP- 1R的激动作用。 GLP-1浓度梯度为 10， 1， 0. 1， Figure 1. Reporter gene method to detect the agonistic effects of compounds on GLP-1R. The GLP-1 concentration gradient is 10, 1, 0.1.

0. 01， 0. 001， 0. 0001 nM, 以 10 nM所诱导的萤光素酶活性为 100% , 测得 GLP - 1的 EC5。 值为 0. 07 nMo 0. 01, 0. 001, 0. 0001 nM, luciferase activity induced by 10 nM was 100%, and EC 5 of GLP-1 was measured. The value is 0. 07 nMo

图 2. 报告基因方法检测 exendin9-39对 GLP- 1的拮抗作用。选取 GLP- 1的浓度为 0. 05 nM, exendi -39的浓度梯度为 10000， 1000， 100, 10, 1， 0. 1， 0 nM, 以不加 exendir 39的活 性设为 100%， 试验表明 exendin^能剂量依赖性地抑制由 GLP- 1诱导的报告基因表达， 其 IC5。值为 68. 22 nM, 表明其生物活性是通过 GLP- 1R介导的。 Figure 2. Reporter gene assay for the antagonism of exendin 9-39 on GLP-1. The concentration of GLP-1 was chosen to be 0.05 nM, and the concentration gradient of exendi- 39 was 10000, 1000, 100, 10, 1, 0. 1, 0 nM, and the activity of exendir 39 was set to 100%. exendin ^ reported dose-dependently induced by inhibition of gene expression of GLP- 1, which IC 5. The value was 68. 22 nM, indicating that its biological activity is mediated by GLP-1R.

图 3. 细胞内 cAMP浓度检测 GLP-1对 GLP-1R信号传导的作用。 GLP- 1浓度梯度为 10， Figure 3. Intracellular cAMP concentration assay The effect of GLP-1 on GLP-1R signaling. The GLP-1 concentration gradient is 10,

1 , 0. 1， 0. 01， 0. 001， 0. 0001， O nM, 以 10 nM所诱导的 cAMP活性为 100% , 测得 GLP- 1 的 EC5。值为 0. 079 nM， 提示其作为 GLP-1R激动剂， 可剂量依赖性地诱导细胞内 cAMP的产 生。 1 , 0. 1, 0. 01, 0. 001, 0. 0001, O nM, the cAMP activity induced by 10 nM was 100%, and the EC 5 of GLP-1 was measured. The value was 0. 079 nM, suggesting that it acts as a GLP-1R agonist and induces intracellular cAMP production in a dose-dependent manner.

图 4. 受体竞争性结合试验方法检测 GLP-1对受体的亲和力。 GLP-1浓度梯度为 1000， 200， 40, 8， 1. 6， 0. 32， 0. 064, 0 nM。 GLP- 1可特异性地与 1251标 GLP- 1竞争性结合 GLP - 1R， 其 IC50值为 0. 66 nMo 具体实施方式 Figure 4. Receptor competitive binding assay method to detect the affinity of GLP-1 for receptors. The GLP-1 concentration gradient is 1000, 200, 40, 8, 1. 6, 0. 32, 0. 064, 0 nM. GLP-1 can specifically bind to GLP-1R in a competitive manner with 125 1 standard GLP-1, and its IC 50 value is 0. 66 nMo

实验仪器及试剂  Experimental instruments and reagents

HP1100 HPLC系统， 具备二元梯度泵、 在线真空脱气机、 自动进样器、 柱温箱和光电 二极管阵列检测器。 色谱柱为 ZORBAX SB-C18 (2. 1 x 150 mm, 3. 5 μιη), 流动相为乙腈 / 水，流速为 0. 2 ml/min,检测波长为 254 nm。熔点采用 IA6304型熔点仪测定； NMR由 Varian Mercury- 300和 Varian Mercury Plus 400型核磁共振仪测得（溶剂为 CDC13， CD30D或 DMS0-d6); ESI-MS由 AB Mariner型质谱仪测得， EI由 Finnigan MAT95型质谱仪测得。 合 成中所用原料除特别指明来源外均为市售产品。 HP1100 HPLC system with binary gradient pump, online vacuum degasser, autosampler, column oven and photodiode array detector. The column was ZORBAX SB-C18 (2.11 x 150 mm, 3. 5 μιη), the mobile phase was acetonitrile/water, the flow rate was 0.2 ml/min, and the detection wavelength was 254 nm. The melting point was measured by an IA6304 melting point apparatus; NMR was measured by Varian Mercury-300 and Varian Mercury Plus 400 nuclear magnetic resonance spectrometer (solvent CDC1 3 , CD 3 0D or DMS0-d 6 ); ESI-MS by AB Mariner mass spectrometer The EI was measured by a Finnigan MAT95 mass spectrometer. The materials used in the synthesis are commercially available products unless otherwise specified.

实施例 1  Example 1

NMR定标: δ Η/C 7. 26/77. 0 ppm (CDC13); δ H/C 2. 50/39. 51 ppm (DMS0- d6)。 NMR calibration: δ Η/C 7. 26/77. 0 ppm (CDC13); δ H/C 2. 50/39. 51 ppm (DMS0-d6).

Figure imgf000034_0001
取氰化钠 （leq)溶于适量的水中， 加入氯化铵 （l. leq)， 室温下搅拌， 当氯化铵完 全溶解后， 加入上述 2， 5二苯基 1， 4一环己二酮（leq)的甲醇溶液。反应温度迅速上升， 继续搅拌 2小时。 加水稀释， 用苯提取。 苯层用水洗， 用 6N盐酸提取 2， 5-二苯基 1 , 4一 二氨基一 1， 4一环己二腈。
Figure imgf000034_0001
Sodium cyanide (leq) is dissolved in an appropriate amount of water, ammonium chloride (l. leq) is added, and stirred at room temperature. When ammonium chloride is completely dissolved, the above 2,5-diphenyl 1,4-cyclohexane is added. A solution of ketone (leq) in methanol. The reaction temperature rose rapidly and stirring was continued for 2 hours. Dilute with water and extract with benzene. The benzene layer was washed with water, and 2,5-diphenyl-1,4-diamino-1,4-cyclohexanedicarbonitrile was extracted with 6N hydrochloric acid.

合并酸液， 回流 2小时， 加水稀释。 减压蒸镏， 去除酮和其他的挥发性物质。  The combined acid solutions were refluxed for 2 hours and diluted with water. Evaporate under reduced pressure to remove ketones and other volatile materials.

加氨水调节 PH至弱碱性， 冷却至室温。 有黄色的晶体出现。 过滤， 滤饼用少量的水 洗， 然后用乙醚和 95%的热乙醇洗。 干燥得到 2， 5-二苯基 1， 4一二氨基一 1， 4_环己二 酸。  Add ammonia to adjust the pH to weakly alkaline and cool to room temperature. There are yellow crystals appearing. After filtration, the filter cake was washed with a small amount of water and then washed with diethyl ether and 95% hot ethanol. Drying gave 2,5-diphenyl 1,4-diamino- 1,4-cyclohexanedioic acid.

取上述 2， 5-二苯基 1 , 4一二氨基一 1， 4一环己二酸（ leq)溶于氢氧化钠溶液 ( 1. 25eq )， 冷却至 3CTC以下， 同时滴加对 Boc氨基苯甲酰氯（l. leq) 和氢氧化钠溶液（2eq)， 始终 维持反应液呈弱碱性。 滴加结束后继续搅拌 0. 5小时。 加浓盐酸调节 ΡΉ至酸性， 冷却， 过滤得到粗品。 用乙醇重结晶得到产物。  The above 2, 5-diphenyl 1 , 4 - diamino - 1 , 4 - cyclohexane adipate ( leq ) was dissolved in sodium hydroxide solution ( 1. 25 eq ), cooled to below 3 CTC, and the Boc amino group was added dropwise. Benzoyl chloride (l. leq) and sodium hydroxide solution (2 eq) always kept the reaction solution weakly alkaline. 5小时。 After the end of the dropwise addition, continue to stir 0. 5 hours. Concentrated hydrochloric acid was added to adjust to hydrazine, cooled, and filtered to give a crude material. Recrystallization from ethanol gave the product.

同样方法得到以下产物：  The same method yields the following products:

Figure imgf000034_0002
Figure imgf000035_0001
Figure imgf000035_0002
Figure imgf000035_0003
T/CN2007/002769
Figure imgf000036_0001
取 2， 5-二苯基 1， 4一环己二酮 （0. 67eq)溶于适量的乙醚和水中， 冰盐浴冷却。 加 入氰化钠（1. 67eq)，剧烈搅拌。当大部分的氰化钠全部溶解后且反应液温度降至 5°C以下， 慢慢滴加适量的浓盐酸， 维持反
Figure imgf000034_0002
Figure imgf000035_0001
Figure imgf000035_0002
Figure imgf000035_0003
T/CN2007/002769
Figure imgf000036_0001
2, 5-Diphenyl 1,4-cyclohexanedione (0.66 eq) was dissolved in an appropriate amount of diethyl ether and water, and cooled in an ice salt bath. Sodium cyanide (1.67 eq) was added and stirred vigorously. When most of the sodium cyanide is dissolved and the temperature of the reaction solution drops below 5 °C, slowly add an appropriate amount of concentrated hydrochloric acid to maintain the reverse.

应温度在 5°C到 10Ό之间。 滴加结束后， 移去冰浴， 同时剧烈搅拌 2小时。 静置， 分离乙 醚层， 将水层倒入反应瓶中， 加水溶解盐。 水层再用乙醚提取， 合并乙醚层， 蒸去乙醚。 将残余物倒入浓盐酸中， 并用氯化氫气体饱和， 放置过夜。然后先用空气带走部分氯化氢 气体， 再慢慢滴加 50%氢氧化钠溶液调节至碱性。 冰浴冷却， 用机械搅拌， 加入氢氧化钠 固体 （0. 6eq)， 水蒸汽蒸馏直至无多余的氨和酮。 加水稀释， 乙醚提取（弃去）。 水层用 浓盐酸酸化， 冷却， 过滤得到 2， 5-二苯基 1， 4一二羟基一 1， 4一环己二腈。 The temperature should be between 5 ° C and 10 °. After the completion of the dropwise addition, the ice bath was removed while vigorously stirring for 2 hours. After standing, the ethyl ether layer was separated, and the aqueous layer was poured into a reaction flask, and water was added to dissolve the salt. The aqueous layer was extracted with diethyl ether. The residue was poured into concentrated hydrochloric acid and saturated with hydrogen chloride gas and stood overnight. Then use the air to remove some of the hydrogen chloride gas, and then slowly add 50% sodium hydroxide solution to adjust to alkaline. Cool in an ice bath, mechanically stir, add sodium hydroxide solid (0.6 eq), steam distilled until free of ammonia and ketone. Dilute with water and extract with ether (discard). The aqueous layer was acidified with concentrated hydrochloric acid, cooled and filtered to give &lt;RTI ID=0.0&gt;&gt;

取 2， 5-二苯基 1， 4一二羟基一 1， 4一环己二腈（0. 69eq)加入对 Boc氨基苯甲酰氯 (0. 69eq), 水浴加热反应。 冷却析晶， 得产物。  2, 5-Diphenyl 1, 4-dihydroxy-1, 4-cyclohexanedicarbonitrile (0.66 eq) was added to a solution of Boc aminobenzoyl chloride (0.66 eq), which was heated in a water bath. The crystallized was cooled to obtain a product.

同样方法得到以下产物：  The same method yields the following products:

Figure imgf000036_0002
实施例 3：
Figure imgf000036_0002
Example 3:

Figure imgf000037_0001
在氮气保护下， 取 LDA (1.2mmol)溶于适量的四氢呋喃中， 冷却至一 50°C， 慢慢滴加 2, 5-二苯基环己二酸 （0.5讓 ol)， 维持该温度继续搅拌 30分钟， 50°C继续搅拌 2小时。 用液氮 /甲醇浴冷却至一 100Ό, 滴加 α—硝基取代苯乙烯（1.5腿 ol)， 反应 5个小时， 反 应液温度慢慢升至 0— 10°C。 加入适量的 17%稀盐酸， 冰浴中搅拌过夜。 加水， 二氯甲烷 提取， 依次用水和饱和食盐水洗涤， 干燥。 蒸去溶剂上柱分离。
Figure imgf000037_0001
Under nitrogen protection, take LDA (1.2mmol) in an appropriate amount of tetrahydrofuran, cool to a temperature of 50 ° C, slowly add 2, 5-diphenylcyclohexanedicarboxylic acid (0.5 let ol), continue to maintain the temperature Stir for 30 minutes and continue stirring at 50 °C for 2 hours. After cooling to 100 Torr with a liquid nitrogen/methanol bath, α-nitro-substituted styrene (1.5 lb ol) was added dropwise, and the reaction temperature was gradually raised to 0-10 ° C for 5 hours. An appropriate amount of 17% dilute hydrochloric acid was added and the mixture was stirred overnight in an ice bath. Water was added, and the mixture was extracted with dichloromethane, washed with water and brine, and dried. The solvent was distilled off and the column was separated.

同样方法得到以下产物：  The same method yields the following products:

Figure imgf000037_0002
实施例 4: 体外药效学试验
Figure imgf000037_0002
Example 4: In vitro pharmacodynamic test

1. 报告基因表达检测  Reporter gene expression detection

GLP-1R为 G蛋白偶联受体， 当 GLP- 1R与激动剂结合后， G蛋白的 G α亚单位被活化， 刺激腺苷酸环化酶， 导致细胞内 cAMP水平升高。 因前胰岛素基因的启动子区域存在 cAMP 反应元件， cAMP与该反应元件结合后， 启动前胰岛素基因的转录， 从而刺激胰岛素的表达 和分泌 (Diabetes, 2000， Vol. 49 : 1156-1164)。 本实验方法采用稳定转染 GLP-1R受体 基因表达载体和受 cAMP反应元件调节的荧光素酶报告基因表达载体的人胚肾细胞株 （HEK 293)，检测其对被测化合物的反应（Cell Biology, 1992, Vol. 89 : 8641-8645； Proc. Natl. Acad. Sci. U. S. A. 1987, Vol. 84 : 3434-3438)。 在对化合物进行筛选时， 可诱导荧光素 酶报告基因表达的样品， 视为具有 GLP- 1R激动活性。 GLP-1R is a G protein-coupled receptor. When GLP-1R binds to an agonist, the G α subunit of the G protein is activated. Stimulation of adenylate cyclase leads to an increase in intracellular cAMP levels. Since the cAMP response element exists in the promoter region of the proinsulin gene, cAMP binds to the response element to initiate transcription of the pre-insulin gene, thereby stimulating insulin expression and secretion (Diabetes, 2000, Vol. 49: 1156-1164). In this experimental method, a human embryonic kidney cell strain (HEK 293) stably transfected with a GLP-1R receptor gene expression vector and a luciferase reporter gene expression vector regulated by a cAMP response element was used to detect its response to a test compound (Cell). Biology, 1992, Vol. 89: 8641-8645; Proc. Natl. Acad. Sci. USA 1987, Vol. 84: 3434-3438). A sample that induces expression of a luciferase reporter gene when screened for a compound is considered to have GLP-1R agonistic activity.

1. 1 试验材料与仪器  1. 1 Test materials and instruments

细胞株： GLP- 1R和荧光素酶稳定表达的 HEK 293/GLP-lR+Luc细胞株 （国家新药筛选 中心自建）  Cell line: HEK 293/GLP-lR+Luc cell line stably expressed by GLP-1R and luciferase (National New Drug Screening Center self-built)

胎牛血清（GIBC0公司） '  Fetal bovine serum (GIBC0 company)

DMEM培养基 （GIBC0公司）  DMEM medium (GIBC0 company)

Steady- Glo™荧光素酶分析系统（Promega公司）  Steady-GloTM Luciferase Assay System (Promega)

GLP- 1标准品 （Sigma公司）  GLP-1 standard (Sigma)

G418 ( Invitrogen公司）  G418 (Invitrogen)

Forma二氧化碳培养箱 （Forma公司）；  Forma Carbon Dioxide Incubator (Forma);

Victor2读板机（Wallac公司）； Victor 2 plate reader (Wallac);

1. 2 试验方法  1. 2 Test methods

HEK293/GLP1R+Luc细胞以 20， 000个 /100 μΐ/孔接入 96孔培养板， 以含 10%胎牛血清 和 500 μ§/πι1 G418的 DMEM培养基于 37°C培养过夜。将 GLP- 1标准品稀释至一定浓度梯度， 然后以 1 μΐ/孔加入上述 96孔微量培养板中。 在 37°C， 5%C02条件下培养 6 小时。 按 Steady- Glo™荧光素酶分析系统试剂盒说明检测荧光素酶活性， Victor2读板机进行读数。 HEK293/GLP1R+Luc cells were inserted into 96-well culture plates at 20,000/100 μΐ/well, and cultured overnight at 37 ° C in DMEM medium containing 10% fetal calf serum and 500 μ § /πι 1 G418. The GLP-1 standard was diluted to a concentration gradient and then added to the above 96-well microplate at 1 μΐ/well. Incubate for 6 hours at 37 ° C under 5% CO 2 . Luciferase activity was measured by the Steady-GloTM Luciferase Assay System Kit, and the Victor 2 reader was used for reading.

1. 3 试验结果  1. 3 test results

研究结果表明 （表 1， 图 1 )， GLP-1的 EC5。值为 0. 07 nM。 The results showed (Table 1, Figure 1), GLP-1 EC 5 is. The value is 0. 07 nM.

表 1. 报告基因表达检测 GLP- 1的激动活性 （％反应， 以 10 nM GLP 1的反应为 100%)  Table 1. Reporter gene expression assay GLP-1 agonistic activity (% response, 100% response to 10 nM GLP 1)

GLP- 1终浓度 (nM)相对激动活性（％) GLP-1 final concentration (nM) relative agonistic activity (%)

10 100. 0  10 100. 0

1 100. 7  1 100. 7

0. 1 61. 4  0. 1 61. 4

0. 01 13. 3  0. 01 13. 3

0. 001 2. 4  0. 001 2. 4

0. 0001 0. 4 2. Exendin9-39抬抗试验 0. 0001 0. 4 2. Exendin 9-39 lift-resistance test

为确证活性化合物对报告基因的活化作用具有受体特异性，我们釆用 GLP- 1R的特异性 拮抗剂 exendir 39 ( Eur. J. Pharmacol. 1994, 269 : 183—191 ; Metabolism 2004, 53 : 252-259. )来验证其能否拮抗上述代表性化合物对 GLP- 1R的激动活性。 To confirm the receptor specificity of the active compound for the activation of the reporter gene, we used the specific antagonist of GLP-1R, exendir 39 (Eur. J. Pharmacol. 1994, 269: 183-191; Metabolism 2004, 53: 252 -259. ) to verify whether it antagonizes the agonistic activity of the above representative compounds on GLP-1R.

2. 1 试验材料与仪器：  2. 1 Test materials and instruments:

细胞株： GLP- 1R和荧光素酶稳定表达的 HEK 293/GLP-lR+Luc细胞株 （国家新药筛选 中心自建）  Cell line: HEK 293/GLP-lR+Luc cell line stably expressed by GLP-1R and luciferase (National New Drug Screening Center self-built)

胎牛血清 （GIBC0公司）  Fetal bovine serum (GIBC0)

DMEM培养基（GIBC0公司）  DMEM medium (GIBC0 company)

Exendin 9-39 (AnaSpec公司）  Exendin 9-39 (AnaSpec)

Steady- Glo™荧光素酶分析系统（Promega公司）  Steady-GloTM Luciferase Assay System (Promega)

G418 (Invitrogen公司）  G418 (Invitrogen)

Forma二氧化碳培养箱（Forma公司）；  Forma Carbon Dioxide Incubator (Forma);

Victor2读板机（Wallac公司）； Victor 2 plate reader (Wallac);

2. 2试验方法  2. 2 test methods

HEK293/GLP1R+Luc细胞以 20， 000个 /100 μΐ/孔接入 96孔培养板， 以含 10%胎牛血清 和 500 μ§/πι1 G418的 DMEM培养基于 37°C培养过夜。将 Exendir 39稀释至一定的浓度梯度， 然后以 1 μΐ/孔加入上述 96孔微量培养板中， 在 37°C， 5%C02条件下孵育 10分钟， 然后加 入 0. 05 nMGLP- 1， 在 37°C， 5%C02条件下培养 6小时。 按 Steady- Glo™荧光素酶分析系统 试剂盒说明检测荧光素酶活性， Victor2读板机进行读数。 HEK293/GLP1R+Luc cells were inserted into 96-well culture plates at 20,000/100 μΐ/well, and cultured overnight at 37 ° C in DMEM medium containing 10% fetal calf serum and 500 μ § /πι 1 G418. The Exendir 39 was diluted to a certain concentration gradient, and then added to the above 96-well microplate at 1 μM/well, incubated at 37 ° C, 5% CO 2 for 10 minutes, and then added 0. 05 nMGLP-1 Incubate for 6 hours at 37 ° C under 5% CO 2 . Luciferase activity was measured by the Steady-GloTM Luciferase Assay System Kit, and the Victor 2 reader was used for reading.

2. 3试验结果  2. 3 test results

Exendirv39能剂量依赖性地抑制由 GLP- 1诱导的报告基因表达（表 2， 图 2)， 其 IC5Q 值为 68. 22 nM, 表明其生物活性是通过 GLP- 1R介导的。 Exendirv 39 dose-dependently inhibited GLP-1-induced reporter gene expression (Table 2, Figure 2) with an IC 5Q value of 68.22 nM, indicating that its biological activity is mediated by GLP-1R.

表 2. Exendin9-3S^4 GLP- 1的拮抗作用 （％反应， 以 0. 05 nM GLP- 1的反应为 100%) Antagonism Table 2. Exendin 9-3S ^ 4 GLP- 1 (the% of the reaction, the reaction to 0. 05 nM GLP- 1 is 100%)

Exendin (nM) 相对活性 （％) Exendin (nM) relative activity (%)

10000 1. 9  10000 1. 9

1000 2. 7  1000 2. 7

100 38. 9  100 38. 9

10 91. 0  10 91. 0

1 97. 1  1 97. 1

0. 1 101. 2  0. 1 101. 2

0 100. 0  0 100. 0

3. 细胞内 cAMP浓度测定 因报告基因检测方法是间接判断细胞内 CAMP浓度水平的方法。 为确定活性化合物确 实可使细胞内 cAMP浓度升高， 直接以 cAMP检测试剂盒进行功能性验证。 3. Determination of intracellular cAMP concentration The reporter gene detection method is a method for indirectly determining the level of intracellular CAMP concentration. To confirm that the active compound does increase intracellular cAMP concentration, functional verification is performed directly using the cAMP assay kit.

3. 1试验材料与仪器  3. 1 test materials and instruments

细胞株： GLP-1R和荧光素酶稳定表达的 HEK 293/GLP-lR+Luc 细胞株 （国家新药筛选 中心自建）  Cell line: HEK 293/GLP-lR+Luc cell line stably expressed by GLP-1R and luciferase (National New Drug Screening Center self-built)

cAMP检测试剂盒（Applied Biosystems公司）  cAMP test kit (Applied Biosystems)

Forma二氧化碳培养箱 （Forma公司）  Forma Carbon Dioxide Incubator (Forma)

Victor2读板机（Wallac公司） Victor 2 plate reader (Wallac)

cAMP标准品 （试剂盒自带， Applied Biosystems公司）  cAMP standard (provided with the kit, Applied Biosystems)

3. 2试验方法 3. 2 test methods

HEK 293细胞以 20000个 /lOOul/孔接入 96孔培养板， 37°C培养过夜， 用二甲亚 砜将 GLP- 1梯度稀释， 并以 lul/孔加入上述 96孔微量培养板中。 37°C、 5%C02条件下 培养 15 min。 按 cAMP-Screen DirectTM Systerm试剂盒说明检测细胞内 cAMP浓度水 平。 HEK 293 cells were incubated at 20,000 cells/lOOul/well in 96-well culture plates, cultured overnight at 37 ° C, GLP-1 was serially diluted with dimethyl sulfoxide, and added to the above 96-well microplates at 1 μl/well. Incubate for 15 min at 37 ° C, 5% CO 2 . Intracellular cAMP levels were measured by cAMP-Screen DirectTM Systerm kit instructions.

3. 3试验结果  3. 3 test results

GLP-1剂量依赖性地诱导细胞内 cAMP的产生（表 3， 图 3)， 其 EC5。值为 0. 079 nM， 提 示其作为 GLP-1R激动剂， 对 GLP-1R的信号传导起了一定作用。 GLP-1 dose-dependently induced cAMP in cells (Table 3, FIG. 3), which EC 5. The value was 0. 079 nM, suggesting that it acts as a GLP-1R agonist and plays a role in GLP-1R signaling.

表 3. GLP-1对细胞内 cAMP的诱导作用 （°/。反应， 以 10 nM GLP- 1的反应为 100%)  Table 3. Induction of intracellular cAMP by GLP-1 (°/. reaction, 100% response to 10 nM GLP-1)

GLP- 1终浓度 (nM) 相对活性 （％) GLP-1 final concentration (nM) relative activity (%)

10 100. 0  10 100. 0

1 94. 4  1 94. 4

0. 1 55. 4  0. 1 55. 4

0. 01 17. 2  0. 01 17. 2

0. 001 3. 3  0. 001 3. 3

0. 0001 1. 1  0. 0001 1. 1

0 0  0 0

4、 受体结合活力测试 4, receptor binding activity test

为确定活性化合物对受体的结合能力， 制备大量表达 GLP— 1R的细胞， 以 1251标记的 GLP-1作为配基， 同时加入待检测化合物。 当待测化合物与 1251标 GLP— 1进行竞争性结 合时， 细胞膜上的同位素标记减少。 据此可评估化合物对受体的的亲和力 （J Mol Endocrinol. 2000 Vol. 25 : 321-35； J Biomol Screen. 2000 Vol. 5 : 377- 84)。 To determine the ability of the active compound to bind to the receptor, a large number of cells expressing GLP-1R were prepared, and 125 1 labeled GLP-1 was used as a ligand, and the compound to be detected was added at the same time. When the test compound is competitively bound to the 125 1 standard GLP-1, the isotope labeling on the cell membrane is reduced. The affinity of the compound for the receptor can be evaluated accordingly (J Mol Endocrinol. 2000 Vol. 25: 321-35; J Biomol Screen. 2000 Vol. 5: 377-84).

4. 1试验材料与仪器：  4. 1 Test materials and instruments:

HEK 293/GLPlR+Luc 细胞株 （国家新药筛选中心自建） 标记化合物： 1251标记的 GLP- 1 (Amersham Biosciences 公司） HEK 293/GLP1R+Luc cell line (self-built by National New Drug Screening Center) Labeled compound: 125 1 labeled GLP-1 (Amersham Biosciences)

Wallac MicroBata工作站 (Perkin Elmer公司) Wallac MicroBata Workstation (Perkin Elmer)

ToraTech细胞收集器 （TomTec公司） ToraTech Cell Collector (TomTec)

闪烁液 (Wallac 公司）Scintillation fluid (Wallac)

. 2试验方法  . 2 test methods

取 105对数生长期的 HEK 293/GLPlR+Luc细胞， 于 25° C条件下， 200μ1测试缓 冲液中， 与 1251标 GLP-1阳性肽 （终浓度 40 M)共孵育 4小时， 同时加入非标记阳 性肽或待筛选药物。 使用细胞收集器， 用洗涤溶液洗涤细胞三次。 加入闪烁液， 在 Microbata计数器上读出每孔读数。 HEK 293/GLP1R+Luc cells in 10 5 logarithmic growth phase were incubated with 125 1 GLP-1 positive peptide (final concentration 40 M) for 4 hours at 25 ° C in 200 μl test buffer. Add a non-labeled positive peptide or a drug to be screened. The cells were washed three times with a washing solution using a cell harvester. Scintillation fluid was added and each well reading was read on a Microbata counter.

4. 3试验结果  4. 3 test results

GLP-1能特异性地与 1251标 GLP-1竞争性结合受体（表 4， 图 4), 其 ICS。值为 0. 66 nM。 GLP-1 specifically binds to receptors that compete with 125 1 GLP-1 (Table 4, Figure 4), its IC S . The value is 0. 66 nM.

表 4. GLP-1对 GLP- 1R的结合活力测试  Table 4. Binding viability test of GLP-1 to GLP-1R

1251标 GLP-1结合百分比 125 1 standard GLP-1 binding percentage

GLP-1终浓度 （nM)  GLP-1 final concentration (nM)

( % )  ( % )

1000 •0. 0  1000 • 0. 0

200 -2. 0  200 -2. 0

40 4. 0  40 4. 0

8 16. 7  8 16. 7

1. 6 33. 7  1. 6 33. 7

0. 32 60. 5  0. 32 60. 5

0. 064 80. 9  0. 064 80. 9

0 100. 0  0 100. 0

Claims

权利要求书 Claim 1、 一类由以下通式 I至 VI任意一个表示的具有取代环己垸结构的化合物或其药物学 上可接受的盐及其所有的立体和光学异构体， 或者与其具有相同药理作用的前药、 其酯、 其溶剂化物或其金属配合物- A compound having a substituted cyclohexanyl structure represented by any one of the following formulae I to VI or a pharmaceutically acceptable salt thereof, and all of the stereo and optical isomers thereof, or having the same pharmacological action thereto Prodrug, its ester, its solvate or its metal complex -
Figure imgf000042_0001
Figure imgf000042_0001
 III  III
Figure imgf000042_0002
Figure imgf000042_0002
 IV V VI  IV V VI 其中 X， Υ, Z分别为（CH ， n为 0-2， 氧， 硫或氮； Wherein X, Υ, Z are (CH, n is 0-2, oxygen, sulfur or nitrogen; 其中 R,， R2， R3， 各自独立地为下列任意一种取代基： 氢； （ ^素； 垸烃； 环烷烃； 羟 基； 硝基； 羧基； 醛基； 垸氧基； 胺基； 胺烷基； 酰胺基； 碳酰胺基； 巯基； 垸硫基； 醚; 硫醚； 取代或未取代的芳基； 取代或未取代的吡啶基； 取代或未取代的呋喃基； 取代或未 取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基； Wherein R, R 2 , R 3 are each independently one of the following substituents: hydrogen; (formin; anthracene; cycloalkane; hydroxy; nitro; carboxy; aldehyde; methoxy; Amine alkyl; amide group; carboxamide; fluorenyl; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted a pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group; R5， Re, R7各自独立地为卞列任意一种取代基： 氢； 烷经； 环烷烃； 院氧基； 胺基； 胺 院基； 酰胺基； 碳酰胺基； 烷硫基； 取代或未取代的芳基； 吡啶基； 取代或未取代的呋喃 基； 取代或未取代的吡喃基； 取代或未取代的噻吩基； 取代或未取代的吡咯基。 R 5 , R e , R 7 are each independently a substituent of any of the following: hydrogen; alkane; cycloalkane; alkoxy; amine; amine-based; amide; carboxamide; alkylthio; a substituted or unsubstituted aryl group; a pyridyl group; a substituted or unsubstituted furyl group; a substituted or unsubstituted pyranyl group; a substituted or unsubstituted thienyl group; a substituted or unsubstituted pyrrolyl group. 2、 根据权利要求 1所述的具有取代环己垸结构的化合物， 其特征在于：  2. A compound having a substituted cyclohexanyl structure according to claim 1 wherein: X、 Y、 Ζ分别是 (C ) n, n为 0—2， 氧， 硫或氮， R R2， R3， 分别各自独立地为：
Figure imgf000042_0003
X, Y, and Ζ are (C) n , n is 0-2, oxygen, sulfur or nitrogen, RR 2 , R 3 are each independently:
Figure imgf000042_0003
 其中 为下列任意一种取代基为 H; d-C6的垸基； 含有包括卤素原子、 d- (：6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 ^-^的浣基； c2- 的烯基； 含有包括卤 原子、 CrC6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 6的烯基； C2-Ce 炔基;含有包括卤素原子、 C6的焼氧基或羟基在内的任意一个、两个或者三个取代的 C2 -^ 的炔基； C3_C6的环烷基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个 或者三个取代的(：3- Ce的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 CrC^烧基、 硝基、羧基、醛基、烷氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-C^嫁基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- ( 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- (：4的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 （^-( 4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、（ ( 4的烷基、 硝基、羧基、醛基、烷氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； - C6的垸酰基； 含 有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 Cr Ce的垸 酰基； C2 Ce的烯酰基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、两个或 者三个取代的 C2- C6的烯酰基； C2-Ce的炔酰基； 含有包括卤素原子、 ^-(：6的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- Ce的炔酰基； C3- C6的环烷酰基； 含有包括卤素 原子、 CrC6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环垸酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（。 )„， η为 0-2， 0， S或者丽时; Wherein any of the following substituents is H ; a fluorenyl group of dC 6 ; containing an alkoxy group including a halogen atom, d- (: 6 ) Or one or two or three substituted fluorenyl groups of the formula: a c 2 -alkenyl group; or any one or two groups including a halogen atom, an alkoxy group of CrC 6 or a hydroxyl group. Or three substituted C 2 -( 6 alkenyl; C 2 -C e alkynyl; any one, two or three substituted C 2 containing a halogen atom, a C 6 decyloxy group or a hydroxyl group - alkynyl; C 3 -C 6 cycloalkyl; any one, two or three substituted (: 3 - C e ring) containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce Alkyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, CrC alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, Any one, two or three substituted aryl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, a dC^ marriage group, a nitro group, a carboxyl group, an aldehyde group, Any one or two of a methoxy group, an amine group, an amide group, a carboxamide group, a thiol group, a methylthio group, and an ethylthio group. Or a three-substituted pyridyl group; containing a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, mercapto group, methylthio group, ethyl sulfide Any one, two or three substituted furanyl groups including a halogen atom, d- (: 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carbon) amide groups, mercapto, methylthio, ethylthio, including one, two or three of the substituents pyranyl; include halogen atom-containing, (^ - (4 embankment group, a nitro group, a carboxyl group, an aldehyde group any alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include a halogen atom-containing, ((4 alkoxy Any one, two or three substituted pyrrolyl groups including a benzyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group and an ethylthio group; embankment C 6 acyl group; a halogen atom-containing include, dC group having 6 or embankment Group, including any one, two or three substituents of the group Cr C e of the embankment; C 2 C e alkylene group; a halogen atom-containing optionally include, d-Ce alkoxy group or a hydroxy group including, two Or three substituted C 2 -C 6 alkenoyl groups; C 2 -C e alkynyl groups; containing any one, two or three including a halogen atom, ^-(: 6 alkoxy group or hydroxyl group) a substituted C 2 -C e alkynyl group; a C 3 -C 6 cycloalkanoyl group; any one, two or three substituted C 3 groups including a halogen atom, an alkoxy group of CrC 6 or a hydroxyl group ; - C 6 cyclodecanoyl; adamantyl, substituted adamantyl form; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrroyl; ) „, η is 0-2, 0, S or Lishi; R5， ， R7， 分别为：
Figure imgf000043_0001
其中 为下列任意一种取代基： H; Cr Ce的烷基； 含有包括卤素原子、 d- 的垸氧基 或羟基在内的任意一个、 两个或者三个取代的 Cr (^的烷基； C2- C6 烯基； 含有包括卤素 原子、 C「C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- (：6的烯基； C2- C6的 炔基；含有包括卤素原子、 Cr 的垸氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3- Ce的环焼基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、两个 或者三个取代的 C3-Ce的环院基； 芳基；苄基； 呋喃基； 吡喃基； 噻吩基；吡咯基； 吡啶基； 含有包括卤素原子、 Cr C4的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 烷基、 硝基、 羧基、 酸基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- C4的垸基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- ( 的烷基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d- ( 4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括卤素原子、 C,-^的烷基、硝基、羧基、 醛基、垸氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； Cr C6的垸酰基； 含 有包括卤素原子、 （ Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的垸 酰基； C2- C6的烯酰基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或 者三个取代的 C2- Ce的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 Cr (6的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 C2-C6的炔酰基； C3- C6的环垸酰基； 含有包括卤素 原子、 （ C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环垸酰基； 金 刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2) n， n为 0-2， 0， S或者 NH时; R 5 , , R 7 , are:
Figure imgf000043_0001
Wherein is any one of the following substituents: H; an alkyl group of Cr C e ; an alkyl group containing any one, two or three substituents including a halogen atom, a decyloxy group or a hydroxyl group of d- ; C 2 - C 6 alkenyl; any one, two or three substituted C 2 - (: 6 alkenyl; C 2 - containing a halogen atom, C "C 6 alkoxy group" or a hydroxyl group; Alkynyl group of C 6 ; any one, two or three substituted C 2 -C 6 alkynyl groups including a halogen atom, a decyloxy group or a hydroxyl group of Cr; a C 3 -C e cyclodecyl group; Any one, two or three substituted C 3 -C e ring-containing groups including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; an aryl group; a benzyl group; a furyl group; a pyranyl group; group; a pyrrolyl group; a pyridyl group; include a halogen atom-containing, Cr C 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio Any one, two or three substituted aryl groups, including a halogen atom, Any one, two or three substituted pyridyl groups of an alkyl group, a nitro group, a carboxyl group, an acid group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one containing a halogen atom, a sulfhydryl group of d-C 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, Two or three substituted furanyl groups; containing a halogen atom, d-(alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio, including any one, two or three of the substituents pyranyl; include a halogen atom-containing, D- (4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide Any one, two or three substituted thienyl groups including a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, C, -^, a nitro group, a carboxyl group, or an aldehyde group , anthraceneoxy, amine, amide, carboxamide, sulfhydryl, methylthio Ethylthio, including any one, two or three substituents pyrrolyl; Cr C 6 acyl embankment; include a halogen atom-containing, (hydroxy or alkoxy of Ce, including any one, two or three Substituted d-C 6 decanoyl; C 2 -C 6 enoyl; any one, two or three substituted C 2 - C e containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group enoyl; C 2 - C 6 alkynyl group; and one, two or three substituents contain any alkynyl group include a halogen atom, Cr embankment or a hydroxyl group (including 6 is C 2 -C 6; C 3 - C 6 cycloalkyl group of embankment; include a halogen atom-containing, any (C6 alkoxy or hydroxy, including one, two or three substituents of C 3 - C 6 cycloalkyl group of embankment; adamantyl embankment formyl, Substituting adamantyl; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrrolyl; (CH 2 ) n , n is 0-2, 0, S or NH; 或者 R5， Ra, R7, 分别为：
Figure imgf000044_0001
Or R 5 , Ra, R 7 , respectively:
Figure imgf000044_0001
 其中 R1()， 各自独立为下列任意一种取代基： H; d- C6的烷基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d- 的垸基； （2-(]6的烯基； 含有包括卤素原子、 （ C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ^的 烯基； C2- C6的炔基； 含有包括卤素原子、 C「C6的垸氧基或羟基在内的任意一个、两个或者 三个取代的 C2- C6的炔基； C3- C6的环垸基； 含有包括 素原子、 C「 Cs的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环烧基； 芳基； 苄基； 呋喃基；吡喃基； 噻吩基; 吡咯基； 吡啶基； 含有包括卤素原子、 d- C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括 素原子、 d- C4的烷基、硝基、羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基；含有包括卤素原子、 -( 4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr 0<的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 d- ( 4的烷基、硝基、羧基、醛基、 烧氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括 素原子、 d- 的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； c广 c6的垸酰基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、两个或者三个 取代的 d- c6的垸酰基； c2- c6的烯酰基； 含有包括 素原子、 d- 的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2- C6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 d-Cs 的焼氧基或羟基在内的任意一个、 两个或者三个取代的 c2-ce的炔酰基； c3- c6的环垸酰基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- Cs的 环浣酰基； 金刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； X (CH ， n为 0-2， 0， S或者 NH时；; X2为（CH ， n为 0-2, 0， S或者 NH时； Wherein R 1( ) is independently one of the following substituents: H; an alkyl group of d-C 6 ; any one, two or three containing an alkoxy group including a halogen atom, dC 6 or a hydroxyl group. Substituted d- fluorenyl; ( 2- ( 6 ) alkenyl; any one, two or three substituted C 2 - ^ olefins including a halogen atom, (C6 alkoxy group or hydroxyl group) groups; C 2 - C 6 alkynyl group; a halogen atom includes any containing, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents of C 2 - C 6 alkynyl group; C. 3 - a cyclic fluorenyl group of C 6 ; a C 3 -C 6 cycloalkyl group containing a aryl group or a hydroxyl group including a C atom, a C s decyl group or a hydroxy group; an aryl group; a furanyl group; a pyrenyl group; a pyrenyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carbon group amide groups, mercapto, methylthio, ethylthio, including one, two or three aryl group substituents; including vegetarian containing atoms, d- C 4 Any one, two or three substituted pyridyl groups such as an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group; Containing any one or two including a halogen atom, -( 4 alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group, methylthio group, ethylthio group) Or three substituted furanyl groups; containing a halogen atom, Cr 0 < alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, B Any one, two or three substituted pyranyl groups including a thio group; containing a halogen atom, d-( 4 alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, Any one, two or three of a carboxamide group, a thiol group, a methylthio group or an ethylthio group Substituted thienyl; containing alkane, d-alkyl, nitro, carboxy, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted pyrrolyl groups; c-C 6 decanoyl group; any one, two or three substituted d- groups including a halogen atom, an alkoxy group of d- or a hydroxyl group c embankment 6 acyl; c 2 - c 6 alkenoyl; comprising pigment containing atoms, d- or hydroxyl group of the embankment, including any one, two or three substituents of C 2 - C 6 alkenyl group; and a C 2 -C 6 alkynyl group; a acetylenic group having any one, two or three substituted c 2 -c e including a halogen atom, a decyloxy group of d-Cs or a hydroxyl group; c 3 - c 6 Cyclodecanoyl; a cyclohexanoyl group containing any one, two or three substituted C 3 - C s including a halogen atom, a decyloxy group of d-Ce; an adamantyl formyl group, a substituted adamantane Formyl; aroyl; benzoyl; furoyl; pyrrolyl; thiophene; pyrrole Group; X (CH, n is 0-2, 0, S or NH ;; X 2 is (CH, n is 0-2, 0, S or NH; 或者 R5， ， R7分别为：
Figure imgf000045_0001
其中 R12为下列任意一种取代基： H; 的垸基； 含有包括卤素原子、 d- ( 6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 C「 (]6的烷基； C2- (6的烯基； 含有包括卤素 原子、 （ Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 的烯基； C2-C6的 炔基;含有包括卤素原子、 Ct-Ce的垸氧基或羟基在内的任意一个、两个或者三个取代的 C2-C3 的炔基； C3- C6的环烷基； 含有包括 素原子、 d-C6的垸氧基或羟基在内的任意一个、两个 或者三个取代的 C3_C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- C4的垸基、硝基、羧基、 醛基、烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 <「(4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 -^的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr ( 4的垸基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 C「 C4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括 素原子、 C「 C4的烷基、硝基、 羧基、 醛基、烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； C6的烷酰基； 含 有包括卤素原子、 d-Cs的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C6的垸 酰基； C2- (；6的烯酰基含有包括卤素原子、 d-Cs的垸氧基或羟基在内的任意一个、两个或者 三个取代的 C2- C6的烯酰基;； C2_Ce的炔酰基； 含有包括卤素原子、 C「 C6的垸氧基或羟基在 内的任意一个、 两个或者三个取代的 C2-C6的炔酰基； C3- C6的环垸酰基； 含有包括卤素原 子、 - 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c3- 6的环烷酰基； 金刚 烷甲酰基、取代金刚烷甲職基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰基; 吡咯甲酰基； 为（CH2) n, n为 0-2， 0， S或者 NH时; Or R 5 , , R 7 are:
Figure imgf000045_0001
Wherein R 12 is any of the following substituent groups: H; embankment group; contain any halogen atom include, d- alkoxy or hydroxy (6, including one, two or three substituents of C "(] 6 Alkyl; C 2 - ( 6 alkenyl; containing any one, two or three substituted C 2 - (alkenyl; C 2 -) including a halogen atom, (alkoxy or hydroxy group of Ce) Alkynyl group of C 6 ; any one, two or three substituted C 2 -C 3 alkynyl groups including a halogen atom, a decyloxy group or a hydroxyl group of Ct-Ce; a C 3 - C 6 naphthenic group; Any one, two or three substituted C 3 -C 6 cycloalkyl groups including a sulfhydryloxy group or a hydroxyl group of a aryl group, dC 6 ; an aryl group; a benzyl group; a furyl group; a pyranyl group; a thiophenyl group; a pyrrolyl group; a pyridyl group; a fluorenyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, ethylthio, including any one, two or three aryl group substituents; include a halogen atom-containing, <"(4 alkyl, nitro, carboxamide Any one, two or three substituted pyridyl groups, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, -^ Any one, two or three substituted furanyl groups such as an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group. Containing any one of a halogen atom, a Cr ( 4 sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group) Two or three substituted pyranyl groups; containing a halogen atom, C "C 4 sulfhydryl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide Any one, two or three substituted thienyl groups including a thiol group; a C, C 4 alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group Any of a group, a carboxamide group, a thiol group, a methylthio group, an ethylthio group Is intended one, two or three substituents pyrrolyl; C 6 alkanoyl; one, two or three of the substituents include a halogen atom contain any C, d-Cs alkoxy group or a hydroxyl group, including the embankment 6 of acyl; C 2 - (; 6 alkenoyl contain any halogen atoms include, d-Cs alkoxy or hydroxy the embankment, including one, two or three substituents of C 2 - C 6 alkenyl group ;; C 2 of _C e alkynyl group; containing optionally include halogen, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents of C 2 -C 6 alkynyl group of; C 3 - C 6 cycloalkyl Decanoyl; Embankment any group or hydroxyl group, including one, two or three substituents of c 3 - - promoter, cycloalkyl of 6 alkanoyl; carbamoyl adamantane, substituted adamantane carboxylic functional group; an aryl group; a benzyl group; furan Formyl; pyranoyl; thiophene; pyrroyl; when (CH 2 ) n , n is 0-2, 0, S or NH; 或者 R5， ， R7分别为：
Figure imgf000046_0001
Or R 5 , , R 7 are:
Figure imgf000046_0001
 其中 R13, 各自独立为下列任意一种取代基： H; d- 的烷基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 (^的垸基； C2- ( 的烯基； 含有包括卤素原子、 -Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 的 烯基； C2- Ce 炔基； 含有包括卤素原子、 C「C6的垸氧基或羟基在内的任意一个、 两个或者 三个取代的 C2-Ce ½炔基； C3- C6的环烷基； 含有包括 素原子、 d- 的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- Ce的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括 素原子、 d- C4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括 素原子、 C「 C4的烷基、 硝基、 羧基、 醛基、垸氧基、 胺基、酰胺基、 碳酰胺基、 琉基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 -^的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、'乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- C4的焼基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的吡喃基； 含有包括卤素原子、 d- C4的烷基、硝基、羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- c4的焼基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基;Wherein R 13 , each independently is any one of the following substituents: H; d-alkyl; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group (^ Alkyl; C 2 - (alkenyl; any one, two or three substituted C 2 - (alkenyl; C 2 - C) including a halogen atom, an alkoxy group of -Ce or a hydroxyl group e alkynyl; optionally include a halogen atom-containing, C "C 6 alkoxy or hydroxy embankment inner one, two or three substituents of C 2 -C e ½ alkynyl group; C 3 - C 6 cycloalkyl Any one, two or three substituted C 3 -C e cycloalkyl groups including a aryl group, a d-alkoxy group or a hydroxy group; an aryl group; a benzyl group; a furyl group; a pyranyl group; a thiophenyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a aryl group, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, ethylthio, including any one, two or three aryl group substituents; including vegetarian containing atoms, C "C 4 alkyl group, a nitro group Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an 'ethylthio group. a furanyl group; a thiol group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, Any one, two or three substituted thienyl groups including a mercapto group, a methylthio group, an ethylthio group; a mercapto group including a halogen atom, d-c 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, Amine, amide, carboxamide, sulfhydryl, methylthio, ethyl sulphide Including any one, two or three substituents pyrrolyl; C「 C6的垸酰基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或者三个 取代的 c「 C6的垸酰基； C2- C6的烯酰基； 含有包括卤素原子、 d- c6 垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2- Ce的烯酰基； C2-C3的炔酰基； 含有包搏卤素原子、 CrCe 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2-C6的炔酰基； C3-Ce的环垸酰基; 含有包括卤素原子、 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- ( 6的 环垸酰基； 金刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； n为 0- 2, 0， S或者雇时; ¾为 ((¾)„， n为 0-2, 0， S或者删寸； C "decanoyl group of C 6 ; any one, two or three substituted c" C 6 decanoyl groups including a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; a C 2 - C 6 alkene An acyl group having any one, two or three substituted C 2 -C e groups including a halogen atom, d-c 6 methoxy group or a hydroxyl group; a C 2 -C 3 alkynyl group; Any one, two or three substituted C 2 -C 6 alkynyl groups of a halogen atom, a decyloxy group or a hydroxyl group of CrC e ; a C 3 -C e cyclodecanoyl group; Any one, two or three substituted C 3 -( 6-cyclodecanoyl; adamantyl form, substituted adamantyl form; aroyl group; benzyl group; furoyl group; pyran Formyl; thiophene; pyrrolyl; n is 0-2, 0, S or hired; 3⁄4 is ((3⁄4)„, n is 0-2, 0, S or deleted; 当！^， R2, R3， 为：
Figure imgf000046_0002
其中 R15, R16各自独立为下列任意一种取代基： H; d- (6的垸基； 含有包括卤素原子、 C 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的垸基； C2- ( 6的烯基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的 烯基； C2- 的炔基； 含有包括卤素原子、 C「Ce的垸氧基或羟基在内的任意一个、两个或者 三个取代的 C2- C6的炔基； C3- C6的环烷基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- Ce的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- 0»的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-C4的垸基、硝基、羧基、 醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基；含有包括卤素原子、 (^-( 的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- C4的烷基、硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的吡喃基； 含有包括卤素原子、 C「( 的浣基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 c「 c4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； c「ce的烷酰基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、两个或者三个 取代的 c「 c6的烷酰基； c2- c6的烯酰基； 含有包括卤素原子、 c「c6 ½烷氧基或羟基在内的 任意一个、两个或者三个取代的 C2-C6的烯酰基； C2- Ce的炔酰基； 含有包括卤素原子、 G-Ce 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c2-c6的炔酰基； c3-cs的环烷酰基； 含有包括卤素原子、 （ Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的 环烷酰基； 金刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基 ·， 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为((¾)„， n为 0-2， 0， S或者 NH时; X 2为 (C ) n， n为 0 - 2， 0， S或者 NH时； when! ^, R 2 , R 3 , are:
Figure imgf000046_0002
Wherein R 15 and R 16 each independently are any one of the following substituents: H; d- ( 6 fluorenyl; any one, two or three substitutions including a halogen atom, an alkoxy group of C or a hydroxyl group) a d-C 6 fluorenyl group; a C 2 - ( 6 alkenyl group; any one, two or three substituted C 2 - C 6 groups including a halogen atom, an alkoxy group of d- or a hydroxyl group; alkenyl; C 2 - alkynyl; containing optionally include halogen, C "C e is a hydroxyl group or embankment, including one, two or three substituents of C 2 - C 6 alkynyl group; C 3 - a cycloalkyl group of C 6 ; a cyclohexyl group containing any one, two or three substituted C 3 - C e including a halogen atom, C "C 6 alkoxy group or a hydroxyl group; aryl group; benzyl group ; furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing an alkyl group including a halogen atom, d-O», a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carbon amide any group, a mercapto group, methylthio, ethylthio, including one, two or three aryl group substituents; containing a halogen atom include, dC 4 Any one, two or three substituted pyridyl groups including a mercapto group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, and an ethylthio group. Any one containing a halogen atom, a sulfhydryl group, a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group , two or three substituted furanyl groups; containing an alkyl group including a halogen atom, d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl sulfide Any one, two or three substituted pyranyl groups including a thiol group; containing a halogen atom, C" (indenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide) Any one, two or three substituted thienyl groups including a carbaryl group, a fluorenyl group, a methylthio group, an ethylthio group; a thiol group including a halogen atom, c "c 4 ", a nitro group, a carboxyl group, an aldehyde Base, oxime, amine, amide, carboxamide, sulfhydryl, a Group, ethylthio, including any one, two or three substituents pyrrolyl; C "c e alkanoyl; contain any halogen atom includes, a hydroxyl group or a dC embankment 6 of the inner one, two, Or three substituted c"c 6 alkanoyl; c 2 - c 6 enoyl; any one, two or three substituted including a halogen atom, c "c 6 1⁄2 alkoxy group or a hydroxyl group" C 2 -C 6 alkenoyl; C 2 -C e alkynyl; any one, two or three substituted c 2 -c 6 containing a halogen atom, a methoxy group or a hydroxyl group of GC e Alkanoyl; a cycloalkanoyl group of c 3 -c s; a cycloalkanoyl group containing any one, two or three substituted C 3 -C 6 groups including a halogen atom, (alkoxy group of Ce or a hydroxyl group); Alkanoyl, substituted adamantyl; aroyl; benzoyl; furoyl, pyranoyl; thiophene; pyrrolyl; ((3⁄4)„, n is 0-2, 0, S Or NH; X 2 is (C ) n , n is 0 - 2, 0, S or NH; R5, R6, R7分别为：
Figure imgf000047_0001
其中 R9为下列任意一种取代基： H; C Ce的烷基； 含有包括卤素原子、 CrCe的垸氧基 或羟基在内的任意一个、 两个或者三个取代的 d- (：6的烷基； C2-Ce的烯基； 含有包括卤素 原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的（2-( 的烯基； （：2-( 6的 炔基；含有包括卤素原子、 C「 C6的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3- C6的环烷基； 含有包括 素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个 或者三个取代的 - 的环烧基； 芳基；苄基；呋喃基； 吡喃基； 噻吩基；吡咯基； 吡啶基； 含有包括 素原子、 d- ( 4的垸基、硝基、羧基、 醛基、烷氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 -( 4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- (：4的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 -(4的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括 素原子、 c「 c4 烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、 d-c4的烷基、硝基、羧基、 醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； - ce的烷酰基； 含 有包括卤素原子、 C^Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的烷 酰基； c2- C6的烯酰基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或 者三个取代的 c2- C6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 d- ( 的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 c2- ce的炔酰基； c3- c6的环烷酰基； 含有包括卤素 原子、 d-c6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c3-c6的环垸酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2)„， n为 0-2， 0， S或者 NH时; R 5 , R 6 and R 7 are:
Figure imgf000047_0001
Wherein R 9 is any one of the following substituents: H; an alkyl group of CC e ; any one, two or three substituted d- ( 6 ) containing a halogen atom, a decyloxy group or a hydroxyl group of CrC e Alkyl; C 2 -C e alkenyl; any one, two or three substituted ( 2- (alkenyl); (: 2 ) containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group - (6 alkynyl; containing optionally include halogen atoms, C "6 alkoxy or hydroxy C inner one, two or three substituents of C 2 -C 6 alkynyl group of; C. 3 - C 6 a cycloalkyl group; a cycloalkyl group containing any one, two or three substituted — including a sulfhydryl group or a hydroxyl group of dC 6 ; an aryl group; a benzyl group; a furyl group; a pyranyl group; Pyrrolyl; pyridyl; Containing any one including a sulfhydryl group, a d-( 4 fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, Two or three substituted aryl groups; containing a halogen atom, -( 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, Any one, two or three substituted pyridyl groups including an ethylthio group; containing a halogen atom, d- (: 4 alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group) , any carbon amide group, a mercapto group, methylthio, ethylthio, including one, two or three substituents furanyl; containing a halogen atom include, - (4 embankment group, a nitro group, a carboxyl group, an aldehyde group, any alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three of the substituents pyranyl; comprising pigment containing atoms, C "c 4 alkoxy Base, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carbon Any amino, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include a halogen atom-containing, dc alkyl, nitro, carboxyl, aldehyde, alkoxy 4 Any one, two or three substituted pyrrolyl groups, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; an alkanoyl group of - c e ; containing a halogen atom, C^ Any one, two or three substituted d-C 6 alkanoyl groups such as a decyloxy group or a hydroxyl group of Ce; a c 2 - C 6 alkenoyl group; a decyloxy group or a hydroxyl group including a halogen atom, dC 6 Any one, two or three substituted c 2 -C 6 alkenoyl groups; C 2 -C 6 alkynyl group; or any one containing a halogen atom, d-(alkoxy group or hydroxyl group) , two or three substituted c 2 - c e alkynyl groups; c 3 - c 6 cycloalkanoyl groups; containing any one, two or three including a halogen atom, an alkoxy group of dc 6 or a hydroxyl group Substituted c 3 -c 6 cyclodecanoyl; adamantyl, substituted adamantyl; aroyl Benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH 2 ), when n is 0-2, 0, S or NH; 或者 R5， R6， R7分别为：
Figure imgf000048_0001
Or R 5 , R 6 , R 7 are:
Figure imgf000048_0001
 其中 Rw， Ru各自独立为下列任意一种取代基： H; (^-( 6的烷基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C「C6的烷基； C2- ( 6的烯基； 含有包括卤素原子、 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2-C3的 烯基； C2- (：6的炔基； 含有包括卤素原子、 C「Ce的垸氧基或羟基在内的任意一个、两个或者 三个取代的 C2- ( 6的炔基； C3- Cs的环烷基； 含有包括 素原子、 d-C6的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- (^的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 (：4的烷基、硝基、羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个^者三个取代的吡啶基；含有包括卤素原子、 (「( 4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- (4的垸基、硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 d- ( 的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- c4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基;Wherein R w , Ru are each independently one of the following substituents: H; (^-( 6 alkyl; any one, two or three containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group) Substituted C "C 6 alkyl group; C 2 - ( 6 alkenyl group; any one, two or three substituted C 2 -C 3 olefins including a halogen atom, a decyloxy group or a hydroxyl group) groups; C 2 - (: 6 alkynyl; includes contain any halogen atom, C "C e is a hydroxyl group or embankment, including one, two or three substituents of C 2 - (6 alkynyl; C a cycloalkyl group of 3 - C s ; a C 3 - C 6 cycloalkyl group containing any one, two or three substituents including a sulfhydryl group or a hydroxyl group of a dC 6 ; an aryl group; ; furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, d-(^, alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide any group, a mercapto group, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, (: 4 Any one, two or three substituted pyridyl groups of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group. Containing any one including a halogen atom, ("( 4 thiol, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) , two or three substituted furanyl groups; containing a halogen atom, d-( 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methyl sulfide Any of the base and ethylthio group One, two or three substituted pyranyl groups; containing a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, fluorenyl group, A Any one, two or three substituted thienyl groups including a thio group and an ethylthio group; containing an alkyl group including a halogen atom, d-c 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, Any one, two or three substituted pyrrolyl groups such as an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group; C-Ce的垸酰基； 含有包括卤素原子、 CrC6的垸氧基或羟基在内的任意一个、两个或者三个 取代的 Cr Ce的烷酰基； C2- C6的烯酰基； 含有包括卤素原子、 d- C6的烷氧基或羟基在内的 任意一个、两个或者三个取代的 C2-C6的烯酰基； C2-C6的炔酰基； 含有包括卤素原子、 d-Qi 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2 C6的炔酰基； C3- C6的环垸酰基; 含有包括卤素原子、 Cr 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的 环烷酰基； 金刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（(¾ ， n为 0-2， 0， S或者 NH时； ¾为（CH2)„， n为 0-2 , 0， S或者 NH时； a decanoyl group of C-Ce; an alkanoyl group containing any one, two or three substituted Cr C e including a halogen atom, a decyloxy group or a hydroxyl group of CrC 6 ; a C 2 - C 6 alkenoyl group; Any one, two or three substituted C 2 -C 6 alkenoyl groups including a halogen atom, a d-C 6 alkoxy group or a hydroxyl group; a C 2 -C 6 alkynyl group; containing a halogen atom, Any one, two or three substituted C 2 C 6 alkynyl groups of a d-Qi oxime or a hydroxyl group; a C 3 - C 6 cyclodecanoyl group; an alkoxy group containing a halogen atom, Cr Or any one, two or three substituted C 3 -C 6 cycloalkanoyl groups, or a hydroxy group; adamantyl, substituted adamantyl form; aroyl; benzyl; furanoyl; pyranoyl ; thiophene acyl; pyrroyl group; ((3⁄4, n is 0-2, 0, S or NH; 3⁄4 is (CH 2 ) „, n is 0-2, 0, S or NH; 或者 R5， R6， R7分别为：
Figure imgf000049_0001
其中 R12为下列任意一种取代基： H; d-C6的烷基； 含有包括卤素原子、 （^-(：6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d- ( 的垸基； （2-( 的烯基； 含有包括卤素 原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的烯基； C2- C6的 炔基;含有包括卤素原子、 d- C6的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3- Ce的环垸基； 含有包括卤素原子、 C「C6的烷氧基或羟基在内的任意一个、两个 或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括 素原子、 C「C4的烷基、硝基、羧基、 醛基、烷氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 (^-(：4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 Ct-C4 烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr (：4的烷基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 C「 C4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、 烷基、硝基、羧基、酸基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d- ( 6的 '烷酰基； 含 有包括卤素原子、 d-Ce的焼氧基或羟基在内的任意一个、 两个或者三个取代的 d- Ce的烷 酰基； c2- C6的烯酰基； 含有包括卤素原子、 d_C6的烧氧基或羟基在内的任意一个、两个或 者三个取代的 c2-c6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 d- (6的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 c2- ce的炔酰基； c3- c6的环烷酰基； 含有包括卤素 原子、 的浣氧基或羟基在内的任意一个、 两个或者三个取代的 c3- c6的环垸酰基； 金 刚垸甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（C¾) n， n为 0-2， 0， S或者腿时; Or R 5 , R 6 , R 7 are:
Figure imgf000049_0001
Wherein R 12 is any one of the following substituents: H; an alkyl group of dC 6 ; an alkyl group containing one, two or three substituents including a halogen atom, (^-(: 6 alkoxy group or hydroxyl group) - (indenyl; ( 2- (alkenyl); any one, two or three substituted C 2 -C 6 alkenyl group including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; C 2 - C 6 alkynyl group; and optionally containing a hydroxyl group or an alkoxy group include a halogen atom, C 6 D- inner one, two or three substituents of C 2 -C 6 alkynyl group of; C 3 - C e cyclic alkyl with; containing optionally include halogen atoms, C "C 6 alkoxy or hydroxy, including one, two or three substituents of C 3 - C 6 cycloalkyl; aryl; benzyl; furan group; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; comprising pigment containing atoms, C "C 1-6 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide group 4, any mercapto, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, (^ - (: 4 embankment group, nitro Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of Ct-C 4 alkyl, nitro, carboxy, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio a furanyl group; containing a halogen atom, Cr (: 4 alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) any one, two or three of the substituents pyranyl; include halogen atom-containing, C "C 4 alkyl with a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, carbonamide group, Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an acid group, an alkoxy group, an amine group, an amide group , carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituents pyrrolyl; d- ( '6 alkanoyl; one, two or three substituents contain any halogen atoms include, d-Ce-alkoxy or hydroxy, including the firing of d An alkanoyl group of C e ; an alkenoyl group of c 2 - C 6 ; any one or two or more containing an alkoxy group or a hydroxyl group including a halogen atom, d_C 6 or a three-substituted c 2 -c 6 alkenoyl group; a C 2 -C 6 alkynyl group; containing any one, two or three substitutions including a halogen atom, d-( 6 oximeoxy group or hydroxyl group) a c 2 - c e alkynyl group; a c 3 - c 6 cycloalkanoyl group; any one, two or three substituted c 3 - c 6 groups including a halogen atom, a decyloxy group or a hydroxyl group Cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrrolyl; (C3⁄4) n , n 0-2, 0, S or leg time; 或者 R5， R6, R7分别为：
Figure imgf000050_0001
Or R 5 , R 6 , R 7 are:
Figure imgf000050_0001
 其中^， R14各自独立为下列任意一种取代基： H; d- C6的烷基； 含有包括卤素原子、 C「Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d-Ce 垸基； C2- Ce 烯基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 6的 烯基； （：2-(：6的炔基； 含有包括卤素原子、 d-C6的院氧基或羟基在内的任意一个、两个或者 三个取代的 -( 6的炔基； C3- Ce的环烷基； 含有包括卤素原子、 d- 的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- Ce的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 ( 的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包卤素原子、括 d- ^的垸基、硝基、羧基、醛基、垸氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 (^-(]4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 - 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 Cr ( 4的烷基、硝基、羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 0(：4的烷基、 硝基、 羧基、 酸基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d- C6的烷酰基； 含有包括卤素原子、 CrC6的浣氧基或羟基在内的任意一个、两个或者三个 取代的 d- c6的烷酰基； c2- c6的烯酰基； 含有包括卤素原子、 c「 的垸氧基或羟基在内的 任意一个、两个或者三个取代的 c2_c6的烯酰基； c2- ce的炔酰基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c2-c6的炔酰基； c3- ce的环烷酰基; 含有包括卤素原子、 d-C^的垸氧基或羟基在内的任意一个、 两个或者三个取代的 c3-c6的 环垸酰基； 金刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（(¾)„， n为 0-2， 0， S或者 NH时； 为 (C¾) n, n为 0-2， 0， S或者 NH时; Wherein, R 14 are each independently a substituent of any of the following: H; an alkyl group of d-C 6 ; any one, two or three containing a halogen atom, an alkoxy group of C "C e or a hydroxyl group" Substituted d-Ce fluorenyl; C 2 -C e alkenyl; any one, two or three substituted C 2 - ( 6 olefins) including a halogen atom, an alkoxy group of dC e or a hydroxyl group (: 2 -(: 6 alkynyl; any one, two or three substituted - ( 6 alkynyl group; C 3 - C containing a halogen atom, a courtoxy group of dC 6 or a hydroxyl group) a cycloalkyl group of e ; any one, two or three substituted C 3 - C e cyclodecyl groups including a halogen atom, an alkoxy group of d- or a hydroxyl group; an aryl group; a benzyl group; a furyl group ; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methyl sulfide Any one, two or three substituted aryl groups including a thiol group; a fluorenyl group containing a halogen atom, including d-^ Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; An atom, an alkyl group of (^-(] 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, or both Or three substituted furanyl groups; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group including any one, two or three of the substituents pyranyl; include a halogen atom-containing, Cr (4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide group Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, an alkyl group of 0 (: 4 , a nitro group, a carboxyl group, an acid group, an alkoxy group) , amine, amide, carboxamide, sulfhydryl, methylthio, B Any one, two or three substituted pyrrolyl groups including a thio group; an alkanoyl group of d-C 6 ; any one, two or three containing a halogen atom, a decyloxy group of CrC 6 or a hydroxyl group Substituted d-c 6 alkanoyl; c 2 - c 6 enoyl; any one, two or three substituted c 2 _c 6 containing a halogen atom, c 垸 methoxy or hydroxy Alkynyl; c 2 - c e alkynyl; any one, two or three substituted c 2 -c 6 alkynyl groups including a halogen atom, an alkoxy group of d- or a hydroxyl group; c 3 - a cycloalkanoyl group of c e ; any one, two or three substituted c 3 -c 6 cyclodecanoyl groups including a halogen atom, a decyloxy group of dC^ or a hydroxyl group; adamantyl group, substituted gold Benzoyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; ((3⁄4)„, n is 0-2, 0, S or NH; (C3⁄4 ) n , n is 0-2, 0, S or NH; 当 ， R2， R3， R4为：
Figure imgf000051_0001
When R 2 , R 3 , R 4 are:
Figure imgf000051_0001
 其中 Rn为下列任意一种取代基： H; Cr (：6的浣基； 含有包括卤素原子、 d- ( 6的垸氧基 或羟基在内的任意一个、 两个或者三个取代的 C Ce的垸基； C2- (：6的烯基； 含有包括卤素 原子、 Cr Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- (：6的烯基； C2-C6的 炔基;含有包括卤素原子、 的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-Ce 的炔基； C3- C6的环烷基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、两个 或者三个取代的 C3- C6的环垸基； 芳基；苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 的烷基、硝基、羧基、醛基、 烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d-C4的垸基、 硝 基、 羧基、 醛基、 焼氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 - 的浣基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d-C4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、 d- (]4的垸基、硝基、羧基、醛基、 烷氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； Ct- C6的垸酰基； 含 有包括卤素原子、 CrCe的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d-Cfi的烷 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或 者三个取代的 C2- C6的烯酰基； C2-Ce的炔酰基； 含有包括卤素原子、 d- (6的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3- C6的环垸酰基； 含有包括卤素 原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环烷酰基； 金 刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； X^ (CH2) n， n为 0-2， 0， S或者 NH时； Wherein Rn is any one of the following substituents: H; Cr (: 6 fluorenyl; any one, two or three substituted CC e including a halogen atom, d- ( 6 decyloxy or hydroxy group) Alkyl; C 2 - (: 6 alkenyl; any one, two or three substituted C 2 - ( 6 alkenyl) containing a halogen atom, a decyloxy group or a hydroxyl group of Cr C e a C 2 -C 6 alkynyl group; any one, two or three substituted C 2 -C e alkynyl groups including a halogen atom, an alkoxy group or a hydroxyl group; a C 3 - C 6 ring; Any one, two or three substituted C 3 -C 6 cyclodecyl groups including a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; an aryl group; a benzyl group; a furyl group; Thienyl; thienyl; pyrrolyl; pyridyl; containing alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, B Any one, two or three substituted aryl groups including a thio group; containing a halogen atom, a fluorenyl group of 4, a nitro group, a carboxyl group, Any, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two, three or substituted pyridyl; include a halogen atom-containing, 4 dC embankment Any one, two or three substituted furyl groups including a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group; Any one, two or three including a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group a substituted pyranyl group; containing an alkyl group including a halogen atom, dC 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted thienyl groups; containing a halogen atom, a fluorenyl group of d-(] 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group Any one of thiol, methylthio, ethylthio Two or three substituents pyrrolyl; C t - C 6 acyl group of the embankment; includes any halogen atom-containing, or hydroxyl group CRCE the embankment, including one, two or three of the substituents dC fi alkanoyl; C 2 - C e, alkenoyl; contain any halogen atom includes, a hydroxyl group or a dC e embankment inner one, two or three substituents of C 2 - C 6 alkenyl group of; C 2 -C e of An alkynyl group; a acetylenedoyl group containing any one, two or three substituted C 2 -C 6 groups including a halogen atom, d-( 6 alkoxy group or a hydroxyl group; a C 3 -C 6 cyclodecanoyl group; Any one, two or three substituted C 3 -C 6 cycloalkanoyl groups including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; an adamantyl formyl group, a substituted adamantyl group; an aroyl group; Benzyl; furoyl; pyranoyl; thiophene; pyrrolyl; X^(CH 2 ) n , n is 0-2, 0, S or NH; R5， R6, RT, 分别为：
Figure imgf000051_0002
其中 为下列任意一种取代基： H; Cr Ce的垸基； 含有包括卤素原子、 （^-(6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d-c6的烷基； C2- ( 6的烯基； 含有包括卤素 原子、 d- 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的烯基； C2- C6的 炔基;含有包括卤素原子、 CrC6的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3- C6的环烷基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、两个 或者三个取代的 c3- c6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、 d- c4的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、R 5 , R 6 , RT, are:
Figure imgf000051_0002
6 DC any one, two or three alkoxy or hydroxy substituted (including the 6 - include a halogen atom-containing, (^; H; Cr C e is alkyl with: wherein any one of the following substituents An alkyl group; a C 2 - ( 6 alkenyl group; any one, two or three substituted C 2 - C 6 alkenyl groups including a halogen atom, a decyloxy group or a hydroxyl group of d-; C 2 - Alkynyl group of C 6 ; any one, two or three substituted C 2 -C 6 alkynyl groups including a halogen atom, an alkoxy group of CrC 6 or a hydroxyl group; a C 3 - C 6 cycloalkyl group; Any one or two containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; Or a three-substituted c 3 - c 6 cycloalkyl group; an aryl group; a benzyl group; a furyl group; a pyranyl group; a thienyl group; a pyrrolyl group; a pyridyl group; and an alkyl group including a halogen atom, d-c 4 , Any one, two or three substituted aryl groups including a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; atom, CrC^烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 · 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 ( 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- ( 的垸基、硝基、羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括 素原子、 d- ^的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的噻吩基; 含有包括卤素原子、 d- (：4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； C6的垸酰基； 含 有包括卤素原子、 -Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d-C3的烷 酰基； c2- c6的烯酰基； 含有包括卤素原子、 d-c 的垸氧基或羟基在内的任意一个、 两个或 者三个取代的 C2-C6的烯酰基； C2-C6的块酰基； 含有包括卤素原子、 CrC6的烷氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3-C6的环烷酰基； 含有包括卤素 原子、 CrCe的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的环烷酰基； 金 刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2) n， η为 0-2， 0， S或者 ΝΗ时; Any one, two or three substituted groups of CrC^alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio a pyridyl group; containing any one of a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, and an ethylthio group. Two or three substituted furanyl groups; containing a halogen atom, d-(indenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, Any one, two or three substituted pyranyl groups including an ethylthio group; an alkyl group including a sulfonate atom, d-^, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, Any one, two or three substituted thienyl groups including a carboxamide group, a fluorenyl group, a methylthio group and an ethylthio group; containing a halogen atom, d- (: 4 fluorenyl group, nitro group, carboxyl group, aldehyde group) , oxime, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted pyrrolyl groups such as a methylthio group or an ethylthio group; a decanoyl group of C 6 ; or any one or two groups including a halogen atom, a decyloxy group of -Ce or a hydroxyl group; Or a substituted alkanoyl group of dC 3 ; an alkenoyl group of c 2 - c 6 ; any one, two or three substituted C 2 -C 6 containing a halogen atom, a decyloxy group of dc or a hydroxyl group; Alkenoyl; C 2 -C 6 block acyl; any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, an alkoxy group of CrC 6 or a hydroxyl group; C 3 -C 6 cycloalkyl group; a halogen atom-containing optionally include, CrC e alkoxy or hydroxy group including one, two or three substituents of C 3 - C 6 cycloalkyl group; a formyl adamantane, substituted Adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH 2 ) n , η is 0-2, 0, S or hydrazine; 或者 R5， R6, R7分别为-
Figure imgf000052_0001
其中 Rw, Ru各自独立为下列任意一种取代基： H; C「 (：6的烷基； 含有包括卤素原子、 d-Ce的烷氧基或轻基在内的任意一个、 两个或者三个取代的 Ct- (6的烷基； C2- ( 6的烯基； 含有包括卤素原子、 c 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- CB的 烯基； C2 - (]6的炔基； 含有包括卤素原子、 CrC6的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2- (；6的炔基； C3- C6的环烧基； 含有包括卤素原子、 CrC^的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基; 吡咯基； 吡啶基； 含有包括卤素原子、 (]4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 ( 4的烧基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d-C4的垸基、 硝基、 羧基、 醛基、 烧氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d_ (^的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 d- ( 4的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 d- 的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； d-C6的嫁酰基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、两个或者三个 取代的 d- C6的烷酰基； C2- Ce的烯酰基； 含有包括 素原子、 CrC6 烷氧基或羟基在内的 任意一个、两个或者三个取代的 C2- Ce的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 Cr 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- Ce的炔酰基； C3- C6的环烷酰基； 含有包括卤素原子、 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- (：6的 环垸酰基； 金刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（(¾)„， n为 0- 2, 0， S或者腿时; 为 (CH2) n， n为 0-2， 0， S或者 NH时； Or R 5 , R 6 , R 7 are -
Figure imgf000052_0001
Wherein R w , Ru are each independently a substituent of any of the following: H; C " ( 6 : alkyl; any one, two or three containing an alkoxy group including a halogen atom, dC e or a light group) Substituted C t - ( 6 alkyl; C 2 - ( 6 alkenyl; any one, two or three substituted C 2 - C containing a halogen atom, c alkoxy or hydroxy group) Alkenyl group of B ; alkynyl group of C 2 - ( 6 ); any one, two or three substituted C 2 - ( 6 alkynyl group) including a halogen atom, an alkoxy group of CrC 6 or a hydroxyl group a C 3 -C 6 cycloalkyl group; any one, two or three substituted C 3 -C 6 cycloalkyl groups including a halogen atom, a CrC^ alkoxy group or a hydroxyl group; an aryl group; benzyl; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, (] 4 embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, an amide group, carbon Any one, two or three substituted aryl groups including an amide group, a fluorenyl group, a methylthio group, an ethylthio group; Any (group 4 of the burn, a nitro group, a carboxyl group, an aldehyde group, embankment group, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents of Pyridyl; containing a halogen atom, dC 4 sulfhydryl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, B Any one, two or three substituted furanyl groups including a thio group; containing a halogen atom, d-(^ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carbon amide any group, a mercapto group, methylthio, ethylthio, including one, two or three of the substituents pyranyl; include a halogen atom-containing, D- (4 embankment group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy Any one, two or three substituted thienyl groups including an oxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, d-, and a nitrate any group, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents pyrrolyl; dC married 6 An acyl group; any one, two or three substituted d-C 6 alkanoyl group including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; an alkenoyl group of C 2 - C e ; Any one, two or three of CrC 6 alkoxy or hydroxyl Substituted C 2 - C e alkylene group; C 2 - C 6 alkynyl group; a halogen atom-containing optionally include, Cr alkoxy or hydroxy group including one, two or three substituents of C 2 - C e Alkynyl; C 3 -C 6 cycloalkanoyl; any one, two or three substituted C 3 - (: 6 cyclodecanoyl group) containing a halogen atom, a decyloxy group or a hydroxyl group; Alkanoyl, substituted adamantyl form; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; ((3⁄4)„, n is 0-2, 0, S or When the leg is; (CH 2 ) n , n is 0-2, 0, S or NH; 或者 R5， R6， R7分别为：
Figure imgf000053_0001
Or R 5 , R 6 , R 7 are:
Figure imgf000053_0001
 其中 R12为下列任意一种取代基： H; d C6的垸基； 含有包括卤素原子、 C「 ( 6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d- Ce '的烷基； C2- ( 6的烯基； 含有包括卤素 原子、 CrC6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2- (：6的烯基； C2- C6的 炔基;含有包括卤素原子、 的垸氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3-Ce的环垸基； 含有包括卤素原子、 的垸氧基或羟基在内的任意一个、 两个 或者三个取代的 C3-C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、（ - C4的烷基、硝基、羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 - 的焼基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 d- 的烷基、硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- C4的烧基、硝基、羧基、醛基、 烧氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 '乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d- (：4的烷基、 硝基、 羧基、 醛基、 烧氧基、 胺基、 酰胺基、碳酰安基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括 素原子、 C「C4的垸基、硝基、 羧基、醛基、烷氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； CrCs的烷酰基； 含 有包括卤素原子、 Cr 的烧氧基或羟基在内的任意一个、 两个或者三个取代的 d- c6的烷 酰基； c2-c6的烯酰基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、两个或 者三个取代的 c2- ce的烯酰基； c2- c6的炔酰基； 含有包括卤素原子、 c「 0>的垸氧基或羟基 在内的任意一个、 两个或者三个取代的 c2- ce的炔酰基； c3- ce的环烷酰基； 含有包括卤素 原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3_Ca的环垸酰基； 金 刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2) n， n为 0-2， 0， S或者 NH时; Wherein R 12 is any of the following substituent groups: H; d C 6 alkyl with; one, two or three substituents containing optionally include halogen atoms, C "(6 alkoxy or hydroxy, including the d- C e 'is alkyl; C 2 - (6 alkenyl; one, two or three substituents include a halogen atom contain any, CrC alkoxy or hydroxy embankment 6 of the inner C 2 - (: 6-ene groups; C 2 - C 6 alkynyl group; and optionally containing a hydroxyl group or a embankment include a halogen atom, the inner one, two or three substituents of C 2 -C 6 alkynyl group of; C 3 -C e a Any one, two or three substituted C 3 -C 6 cyclodecyl groups containing a halogen atom, a decyloxy group or a hydroxyl group; an aryl group; a benzyl group; a furyl group; a pyranyl group; ; thienyl; pyrrolyl; pyridyl; containing halogen atom, (-C 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio Any one, two or three substituted aryl groups including an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group Any one, two or three substituted pyridyl groups including an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- Any one, two or three substituted furanyl groups such as an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group; Any one containing a halogen atom, a d-C 4 alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an 'ethylthio group. , two or three substituted pyranyl groups; containing a halogen atom, d- (: 4 alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carbonyl group, fluorenyl group) , methylthio, ethylthio, including any one, two or three substituents thienyl; comprising pigment containing atoms, C "4 alkyl with C, nitro, carboxyl, aldehyde, alkoxy, amine Any of a group, an amide group, a carboxamide group, a thiol group, a methylthio group, an ethylthio group One, two or three substituents pyrrolyl; CRCS alkanoyl; containing Any one, two or three substituted d-c 6 alkanoyl groups including a halogen atom, an alkoxy group of a Cr or a hydroxyl group; an alkenoyl group of c 2 -c 6 ; containing a halogen atom, dC e Any one, two or three substituted c 2 - c e enoyl groups such as a decyloxy group or a hydroxyl group; a c 2 - c 6 alkynyl group; a decyloxy group including a halogen atom, c "0" or Any one, two or three substituted c 2 - c e alkynyl groups including a hydroxyl group; a c 3 - c e cycloalkanoyl group; a halogen atom or a hydroxyl group including a halogen atom, d-Ce Any one, two or three substituted C 3 _C a cyclodecanoyl; adamantyl form, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrole Formyl; when (CH 2 ) n , n is 0-2, 0, S or NH; 或者 R5， ， R7分别为：
Figure imgf000054_0001
其中^， R 各自独立为下列任意一种取代基： H; -( 6的垸基； 含有包括卤素原子、 CrC6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d- C6的烷基； C2- ( 的烯基； 含有包括卤素原子、 C,- C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的（2-( 6的 烯基； C2- 06的炔基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2- (：6的炔基； C3- C6的环垸基； 含有包括卤素原子、 d- C6的垸氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基; 吡咯基； 吡啶基； 含有包括卤素原子、 d- (：4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d- (；4的烧基、硝基、羧基、 醛基、烷氧基、 胺基、酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d_C4的焼基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 （^-(4的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、 ( 的烷基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 -( 的烷基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基; d-Ce的垸酰基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、两个或者三个 取代的 的烷酰基； C2- Ce的烯酰基； 含有包括卤素原子、 d- C6的烷氧基或羟基在内的 任意一个、两个或者三个取代的 C2- C6的烯酰基； C2- CB的炔酰基；含有包括卤素原子、 C,-C6 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c2-ce的炔酰基； c3- c6的环垸酰基; 含有包括卤素原子、 CrC6的烧氧基或羟基在内的任意一个、 两个或者三个取代的 C3- (：6的 环垸酰基； 金刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为 (C ) n， n为 0-2， 0， S或者 NH时； ¾为（CH ， n为 0 - 2， 0, S或者 NH时； Or R 5 , , R 7 are:
Figure imgf000054_0001
Wherein ^, R are each independently one of the following substituents: H; - ( 6 fluorenyl; any one, two or three substituted d including a halogen atom, a decyloxy group of CrC 6 or a hydroxyl group - C 6 alkyl; C 2 - (alkenyl; include a halogen atom-containing, C, - any C 6 alkoxy or hydroxy inner one, two or three substituents of (2 - (6 Alkenyl; C 2 - 0 6 alkynyl; any one, two or three substituted C 2 - (: 6 alkynyl group; C 3 containing a halogen atom, dC 6 alkoxy group or hydroxyl group; - a cyclic fluorenyl group of C 6 ; any one, two or three substituted C 3 - C 6 cyclodecyl groups containing a halogen atom, a decyloxy group or a hydroxyl group of d-C 6 ; an aryl group; ; furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, d- (: 4 fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, Any one, two or three substituted aryl groups including a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three of d- (; 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) a substituted pyridyl group; include a halogen atom-containing, 4 d_c firing group, a nitro group, a carboxyl group, an aldehyde group, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including any one, two or three substituents furanyl; containing a halogen atom include, (^ - (alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide group 4, Any one, two or three substituted pyranyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group Any one, two or three substituted thienyl groups including an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; and an alkyl group including a halogen atom, - (alkyl group, nitro group, carboxyl group, aldehyde) Base, alkoxy group, amine group, amide group, carboxamide group, fluorenyl group Methylthio, ethylthio, including any one, two or three substituents pyrrolyl; d-Ce acyl group of the embankment; containing optionally include a halogen atom, an alkoxy group or a hydroxyl dC 6 including a two Or a substituted alkanoyl group; a C 2 -C e alkenoyl group; any one, two or three substituted C 2 - including a halogen atom, a d-C 6 alkoxy group or a hydroxyl group ; Alkenoyl group of C 6 ; acetylene group of C 2 - C B ; any one, two or three substituted c 2 -c e containing an alkoxy group including a halogen atom, C, -C 6 or a hydroxyl group Alkynyl; c 3 - c 6 cyclodecanoyl; any one, two or three substituted C 3 - (: 6 cyclodecanoyl group) including a halogen atom, an alkoxy group of a CrC 6 or a hydroxyl group; Amantaformyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl a thiophene acyl group; a pyrrolyl group; when (C) n , n is 0-2, 0, S or NH; 3⁄4 is (CH, n is 0 - 2, 0, S or NH; 当 Ri， R2> RJ， 4为：
Figure imgf000055_0001
When Ri, R 2 > RJ, 4 is:
Figure imgf000055_0001
 其中 R18， R19各自独立为下列任意一种取代基： H; d- 0>的烷基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 垸基； C2- ( 的烯基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 6的 烯基； C2- (：6的炔基； 含有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者 三个取代的 C2-C6的炔基； C3_C6的环烷基； 含有包括 素原子、 d- C6的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 Cr 的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 C「 C4的'垸基、硝基、羧基、醛基、垸氧基、胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基；含有包括卤素原子、 (「( 4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基; 含有包括卤素原子、 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基；含有包括卤素原子、 Cr C4的烷基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基； CrC6的烷酰基； 含有包括卤素原子、 CrCe的焼氧基或羟基在内的任意一个、两个或者三个 取代的 d-Ce的垸酰基； C2- Ce的烯酰基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2-C6的烯酰基； C2-C6的炔酰基； 含有包括卤素原子、 d-C6 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3- Ce的环垸酰基； 含有包括卤素原子、 C,- C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C3- C6的 环垸酰基； 金刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 酷基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； Xi ¾ (¾)„, n为 0-2， 0， S或者 NH时; 为 (CH2) n， n为 0-2， 0, S或者 NH时， Wherein R 18 and R 19 are each independently one of the following substituents: H ; d- 0>alkyl; any one, two or three containing a halogen atom, an alkoxy group of dC 6 or a hydroxyl group. Substituted indenyl; C 2 - (alkenyl; any one, two or three substituted C 2 - ( 6 alkenyl; C) containing a halogen atom, an alkoxy group of d-Ce or a hydroxyl group 2 - (: 6 alkynyl group; a halogen atom includes contain any, or a hydroxyl group dC embankment 6 of the inner one, two or three substituents of C 2 -C 6 alkynyl group of; C 3 _C ring 6 Any one, two or three substituted C 3 -C 6 cyclodecyl groups including a sulfonate atom, a d-C 6 alkoxy group or a hydroxyl group; an aryl group; a benzyl group; a furyl group; a pyranyl group; a pyrenyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a halogen atom, Cr, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl group , ethylthio, including any one, two or three aryl group substituents; include a halogen atom-containing, C 'is C 4' Any one, two or three substituted pyridyl groups including a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Including a halogen atom, ("( 4 alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio, etc.) Or three substituted furanyl groups; containing an alkyl group including a halogen atom, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, Cr C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group , carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituents pyrrolyl; CrC 6 alkanoyl; contain any halogen atom include, CRCE the firing, including a hydroxyl group or, two or three substituents of the d-Ce acyl embankment a C 2 -C e enoyl group; any one, two or three substituted C 2 -C 6 enoyl groups including a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; C 2 -C An alkynyl group of 6; a acetylenedoyl group containing any one, two or three substituted C 2 -C 6 groups including a halogen atom, an alkoxy group of dC 6 or a hydroxyl group; a cyclodecanoyl group of C 3 -C e ; Any one, two or three substituted C 3 -C 6 cyclodecanoyl groups including a halogen atom, a C,-C 6 decyloxy group or a hydroxyl group; an adamantyl group, a substituted adamantyl group; Aroyl; sulfoyl; furoyl; pyranoyl; thiophene; pyrroyl; Xi 3⁄4 (3⁄4), when n is 0-2, 0, S or NH; (CH 2 ) n , When n is 0-2, 0, S or NH, ， R6, R7分别为：
Figure imgf000055_0002
其中 为下列任意一种取代基： H; -( 6的烷基； 含有包括卤素原子、 -( 6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 C「C6的烷基； C2-C6的烯基； 含有包括卤素 原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的（2 6的烯基； C2- ^的 炔基;含有包括卤素原子、 的烷氧基或羟基在内的任意一个、两个或者三个取代的 C2-Ce 的炔基； C3-C6的环垸基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个 或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基； 含有包括卤素原子、 d- (；4的烷基、 硝基、羧基、醛基、烷氧基、胺基、酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 C「C4 ¾烧基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的吡啶基； 含有包括卤素原子、 CrC4的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的呋喃基； 含有包括卤素原子、 d- C4的垸基、硝基、羧基、醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 d- (：4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基； 含有包括卤素原子、（ - ( 4的烷基、硝基、羧基、醛基、烷氧基、 胺基、酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； 的垸酰基； 含 有包括卤素原子、 CrCs的烷氧基或羟基在内的任意一个、 两个或者三个取代的 Cr Ce的烷 酰基； C2- Ce的烯酰基； 含有包括卤素原子、 的烷氧基或羟基在内的任意一个、两个或 者三个取代的 C2- Ce的烯酰基； C2-C6的炔酰基； 含有包括卤素原子、 CrC6的烧氧基或羟基 在内的任意一个、 两个或者三个取代的 C2- C6的炔酰基； C3-C6的环垸酰基； 含有包括卤素 原子、 d-C6的焼氧基或羟基在内的任意一个、 两个或者三个取代的 C3-C3的环烷酰基； 金 刚烷甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； 为（CH2) n， n为 0- 2, 0， S或者 NH时; , R 6 , R 7 are:
Figure imgf000055_0002
Wherein any one of the following substituent groups: H; - (6 alkyl group; a halogen atom-containing comprising, - one, two or three of any alkoxy or hydroxy substituted (C 6 including the "C 6 An alkyl group; a C 2 -C 6 alkenyl group; any one, two or three substituted ( 2 6 alkenyl groups; C 2 - ^) containing a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; An alkynyl group; any one, two or three substituted C 2 -C e alkynyl groups including a halogen atom, an alkoxy group or a hydroxyl group; a C 3 -C 6 cyclodecyl group; Any one, two or three substituted C 3 -C 6 cyclodecyl groups such as alkoxy or d-Ce; aryl; benzyl; furyl; pyranyl; thienyl; pyrrole Pyridyl; containing a halogen atom, d- (; 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted aryl groups; containing a halogen atom, C "C 4 3⁄4 alkyl, nitro, carboxyl, aldehyde Any one, two or three substituted pyridyl groups including a base, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; and an alkyl group including a halogen atom, CrC 4 Any one, two or three substituted furanyl groups including a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group; Any one or two including a halogen atom, a fluorenyl group of d-C 4 , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and two Or a three-substituted pyranyl group; containing a halogen atom, d- (: 4 alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide group, ethylthio, including any one, two or three substituents thienyl; containing a halogen atom include, (- (4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide Any of a group, a carboxamide group, a thiol group, a methylthio group, an ethylthio group One, two or three substituents pyrrolyl group; an acyl group of the embankment; containing optionally include a halogen atom, a hydroxyl group or an alkoxy group CRCS, including one, two or three substituents of Cr C e alkanoyl; C 2 - an enoyl group of C e ; an acyl group of any one, two or three substituted C 2 - C e containing a halogen atom, an alkoxy group or a hydroxyl group; a C 2 -C 6 alkynyl group; Any one, two or three substituted C 2 -C 6 alkynyl groups including a halogen atom, an alkoxy group or a hydroxyl group of CrC 6 ; a C 3 -C 6 cyclodecanoyl group; containing a halogen atom, dC Any one, two or three substituted C 3 -C 3 cycloalkanoyl groups of 6 decyloxy or hydroxy; adamantyl formyl, substituted adamantyl; aroyl; benzoyl; furoyl ; pyranoyl; thiophene; pyrroyl; when (CH 2 ) n , n is 0-2, 0, S or NH; 或者 R5， Re， R7分别为-
Figure imgf000056_0001
其中 。， 各自独立为下列任意一种取代基： H; C「 ( 6的烷基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C「Ce的烷基； C2- C6的烯基； 含有包括卤素原子、 （ 的烧氧基或羟基在内的任意一个、 两个或者三个取代的（2-( 6的 烯基； C2- ( 6的炔基； 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者 三个取代的 C2-C6的炔基； C3- C6的环垸基； 含有包括卤素原子、 d-Ce的烧氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环垸基； 芳基； 苄基； 呋喃基；吡喃基； 噻吩基; 吡咯基； 吡啶基； 含有包括 素原子、 d- 的烷基、 摘基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d- 的垸基、 硝基、 羧基、 醛基、垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 d-c4的垸基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 ( 的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的吡喃基； 含有包括卤素原子、 d- 的烷基、 硝基、羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括卤素原子、 （ _(]4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； ( 的垸酰基； 含有包括卤素原子、 d-Ce的垸氧基或羟基在内的任意一个、 两个或者三个 取代的 Ct- C6的烷酰基； C2-C6的烯酰基； 含有包括卤素原子、 d- ^的垸氧基或羟基在内的 任意一个、两个或者三个取代的 C2_C6的烯酰基； C2- C6的炔酰基； 含有包括卤素原子、 CrCs 的垸氧基或羟基在内的任意一个、 两个或者三个取代的 C2-C3的炔酰基； C3-Ce的环烷酰基; 含有包括卤素原子、 d-Ce的烷氧基或羟基在内的任意一个、 两个或者三个取代的 （：3-(：6的 环烷酰基； 金刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为（(¾)„， n为 0 - 2， 0， S或者 NH时; 为 (CH2) n， n为 0-2， 0， S或者 NH时; Or R 5 , R e , R 7 are -
Figure imgf000056_0001
among them. , each independently of any of the following substituents: H; C" (alkyl group of 6 ; containing any one, two or three substituted C's including a halogen atom, an alkoxy group of d-Ce or a hydroxyl group" An alkyl group of C e ; a C 2 -C 6 alkenyl group; an alkyl group containing 2 , 6 or 3 substituted groups including a halogen atom, an alkoxy group or a hydroxyl group; 2- ( 6 alkynyl; any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, an alkoxy group of dC e or a hydroxyl group; a ring of C 3 - C 6 Any one, two or three substituted C 3 -C 6 cyclodecyl groups containing a halogen atom, an alkoxy group or a hydroxyl group of dC e ; an aryl group; a benzyl group; a furyl group; a pyran group; Thiophene; Pyrrolyl; pyridyl; containing alkane, d-alkyl, exfoliation, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted aryl groups; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group Any one, two or three substituted pyridyl groups including a thio group or an ethylthio group; a fluorenyl group including a halogen atom, dc 4 , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group Any one, two or three substituted furanyl groups including a carboxamide group, a fluorenyl group, a methylthio group and an ethylthio group; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, and an anthracene group Any one, two or three substituted pyranyl groups including an amino group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, d-, and a nitrate Base, carboxyl group, aldehyde group, decyloxy group, amine , Amide groups, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include a halogen atom-containing, (_ (] 4 embankment group, a nitro group, Any one, two or three substituted pyrrolyl groups of a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substituted Ct-C 6 alkanoyl group including a halogen atom, a decyloxy group of d-Ce or a hydroxyl group; a C 2 -C 6 alkenoyl group; containing a halogen atom, d- any of the embankment ^ alkoxy or hydroxy, including one, two or three substituents of C 2 _C 6 alkenyl group; a C 2 - C 6 alkynyl group; a halogen atom-containing include, CrC s is a hydroxyl group or a embankment Any one, two or three substituted C 2 -C 3 alkynyl groups; a C 3 -C e cycloalkanoyl group; an alkoxy group containing a halogen atom, d-Ce or a hydroxyl group one, two or three substituents of (: 3 - (: 6 cycloalkyl group; adamantane formyl, Adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; ((3⁄4) „, n is 0 - 2, 0, S or NH; (CH 2 ) n , when n is 0-2, 0, S or NH; 或者 R5， R6, R7， ， ， 。分别为：
Figure imgf000057_0001
其中 R12为下列任意一种取代基： H; d- C6的烷基； 含有包括卤素原子、 d- (：6的烷氧基 或羟基在内的任意一个、 两个或者三个取代的 d- 的烷基； C2- (：6的烯基； 含有包括卤素 原子、 ^-( 6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- ( 6的烯基； C2- (：6的 炔基;含有包括卤素原子、 C「C6的垸氧基或羟基在内的任意一个、两个或者三个取代的 C2-C6 的炔基； C3-C6的环垸基； 含有包括卤素原子、 C,- C6的垸氧基或羟基在内的任意一个、 两个 或者三个取代的 C3- Cs的环垸基； 芳基； 节基； 呋喃基； 吡喃基； 噻吩基； 吡咯基； 吡啶基; 含有包括卤素原子、 -(：4的烷基、 硝基、 羧基、 醛基、烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括卤素原子、 d-C^烷基、 硝基、 羧基、 酸基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或 ¾·三个取代的吡啶基； 含有包括卤素原子、 - ( 的烷基、 硝 基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 d- ( 4的烷基、硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的吡喃基； 含有包括卤素原子、 （^-( 4的烧基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的噻吩基; 含有包括卤素原子、 d- ( 的烷基、硝基、 羧基、 醛基、烷氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的吡咯基； d-Ce的烷酰基； 含 有包括卤素原子、 d-C6的垸氧基或羟基在内的任意一个、 两个或者三个取代的 d-ce的烷 酰基； C2-C6的烯酰基； 含有包括卤素原子、 d- 的垸氧基或羟基在内的任意一个、两个或 者三个取代的 c2-c6的烯酰基； c2- ce的炔酰基； 含有包括卤素原子、 c「ce 烷氧基或羟基 在内的任意一个、 两个或者三个取代的 c2- c6的炔酰基； c3-c6的环垸酰基； 含有包括卤素 原子、 d-c6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 c3-ce的环烷酰基； 金 刚烷甲酰基、 取代金刚烷甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰基； 噻吩甲酰 基； 吡咯甲酰基； ¾为（C¾)n， n为 0-2， 0， S或者 NH时; Or R 5 , R 6 , R 7 , , , . They are:
Figure imgf000057_0001
Wherein R 12 is any one of the following substituents: H; an alkyl group of d-C 6 ; containing any one, two or three substituents including a halogen atom, an alkoxy group of d- (: 6 or a hydroxyl group) d- alkyl; C 2 - (: 6 alkenyl group; a halogen atom-containing include, ^ - alkoxy or hydroxy arbitrary (6, including one, two or three substituents of C 2 - (6 in Alkenyl; C 2 - (: 6 alkynyl; any one, two or three substituted C 2 -C 6 alkynyl group including a halogen atom, C "C 6 decyloxy group or hydroxy group"; a C 3 -C 6 cyclodecyl group; a cyclo, fluorenyl group containing any one, two or three substituted C 3 - C s including a halogen atom, a C, a C 6 decyloxy group or a hydroxyl group; Base; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, -(: 4 alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and a halogen atom, dC^alkyl group, Any one, two or 3⁄4·three substituted pyridyl groups including a carboxy group, a carboxyl group, an acid group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one, two or three of a halogen atom, - (alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) a substituted furanyl group; containing a halogen atom, d-( 4 alkyl group, nitro group, carboxyl group, aldehyde group, Any one, two or three substituted pyranyl groups including an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, (^-( 4) Any one, two or three substituted thienyl groups including a pyridyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group. Any one containing a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group, a two or three substituted pyrrolyl group; an alkanoyl group of d-Ce; an alkanoyl group having any one, two or three substituted dc e including a halogen atom, a decyloxy group of dC 6 or a hydroxyl group; 2- C6 alkenoyl; any one, two or three substituted c 2 -c 6 enoyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a c 2 - c e alkyne acyl; optionally include a halogen atom-containing, C "c e alkoxy or hydroxy, including one, two, Substituted by three c 2 - C 6 alkynyl group; c 3 -c 6 cycloalkyl group embankment; include a halogen atom-containing, any dc 6 alkoxy or hydroxy, including one, two or three substituents of a cycloalkanoyl group of c 3 -c e ; an adamantyl formyl group, a substituted adamantyl formyl group; an aroyl group; a benzyl group; a furoyl group; a pyroyl group; a thiophene group; a pyrroyl group; 3⁄4 is (C3⁄4) n , when n is 0-2, 0, S or NH; 或者 R5， Re, R" ， ， 。分别为：
Figure imgf000058_0001
Or R 5 , Re, R" , , are respectively:
Figure imgf000058_0001
 其中 R13， R14各自独立为下列任意一种取代基： H; d- C6的烷基； 含有包括卤素原子、 d-c6的烷氧基或羟基在内的任意一个、 两个或者三个取代的 d- 的浣基； C2- (：6的烯基； 含有包括卤素原子、 d- 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 （2-( 6的 烯基； C2-C6的炔基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、两个或者 三个取代的 C2- C6的炔基； C3-C6的环垸基； 含有包括卤素原子、 d- C6的烷氧基或羟基在内 的任意一个、两个或者三个取代的 C3- C6的环烷基； 芳基； 苄基； 呋喃基； 吡喃基;'噻吩基; 吡咯基； 吡啶基； 含有包括卤素原子、 （ C4的烷基、 硝基、 羧基、 醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三个取代的芳基； 含有包括 素原子、 d- ( 的烷基、 硝基、羧基、 醛基、烷氧基、胺基、 酰胺基、碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡啶基； 含有包括卤素原子、 -( 4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙 硫基在内的任意一个、 两个或者三个取代的呋喃基； 含有包括卤素原子、 Cr 的烷基、 硝 基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意 一个、两个或者三个取代的吡喃基； 含有包括卤素原子、（ C4的烷基、硝基、羧基、醛基、 垸氧基、 胺基、 酰胺基、 碳酰胺基、 巯基、 甲硫基、 乙硫基在内的任意一个、 两个或者三 个取代的噻吩基； 含有包括 素原子、 d- (：4的垸基、 硝基、 羧基、 醛基、 烷氧基、 胺基、 酰胺基、碳酰胺基、巯基、 甲硫基、 乙硫基在内的任意一个、两个或者三个取代的吡咯基; d-Ce的垸酰基； 含有包括卤素原子、 d-C6的烷氧基或羟基在内的任意一个、两个或者三个 取代的（ Ce的垸酰基； C2-C6的烯酰基； 含有包括卤素原子、 d- Ce 焼氧基或羟基在内的 任意一个、两个或者三个取代的 C2- C6的烯酰基； C2-C6的炔酰基； 含有包括卤素原子、 CrC6 的烷氧基或羟基在内的任意一个、 两个或者三个取代的 C2- Ce的炔酰基； C3-C6的环烷酰基; 含有包括卤素原子、 d-Cs的烷氧基或羟基在内的任意一个、 两个或者三个取代的 03-( 6的 环垸酰基； 金刚垸甲酰基、 取代金刚垸甲酰基； 芳酰基； 苄酰基； 呋喃甲酰基； 吡喃甲酰 基； 噻吩甲酰基； 吡咯甲酰基； 为(《12)„， n为 0-2， 0， S或者 NH时； ¾为（CH2) n， n为 0-2, 0， S或者 NH时。 Wherein R 13 and R 14 are each independently a substituent of any of the following: H; an alkyl group of d-C 6 ; any one, two or three containing an alkoxy group including a halogen atom, dc 6 or a hydroxyl group; Substituted d- fluorenyl; C 2 - (: 6 alkenyl; any one, two or three substituted (including 2 - ( 6 ) containing a halogen atom, d- alkoxy group or hydroxy group alkenyl; C 2 -C 6 alkynyl group; a halogen atom-containing optionally include, dC 6 alkoxy or hydroxy, including one, two or three substituents of C 2 - C 6 alkynyl group; C 3 - a cycloalkyl group of C 6 ; any one, two or three substituted C 3 -C 6 cycloalkyl groups including a halogen atom, an alkoxy group of d-C 6 or a hydroxyl group; an aryl group; a benzyl group ; furanyl; pyranyl; 'thienyl;pyrrolyl;pyridyl; containing halogen atom, (C 4 alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide) Any one, two or three substituted aryl groups including a sulfhydryl group, a thiol group, an ethylthio group; Any one, two or three substituted pyridyl groups of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Containing any one or two including a halogen atom, -( 4 fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) Or three substituted furanyl groups; containing an alkyl group including a halogen atom, Cr, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, (C 4 alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group) Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group or an ethylthio group; containing a sulfhydryl group, a d- (: 4 fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group) Base, amine group, amide group, carboxamide group, sulfhydryl group, methylthio group Ethylthio, including any one, two or three substituents pyrrolyl; d-Ce acyl group of the embankment; containing optionally include a halogen atom, an alkoxy group or a hydroxyl dC 6, including one, two or three substituted (C e of the embankment acyl; C 2 -C 6 alkenyl group; a halogen atom-containing include, d- C e alkoxy or hydroxy, including firing Any one, two or three substituents of C 2 - C 6 alkenyl group; a C 2 -C 6 alkynyl group; a halogen atom-containing optionally include, CrC 6 alkoxy or hydroxy, including one, two, or a three-substituted C 2 -C e alkynyl group; a C 3 -C 6 cycloalkanoyl group; any one, two or three substituted groups including a halogen atom, an alkoxy group of d-Cs or a hydroxyl group; 0 3 -( 6 -cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; (1 2 ) „, when n is 0-2, 0, S or NH; 3⁄4 is (CH 2 ) n , and n is 0-2, 0, S or NH. 3、 根据权利要求 1至 2任意一项所述的具有取代环己垸结构的化合物， 其特征在于 当分子中存在几何异构体时， 所述化合物为各种单独的几何异构体或者其混合物。  The compound having a substituted cyclohexyl structure according to any one of claims 1 to 2, characterized in that, when geometric isomers are present in the molecule, the compounds are various individual geometric isomers or mixture. 4、 根据权利要求 1至 3任意一项所述的具有取代环己垸结构的化合物， 其特征在于 当分子中存在手性碳时， 所述化合物为消旋体或光学活性体。  The compound having a substituted cyclohexyl structure according to any one of claims 1 to 3, characterized in that when a chiral carbon is present in the molecule, the compound is a racemate or an optically active substance. 5、权利要求 1至 4所述的具有取代环己烷结构的化合物的制备方法， 包括以下步骤：  5. A method of preparing a compound having a substituted cyclohexane structure according to any of claims 1 to 4, comprising the steps of:
Figure imgf000059_0001
取氰化钠溶于适量的水中， 加入氯化铵， 室温下搅拌至氯化铵完全溶解后， 加入上述 酮的甲醇溶液， 反应温度迅速上升， 继续搅拌。 加水稀释， 用苯提取。 苯层用水洗， 用盐 酸提取氨基腈；
Figure imgf000059_0001
Sodium cyanide is dissolved in an appropriate amount of water, ammonium chloride is added, and the mixture is stirred at room temperature until the ammonium chloride is completely dissolved. Then, the methanol solution of the above ketone is added, and the reaction temperature rises rapidly, and stirring is continued. Dilute with water and extract with benzene. The benzene layer is washed with water, and the aminonitrile is extracted with hydrochloric acid; 合并酸液， 回流， 加水稀释， 减压蒸馏， 去除酮和其他的挥发性物质；  Combine the acid solution, reflux, dilute with water, distillate under reduced pressure to remove ketones and other volatile substances; 加氨水调节 ra至弱碱性， 冷却至室温有黄色的晶体出现， 过滤， 滤饼用少量的水洗， 然后用乙醚和 95 %的热乙醇洗， 然后干燥得到氨基酸；  Add ammonia to adjust ra to weakly alkaline. After cooling to room temperature, yellow crystals appear. Filter, filter cake with a small amount of water, then wash with ether and 95% hot ethanol, then dry to obtain amino acid; 取上述氨基酸溶于氢氧化钠溶液， 冷却， 同时滴加酰氯和氢氧化钠溶液， 始终维持反 应液呈弱碱性。 加浓盐酸调节 ra至酸性， 冷却， 过滤得到粗品， 用乙醇重结晶得到产物。  The above amino acid is dissolved in a sodium hydroxide solution, cooled, and the acid chloride and sodium hydroxide solution are added dropwise, and the reaction solution is always weakly alkaline. Concentrated hydrochloric acid was added to adjust the acid to acidity, cooled, and filtered to give a crude material which was crystallised from ethyl ether. 6、权利要求 1至 4所述的具有取代环己烷结构的化合物的制备方法， 包括以下步骤: Η . ^ _ ^ The method for preparing a compound having a substituted cyclohexane structure according to any one of claims 1 to 4, comprising the steps of: Η . ^ _ ^ ：。 ~~ ^ 、K ΟΗ \ :. ~~ ^, K ΟΗ \ 。  . CNM ^ ^ 、 CN M ^ ^ , ,Kς CUOH , K ς C U O H 一'' NH ½, —— ^ ' C0OHOH
Figure imgf000059_0002
One ''NH 1⁄2, —— ^ ' C0OHOH
Figure imgf000059_0002
 取酮溶于适量的乙醚和水中， 冰盐浴冷却， 加入氰化钠， 剧烈搅拌， 当大部分的氰化 钠全部溶解后且反应液温度降至 5°C以下， 慢慢滴加适量的浓盐酸， 维持反应温度在 5°C 到 10°C之间， 滴加结束后， 移去冰浴， 同时剧烈搅拌， 静置， 分离乙醚层， 将水层倒入反 应瓶中， 加水溶解盐， 水层再用乙醚提取， 合并乙醚层， 蒸去乙醚， 将残佘物倒入浓盐酸 中， 并用氯化氢气体饱和， 放置过夜， 然后先用空气带走部分氯化氢气体， 再慢慢滴加 50 %氢氧化钠溶液调节至碱性， 冰浴冷却并搅拌， 加入氢氧化钠固体， 水蒸汽蒸馏直至无多 余的氨和酮， 加水稀释， 乙醚提取， 水层用浓盐酸酸化， 冷却， 过滤得到 α—羟基酸， 向上述 α—羟基酸中加入酰氯， 水浴加热反应， 冷却析晶， 得产物。 Take the ketone dissolved in an appropriate amount of ether and water, cool in an ice salt bath, add sodium cyanide, stir vigorously. When most of the sodium cyanide is dissolved and the temperature of the reaction solution drops below 5 °C, slowly add the appropriate amount. Concentrated hydrochloric acid, maintain the reaction temperature between 5 ° C and 10 ° C, after the end of the dropwise addition, remove the ice bath, while stirring vigorously, let stand, separate the ether layer, pour the water layer into the reaction bottle, add water to dissolve the salt The aqueous layer was extracted with diethyl ether, and the ether layer was combined, evaporated to diethyl ether, and the residue was poured into concentrated hydrochloric acid. Medium, and saturated with hydrogen chloride gas, left overnight, then take some hydrogen chloride gas away with air, then slowly add 50% sodium hydroxide solution to adjust to alkaline, cool and stir in ice bath, add sodium hydroxide solid, water vapor Distillation until there is no excess ammonia and ketone, diluted with water, extracted with ether, the aqueous layer is acidified with concentrated hydrochloric acid, cooled, filtered to obtain α-hydroxy acid, acid chloride is added to the above α-hydroxy acid, heated in a water bath, cooled and crystallized, product. 7. 权利要求 1至 4所述的具有取代环己垸结构的化合物的制备方法， 包括以下步骤:
Figure imgf000060_0001
氮气保护下， 取 LDA溶于适量的四氢呋喃中， 冷却至一 50°C， 慢慢滴加羧酸， 维持该 温度继续搅拌， 50°C继续搅拌， 用液氮 /甲醇浴冷却， 滴加硝基取代的烯烃， 反应 2〜10 个小时， 反应液温度升至 0〜10Ό， 加入适量的稀盐酸， 冰浴中搅拌过夜， 加水和二氯甲 烷提取， 依次用水和饱和食盐水洗涤， 干燥， 蒸去溶剂后进行柱分离。 7. A method of preparing a compound having a substituted cyclohexanyl structure according to any of claims 1 to 4, comprising the steps of:
Figure imgf000060_0001
Under nitrogen protection, take LDA in an appropriate amount of tetrahydrofuran, cool to a temperature of 50 ° C, slowly add carboxylic acid, continue to stir at this temperature, continue stirring at 50 ° C, cool with liquid nitrogen / methanol bath, add nitrate The base-substituted olefin is reacted for 2 to 10 hours, the temperature of the reaction solution is raised to 0 to 10 Torr, and an appropriate amount of diluted hydrochloric acid is added thereto, and the mixture is stirred overnight in an ice bath, extracted with water and dichloromethane, washed successively with water and saturated brine, and dried. The solvent was distilled off and the column was separated. 8、根据权利要求 1至 4中任意一项所述化合物或其可药用盐用于制备预防和 /或治疗 代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症）、 心血管疾病和神经退 行性疾病 （如 Alzheimer' s病） 等的用途。  A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, for use in the preparation of a prophylactic and/or therapeutic metabolic disorder (including but not limited to diabetes, insulin resistance and obesity), cardiovascular Uses of diseases and neurodegenerative diseases such as Alzheimer's disease. 9、一种用于预防和 /或治疗代谢紊乱性疾病（包括但不局限于糖尿病、胰岛素抵抗和 肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病）等的药物组合物， 该组合 物含有作为活性成分的权利要求 1至 4中任一项所述的化合物以及这类化合物在治疗上可 接受的盐类及其与其它分子或载体的连结物。  9. A pharmaceutical composition for preventing and/or treating metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease The composition contains, as an active ingredient, a compound according to any one of claims 1 to 4 and a therapeutically acceptable salt of such a compound and a linker with other molecules or carriers. 10、根据权利要求 9所述的药物组合物， 其特征在于进一步含有药物学上可接受的载 体和赋形剂。  10. A pharmaceutical composition according to claim 9 further comprising a pharmaceutically acceptable carrier and excipient. 11、如权利要求 9所述药物组合物，其特征在于所述疾病或症状可以因对已经上市的 治疗药物产生耐药性或毒副反应而引起。  The pharmaceutical composition according to claim 9, wherein the disease or symptom can be caused by resistance or toxic side effects to a therapeutic drug already on the market. 12、一种联合制剂， 包括如权利要求 1至 4中任意一项所述化合物或其药物学上可接 受的盐和其他治疗药物。  A combination preparation comprising a compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, and other therapeutic agents. 13、 一种药盒， 其包括权利要求 1至 4中任意一项所述的化合物或其药物学上可接 受的盐，以及使用所述化合物或其药物学上可接受的盐预防和 /或治疗代谢紊乱性疾病（包 括但不局限于糖尿病、 胰岛素抵抗和肥胖症）、 心血管疾病和神经退行性疾病 （如 Alzheimer' s病）等的说明。  A kit comprising the compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, and the use of the compound or a pharmaceutically acceptable salt thereof for prevention and/or prevention Description of the treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease). 14、 一种药盒， 其包括权利要求 12所述的联合制剂， 和使用所述联合制剂预防和 /或 治疗代谢紊乱性疾病 （包括但不局限于糖尿病、 胰岛素抵抗和肥胖症）、 心血管疾病和神 经退行性疾病 （如 Alzheimer' s病）等的说明。  14. A kit comprising the combination of claim 12, and using the combination to prevent and/or treat metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular Description of diseases and neurodegenerative diseases (such as Alzheimer's disease).
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