NZ736551B2 - Indole derivatives - Google Patents
Indole derivatives Download PDFInfo
- Publication number
- NZ736551B2 NZ736551B2 NZ736551A NZ73655116A NZ736551B2 NZ 736551 B2 NZ736551 B2 NZ 736551B2 NZ 736551 A NZ736551 A NZ 736551A NZ 73655116 A NZ73655116 A NZ 73655116A NZ 736551 B2 NZ736551 B2 NZ 736551B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- meaning
- diazepino
- dihydropyridinone
- general formula
- Prior art date
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- 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
- 150000002475 indoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 21
- 230000002265 prevention Effects 0.000 claims abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 4
- 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 claims abstract 3
- 102000044674 Melanin-concentrating hormone receptor 1 Human genes 0.000 claims abstract 3
- 230000000694 effects Effects 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- -1 chloro-pyridinyl Chemical group 0.000 claims 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 239000001257 hydrogen Substances 0.000 claims 8
- 125000000217 alkyl group Chemical group 0.000 claims 7
- 208000008589 Obesity Diseases 0.000 claims 4
- 229910052801 chlorine Chemical group 0.000 claims 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 229910052731 fluorine Inorganic materials 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 235000020824 obesity Nutrition 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 239000011737 fluorine Chemical group 0.000 claims 3
- 125000001188 haloalkyl group Chemical group 0.000 claims 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 2
- 208000019901 Anxiety disease Diseases 0.000 claims 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 230000004064 dysfunction Effects 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 208000020016 psychiatric disease Diseases 0.000 claims 2
- 201000009032 substance abuse Diseases 0.000 claims 2
- 231100000736 substance abuse Toxicity 0.000 claims 2
- 208000011117 substance-related disease Diseases 0.000 claims 2
- 230000004584 weight gain Effects 0.000 claims 2
- 235000019786 weight gain Nutrition 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 239000012876 carrier material Substances 0.000 claims 1
- 238000013329 compounding Methods 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- BSYFXFLGOGQHFU-UHFFFAOYSA-N pyrrolo[2,3-g][1,2]benzodiazepine Chemical class N1=NC=CC=C2C3=NC=CC3=CC=C21 BSYFXFLGOGQHFU-UHFFFAOYSA-N 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P3/04—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Abstract
The present invention relates to compounds of the general form (I). The present invention relates to new substituted diazepino-indole derivatives of the general formula (I), and to pharmaceutically acceptable salts thereof, as well as to pharmaceutical compositions comprising such compounds, to new intermediate thereof, as well as to the use of such compounds in treatment or prevention of disorders associated with melanin-concentrating hormone receptor 1 activity.
Claims (23)
1. A compound of general formula (I) R A O 1 N R R O N N 5 wherein the meaning of A is CH or nitrogen atom; the meaning of R is hydrogen or halogen atom or C1-C6 straight or branched chain alkyl group; the g of R1 is hydrogen or halogen atom or 10 C1-C6 straight or branched chain alkyl group, or C1-C6 straight or branched chain alkoxy group, or mono- or polyhalogenated C1-C6 straight or branched chain haloalkyl group; the meaning of R2 is hydrogen or n atom or C1-C6 straight or branched chain alkyl group, or 15 C1-C6 straight or ed chain alkoxy group or mono- or polyhalogenated C1-C4 straight or branched chain haloalkyl group; the meaning of R3 is hydrogen or C1-C6 straight or branched chain alkyl group, optionally substituted with C3-C6 cycloalkyl group, or 20 mono- or polyhalogenated C1-C6 straight or branched chain haloalkyl group; or C3-C6 cycloalkyl group, or C1-C6 straight or branched chain alkanoyl group, or a salt, or geometric or stereoisomer, or diastereomer, or hydrate, or solvate, or polymorph modification thereof.
2. The compound of general formula (I) according to claim 1 wherein the meaning of R3 is: en atom, or C1-C4 straight or branched chain alkyl group, optionally substituted with C3-C6 30 cycloalkyl group, or C3-C6 cycloalkyl group, or C1-C4 straight or branched chain alkanoyl group.
3. The compound of general formula (I) according to claim 1 or claim 2 wherein that 5 the meaning of R3 is: hydrogen atom, C1-C4 straight or branched chain alkyl group, optionally substituted with C3-C4 cycloalkyl group or fluorine atom, or C3-C4 cycloalkyl group, or 10 acetyl group.
4. The nd of general formula (I) according to any one of claims 1-3 wherein the meaning of R3 is methyl, ethyl, isopropyl, cyclopropylmethyl, cyclobutyl or fluoroethyl group.
5. The compound of general formula (I) according to any one of claims 1-4 wherein the g of R3 is isopropyl or cyclopropylmethyl.
6. The compound of general formula (I) according to any one of claims 1-5 wherein 20 the g of R2 is hydrogen or halogen atom, oromethyl or C1-C3 alkyl group.
7. The compound of general formula (I) according to any one of claims 1-6 n the meaning of R2 is hydrogen, fluorine or chlorine atom, or methyl group. 25
8. The compound of general formula (I) according to any one of claims 1-7 wherein the meaning of R2 is hydrogen atom.
9. The compound of general formula (I) according to any one of claims 1-8 wherein the meaning of R1 is 30 en or halogen atom, or C1-C4 straight or branched chain alkyl group, optionally mono- or polyhalogenated; C1-C3 alkoxy group.
10. The compound of general formula (I) according to any one of claims 1-9 n the meaning of R1 is hydrogen, fluorine or chlorine atom, or methoxy or trifluoromethyl group.
11. The compound of general formula (I) according to any one of claims 1-10 wherein the meaning of R1 is hydrogen, fluorine or chlorine atom.
12. The compound of general formula (I) according to any one of claims 1-11 n 10 the meaning of R is hydrogen atom.
13. The compound of general formula (I) according to any one of claims 1-12 wherein the meaning of R is hydrogen atom and the meaning of R1 is chlorine atom. 15
14. The nd of general formula (I) according to any one of claims 1-13 n the meaning of A is nitrogen atom.
15. The compound of general formula (I) ing to any one of claims 1-14 wherein the meaning of A is CH.
16. A compound according to claim 1 selected from: chloro-pyridinyl)methoxy]{1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol yl}-1,2-dihydropyridinone; 4-[(5-chloro-pyridinyl)methoxy]{3-methyl-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- 25 a]indolyl}-1,2-dihydropyridinone; 4-[(5-chloro-pyridinyl)methoxy]{3-ethyl-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- a]indolyl}-1,2-dihydropyridinone; 4-[(5-fluoro-pyridinyl)methoxy][3-(propanyl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indolyl]-1,2-dihydropyridinone; 30 4-(benzyloxy)[3-(propanyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indolyl]-1,2- dihydropyridinone; 4-[(5-chloro-pyridinyl)methoxy][3-(propanyl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indolyl]-1,2-dihydropyridinone; 4-[(4-fluoro-phenyl)methoxy][3-(propanyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- a]indolyl]-1,2-dihydropyridinone; 4-[(4-chloro-phenyl)methoxy][3-(propanyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- a]indolyl]-1,2-dihydropyridinone; 5 4-[(2-fluoro-phenyl)methoxy][3-(propanyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- a]indolyl]-1,2-dihydropyridinone; 1-[11-chloro(propanyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indolyl][(5- chloro-pyridinyl)methoxy]-1,2-dihydropyridinone; 4-(benzyloxy)[11-chloro(propanyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol- 10 9-yl]-1,2-dihydropyridinone; 4-[(5-chloro-pyridinyl)methoxy][3-(cyclopropylmethyl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indolyl]-1,2-dihydropyridinone; 4-[(5-chloro-pyridinyl)methoxy]{3-cyclopropyl-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indolyl}-1,2-dihydropyridinone; 15 4-[(5-chloro-pyridinyl)methoxy]{3-cyclobutyl-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- a]indolyl}-1,2-dihydropyridinone; and 4-[(5-chloro-pyridinyl)methoxy][11-methyl(propanyl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indolyl]-1,2-dihydropyridinone, or a pharmaceutically able salt thereof.
17. Use of a compound according to any one of claims 1-16 in the manufacture of a medicament for treatment or prevention of a disorder or condition associated with melanin concentrating hormone receptor 1 activity. 25
18. Use of a compound ing to any one of claims 1-16 in the manufacture of a medicament for ent or prevention of obesity, an obesity related comorbid condition or complication, diabetes, a metabolic disorder, a psychiatric disease accompanied by weight gain, an inflammatory bowel disease, an ive dysfunction, an anxiety disorder, a sleep-wake cycle disorder, or a substance abuse or ive disorder.
19. Use of a compound according to any one of claims 1-16 for manufacturing a ceutical composition.
20. A ceutical composition comprising a compound according to any one of claims 1-16 together with an excipient or carrier material lly used for cturing pharmaceutical compositions. 5
21. Use of a pharmaceutical composition according to claim 20 in the cture of a medicament for treatment or prevention of a disorder or condition associated with melanin concentrating hormone receptor 1 activity.
22. Use of a pharmaceutical composition according to claim 20 in the manufacture of a 10 medicament for treatment or prevention of obesity, an obesity related comorbid condition or complication, diabetes, a metabolic disorder, a psychiatric disease accompanied by weight gain, an inflammatory bowel disease, an affective dysfunction, an anxiety disorder, a sleep-wake cycle disorder, or a substance abuse or addictive er. 15
23. A compound of formula (2), tert-butyl 9-bromo-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indolcarboxylate
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUP1500169A HU230880B1 (en) | 2015-04-15 | 2015-04-15 | Indole derivatives |
| PCT/IB2016/052110 WO2016166684A1 (en) | 2015-04-15 | 2016-04-14 | Indole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ736551A NZ736551A (en) | 2024-08-30 |
| NZ736551B2 true NZ736551B2 (en) | 2024-12-03 |
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