[go: up one dir, main page]

WO2010148632A1 - Composés de dihydropyridine et leurs procédés de préparation, leurs compositions pharmaceutiques et leurs utilisations - Google Patents

Composés de dihydropyridine et leurs procédés de préparation, leurs compositions pharmaceutiques et leurs utilisations Download PDF

Info

Publication number
WO2010148632A1
WO2010148632A1 PCT/CN2010/000758 CN2010000758W WO2010148632A1 WO 2010148632 A1 WO2010148632 A1 WO 2010148632A1 CN 2010000758 W CN2010000758 W CN 2010000758W WO 2010148632 A1 WO2010148632 A1 WO 2010148632A1
Authority
WO
WIPO (PCT)
Prior art keywords
amino
nitro
oxy
hydrogen
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2010/000758
Other languages
English (en)
Chinese (zh)
Inventor
李松
郭真
赵国明
王莉莉
关华
肖军海
钟武
郑志兵
谢云德
李行舟
王晓奎
周辛波
刘洪英
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Pharmacology and Toxicology of AMMS
Original Assignee
Institute of Pharmacology and Toxicology of AMMS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institute of Pharmacology and Toxicology of AMMS filed Critical Institute of Pharmacology and Toxicology of AMMS
Publication of WO2010148632A1 publication Critical patent/WO2010148632A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
    • C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • 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
    • C07D409/04—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 directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to a hydroquinone compound and a process for the preparation thereof, and a composition comprising the above compound, and a use of a US compound or Hume or a hydrate as an antiviral, especially for the treatment and/or Use of a substance for preventing hepatitis.
  • Chronic hepatitis is a disease caused by the hepatitis B virus (B), which is closely related to cirrhosis and liver cancer. I am a high hepatitis type, 1 1 whole viral hepatitis clear epidemic investigation results show that I am due to hepatitis B virus surface antigen (B g)
  • Chronic hepatitis has been a major public worker.
  • the chronic diseases are mainly caused by the rabbit market and N polymerization inhibition (Loo ba. L ang TJ, nv . The. 1 1 1 ).
  • the former includes dry anti-b FN b, nt on and a Peg F a Pega y Q includes Lamy La vde, Ep v BO A de ov p vox Hep ea,
  • the hydrogen physin has physiological activity and can work as a N-channel antagonist (U5 0 ) and a L-channel antagonism (U5 1 ) with [ [ [ [ c ) N
  • Hydroquinone compounds have and act (U5 1). However, there is no such thing as a hydroquinone compound hepatitis virus.
  • novel hydrogen compounds provided by the present invention have potent antiviral effects, particularly the role of hepatitis B virus. This was done on the top.
  • This aspect provides compounds
  • Or Hugh can or hydrate.
  • Or Hugh can or hydrate.
  • substitutions are the same or different from the lower gene hydrogen, , , , oxy, oxycarbon, nitro, amino, amino, amino and amino groups.
  • Or Hugh can or hydrate.
  • the second aspect provides a method of each of the compounds of the first aspect, which comprises
  • Step B In the remainder, in the inertia, the compound of the above step, the compound is obtained, and the compound is obtained.
  • prime examples and , , , , , , and are each of the compounds of the first aspect of the invention.
  • the third aspect provides a composition comprising a compound which is useful in the treatment and/or prevention of a quantity of the compound of any of the above aspects, and other active compounds.
  • the first aspect provides the use of a compound according to any of the above aspects in the treatment and/or prevention of an acute or chronic viral disease.
  • the fifth aspect provides the use of the compound of any of the above aspects in the treatment and/or prevention of acute or chronic hepatitis virus infection.
  • the sixth aspect provides a method of treating and/or preventing an acute or chronic viral disease comprising administering a therapeutically and/or prophylactically effective amount of a compound of any of the above aspects to a subject in need thereof.
  • the present invention provides a method of treating and/or preventing an acute or chronic hepatitis virus infection comprising administering a therapeutically effective and/or prophylactic amount of a compound of any of the above aspects.
  • Mid (d, d) refers to a straight or carbon atom having a carbon atom, including but not limited to ethylene, propylene, and .
  • wood "(d, d)" means a straight or a carbon atom having a straight or a carbon atom.
  • wood generally refers to a system of 1, or may include, or is not limited to, phenyl and .
  • ⁇ usually refers to the atomic N, , etc., or may contain a combined OR.
  • Ben, wood "(d, )” refers to a straight or a gene containing one carbon atom, including but not limited to , , , , , , , and .
  • wood "(d d)oxy" means a straight or oxy group containing 1 carbon atom, having a straightness of 1 carbon atom or
  • the oxy group includes, but is not limited to, an oxy group, an oxy group, an oxy group, an oxy group, an oxy group, an oxy group, an oxy group and the like.
  • wood "(d, d)" means a straight or 1 carbon atom straight or
  • wood "( ) oxycarbon” means a straight or oxygen carbon with 1 carbon atom, a straight or oxygen carbon with 1 carbon atom, including but not limited to oxygen, oxygen, oxygen, oxygen , oxygen carbon, oxygen and carbon, and oxygen.
  • the compound may exist in the form of an optical hoop in the form of a Hugh or a Hugh. This involves
  • the method of non-external rest can be divided into optical components of the sheep, the method of rest and relaxation of the compound and respectively dissolved, then mixed, placed, precipitated solid rest.
  • the solid solution can be extracted separately.
  • Acidity includes, but is not limited to, fatty acids, sulfonic acids, or L-forms, lactic acid, natural or non-natural amino acids, and derivatives thereof.
  • the methods used in the above methods include, but are not limited to, ethanol, , , , petroleum, and the like.
  • the gene is introduced into the molecule, so that it can be annihilated, and the method of removing the introduced gene can be taken.
  • At least mediators of the molecule include, but are not limited to, fatty acids, sulfonic acids, or L-forms, lactic acid, natural or unnatural amino acids, and derivatives thereof.
  • This compound can be in the form. It is available.
  • the materials that may be used include, but are not limited to, phosphoric acid, phosphoric acid, hydrogen, and nitric acid, and each of which has not, , , , , , , lactic acid, benzoic acid, sulfonic acid, sulfonic acid, sulfonic acid, toluenesulfonic acid, etc. Made of.
  • Useful gold including but not limited to the present compound , or, or, or, diethyl, diethanol, ethanol, dimethylaminoethanol, , , or phenyl.
  • Some of the compounds in the present invention may be crystallized with water or various families, and in some cases, various compounds may be formed. These include the amount of solvate, including hydrates, which are also included in the low-profile process.
  • substitutions are the same or different, from the lower gene hydrogen, , , , oxy, oxycarbon, nitro, amino, amino, amino and amino.
  • Phenylnitro(phenyl) 1 hydrogen ( ) (phenyl) nitro (phenyl) 1, hydrogen Adjacent to ethyl citrate;
  • the compound (1) compound can be prepared by the following methods.
  • the solution used is all inert. Including alcohol, ethanol, propanol, dihydrogen, hydrogen, methyl, dimethyl or acetic acid, dimethyl, dimethyl, and hexamethyl.
  • the reverse temperature can be internalized.
  • the nuclear counter is in 1 C but in each.
  • the reverse can be, but it can also be raised. Usually reversed.
  • the opposite may or may not be acid.
  • Nuclear anti-use includes, diethyl, hydrogen, potassium carbonate, potassium carbonate, hydrogencarbonate, acetic acid, sodium hydroxide, potassium hydroxide.
  • the D) used as the starting point is already in some cases, or it can be found in accordance with the methods in the text. See Ma a B. F. B. , Hugo. B. Lau , ea . y he 1 )
  • the ( ) used as the starting point is already, or it can be made according to the methods in the text ( av d . Bake , e ng . yn he , 1 , .).
  • the compounds of the present invention can be synthesized by a conventional method, or by a combined method or a parallel synthesis method.
  • Or 1 is preferably a compound of 1 10). It can be synthesized in liquid phase or in solid phase synthesis.
  • test mixture is available under C 0 . However, in the new, each new growth. once again This compound, the solution is closed. The mixture was again found. Before the determination of the antiviral effect, light micromirror or biochemical method aa B ue dye or T ypan B ue staining was used to investigate ep . . Cytotoxicity.
  • Hep . . 1 Toxicity in cells or inhibition of cell formation was not measured and expressed as cells.
  • cells are compared to unreasonable cells, such as cells that dissolve, form, or cells.
  • T is a cell with a phase of cells similar to the shape of this compound.
  • the rabbit of Gao Xin's N is born. Sheep, and (manufacturer's), but use the prior to the phosphoric acid
  • Inhibition means that the compound is not specifically reduced compared to hepatitis.
  • Governance can be an acute and chronic viral infection of infectious hepatitis, a case of hepatitis virus infection.
  • the treatment of chronic hepatitis infection and the treatment of acute hepatitis virus infection can be an acute and chronic viral infection of infectious hepatitis, a case of hepatitis virus infection.
  • composition of the compound can be administered orally, straight, nasal, clear, local, parenteral subcutaneous, intradermal, intraperitoneal, internal, indoor, sternum in any of the following ways.
  • the present compound or a composition containing the same may be in the form of a sheep. It can be Hugh and Solid. Hugh can be solution, rest, particles, , . Other examples, , , , , , , solutions , , , particles , , , , , , etc.
  • the composition of the present invention may contain a commonly used rest, including but not limited to sub-exchange, alumina, aluminum, serum serum, phosphoric acid, glycerin, potassium acetate, a mixture of partial glycerin of saturated vegetable fatty acids, water or Acid to protein hydrogen phosphate, sodium hydrogen phosphate, oxidation, Sangui, vinyl hydride, polypropylene, wool, and the like.
  • the content of the composition of the composition may be 1 weight, usually about the weight. Seeing local anesthesia, anti-corruption, etc., can be directly in the rest.
  • And may contain a complex , , arabic , or ethylene , filled , lactose sucrose corn , calcium phosphate , , amino ,
  • the system can contain regular additions.
  • External injection usually by compound and family disinfection. Drinking water. Depending on the degree of rest, the compound is soluble in both the rest and the solution. The compound is dissolved in water, sterilized or encapsulated in the injection solution.
  • the compound may be in the form of an ointment, or , wherein the active ingredient is dissolved in or at rest.
  • ointments that can be used are, but are not limited to, oils, Vaseline, Vaseline, ethylene oxide, propylene oxide, emulsification and water, and available Hugh, including but not limited to oils, dehydrated sheep, and 16 carbons.
  • the temperature is not comparable. Determined by c o a ab pec high resolution (resolution 1). N is determined by JN B N, operating frequency N z 1 phenyl nitro ( benzene
  • Step 3 2-Methyl-4-phenyl-5-nitro-6-(4.methylphenyl)-1,4 dihydro _ _
  • the method comprises the benzene and amino groups respectively, and the benzyl group is obtained, and the yellow crystal is obtained.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des composés de dihydropyridine et sur leurs procédés de préparation, leurs compositions pharmaceutiques et leurs utilisations. En particulier, l'invention porte sur des composés représentés par la formule générale (I) et des isomères, des sels à usage médicinal ou des hydrates de ceux-ci, chaque variable étant telle que définie dans la description. L'invention porte également sur des procédés de préparation des composés représentés par la formule générale (I) et sur des utilisations, pour la préparation de médicaments, des composés représentés par la formule générale (I) et des isomères, des sels à usage médicinal ou des hydrates de ceux-ci, en particulier sur des utilisations pour la préparation de médicaments destinés à guérir et/ou à prévenir une affection par le virus de l'hépatite B.
PCT/CN2010/000758 2009-06-25 2010-05-27 Composés de dihydropyridine et leurs procédés de préparation, leurs compositions pharmaceutiques et leurs utilisations Ceased WO2010148632A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200910148629XA CN101575314B (zh) 2009-06-25 2009-06-25 二氢吡啶类化合物及其用于制备治疗和/或预防病毒性疾病的药物的用途
CN200910148629.X 2009-06-25

Publications (1)

Publication Number Publication Date
WO2010148632A1 true WO2010148632A1 (fr) 2010-12-29

Family

ID=41270404

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2010/000758 Ceased WO2010148632A1 (fr) 2009-06-25 2010-05-27 Composés de dihydropyridine et leurs procédés de préparation, leurs compositions pharmaceutiques et leurs utilisations

Country Status (2)

Country Link
CN (1) CN101575314B (fr)
WO (1) WO2010148632A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024503571A (ja) * 2020-11-30 2024-01-26 カニアンタラ チャンディ，ジョージ プラットフォーム治療薬として使用するための、カルシウム活性化カリウムチャネルＫＣａ３．１の強力かつ選択的阻害剤

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101575314B (zh) * 2009-06-25 2011-05-11 中国人民解放军军事医学科学院毒物药物研究所 二氢吡啶类化合物及其用于制备治疗和/或预防病毒性疾病的药物的用途
US20130267517A1 (en) 2012-03-31 2013-10-10 Hoffmann-La Roche Inc. Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection
KR20150054795A (ko) 2012-09-10 2015-05-20 에프. 호프만-라 로슈 아게 B형 간염 바이러스 감염의 치료 및 예방을 위한 6-아미노산 헤테로아릴다이하이드로피리미딘
CN108840800A (zh) * 2018-05-28 2018-11-20 上海华堇生物技术有限责任公司 一种苯基硝基乙酮的新制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999025347A2 (fr) * 1997-11-14 1999-05-27 Neurosearch A/S Composes chimiques ayant une activite de blocage des canaux ioniques et servant au traitement de troubles immunitaires
CN101575314A (zh) * 2009-06-25 2009-11-11 中国人民解放军军事医学科学院毒物药物研究所 二氢吡啶类化合物及其用于制备治疗和/或预防病毒性疾病的药物的用途

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999025347A2 (fr) * 1997-11-14 1999-05-27 Neurosearch A/S Composes chimiques ayant une activite de blocage des canaux ioniques et servant au traitement de troubles immunitaires
CN101575314A (zh) * 2009-06-25 2009-11-11 中国人民解放军军事医学科学院毒物药物研究所 二氢吡啶类化合物及其用于制备治疗和/或预防病毒性疾病的药物的用途

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
SAGITULLINA, G. P. ET AL.: "Nitropyridines: III. Synthesis of meta-terphenyls by recyclization of nitropyridinium salts.", RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, vol. 42, no. 8, 2006, pages 1203 - 1207, XP019407562, DOI: doi:10.1134/S1070428006080173 *
SAGITULLINA, G. P. ET AL.: "Nitropyridines: IV Synthesis of 3-(2-furyl)biphenyls by recyclization of nitropyridinium salts.", RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 4, 2007, pages 602 - 606 *
SAGITULLINA,GP. ET AL.: "Nitropyridines. 1. Hantzsch synthesis ofnitropyridines and their quaternary salts.", CHEMISTRY OF HETEROCYCLIC COMPOUNDS., vol. 38, no. 11, 2002, pages 1336 - 1341 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024503571A (ja) * 2020-11-30 2024-01-26 カニアンタラ チャンディ，ジョージ プラットフォーム治療薬として使用するための、カルシウム活性化カリウムチャネルＫＣａ３．１の強力かつ選択的阻害剤

Also Published As

Publication number Publication date
CN101575314A (zh) 2009-11-11
CN101575314B (zh) 2011-05-11

Similar Documents

Publication Publication Date Title
ES2275758T3 (es) Compuestos de isoindol-imida, sus composiciones y sus usos.
JP3528968B2 (ja) 三環式複素環誘導体化合物およびその化合物を有効成分とする医薬
EP1423115B9 (fr) Activite antiangiogenetique d'analogues de thalidomide substitues par azote
CN101247807A (zh) 噻唑化合物及使用方法
AU2002323063A1 (en) Synthesis and anti-tumor activity of nitrogen substituted thalidomide analogs
WO2011134283A1 (fr) Dérivés d'acide matrinique/matrine et leurs procédés de préparation et utilisations
TW200306830A (en) N-[phenyl (piperidin-2-yl) methyl] benzamide derivatives, their preparation and their application in therapy
JP2020526569A (ja) 環内チアミジノアミド−アリールアミド系化合物及びｂ型肝炎を治療するためのその用途
JP2015501788A (ja) Ｇタンパク質共役Ｍａｓ受容体調節因子およびそれに関連する障害の処置
WO2010148632A1 (fr) Composés de dihydropyridine et leurs procédés de préparation, leurs compositions pharmaceutiques et leurs utilisations
JPH05501886A (ja) 抗アテローム性動脈硬化症性および抗血栓性２―アミノ―６―フェニル―４ｈ―ピラン―４―オン類
JPH03503525A (ja) 腫瘍疾患治療用の光学的に純粋なｒ‐（‐）‐ニグルジピン及びその誘導体
WO2012146067A1 (fr) Dérivés de 1,4-dihydropyridine-3,5-dicarboxylate, procédés de préparation et utilisations
JPS5965089A (ja) ジヒドロピラゾロ〔３，４−ｂ〕ピリジン誘導体およびその製造法
TW200811100A (en) Compounds and methods for inhibiting the interaction of BCL proteins with binding partners
TW201136922A (en) New oxadiazole derivatives
JP7603320B2 (ja) 環内チアミジノアミド－アリールアミド系化合物及びｂ型肝炎を治療するためのその使用
CN102271671B (zh) 3，5-断-4-去甲-胆甾烷肟的衍生物、包含它们的药物组合物及其制备方法
JPS62281860A (ja) アルキレンアミノアルキレン　ヘテロ原子基を有するジヒドロ−３，５−ジカルボキシレ−ト
CN112189009A (zh) 作为tcr-nck相互作用的抑制剂的色烯衍生物
JPS62174050A (ja) ３−アミノカルボニル−１，４−ジヒドロピリジン−５−カルボン酸誘導体、その製法および医薬組成物
TW577877B (en) Improved methods of preparing 4-cyano-4-(substituted indazole)cyclohexane-carboxylic acids useful as PDE4 inhibitors
JPH05502867A (ja) ピペリジン化合物及び医薬組成物
JPH05504345A (ja) 新規ジヒドロピリジン
JP2791069B2 (ja) シクロオクタン神経保護剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10791139

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10791139

Country of ref document: EP

Kind code of ref document: A1