CN114901641A - 芳香族化合物及其药物组合物和用途 - Google Patents
芳香族化合物及其药物组合物和用途 Download PDFInfo
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- CN114901641A CN114901641A CN202180007741.0A CN202180007741A CN114901641A CN 114901641 A CN114901641 A CN 114901641A CN 202180007741 A CN202180007741 A CN 202180007741A CN 114901641 A CN114901641 A CN 114901641A
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- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical group OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000013577 regulation of ventricular cardiomyocyte membrane repolarization Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- ZZPIFLXDERHOAP-UHFFFAOYSA-N tert-butyl 2-(4-formyl-2,6-dimethylphenoxy)-2-methylpropanoate Chemical compound CC1=CC(C=O)=CC(C)=C1OC(C)(C)C(=O)OC(C)(C)C ZZPIFLXDERHOAP-UHFFFAOYSA-N 0.000 description 1
- IGVNJALYNQVQIT-UHFFFAOYSA-N tert-butyl 2-bromo-2-methylpropanoate Chemical compound CC(C)(C)OC(=O)C(C)(C)Br IGVNJALYNQVQIT-UHFFFAOYSA-N 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 238000012403 whole-cell patch-clamp technology Methods 0.000 description 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本申请公开了一种芳香族化合物及其药物组合物的用途,含有所述化合物的药物组合物,以及该类化合物及其中间体的制备方法。本申请还公开了所述化合物用于制备预防或治疗肝脏疾病和/或胆管疾病相关疾病或病症的药物用途。
Description
PCT国内申请,说明书已公开。
Claims (19)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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CN2020101300244 | 2020-02-28 | ||
CN202010130024 | 2020-02-28 | ||
PCT/CN2021/075433 WO2021169769A1 (zh) | 2020-02-28 | 2021-02-05 | 芳香族化合物及其药物组合物和用途 |
Publications (1)
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CN114901641A true CN114901641A (zh) | 2022-08-12 |
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CN202180007741.0A Pending CN114901641A (zh) | 2020-02-28 | 2021-02-05 | 芳香族化合物及其药物组合物和用途 |
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WO (1) | WO2021169769A1 (zh) |
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CN118359543A (zh) * | 2023-01-18 | 2024-07-19 | 哈尔滨三联药业股份有限公司 | 五元杂环类化合物及其医药用途 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003072099A1 (en) * | 2002-02-21 | 2003-09-04 | Eli Lilly And Company | Peroxisome proliferator activated receptor modulators |
WO2005019151A1 (en) * | 2003-08-20 | 2005-03-03 | Eli Lilly And Company | Ppar modulators |
WO2005040102A2 (en) * | 2003-10-28 | 2005-05-06 | Dr. Reddy's Laboratories Ltd. | Novel compounds and their use as antidiabetic and hypolipidemic agents, process for their preparation and pharmaceutical compositions containing them |
CN1668565A (zh) * | 2002-07-08 | 2005-09-14 | 基恩菲特公司 | 取代的1,3-二苯基丙-2-烯-1-酮衍生物、其制备及其用途 |
WO2008087365A2 (fr) * | 2006-12-29 | 2008-07-24 | Genfit | Derives de 1,3-diphenylpropane substitues, preparations et utilisations |
WO2008087367A2 (fr) * | 2006-12-29 | 2008-07-24 | Genfit | Derives de (phenylthiazolyl)-phenyl-propan-1-one et de (phenyloxazodyl)-phenyl-propan-1-one substitues, preparations et utilisations |
CN101506138A (zh) * | 2006-06-21 | 2009-08-12 | 基恩菲特 | 取代的1,3-二苯基丙烷衍生物、它们的制备及用途 |
CN101605775A (zh) * | 2006-12-29 | 2009-12-16 | 基恩菲特公司 | 取代的3-苯基-1-(苯基噻吩基)丙-1-酮类以及3-苯基-1-(苯基呋喃基)丙-1-酮类的衍生物、制备以及用途 |
WO2019105234A1 (zh) * | 2017-11-30 | 2019-06-06 | 四川科伦博泰生物医药股份有限公司 | 芳香族化合物及其药物组合物和用途 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1177187E (pt) * | 1999-04-28 | 2007-09-03 | Sanofi Aventis Deutschland | Derivados ácidos de di-arilo como ligados do receptor ppar. |
ITRM20020629A1 (it) * | 2002-12-19 | 2004-06-20 | Sigma Tau Ind Farmaceuti | Uso di acidi alfa-feniltiocarbossilici e alfa-fenilossicarbossilici ad attivita' ipoglicemizzante e/o ipolipidemizzante. |
-
2021
- 2021-02-05 CN CN202180007741.0A patent/CN114901641A/zh active Pending
- 2021-02-05 WO PCT/CN2021/075433 patent/WO2021169769A1/zh active Application Filing
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003072099A1 (en) * | 2002-02-21 | 2003-09-04 | Eli Lilly And Company | Peroxisome proliferator activated receptor modulators |
CN1668565A (zh) * | 2002-07-08 | 2005-09-14 | 基恩菲特公司 | 取代的1,3-二苯基丙-2-烯-1-酮衍生物、其制备及其用途 |
WO2005019151A1 (en) * | 2003-08-20 | 2005-03-03 | Eli Lilly And Company | Ppar modulators |
WO2005040102A2 (en) * | 2003-10-28 | 2005-05-06 | Dr. Reddy's Laboratories Ltd. | Novel compounds and their use as antidiabetic and hypolipidemic agents, process for their preparation and pharmaceutical compositions containing them |
CN101506138A (zh) * | 2006-06-21 | 2009-08-12 | 基恩菲特 | 取代的1,3-二苯基丙烷衍生物、它们的制备及用途 |
WO2008087365A2 (fr) * | 2006-12-29 | 2008-07-24 | Genfit | Derives de 1,3-diphenylpropane substitues, preparations et utilisations |
WO2008087367A2 (fr) * | 2006-12-29 | 2008-07-24 | Genfit | Derives de (phenylthiazolyl)-phenyl-propan-1-one et de (phenyloxazodyl)-phenyl-propan-1-one substitues, preparations et utilisations |
CN101605775A (zh) * | 2006-12-29 | 2009-12-16 | 基恩菲特公司 | 取代的3-苯基-1-(苯基噻吩基)丙-1-酮类以及3-苯基-1-(苯基呋喃基)丙-1-酮类的衍生物、制备以及用途 |
WO2019105234A1 (zh) * | 2017-11-30 | 2019-06-06 | 四川科伦博泰生物医药股份有限公司 | 芳香族化合物及其药物组合物和用途 |
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