CN101743232B - 调节fxr的化合物和方法 - Google Patents
调节fxr的化合物和方法 Download PDFInfo
- Publication number
- CN101743232B CN101743232B CN2008800247651A CN200880024765A CN101743232B CN 101743232 B CN101743232 B CN 101743232B CN 2008800247651 A CN2008800247651 A CN 2008800247651A CN 200880024765 A CN200880024765 A CN 200880024765A CN 101743232 B CN101743232 B CN 101743232B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- cyclopropyl
- dichloro
- ylmethoxy
- methyl
- 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.)
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- 0 C[U](C(*)=C1C*)NN1c1c(*)cccc1* Chemical compound C[U](C(*)=C1C*)NN1c1c(*)cccc1* 0.000 description 2
- RPVDFHPBGBMWID-UHFFFAOYSA-N C[n]1c2cc(N(CC3)CCC3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc2c(C(O)=O)c1 Chemical compound C[n]1c2cc(N(CC3)CCC3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc2c(C(O)=O)c1 RPVDFHPBGBMWID-UHFFFAOYSA-N 0.000 description 2
- WQOFPZFDXPHYLX-UHFFFAOYSA-N Clc1c(-c2n[o]c(C3CC3)c2COC2CCNCC2)c(Cl)ccc1 Chemical compound Clc1c(-c2n[o]c(C3CC3)c2COC2CCNCC2)c(Cl)ccc1 WQOFPZFDXPHYLX-UHFFFAOYSA-N 0.000 description 2
- QEPDFQBZEHAKMC-UHFFFAOYSA-N CC(C)c1c(COC(CC2)CCN2c2ccc(c(C(O)=O)c[n]3C)c3c2)c(-c(c(Cl)ccc2)c2Cl)n[o]1 Chemical compound CC(C)c1c(COC(CC2)CCN2c2ccc(c(C(O)=O)c[n]3C)c3c2)c(-c(c(Cl)ccc2)c2Cl)n[o]1 QEPDFQBZEHAKMC-UHFFFAOYSA-N 0.000 description 1
- CDRNGLZPBHHCLC-UHFFFAOYSA-N CCOC(c(cc1)ccc1N(CCC1)CCC1OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=N Chemical compound CCOC(c(cc1)ccc1N(CCC1)CCC1OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=N CDRNGLZPBHHCLC-UHFFFAOYSA-N 0.000 description 1
- QUTMBOOKAHXKGE-UHFFFAOYSA-N C[n]1c(cc(cc2)N(CC3)CCC3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2c(C(C=O)=O)c1 Chemical compound C[n]1c(cc(cc2)N(CC3)CCC3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2c(C(C=O)=O)c1 QUTMBOOKAHXKGE-UHFFFAOYSA-N 0.000 description 1
- HWBMHQHCLGJHBY-UHFFFAOYSA-N Clc1c(-c2n[o]c(C3CC3)c2COC2CCNCCC2)c(Cl)ccc1 Chemical compound Clc1c(-c2n[o]c(C3CC3)c2COC2CCNCCC2)c(Cl)ccc1 HWBMHQHCLGJHBY-UHFFFAOYSA-N 0.000 description 1
- LXWQVTNZUIURFE-XFFZJAGNSA-N O/N=C(/c(c(Cl)ccc1)c1Cl)\Cl Chemical compound O/N=C(/c(c(Cl)ccc1)c1Cl)\Cl LXWQVTNZUIURFE-XFFZJAGNSA-N 0.000 description 1
- BHHQDQJNIROKNF-UHFFFAOYSA-N OC(c(cc1)ccc1N(CCC1)CCC1OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=O Chemical compound OC(c(cc1)ccc1N(CCC1)CCC1OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=O BHHQDQJNIROKNF-UHFFFAOYSA-N 0.000 description 1
- ANGDXDPWIYHNID-UHFFFAOYSA-N OC(c1n[s]c2c1ccc(N(CCC1)CCC1OCc1c(C3CC3)[o]nc1-c(c(Cl)ccc1)c1Cl)c2)=O Chemical compound OC(c1n[s]c2c1ccc(N(CCC1)CCC1OCc1c(C3CC3)[o]nc1-c(c(Cl)ccc1)c1Cl)c2)=O ANGDXDPWIYHNID-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94997407P | 2007-07-16 | 2007-07-16 | |
| US60/949,974 | 2007-07-16 | ||
| PCT/US2008/069719 WO2009012125A1 (en) | 2007-07-16 | 2008-07-11 | Compounds and methods for modulating fxr |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101743232A CN101743232A (zh) | 2010-06-16 |
| CN101743232B true CN101743232B (zh) | 2013-03-06 |
Family
ID=39855171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008800247651A Active CN101743232B (zh) | 2007-07-16 | 2008-07-11 | 调节fxr的化合物和方法 |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US8153624B2 (https=) |
| EP (1) | EP2178851B1 (https=) |
| JP (1) | JP5373788B2 (https=) |
| KR (1) | KR101157334B1 (https=) |
| CN (1) | CN101743232B (https=) |
| AR (1) | AR067540A1 (https=) |
| AT (1) | ATE539065T1 (https=) |
| AU (1) | AU2008276236B2 (https=) |
| BR (1) | BRPI0814571A2 (https=) |
| CA (1) | CA2693406C (https=) |
| CL (1) | CL2008002051A1 (https=) |
| CO (1) | CO6270212A2 (https=) |
| CY (1) | CY1112298T1 (https=) |
| DK (1) | DK2178851T3 (https=) |
| DO (1) | DOP2010000018A (https=) |
| EA (1) | EA016475B1 (https=) |
| EC (1) | ECSP109879A (https=) |
| ES (1) | ES2376176T3 (https=) |
| HR (1) | HRP20120048T1 (https=) |
| IL (1) | IL202234A0 (https=) |
| MA (1) | MA31683B1 (https=) |
| MX (1) | MX2010000502A (https=) |
| PE (1) | PE20090809A1 (https=) |
| PL (1) | PL2178851T3 (https=) |
| PT (1) | PT2178851E (https=) |
| RS (1) | RS52216B (https=) |
| SI (1) | SI2178851T1 (https=) |
| SV (1) | SV2010003458A (https=) |
| TN (1) | TN2010000028A1 (https=) |
| TW (1) | TW200906823A (https=) |
| WO (1) | WO2009012125A1 (https=) |
Families Citing this family (83)
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| EP2289883A1 (en) | 2009-08-19 | 2011-03-02 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| JP2014500319A (ja) * | 2010-12-20 | 2014-01-09 | アイアールエム・リミテッド・ライアビリティ・カンパニー | ファルネソイドｘ受容体を調節するための組成物および方法 |
| WO2012087520A1 (en) * | 2010-12-20 | 2012-06-28 | Irm Llc | Compositions and methods for modulating farnesoid x receptors |
| CU24152B1 (es) * | 2010-12-20 | 2016-02-29 | Irm Llc | 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| WO2013037482A1 (en) | 2011-09-15 | 2013-03-21 | Phenex Pharmaceuticals Ag | Farnesoid x receptor agonists for cancer treatment and prevention |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| EP2970177A1 (en) | 2013-03-15 | 2016-01-20 | Pfizer Inc. | Indole compounds that activate ampk |
| SI3043865T1 (sl) | 2013-09-11 | 2021-04-30 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Metode in farmacevtski sestavki za zdravljenje virusne okužbe s hepatitisom B |
| KR102350357B1 (ko) * | 2013-11-05 | 2022-01-14 | 노파르티스 아게 | 파르네소이드 x 수용체의 조정을 위한 조성물 및 방법 |
| CN104045635A (zh) * | 2014-06-23 | 2014-09-17 | 华东理工大学 | 3,4,5-三取代异恶唑类化合物及其用途 |
| EP3006939A1 (en) | 2014-10-06 | 2016-04-13 | Gilead Sciences, Inc. | Histidine-rich Glycoprotein as a marker for hepatic Farnesoid X receptor activation |
| US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| EP3034501A1 (en) * | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Hydroxy containing FXR (NR1H4) modulating compounds |
| EP3034499A1 (en) * | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Novel FXR (NR1H4) modulating compounds |
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| EP4210705A4 (en) * | 2020-09-11 | 2024-11-13 | Terns Pharmaceuticals, Inc. | SOLID DISPERSION FORMULATIONS OF A FXR AGONIST |
| AU2021359895A1 (en) * | 2020-10-15 | 2023-06-15 | Eli Lilly And Company | Polymorphs of an fxr agonist |
| KR20230154806A (ko) | 2021-01-14 | 2023-11-09 | 엔요 파마 | Hbv 감염 치료를 위한 fxr 작용제 및 ifn의 상승작용효과 |
| CN117320722A (zh) | 2021-04-28 | 2023-12-29 | 埃尼奥制药公司 | 使用fxr激动剂作为联合治疗强烈增强tlr3激动剂的作用 |
| CN119013027A (zh) | 2021-11-11 | 2024-11-22 | 拓臻制药公司 | 用于治疗肝脏病症的SSAO抑制剂和THR-β激动剂的组合 |
| WO2023220404A1 (en) * | 2022-05-13 | 2023-11-16 | Terns Pharmaceuticals, Inc. | Treatment of non-alcoholic steatohepatitis |
| CN115850152B (zh) * | 2022-12-20 | 2025-10-31 | 河北鼎泰制药有限公司 | 一种杂质A-7-imp3的制备方法及其用途 |
| EP4568664B1 (en) | 2023-04-07 | 2026-04-01 | Terns Pharmaceuticals, Inc. | Combination comprising a thr-beta agonist and a glp-1r agonist for use in treating obesity |
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| JPH07138258A (ja) * | 1993-11-16 | 1995-05-30 | Taiho Yakuhin Kogyo Kk | チアゾリジンジオン誘導体又はその塩 |
| JP2002532729A (ja) | 1998-12-23 | 2002-10-02 | グラクソ グループ リミテッド | 核内受容体のリガンドのアッセイ |
| US7105556B2 (en) * | 2001-05-30 | 2006-09-12 | Bristol-Myers Squibb Company | Conformationally constrained analogs useful as antidiabetic and antiobesity agents and method |
| US6967212B2 (en) * | 2001-05-30 | 2005-11-22 | Bristol-Myers Squibb Company | Substituted azole acid derivatives useful as antidiabetic and antiobesity agents and method |
| ATE381542T1 (de) | 2001-08-13 | 2008-01-15 | Phenex Pharmaceuticals Ag | Nr1h4-kern-rezeptor-bindende verbindungen |
| BR0312503A (pt) | 2002-07-09 | 2007-06-26 | Bristol Myers Squibb Co | derivados heterocìclicos substituìdos úteis como agentes antidiabéticos e antiobesidade, composição farmacêutica, uso e combinação dos mesmos |
| JP2006515838A (ja) * | 2002-11-22 | 2006-06-08 | スミスクライン ビーチャム コーポレーション | ファルネソイドｘ受容体アゴニスト |
| CA2640476A1 (en) | 2006-02-03 | 2007-08-16 | Eli Lilly And Company | Compounds and methods for modulating fx-receptors |
| BRPI0712262A2 (pt) | 2006-05-24 | 2012-07-10 | Lilly Co Eli | agonistas de fxr |
| US8106077B2 (en) | 2006-05-24 | 2012-01-31 | Eli Lilly And Company | Compounds and methods for modulating FXR |
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