JP2020534275A5 - - Google Patents
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- Publication number
- JP2020534275A5 JP2020534275A5 JP2020515081A JP2020515081A JP2020534275A5 JP 2020534275 A5 JP2020534275 A5 JP 2020534275A5 JP 2020515081 A JP2020515081 A JP 2020515081A JP 2020515081 A JP2020515081 A JP 2020515081A JP 2020534275 A5 JP2020534275 A5 JP 2020534275A5
- Authority
- JP
- Japan
- Prior art keywords
- azabicyclo
- cyclopropyl
- methoxy
- heptane
- dichlorophenyl
- 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.)
- Granted
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 58
- -1 2,6-dimethylphenyl Chemical group 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- 150000001875 compounds Chemical class 0.000 claims description 46
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 44
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 44
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000001188 haloalkyl group Chemical group 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000004429 atom Chemical group 0.000 claims description 28
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 24
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 24
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 16
- 102100038495 Bile acid receptor Human genes 0.000 claims description 14
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 13
- 235000019260 propionic acid Nutrition 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 12
- 229940002612 prodrug Drugs 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
- 208000017169 kidney disease Diseases 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 6
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 6
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 6
- DMPZJACLHDWUFS-UHFFFAOYSA-N 1,3-benzothiazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2N=CSC2=C1 DMPZJACLHDWUFS-UHFFFAOYSA-N 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 208000028774 intestinal disease Diseases 0.000 claims description 5
- 208000019423 liver disease Diseases 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 4
- 201000011374 Alagille syndrome Diseases 0.000 claims description 4
- PJVIEYZTOPCQDD-WVMBUTMQSA-N C1CC(C2=C3N=C(SC3=CC(C(=O)O)=C2)N2[C@@H]3C[C@@H](OCC4=C(N=NN4C4CC4)C4=C(C=CC=C4Cl)Cl)[C@H](C2)C3)C1 Chemical compound C1CC(C2=C3N=C(SC3=CC(C(=O)O)=C2)N2[C@@H]3C[C@@H](OCC4=C(N=NN4C4CC4)C4=C(C=CC=C4Cl)Cl)[C@H](C2)C3)C1 PJVIEYZTOPCQDD-WVMBUTMQSA-N 0.000 claims description 4
- 206010010317 Congenital absence of bile ducts Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 201000005271 biliary atresia Diseases 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 208000007232 portal hypertension Diseases 0.000 claims description 4
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- YUDXCYAQSGDLCV-WQDYTSBFSA-N 4-[(1R,3S,4R,5S)-5-[[4-cyclopropyl-2-(2,6-dichlorophenyl)pyrazol-3-yl]methoxy]-3-ethyl-2-azabicyclo[2.2.1]heptan-2-yl]benzoic acid Chemical compound C1(CC1)C=1C=NN(C=1CO[C@@H]1[C@H]2[C@@H](N([C@@H](C1)C2)C1=CC=C(C(=O)O)C=C1)CC)C1=C(C=CC=C1Cl)Cl YUDXCYAQSGDLCV-WQDYTSBFSA-N 0.000 claims description 2
- 208000003200 Adenoma Diseases 0.000 claims description 2
- 206010001233 Adenoma benign Diseases 0.000 claims description 2
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 2
- 206010004593 Bile duct cancer Diseases 0.000 claims description 2
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| MA55632A (fr) | 2016-08-23 | 2022-02-16 | Ardelyx Inc | Procédé de preparation de modulateurs du récepteur hormonal pour le traitement d'états et de troubles métaboliques |
| US11091482B2 (en) | 2016-08-23 | 2021-08-17 | Ardelyx, Inc. | Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators |
| CN110128432B (zh) | 2018-02-02 | 2021-03-02 | 广东东阳光药业有限公司 | 含氮三环化合物及其在药物中的应用 |
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| IT1228288B (it) | 1989-01-09 | 1991-06-07 | Zambon Spa | Composti ad attivita' antiserotoninica |
| US5262564A (en) | 1992-10-30 | 1993-11-16 | Octamer, Inc. | Sulfinic acid adducts of organo nitroso compounds useful as retroviral inactivating agents anti-retroviral agents and anti-tumor agents |
| TW200906823A (en) | 2007-07-16 | 2009-02-16 | Lilly Co Eli | Compounds and methods for modulating FXR |
| EP2289883A1 (en) | 2009-08-19 | 2011-03-02 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| 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 |
| JP2014533258A (ja) | 2011-11-15 | 2014-12-11 | ゼンション・リミテッドＸｅｎｔｉｏｎ Ｌｉｍｉｔｅｄ | カリウムチャネル阻害剤としてのチエノ［２，３−ｃ］ピラゾールの使用 |
| EP3034501A1 (en) * | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Hydroxy containing FXR (NR1H4) modulating compounds |
| US20170368038A1 (en) * | 2014-12-18 | 2017-12-28 | Novartis Ag | Azabicyclooctane derivatives as fxr agonists for use in the treatment of liver and gastrointestinal diseases |
| TWI698430B (zh) | 2015-02-13 | 2020-07-11 | 南北兄弟藥業投資有限公司 | 三環化合物及其在藥物中的應用 |
| MA55632A (fr) | 2016-08-23 | 2022-02-16 | Ardelyx Inc | Procédé de preparation de modulateurs du récepteur hormonal pour le traitement d'états et de troubles métaboliques |
| US11091482B2 (en) | 2016-08-23 | 2021-08-17 | Ardelyx, Inc. | Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators |
| KR102400183B1 (ko) | 2017-07-06 | 2022-05-18 | 수안주 바이오파마슈티컬 컴퍼니 리미티드 | Fxr 작용제 |
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- 2018-09-14 MA MA050242A patent/MA50242A/fr unknown
- 2018-09-14 WO PCT/US2018/051122 patent/WO2019055808A1/en not_active Ceased
- 2018-09-18 US US16/647,385 patent/US11753410B2/en active Active
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2023
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