JP2017510572A5 - - Google Patents
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- JP2017510572A5 JP2017510572A5 JP2016556962A JP2016556962A JP2017510572A5 JP 2017510572 A5 JP2017510572 A5 JP 2017510572A5 JP 2016556962 A JP2016556962 A JP 2016556962A JP 2016556962 A JP2016556962 A JP 2016556962A JP 2017510572 A5 JP2017510572 A5 JP 2017510572A5
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- 150000001875 compounds Chemical class 0.000 description 63
- 125000000217 alkyl group Chemical group 0.000 description 32
- 125000001931 aliphatic group Chemical group 0.000 description 31
- 229910052739 hydrogen Inorganic materials 0.000 description 22
- 229910052736 halogen Inorganic materials 0.000 description 20
- 150000002367 halogens Chemical class 0.000 description 20
- -1 hydrate Substances 0.000 description 19
- 239000001257 hydrogen Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- 229910052805 deuterium Inorganic materials 0.000 description 13
- YZCKVEUIGOORGS-OUBTZVSYSA-N deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 13
- 150000002431 hydrogen Chemical class 0.000 description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 230000000968 intestinal Effects 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 102100020059 NR1H4 Human genes 0.000 description 6
- 101700077249 NR1H4 Proteins 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 101700056534 farnesoid X receptors Proteins 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 208000008466 Metabolic Disease Diseases 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 5
- 125000004431 deuterium atoms Chemical group 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 0 *C(C1C*c2cc(*)c(C=CC(C=*)=CC=C*)c(*)c2)ON=C1c1c(*)cccc1* Chemical compound *C(C1C*c2cc(*)c(C=CC(C=*)=CC=C*)c(*)c2)ON=C1c1c(*)cccc1* 0.000 description 4
- 210000001035 Gastrointestinal Tract Anatomy 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 210000004185 Liver Anatomy 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- 210000003486 Adipose Tissue, Brown Anatomy 0.000 description 3
- 206010012601 Diabetes mellitus Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000002496 gastric Effects 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 2
- 206010009839 Coeliac disease Diseases 0.000 description 2
- 102100012353 DPP4 Human genes 0.000 description 2
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- 208000009471 Gastroesophageal Reflux Diseases 0.000 description 2
- 206010017885 Gastrooesophageal reflux disease Diseases 0.000 description 2
- 206010022489 Insulin resistance Diseases 0.000 description 2
- 210000003734 Kidney Anatomy 0.000 description 2
- JLEBZPBDRKPWTD-TURQNECASA-O N-ribosylnicotinamide Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 JLEBZPBDRKPWTD-TURQNECASA-O 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 201000006860 gastroesophageal reflux disease Diseases 0.000 description 2
- 101710038873 glc-1 Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000037323 metabolic rate Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000002062 proliferating Effects 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 230000001225 therapeutic Effects 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 description 1
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- RGHPCLZJAFCTIK-UHFFFAOYSA-N 2-methylpyrrolidine Chemical compound CC1CCCN1 RGHPCLZJAFCTIK-UHFFFAOYSA-N 0.000 description 1
- 102100014184 ADRB3 Human genes 0.000 description 1
- 101700073744 ADRB3 Proteins 0.000 description 1
- 208000009956 Adenocarcinoma Diseases 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N Azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010011401 Crohn's disease Diseases 0.000 description 1
- 206010058108 Dyslipidaemia Diseases 0.000 description 1
- 102100015614 FGF19 Human genes 0.000 description 1
- 101700047578 FGF19 Proteins 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 108009000020 Glucose Homeostasis Proteins 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010021972 Inflammatory bowel disease Diseases 0.000 description 1
- 210000000936 Intestines Anatomy 0.000 description 1
- 208000002551 Irritable Bowel Syndrome Diseases 0.000 description 1
- 206010061227 Lipid metabolism disease Diseases 0.000 description 1
- 206010051606 Necrotising colitis Diseases 0.000 description 1
- 208000004995 Necrotizing Enterocolitis Diseases 0.000 description 1
- 101700022251 PER1 Proteins 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 102100001195 SLC51A Human genes 0.000 description 1
- 108091007340 SLC51A1 Proteins 0.000 description 1
- 230000037165 Serum Concentration Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 230000003115 biocidal Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000002519 immonomodulatory Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 229940113083 morpholine Drugs 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 230000010627 oxidative phosphorylation Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
- 239000000546 pharmaceutic aid Substances 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000865 phosphorylative Effects 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 230000002980 postoperative Effects 0.000 description 1
- 230000000580 secretagogue Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 201000006704 ulcerative colitis Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461952754P | 2014-03-13 | 2014-03-13 | |
| US61/952,754 | 2014-03-13 | ||
| US201462061463P | 2014-10-08 | 2014-10-08 | |
| US62/061,463 | 2014-10-08 | ||
| PCT/US2015/020582 WO2015138986A1 (en) | 2014-03-13 | 2015-03-13 | Fxr agonists and methods for making and using |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017510572A JP2017510572A (ja) | 2017-04-13 |
| JP2017510572A5 true JP2017510572A5 (ru) | 2017-06-29 |
Family
ID=54072502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016556962A Pending JP2017510572A (ja) | 2014-03-13 | 2015-03-13 | Ｆｘｒアゴニストならびに作製および使用のための方法 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3116878A4 (ru) |
| JP (1) | JP2017510572A (ru) |
| KR (1) | KR20160132111A (ru) |
| AU (1) | AU2015229072A1 (ru) |
| CA (1) | CA2942403A1 (ru) |
| WO (1) | WO2015138986A1 (ru) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| US10301268B2 (en) | 2014-03-13 | 2019-05-28 | The Salk Institute For Biological Studies | Analogs of fexaramine and methods of making and using |
| US10077268B2 (en) | 2014-03-13 | 2018-09-18 | Salk Institute For Biological Studies | FXR agonists and methods for making and using |
| ES2908332T3 (es) | 2014-07-24 | 2022-04-28 | Grace W R & Co | Forma cristalina de cloruro de ribosilnicotinamida |
| 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 |
| BR112017019409A2 (pt) | 2015-03-09 | 2018-04-24 | Grace W R & Co | forma cristalina de ribosídeo de nicotinamida |
| AU2016323992B2 (en) | 2015-09-16 | 2021-05-06 | Organovo, Inc. | Farnesoid X receptor agonists and uses thereof |
| WO2017078928A1 (en) * | 2015-11-06 | 2017-05-11 | Salk Institute For Biological Studies | Fxr agonists and methods for making and using |
| WO2017143134A1 (en) * | 2016-02-19 | 2017-08-24 | Alios Biopharma, Inc. | Fxr modulators and methods of their use |
| ES2921432T3 (es) | 2016-06-13 | 2022-08-25 | Gilead Sciences Inc | Derivados de azetidina como moduladores de FXR (NR1H4) |
| CA2968836A1 (en) | 2016-06-13 | 2017-12-13 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| JOP20190040A1 (ar) * | 2016-09-14 | 2019-03-10 | Novartis Ag | توليفة من ناهضات fxr |
| MX2019009908A (es) | 2017-02-21 | 2019-10-14 | Genfit | Combinacion de un agonista de ppar con un agonista de fxr. |
| ES2927019T3 (es) | 2017-03-28 | 2022-11-02 | Gilead Sciences Inc | Combinaciones terapéuticas para el tratamiento de enfermedades hepáticas |
| BR112021004919A2 (pt) | 2018-09-18 | 2021-06-01 | Metacrine, Inc. | agonistas de receptor farnesoide x e usos dos mesmos |
| DK3911647T3 (da) | 2019-01-15 | 2024-02-26 | Gilead Sciences Inc | Isoxazol-forbindelse som FXR-agonist og farmaceutiske sammensætninger, der omfatter en sådan |
| CN113439078B (zh) | 2019-02-19 | 2024-04-23 | 吉利德科学公司 | Fxr激动剂的固体形式 |
| MX2022000742A (es) | 2019-07-18 | 2022-02-14 | Enyo Pharma | Metodo para disminuir los efectos adversos del interferon. |
| US20220265619A1 (en) | 2019-07-23 | 2022-08-25 | Novartis Ag | Combination treatment of liver diseases using fxr agonists |
| CN114080234A (zh) | 2019-07-23 | 2022-02-22 | 诺华股份有限公司 | 包含fxr激动剂的治疗 |
| MX2022002636A (es) | 2019-09-03 | 2022-03-25 | Novartis Ag | Tratamiento de la enfermedad o trastorno hepatico que comprende los antagonistas del receptor de actrii. |
| US20220347190A1 (en) | 2019-09-19 | 2022-11-03 | Novartis Ag | Treatment comprising fxr agonists |
| EP4041233A1 (en) | 2019-09-30 | 2022-08-17 | Novartis AG | Treatment comprising the use of fxr agonists |
| AU2020408067B2 (en) | 2019-12-20 | 2024-03-28 | Novartis Ag | Combination treatment of liver diseases using integrin inhibitors |
| EP4090327A1 (en) | 2020-01-15 | 2022-11-23 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Use of fxr agonists for treating an infection by hepatitis d virus |
| WO2022101853A1 (en) | 2020-11-16 | 2022-05-19 | Novartis Ag | Method of determining liver fibrosis |
| CN117202905A (zh) | 2021-01-14 | 2023-12-08 | 埃尼奥制药公司 | Fxr激动剂和ifn用于治疗hbv感染的协同效果 |
| JP2024517181A (ja) | 2021-04-28 | 2024-04-19 | ウエヌイグレックオ・ファーマ | 組合せ治療としてｆｘｒアゴニストを使用するｔｌｒ３アゴニストの効果の強い増強 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI329111B (en) * | 2002-05-24 | 2010-08-21 | X Ceptor Therapeutics Inc | Azepinoindole and pyridoindole derivatives as pharmaceutical agents |
| EP1963331A1 (en) * | 2005-12-15 | 2008-09-03 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| US20080300235A1 (en) * | 2007-06-01 | 2008-12-04 | Wyeth | FXR Agonists for Reducing LOX-1 Expression |
| US20090163474A1 (en) * | 2007-10-19 | 2009-06-25 | Wyeth | FXR Agonists for the Treatment of Nonalcoholic Fatty Liver and Cholesterol Gallstone Diseases |
| US20090215748A1 (en) * | 2007-12-20 | 2009-08-27 | Wyeth | FXR agonists for treating vitamin D associated diseases |
| EP2334681A1 (en) * | 2008-09-26 | 2011-06-22 | Wyeth LLC | 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate nuclear receptor inhibitors |
| EP2995317A1 (en) * | 2010-05-26 | 2016-03-16 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| WO2013020108A2 (en) * | 2011-08-04 | 2013-02-07 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of pancreatitis |
-
2015
- 2015-03-13 KR KR1020167028569A patent/KR20160132111A/ko unknown
- 2015-03-13 WO PCT/US2015/020582 patent/WO2015138986A1/en active Application Filing
- 2015-03-13 CA CA2942403A patent/CA2942403A1/en not_active Abandoned
- 2015-03-13 EP EP15761517.0A patent/EP3116878A4/en not_active Withdrawn
- 2015-03-13 JP JP2016556962A patent/JP2017510572A/ja active Pending
- 2015-03-13 AU AU2015229072A patent/AU2015229072A1/en not_active Abandoned
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