JP2018505203A5 - - Google Patents
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- JP2018505203A5 JP2018505203A5 JP2017542165A JP2017542165A JP2018505203A5 JP 2018505203 A5 JP2018505203 A5 JP 2018505203A5 JP 2017542165 A JP2017542165 A JP 2017542165A JP 2017542165 A JP2017542165 A JP 2017542165A JP 2018505203 A5 JP2018505203 A5 JP 2018505203A5
- Authority
- JP
- Japan
- Prior art keywords
- independently
- alkyl
- aryl
- cycloalkyl
- heterocyclyl
- 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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- 125000000217 alkyl group Chemical group 0.000 claims 38
- 125000000623 heterocyclic group Chemical group 0.000 claims 38
- 125000003118 aryl group Chemical group 0.000 claims 35
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 30
- 229910052805 deuterium Inorganic materials 0.000 claims 30
- -1 hydroxy, amino Chemical group 0.000 claims 29
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 25
- 125000004103 aminoalkyl group Chemical group 0.000 claims 20
- 125000001072 heteroaryl group Chemical group 0.000 claims 16
- 125000003342 alkenyl group Chemical group 0.000 claims 15
- 125000003545 alkoxy group Chemical group 0.000 claims 15
- 125000000304 alkynyl group Chemical group 0.000 claims 15
- 239000002207 metabolite Substances 0.000 claims 15
- 150000003839 salts Chemical class 0.000 claims 15
- 239000012453 solvate Substances 0.000 claims 15
- 150000001204 N-oxides Chemical class 0.000 claims 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims 14
- 239000000651 prodrug Substances 0.000 claims 14
- 229940002612 prodrug Drugs 0.000 claims 14
- 150000001875 compounds Chemical class 0.000 claims 13
- 201000010099 disease Diseases 0.000 claims 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 12
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims 11
- 125000001188 haloalkyl group Chemical group 0.000 claims 11
- 125000004432 carbon atom Chemical group C* 0.000 claims 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 9
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 8
- 125000004438 haloalkoxy group Chemical group 0.000 claims 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 7
- 125000003282 alkyl amino group Chemical group 0.000 claims 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 6
- 125000004043 oxo group Chemical group O=* 0.000 claims 6
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 5
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 4
- 125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 4
- 206010016654 Fibrosis Diseases 0.000 claims 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- 229940127557 pharmaceutical product Drugs 0.000 claims 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 3
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims 3
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 3
- 208000008589 Obesity Diseases 0.000 claims 3
- 125000002947 alkylene group Chemical group 0.000 claims 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims 3
- 235000020824 obesity Nutrition 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 201000001320 Atherosclerosis Diseases 0.000 claims 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims 2
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 2
- 201000002150 Progressive familial intrahepatic cholestasis Diseases 0.000 claims 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 210000000013 bile duct Anatomy 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims 2
- 230000007882 cirrhosis Effects 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 230000004761 fibrosis Effects 0.000 claims 2
- 210000000232 gallbladder Anatomy 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 230000003463 hyperproliferative effect Effects 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 210000004185 liver Anatomy 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 125000000466 oxiranyl group Chemical group 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 claims 1
- 208000003200 Adenoma Diseases 0.000 claims 1
- 206010001233 Adenoma benign Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010008635 Cholestasis Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 201000003883 Cystic fibrosis Diseases 0.000 claims 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims 1
- 208000002249 Diabetes Complications Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 206010012655 Diabetic complications Diseases 0.000 claims 1
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 206010019695 Hepatic neoplasm Diseases 0.000 claims 1
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims 1
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 208000012868 Overgrowth Diseases 0.000 claims 1
- 201000001880 Sexual dysfunction Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 206010000891 acute myocardial infarction Diseases 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 208000007502 anemia Diseases 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 230000036765 blood level Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 201000001883 cholelithiasis Diseases 0.000 claims 1
- 230000007870 cholestasis Effects 0.000 claims 1
- 231100000359 cholestasis Toxicity 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 229930195729 fatty acid Natural products 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 150000004665 fatty acids Chemical class 0.000 claims 1
- 208000001130 gallstones Diseases 0.000 claims 1
- 210000004907 gland Anatomy 0.000 claims 1
- 208000002672 hepatitis B Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 201000001421 hyperglycemia Diseases 0.000 claims 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims 1
- 201000008980 hyperinsulinism Diseases 0.000 claims 1
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 208000004235 neutropenia Diseases 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 208000015768 polyposis Diseases 0.000 claims 1
- 208000007232 portal hypertension Diseases 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 229960002477 riboflavin Drugs 0.000 claims 1
- 235000019192 riboflavin Nutrition 0.000 claims 1
- 239000002151 riboflavin Substances 0.000 claims 1
- 208000010157 sclerosing cholangitis Diseases 0.000 claims 1
- 231100000872 sexual dysfunction Toxicity 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims 1
- 0 *C(*=*1)=C(CO*)*1I Chemical compound *C(*=*1)=C(CO*)*1I 0.000 description 50
- OVSYLHPLZZTPPK-UHFFFAOYSA-N CC(C)c1c(COc(cc2CCc(cc3)c4cc3C(O)=O)ccc2C4=O)[n](-c(c(Cl)ccc2)c2Cl)nn1 Chemical compound CC(C)c1c(COc(cc2CCc(cc3)c4cc3C(O)=O)ccc2C4=O)[n](-c(c(Cl)ccc2)c2Cl)nn1 OVSYLHPLZZTPPK-UHFFFAOYSA-N 0.000 description 1
- DGCCINFOBUGQPT-UHFFFAOYSA-N CC(C)c1c(COc(nc2CC3)ccc2Oc2c3ccc(C(O)=O)c2)[n](-c(c(Cl)ccc2)c2Cl)nc1 Chemical compound CC(C)c1c(COc(nc2CC3)ccc2Oc2c3ccc(C(O)=O)c2)[n](-c(c(Cl)ccc2)c2Cl)nc1 DGCCINFOBUGQPT-UHFFFAOYSA-N 0.000 description 1
- JWTATIZVPYVLKT-UHFFFAOYSA-N CCc(cc1CCc2c3cccc2)ccc1S3=O Chemical compound CCc(cc1CCc2c3cccc2)ccc1S3=O JWTATIZVPYVLKT-UHFFFAOYSA-N 0.000 description 1
- HXCRWRPVGDCJFH-UHFFFAOYSA-N COC(c1cc(Oc(c(C2C3C2)n2)ccc2OCc2c(C4CC4)[o]nc2-c(c(Cl)ccc2)c2Cl)c3cc1)=O Chemical compound COC(c1cc(Oc(c(C2C3C2)n2)ccc2OCc2c(C4CC4)[o]nc2-c(c(Cl)ccc2)c2Cl)c3cc1)=O HXCRWRPVGDCJFH-UHFFFAOYSA-N 0.000 description 1
- ADZBYRFCADJPGB-UHFFFAOYSA-N CS(NC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1)=O)(=O)=O Chemical compound CS(NC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1)=O)(=O)=O ADZBYRFCADJPGB-UHFFFAOYSA-N 0.000 description 1
- SNDHEQTYQPYSEL-UHFFFAOYSA-N CSc1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1 Chemical compound CSc1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1 SNDHEQTYQPYSEL-UHFFFAOYSA-N 0.000 description 1
- VYQLNYNFVHGKLB-UHFFFAOYSA-N C[n]1nc(C(O)=O)c2c1-c1cc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc1OC2 Chemical compound C[n]1nc(C(O)=O)c2c1-c1cc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc1OC2 VYQLNYNFVHGKLB-UHFFFAOYSA-N 0.000 description 1
- KHBOTBWWFUPYDQ-UHFFFAOYSA-N Cc(cc1)cc2c1Oc(cccc1)c1C=C2 Chemical compound Cc(cc1)cc2c1Oc(cccc1)c1C=C2 KHBOTBWWFUPYDQ-UHFFFAOYSA-N 0.000 description 1
- UCJYQGLMLCTOEH-UHFFFAOYSA-N Cc(cc1)cc2c1Oc1ccccc1CC2=O Chemical compound Cc(cc1)cc2c1Oc1ccccc1CC2=O UCJYQGLMLCTOEH-UHFFFAOYSA-N 0.000 description 1
- CGHZXICFAQJQIW-UHFFFAOYSA-N Cc(cc1)cc2c1Oc1ccccc1S2(=O)=O Chemical compound Cc(cc1)cc2c1Oc1ccccc1S2(=O)=O CGHZXICFAQJQIW-UHFFFAOYSA-N 0.000 description 1
- UTDPEJQJFUABQF-UHFFFAOYSA-N Cc(cc1CCc2c3cccc2)ccc1S3(=O)=O Chemical compound Cc(cc1CCc2c3cccc2)ccc1S3(=O)=O UTDPEJQJFUABQF-UHFFFAOYSA-N 0.000 description 1
- YXDDEQLSBHOBAP-UHFFFAOYSA-N Cc1ccc2Oc(cccc3)c3C=Cc2n1 Chemical compound Cc1ccc2Oc(cccc3)c3C=Cc2n1 YXDDEQLSBHOBAP-UHFFFAOYSA-N 0.000 description 1
- WBZVVEKLEITEPV-UHFFFAOYSA-N O=Sc1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1 Chemical compound O=Sc1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1 WBZVVEKLEITEPV-UHFFFAOYSA-N 0.000 description 1
- NCHGSQYAGQLFHQ-UHFFFAOYSA-N OC(c(cc1)cc(CCc2cc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc22)c1C2=O)=O Chemical compound OC(c(cc1)cc(CCc2cc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc22)c1C2=O)=O NCHGSQYAGQLFHQ-UHFFFAOYSA-N 0.000 description 1
- ONLLPPHAKJSQDM-UHFFFAOYSA-N OC(c(cc1)cc(CCc2n3)c1Oc2ccc3OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=O Chemical compound OC(c(cc1)cc(CCc2n3)c1Oc2ccc3OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=O ONLLPPHAKJSQDM-UHFFFAOYSA-N 0.000 description 1
- YTGLCGPNUXIJTI-UHFFFAOYSA-N OC(c(cc1)cc(CS(c2c3)(=O)=O)c1Oc2ccc3OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=O Chemical compound OC(c(cc1)cc(CS(c2c3)(=O)=O)c1Oc2ccc3OCc1c(C2CC2)[o]nc1-c(c(Cl)ccc1)c1Cl)=O YTGLCGPNUXIJTI-UHFFFAOYSA-N 0.000 description 1
- BIBVKXXJSSRWFM-UHFFFAOYSA-N OC(c(cc1)cc2c1C=Cc1nc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc1O2)=O Chemical compound OC(c(cc1)cc2c1C=Cc1nc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc1O2)=O BIBVKXXJSSRWFM-UHFFFAOYSA-N 0.000 description 1
- ZMXMCADJXDXKDS-UHFFFAOYSA-N OC(c1cc(C(c(c(CC2)c3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)(F)F)c2cc1)=O Chemical compound OC(c1cc(C(c(c(CC2)c3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)(F)F)c2cc1)=O ZMXMCADJXDXKDS-UHFFFAOYSA-N 0.000 description 1
- MYUKLYOYWGNVEN-UHFFFAOYSA-N OC(c1cc(C(c(c(CC2)c3)ccc3OCc3c(C4CC4)nn[n]3-c(c(Cl)ccc3)c3Cl)=O)c2cc1)=O Chemical compound OC(c1cc(C(c(c(CC2)c3)ccc3OCc3c(C4CC4)nn[n]3-c(c(Cl)ccc3)c3Cl)=O)c2cc1)=O MYUKLYOYWGNVEN-UHFFFAOYSA-N 0.000 description 1
- ALIAXGDRFBLIMA-UHFFFAOYSA-N OC(c1cc(Cc(c(CC2)c3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1)=O Chemical compound OC(c1cc(Cc(c(CC2)c3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1)=O ALIAXGDRFBLIMA-UHFFFAOYSA-N 0.000 description 1
- UQYZGCFHAXXODZ-UHFFFAOYSA-N OC(c1cc(Oc(c(CC2)c3)cnc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2nc1)=O Chemical compound OC(c1cc(Oc(c(CC2)c3)cnc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2nc1)=O UQYZGCFHAXXODZ-UHFFFAOYSA-N 0.000 description 1
- BTRSTRUBKLGUAR-UHFFFAOYSA-N OC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(-c(c(Cl)ccc4)c4Cl)nn[n]3C3CC3)c2cc1)=O Chemical compound OC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(-c(c(Cl)ccc4)c4Cl)nn[n]3C3CC3)c2cc1)=O BTRSTRUBKLGUAR-UHFFFAOYSA-N 0.000 description 1
- UFXSVFFMEZKTLA-UHFFFAOYSA-N OC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)cn[n]3-c(c(Cl)ccc3)c3Cl)c2cc1)=O Chemical compound OC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)cn[n]3-c(c(Cl)ccc3)c3Cl)c2cc1)=O UFXSVFFMEZKTLA-UHFFFAOYSA-N 0.000 description 1
- NDBPEPMPSZISCG-UHFFFAOYSA-N OC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)nn[n]3-c(c(Cl)ccc3)c3Cl)c2cc1)=O Chemical compound OC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)nn[n]3-c(c(Cl)ccc3)c3Cl)c2cc1)=O NDBPEPMPSZISCG-UHFFFAOYSA-N 0.000 description 1
- PEHXMPMZSCHSLM-UHFFFAOYSA-N OC(c1cc(S(c(c(CC2)c3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)=O)c2cc1)=O Chemical compound OC(c1cc(S(c(c(CC2)c3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)=O)c2cc1)=O PEHXMPMZSCHSLM-UHFFFAOYSA-N 0.000 description 1
- GOBMXBCGSBBCPW-UHFFFAOYSA-N OC(c1ccc(CCCc2nc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc2O2)c2c1)=O Chemical compound OC(c1ccc(CCCc2nc(OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)ccc2O2)c2c1)=O GOBMXBCGSBBCPW-UHFFFAOYSA-N 0.000 description 1
- BUTUNTNHGZBRRP-UHFFFAOYSA-N OS(CCNC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1)=O)(=O)=O Chemical compound OS(CCNC(c1cc(Oc(c(CC2)n3)ccc3OCc3c(C4CC4)[o]nc3-c(c(Cl)ccc3)c3Cl)c2cc1)=O)(=O)=O BUTUNTNHGZBRRP-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510083621.5 | 2015-02-13 | ||
| CN201510083621 | 2015-02-13 | ||
| PCT/CN2016/073617 WO2016127924A1 (en) | 2015-02-13 | 2016-02-05 | Tricyclic compounds and uses thereof in medicine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018505203A JP2018505203A (ja) | 2018-02-22 |
| JP2018505203A5 true JP2018505203A5 (enExample) | 2018-11-01 |
| JP6661070B2 JP6661070B2 (ja) | 2020-03-11 |
Family
ID=56614145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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Families Citing this family (53)
| 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 |
| US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| NZ735126A (en) | 2015-03-31 | 2022-10-28 | Enanta Pharm Inc | Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof |
| WO2017189663A1 (en) | 2016-04-26 | 2017-11-02 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
| WO2017189652A1 (en) | 2016-04-26 | 2017-11-02 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
| US10080742B2 (en) | 2016-04-26 | 2018-09-25 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as FXR agonists and methods of use thereof |
| US10149835B2 (en) | 2016-05-18 | 2018-12-11 | Elmore Patent Law Group, P.C. | Isoxazole derivatives as FXR agonists and methods of use thereof |
| WO2017201152A1 (en) | 2016-05-18 | 2017-11-23 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
| WO2017201150A1 (en) | 2016-05-18 | 2017-11-23 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as fxr agonists and methods of use thereof |
| SI3730487T1 (sl) | 2016-06-13 | 2022-08-31 | Gilead Sciences, Inc. | Azetidinski derivati kot modulatorji FXR (NR1H4) |
| CA3252823A1 (en) | 2016-06-13 | 2025-02-25 | Gilead Sciences Inc | Fxr (nr1h4) modulating compounds |
| TW201808283A (zh) * | 2016-08-05 | 2018-03-16 | 廣東東陽光藥業有限公司 | 含氮三環化合物及其在藥物中的應用 |
| WO2018039384A1 (en) | 2016-08-23 | 2018-03-01 | Ardelyx, Inc. | Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as fxr activators |
| EP3954684A1 (en) * | 2016-08-23 | 2022-02-16 | Ardelyx, Inc. | Process for the preparation of hormone receptor modulators for treating metabolic conditions and disorders |
| CA3039124A1 (en) | 2016-10-04 | 2018-04-12 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as fxr agonists and methods of use thereof |
| CN107973790A (zh) * | 2016-10-22 | 2018-05-01 | 合帕吉恩治疗公司 | 杂环fxr调节剂 |
| US10597391B2 (en) | 2016-10-26 | 2020-03-24 | Enanta Pharmaceuticals, Inc. | Urea-containing isoxazole derivatives as FXR agonists and methods of use thereof |
| WO2018082596A1 (en) | 2016-11-03 | 2018-05-11 | Sunshine Lake Pharma Co., Ltd. | Solid forms of an adamantyl compound, compositions and uses thereof |
| CN106631991B (zh) * | 2016-12-16 | 2021-04-16 | 常州南京大学高新技术研究院 | 一种n-丁基-2,2,6,6-四甲基-4-哌啶胺的简便合成方法 |
| CN108329330B (zh) * | 2017-01-20 | 2021-05-04 | 复旦大学 | 2-苄氧苯基噁唑并吡啶类化合物及其药物用途 |
| JP6906626B2 (ja) | 2017-03-28 | 2021-07-21 | ギリアード サイエンシーズ， インコーポレイテッド | 肝疾患を処置するための治療的組み合わせ |
| IL271035B (en) * | 2017-06-05 | 2022-09-01 | Nat Univ Singapore | Compounds useful in inhibiting human trefoil factor 3 |
| WO2019034693A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
| JP2020531453A (ja) | 2017-08-15 | 2020-11-05 | インフレイゾーム リミテッド | Ｎｌｒｐ３阻害剤としてのスルホニルウレアおよびスルホニルチオウレア |
| WO2019034692A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
| EP3681881B1 (en) | 2017-09-14 | 2022-11-02 | Ardelyx, Inc. | Hormone receptor modulators for treating metabolic mutagenic and fibrotic conditions and disorders |
| US12221434B2 (en) | 2017-11-09 | 2025-02-11 | Inflazome Limited | Sulfonamide carboxamide compounds |
| JP2021502364A (ja) | 2017-11-09 | 2021-01-28 | インフレイゾーム リミテッド | 新規なスルホンアミドカルボキサミド化合物 |
| WO2019118571A1 (en) | 2017-12-12 | 2019-06-20 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as fxr agonists and methods of use thereof |
| 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 |
| US10829486B2 (en) | 2018-02-14 | 2020-11-10 | Enanta Pharmacueticals, Inc. | Isoxazole derivatives as FXR agonists and methods of use thereof |
| WO2019166619A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| US11225473B2 (en) | 2019-01-15 | 2022-01-18 | Gilead Sciences, Inc. | FXR (NR1H4) modulating compounds |
| EP3927683A1 (en) | 2019-02-19 | 2021-12-29 | Gilead Sciences, Inc. | Solid forms of fxr agonists |
| US11555032B2 (en) | 2019-05-13 | 2023-01-17 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as FXR agonists and methods of use thereof |
| CN110028443B (zh) * | 2019-05-29 | 2022-03-04 | 济南周行医药科技有限公司 | 一种调节fxr活性的三环化合物类药物中间体的制备方法 |
| EP4003350A1 (en) | 2019-07-23 | 2022-06-01 | Novartis AG | Treatment comprising fxr agonists |
| WO2021014350A1 (en) | 2019-07-23 | 2021-01-28 | Novartis Ag | Combination treatment of liver diseases using fxr agonists |
| CN112300120B (zh) * | 2019-07-31 | 2023-04-14 | 北京四环制药有限公司 | 一种用于制备巴罗萨韦或其衍生物的化合物及其制备方法和其应用 |
| EP4025248A1 (en) | 2019-09-03 | 2022-07-13 | Novartis AG | Treatment of liver disease or disorder comprising actrii receptor antagonists |
| EP4031137A1 (en) | 2019-09-19 | 2022-07-27 | Novartis AG | Treatment comprising fxr agonists |
| JP2022550312A (ja) | 2019-09-30 | 2022-12-01 | ノバルティス アーゲー | Ｆｘｒアゴニストの使用を含む処置 |
| WO2021102204A1 (en) * | 2019-11-20 | 2021-05-27 | Vivace Therapeutics, Inc. | Heteroaryl compounds |
| AU2020390308A1 (en) * | 2019-11-29 | 2022-06-09 | Sunshine Lake Pharma Co., Ltd. | Amorphous form of nitrogen-containing tricyclic compound and use thereof |
| AU2020390992A1 (en) * | 2019-11-29 | 2022-06-09 | Sunshine Lake Pharma Co., Ltd. | Crystalline form of nitrogen-containing tricyclic compound and use thereof |
| CN112876490A (zh) * | 2019-11-29 | 2021-06-01 | 广东东阳光药业有限公司 | 含氮三环化合物的晶型及其用途 |
| CA3161323A1 (en) | 2019-12-10 | 2021-06-17 | Shanghai Zhimeng Biopharma, Inc. | Compound having neuroprotective effect, preparation method therefor and use thereof |
| JP2023507364A (ja) | 2019-12-20 | 2023-02-22 | ノバルティス アーゲー | インテグリン阻害剤を使用する肝疾患の治療の組み合わせ |
| WO2021254470A1 (zh) * | 2020-06-19 | 2021-12-23 | 江苏恒瑞医药股份有限公司 | 6-氧代-3,6-二氢吡啶类衍生物、其制备方法及其在医药上的应用 |
| WO2022101853A1 (en) | 2020-11-16 | 2022-05-19 | Novartis Ag | Method of determining liver fibrosis |
| CN114235976B (zh) * | 2021-11-09 | 2023-11-03 | 暨南大学 | 一种含氮杂环有机化合物中间产物的合成和分析方法 |
| CN118271327A (zh) * | 2022-12-30 | 2024-07-02 | 广东东阳光药业股份有限公司 | 三环化合物的晶型及其用途 |
| CN116283895A (zh) * | 2023-01-09 | 2023-06-23 | 怀化宝华生物科技有限公司 | 一种2-[2-(噻吩基)乙基]苯甲酸的制备方法 |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR002459A1 (es) * | 1995-01-17 | 1998-03-25 | American Cyanamid Co | Antagonistas de vasopresina de benzacepina triciclicos, una composicion farmaceutica que los contiene, un metodo para tratar enfermedades y unprocedimiento para su preparacion. |
| EP1140079B1 (en) | 1998-12-23 | 2009-06-03 | Glaxo Group Limited | Assays for ligands for nuclear receptors |
| ATE303376T1 (de) | 1999-06-03 | 2005-09-15 | Nippon Suisan Kaisha Ltd | Tricyclische kondensierte heterocyclische verbindungen, verfahren zu ihrer herstellung und ihre verwendung |
| DE60131967D1 (de) | 2001-08-13 | 2008-01-31 | Phenex Pharmaceuticals Ag | Nr1h4-kern-rezeptor-bindende verbindungen |
| CN1681388A (zh) * | 2002-09-18 | 2005-10-12 | Fmc有限公司 | 三环衍生物杀虫剂 |
| US7319109B2 (en) | 2002-11-22 | 2008-01-15 | Smith Kline Beecham Corporation | Farnesoid X receptor agonists |
| BRPI0412262A (pt) * | 2003-07-23 | 2006-09-19 | X Ceptor Therapeutics Inc | derivados de azepina como agentes farmacêuticos |
| US7705028B2 (en) | 2005-12-19 | 2010-04-27 | Glaxosmithkline Llc | Farnesoid X receptor agonists |
| CN101374834B (zh) | 2006-02-03 | 2011-12-14 | 伊莱利利公司 | 用于调节fxr的化合物和方法 |
| US8703804B2 (en) * | 2006-03-26 | 2014-04-22 | Uti Limited Partnership | Ryanodine receptor inhibitors and methods relating thereto |
| US7846960B2 (en) | 2006-05-24 | 2010-12-07 | Eli Lilly And Company | FXR agonists |
| PE20080259A1 (es) | 2006-05-24 | 2008-04-10 | Lilly Co Eli | Compuestos y metodos para modular fxr |
| EP1894924A1 (en) | 2006-08-29 | 2008-03-05 | Phenex Pharmaceuticals AG | Heterocyclic FXR binding compounds |
| EP1894928A1 (en) | 2006-08-29 | 2008-03-05 | PheneX Pharmaceuticals AG | Heterocyclic fxr binding compounds |
| CL2007003035A1 (es) | 2006-10-24 | 2008-05-16 | Smithkline Beechman Corp | Compuestos derivados de isoxazol sustituidos, agonistas de receptores farnesoid x; procedimiento de preparacion; composicion farmaceutica que lo comprende; y uso del compuesto en el tratamiento de la obesidad, diabetes mellitus, fibrosis en organos, |
| EP2121621B1 (en) * | 2006-12-08 | 2014-05-07 | Exelixis Patent Company LLC | Lxr and fxr modulators |
| CA2689980A1 (en) | 2007-06-13 | 2008-12-24 | Glaxosmithkline Llc | Farnesoid x receptor agonists |
| EP2173174A4 (en) | 2007-07-02 | 2010-08-04 | Glaxosmithkline Llc | FARNESOID X RECEPTOR AGONISTS |
| TW200906823A (en) | 2007-07-16 | 2009-02-16 | Lilly Co Eli | Compounds and methods for modulating FXR |
| JP2011518221A (ja) | 2008-04-21 | 2011-06-23 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｊａｎｕｓキナーゼの阻害剤 |
| EP2128158A1 (en) | 2008-05-26 | 2009-12-02 | Phenex Pharmaceuticals AG | Heterocyclic cyclopropyl-substituted FXR binding compounds |
| EP2334681A1 (en) | 2008-09-26 | 2011-06-22 | Wyeth LLC | 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate nuclear receptor inhibitors |
| UA107917C2 (ru) | 2008-10-21 | 2015-03-10 | Сімабей Терапьютікс, Інк. | Арильный агонист рецептора gpr120 и его применение |
| EP2289883A1 (en) | 2009-08-19 | 2011-03-02 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| EA028869B1 (ru) | 2010-02-16 | 2018-01-31 | Арагон Фармасьютикалс, Инк. | Модуляторы рецептора андрогенов и их применение |
| 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 |
| WO2012087521A1 (en) | 2010-12-20 | 2012-06-28 | Irm Llc | Compositions and methods for modulating farnesoid x receptors |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| LT3043865T (lt) | 2013-09-11 | 2021-04-26 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Hepatito b viruso infekcijos gydymo būdai ir farmacinė kompozicija |
| CN104513213A (zh) | 2013-09-28 | 2015-04-15 | 山东亨利医药科技有限责任公司 | Fxr激动剂 |
| MX364834B (es) | 2013-11-05 | 2019-05-08 | Novartis Ag | Composiciones y metodos para modular los receptores x farnesoides. |
| WO2015138986A1 (en) | 2014-03-13 | 2015-09-17 | Salk Institute For Biological Studies | Fxr agonists and methods for making and using |
| 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 |
| 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 |
| MX369623B (es) | 2014-12-22 | 2019-11-14 | Akarna Therapeutics Ltd | Compuestos biciclicos fusionados para el tratamiento de enfermedades. |
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