BRPI0718510A2 - Derivados de 3-amino piridina para o tratamento de desordens metabólicas - Google Patents
Derivados de 3-amino piridina para o tratamento de desordens metabólicas Download PDFInfo
- Publication number
- BRPI0718510A2 BRPI0718510A2 BRPI0718510-3A BRPI0718510A BRPI0718510A2 BR PI0718510 A2 BRPI0718510 A2 BR PI0718510A2 BR PI0718510 A BRPI0718510 A BR PI0718510A BR PI0718510 A2 BRPI0718510 A2 BR PI0718510A2
- Authority
- BR
- Brazil
- Prior art keywords
- chloro
- yloxy
- pyridin
- formula
- quinolin
- Prior art date
Links
- 208000030159 metabolic disease Diseases 0.000 title claims description 25
- 238000011282 treatment Methods 0.000 title claims description 17
- 150000003929 3-aminopyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 215
- -1 3,5-dimethylphenyl Chemical group 0.000 claims description 127
- 238000000034 method Methods 0.000 claims description 82
- 238000002360 preparation method Methods 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 62
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 56
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 206010022489 Insulin Resistance Diseases 0.000 claims description 40
- 239000012453 solvate Substances 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 29
- 239000000460 chlorine Substances 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- 201000001421 hyperglycemia Diseases 0.000 claims description 27
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 16
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 206010020772 Hypertension Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 13
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 8
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 8
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 239000011630 iodine Substances 0.000 claims description 8
- ZQDAOFZWMRGACM-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-2,4-difluorobenzenesulfonamide Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 ZQDAOFZWMRGACM-UHFFFAOYSA-N 0.000 claims description 8
- BCMWMAIMINSPJP-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-4-methoxybenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 BCMWMAIMINSPJP-UHFFFAOYSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 8
- VZDJWWHLGCWIIA-UHFFFAOYSA-N 2,4-dichloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 VZDJWWHLGCWIIA-UHFFFAOYSA-N 0.000 claims description 7
- VEIZLLKUMTZAMG-UHFFFAOYSA-N 2,4-dichloro-n-(5-chloro-6-quinolin-6-yloxypyridin-3-yl)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC=C(N=CC=C2)C2=C1 VEIZLLKUMTZAMG-UHFFFAOYSA-N 0.000 claims description 7
- OTZUJWVQVDBYIR-UHFFFAOYSA-N 2-chloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-fluorobenzenesulfonamide Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 OTZUJWVQVDBYIR-UHFFFAOYSA-N 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 7
- 201000008980 hyperinsulinism Diseases 0.000 claims description 7
- XJFSPAKUIBPXBM-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 XJFSPAKUIBPXBM-UHFFFAOYSA-N 0.000 claims description 7
- NTMPTZVLGPNHAL-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-3,4-dimethoxybenzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 NTMPTZVLGPNHAL-UHFFFAOYSA-N 0.000 claims description 7
- LSZBUURANWKKIQ-UHFFFAOYSA-N n-(5-chloro-6-quinolin-6-yloxypyridin-3-yl)-2,4-difluorobenzenesulfonamide Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC=C(N=CC=C2)C2=C1 LSZBUURANWKKIQ-UHFFFAOYSA-N 0.000 claims description 7
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 230000003143 atherosclerotic effect Effects 0.000 claims description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 229940086542 triethylamine Drugs 0.000 claims description 6
- ZHAUHZOLQWLUJT-UHFFFAOYSA-N 3,5-dichloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3N=CC4=CC=CC=C4C=3)=NC=2)=C1 ZHAUHZOLQWLUJT-UHFFFAOYSA-N 0.000 claims description 5
- ZXWFQDWSPOMACE-UHFFFAOYSA-N 3-[(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)sulfamoyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3N=CC4=CC=CC=C4C=3)=NC=2)=C1 ZXWFQDWSPOMACE-UHFFFAOYSA-N 0.000 claims description 5
- VKKUDNYFCLTYGI-UHFFFAOYSA-N 4-[(5-chloro-6-quinolin-3-yloxypyridin-3-yl)amino]-4-oxobutanoic acid Chemical compound ClC1=CC(NC(=O)CCC(=O)O)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 VKKUDNYFCLTYGI-UHFFFAOYSA-N 0.000 claims description 5
- SOFSFQBXIBUYAG-UHFFFAOYSA-N 4-chloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 SOFSFQBXIBUYAG-UHFFFAOYSA-N 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- ILOLNGWDSKSMIW-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-2,4,6-trimethylbenzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 ILOLNGWDSKSMIW-UHFFFAOYSA-N 0.000 claims description 5
- CCKWNRFUKKIUKZ-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-2,4-difluorobenzenesulfonamide Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 CCKWNRFUKKIUKZ-UHFFFAOYSA-N 0.000 claims description 5
- ZLMHPUOCKWQOLR-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-2,4-dimethoxybenzenesulfonamide Chemical compound COC1=CC(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 ZLMHPUOCKWQOLR-UHFFFAOYSA-N 0.000 claims description 5
- RFBXZEABAFUCEC-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-3-methylbenzenesulfonamide Chemical compound CC1=CC=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3N=CC4=CC=CC=C4C=3)=NC=2)=C1 RFBXZEABAFUCEC-UHFFFAOYSA-N 0.000 claims description 5
- YQCUAEZAIKDFGV-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-(trifluoromethyl)benzenesulfonamide Chemical compound C1=CC(C(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 YQCUAEZAIKDFGV-UHFFFAOYSA-N 0.000 claims description 5
- BQLZNDWIVXNZPE-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-fluorobenzenesulfonamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 BQLZNDWIVXNZPE-UHFFFAOYSA-N 0.000 claims description 5
- XAXFAGJYAZYRDM-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-3,4-difluorobenzenesulfonamide Chemical compound C1=C(F)C(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 XAXFAGJYAZYRDM-UHFFFAOYSA-N 0.000 claims description 5
- UOMJPYKCSPHWLM-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-3,5-dimethylbenzenesulfonamide Chemical compound CC1=CC(C)=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3C=C4C=CC=CC4=NC=3)=NC=2)=C1 UOMJPYKCSPHWLM-UHFFFAOYSA-N 0.000 claims description 5
- ZWKVWTXANSHLFR-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-4-fluorobenzenesulfonamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 ZWKVWTXANSHLFR-UHFFFAOYSA-N 0.000 claims description 5
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 5
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- AYIWOLSTBMMCLV-UHFFFAOYSA-N 2,4-dichloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 AYIWOLSTBMMCLV-UHFFFAOYSA-N 0.000 claims description 4
- HKUPFCKQZZWEBL-UHFFFAOYSA-N 3,5-dichloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3C=C4C=CC=CC4=NC=3)=NC=2)=C1 HKUPFCKQZZWEBL-UHFFFAOYSA-N 0.000 claims description 4
- SAGNTHHJMFQCPG-UHFFFAOYSA-N 3-chloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-methylbenzenesulfonamide Chemical compound C1=C(Cl)C(C)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 SAGNTHHJMFQCPG-UHFFFAOYSA-N 0.000 claims description 4
- GASULYATUXNMLB-UHFFFAOYSA-N 4-chloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-2-fluorobenzenesulfonamide Chemical compound FC1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 GASULYATUXNMLB-UHFFFAOYSA-N 0.000 claims description 4
- RJWQBOJEEVCLFW-UHFFFAOYSA-N 4-chloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-2-fluorobenzenesulfonamide Chemical compound FC1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 RJWQBOJEEVCLFW-UHFFFAOYSA-N 0.000 claims description 4
- FDEQPAMALQUOJQ-UHFFFAOYSA-N 4-chloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 FDEQPAMALQUOJQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
- 208000029078 coronary artery disease Diseases 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- ACNJIGDENNMIRR-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-2,5-dimethoxybenzenesulfonamide Chemical compound COC1=CC=C(OC)C(S(=O)(=O)NC=2C=C(Cl)C(OC=3N=CC4=CC=CC=C4C=3)=NC=2)=C1 ACNJIGDENNMIRR-UHFFFAOYSA-N 0.000 claims description 4
- SRAUQIHFKZWWLM-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-3,4-dimethoxybenzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 SRAUQIHFKZWWLM-UHFFFAOYSA-N 0.000 claims description 4
- RQPMOZXMHUMIQH-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-(trifluoromethoxy)benzenesulfonamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 RQPMOZXMHUMIQH-UHFFFAOYSA-N 0.000 claims description 4
- LUEZRZJLNQHEJE-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-cyanobenzenesulfonamide Chemical compound C=1N=C(OC=2N=CC3=CC=CC=C3C=2)C(Cl)=CC=1NS(=O)(=O)C1=CC=C(C#N)C=C1 LUEZRZJLNQHEJE-UHFFFAOYSA-N 0.000 claims description 4
- HSGNEZLCABGBIV-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-methoxybenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 HSGNEZLCABGBIV-UHFFFAOYSA-N 0.000 claims description 4
- HOAFUMGCISXINX-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-2,4,6-trimethylbenzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 HOAFUMGCISXINX-UHFFFAOYSA-N 0.000 claims description 4
- TUOFVNQTMUJPTI-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-2,4-dimethoxybenzenesulfonamide Chemical compound COC1=CC(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 TUOFVNQTMUJPTI-UHFFFAOYSA-N 0.000 claims description 4
- ZOHQVCMGEKBEQZ-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-4-(trifluoromethoxy)benzenesulfonamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 ZOHQVCMGEKBEQZ-UHFFFAOYSA-N 0.000 claims description 4
- BFQZJTJNERTMAV-UHFFFAOYSA-N n-[4-[(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)sulfamoyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 BFQZJTJNERTMAV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- MWPGLYUVXSTKSC-UHFFFAOYSA-N 2,4-dichloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-n-(2,4-dichlorophenyl)sulfonylbenzenesulfonamide Chemical compound ClC1=CC(Cl)=CC=C1S(=O)(=O)N(S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)C(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 MWPGLYUVXSTKSC-UHFFFAOYSA-N 0.000 claims description 3
- GGLOWKLJQFGKOL-UHFFFAOYSA-N 2-chloro-n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-(trifluoromethyl)benzenesulfonamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 GGLOWKLJQFGKOL-UHFFFAOYSA-N 0.000 claims description 3
- ZPGFCNQSTHXLPQ-UHFFFAOYSA-N 2-chloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-4-(trifluoromethyl)benzenesulfonamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 ZPGFCNQSTHXLPQ-UHFFFAOYSA-N 0.000 claims description 3
- RRULZHKUVUYAEG-UHFFFAOYSA-N 3,4-dichloro-n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound C1=C(Cl)C(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 RRULZHKUVUYAEG-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- UONSDGCPHQGLCW-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-2-methylbenzenesulfonamide Chemical compound CC1=CC=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC2=CC=CC=C2C=N1 UONSDGCPHQGLCW-UHFFFAOYSA-N 0.000 claims description 3
- SIAKSPQCVSJZKR-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-3,5-dimethylbenzenesulfonamide Chemical compound CC1=CC(C)=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3N=CC4=CC=CC=C4C=3)=NC=2)=C1 SIAKSPQCVSJZKR-UHFFFAOYSA-N 0.000 claims description 3
- AIMRNFGTBBQLBK-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-2,6-difluorobenzenesulfonamide Chemical compound FC1=CC=CC(F)=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 AIMRNFGTBBQLBK-UHFFFAOYSA-N 0.000 claims description 3
- KKVWTUIKVYMZPQ-UHFFFAOYSA-N n-(5-chloro-6-quinolin-6-yloxypyridin-3-yl)-3,4-dimethoxybenzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CC=C(N=CC=C2)C2=C1 KKVWTUIKVYMZPQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 2
- 150000003248 quinolines Chemical class 0.000 claims 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 4
- 150000002828 nitro derivatives Chemical class 0.000 claims 4
- 210000004351 coronary vessel Anatomy 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- WIKSJXSVBYOOFM-UHFFFAOYSA-N CC(C=CC(S(N)(=O)=O)=C1C(C=N2)=CC(Cl)=C2OC2=CC3=CC=CC=C3N=C2)=C1F Chemical compound CC(C=CC(S(N)(=O)=O)=C1C(C=N2)=CC(Cl)=C2OC2=CC3=CC=CC=C3N=C2)=C1F WIKSJXSVBYOOFM-UHFFFAOYSA-N 0.000 claims 1
- AYDKPJJYWRZMHL-UHFFFAOYSA-N N-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-4-cyanobenzenesulfonamide N-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-3,5-dimethylbenzenesulfonamide Chemical compound ClC=1C=C(C=NC1OC=1N=CC2=CC=CC=C2C1)NS(=O)(=O)C1=CC(=CC(=C1)C)C.ClC=1C=C(C=NC1OC=1N=CC2=CC=CC=C2C1)NS(=O)(=O)C1=CC=C(C=C1)C#N AYDKPJJYWRZMHL-UHFFFAOYSA-N 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 230000035879 hyperinsulinaemia Effects 0.000 claims 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 104
- 238000005160 1H NMR spectroscopy Methods 0.000 description 58
- 238000006243 chemical reaction Methods 0.000 description 52
- 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 45
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 22
- 102000004877 Insulin Human genes 0.000 description 22
- 108090001061 Insulin Proteins 0.000 description 22
- 239000008103 glucose Substances 0.000 description 22
- 229940125396 insulin Drugs 0.000 description 22
- 229960004586 rosiglitazone Drugs 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- GATZZAJQDSPGFG-UHFFFAOYSA-N 5-chloro-6-isoquinolin-3-yloxypyridin-3-amine Chemical compound ClC1=CC(N)=CN=C1OC1=CC2=CC=CC=C2C=N1 GATZZAJQDSPGFG-UHFFFAOYSA-N 0.000 description 19
- 238000003556 assay Methods 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- HWYUMMAPPQQIDI-UHFFFAOYSA-N 5-chloro-6-quinolin-3-yloxypyridin-3-amine Chemical compound ClC1=CC(N)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 HWYUMMAPPQQIDI-UHFFFAOYSA-N 0.000 description 16
- 239000000203 mixture Substances 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 125000003545 alkoxy group Chemical group 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 206010012601 diabetes mellitus Diseases 0.000 description 11
- 241001139947 Mida Species 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 229940124530 sulfonamide Drugs 0.000 description 8
- 150000003456 sulfonamides Chemical class 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- XLPDVAVQKGDHNO-UHFFFAOYSA-N 2,3-dichloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Cl)C(Cl)=C1 XLPDVAVQKGDHNO-UHFFFAOYSA-N 0.000 description 5
- UGKCEXXIYINZIN-UHFFFAOYSA-N 5-chloro-6-quinolin-6-yloxypyridin-3-amine Chemical compound ClC1=CC(N)=CN=C1OC1=CC=C(N=CC=C2)C2=C1 UGKCEXXIYINZIN-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 210000001789 adipocyte Anatomy 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- FDTPBIKNYWQLAE-UHFFFAOYSA-N 2,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C(Cl)=C1 FDTPBIKNYWQLAE-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 4
- 229960003957 dexamethasone Drugs 0.000 description 4
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000010606 normalization Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- FJSAJUXIHJIAMD-UHFFFAOYSA-N 2,4-difluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C(F)=C1 FJSAJUXIHJIAMD-UHFFFAOYSA-N 0.000 description 3
- RSJSYCZYQNJQPY-UHFFFAOYSA-N 3,4-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1OC RSJSYCZYQNJQPY-UHFFFAOYSA-N 0.000 description 3
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 101000741790 Homo sapiens Peroxisome proliferator-activated receptor gamma Proteins 0.000 description 3
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 3
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- JWJYWVGWLLHCRA-UHFFFAOYSA-N n-(5-chloro-6-isoquinolin-3-yloxypyridin-3-yl)-3-(trifluoromethyl)benzenesulfonamide Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)NC=2C=C(Cl)C(OC=3N=CC4=CC=CC=C4C=3)=NC=2)=C1 JWJYWVGWLLHCRA-UHFFFAOYSA-N 0.000 description 3
- NYYBXKYKGYDSBX-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)benzenesulfonamide Chemical compound C=1N=C(OC=2C=C3C=CC=CC3=NC=2)C(Cl)=CC=1NS(=O)(=O)C1=CC=CC=C1 NYYBXKYKGYDSBX-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- RJSQINMKOSOUGT-UHFFFAOYSA-N 3,5-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC(Cl)=CC(S(Cl)(=O)=O)=C1 RJSQINMKOSOUGT-UHFFFAOYSA-N 0.000 description 2
- LSAGRAXLOLZVKO-UHFFFAOYSA-N 3,5-dimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=CC(S(Cl)(=O)=O)=C1 LSAGRAXLOLZVKO-UHFFFAOYSA-N 0.000 description 2
- DTTHYHBCSITYOW-UHFFFAOYSA-N 3-(3-chloro-5-nitropyridin-2-yl)oxyquinoline Chemical compound ClC1=CC([N+](=O)[O-])=CN=C1OC1=CN=C(C=CC=C2)C2=C1 DTTHYHBCSITYOW-UHFFFAOYSA-N 0.000 description 2
- GTOXJMNILNYXLE-UHFFFAOYSA-N 3-chloro-5-nitro-1h-pyridin-2-one Chemical compound OC1=NC=C([N+]([O-])=O)C=C1Cl GTOXJMNILNYXLE-UHFFFAOYSA-N 0.000 description 2
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 2
- BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 2
- DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 2
- LQVXSNNAFNGRAH-QHCPKHFHSA-N BMS-754807 Chemical compound C([C@@]1(C)C(=O)NC=2C=NC(F)=CC=2)CCN1C(=NN1C=CC=C11)N=C1NC(=NN1)C=C1C1CC1 LQVXSNNAFNGRAH-QHCPKHFHSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- 102000000536 PPAR gamma Human genes 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical class ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 229940014259 gelatin Drugs 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000006377 glucose transport Effects 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- RWEFGDWMJMRXLB-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 RWEFGDWMJMRXLB-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 238000007410 oral glucose tolerance test Methods 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- JPBGQGOQYGYTTA-UHFFFAOYSA-N 1,3,5-trimethylbenzene;hydrochloride Chemical compound Cl.CC1=CC(C)=CC(C)=C1 JPBGQGOQYGYTTA-UHFFFAOYSA-N 0.000 description 1
- 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- AYGZKRRIULCJKC-UHFFFAOYSA-N 2,4-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C(OC)=C1 AYGZKRRIULCJKC-UHFFFAOYSA-N 0.000 description 1
- SHELADVIRCCTFN-UHFFFAOYSA-N 2,5-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(OC)C(S(Cl)(=O)=O)=C1 SHELADVIRCCTFN-UHFFFAOYSA-N 0.000 description 1
- QXWAUQMMMIMLTO-UHFFFAOYSA-N 2,6-difluorobenzenesulfonyl chloride Chemical compound FC1=CC=CC(F)=C1S(Cl)(=O)=O QXWAUQMMMIMLTO-UHFFFAOYSA-N 0.000 description 1
- JHGNABNBNPGCJG-UHFFFAOYSA-N 2-(3-chloro-5-nitropyridin-2-yl)oxyquinoline Chemical compound ClC=1C(=NC=C(C=1)[N+](=O)[O-])OC1=NC2=CC=CC=C2C=C1 JHGNABNBNPGCJG-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- FCFPJKHVCHKCMP-UHFFFAOYSA-N 2-chloro-4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C(Cl)=C1 FCFPJKHVCHKCMP-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- NYIBPWGZGSXURD-UHFFFAOYSA-N 3,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1Cl NYIBPWGZGSXURD-UHFFFAOYSA-N 0.000 description 1
- FSGLUBQENACWCC-UHFFFAOYSA-N 3,4-difluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1F FSGLUBQENACWCC-UHFFFAOYSA-N 0.000 description 1
- SADBYVBEUSBDSW-UHFFFAOYSA-N 3-(3-chloro-5-nitropyridin-2-yl)oxyisoquinoline Chemical compound ClC1=CC([N+](=O)[O-])=CN=C1OC1=CC2=CC=CC=C2C=N1 SADBYVBEUSBDSW-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- GNYVVCRRZRVBDD-UHFFFAOYSA-N 3-chloro-4-methylbenzenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1Cl GNYVVCRRZRVBDD-UHFFFAOYSA-N 0.000 description 1
- MUTXEQVAHJCPSL-UHFFFAOYSA-N 3-chloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CN=CC(Cl)=C1 MUTXEQVAHJCPSL-UHFFFAOYSA-N 0.000 description 1
- LMRKXSDOAFUINK-UHFFFAOYSA-N 3-chlorosulfonylbenzoic acid Chemical compound OC(=O)C1=CC=CC(S(Cl)(=O)=O)=C1 LMRKXSDOAFUINK-UHFFFAOYSA-N 0.000 description 1
- YDUHIMCRFRIVFI-UHFFFAOYSA-N 3-fluoro-4-methylbenzenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1F YDUHIMCRFRIVFI-UHFFFAOYSA-N 0.000 description 1
- KFPMLWUKHQMEBU-UHFFFAOYSA-N 3-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC(S(Cl)(=O)=O)=C1 KFPMLWUKHQMEBU-UHFFFAOYSA-N 0.000 description 1
- UHCDBMIOLNKDHG-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenesulfonyl chloride Chemical compound FC(F)(F)OC1=CC=C(S(Cl)(=O)=O)C=C1 UHCDBMIOLNKDHG-UHFFFAOYSA-N 0.000 description 1
- GRDXCFKBQWDAJH-UHFFFAOYSA-N 4-acetamidobenzenesulfonyl chloride Chemical compound CC(=O)NC1=CC=C(S(Cl)(=O)=O)C=C1 GRDXCFKBQWDAJH-UHFFFAOYSA-N 0.000 description 1
- ZFZRENUEJCOCRE-UHFFFAOYSA-N 4-chloro-2-fluorobenzenesulfonyl chloride Chemical compound FC1=CC(Cl)=CC=C1S(Cl)(=O)=O ZFZRENUEJCOCRE-UHFFFAOYSA-N 0.000 description 1
- DBMFYTQPPBBKHI-UHFFFAOYSA-N 4-cyanobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(C#N)C=C1 DBMFYTQPPBBKHI-UHFFFAOYSA-N 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- XKWSQIMYNVLGBO-UHFFFAOYSA-N 5-nitro-1h-pyridin-2-one Chemical compound OC1=CC=C([N+]([O-])=O)C=N1 XKWSQIMYNVLGBO-UHFFFAOYSA-N 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- PJRWPRKIVANMBP-UHFFFAOYSA-N 6-(3-chloro-5-nitropyridin-2-yl)oxyquinoline Chemical compound ClC1=CC([N+](=O)[O-])=CN=C1OC1=CC=C(N=CC=C2)C2=C1 PJRWPRKIVANMBP-UHFFFAOYSA-N 0.000 description 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
- 208000011732 Abnormal glucose homeostasis Diseases 0.000 description 1
- 102000004539 Acyl-CoA Oxidase Human genes 0.000 description 1
- 108020001558 Acyl-CoA oxidase Proteins 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 101000741806 Mus musculus Peroxisome proliferator-activated receptor gamma Proteins 0.000 description 1
- 101100464833 Mus musculus Ppara gene Proteins 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 206010036049 Polycystic ovaries Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010005991 Pork Regular Insulin Proteins 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000010210 aluminium Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- UCOHKZKRNWNULS-UHFFFAOYSA-N aminocyanamide Chemical compound NNC#N UCOHKZKRNWNULS-UHFFFAOYSA-N 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000004421 aryl sulphonamide group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- HJMZMZRCABDKKV-UHFFFAOYSA-N carbonocyanidic acid Chemical compound OC(=O)C#N HJMZMZRCABDKKV-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 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 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000000081 effect on glucose Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003983 inhalation anesthetic agent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- UBPOEWANSHVLDR-UHFFFAOYSA-N n-(5-chloro-6-quinolin-3-yloxypyridin-3-yl)-3-fluoro-4-methylbenzenesulfonamide Chemical compound C1=C(F)C(C)=CC=C1S(=O)(=O)NC(C=C1Cl)=CN=C1OC1=CN=C(C=CC=C2)C2=C1 UBPOEWANSHVLDR-UHFFFAOYSA-N 0.000 description 1
- FKWFAGVNFACUQB-UHFFFAOYSA-N n-(trifluoromethoxy)benzenesulfonamide Chemical compound FC(F)(F)ONS(=O)(=O)C1=CC=CC=C1 FKWFAGVNFACUQB-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- ZGSXCGTUPZOUPE-UHFFFAOYSA-N oxolane;tetrachloromethane Chemical compound C1CCOC1.ClC(Cl)(Cl)Cl ZGSXCGTUPZOUPE-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000000858 peroxisomal effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene 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
- 235000017924 poor diet Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IQQDNMHUOLMLNJ-UHFFFAOYSA-N quinolin-3-ol Chemical compound C1=CC=CC2=CC(O)=CN=C21 IQQDNMHUOLMLNJ-UHFFFAOYSA-N 0.000 description 1
- OVYWMEWYEJLIER-UHFFFAOYSA-N quinolin-6-ol Chemical compound N1=CC=CC2=CC(O)=CC=C21 OVYWMEWYEJLIER-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000276 sedentary effect Effects 0.000 description 1
- 238000003375 selectivity assay Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005888 tetrahydroindolyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 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
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- DTZOCKDNFAGLSB-UHFFFAOYSA-N trifluoromethoxycyanamide Chemical compound FC(ONC#N)(F)F DTZOCKDNFAGLSB-UHFFFAOYSA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Reproductive Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Emergency Medicine (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84619406P | 2006-09-21 | 2006-09-21 | |
| US60/846,194 | 2006-09-21 | ||
| US87567206P | 2006-12-18 | 2006-12-18 | |
| US60/875,672 | 2006-12-18 | ||
| PCT/IB2007/053812 WO2008035306A1 (en) | 2006-09-21 | 2007-09-20 | 3 -amino- pyridine derivatives for the treatment of metabolic disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0718510A2 true BRPI0718510A2 (pt) | 2013-11-19 |
Family
ID=39048032
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0718510-3A BRPI0718510A2 (pt) | 2006-09-21 | 2007-09-20 | Derivados de 3-amino piridina para o tratamento de desordens metabólicas |
| BRPI0717106-4A BRPI0717106A2 (pt) | 2006-09-21 | 2007-09-20 | Compostos para o tratamento de distúrbios metabólicos |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0717106-4A BRPI0717106A2 (pt) | 2006-09-21 | 2007-09-20 | Compostos para o tratamento de distúrbios metabólicos |
Country Status (19)
| Country | Link |
|---|---|
| US (5) | US8030324B2 (enExample) |
| EP (2) | EP2094663B1 (enExample) |
| JP (2) | JP5331953B2 (enExample) |
| KR (2) | KR20090075827A (enExample) |
| AR (2) | AR062941A1 (enExample) |
| AT (1) | ATE496890T1 (enExample) |
| AU (2) | AU2007298539B2 (enExample) |
| BR (2) | BRPI0718510A2 (enExample) |
| CA (2) | CA2663901A1 (enExample) |
| DE (1) | DE602007012299D1 (enExample) |
| DK (1) | DK2094663T3 (enExample) |
| IL (2) | IL197695A0 (enExample) |
| MX (2) | MX2009002905A (enExample) |
| NZ (2) | NZ576197A (enExample) |
| PL (1) | PL2094663T3 (enExample) |
| PT (1) | PT2094663E (enExample) |
| RU (2) | RU2448093C2 (enExample) |
| TW (2) | TW200820970A (enExample) |
| WO (2) | WO2008035305A2 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013117963A1 (en) | 2012-02-09 | 2013-08-15 | Piramal Enterprises Limited | Stable oral tablet dosage form of an antidiabetic compound |
| PE20160664A1 (es) | 2013-06-27 | 2016-07-09 | Pfizer | Compuestos heteroaromaticos y su uso como ligandos d1 de dopamina |
| WO2014207508A1 (en) * | 2013-06-27 | 2014-12-31 | Piramal Enterprises Limited | Pyridyl compound suitable for the treatment of metabolic disorders |
| EA028614B1 (ru) * | 2014-05-22 | 2017-12-29 | Общество С Ограниченной Ответственностью "Русские Фармацевтические Технологии" | Селективные ингибиторы, нарушающие взаимодействие рецептора фактора роста фибробластов и frs2, для профилактики и лечения рака |
| EP2974729A1 (en) | 2014-07-17 | 2016-01-20 | Abivax | Quinoline derivatives for use in the treatment of inflammatory diseases |
| EP3669873A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Quinoline derivatives for use ine the traeatment of inflammation diseases |
| MX2023005371A (es) | 2020-11-09 | 2023-05-22 | Eisai R&D Man Co Ltd | Moduladores de receptor gamma activado por proliferador de peroxisoma (ppar gamma) y metodos de uso. |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5084085A (en) * | 1986-08-20 | 1992-01-28 | Fmc Corporation | Herbicidal aryloxyphenyltriazolinones and related compounds |
| UA58494C2 (uk) * | 1995-06-07 | 2003-08-15 | Зенека Лімітед | Похідні n-гетероарилпіридинсульфонаміду, фармацевтична композиція, спосіб одержання та спосіб протидії впливам ендотеліну |
| US6583157B2 (en) * | 1998-01-29 | 2003-06-24 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| NZ515087A (en) * | 1999-04-28 | 2003-11-28 | Aventis Pharma Gmbh | Tri-aryl acid derivatives as PPAR receptor ligands |
| WO2001000579A1 (en) * | 1999-06-30 | 2001-01-04 | Tularik Inc. | COMPOUNDS FOR THE MODULATION OF PPARη ACTIVITY |
| US7041691B1 (en) * | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| HK1052351B (en) * | 2000-06-28 | 2006-11-03 | Japan Tobacco Inc. | Benzothiazolyl ppar-gamma modulators |
| CA2526204A1 (en) * | 2003-06-12 | 2004-12-23 | Novo Nordisk A/S | Pyridinyl carbamates as hormone-sensitive lipase inhibitors |
| US7223761B2 (en) * | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| US8188277B2 (en) * | 2004-08-06 | 2012-05-29 | Otsuka Pharmaceutical Co., Ltd. | Aromatic compounds for suppressing the generation of collagen |
| RU2383533C2 (ru) * | 2004-10-04 | 2010-03-10 | Ф.Хоффманн-Ля Рош Аг | Алкилированные производные пиридина в качестве ингибиторов 11-бета при диабете |
-
2007
- 2007-09-20 US US12/441,802 patent/US8030324B2/en not_active Expired - Fee Related
- 2007-09-20 CA CA002663901A patent/CA2663901A1/en not_active Abandoned
- 2007-09-20 NZ NZ576197A patent/NZ576197A/en not_active IP Right Cessation
- 2007-09-20 US US12/441,891 patent/US8269010B2/en not_active Expired - Fee Related
- 2007-09-20 KR KR1020097008115A patent/KR20090075827A/ko not_active Ceased
- 2007-09-20 TW TW096135229A patent/TW200820970A/zh unknown
- 2007-09-20 KR KR1020097008116A patent/KR20090074775A/ko not_active Ceased
- 2007-09-20 DK DK07826467.8T patent/DK2094663T3/da active
- 2007-09-20 AU AU2007298539A patent/AU2007298539B2/en not_active Ceased
- 2007-09-20 WO PCT/IB2007/053811 patent/WO2008035305A2/en not_active Ceased
- 2007-09-20 PL PL07826467T patent/PL2094663T3/pl unknown
- 2007-09-20 DE DE602007012299T patent/DE602007012299D1/de active Active
- 2007-09-20 PT PT07826467T patent/PT2094663E/pt unknown
- 2007-09-20 RU RU2009114544/04A patent/RU2448093C2/ru not_active IP Right Cessation
- 2007-09-20 EP EP07826467A patent/EP2094663B1/en not_active Not-in-force
- 2007-09-20 NZ NZ576196A patent/NZ576196A/en not_active IP Right Cessation
- 2007-09-20 AT AT07826467T patent/ATE496890T1/de active
- 2007-09-20 EP EP07826468A patent/EP2094687A1/en not_active Withdrawn
- 2007-09-20 MX MX2009002905A patent/MX2009002905A/es active IP Right Grant
- 2007-09-20 RU RU2009114545/04A patent/RU2460729C2/ru not_active IP Right Cessation
- 2007-09-20 BR BRPI0718510-3A patent/BRPI0718510A2/pt not_active IP Right Cessation
- 2007-09-20 WO PCT/IB2007/053812 patent/WO2008035306A1/en not_active Ceased
- 2007-09-20 TW TW096135227A patent/TW200817364A/zh unknown
- 2007-09-20 JP JP2009528851A patent/JP5331953B2/ja not_active Expired - Fee Related
- 2007-09-20 AU AU2007298540A patent/AU2007298540B2/en not_active Ceased
- 2007-09-20 MX MX2009002906A patent/MX2009002906A/es active IP Right Grant
- 2007-09-20 JP JP2009528850A patent/JP2010504321A/ja not_active Ceased
- 2007-09-20 CA CA002663943A patent/CA2663943A1/en not_active Abandoned
- 2007-09-20 BR BRPI0717106-4A patent/BRPI0717106A2/pt not_active IP Right Cessation
- 2007-09-21 AR ARP070104184A patent/AR062941A1/es not_active Application Discontinuation
- 2007-09-21 AR ARP070104183A patent/AR062940A1/es unknown
-
2009
- 2009-03-19 IL IL197695A patent/IL197695A0/en unknown
- 2009-03-19 IL IL197694A patent/IL197694A0/en unknown
-
2011
- 2011-08-31 US US13/222,662 patent/US8349862B2/en not_active Expired - Fee Related
-
2012
- 2012-08-13 US US13/584,134 patent/US20120309786A1/en not_active Abandoned
- 2012-08-13 US US13/584,043 patent/US20130040988A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110121343B (zh) | 用作gpr120调节剂的双环化合物 | |
| BRPI0712332A2 (pt) | composto e derivados farmaceuticamente aceitáveis dos mesmos, composição farmacêutica, método de antagonização de um receptor dp-2, e, uso de um composto | |
| RU2460729C2 (ru) | Производные 3-амино-пиридина для лечения метаболических нарушений | |
| KR20200126988A (ko) | 뉴로트로핀과 관련된 질병을 치료하기 위한 트리아진 유도체 | |
| JP6859358B2 (ja) | テトラヒドロインダゾール及びその医学的使用 | |
| WO2014086102A1 (zh) | 作为酪氨酸激酶抑制剂的吲哚满酮衍生物 | |
| JP7041141B2 (ja) | 置換された二環式ヘテロアリール系ニコチン性アセチルコリン受容体アロステリック調節剤 | |
| EP3891130B1 (en) | Ire1 small molecule inhibitors | |
| JP2025510348A (ja) | Ｐ２ｘ３阻害剤化合物及びその塩、結晶多形並びに使用 | |
| WO2025021033A1 (zh) | 成纤维细胞生长因子受体抑制剂、药物组合物及其应用 | |
| BR112018012934A2 (en) | cftr regulators and methods of use | |
| TW201736366A (zh) | 吲嗪類衍生物、組合物及使用方法 | |
| ES2360763T3 (es) | Derivados de piridina para el tratamiento de desórdenes metabólicos relacionados con la resistencia a la insulina o hiperglucemia. | |
| TW202604490A (zh) | Ｍａｓ相關ｇ蛋白受體ｘ４調節劑及用途 | |
| WO2025098212A1 (zh) | 一种n,n-二甲基色胺衍生物及其药物组合物、制备方法和用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 7A ANUIDADE. |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2277 DE 26/08/2014. |