CA2507186A1 - Anilinopyrazole derivatives useful for the treatment of diabetes - Google Patents
Anilinopyrazole derivatives useful for the treatment of diabetes Download PDFInfo
- Publication number
- CA2507186A1 CA2507186A1 CA002507186A CA2507186A CA2507186A1 CA 2507186 A1 CA2507186 A1 CA 2507186A1 CA 002507186 A CA002507186 A CA 002507186A CA 2507186 A CA2507186 A CA 2507186A CA 2507186 A1 CA2507186 A1 CA 2507186A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- alkoxy
- pyrazol
- amino
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 53
- 238000011282 treatment Methods 0.000 title claims description 27
- CMAOIURPBUCSJE-UHFFFAOYSA-N n-phenyl-1h-pyrazol-5-amine Chemical class C=1C=CC=CC=1NC=1C=CNN=1 CMAOIURPBUCSJE-UHFFFAOYSA-N 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 87
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 189
- -1 NR8R8 Chemical group 0.000 claims description 152
- 239000000203 mixture Substances 0.000 claims description 97
- 125000001424 substituent group Chemical group 0.000 claims description 81
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 68
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 67
- 125000001475 halogen functional group Chemical group 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
- 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 claims description 48
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
- 239000003814 drug Substances 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 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 claims description 33
- 229940079593 drug Drugs 0.000 claims description 28
- 239000008103 glucose Substances 0.000 claims description 27
- 229940125396 insulin Drugs 0.000 claims description 25
- 102000004877 Insulin Human genes 0.000 claims description 23
- 108090001061 Insulin Proteins 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 17
- 239000008177 pharmaceutical agent Substances 0.000 claims description 17
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 17
- 125000001188 haloalkyl group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 14
- DPXRSDZSUCTWBU-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1C DPXRSDZSUCTWBU-UHFFFAOYSA-N 0.000 claims description 13
- 230000003914 insulin secretion Effects 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 12
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 229940122199 Insulin secretagogue Drugs 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 229940122355 Insulin sensitizer Drugs 0.000 claims description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
- 229940100389 Sulfonylurea Drugs 0.000 claims description 8
- 239000000883 anti-obesity agent Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 8
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 8
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000002440 hepatic effect Effects 0.000 claims description 7
- BNYHRGTXRPWASY-UHFFFAOYSA-N nonylsulfonylurea Chemical compound CCCCCCCCCS(=O)(=O)NC(N)=O BNYHRGTXRPWASY-UHFFFAOYSA-N 0.000 claims description 7
- 229920000642 polymer Polymers 0.000 claims description 7
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 7
- 230000000580 secretagogue effect Effects 0.000 claims description 7
- 206010056997 Impaired fasting glucose Diseases 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- TVYNJEQUZKNBAI-UHFFFAOYSA-N 2-[(2,5-diphenylpyrazol-3-yl)amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 TVYNJEQUZKNBAI-UHFFFAOYSA-N 0.000 claims description 5
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 4
- OIDPPOQHTRYROA-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methoxyphenyl)-4-methylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C)C(C(C)(C)C)=NN1C1=CC=CC=C1OC OIDPPOQHTRYROA-UHFFFAOYSA-N 0.000 claims description 4
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 4
- 206010022489 Insulin Resistance Diseases 0.000 claims description 4
- 208000035180 MODY Diseases 0.000 claims description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 4
- 201000008980 hyperinsulinism Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 201000006950 maturity-onset diabetes of the young Diseases 0.000 claims description 4
- 235000001968 nicotinic acid Nutrition 0.000 claims description 4
- 229960003512 nicotinic acid Drugs 0.000 claims description 4
- 239000011664 nicotinic acid Substances 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 3
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 3
- 229940096699 bile acid sequestrants Drugs 0.000 claims description 3
- 239000012472 biological sample Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 208000004104 gestational diabetes Diseases 0.000 claims description 3
- 239000003862 glucocorticoid Substances 0.000 claims description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 3
- IUUZXUVQYMPZGD-UHFFFAOYSA-N 2-[[4-(2,4-dimethoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COC1=CC(OC)=CC=C1C1=C(NC=2C(=CC(OC)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C IUUZXUVQYMPZGD-UHFFFAOYSA-N 0.000 claims description 2
- NHKSFTWZJYECNC-UHFFFAOYSA-N 2-[[4-(2-fluorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC=CC=2)F)C(C)=NN1C1=CC=CC=C1C NHKSFTWZJYECNC-UHFFFAOYSA-N 0.000 claims description 2
- GYQDDDHUXXWBRB-UHFFFAOYSA-N 2-[[5-ethyl-4-(6-methoxypyridin-3-yl)-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound C=1C=C(OC)N=CC=1C=1C(CC)=NN(C=2C(=CC=CC=2)C)C=1NC1=CC=C(OC)C=C1C(O)=O GYQDDDHUXXWBRB-UHFFFAOYSA-N 0.000 claims description 2
- JEHNTRZLCOFDBK-UHFFFAOYSA-N 2-[[5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzamide Chemical compound C=1C=CC=C(C)C=1N1N=C(C)C=C1NC1=CC=CC=C1C(N)=O JEHNTRZLCOFDBK-UHFFFAOYSA-N 0.000 claims description 2
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 2
- LVSQVORYVDULSC-UHFFFAOYSA-N 5-methoxy-2-[[2-(2-methoxyphenyl)-5-methyl-4-phenylpyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C)=NN1C1=CC=CC=C1OC LVSQVORYVDULSC-UHFFFAOYSA-N 0.000 claims description 2
- OCZOTOZJCRJWAU-UHFFFAOYSA-N 5-methoxy-2-[[2-(2-methylphenyl)-4-pyridin-4-yl-5-(trifluoromethyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CN=CC=2)C(C(F)(F)F)=NN1C1=CC=CC=C1C OCZOTOZJCRJWAU-UHFFFAOYSA-N 0.000 claims description 2
- DTZMRSQXUMFQTF-UHFFFAOYSA-N 5-methoxy-2-[[4-(4-methoxyphenyl)-2-(2-methylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]amino]benzoic acid Chemical compound C1=CC(OC)=CC=C1C(C(=NN1C=2C(=CC=CC=2)C)C(F)(F)F)=C1NC1=CC=C(OC)C=C1C(O)=O DTZMRSQXUMFQTF-UHFFFAOYSA-N 0.000 claims description 2
- VKYSDBRFDIGIDK-UHFFFAOYSA-N 5-methoxy-2-[[4-(6-methoxypyridin-3-yl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=NC(OC)=CC=2)C(C)=NN1C1=CC=CC=C1C VKYSDBRFDIGIDK-UHFFFAOYSA-N 0.000 claims description 2
- XHQHCXZEPXDRLH-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-phenylpyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C)=NN1C1=CC=CC=C1C XHQHCXZEPXDRLH-UHFFFAOYSA-N 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 108010051696 Growth Hormone Proteins 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 229940125753 fibrate Drugs 0.000 claims description 2
- 239000000122 growth hormone Substances 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 208000028591 pheochromocytoma Diseases 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 53
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 37
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 37
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 33
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 33
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 18
- 229940125710 antiobesity agent Drugs 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
- 208000032928 Dyslipidaemia Diseases 0.000 claims 3
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 3
- 201000001421 hyperglycemia Diseases 0.000 claims 3
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 3
- 238000011321 prophylaxis Methods 0.000 claims 3
- 229940030600 antihypertensive agent Drugs 0.000 claims 2
- CWUFCHYCMHXCMB-UHFFFAOYSA-N 2-[(5-tert-butyl-2-methylpyrazol-3-yl)amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C CWUFCHYCMHXCMB-UHFFFAOYSA-N 0.000 claims 1
- PTPTXMIUFHELGS-UHFFFAOYSA-N 2-[(5-tert-butyl-2-phenylpyrazol-3-yl)amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1 PTPTXMIUFHELGS-UHFFFAOYSA-N 0.000 claims 1
- IEOICNMIUQLXOE-UHFFFAOYSA-N 2-[[2-(2,6-dimethylphenyl)-5-(1-methylcyclopropyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=CC(C)=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C2(C)CC2)=N1 IEOICNMIUQLXOE-UHFFFAOYSA-N 0.000 claims 1
- WXQAIZBHCIUKRG-UHFFFAOYSA-N 2-[[5-(3-methoxyphenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound COC1=CC=CC(C2=NN(C(NC=3C(=CC(C)=CC=3)C(O)=O)=C2)C=2C(=CC=CC=2)C)=C1 WXQAIZBHCIUKRG-UHFFFAOYSA-N 0.000 claims 1
- CDCPTBGPKQMRED-UHFFFAOYSA-N 2-[[5-(3-methoxyphenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound COC1=CC=CC(C2=NN(C(NC=3C(=CC=CC=3)C(O)=O)=C2)C=2C(=CC=CC=2)C)=C1 CDCPTBGPKQMRED-UHFFFAOYSA-N 0.000 claims 1
- QFFAKBRCYHZZNT-UHFFFAOYSA-N 2-[[5-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=CC=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C=2C=CC(F)=CC=2)=N1 QFFAKBRCYHZZNT-UHFFFAOYSA-N 0.000 claims 1
- XWFUKNZKYZNJCG-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2,3-dimethylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC(C)=C1C XWFUKNZKYZNJCG-UHFFFAOYSA-N 0.000 claims 1
- WYDDJHVVQWLCPB-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2,6-dimethylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=C(C)C=CC=C1C WYDDJHVVQWLCPB-UHFFFAOYSA-N 0.000 claims 1
- STVZMCWHWRPKLW-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2,6-dimethylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=CC(C)=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C(C)(C)C)=N1 STVZMCWHWRPKLW-UHFFFAOYSA-N 0.000 claims 1
- DRDCSOYROQGYBO-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-ethoxyphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCOC1=CC=CC=C1N1C(NC=2C(=CC(OC)=CC=2)C(O)=O)=CC(C(C)(C)C)=N1 DRDCSOYROQGYBO-UHFFFAOYSA-N 0.000 claims 1
- DRCPLNPPNOXXAJ-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-ethoxyphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CCOC1=CC=CC=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C(C)(C)C)=N1 DRCPLNPPNOXXAJ-UHFFFAOYSA-N 0.000 claims 1
- UNSXSYFBXLWJLR-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methoxy-5-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound COC1=CC=C(C)C=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C(C)(C)C)=N1 UNSXSYFBXLWJLR-UHFFFAOYSA-N 0.000 claims 1
- RPJMQJRLXOLESP-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methoxy-6-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=C(C)C=CC=C1OC RPJMQJRLXOLESP-UHFFFAOYSA-N 0.000 claims 1
- DRZLAROFLUFDGC-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methoxyphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1OC DRZLAROFLUFDGC-UHFFFAOYSA-N 0.000 claims 1
- JVYBEYCMSGSXBT-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methylsulfanylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1SC JVYBEYCMSGSXBT-UHFFFAOYSA-N 0.000 claims 1
- OSOFUBGPFZFAOQ-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(5-fluoro-2-methylphenyl)pyrazol-3-yl]amino]-6-fluorobenzoic acid Chemical compound CC1=CC=C(F)C=C1N1C(NC=2C(=C(F)C=CC=2)C(O)=O)=CC(C(C)(C)C)=N1 OSOFUBGPFZFAOQ-UHFFFAOYSA-N 0.000 claims 1
- WQNLZMSCTZADHA-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(5-fluoro-2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=C(F)C=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C(C)(C)C)=N1 WQNLZMSCTZADHA-UHFFFAOYSA-N 0.000 claims 1
- XPSNAKCMUNSHOI-UHFFFAOYSA-N 2-fluoro-6-[[2-(2-methylphenyl)-5-(4-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound C1=CC(C)=CC=C1C1=NN(C=2C(=CC=CC=2)C)C(NC=2C(=C(F)C=CC=2)C(O)=O)=C1 XPSNAKCMUNSHOI-UHFFFAOYSA-N 0.000 claims 1
- RFYHZTKILJZFKL-UHFFFAOYSA-N 2-fluoro-6-[[5-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=CC=C1N1C(NC=2C(=C(F)C=CC=2)C(O)=O)=CC(C=2C=CC(F)=CC=2)=N1 RFYHZTKILJZFKL-UHFFFAOYSA-N 0.000 claims 1
- KLUDNRDSXNPPLA-UHFFFAOYSA-N 5-methoxy-2-[[5-(3-methoxyphenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound COC1=CC=CC(C2=NN(C(NC=3C(=CC(OC)=CC=3)C(O)=O)=C2)C=2C(=CC=CC=2)C)=C1 KLUDNRDSXNPPLA-UHFFFAOYSA-N 0.000 claims 1
- 102000018997 Growth Hormone Human genes 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 169
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 132
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- 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 114
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 83
- 238000006243 chemical reaction Methods 0.000 description 75
- 239000000243 solution Substances 0.000 description 75
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- 238000004128 high performance liquid chromatography Methods 0.000 description 71
- 238000002360 preparation method Methods 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- 230000002829 reductive effect Effects 0.000 description 59
- 238000005481 NMR spectroscopy Methods 0.000 description 55
- 239000007787 solid Substances 0.000 description 52
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 51
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 49
- 235000019439 ethyl acetate Nutrition 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
- 125000000217 alkyl group Chemical group 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 239000000543 intermediate Substances 0.000 description 36
- 239000005711 Benzoic acid Substances 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 235000010233 benzoic acid Nutrition 0.000 description 33
- 229960004365 benzoic acid Drugs 0.000 description 33
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 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 26
- 238000005859 coupling reaction Methods 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 238000000746 purification Methods 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 125000005843 halogen group Chemical group 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 239000003826 tablet Substances 0.000 description 19
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000002585 base Substances 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 14
- 125000004414 alkyl thio group Chemical group 0.000 description 14
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 14
- 125000004438 haloalkoxy group Chemical group 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 235000014113 dietary fatty acids Nutrition 0.000 description 13
- 239000000194 fatty acid Substances 0.000 description 13
- 229930195729 fatty acid Natural products 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 230000008878 coupling Effects 0.000 description 12
- 238000010168 coupling process Methods 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 11
- 239000002775 capsule Substances 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000010828 elution Methods 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 150000004665 fatty acids Chemical class 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 235000011187 glycerol Nutrition 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 7
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 238000006069 Suzuki reaction reaction Methods 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229960004132 diethyl ether Drugs 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 239000003755 preservative agent Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- KJGFNDCSTWGUDT-UHFFFAOYSA-N (2-methylanilino)azanium;chloride Chemical compound Cl.CC1=CC=CC=C1NN KJGFNDCSTWGUDT-UHFFFAOYSA-N 0.000 description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 6
- MNWSGMTUGXNYHJ-UHFFFAOYSA-N 2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(N)=O MNWSGMTUGXNYHJ-UHFFFAOYSA-N 0.000 description 6
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 6
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000003599 detergent Substances 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 239000008273 gelatin Substances 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 239000000375 suspending agent Substances 0.000 description 6
- 235000020357 syrup Nutrition 0.000 description 6
- 239000006188 syrup Substances 0.000 description 6
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- 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 5
- 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 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 5
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229940099112 cornstarch Drugs 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000004949 mass spectrometry Methods 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 229960002900 methylcellulose Drugs 0.000 description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 235000013772 propylene glycol Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000000600 sorbitol Substances 0.000 description 5
- 235000010356 sorbitol Nutrition 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 239000000080 wetting agent Substances 0.000 description 5
- SDYIZAANGZBOSO-UHFFFAOYSA-N 2,3-dimethoxybenzamide Chemical compound COC1=CC=CC(C(N)=O)=C1OC SDYIZAANGZBOSO-UHFFFAOYSA-N 0.000 description 4
- XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical group OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 description 4
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 4
- NNJQPZQIUUZUEP-UHFFFAOYSA-N 5-cyclopentyl-2-(2-methylphenyl)pyrazol-3-amine Chemical compound CC1=CC=CC=C1N1C(N)=CC(C2CCCC2)=N1 NNJQPZQIUUZUEP-UHFFFAOYSA-N 0.000 description 4
- KZPZKAVOPDSURE-UHFFFAOYSA-N 5-methyl-2-(2-methylphenyl)pyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1=CC=CC=C1C KZPZKAVOPDSURE-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000416162 Astragalus gummifer Species 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 4
- 240000007472 Leucaena leucocephala Species 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 235000019483 Peanut oil Nutrition 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 239000000783 alginic acid Substances 0.000 description 4
- 229960001126 alginic acid Drugs 0.000 description 4
- 150000004781 alginic acids Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229960000541 cetyl alcohol Drugs 0.000 description 4
- GTBRTGPZZALPNS-MXHVRSFHSA-N cyanoketone Chemical compound C1C=C2C(C)(C)C(=O)[C@H](C#N)C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GTBRTGPZZALPNS-MXHVRSFHSA-N 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
- 238000007429 general method Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 210000004153 islets of langerhan Anatomy 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000010445 lecithin Nutrition 0.000 description 4
- 239000000787 lecithin Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000004006 olive oil Substances 0.000 description 4
- 235000008390 olive oil Nutrition 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000000312 peanut oil Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920000573 polyethylene Polymers 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 description 4
- 239000008159 sesame oil Substances 0.000 description 4
- 235000011803 sesame oil Nutrition 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000008117 stearic acid Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 229940124530 sulfonamide Drugs 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000008158 vegetable oil Substances 0.000 description 4
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 3
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- RIGNXPFQJWSYOB-UHFFFAOYSA-N 2-[[2-(4-methoxyphenyl)-5-methylpyrazol-3-yl]amino]benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC=2C(=CC=CC=2)C(N)=O)=CC(C)=N1 RIGNXPFQJWSYOB-UHFFFAOYSA-N 0.000 description 3
- ODHJOROUCITYNF-UHFFFAOYSA-N 2-bromo-5-methoxybenzoic acid Chemical compound COC1=CC=C(Br)C(C(O)=O)=C1 ODHJOROUCITYNF-UHFFFAOYSA-N 0.000 description 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- VTGDDNFMPKGIHL-UHFFFAOYSA-N 5-butyl-2-(2-methylphenyl)pyrazol-3-amine Chemical compound N1=C(CCCC)C=C(N)N1C1=CC=CC=C1C VTGDDNFMPKGIHL-UHFFFAOYSA-N 0.000 description 3
- DRQZAKSSOJFKQF-UHFFFAOYSA-N 5-methoxy-2-[(2-phenylpyrazol-3-yl)amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 DRQZAKSSOJFKQF-UHFFFAOYSA-N 0.000 description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 239000005642 Oleic acid Substances 0.000 description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
- 239000004264 Petrolatum Substances 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 238000006619 Stille reaction Methods 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 3
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000010640 amide synthesis reaction Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000440 bentonite Substances 0.000 description 3
- 229910000278 bentonite Inorganic materials 0.000 description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 3
- 229940050390 benzoate Drugs 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 150000001642 boronic acid derivatives Chemical class 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 3
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000005687 corn oil Nutrition 0.000 description 3
- 239000002285 corn oil Substances 0.000 description 3
- 235000012343 cottonseed oil Nutrition 0.000 description 3
- 239000002385 cottonseed oil Substances 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 238000011262 co‐therapy Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000000132 electrospray ionisation Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 150000002429 hydrazines Chemical class 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 235000019271 petrolatum Nutrition 0.000 description 3
- 229940066842 petrolatum Drugs 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000002821 scintillation proximity assay Methods 0.000 description 3
- 150000003334 secondary amides Chemical class 0.000 description 3
- 239000012363 selectfluor Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 235000011069 sorbitan monooleate Nutrition 0.000 description 3
- 239000001593 sorbitan monooleate Substances 0.000 description 3
- 229940035049 sorbitan monooleate Drugs 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 150000003511 tertiary amides Chemical class 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- MDIZFFXVLURJBF-UHFFFAOYSA-N (4-methoxyphenyl)methyl 5-methoxy-2-[(2-phenylpyrazol-3-yl)amino]benzoate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=CC(OC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 MDIZFFXVLURJBF-UHFFFAOYSA-N 0.000 description 2
- ORPYPQORYFJOFC-UITAMQMPSA-N (z)-3-amino-3-(4-fluorophenyl)prop-2-enenitrile Chemical compound N#C\C=C(/N)C1=CC=C(F)C=C1 ORPYPQORYFJOFC-UITAMQMPSA-N 0.000 description 2
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- DACDUXZWLPUCRG-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-pyrazolo[3,4-c]pyridine;2,3,3a,4-tetrahydro-1h-pyrazolo[4,3-c]pyridine Chemical compound N1=CCC2CNNC2=C1.C1=NCC2CNNC2=C1 DACDUXZWLPUCRG-UHFFFAOYSA-N 0.000 description 2
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 2
- IFYAARDLWVFLNG-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-(4-fluorophenyl)pyrazol-3-yl]amino]-5-ethylbenzoic acid Chemical compound OC(=O)C1=CC(CC)=CC=C1NC1=CC(C=2C=CC(F)=CC=2)=NN1C1=CC(C)=CC=C1C IFYAARDLWVFLNG-UHFFFAOYSA-N 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- FOCJXECLIBAZSA-UHFFFAOYSA-N 3-cyclopentyl-3-oxopropanenitrile Chemical compound N#CCC(=O)C1CCCC1 FOCJXECLIBAZSA-UHFFFAOYSA-N 0.000 description 2
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 description 2
- JOPWJJOGCBPJML-UHFFFAOYSA-N 4-bromo-5-methyl-2-(2-methylphenyl)pyrazol-3-amine Chemical compound NC1=C(Br)C(C)=NN1C1=CC=CC=C1C JOPWJJOGCBPJML-UHFFFAOYSA-N 0.000 description 2
- XXVQSFLPPBFWQA-UHFFFAOYSA-N 4-ethenyl-5-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-amine Chemical compound CC1=CC=CC=C1N1C(N)=C(C=C)C(C=2C=CC(F)=CC=2)=N1 XXVQSFLPPBFWQA-UHFFFAOYSA-N 0.000 description 2
- KDXOONIQRUZGSY-UHFFFAOYSA-N 4-fluoro-2-methylbenzoic acid Chemical compound CC1=CC(F)=CC=C1C(O)=O KDXOONIQRUZGSY-UHFFFAOYSA-N 0.000 description 2
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 2
- HCJHEXJNIKHRJC-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-amine Chemical compound CC1=CC=CC=C1N1C(N)=CC(C=2C=CC(F)=CC=2)=N1 HCJHEXJNIKHRJC-UHFFFAOYSA-N 0.000 description 2
- OLKMTQUEGAIBHP-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-(2-methylsulfanylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC=CC=2)SC)C(C)=NN1C1=CC=CC=C1C OLKMTQUEGAIBHP-UHFFFAOYSA-N 0.000 description 2
- SNMGAKOWUHTEKD-UHFFFAOYSA-N 5-tert-butyl-2-(2-methylphenyl)pyrazol-3-amine Chemical compound CC1=CC=CC=C1N1C(N)=CC(C(C)(C)C)=N1 SNMGAKOWUHTEKD-UHFFFAOYSA-N 0.000 description 2
- XSCDSAMVQLKDNI-UHFFFAOYSA-N 5-tert-butyl-2-methylpyrazol-3-amine Chemical compound CN1N=C(C(C)(C)C)C=C1N XSCDSAMVQLKDNI-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 229940126033 PPAR agonist Drugs 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229920001800 Shellac Polymers 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 235000009470 Theobroma cacao Nutrition 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000003579 anti-obesity Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- 150000008366 benzophenones Chemical group 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000036983 biotransformation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 239000007963 capsule composition Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 229960001761 chlorpropamide Drugs 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000006900 dealkylation reaction Methods 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 229940052303 ethers for general anesthesia Drugs 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- PAVZHTXVORCEHP-UHFFFAOYSA-N ethylboronic acid Chemical compound CCB(O)O PAVZHTXVORCEHP-UHFFFAOYSA-N 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 229960004580 glibenclamide Drugs 0.000 description 2
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 2
- 229960004346 glimepiride Drugs 0.000 description 2
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 2
- 229960001381 glipizide Drugs 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- YDGSUPBDGKOGQT-UHFFFAOYSA-N lithium;dimethylazanide Chemical compound [Li+].C[N-]C YDGSUPBDGKOGQT-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 2
- AIWIFVOBRBJANE-UHFFFAOYSA-N methyl 2-bromo-5-hydroxybenzoate Chemical compound COC(=O)C1=CC(O)=CC=C1Br AIWIFVOBRBJANE-UHFFFAOYSA-N 0.000 description 2
- VRTQLDFCPNVQNT-UHFFFAOYSA-N methyl 2-bromo-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1Br VRTQLDFCPNVQNT-UHFFFAOYSA-N 0.000 description 2
- ZQFCTCYDRQFPBU-UHFFFAOYSA-N methyl 4-fluoro-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1C ZQFCTCYDRQFPBU-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 description 2
- 239000008180 pharmaceutical surfactant Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229960005235 piperonyl butoxide Drugs 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229920003124 powdered cellulose Polymers 0.000 description 2
- 235000019814 powdered cellulose Nutrition 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 2
- 239000004208 shellac Substances 0.000 description 2
- 229940113147 shellac Drugs 0.000 description 2
- 235000013874 shellac Nutrition 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 239000000344 soap Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 229960004418 trolamine Drugs 0.000 description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 229940045860 white wax Drugs 0.000 description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- XFQNWPYGEGCIMF-HCUGAJCMSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].[Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 XFQNWPYGEGCIMF-HCUGAJCMSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- CNVRALIOWLIHEP-UHFFFAOYSA-N (5,5-dimethyloxolan-3-yl)methanol Chemical compound CC1(C)CC(CO)CO1 CNVRALIOWLIHEP-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- DELJOESCKJGFML-DUXPYHPUSA-N (e)-3-aminobut-2-enenitrile Chemical compound C\C(N)=C/C#N DELJOESCKJGFML-DUXPYHPUSA-N 0.000 description 1
- PQXJWVWZZGZNBE-VBKFSLOCSA-N (z)-2-anilino-4-phenylbut-2-enenitrile Chemical compound C=1C=CC=CC=1C/C=C(/C#N)NC1=CC=CC=C1 PQXJWVWZZGZNBE-VBKFSLOCSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 description 1
- ZQGDSZPGKPJABN-UHFFFAOYSA-N 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane Chemical compound C1C[N+]2(CCl)CC[N+]1(F)CC2 ZQGDSZPGKPJABN-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 1
- RJPNVPITBYXBNB-UHFFFAOYSA-N 1-bromo-4-fluoro-2-methylbenzene Chemical compound CC1=CC(F)=CC=C1Br RJPNVPITBYXBNB-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 1
- WRLCLLXPCZJIIH-UHFFFAOYSA-N 2,2,2-trifluoro-n-[2-(4-methoxyphenyl)ethyl]acetamide Chemical compound COC1=CC=C(CCNC(=O)C(F)(F)F)C=C1 WRLCLLXPCZJIIH-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- NYOWYNSNCXRVNQ-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-indazole Chemical group C1=CCC2CNNC2=C1 NYOWYNSNCXRVNQ-UHFFFAOYSA-N 0.000 description 1
- SRPARXVFWQVJKS-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-pyrazolo[4,3-c]pyridine Chemical compound C1=NCC2CNNC2=C1 SRPARXVFWQVJKS-UHFFFAOYSA-N 0.000 description 1
- PTMNYMOCFTXMBN-UHFFFAOYSA-N 2,3-dibromobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC(Br)=C1Br PTMNYMOCFTXMBN-UHFFFAOYSA-N 0.000 description 1
- YNVNFMCYBIBHLH-UHFFFAOYSA-N 2,3-dibromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1Br YNVNFMCYBIBHLH-UHFFFAOYSA-N 0.000 description 1
- FODBVCSYJKNBLO-UHFFFAOYSA-N 2,3-dimethoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1OC FODBVCSYJKNBLO-UHFFFAOYSA-N 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- NFGJFMYUVZKOMN-UHFFFAOYSA-N 2-(2-methylphenyl)-4,5,6,7-tetrahydroindazol-3-amine Chemical compound CC1=CC=CC=C1N1C(N)=C2CCCCC2=N1 NFGJFMYUVZKOMN-UHFFFAOYSA-N 0.000 description 1
- WFWJAFYZSWNMPI-UHFFFAOYSA-N 2-(2-methylphenyl)-4,5,6,7-tetrahydroindazol-3-amine;hydrochloride Chemical compound Cl.CC1=CC=CC=C1N1C(N)=C2CCCCC2=N1 WFWJAFYZSWNMPI-UHFFFAOYSA-N 0.000 description 1
- KUXGUCNZFCVULO-UHFFFAOYSA-N 2-(4-nonylphenoxy)ethanol Chemical compound CCCCCCCCCC1=CC=C(OCCO)C=C1 KUXGUCNZFCVULO-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- BNOAMUMKLPLJLR-UHFFFAOYSA-N 2-[(2,4-diphenylpyrazol-3-yl)amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C=NN1C1=CC=CC=C1 BNOAMUMKLPLJLR-UHFFFAOYSA-N 0.000 description 1
- FRKYLFXPAJGZJZ-UHFFFAOYSA-N 2-[(2,5-dimethylpyrazol-3-yl)amino]-3-(trifluoromethyl)benzoic acid Chemical compound CN1N=C(C)C=C1NC1=C(C(O)=O)C=CC=C1C(F)(F)F FRKYLFXPAJGZJZ-UHFFFAOYSA-N 0.000 description 1
- UENHHGHFNRGQDL-UHFFFAOYSA-N 2-[(2,5-diphenylpyrazol-3-yl)amino]-5-methoxybenzamide Chemical compound NC(=O)C1=CC(OC)=CC=C1NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 UENHHGHFNRGQDL-UHFFFAOYSA-N 0.000 description 1
- ZABVVQLGPIJZKJ-UHFFFAOYSA-N 2-[(2-benzyl-5-tert-butylpyrazol-3-yl)amino]benzamide Chemical compound C=1C=CC=CC=1CN1N=C(C(C)(C)C)C=C1NC1=CC=CC=C1C(N)=O ZABVVQLGPIJZKJ-UHFFFAOYSA-N 0.000 description 1
- ACTKAZUTVUVIGV-UHFFFAOYSA-N 2-[(2-ethylpyrazol-3-yl)amino]benzoic acid Chemical compound CCN1N=CC=C1NC1=CC=CC=C1C(O)=O ACTKAZUTVUVIGV-UHFFFAOYSA-N 0.000 description 1
- BEBPGMIPMSDXPR-UHFFFAOYSA-N 2-[(5-methyl-2-phenylpyrazol-3-yl)amino]benzoic acid Chemical compound C=1C=CC=CC=1N1N=C(C)C=C1NC1=CC=CC=C1C(O)=O BEBPGMIPMSDXPR-UHFFFAOYSA-N 0.000 description 1
- YUICOJXKOJERFW-UHFFFAOYSA-N 2-[(5-tert-butyl-2-methyl-4-phenylpyrazol-3-yl)amino]-5-methylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1NC1=C(C=2C=CC=CC=2)C(C(C)(C)C)=NN1C YUICOJXKOJERFW-UHFFFAOYSA-N 0.000 description 1
- ALTCAIDXWQLHGT-UHFFFAOYSA-N 2-[(5-tert-butyl-2-methyl-4-pyridin-4-ylpyrazol-3-yl)amino]-5-methylbenzoic acid Chemical compound Cc1ccc(Nc2c(c(nn2C)C(C)(C)C)-c2ccncc2)c(c1)C(O)=O ALTCAIDXWQLHGT-UHFFFAOYSA-N 0.000 description 1
- DBHPMEHYRYJQOQ-UHFFFAOYSA-N 2-[(5-tert-butyl-2-methylpyrazol-3-yl)amino]-5-methylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1NC1=CC(C(C)(C)C)=NN1C DBHPMEHYRYJQOQ-UHFFFAOYSA-N 0.000 description 1
- FHBWGKMGYHIEHI-UHFFFAOYSA-N 2-[(5-tert-butyl-2-phenylpyrazol-3-yl)amino]-5-methoxybenzamide Chemical compound NC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1 FHBWGKMGYHIEHI-UHFFFAOYSA-N 0.000 description 1
- KCEWYUQVIWBBBG-UHFFFAOYSA-N 2-[(5-tert-butyl-2-phenylpyrazol-3-yl)amino]benzamide Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC1=CC=CC=C1C(N)=O KCEWYUQVIWBBBG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- YFNADPPGFPFIID-UHFFFAOYSA-N 2-[[2,5-bis(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C=2C(=CC=CC=2)C)=NN1C1=CC=CC=C1C YFNADPPGFPFIID-UHFFFAOYSA-N 0.000 description 1
- ZCAJYWWQWLHIDI-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-(1-methylcyclopropyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2cc(nn2-c2cc(C)ccc2C)C2(C)CC2)c(c1)C(O)=O ZCAJYWWQWLHIDI-UHFFFAOYSA-N 0.000 description 1
- GVLKAACWVCDMLS-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-(1-methylcyclopropyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=C(C)C(N2C(=CC(=N2)C2(C)CC2)NC=2C(=CC=CC=2)C(O)=O)=C1 GVLKAACWVCDMLS-UHFFFAOYSA-N 0.000 description 1
- CPHFZGCRUAEXTG-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-ethyl-4-(4-fluorophenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound C=1C=C(F)C=CC=1C=1C(CC)=NN(C=2C(=CC=C(C)C=2)C)C=1NC1=CC=C(OC)C=C1C(O)=O CPHFZGCRUAEXTG-UHFFFAOYSA-N 0.000 description 1
- BKDXBFOYUDEEEV-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-ethyl-4-(4-methoxyphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound C=1C=C(OC)C=CC=1C=1C(CC)=NN(C=2C(=CC=C(C)C=2)C)C=1NC1=CC=C(OC)C=C1C(O)=O BKDXBFOYUDEEEV-UHFFFAOYSA-N 0.000 description 1
- CXPQIBIZLCVRBG-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-ethyl-4-phenylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1nn(c(Nc2ccc(OC)cc2C(O)=O)c1-c1ccccc1)-c1cc(C)ccc1C CXPQIBIZLCVRBG-UHFFFAOYSA-N 0.000 description 1
- ZCOAWKPJXYOZQV-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-ethyl-4-pyridin-4-ylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1nn(c(Nc2ccc(OC)cc2C(O)=O)c1-c1ccncc1)-c1cc(C)ccc1C ZCOAWKPJXYOZQV-UHFFFAOYSA-N 0.000 description 1
- ATQYWUZTAVBNRL-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-methyl-4-phenylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2c(c(C)nn2-c2cc(C)ccc2C)-c2ccccc2)c(c1)C(O)=O ATQYWUZTAVBNRL-UHFFFAOYSA-N 0.000 description 1
- AOTUYNXMJOEVGH-UHFFFAOYSA-N 2-[[2-(2,5-dimethylphenyl)-5-phenylpyrazol-3-yl]amino]-5-ethylbenzoic acid Chemical compound OC(=O)C1=CC(CC)=CC=C1NC1=CC(C=2C=CC=CC=2)=NN1C1=CC(C)=CC=C1C AOTUYNXMJOEVGH-UHFFFAOYSA-N 0.000 description 1
- ZHUMIOHSMXNCON-UHFFFAOYSA-N 2-[[2-(2,6-dimethylphenyl)-5-propan-2-ylpyrazol-3-yl]amino]benzoic acid Chemical compound CC=1C=CC=C(C)C=1N1N=C(C(C)C)C=C1NC1=CC=CC=C1C(O)=O ZHUMIOHSMXNCON-UHFFFAOYSA-N 0.000 description 1
- RJBNNFSMFMHXFR-UHFFFAOYSA-N 2-[[2-(2-ethylphenyl)-5-(4-fluorophenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1ccccc1-n1nc(cc1Nc1ccc(OC)cc1C(O)=O)-c1ccc(F)cc1 RJBNNFSMFMHXFR-UHFFFAOYSA-N 0.000 description 1
- WWYUIUFOBAMZBD-UHFFFAOYSA-N 2-[[2-(2-methylphenyl)-5-phenylpyrazol-3-yl]amino]benzamide Chemical compound CC1=CC=CC=C1N1C(NC=2C(=CC=CC=2)C(N)=O)=CC(C=2C=CC=CC=2)=N1 WWYUIUFOBAMZBD-UHFFFAOYSA-N 0.000 description 1
- HEHVYVPFHSOSST-UHFFFAOYSA-N 2-[[2-(4-chloro-2-methylphenyl)-5-methyl-4-phenylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2c(c(C)nn2-c2ccc(Cl)cc2C)-c2ccccc2)c(c1)C(O)=O HEHVYVPFHSOSST-UHFFFAOYSA-N 0.000 description 1
- JWOVTOSEJIYFPC-UHFFFAOYSA-N 2-[[4-(2,2-difluoro-1,3-benzodioxol-4-yl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=3OC(F)(F)OC=3C=CC=2)C(C)=NN1C1=CC=CC=C1C JWOVTOSEJIYFPC-UHFFFAOYSA-N 0.000 description 1
- DAVBFWOJWLHSCQ-UHFFFAOYSA-N 2-[[4-(2,4-dichlorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC(Cl)=CC=2)Cl)C(C)=NN1C1=CC=CC=C1C DAVBFWOJWLHSCQ-UHFFFAOYSA-N 0.000 description 1
- IUWFZYXTAPPGKW-UHFFFAOYSA-N 2-[[4-(2,4-difluorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC(F)=CC=2)F)C(C)=NN1C1=CC=CC=C1C IUWFZYXTAPPGKW-UHFFFAOYSA-N 0.000 description 1
- LJMRQAPFUDVYBV-UHFFFAOYSA-N 2-[[4-(2-butoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound CCCCOc1ccccc1-c1c(C)nn(c1Nc1ccc(C)cc1C(O)=O)-c1ccccc1C LJMRQAPFUDVYBV-UHFFFAOYSA-N 0.000 description 1
- USVAKNAVZCTGDB-UHFFFAOYSA-N 2-[[4-(2-chlorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2c(c(C)nn2-c2ccccc2C)-c2ccccc2Cl)c(c1)C(O)=O USVAKNAVZCTGDB-UHFFFAOYSA-N 0.000 description 1
- OLOBSPZGGKDISL-UHFFFAOYSA-N 2-[[4-(2-ethoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCOc1ccccc1-c1c(C)nn(c1Nc1ccc(OC)cc1C(O)=O)-c1ccccc1C OLOBSPZGGKDISL-UHFFFAOYSA-N 0.000 description 1
- AATXYYLRVGKBAY-UHFFFAOYSA-N 2-[[4-(2-ethoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound CCOc1ccccc1-c1c(C)nn(c1Nc1ccc(C)cc1C(O)=O)-c1ccccc1C AATXYYLRVGKBAY-UHFFFAOYSA-N 0.000 description 1
- FESGQCGKMQPEIZ-UHFFFAOYSA-N 2-[[4-(2-ethylphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1ccccc1-c1c(C)nn(c1Nc1ccc(OC)cc1C(O)=O)-c1ccccc1C FESGQCGKMQPEIZ-UHFFFAOYSA-N 0.000 description 1
- PABSDMPVVUJKGD-UHFFFAOYSA-N 2-[[4-(2-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound COC1=CC=CC=C1C1=C(NC=2C(=CC(C)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C PABSDMPVVUJKGD-UHFFFAOYSA-N 0.000 description 1
- PPNKJRXRUPMCOM-UHFFFAOYSA-N 2-[[4-(3-chlorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2c(c(C)nn2-c2ccccc2C)-c2cccc(Cl)c2)c(c1)C(O)=O PPNKJRXRUPMCOM-UHFFFAOYSA-N 0.000 description 1
- RPMNHGVNCJPMCH-UHFFFAOYSA-N 2-[[4-(3-fluoro-4-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=C(F)C(OC)=CC=2)C(C)=NN1C1=CC=CC=C1C RPMNHGVNCJPMCH-UHFFFAOYSA-N 0.000 description 1
- NCVUUFGLQRYXPO-UHFFFAOYSA-N 2-[[4-(3-fluoro-4-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound C1=C(F)C(OC)=CC=C1C1=C(NC=2C(=CC(C)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C NCVUUFGLQRYXPO-UHFFFAOYSA-N 0.000 description 1
- PAWUEYQRCUJRNM-UHFFFAOYSA-N 2-[[4-(3-fluorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2c(c(C)nn2-c2ccccc2C)-c2cccc(F)c2)c(c1)C(O)=O PAWUEYQRCUJRNM-UHFFFAOYSA-N 0.000 description 1
- HFHYMWKJTKTNGW-UHFFFAOYSA-N 2-[[4-(4-acetylphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC(=CC=2)C(C)=O)C(C)=NN1C1=CC=CC=C1C HFHYMWKJTKTNGW-UHFFFAOYSA-N 0.000 description 1
- FRRDHCAPYNQHAP-UHFFFAOYSA-N 2-[[4-(4-benzoylphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC(=CC=2)C(=O)C=2C=CC=CC=2)C(C)=NN1C1=CC=CC=C1C FRRDHCAPYNQHAP-UHFFFAOYSA-N 0.000 description 1
- NRHBPLBQXIPMRY-UHFFFAOYSA-N 2-[[4-(4-fluoro-2-methylphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC(F)=CC=2)C)C(C)=NN1C1=CC=CC=C1C NRHBPLBQXIPMRY-UHFFFAOYSA-N 0.000 description 1
- LHXNHPHRDJHEHV-UHFFFAOYSA-N 2-[[4-(4-fluoro-3-methylphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=C(C)C(F)=CC=2)C(C)=NN1C1=CC=CC=C1C LHXNHPHRDJHEHV-UHFFFAOYSA-N 0.000 description 1
- FRXOADVRGGGTIS-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)-2-(2-methylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC(F)=CC=2)C(C(F)(F)F)=NN1C1=CC=CC=C1C FRXOADVRGGGTIS-UHFFFAOYSA-N 0.000 description 1
- RXDUDOIUDWHIEC-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC(F)=CC=2)C(C)=NN1C1=CC=CC=C1C RXDUDOIUDWHIEC-UHFFFAOYSA-N 0.000 description 1
- AFIXLMWGPLZDQN-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound Cc1nn(c(Nc2ccc(C)cc2C(O)=O)c1-c1ccc(F)cc1)-c1ccccc1C AFIXLMWGPLZDQN-UHFFFAOYSA-N 0.000 description 1
- VFTKHKRBKCKGMR-UHFFFAOYSA-N 2-[[4-(4-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methylbenzoic acid Chemical compound C1=CC(OC)=CC=C1C1=C(NC=2C(=CC(C)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C VFTKHKRBKCKGMR-UHFFFAOYSA-N 0.000 description 1
- UYABPKJFLCCLAH-UHFFFAOYSA-N 2-[[4-(5-chloro-2-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC=C(Cl)C=2)OC)C(C)=NN1C1=CC=CC=C1C UYABPKJFLCCLAH-UHFFFAOYSA-N 0.000 description 1
- XSJJYNVXNJSAKD-UHFFFAOYSA-N 2-[[4-(5-fluoro-2-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC=C(F)C=2)OC)C(C)=NN1C1=CC=CC=C1C XSJJYNVXNJSAKD-UHFFFAOYSA-N 0.000 description 1
- WQDALZPYQLGKDR-UHFFFAOYSA-N 2-[[5-(4-chlorophenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]-4,5-dimethoxybenzoic acid Chemical compound COc1cc(Nc2cc(nn2-c2ccccc2C)-c2ccc(Cl)cc2)c(cc1OC)C(O)=O WQDALZPYQLGKDR-UHFFFAOYSA-N 0.000 description 1
- GUODPMFEWQITMP-UHFFFAOYSA-N 2-[[5-(4-fluoro-2-methylphenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC1=CC=CC=C1N1C(NC=2C(=CC=CC=2)C(O)=O)=CC(C=2C(=CC(F)=CC=2)C)=N1 GUODPMFEWQITMP-UHFFFAOYSA-N 0.000 description 1
- NXZDYZXQCHKIMG-UHFFFAOYSA-N 2-[[5-cyclopentyl-2-(2,5-dimethylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2cc(nn2-c2cc(C)ccc2C)C2CCCC2)c(c1)C(O)=O NXZDYZXQCHKIMG-UHFFFAOYSA-N 0.000 description 1
- DOAOZHUYHBJPJG-UHFFFAOYSA-N 2-[[5-cyclopentyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2cc(nn2-c2ccccc2C)C2CCCC2)c(c1)C(O)=O DOAOZHUYHBJPJG-UHFFFAOYSA-N 0.000 description 1
- PQSBSHFUCBNXMJ-UHFFFAOYSA-N 2-[[5-ethyl-2-(2-methylphenyl)-4-phenylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1nn(c(Nc2ccc(OC)cc2C(O)=O)c1-c1ccccc1)-c1ccccc1C PQSBSHFUCBNXMJ-UHFFFAOYSA-N 0.000 description 1
- QAAWPPWPYDLYRB-UHFFFAOYSA-N 2-[[5-ethyl-2-(2-methylphenyl)-4-pyridin-4-ylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1nn(c(Nc2ccc(OC)cc2C(O)=O)c1-c1ccncc1)-c1ccccc1C QAAWPPWPYDLYRB-UHFFFAOYSA-N 0.000 description 1
- WLOHAHCXGBORLV-UHFFFAOYSA-N 2-[[5-ethyl-4-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1nn(c(Nc2ccc(OC)cc2C(O)=O)c1-c1ccc(F)cc1)-c1ccccc1C WLOHAHCXGBORLV-UHFFFAOYSA-N 0.000 description 1
- ILNJIKISMCQNST-UHFFFAOYSA-N 2-[[5-ethyl-4-(4-methoxyphenyl)-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound CCc1nn(c(Nc2ccc(OC)cc2C(O)=O)c1-c1ccc(OC)cc1)-c1ccccc1C ILNJIKISMCQNST-UHFFFAOYSA-N 0.000 description 1
- CWDOKBUERKJMJZ-UHFFFAOYSA-N 2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-4-fluorobenzoic acid Chemical compound CC1=CC=CC=C1N1C(NC=2C(=CC=C(F)C=2)C(O)=O)=CC(C(C)(C)C)=N1 CWDOKBUERKJMJZ-UHFFFAOYSA-N 0.000 description 1
- RVEJTZSAFRQYRF-UHFFFAOYSA-N 2-[[5-tert-butyl-4-(4-fluorophenyl)-2-methylpyrazol-3-yl]amino]-5-methoxybenzoic acid Chemical compound COc1ccc(Nc2c(c(nn2C)C(C)(C)C)-c2ccc(F)cc2)c(c1)C(O)=O RVEJTZSAFRQYRF-UHFFFAOYSA-N 0.000 description 1
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
- HWFCHCRFQWEFMU-UHFFFAOYSA-N 2-bromo-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(Br)=C(C(O)=O)C=C1OC HWFCHCRFQWEFMU-UHFFFAOYSA-N 0.000 description 1
- NHNAEZDWNCRWRW-UHFFFAOYSA-N 2-bromobenzamide Chemical compound NC(=O)C1=CC=CC=C1Br NHNAEZDWNCRWRW-UHFFFAOYSA-N 0.000 description 1
- VFPWGZNNRSQPBT-UHFFFAOYSA-N 2-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1Br VFPWGZNNRSQPBT-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006077 2-ethyl-2-butenyl group Chemical group 0.000 description 1
- CGMMPMYKMDITEA-UHFFFAOYSA-N 2-ethylbenzoic acid Chemical compound CCC1=CC=CC=C1C(O)=O CGMMPMYKMDITEA-UHFFFAOYSA-N 0.000 description 1
- VWQZDNIZIJMJMA-UHFFFAOYSA-N 2-fluoro-6-[[4-(4-fluorophenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound C=1C=C(F)C=CC=1C=1C(C)=NN(C=2C(=CC=CC=2)C)C=1NC1=CC=CC(F)=C1C(O)=O VWQZDNIZIJMJMA-UHFFFAOYSA-N 0.000 description 1
- NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 description 1
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 1
- FHEHQOHZZRIRFD-UHFFFAOYSA-N 2-methylpropyl 5-methoxy-2-[(2-phenylpyrazol-3-yl)amino]benzoate Chemical compound CC(C)COC(=O)C1=CC(OC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 FHEHQOHZZRIRFD-UHFFFAOYSA-N 0.000 description 1
- RWMVCOUKVCLWIC-UHFFFAOYSA-N 2-oxocyclohexane-1-carbonitrile Chemical compound O=C1CCCCC1C#N RWMVCOUKVCLWIC-UHFFFAOYSA-N 0.000 description 1
- GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 description 1
- ZVNYYNAAEVZNDW-UHFFFAOYSA-N 2-phenylpyrazol-3-amine Chemical compound NC1=CC=NN1C1=CC=CC=C1 ZVNYYNAAEVZNDW-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- FXHXMEMEXGYHIX-UHFFFAOYSA-N 3-(4-fluoro-2-methylphenyl)-3-oxopropanenitrile Chemical compound CC1=CC(F)=CC=C1C(=O)CC#N FXHXMEMEXGYHIX-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FNANHHMIDQRIIZ-UHFFFAOYSA-N 3-butyl-1-methylpyrazole Chemical compound CCCCC=1C=CN(C)N=1 FNANHHMIDQRIIZ-UHFFFAOYSA-N 0.000 description 1
- RRRCPCOJPQLWEP-UHFFFAOYSA-N 3-hydroxytriazolo[4,5-b]pyridine Chemical compound C1=CN=C2N(O)N=NC2=C1.C1=CN=C2N(O)N=NC2=C1 RRRCPCOJPQLWEP-UHFFFAOYSA-N 0.000 description 1
- MXZMACXOMZKYHJ-UHFFFAOYSA-N 4,4-dimethyl-3-oxopentanenitrile Chemical compound CC(C)(C)C(=O)CC#N MXZMACXOMZKYHJ-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- PFOZNCLQTFVEGM-UHFFFAOYSA-N 4-bromo-5-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-amine Chemical compound CC1=CC=CC=C1N1C(N)=C(Br)C(C=2C=CC(F)=CC=2)=N1 PFOZNCLQTFVEGM-UHFFFAOYSA-N 0.000 description 1
- DZURKNOWQAMQKZ-UHFFFAOYSA-N 4-ethyl-5-(4-fluorophenyl)-2-(2-methylphenyl)pyrazol-3-amine Chemical compound CCC1=C(N)N(C=2C(=CC=CC=2)C)N=C1C1=CC=C(F)C=C1 DZURKNOWQAMQKZ-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- ZSFCXTGPGSAWFT-UHFFFAOYSA-N 5-(4-chlorophenyl)-2-methylpyrazol-3-amine Chemical compound C1=C(N)N(C)N=C1C1=CC=C(Cl)C=C1 ZSFCXTGPGSAWFT-UHFFFAOYSA-N 0.000 description 1
- NGHBWIZKKRDUGX-UHFFFAOYSA-N 5-ethyl-2-[[2-(2-methylphenyl)-5-(4-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(CC)=CC=C1NC1=CC(C=2C=CC(C)=CC=2)=NN1C1=CC=CC=C1C NGHBWIZKKRDUGX-UHFFFAOYSA-N 0.000 description 1
- RSAMQYSEMXCFQG-UHFFFAOYSA-N 5-ethyl-2-[[2-(2-methylphenyl)-5-phenylpyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(CC)=CC=C1NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1C RSAMQYSEMXCFQG-UHFFFAOYSA-N 0.000 description 1
- WUTBLCYSCSJHEH-UHFFFAOYSA-N 5-fluoro-2-[[5-methyl-2-(2-methylphenyl)-4-pyridin-3-ylpyrazol-3-yl]amino]benzoic acid Chemical compound C=1C=CN=CC=1C=1C(C)=NN(C=2C(=CC=CC=2)C)C=1NC1=CC=C(F)C=C1C(O)=O WUTBLCYSCSJHEH-UHFFFAOYSA-N 0.000 description 1
- HPJVFVJRWAZQRO-UHFFFAOYSA-N 5-methoxy-2-[(2-phenyl-4,5,6,7-tetrahydroindazol-3-yl)amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(CCCC2)C2=NN1C1=CC=CC=C1 HPJVFVJRWAZQRO-UHFFFAOYSA-N 0.000 description 1
- ULDAAOUBLOEXQS-UHFFFAOYSA-N 5-methoxy-2-[(2-phenyl-4-pyridin-3-ylpyrazol-3-yl)amino]benzoic acid 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COc1ccc(Nc2c(cnn2-c2ccccc2)-c2cccnc2)c(c1)C(O)=O ULDAAOUBLOEXQS-UHFFFAOYSA-N 0.000 description 1
- XJQGUYCIQKKDKB-UHFFFAOYSA-N 5-methoxy-2-[(5-methyl-2,4-diphenylpyrazol-3-yl)amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C)=NN1C1=CC=CC=C1 XJQGUYCIQKKDKB-UHFFFAOYSA-N 0.000 description 1
- QODQBLZCSVJNQV-UHFFFAOYSA-N 5-methoxy-2-[[2-(2-methylphenyl)-4-phenyl-5-(trifluoromethyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C(F)(F)F)=NN1C1=CC=CC=C1C QODQBLZCSVJNQV-UHFFFAOYSA-N 0.000 description 1
- ZBBRJCLOQPDTAG-UHFFFAOYSA-N 5-methoxy-2-[[2-(2-methylphenyl)-5-(2-methylpropyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(CC(C)C)=NN1C1=CC=CC=C1C ZBBRJCLOQPDTAG-UHFFFAOYSA-N 0.000 description 1
- SJLLAJCSYWKURO-UHFFFAOYSA-N 5-methoxy-2-[[2-(2-methylphenyl)-5-(3-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC(C=2C=C(C)C=CC=2)=NN1C1=CC=CC=C1C SJLLAJCSYWKURO-UHFFFAOYSA-N 0.000 description 1
- QVXQMMYUSXFOJE-UHFFFAOYSA-N 5-methoxy-2-[[2-(4-methoxyphenyl)pyrazol-3-yl]amino]benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC=2C(=CC(OC)=CC=2)C(N)=O)=CC=N1 QVXQMMYUSXFOJE-UHFFFAOYSA-N 0.000 description 1
- XLTLSDJINOHNPI-UHFFFAOYSA-N 5-methoxy-2-[[2-methyl-4-phenyl-5-(trifluoromethyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C(F)(F)F)=NN1C XLTLSDJINOHNPI-UHFFFAOYSA-N 0.000 description 1
- IYHCISZGMXVKOD-UHFFFAOYSA-N 5-methoxy-2-[[4-(2-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC=CC=2)OC)C(C)=NN1C1=CC=CC=C1C IYHCISZGMXVKOD-UHFFFAOYSA-N 0.000 description 1
- BSXBNYZIBYVRKS-UHFFFAOYSA-N 5-methoxy-2-[[4-(3-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound COC1=CC=CC(C2=C(N(N=C2C)C=2C(=CC=CC=2)C)NC=2C(=CC(OC)=CC=2)C(O)=O)=C1 BSXBNYZIBYVRKS-UHFFFAOYSA-N 0.000 description 1
- JTMHSPPTNSTWFI-UHFFFAOYSA-N 5-methoxy-2-[[4-(4-methoxyphenyl)-2-phenylpyrazol-3-yl]amino]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1=C(NC=2C(=CC(OC)=CC=2)C(O)=O)N(C=2C=CC=CC=2)N=C1 JTMHSPPTNSTWFI-UHFFFAOYSA-N 0.000 description 1
- AKFTWGIHLCFSSO-UHFFFAOYSA-N 5-methoxy-2-[[4-(4-methoxyphenyl)-5-methyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1=C(NC=2C(=CC(OC)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C AKFTWGIHLCFSSO-UHFFFAOYSA-N 0.000 description 1
- WCSNVUMVMOYFPP-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-(2-propan-2-yloxyphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C(=CC=CC=2)OC(C)C)C(C)=NN1C1=CC=CC=C1C WCSNVUMVMOYFPP-UHFFFAOYSA-N 0.000 description 1
- QLOVYLBYXLTNDJ-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-(2-propoxyphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CCCOC1=CC=CC=C1C1=C(NC=2C(=CC(OC)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C QLOVYLBYXLTNDJ-UHFFFAOYSA-N 0.000 description 1
- BIAJQKYESNTGSB-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-(3-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=C(C)C=CC=2)C(C)=NN1C1=CC=CC=C1C BIAJQKYESNTGSB-UHFFFAOYSA-N 0.000 description 1
- RGOMOKAIBFFXDT-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-[4-(trifluoromethoxy)phenyl]pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC(OC(F)(F)F)=CC=2)C(C)=NN1C1=CC=CC=C1C RGOMOKAIBFFXDT-UHFFFAOYSA-N 0.000 description 1
- PTAAKHGIXFKBMQ-UHFFFAOYSA-N 5-methoxy-2-[[5-methyl-4-phenyl-2-[2-(trifluoromethyl)phenyl]pyrazol-3-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C)=NN1C1=CC=CC=C1C(F)(F)F PTAAKHGIXFKBMQ-UHFFFAOYSA-N 0.000 description 1
- NEJDDAWQGIPNTA-UHFFFAOYSA-N 5-methyl-2-[[2-(2-methylphenyl)-5-(4-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound C1=CC(C)=CC=C1C1=NN(C=2C(=CC=CC=2)C)C(NC=2C(=CC(C)=CC=2)C(O)=O)=C1 NEJDDAWQGIPNTA-UHFFFAOYSA-N 0.000 description 1
- VKVHMNAUZGLWRD-UHFFFAOYSA-N 5-methyl-2-[[5-methyl-2-(2-methylphenyl)-4-(2-propan-2-yloxyphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CC(C)OC1=CC=CC=C1C1=C(NC=2C(=CC(C)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C VKVHMNAUZGLWRD-UHFFFAOYSA-N 0.000 description 1
- ANIYITCBCVWCAU-UHFFFAOYSA-N 5-methyl-2-[[5-methyl-2-(2-methylphenyl)-4-(2-propoxyphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound CCCOC1=CC=CC=C1C1=C(NC=2C(=CC(C)=CC=2)C(O)=O)N(C=2C(=CC=CC=2)C)N=C1C ANIYITCBCVWCAU-UHFFFAOYSA-N 0.000 description 1
- IJNAAMWGMPZCRO-UHFFFAOYSA-N 5-methyl-2-[[5-methyl-2-(2-methylphenyl)-4-(4-methylphenyl)pyrazol-3-yl]amino]benzoic acid Chemical compound C=1C=C(C)C=CC=1C=1C(C)=NN(C=2C(=CC=CC=2)C)C=1NC1=CC=C(C)C=C1C(O)=O IJNAAMWGMPZCRO-UHFFFAOYSA-N 0.000 description 1
- GLCNPGWASSVTAK-UHFFFAOYSA-N 5-methyl-2-[[5-methyl-2-(2-methylphenyl)-4-pyridin-3-ylpyrazol-3-yl]amino]benzoic acid Chemical compound C=1C=CN=CC=1C=1C(C)=NN(C=2C(=CC=CC=2)C)C=1NC1=CC=C(C)C=C1C(O)=O GLCNPGWASSVTAK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 201000005670 Anovulation Diseases 0.000 description 1
- 206010002659 Anovulatory cycle Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 102100025892 Complement C1q tumor necrosis factor-related protein 1 Human genes 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 1
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 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 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229940127470 Lipase Inhibitors Drugs 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
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PMOHBGYXZBGQIO-UHFFFAOYSA-N OC(=O)C(F)(F)F.COc1cc(Nc2cc(nn2C)-c2ccccc2)c(cc1OC)C(O)=O Chemical compound OC(=O)C(F)(F)F.COc1cc(Nc2cc(nn2C)-c2ccccc2)c(cc1OC)C(O)=O PMOHBGYXZBGQIO-UHFFFAOYSA-N 0.000 description 1
- SIKQPINGRYSTPA-UHFFFAOYSA-N OC(=O)C(F)(F)F.COc1ccc(Nc2c(cnn2-c2ccccc2)-c2ccncc2)c(c1)C(O)=O Chemical compound OC(=O)C(F)(F)F.COc1ccc(Nc2c(cnn2-c2ccccc2)-c2ccncc2)c(c1)C(O)=O SIKQPINGRYSTPA-UHFFFAOYSA-N 0.000 description 1
- CXOWOXCZDAZCHG-UHFFFAOYSA-N OC(=O)C(F)(F)F.Cc1cc(Nc2cc(F)ccc2C(O)=O)n(C)n1 Chemical compound OC(=O)C(F)(F)F.Cc1cc(Nc2cc(F)ccc2C(O)=O)n(C)n1 CXOWOXCZDAZCHG-UHFFFAOYSA-N 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 108010086019 Secretin Proteins 0.000 description 1
- 102100037505 Secretin Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical class OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- UWAOJIWUVCMBAZ-UHFFFAOYSA-N [1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl]-dimethylazanium;chloride Chemical compound Cl.C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UWAOJIWUVCMBAZ-UHFFFAOYSA-N 0.000 description 1
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 1
- 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 150000007960 acetonitrile Chemical class 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000010617 anise oil Substances 0.000 description 1
- 231100000552 anovulation Toxicity 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003911 antiadherent Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000007262 aromatic hydroxylation reaction Methods 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- SJSWRKNSCWKNIR-UHFFFAOYSA-N azane;dihydrochloride Chemical compound N.Cl.Cl SJSWRKNSCWKNIR-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000008228 bacteriostatic water for injection Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical group C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- RVNZNDXHCVTOGV-UHFFFAOYSA-N benzyl 5-methoxy-2-[(2-phenylpyrazol-3-yl)amino]benzoate Chemical compound C=1C=CC=CC=1COC(=O)C1=CC(OC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 RVNZNDXHCVTOGV-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- XKXHCNPAFAXVRZ-UHFFFAOYSA-N benzylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=CC=C1 XKXHCNPAFAXVRZ-UHFFFAOYSA-N 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 229940067596 butylparaben Drugs 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
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000004289 cerebral ventricle Anatomy 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000020426 cherry syrup Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000010630 cinnamon oil Substances 0.000 description 1
- 239000008395 clarifying agent Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 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
- 229940095074 cyclic amp Drugs 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000006210 cyclodehydration reaction Methods 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229940075482 d & c green 5 Drugs 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000007907 direct compression Methods 0.000 description 1
- FPAYXBWMYIMERV-UHFFFAOYSA-L disodium;5-methyl-2-[[4-(4-methyl-2-sulfonatoanilino)-9,10-dioxoanthracen-1-yl]amino]benzenesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(C)=CC=C1NC(C=1C(=O)C2=CC=CC=C2C(=O)C=11)=CC=C1NC1=CC=C(C)C=C1S([O-])(=O)=O FPAYXBWMYIMERV-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229940124274 edetate disodium Drugs 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 1
- 235000012732 erythrosine Nutrition 0.000 description 1
- 239000004174 erythrosine Substances 0.000 description 1
- 229940011411 erythrosine Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- OHBWKDVNABICJS-UHFFFAOYSA-N ethyl 5-methoxy-2-[(2-phenylpyrazol-3-yl)amino]benzoate Chemical compound CCOC(=O)C1=CC(OC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 OHBWKDVNABICJS-UHFFFAOYSA-N 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000010228 ex vivo assay Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 150000002194 fatty esters Chemical class 0.000 description 1
- 229940051147 fd&c yellow no. 6 Drugs 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 229960005191 ferric oxide Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940095884 glucophage Drugs 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 230000023611 glucuronidation Effects 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229960000443 hydrochloric acid Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000008311 hydrophilic ointment Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- GQZXNSPRSGFJLY-UHFFFAOYSA-N hydroxyphosphanone Chemical compound OP=O GQZXNSPRSGFJLY-UHFFFAOYSA-N 0.000 description 1
- 201000010066 hyperandrogenism Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 229940046817 hypophosphorus acid Drugs 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 description 1
- 239000004179 indigotine Substances 0.000 description 1
- 235000012738 indigotine Nutrition 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 229960000829 kaolin Drugs 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229940045623 meridia Drugs 0.000 description 1
- 208000011661 metabolic syndrome X Diseases 0.000 description 1
- RBCUIRIGTNHLPS-UHFFFAOYSA-N methyl 2,5-dibromobenzoate Chemical compound COC(=O)C1=CC(Br)=CC=C1Br RBCUIRIGTNHLPS-UHFFFAOYSA-N 0.000 description 1
- SRWMPFNZPLSVAD-UHFFFAOYSA-N methyl 2-[(4,5-dimethyl-2-phenylpyrazol-3-yl)amino]-5-methoxybenzoate Chemical compound COC(=O)c1cc(OC)ccc1Nc1c(C)c(C)nn1-c1ccccc1 SRWMPFNZPLSVAD-UHFFFAOYSA-N 0.000 description 1
- XZZHWPVCMBHCNG-UHFFFAOYSA-N methyl 2-[(5-cyclopropyl-2-phenylpyrazol-3-yl)amino]-5-methoxybenzoate Chemical compound COC(=O)c1cc(OC)ccc1Nc1cc(nn1-c1ccccc1)C1CC1 XZZHWPVCMBHCNG-UHFFFAOYSA-N 0.000 description 1
- ZROANSCHXQRXGC-UHFFFAOYSA-N methyl 2-[(5-methyl-2-phenyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-3-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC=C1NC1=C(CN(C)CC2)C2=NN1C1=CC=CC=C1 ZROANSCHXQRXGC-UHFFFAOYSA-N 0.000 description 1
- GVOXEXUEYIWADY-UHFFFAOYSA-N methyl 2-[(5-tert-butyl-2-methylpyrazol-3-yl)amino]-3-methylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1NC1=CC(C(C)(C)C)=NN1C GVOXEXUEYIWADY-UHFFFAOYSA-N 0.000 description 1
- OOFYXHKUXWTBFT-UHFFFAOYSA-N methyl 2-[(5-tert-butyl-2-methylpyrazol-3-yl)amino]-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C OOFYXHKUXWTBFT-UHFFFAOYSA-N 0.000 description 1
- UKMVHEFTKGJUGL-UHFFFAOYSA-N methyl 2-[[2-(4-methoxyphenyl)pyrazol-3-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC=C1NC1=CC=NN1C1=CC=C(OC)C=C1 UKMVHEFTKGJUGL-UHFFFAOYSA-N 0.000 description 1
- WYNHUEIEXKPQTH-UHFFFAOYSA-N methyl 2-[[5-cyclohexyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=CC(C2CCCCC2)=NN1C1=CC=CC=C1C WYNHUEIEXKPQTH-UHFFFAOYSA-N 0.000 description 1
- FKDNIHMMBNNRGO-UHFFFAOYSA-N methyl 2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-4-chlorobenzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1C FKDNIHMMBNNRGO-UHFFFAOYSA-N 0.000 description 1
- KMVCPZJGBHETCS-UHFFFAOYSA-N methyl 2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1C KMVCPZJGBHETCS-UHFFFAOYSA-N 0.000 description 1
- UUCMPGBCFFEJSE-UHFFFAOYSA-N methyl 2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]-5-ethylbenzoate Chemical compound COC(=O)C1=CC(CC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1C UUCMPGBCFFEJSE-UHFFFAOYSA-N 0.000 description 1
- CZHYQFOBFUGSTN-UHFFFAOYSA-N methyl 2-[[5-tert-butyl-2-(5-methoxy-2-methylphenyl)pyrazol-3-yl]amino]-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC(OC)=CC=C1C CZHYQFOBFUGSTN-UHFFFAOYSA-N 0.000 description 1
- BIFARHLBYAKSSN-UHFFFAOYSA-N methyl 2-bromo-4-chlorobenzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1Br BIFARHLBYAKSSN-UHFFFAOYSA-N 0.000 description 1
- JENBPOJAZCPSEW-UHFFFAOYSA-N methyl 2-bromo-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1Br JENBPOJAZCPSEW-UHFFFAOYSA-N 0.000 description 1
- UECTUFPIUZYTQW-UHFFFAOYSA-N methyl 2-bromo-5-(difluoromethoxy)benzoate Chemical compound COC(=O)C1=CC(OC(F)F)=CC=C1Br UECTUFPIUZYTQW-UHFFFAOYSA-N 0.000 description 1
- SWGQITQOBPXVRC-UHFFFAOYSA-N methyl 2-bromobenzoate Chemical compound COC(=O)C1=CC=CC=C1Br SWGQITQOBPXVRC-UHFFFAOYSA-N 0.000 description 1
- AWUPLMYXZJKHEG-UHFFFAOYSA-N methyl 2-chloro-2,2-difluoroacetate Chemical compound COC(=O)C(F)(F)Cl AWUPLMYXZJKHEG-UHFFFAOYSA-N 0.000 description 1
- CYHGFBZLYZWIRI-UHFFFAOYSA-N methyl 5-bromo-2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzoate Chemical compound COC(=O)C1=CC(Br)=CC=C1NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1C CYHGFBZLYZWIRI-UHFFFAOYSA-N 0.000 description 1
- IGCQDHGJVSMDOS-UHFFFAOYSA-N methyl 5-methoxy-2-[(2-phenylpyrazol-3-yl)amino]benzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 IGCQDHGJVSMDOS-UHFFFAOYSA-N 0.000 description 1
- ADRQGMAZVXZCDV-UHFFFAOYSA-N methyl 5-methoxy-2-[(5-methyl-2-phenyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-3-yl)amino]benzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=C(CN(C)CC2)C2=NN1C1=CC=CC=C1 ADRQGMAZVXZCDV-UHFFFAOYSA-N 0.000 description 1
- YCKKSGYTJQLLJZ-UHFFFAOYSA-N methyl 5-methoxy-2-[(5-methyl-2-phenylpyrazol-3-yl)amino]benzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=CC(C)=NN1C1=CC=CC=C1 YCKKSGYTJQLLJZ-UHFFFAOYSA-N 0.000 description 1
- IPYKPUDAYVJDON-UHFFFAOYSA-N methyl 5-methoxy-2-[[2-(2-methylphenyl)-5-(2-methylpropyl)pyrazol-3-yl]amino]benzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=CC(CC(C)C)=NN1C1=CC=CC=C1C IPYKPUDAYVJDON-UHFFFAOYSA-N 0.000 description 1
- PXNMBLUVQIXEJR-UHFFFAOYSA-N methyl 5-methoxy-2-[[2-(4-methoxyphenyl)pyrazol-3-yl]amino]benzoate Chemical compound COC(=O)c1cc(OC)ccc1Nc1ccnn1-c1ccc(OC)cc1 PXNMBLUVQIXEJR-UHFFFAOYSA-N 0.000 description 1
- QCTNMSQLLRKZSM-UHFFFAOYSA-N methyl 5-methoxy-2-[[5-methyl-2-(2-methylphenyl)-4-phenylpyrazol-3-yl]amino]benzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1NC1=C(C=2C=CC=CC=2)C(C)=NN1C1=CC=CC=C1C QCTNMSQLLRKZSM-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- IIHIJFJSXPDTNO-UHFFFAOYSA-N methyl cyclopentanecarboxylate Chemical compound COC(=O)C1CCCC1 IIHIJFJSXPDTNO-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- CBKKSEQQFZNYSX-UHFFFAOYSA-N n,n-dibenzyl-2-[[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]amino]benzenesulfonamide Chemical compound CC1=CC=CC=C1N1C(NC=2C(=CC=CC=2)S(=O)(=O)N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)=CC(C(C)(C)C)=N1 CBKKSEQQFZNYSX-UHFFFAOYSA-N 0.000 description 1
- KCJRHWIGQZHUPP-UHFFFAOYSA-N n,n-dibenzyl-2-bromobenzenesulfonamide Chemical compound BrC1=CC=CC=C1S(=O)(=O)N(CC=1C=CC=CC=1)CC1=CC=CC=C1 KCJRHWIGQZHUPP-UHFFFAOYSA-N 0.000 description 1
- OSLRCXMQCVDZNO-UHFFFAOYSA-N n-[1-(hydroxyamino)ethylidene]-2-[(5-methyl-2-phenylpyrazol-3-yl)amino]benzamide Chemical compound O/N=C(/C)NC(=O)C1=CC=CC=C1NC1=CC(C)=NN1C1=CC=CC=C1 OSLRCXMQCVDZNO-UHFFFAOYSA-N 0.000 description 1
- YLDSUVUVWQQIRS-UHFFFAOYSA-N n-ethyl-5-methylsulfanyl-2-[(2-phenylpyrazol-3-yl)amino]benzamide Chemical compound CCNC(=O)C1=CC(SC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 YLDSUVUVWQQIRS-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- QAYQDNJYLMHDDV-UHFFFAOYSA-N n-methyl-5-methylsulfanyl-2-[(2-phenylpyrazol-3-yl)amino]benzamide Chemical compound CNC(=O)C1=CC(SC)=CC=C1NC1=CC=NN1C1=CC=CC=C1 QAYQDNJYLMHDDV-UHFFFAOYSA-N 0.000 description 1
- FRZFJTUTPKVROY-UHFFFAOYSA-N n-phenylbenzamide Chemical compound C=1C=CC=CC=1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C(=O)NC1=CC=CC=C1 FRZFJTUTPKVROY-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229940074355 nitric acid Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229940073555 nonoxynol-10 Drugs 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 238000000238 one-dimensional nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 238000005222 photoaffinity labeling Methods 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- OQZCJRJRGMMSGK-UHFFFAOYSA-M potassium metaphosphate Chemical compound [K+].[O-]P(=O)=O OQZCJRJRGMMSGK-UHFFFAOYSA-M 0.000 description 1
- 229940099402 potassium metaphosphate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 239000008132 rose water Substances 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229960002101 secretin Drugs 0.000 description 1
- OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- LLELVHKMCSBMCX-UHFFFAOYSA-M sodium 1-[(4-chloro-5-methyl-2-sulfophenyl)diazenyl]naphthalen-2-olate Chemical compound [Na+].Cc1cc(N=Nc2c(O)ccc3ccccc23)c(cc1Cl)S([O-])(=O)=O LLELVHKMCSBMCX-UHFFFAOYSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940105067 sodium chloride 9 mg/ml Drugs 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229960003339 sodium phosphate Drugs 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 229940100515 sorbitan Drugs 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000008229 sterile water for irrigation Substances 0.000 description 1
- 230000010009 steroidogenesis Effects 0.000 description 1
- 239000003351 stiffener Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229920003048 styrene butadiene rubber Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 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
- WAAWARRPZBNTNS-UHFFFAOYSA-N trimethylbenzylammonium dichloroiodate Chemical compound ClI(=O)=O.ClI(=O)=O.C[N+](C)(C)CC1=CC=CC=C1 WAAWARRPZBNTNS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 229940002552 xenical Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—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
- 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
- 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
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42991702P | 2002-11-27 | 2002-11-27 | |
| US60/429,917 | 2002-11-27 | ||
| US49821403P | 2003-08-27 | 2003-08-27 | |
| US60/498,214 | 2003-08-27 | ||
| PCT/US2003/037829 WO2004050651A1 (en) | 2002-11-27 | 2003-11-25 | Anilinopyrazole derivatives useful for the treatment of diabetes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2507186A1 true CA2507186A1 (en) | 2004-06-17 |
Family
ID=32474531
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002507186A Abandoned CA2507186A1 (en) | 2002-11-27 | 2003-11-25 | Anilinopyrazole derivatives useful for the treatment of diabetes |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7265144B2 (enExample) |
| EP (1) | EP1567517A1 (enExample) |
| JP (1) | JP2006510728A (enExample) |
| KR (1) | KR20050085170A (enExample) |
| AR (1) | AR042067A1 (enExample) |
| AU (2) | AU2003295890A1 (enExample) |
| BR (1) | BR0316723A (enExample) |
| CA (1) | CA2507186A1 (enExample) |
| HN (1) | HN2003000379A (enExample) |
| MX (1) | MXPA05004621A (enExample) |
| MY (1) | MY141528A (enExample) |
| PE (1) | PE20040907A1 (enExample) |
| PL (1) | PL377164A1 (enExample) |
| TW (1) | TW200418803A (enExample) |
| UY (1) | UY28098A1 (enExample) |
| WO (2) | WO2004050650A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2567352A1 (en) * | 2004-05-20 | 2005-12-01 | Bayer Pharmaceuticals Corporation | 5-anilino-4-heteroarylpyrazole derivatives useful for the treatment of diabetes |
| CA2602609A1 (en) * | 2005-03-16 | 2006-09-21 | Junichi Yokotani | Novel anthranilic acid derivative or salt thereof |
| MX2007016070A (es) * | 2005-07-07 | 2008-03-10 | Abbott Lab | Promotores de apoptosis. |
| CA2620425A1 (en) * | 2005-08-31 | 2007-03-08 | Bayer Healthcare Llc | Anilinopyrazole derivatives useful for the treatment of diabetes |
| WO2007129195A2 (en) * | 2006-05-04 | 2007-11-15 | Pfizer Products Inc. | 4-pyrimidine-5-amino-pyrazole compounds |
| US8022217B2 (en) | 2006-07-31 | 2011-09-20 | Cadila Healthcare Limited | Compounds suitable as modulators of HDL |
| CN103739595A (zh) | 2006-10-02 | 2014-04-23 | Irm责任有限公司 | 作为蛋白激酶抑制剂的化合物和组合物 |
| EP2128138A1 (en) | 2007-01-29 | 2009-12-02 | Takeda Pharmaceutical Company Limited | Pyrazole compound |
| US20110034521A1 (en) * | 2007-09-28 | 2011-02-10 | Alan Jacobson | Compounds and methods for treating zinc matrix metalloprotease dependent diseases |
| DE102008039083A1 (de) | 2008-08-21 | 2010-02-25 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Aminopyrazole und ihre Verwendung |
| DE102008039082A1 (de) | 2008-08-21 | 2010-02-25 | Bayer Schering Pharma Aktiengesellschaft | Azabicyclisch-substituierte 5-Aminopyrazole und ihre Verwendung |
| WO2010033360A1 (en) * | 2008-09-19 | 2010-03-25 | 1/3 Absolute Science, Inc. | Methods of treating a botulinum toxin related condition in a subject |
| BRPI0919248A2 (pt) | 2008-09-25 | 2019-09-24 | Hoffmann La Roche | derivados de 3-amino-indazol ou 3-amino-4,5,6,7-tetraidroindazol |
| AR075713A1 (es) | 2009-03-03 | 2011-04-20 | Du Pont | Pirazoles fungicidas |
| TWI504350B (zh) * | 2010-09-01 | 2015-10-21 | Du Pont | 殺真菌吡唑及其混合物 |
| TWI568721B (zh) | 2012-02-01 | 2017-02-01 | 杜邦股份有限公司 | 殺真菌之吡唑混合物 |
| US9630976B2 (en) | 2012-07-03 | 2017-04-25 | Ono Pharmaceutical Co., Ltd. | Compound having agonistic activity on somatostatin receptor, and use thereof for medical purposes |
| CN103074693A (zh) * | 2013-01-18 | 2013-05-01 | 桐昆集团股份有限公司 | 带双导丝辊的poy纺丝卷绕装置 |
| WO2015100213A2 (en) | 2013-12-23 | 2015-07-02 | Amazentis Sa | Process-scale synthesis of urolithins |
| WO2016204270A1 (ja) * | 2015-06-18 | 2016-12-22 | 日本曹達株式会社 | ジアリールアゾール化合物および有害生物防除剤 |
| EP3632904B1 (en) * | 2017-05-26 | 2022-04-20 | Jiangsu Atom Bioscience and Pharmaceutical Co., Ltd. | Urat1 inhibitors for promoting uric acid excretion |
| WO2020227368A1 (en) * | 2019-05-08 | 2020-11-12 | Trustees Of Boston University | Hsp90 inhibitors and uses thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL134200C (enExample) * | 1960-04-14 | |||
| US3790576A (en) * | 1972-03-20 | 1974-02-05 | Parke Davis & Co | 9 substituted 4,9-dihydro-1,3,4,4-tetraalkyl-1h-pyrazolo(3,4-b)quinolines |
| EP0586686A1 (en) | 1992-03-26 | 1994-03-16 | Dowelanco | N-heterocyclic nitro anilines as fungicides |
| EP0788358B1 (en) * | 1994-11-10 | 2004-03-31 | Millennium Pharmaceuticals, Inc. | Use of pyrazole compounds for the treatment of glomerulonephritis, cancer, atherosclerosis or restenosis |
| DE19532066A1 (de) | 1995-08-31 | 1997-03-06 | Bayer Ag | Substituierte 5-Aminopyrazole |
| FR2763334A1 (fr) * | 1997-05-13 | 1998-11-20 | Lipha | Derives anthraniliques |
| US5998424A (en) * | 1997-06-19 | 1999-12-07 | Dupont Pharmaceuticals Company | Inhibitors of factor Xa with a neutral P1 specificity group |
| US5942520A (en) * | 1998-01-27 | 1999-08-24 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells by exposure to substituted N-cycloalkylmethyl-1-H-pyrazolo (3,4-B) quinolone-4 amines |
| ATE410415T1 (de) * | 2003-02-27 | 2008-10-15 | Smithkline Beecham Corp | Neue verbindungen |
-
2003
- 2003-11-18 AR ARP030104252A patent/AR042067A1/es unknown
- 2003-11-21 US US10/719,485 patent/US7265144B2/en not_active Expired - Fee Related
- 2003-11-21 AU AU2003295890A patent/AU2003295890A1/en not_active Abandoned
- 2003-11-21 WO PCT/US2003/037578 patent/WO2004050650A1/en not_active Ceased
- 2003-11-25 JP JP2004570952A patent/JP2006510728A/ja active Pending
- 2003-11-25 PL PL377164A patent/PL377164A1/pl not_active Application Discontinuation
- 2003-11-25 KR KR1020057009560A patent/KR20050085170A/ko not_active Withdrawn
- 2003-11-25 AU AU2003297565A patent/AU2003297565A1/en not_active Abandoned
- 2003-11-25 WO PCT/US2003/037829 patent/WO2004050651A1/en not_active Ceased
- 2003-11-25 CA CA002507186A patent/CA2507186A1/en not_active Abandoned
- 2003-11-25 MX MXPA05004621A patent/MXPA05004621A/es not_active Application Discontinuation
- 2003-11-25 BR BR0316723-2A patent/BR0316723A/pt not_active IP Right Cessation
- 2003-11-25 EP EP03812454A patent/EP1567517A1/en not_active Withdrawn
- 2003-11-26 PE PE2003001198A patent/PE20040907A1/es not_active Application Discontinuation
- 2003-11-26 TW TW092133242A patent/TW200418803A/zh unknown
- 2003-11-26 HN HN2003000379A patent/HN2003000379A/es unknown
- 2003-11-26 UY UY28098A patent/UY28098A1/es not_active Application Discontinuation
- 2003-11-27 MY MYPI20034545A patent/MY141528A/en unknown
-
2007
- 2007-08-31 US US11/897,620 patent/US20080064734A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004050651A1 (en) | 2004-06-17 |
| AU2003295890A1 (en) | 2004-06-23 |
| US20080064734A1 (en) | 2008-03-13 |
| US20040157904A1 (en) | 2004-08-12 |
| EP1567517A1 (en) | 2005-08-31 |
| PE20040907A1 (es) | 2005-01-27 |
| WO2004050650A1 (en) | 2004-06-17 |
| KR20050085170A (ko) | 2005-08-29 |
| US7265144B2 (en) | 2007-09-04 |
| AR042067A1 (es) | 2005-06-08 |
| HN2003000379A (es) | 2005-12-20 |
| TW200418803A (en) | 2004-10-01 |
| UY28098A1 (es) | 2004-06-30 |
| AU2003297565A1 (en) | 2004-06-23 |
| MXPA05004621A (es) | 2005-06-08 |
| BR0316723A (pt) | 2005-10-18 |
| PL377164A1 (pl) | 2006-01-23 |
| JP2006510728A (ja) | 2006-03-30 |
| HK1087103A1 (zh) | 2006-10-06 |
| MY141528A (en) | 2010-05-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20080064734A1 (en) | Anilinopyrazole derivatives useful for the treatment of diabetes | |
| JP5767631B2 (ja) | バニロイド受容体リガンドとしての置換された芳香族カルボキサミドおよび尿素誘導体 | |
| JP6948322B2 (ja) | Ａｐｊ受容体のａｐｊアゴニストとしてのヘテロアリールヒドロキシピリミジノン | |
| US20090209451A1 (en) | Heteroarylaminopyrazole derivatives useful for the treatment of diabetes | |
| JP2013545740A (ja) | バニロイド受容体リガンドとしての置換された複素芳香族カルボキサミド誘導体および尿素誘導体 | |
| CN101679279B (zh) | 作为5-ht6拮抗剂的磺酰吡唑啉甲脒衍生物 | |
| PT1024138E (pt) | Derivados de pirazole | |
| JP7492597B2 (ja) | Ｇｐｒ５２モジュレーター化合物 | |
| US10954232B2 (en) | Pyrazole derivative as ALK5 inhibitor and uses thereof | |
| JP2013534229A (ja) | バニロイド受容体リガンドとしての置換された環状カルボキサミド誘導体および尿素誘導体 | |
| JP2013253019A (ja) | 新規なピペリジン誘導体及びこれを含有する医薬 | |
| CA2743489A1 (en) | Substituted bicyclic amines for the treatment of diabetes | |
| WO2007027842A1 (en) | Anilinopyrazole derivatives useful for the treatment of diabetes | |
| TW200533656A (en) | Therapeutic agents | |
| JP2019001715A (ja) | 三環性化合物 | |
| JP2020524660A (ja) | Ｒｏｒ−ガンマモジュレーターとして有用な２，３−ジヒドロイソインドール−１−カルボキサミド | |
| US11597702B2 (en) | Substituted pyrazoles FFA4/GPR120 receptor agonists | |
| US20080009531A1 (en) | 5-Anilino-4-Heteroarylpyrazole Derivatives Useful for the Treatment of Diabetes | |
| CN114591317A (zh) | P2x3抑制剂及其用途 | |
| HK1087103B (en) | Anilinopyrazole derivatives useful for the treatment of diabetes | |
| JP2013542231A (ja) | バニロイド受容体リガンドとしての置換された二環式芳香族カルボキサミド誘導体および尿素誘導体 | |
| ZA200505055B (en) | Anilinopyrazole derivatives useful for the treatment of diabetes | |
| WO2019188456A1 (ja) | 新規抗腫瘍剤 | |
| MXPA06008833A (en) | Heteroarylaminopyrazole derivatives useful for the treatment of diabetes | |
| TW200916442A (en) | 4, 5-dihydro-(1H)-pyrazole derivatives as cannabinoid CB1receptor modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |