JP5735412B2 - １１−ベータ−ヒドロキシステロイドデヒドロゲナーゼ−１の阻害剤としてのｎｉｐチアゾール誘導体 - Google Patents
１１−ベータ−ヒドロキシステロイドデヒドロゲナーゼ−１の阻害剤としてのｎｉｐチアゾール誘導体 Download PDFInfo
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- JP5735412B2 JP5735412B2 JP2011507806A JP2011507806A JP5735412B2 JP 5735412 B2 JP5735412 B2 JP 5735412B2 JP 2011507806 A JP2011507806 A JP 2011507806A JP 2011507806 A JP2011507806 A JP 2011507806A JP 5735412 B2 JP5735412 B2 JP 5735412B2
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- Japan
- Prior art keywords
- piperidin
- thiazol
- carboxylic acid
- carbonyl
- piperidine
- 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.)
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- 150000007979 thiazole derivatives Chemical class 0.000 title claims description 16
- 239000003112 inhibitor Substances 0.000 title description 32
- 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title description 3
- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 161
- -1 4-trifluoromethoxy-benzoyl Chemical group 0.000 claims description 129
- 150000003839 salts Chemical class 0.000 claims description 55
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 45
- 238000011282 treatment Methods 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 239000012453 solvate Substances 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 27
- 239000003862 glucocorticoid Substances 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 208000035475 disorder Diseases 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 19
- 201000001320 Atherosclerosis Diseases 0.000 claims description 18
- 239000013543 active substance Substances 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 206010020772 Hypertension Diseases 0.000 claims description 15
- 206010022489 Insulin Resistance Diseases 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 208000008589 Obesity Diseases 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 12
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims description 11
- 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 10
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 10
- 239000008103 glucose Substances 0.000 claims description 10
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 9
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 9
- 150000002632 lipids Chemical class 0.000 claims description 9
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 8
- 208000010877 cognitive disease Diseases 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 206010033645 Pancreatitis Diseases 0.000 claims description 6
- 208000017442 Retinal disease Diseases 0.000 claims description 6
- 206010038923 Retinopathy Diseases 0.000 claims description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
- 201000001421 hyperglycemia Diseases 0.000 claims description 6
- 208000017169 kidney disease Diseases 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- MCQSVVAOVRESQK-UHFFFAOYSA-N n-cyclopropylcyclohexanamine Chemical compound C1CC1NC1CCCCC1 MCQSVVAOVRESQK-UHFFFAOYSA-N 0.000 claims description 6
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- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
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- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 230000004963 pathophysiological condition Effects 0.000 claims description 5
- 230000004962 physiological condition Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 230000020477 pH reduction Effects 0.000 claims description 4
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 claims description 4
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 3
- PCVNBERATKXZAC-UHFFFAOYSA-N 4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 PCVNBERATKXZAC-UHFFFAOYSA-N 0.000 claims description 3
- BQESEIOJRSYYHH-UHFFFAOYSA-N 4-[4-(piperidine-1-carbonyl)-1,3-thiazol-2-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C1=NC(C(=O)N2CCCCC2)=CS1 BQESEIOJRSYYHH-UHFFFAOYSA-N 0.000 claims description 3
- CEZAIWXFJSUZSC-UHFFFAOYSA-N 4-[4-[cyclohexyl(cyclopropyl)carbamoyl]-1,3-thiazol-2-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C1=NC(C(=O)N(C2CC2)C2CCCCC2)=CS1 CEZAIWXFJSUZSC-UHFFFAOYSA-N 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010024229 Leprosy Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 150000001263 acyl chlorides Chemical class 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 239000012948 isocyanate Substances 0.000 claims description 3
- 150000002513 isocyanates Chemical class 0.000 claims description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 3
- SCGQNJHAAYUQOO-UHFFFAOYSA-N tert-butyl 4-carbamothioylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(N)=S)CC1 SCGQNJHAAYUQOO-UHFFFAOYSA-N 0.000 claims description 3
- 201000008827 tuberculosis Diseases 0.000 claims description 3
- ZFQHRHCKIRAYMM-UHFFFAOYSA-N 1-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]-2-(4-methoxyphenyl)ethanone Chemical compound C1=CC(OC)=CC=C1CC(=O)N1CCC(C=2SC=C(N=2)C(=O)N2C3CCCCC3CCC2)CC1 ZFQHRHCKIRAYMM-UHFFFAOYSA-N 0.000 claims description 2
- VYGVKAKPUCQPRL-UHFFFAOYSA-N 1-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]-2-ethylbutan-1-one Chemical compound C1CN(C(=O)C(CC)CC)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 VYGVKAKPUCQPRL-UHFFFAOYSA-N 0.000 claims description 2
- BDSZDAAHVJXVQP-UHFFFAOYSA-N 1-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]-2-methylpropan-1-one Chemical compound C1CN(C(=O)C(C)C)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 BDSZDAAHVJXVQP-UHFFFAOYSA-N 0.000 claims description 2
- BQXONXHHJWXYNL-UHFFFAOYSA-N 1-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]-3,3-dimethylbutan-1-one Chemical compound C1CN(C(=O)CC(C)(C)C)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 BQXONXHHJWXYNL-UHFFFAOYSA-N 0.000 claims description 2
- YUNJQSHWFZNSTH-UHFFFAOYSA-N 1-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]-3-cyclopentylpropan-1-one Chemical compound C1CC(C=2SC=C(N=2)C(=O)N2C3CCCCC3CCC2)CCN1C(=O)CCC1CCCC1 YUNJQSHWFZNSTH-UHFFFAOYSA-N 0.000 claims description 2
- MIRDCQSJZHXXHL-UHFFFAOYSA-N 1-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 MIRDCQSJZHXXHL-UHFFFAOYSA-N 0.000 claims description 2
- DNJJHCUKDHGAQC-UHFFFAOYSA-N 2-(1-acetylpiperidin-4-yl)-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1CN(C(=O)C)CCC1C1=NC(C(=O)N(C2CC2)C2CCCCC2)=CS1 DNJJHCUKDHGAQC-UHFFFAOYSA-N 0.000 claims description 2
- DNESMUNOEGXHTQ-UHFFFAOYSA-N 2-(1-butylsulfonylpiperidin-4-yl)-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1CN(S(=O)(=O)CCCC)CCC1C1=NC(C(=O)N(C2CC2)C2CCCCC2)=CS1 DNESMUNOEGXHTQ-UHFFFAOYSA-N 0.000 claims description 2
- MKZMBJQNLLGAJR-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1-[4-[4-(piperidine-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]ethanone Chemical compound C1=CC(OC)=CC=C1CC(=O)N1CCC(C=2SC=C(N=2)C(=O)N2CCCCC2)CC1 MKZMBJQNLLGAJR-UHFFFAOYSA-N 0.000 claims description 2
- DCELNKSXQZPVQH-UHFFFAOYSA-N 2-[1-(2-amino-2-oxoethyl)piperidin-4-yl]-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1CN(CC(=O)N)CCC1C1=NC(C(=O)N(C2CC2)C2CCCCC2)=CS1 DCELNKSXQZPVQH-UHFFFAOYSA-N 0.000 claims description 2
- XJWZLBWQFHBFIM-UHFFFAOYSA-N 2-[1-(3-methylbutanoyl)piperidin-4-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)CC(C)C)CCC1C1=NC(C(O)=O)=CS1 XJWZLBWQFHBFIM-UHFFFAOYSA-N 0.000 claims description 2
- RHWOGLOTEZYQSG-UHFFFAOYSA-N 2-[1-(4-tert-butylphenyl)sulfonylpiperidin-4-yl]-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)N1CCC(C=2SC=C(N=2)C(=O)N(C2CC2)C2CCCCC2)CC1 RHWOGLOTEZYQSG-UHFFFAOYSA-N 0.000 claims description 2
- AEORGMRUYYPTMV-UHFFFAOYSA-N 2-[1-(cyanomethyl)piperidin-4-yl]-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C=1SC(C2CCN(CC#N)CC2)=NC=1C(=O)N(C1CCCCC1)C1CC1 AEORGMRUYYPTMV-UHFFFAOYSA-N 0.000 claims description 2
- HBEDEXPLRRRXAF-UHFFFAOYSA-N 2-[1-(cyclobutanecarbonyl)piperidin-4-yl]-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1CC(C=2SC=C(N=2)C(=O)N(C2CC2)C2CCCCC2)CCN1C(=O)C1CCC1 HBEDEXPLRRRXAF-UHFFFAOYSA-N 0.000 claims description 2
- DOHDPSHOOPLJKI-UHFFFAOYSA-N 2-[1-(cyclohexanecarbonyl)piperidin-4-yl]-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1CC(C=2SC=C(N=2)C(=O)N(C2CC2)C2CCCCC2)CCN1C(=O)C1CCCCC1 DOHDPSHOOPLJKI-UHFFFAOYSA-N 0.000 claims description 2
- XCGXGVUKJHLKIK-UHFFFAOYSA-N 2-[1-(tert-butylcarbamoyl)piperidin-4-yl]-n-cyclohexyl-n-cyclopropyl-1,3-thiazole-4-carboxamide Chemical compound C1CN(C(=O)NC(C)(C)C)CCC1C1=NC(C(=O)N(C2CC2)C2CCCCC2)=CS1 XCGXGVUKJHLKIK-UHFFFAOYSA-N 0.000 claims description 2
- KIRRXZPLONWSFO-UHFFFAOYSA-N 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(C(O)=O)=CS1 KIRRXZPLONWSFO-UHFFFAOYSA-N 0.000 claims description 2
- ZDTJGHRWVLVYLB-UHFFFAOYSA-N 2-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]acetonitrile Chemical compound C1CCC2CCCCC2N1C(=O)C(N=1)=CSC=1C1CCN(CC#N)CC1 ZDTJGHRWVLVYLB-UHFFFAOYSA-N 0.000 claims description 2
- IFEMYUAYYDZALW-UHFFFAOYSA-N 2-phenoxy-1-[4-[4-(piperidine-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]ethanone Chemical compound C1CC(C=2SC=C(N=2)C(=O)N2CCCCC2)CCN1C(=O)COC1=CC=CC=C1 IFEMYUAYYDZALW-UHFFFAOYSA-N 0.000 claims description 2
- KOXAZLGZEPULHE-UHFFFAOYSA-N 2-phenyl-1-[4-[4-(piperidine-1-carbonyl)-1,3-thiazol-2-yl]piperidin-1-yl]butan-1-one Chemical compound C=1C=CC=CC=1C(CC)C(=O)N(CC1)CCC1C(SC=1)=NC=1C(=O)N1CCCCC1 KOXAZLGZEPULHE-UHFFFAOYSA-N 0.000 claims description 2
- FTLXRJLIYRYDGQ-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-(1-butylpiperidin-4-yl)-1,3-thiazol-4-yl]methanone Chemical compound C1CN(CCCC)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 FTLXRJLIYRYDGQ-UHFFFAOYSA-N 0.000 claims description 2
- AJASMJHXRUZIJI-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-(1-butylsulfonylpiperidin-4-yl)-1,3-thiazol-4-yl]methanone Chemical compound C1CN(S(=O)(=O)CCCC)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 AJASMJHXRUZIJI-UHFFFAOYSA-N 0.000 claims description 2
- DCJFVXNAZXQZAY-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-(1-ethylsulfonylpiperidin-4-yl)-1,3-thiazol-4-yl]methanone Chemical compound C1CN(S(=O)(=O)CC)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 DCJFVXNAZXQZAY-UHFFFAOYSA-N 0.000 claims description 2
- GOMZCHQVMKVYSB-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-(1-pentylpiperidin-4-yl)-1,3-thiazol-4-yl]methanone Chemical compound C1CN(CCCCC)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 GOMZCHQVMKVYSB-UHFFFAOYSA-N 0.000 claims description 2
- AOEYDGGZXVVTOR-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-(1-propylsulfonylpiperidin-4-yl)-1,3-thiazol-4-yl]methanone Chemical compound C1CN(S(=O)(=O)CCC)CCC1C1=NC(C(=O)N2C3CCCCC3CCC2)=CS1 AOEYDGGZXVVTOR-UHFFFAOYSA-N 0.000 claims description 2
- BTHBYQWWYHIEFU-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-(1-thiophen-2-ylsulfonylpiperidin-4-yl)-1,3-thiazol-4-yl]methanone Chemical compound C1CCC2CCCCC2N1C(=O)C(N=1)=CSC=1C(CC1)CCN1S(=O)(=O)C1=CC=CS1 BTHBYQWWYHIEFU-UHFFFAOYSA-N 0.000 claims description 2
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- PACUUHNWXXCKOI-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-[1-(4-fluorophenyl)sulfonylpiperidin-4-yl]-1,3-thiazol-4-yl]methanone Chemical compound C1=CC(F)=CC=C1S(=O)(=O)N1CCC(C=2SC=C(N=2)C(=O)N2C3CCCCC3CCC2)CC1 PACUUHNWXXCKOI-UHFFFAOYSA-N 0.000 claims description 2
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- BUDXIHRTTHMQDD-UHFFFAOYSA-N 4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-1-carbonyl)-1,3-thiazol-2-yl]-n-cyclopentylpiperidine-1-carboxamide Chemical compound C1CC(C=2SC=C(N=2)C(=O)N2C3CCCCC3CCC2)CCN1C(=O)NC1CCCC1 BUDXIHRTTHMQDD-UHFFFAOYSA-N 0.000 claims description 2
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- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
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Landscapes
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| EP08290424.4 | 2008-05-05 | ||
| PCT/EP2009/002607 WO2009135581A2 (en) | 2008-05-05 | 2009-04-08 | Novel nip thiazole derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1 |
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| CA2689383C (en) * | 2007-06-01 | 2013-10-08 | F. Hoffmann-La Roche Ag | Piperidine-amide derivatives |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US9771357B2 (en) | 2013-07-09 | 2017-09-26 | Ono Pharmaceutical Co., Ltd. | ALXR agonist compound |
| CN104910084A (zh) * | 2015-07-13 | 2015-09-16 | 佛山市赛维斯医药科技有限公司 | 末端胺基取代的三氮唑亚砜类化合物、其制备方法及其用途 |
| CN104910083A (zh) * | 2015-07-13 | 2015-09-16 | 佛山市赛维斯医药科技有限公司 | 烷氧苯基三氮唑亚砜类11β-HSD1抑制剂、制备方法及其用途 |
| EP3235813A1 (en) | 2016-04-19 | 2017-10-25 | Cidqo 2012, S.L. | Aza-tetra-cyclo derivatives |
| CN111655687A (zh) * | 2017-09-08 | 2020-09-11 | Pi工业有限公司 | 新型杀真菌杂环化合物 |
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| US7754709B2 (en) * | 2003-06-10 | 2010-07-13 | Solvay Pharmaceuticals Bv | Tetracyclic thiophenepyrimidinone compounds as inhibitors of 17β hydroxysteroid dehydrogenase compounds |
| US20070231263A1 (en) | 2004-04-13 | 2007-10-04 | Jun Qiu | Human G protein-coupled receptor and modulators thereof for the treatment of hyperglycemia and related disorders |
| EP1637529A1 (en) * | 2004-09-20 | 2006-03-22 | 4Sc Ag | Novel piperidin-4-yl-thiazole-carboxamide analogues as inhibitors of T-cell proliferation and uses thereof |
| DE102006010923A1 (de) | 2006-03-09 | 2007-09-13 | Saltigo Gmbh | Verfahren zur Herstellung von Chlor-1,4-dimethoxybenzol |
| MX2008011696A (es) * | 2006-03-15 | 2008-11-12 | 4Sc Ag | Inhibidores de nf-kb heterociclicos novedosos. |
| CN101405278A (zh) * | 2006-03-15 | 2009-04-08 | 4Sc股份公司 | 新颖的杂环NF-κB抑制剂 |
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| EA201001737A1 (ru) | 2011-06-30 |
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| EA018920B1 (ru) | 2013-11-29 |
| EP2271405A2 (en) | 2011-01-12 |
| CN102015026B (zh) | 2015-11-25 |
| ES2432383T3 (es) | 2013-12-03 |
| JP2011521907A (ja) | 2011-07-28 |
| EP2271405B1 (en) | 2013-07-24 |
| CO6331305A2 (es) | 2011-10-20 |
| US20110060007A1 (en) | 2011-03-10 |
| EA201300759A1 (ru) | 2013-11-29 |
| AU2009243812A1 (en) | 2009-11-12 |
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