JP2008222714A5 - - Google Patents

Info

Publication number

JP2008222714A5

JP2008222714A5 JP2008054948A JP2008054948A JP2008222714A5 JP 2008222714 A5 JP2008222714 A5 JP 2008222714A5 JP 2008054948 A JP2008054948 A JP 2008054948A JP 2008054948 A JP2008054948 A JP 2008054948A JP 2008222714 A5 JP2008222714 A5 JP 2008222714A5

Authority

JP

Japan

Prior art keywords

group

different

alkyl group

same

substituted

Prior art date

2008-03-05

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 343
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 246
• -1 2-trifluoromethylphenyl Chemical group 0.000 claims 212
• 125000001424 substituent group Chemical group 0.000 claims 179
• 125000005843 halogen group Chemical group 0.000 claims 170
• 125000000623 heterocyclic group Chemical group 0.000 claims 149
• 125000003118 aryl group Chemical group 0.000 claims 120
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 112
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 99
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 96
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 91
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 91
• 229910052757 nitrogen Inorganic materials 0.000 claims 86
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 86
• 125000000753 cycloalkyl group Chemical group 0.000 claims 53
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 51
• FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 claims 45
• 239000003795 chemical substances by application Substances 0.000 claims 41
• 125000004043 oxo group Chemical group O=* 0.000 claims 34
• 230000001225 therapeutic effect Effects 0.000 claims 29
• 230000000069 prophylactic effect Effects 0.000 claims 22
• 239000008194 pharmaceutical composition Substances 0.000 claims 16
• 125000000217 alkyl group Chemical group 0.000 claims 14
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 12
• 239000003862 glucocorticoid Substances 0.000 claims 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 10
• 208000002249 Diabetes Complications Diseases 0.000 claims 9
• 206010012655 Diabetic complications Diseases 0.000 claims 9
• 208000031226 Hyperlipidaemia Diseases 0.000 claims 9
• 206010020772 Hypertension Diseases 0.000 claims 9
• 208000008589 Obesity Diseases 0.000 claims 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims 9
• 206010012601 diabetes mellitus Diseases 0.000 claims 9
• 125000002950 monocyclic group Chemical group 0.000 claims 9
• 235000020824 obesity Nutrition 0.000 claims 9
• 125000003944 tolyl group Chemical group 0.000 claims 9
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 8
• 150000001875 compounds Chemical class 0.000 claims 8
• 150000003839 salts Chemical class 0.000 claims 8
• 201000010099 disease Diseases 0.000 claims 7
• 230000002265 prevention Effects 0.000 claims 7
• 230000003449 preventive effect Effects 0.000 claims 7
• 125000003545 alkoxy group Chemical group 0.000 claims 6
• 125000004104 aryloxy group Chemical group 0.000 claims 6
• 125000004429 atom Chemical group 0.000 claims 6
• 239000008280 blood Substances 0.000 claims 6
• 210000004369 blood Anatomy 0.000 claims 6
• 229940126558 11β-HSD1 inhibitor Drugs 0.000 claims 5
• 208000032841 Bulimia Diseases 0.000 claims 3
• 206010006550 Bulimia nervosa Diseases 0.000 claims 3
• 208000027534 Emotional disease Diseases 0.000 claims 3
• 208000004930 Fatty Liver Diseases 0.000 claims 3
• 208000010412 Glaucoma Diseases 0.000 claims 3
• 206010019708 Hepatic steatosis Diseases 0.000 claims 3
• 206010022489 Insulin Resistance Diseases 0.000 claims 3
• 208000001145 Metabolic Syndrome Diseases 0.000 claims 3
• 208000001132 Osteoporosis Diseases 0.000 claims 3
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 3
• 239000002253 acid Substances 0.000 claims 3
• 208000010877 cognitive disease Diseases 0.000 claims 3
• 230000003247 decreasing effect Effects 0.000 claims 3
• 208000035475 disorder Diseases 0.000 claims 3
• 229940079593 drug Drugs 0.000 claims 3
• 239000003814 drug Substances 0.000 claims 3
• 230000001747 exhibiting effect Effects 0.000 claims 3
• 208000010706 fatty liver disease Diseases 0.000 claims 3
• 206010021654 increased appetite Diseases 0.000 claims 3
• 208000030159 metabolic disease Diseases 0.000 claims 3
• 208000010125 myocardial infarction Diseases 0.000 claims 3
• 230000004770 neurodegeneration Effects 0.000 claims 3
• 208000015122 neurodegenerative disease Diseases 0.000 claims 3
• 230000009251 neurologic dysfunction Effects 0.000 claims 3
• 208000015015 neurological dysfunction Diseases 0.000 claims 3
• 201000000980 schizophrenia Diseases 0.000 claims 3
• 231100000240 steatosis hepatitis Toxicity 0.000 claims 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 3
• 230000006441 vascular event Effects 0.000 claims 3
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
• LMQIMNGGVZHHNW-UHFFFAOYSA-N [3-(4-fluorophenyl)-3-(hydroxymethyl)pyrrolidin-1-yl]-[5-(1-methylcyclopropyl)-1-(1-pyrimidin-2-ylpiperidin-4-yl)pyrazol-4-yl]methanone;hydrochloride Chemical compound Cl.C1CC(CO)(C=2C=CC(F)=CC=2)CN1C(=O)C=1C=NN(C2CCN(CC2)C=2N=CC=CN=2)C=1C1(C)CC1 LMQIMNGGVZHHNW-UHFFFAOYSA-N 0.000 claims 2
• 125000002837 carbocyclic group Chemical group 0.000 claims 2
• 230000007170 pathology Effects 0.000 claims 2
• 229940037128 systemic glucocorticoids Drugs 0.000 claims 2
• AQPGDKRQVLWWOV-UHFFFAOYSA-N (2-chlorophenyl)-[4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidin-1-yl]methanone Chemical compound ClC1=CC=CC=C1C(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CC1 AQPGDKRQVLWWOV-UHFFFAOYSA-N 0.000 claims 1
• ZAGDEXKFNTYEPV-KUXBLMNESA-N (2s)-2-[[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidine-1-carbonyl]-methylamino]-3-methylbutanoic acid Chemical compound C1CN(C(=O)N(C)[C@@H](C(C)C)C(O)=O)CCC1N1C(C2CC2)=C(C(=O)N2CC(CC2)C=2C(=CC=CC=2)C(F)(F)F)C=N1 ZAGDEXKFNTYEPV-KUXBLMNESA-N 0.000 claims 1
• YUNYHVIUEFMSLM-UHFFFAOYSA-N (4-chlorophenyl)-[4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CC1 YUNYHVIUEFMSLM-UHFFFAOYSA-N 0.000 claims 1
• BPNDYJGZVPKAMM-UHFFFAOYSA-N (5-cyclopropyl-1-piperidin-4-ylpyrazol-4-yl)-(3-pyridin-3-ylpyrrolidin-1-yl)methanone Chemical compound C1=NN(C2CCNCC2)C(C2CC2)=C1C(=O)N(C1)CCC1C1=CC=CN=C1 BPNDYJGZVPKAMM-UHFFFAOYSA-N 0.000 claims 1
• WRLPAQVKZHWYMP-UHFFFAOYSA-N 1-[4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]phenyl]-3-methoxyurea Chemical compound C1=CC(NC(=O)NOC)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 WRLPAQVKZHWYMP-UHFFFAOYSA-N 0.000 claims 1
• OSETYOYQMMUJPR-UHFFFAOYSA-N 1-[4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidin-1-yl]-2-(4-fluorophenyl)ethanone Chemical compound C1=CC(F)=CC=C1CC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CC1 OSETYOYQMMUJPR-UHFFFAOYSA-N 0.000 claims 1
• VKXSPBNAHVAFJM-UHFFFAOYSA-N 1-[4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidin-1-yl]-2-phenoxyethanone Chemical compound C1CC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CCN1C(=O)COC1=CC=CC=C1 VKXSPBNAHVAFJM-UHFFFAOYSA-N 0.000 claims 1
• NOJVSTUCEBMSGK-UHFFFAOYSA-N 2-[3-(4-fluorophenyl)-1-[5-(1-methylcyclopropyl)-1-(1-pyrimidin-2-ylpiperidin-4-yl)pyrazole-4-carbonyl]pyrrolidin-3-yl]ethyl acetate;hydrochloride Chemical compound Cl.C1C(CCOC(=O)C)(C=2C=CC(F)=CC=2)CCN1C(=O)C(=C1C2(C)CC2)C=NN1C(CC1)CCN1C1=NC=CC=N1 NOJVSTUCEBMSGK-UHFFFAOYSA-N 0.000 claims 1
• NUPBAOHJXJSIKG-UHFFFAOYSA-N 3-[4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]phenyl]-1,3-oxazolidin-2-one Chemical compound FC(F)(F)C1=CC=CC=C1C1CN(C(=O)C2=C(N(C3CCN(CC3)C=3C=CC(=CC=3)N3C(OCC3)=O)N=C2)C2CC2)CC1 NUPBAOHJXJSIKG-UHFFFAOYSA-N 0.000 claims 1
• COXCQWZOTQRMNB-UHFFFAOYSA-N 3-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(N2CCC(CC2)N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)=C1 COXCQWZOTQRMNB-UHFFFAOYSA-N 0.000 claims 1
• RXEOIYYXBBSACI-UHFFFAOYSA-N 4-[4-[3-(2-chlorophenyl)pyrrolidine-1-carbonyl]-5-cyclopropylpyrazol-1-yl]-n-(2,4-difluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC(F)=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)Cl)C=N2)C2CC2)CC1 RXEOIYYXBBSACI-UHFFFAOYSA-N 0.000 claims 1
• KKGFIAWRPOKCSK-UHFFFAOYSA-N 4-[4-[3-(2-chloropyridin-3-yl)pyrrolidine-1-carbonyl]-5-cyclopropylpyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=NC=CC=3)Cl)C=N2)C2CC2)CC1 KKGFIAWRPOKCSK-UHFFFAOYSA-N 0.000 claims 1
• MNWGJQYOVJJJSC-UHFFFAOYSA-N 4-[4-[3-(2-cyanophenyl)pyrrolidine-1-carbonyl]-5-cyclopropylpyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C#N)C=N2)C2CC2)CC1 MNWGJQYOVJJJSC-UHFFFAOYSA-N 0.000 claims 1
• MKJBHIGXSMSJLY-UHFFFAOYSA-N 4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]-2,2-dimethyl-4-oxobutanoic acid Chemical compound C1CN(C(=O)CC(C)(C)C(O)=O)CCC1N1C(C2CC2)=C(C(=O)N2CC(CC2)C=2C(=CC=CC=2)C(F)(F)F)C=N1 MKJBHIGXSMSJLY-UHFFFAOYSA-N 0.000 claims 1
• IPMUCBQYRCXVFB-UHFFFAOYSA-N 4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 IPMUCBQYRCXVFB-UHFFFAOYSA-N 0.000 claims 1
• BPKQAGPZDMDPKM-UHFFFAOYSA-N 4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 BPKQAGPZDMDPKM-UHFFFAOYSA-N 0.000 claims 1
• IRNOWNPCLJYZNF-UHFFFAOYSA-N 4-[5-(1-methylcyclopropyl)-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-propan-2-yloxypiperidine-1-carboxamide Chemical compound C1CN(C(=O)NOC(C)C)CCC1N1C(C2(C)CC2)=C(C(=O)N2CC(CC2)C=2C(=CC=CC=2)C(F)(F)F)C=N1 IRNOWNPCLJYZNF-UHFFFAOYSA-N 0.000 claims 1
• OBCUFIVKQNXJHT-UHFFFAOYSA-N 4-[5-cyclohexyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CCCCC2)CC1 OBCUFIVKQNXJHT-UHFFFAOYSA-N 0.000 claims 1
• WOFZDCPBYGVHFK-UHFFFAOYSA-N 4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CC1 WOFZDCPBYGVHFK-UHFFFAOYSA-N 0.000 claims 1
• JOYJKJFLYSSISU-UHFFFAOYSA-N 4-[5-cyclopropyl-4-[3-(1,3-thiazol-2-yl)pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3SC=CN=3)C=N2)C2CC2)CC1 JOYJKJFLYSSISU-UHFFFAOYSA-N 0.000 claims 1
• LSKLPADXHVDMSO-UHFFFAOYSA-N 4-[5-cyclopropyl-4-[3-[2-(trifluoromethoxy)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound FC1=CC=CC=C1NC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)OC(F)(F)F)C=N2)C2CC2)CC1 LSKLPADXHVDMSO-UHFFFAOYSA-N 0.000 claims 1
• MROMMQDPVFYEDQ-UHFFFAOYSA-N 4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-(1,3-thiazol-2-yl)piperidine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1C1CN(C(=O)C2=C(N(C3CCN(CC3)C(=O)NC=3SC=CN=3)N=C2)C2CC2)CC1 MROMMQDPVFYEDQ-UHFFFAOYSA-N 0.000 claims 1
• XXWWSKPRLZNFPF-UHFFFAOYSA-N 4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-(2,6-dichloropyridin-3-yl)piperidine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1C1CN(C(=O)C2=C(N(C3CCN(CC3)C(=O)NC=3C(=NC(Cl)=CC=3)Cl)N=C2)C2CC2)CC1 XXWWSKPRLZNFPF-UHFFFAOYSA-N 0.000 claims 1
• QJGXJERKTLAKSA-UHFFFAOYSA-N 4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-[(4-fluorophenyl)methyl]piperidine-1-carboxamide Chemical compound C1=CC(F)=CC=C1CNC(=O)N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 QJGXJERKTLAKSA-UHFFFAOYSA-N 0.000 claims 1
• PSXBRDJWUSCHGZ-UHFFFAOYSA-N 4-[5-cyclopropyl-4-[3-methoxy-3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]-n-(2-fluorophenyl)piperidine-1-carboxamide Chemical compound C1C(OC)(C=2C(=CC=CC=2)C(F)(F)F)CCN1C(=O)C(=C1C2CC2)C=NN1C(CC1)CCN1C(=O)NC1=CC=CC=C1F PSXBRDJWUSCHGZ-UHFFFAOYSA-N 0.000 claims 1
• CRYVTOJUPAAIDH-UHFFFAOYSA-N 5-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 CRYVTOJUPAAIDH-UHFFFAOYSA-N 0.000 claims 1
• WJILLQIANBXGHG-UHFFFAOYSA-N 6-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]pyridine-3-carbonitrile Chemical compound FC(F)(F)C1=CC=CC=C1C1CN(C(=O)C2=C(N(C3CCN(CC3)C=3N=CC(=CC=3)C#N)N=C2)C2CC2)CC1 WJILLQIANBXGHG-UHFFFAOYSA-N 0.000 claims 1
• OMSVJBDARAZOIZ-UHFFFAOYSA-N 6-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 OMSVJBDARAZOIZ-UHFFFAOYSA-N 0.000 claims 1
• OUEUBSANRTXAEA-YZOIIVLCSA-N C1CC(C=2C(=CC=CC=2)C(F)(F)F)CN1C(=O)C=1C=NN([C@@H]2CC[C@H](CC2)C(=O)NC=2C(=CC=CC=2)F)C=1C1(C)CC1 Chemical compound C1CC(C=2C(=CC=CC=2)C(F)(F)F)CN1C(=O)C=1C=NN([C@@H]2CC[C@H](CC2)C(=O)NC=2C(=CC=CC=2)F)C=1C1(C)CC1 OUEUBSANRTXAEA-YZOIIVLCSA-N 0.000 claims 1
• CXGUYDCRKBQRIN-AZMKCDNPSA-N C1C[C@@H](C(=O)N(C)[C@@H](C(C)C)C(O)=O)CC[C@@H]1N1C(C2CC2)=C(C(=O)N2CC(CC2)C=2C(=CC=CC=2)C(F)(F)F)C=N1 Chemical compound C1C[C@@H](C(=O)N(C)[C@@H](C(C)C)C(O)=O)CC[C@@H]1N1C(C2CC2)=C(C(=O)N2CC(CC2)C=2C(=CC=CC=2)C(F)(F)F)C=N1 CXGUYDCRKBQRIN-AZMKCDNPSA-N 0.000 claims 1
• 239000005973 Carvone Substances 0.000 claims 1
• QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 1
• YNBADRVTZLEFNH-UHFFFAOYSA-N Methyl nicotinate Natural products COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 claims 1
• DVKULAOXGFCYNI-UHFFFAOYSA-N [1-[1-(2,3-dihydro-1,4-oxazine-4-carbonyl)piperidin-4-yl]-5-(1-methylcyclopropyl)pyrazol-4-yl]-(3-pyridin-3-ylpyrrolidin-1-yl)methanone Chemical compound C1CC(C=2C=NC=CC=2)CN1C(=O)C=1C=NN(C2CCN(CC2)C(=O)N2C=COCC2)C=1C1(C)CC1 DVKULAOXGFCYNI-UHFFFAOYSA-N 0.000 claims 1
• FVAFVJJHEGGRNI-UHFFFAOYSA-N [1-[1-(2,3-dihydroindole-1-carbonyl)piperidin-4-yl]-5-(1-methylcyclopropyl)pyrazol-4-yl]-(3-pyridin-3-ylpyrrolidin-1-yl)methanone Chemical compound C1CC(C=2C=NC=CC=2)CN1C(=O)C=1C=NN(C2CCN(CC2)C(=O)N2C3=CC=CC=C3CC2)C=1C1(C)CC1 FVAFVJJHEGGRNI-UHFFFAOYSA-N 0.000 claims 1
• TXBPMGSICQMVFB-UHFFFAOYSA-N [1-[1-(3-chloropyridin-2-yl)piperidin-4-yl]-5-cyclopropylpyrazol-4-yl]-(3-pyridin-3-ylpyrrolidin-1-yl)methanone Chemical compound ClC1=CC=CN=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CC1 TXBPMGSICQMVFB-UHFFFAOYSA-N 0.000 claims 1
• QZTHMVJGDFRLLH-UHFFFAOYSA-N [1-[1-(4-aminophenyl)piperidin-4-yl]-5-cyclopropylpyrazol-4-yl]-[3-[2-(trifluoromethyl)phenyl]pyrrolidin-1-yl]methanone Chemical compound C1=CC(N)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 QZTHMVJGDFRLLH-UHFFFAOYSA-N 0.000 claims 1
• VLNZYQMAUJZRJG-UHFFFAOYSA-N [1-[1-(5-chloropyridin-2-yl)piperidin-4-yl]-5-(1-methylcyclopropyl)pyrazol-4-yl]-[3-(methoxymethyl)-3-phenylpyrrolidin-1-yl]methanone Chemical compound C1C(COC)(C=2C=CC=CC=2)CCN1C(=O)C(=C1C2(C)CC2)C=NN1C(CC1)CCN1C1=CC=C(Cl)C=N1 VLNZYQMAUJZRJG-UHFFFAOYSA-N 0.000 claims 1
• IOYKDRALVOIDLE-UHFFFAOYSA-N [1-[1-(benzenesulfonyl)piperidin-4-yl]-5-cyclopropylpyrazol-4-yl]-(3-pyridin-3-ylpyrrolidin-1-yl)methanone Chemical compound C1=NN(C2CCN(CC2)S(=O)(=O)C=2C=CC=CC=2)C(C2CC2)=C1C(=O)N(C1)CCC1C1=CC=CN=C1 IOYKDRALVOIDLE-UHFFFAOYSA-N 0.000 claims 1
• KXYZORBYABXTLK-UHFFFAOYSA-N [1-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-5-(1-methylcyclopropyl)pyrazol-4-yl]-[3-[2-(trifluoromethyl)phenyl]pyrrolidin-1-yl]methanone;hydrochloride Chemical compound Cl.C1CC(C=2C(=CC=CC=2)C(F)(F)F)CN1C(=O)C=1C=NN(C2CCN(CC=3C=CC(F)=CC=3)CC2)C=1C1(C)CC1 KXYZORBYABXTLK-UHFFFAOYSA-N 0.000 claims 1
• CKQQJQKBFIBSGD-UHFFFAOYSA-N [3-(3,5-difluorophenyl)-3-(hydroxymethyl)pyrrolidin-1-yl]-[5-(1-methylcyclopropyl)-1-(1-pyrimidin-2-ylpiperidin-4-yl)pyrazol-4-yl]methanone;hydrochloride Chemical compound Cl.C1CC(CO)(C=2C=C(F)C=C(F)C=2)CN1C(=O)C=1C=NN(C2CCN(CC2)C=2N=CC=CN=2)C=1C1(C)CC1 CKQQJQKBFIBSGD-UHFFFAOYSA-N 0.000 claims 1
• KOVKIVLDEYVCLM-UHFFFAOYSA-N [3-(hydroxymethyl)-3-phenylpyrrolidin-1-yl]-[1-[1-(4-methoxypyrimidin-2-yl)piperidin-4-yl]-5-(1-methylcyclopropyl)pyrazol-4-yl]methanone;hydrochloride Chemical compound Cl.COC1=CC=NC(N2CCC(CC2)N2C(=C(C(=O)N3CC(CO)(CC3)C=3C=CC=CC=3)C=N2)C2(C)CC2)=N1 KOVKIVLDEYVCLM-UHFFFAOYSA-N 0.000 claims 1
• NHYWTTISXCLLRD-UHFFFAOYSA-N [3-[2-(hydroxymethyl)phenyl]pyrrolidin-1-yl]-[5-(1-methylcyclopropyl)-1-(1-pyrimidin-2-ylpiperidin-4-yl)pyrazol-4-yl]methanone;hydrochloride Chemical compound Cl.C1CC(C=2C(=CC=CC=2)CO)CN1C(=O)C=1C=NN(C2CCN(CC2)C=2N=CC=CN=2)C=1C1(C)CC1 NHYWTTISXCLLRD-UHFFFAOYSA-N 0.000 claims 1
• XNVXYBPECKTOLO-UHFFFAOYSA-N [4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidin-1-yl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)N2CCC(CC2)N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)=C1 XNVXYBPECKTOLO-UHFFFAOYSA-N 0.000 claims 1
• BLELNBKYXMJVKK-UHFFFAOYSA-N [4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidin-1-yl]-[3-(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC=CC(C(=O)N2CCC(CC2)N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)=C1 BLELNBKYXMJVKK-UHFFFAOYSA-N 0.000 claims 1
• PPFRABASRVDSCT-UHFFFAOYSA-N [5-(1-methylcyclopropyl)-1-[1-(2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)piperidin-4-yl]pyrazol-4-yl]-(3-pyridin-3-ylpyrrolidin-1-yl)methanone Chemical compound C1CC(C=2C=NC=CC=2)CN1C(=O)C=1C=NN(C2CCN(CC2)C(=O)N2C3=CC=CC=C3CCCC2)C=1C1(C)CC1 PPFRABASRVDSCT-UHFFFAOYSA-N 0.000 claims 1
• BEFGBKYDQWNICH-UHFFFAOYSA-N [5-cyclopropyl-1-[1-[4-(hydroxymethyl)phenyl]piperidin-4-yl]pyrazol-4-yl]-[3-[2-(trifluoromethyl)phenyl]pyrrolidin-1-yl]methanone Chemical compound C1=CC(CO)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 BEFGBKYDQWNICH-UHFFFAOYSA-N 0.000 claims 1
• FLZPWMZOJKEUJE-UHFFFAOYSA-N [Na].FC1=CC(C(=O)O)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 Chemical compound [Na].FC1=CC(C(=O)O)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 FLZPWMZOJKEUJE-UHFFFAOYSA-N 0.000 claims 1
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 1
• MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims 1
• IROQJLUJFHKAKC-UHFFFAOYSA-N benzyl 4-[5-cyclopropyl-4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)pyrazol-1-yl]piperidine-1-carboxylate Chemical compound C1CC(N2C(=C(C(=O)N3CC(CC3)C=3C=NC=CC=3)C=N2)C2CC2)CCN1C(=O)OCC1=CC=CC=C1 IROQJLUJFHKAKC-UHFFFAOYSA-N 0.000 claims 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 claims 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
• WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical group CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 claims 1
• 229940095102 methyl benzoate Drugs 0.000 claims 1
• 229960001238 methylnicotinate Drugs 0.000 claims 1
• OQYGSZCTJCUOBF-UHFFFAOYSA-N n-(2-fluorophenyl)-4-[4-(3-pyridin-3-ylpyrrolidine-1-carbonyl)-5-(2,2,3,3-tetramethylcyclopropyl)pyrazol-1-yl]piperidine-1-carboxamide Chemical compound CC1(C)C(C)(C)C1C1=C(C(=O)N2CC(CC2)C=2C=NC=CC=2)C=NN1C1CCN(C(=O)NC=2C(=CC=CC=2)F)CC1 OQYGSZCTJCUOBF-UHFFFAOYSA-N 0.000 claims 1
• YSQKRUQUNNRNRV-UHFFFAOYSA-N n-(2-fluorophenyl)-4-[5-(1-methoxycyclopropyl)-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidine-1-carboxamide Chemical compound C1CC(C=2C(=CC=CC=2)C(F)(F)F)CN1C(=O)C=1C=NN(C2CCN(CC2)C(=O)NC=2C(=CC=CC=2)F)C=1C1(OC)CC1 YSQKRUQUNNRNRV-UHFFFAOYSA-N 0.000 claims 1
• AKQHEYHIJDBVRK-UHFFFAOYSA-N n-(2-fluorophenyl)-4-[5-(1-methylcyclopropyl)-4-[3-phenyl-3-(trifluoromethyl)pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidine-1-carboxamide Chemical compound C1CC(C(F)(F)F)(C=2C=CC=CC=2)CN1C(=O)C=1C=NN(C2CCN(CC2)C(=O)NC=2C(=CC=CC=2)F)C=1C1(C)CC1 AKQHEYHIJDBVRK-UHFFFAOYSA-N 0.000 claims 1
• UCHPKEPCLLOVFY-UHFFFAOYSA-N n-(2-fluorophenyl)-4-[5-[1-(hydroxymethyl)cyclopropyl]-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidine-1-carboxamide Chemical compound C1CC(C=2C(=CC=CC=2)C(F)(F)F)CN1C(=O)C=1C=NN(C2CCN(CC2)C(=O)NC=2C(=CC=CC=2)F)C=1C1(CO)CC1 UCHPKEPCLLOVFY-UHFFFAOYSA-N 0.000 claims 1
• IOUGUUXDFKCDEJ-UHFFFAOYSA-N n-[4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 IOUGUUXDFKCDEJ-UHFFFAOYSA-N 0.000 claims 1
• LVUIACPDMJDVCF-UHFFFAOYSA-N n-[4-[4-[5-cyclopropyl-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidin-1-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1N1CCC(N2C(=C(C(=O)N3CC(CC3)C=3C(=CC=CC=3)C(F)(F)F)C=N2)C2CC2)CC1 LVUIACPDMJDVCF-UHFFFAOYSA-N 0.000 claims 1
• DBPMNODCZTWFCL-UHFFFAOYSA-N n-ethoxy-4-[5-(1-methylcyclopropyl)-4-[3-[2-(trifluoromethyl)phenyl]pyrrolidine-1-carbonyl]pyrazol-1-yl]piperidine-1-carboxamide Chemical compound C1CN(C(=O)NOCC)CCC1N1C(C2(C)CC2)=C(C(=O)N2CC(CC2)C=2C(=CC=CC=2)C(F)(F)F)C=N1 DBPMNODCZTWFCL-UHFFFAOYSA-N 0.000 claims 1
• 230000001575 pathological effect Effects 0.000 claims 1