JP2018532778A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018532778A5 JP2018532778A5 JP2018541471A JP2018541471A JP2018532778A5 JP 2018532778 A5 JP2018532778 A5 JP 2018532778A5 JP 2018541471 A JP2018541471 A JP 2018541471A JP 2018541471 A JP2018541471 A JP 2018541471A JP 2018532778 A5 JP2018532778 A5 JP 2018532778A5
- Authority
- JP
- Japan
- Prior art keywords
- aryl
- alkyl
- azabicyclo
- hexane
- ylethynyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 —OH Chemical group 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000002837 carbocyclic group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 239000012458 free base Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims description 4
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 230000009206 glutamatergic signaling Effects 0.000 claims description 4
- 125000005253 heteroarylacyl group Chemical group 0.000 claims description 4
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 3
- RRFMTSWDQMYXBG-UHFFFAOYSA-N (2-chlorophenyl)-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC1=C(C=CC=C1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 RRFMTSWDQMYXBG-UHFFFAOYSA-N 0.000 claims description 2
- BYYURKCCSXKSEA-UHFFFAOYSA-N (3-chlorophenyl)-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC=1C=C(C=CC=1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 BYYURKCCSXKSEA-UHFFFAOYSA-N 0.000 claims description 2
- ZGWFIZXNWYZIIW-UHFFFAOYSA-N (3-chlorophenyl)-[1-(2-pyrimidin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC=1C=C(C=CC=1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=N1 ZGWFIZXNWYZIIW-UHFFFAOYSA-N 0.000 claims description 2
- JZAOWBFWHIBGBX-UHFFFAOYSA-N (3-chlorophenyl)-[1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC=1C=C(C=CC=1)C(=O)N1CC2(CC2C1)C#CC=1N=C(SC=1)C JZAOWBFWHIBGBX-UHFFFAOYSA-N 0.000 claims description 2
- SRKDGOFYDUMUQM-UHFFFAOYSA-N (3-fluorophenyl)-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound FC=1C=C(C=CC=1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 SRKDGOFYDUMUQM-UHFFFAOYSA-N 0.000 claims description 2
- LQHJNSXNAFLXGX-UHFFFAOYSA-N (3-fluorophenyl)-[1-[2-(6-methylpyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound FC=1C=C(C=CC=1)C(=O)N1CC2(CC2C1)C#CC1=NC(=CC=C1)C LQHJNSXNAFLXGX-UHFFFAOYSA-N 0.000 claims description 2
- FTRRTKIOAAHQNS-UHFFFAOYSA-N (4-chlorophenyl)-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC1=CC=C(C=C1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 FTRRTKIOAAHQNS-UHFFFAOYSA-N 0.000 claims description 2
- YERWDFNZJKSTHI-UHFFFAOYSA-N (4-chloropyridin-2-yl)-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC1=CC(=NC=C1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 YERWDFNZJKSTHI-UHFFFAOYSA-N 0.000 claims description 2
- VXECEOVRTRIWBW-UHFFFAOYSA-N (6-chloropyridin-3-yl)-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound ClC1=CC=C(C=N1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 VXECEOVRTRIWBW-UHFFFAOYSA-N 0.000 claims description 2
- GHPGNSRANXVTCZ-UHFFFAOYSA-N 1-(2-pyridin-2-ylethynyl)-3-[4-(trifluoromethoxy)phenyl]-3-azabicyclo[3.1.0]hexane Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C1=CC=C(C=C1)OC(F)(F)F GHPGNSRANXVTCZ-UHFFFAOYSA-N 0.000 claims description 2
- PYKGETOIFSHXNK-UHFFFAOYSA-N 1-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]pentan-1-one Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C(CCCC)=O PYKGETOIFSHXNK-UHFFFAOYSA-N 0.000 claims description 2
- YHUAGAGVBHHASJ-UHFFFAOYSA-N 1-[1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]pentan-1-one Chemical compound CC=1SC=C(N=1)C#CC12CN(CC2C1)C(CCCC)=O YHUAGAGVBHHASJ-UHFFFAOYSA-N 0.000 claims description 2
- HOUHCIQJQCZGDU-UHFFFAOYSA-N 1-[1-[2-(6-chloropyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methylpropan-1-one Chemical compound ClC1=CC=CC(=N1)C#CC12CN(CC2C1)C(C(C)C)=O HOUHCIQJQCZGDU-UHFFFAOYSA-N 0.000 claims description 2
- KNDOFIXPZYCNLL-UHFFFAOYSA-N 2,2-dimethyl-1-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one Chemical compound CC(C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1)(C)C KNDOFIXPZYCNLL-UHFFFAOYSA-N 0.000 claims description 2
- SDXHWDHDPNOTOM-UHFFFAOYSA-N 2,2-dimethyl-1-[1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one Chemical compound CC(C(=O)N1CC2(CC2C1)C#CC=1N=C(SC=1)C)(C)C SDXHWDHDPNOTOM-UHFFFAOYSA-N 0.000 claims description 2
- XYZWHNNWYMUKOW-UHFFFAOYSA-N 2-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]pyridine-4-carbonitrile Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C=1C=C(C#N)C=CN=1 XYZWHNNWYMUKOW-UHFFFAOYSA-N 0.000 claims description 2
- RWCNOTNVDWUPDK-UHFFFAOYSA-N 2-methyl-1-[1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one Chemical compound CC(C(=O)N1CC2(CC2C1)C#CC=1N=C(SC=1)C)C RWCNOTNVDWUPDK-UHFFFAOYSA-N 0.000 claims description 2
- FIAAAJATPWDIEE-UHFFFAOYSA-N 2-methyl-1-[1-[2-(6-methylpyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one Chemical compound CC(C(=O)N1CC2(CC2C1)C#CC1=NC(=CC=C1)C)C FIAAAJATPWDIEE-UHFFFAOYSA-N 0.000 claims description 2
- WOYWTLBNAYSLEE-UHFFFAOYSA-N 2-phenyl-1-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]ethanone Chemical compound C1(=CC=CC=C1)CC(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 WOYWTLBNAYSLEE-UHFFFAOYSA-N 0.000 claims description 2
- SYCIGOMQMSVQPB-UHFFFAOYSA-N 3-(2-chlorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC1=C(C=CC=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1 SYCIGOMQMSVQPB-UHFFFAOYSA-N 0.000 claims description 2
- XRTOCUTVIAEUHK-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfonyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC1=C(C=CC=C1)S(=O)(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 XRTOCUTVIAEUHK-UHFFFAOYSA-N 0.000 claims description 2
- NRLMOBIDIVRKGO-UHFFFAOYSA-N 3-(2-fluorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC1=C(C=CC=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1 NRLMOBIDIVRKGO-UHFFFAOYSA-N 0.000 claims description 2
- WNPNSGRJGZAXDD-UHFFFAOYSA-N 3-(2-fluorophenyl)sulfonyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC1=C(C=CC=C1)S(=O)(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 WNPNSGRJGZAXDD-UHFFFAOYSA-N 0.000 claims description 2
- VOOLGEDNKZKXCN-UHFFFAOYSA-N 3-(3,5-difluorophenyl)-1-(2-pyrimidin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC=1C=C(C=C(C=1)F)N1CC2(CC2C1)C#CC1=NC=CC=N1 VOOLGEDNKZKXCN-UHFFFAOYSA-N 0.000 claims description 2
- IJRRLBIJFYZFRM-UHFFFAOYSA-N 3-(3-chloro-5-fluorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC=1C=C(C=C(C=1)F)N1CC2(CC2C1)C#CC1=NC=CC=C1 IJRRLBIJFYZFRM-UHFFFAOYSA-N 0.000 claims description 2
- YAGQUOVWLDODNN-UHFFFAOYSA-N 3-(3-chlorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC=1C=C(C=CC=1)N1CC2(CC2C1)C#CC1=NC=CC=C1 YAGQUOVWLDODNN-UHFFFAOYSA-N 0.000 claims description 2
- OUTMSFPFCKZTNU-UHFFFAOYSA-N 3-(3-chlorophenyl)sulfonyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC=1C=C(C=CC=1)S(=O)(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 OUTMSFPFCKZTNU-UHFFFAOYSA-N 0.000 claims description 2
- PSMGEHUVWDNIKB-UHFFFAOYSA-N 3-(3-fluorophenyl)-1-(2-pyrimidin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC=1C=C(C=CC=1)N1CC2(CC2C1)C#CC1=NC=CC=N1 PSMGEHUVWDNIKB-UHFFFAOYSA-N 0.000 claims description 2
- YXUHFVOJNORMBN-UHFFFAOYSA-N 3-(4-chloro-2-fluorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC1=CC(=C(C=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1)F YXUHFVOJNORMBN-UHFFFAOYSA-N 0.000 claims description 2
- UFCMTQUQWOJROL-UHFFFAOYSA-N 3-(4-chloro-3-fluorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC1=C(C=C(C=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1)F UFCMTQUQWOJROL-UHFFFAOYSA-N 0.000 claims description 2
- NQSKTONEMVXXOY-UHFFFAOYSA-N 3-(4-chlorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC1=CC=C(C=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1 NQSKTONEMVXXOY-UHFFFAOYSA-N 0.000 claims description 2
- ONEXZYXQYWFFHK-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfonyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound ClC1=CC=C(C=C1)S(=O)(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 ONEXZYXQYWFFHK-UHFFFAOYSA-N 0.000 claims description 2
- ZFMQREIRKVLANR-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC1=CC=C(C=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1 ZFMQREIRKVLANR-UHFFFAOYSA-N 0.000 claims description 2
- HDFOBEKQKLSNKC-UHFFFAOYSA-N 3-(4-methylphenyl)sulfonyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)S(=O)(=O)C1=CC=C(C)C=C1 HDFOBEKQKLSNKC-UHFFFAOYSA-N 0.000 claims description 2
- GLQMDADCZCMFFM-UHFFFAOYSA-N 3-(5-fluoropyridin-2-yl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC=1C=CC(=NC=1)N1CC2(CC2C1)C#CC1=NC=CC=C1 GLQMDADCZCMFFM-UHFFFAOYSA-N 0.000 claims description 2
- AGZMRMJGSWURSB-UHFFFAOYSA-N 3-(5-fluoropyridin-3-yl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC=1C=C(C=NC=1)N1CC2(CC2C1)C#CC1=NC=CC=C1 AGZMRMJGSWURSB-UHFFFAOYSA-N 0.000 claims description 2
- BGDPWJGYSUFIEL-UHFFFAOYSA-N 3-(5-fluoropyridin-3-yl)-1-[2-(6-methylpyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexane Chemical compound FC=1C=C(C=NC=1)N1CC2(CC2C1)C#CC1=NC(=CC=C1)C BGDPWJGYSUFIEL-UHFFFAOYSA-N 0.000 claims description 2
- UYTXNBPVMVNBSF-UHFFFAOYSA-N 3-(benzenesulfonyl)-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 UYTXNBPVMVNBSF-UHFFFAOYSA-N 0.000 claims description 2
- AFXIRFMTXCQKKT-UHFFFAOYSA-N 3-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C=1C=C(C#N)C=CC=1 AFXIRFMTXCQKKT-UHFFFAOYSA-N 0.000 claims description 2
- QTCJDVUVURTYLI-UHFFFAOYSA-N 3-[1-(6-chloropyridin-2-yl)-3-azabicyclo[3.1.0]hexan-3-yl]-5-fluorobenzonitrile Chemical compound ClC1=CC=CC(=N1)C12CN(CC2C1)C=1C=C(C#N)C=C(C=1)F QTCJDVUVURTYLI-UHFFFAOYSA-N 0.000 claims description 2
- JFDIGROWXYPVSN-UHFFFAOYSA-N 3-[1-[2-(2-chloropyridin-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]-5-fluorobenzonitrile Chemical compound ClC1=NC=CC(=C1)C#CC12CN(CC2C1)C=1C=C(C#N)C=C(C=1)F JFDIGROWXYPVSN-UHFFFAOYSA-N 0.000 claims description 2
- HVIXKKSJSQREQX-UHFFFAOYSA-N 3-[1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound CC=1SC=C(N=1)C#CC12CN(CC2C1)C=1C=C(C#N)C=CC=1 HVIXKKSJSQREQX-UHFFFAOYSA-N 0.000 claims description 2
- DNZRWRRBOIRHMR-UHFFFAOYSA-N 3-fluoro-5-[1-(2-pyrazin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC1=NC=CN=C1 DNZRWRRBOIRHMR-UHFFFAOYSA-N 0.000 claims description 2
- ZRHOWJQJWAXAEO-UHFFFAOYSA-N 3-fluoro-5-[1-(2-pyridazin-3-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC=1N=NC=CC=1 ZRHOWJQJWAXAEO-UHFFFAOYSA-N 0.000 claims description 2
- MYRISJLONLWHHS-UHFFFAOYSA-N 3-fluoro-5-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC1=NC=CC=C1 MYRISJLONLWHHS-UHFFFAOYSA-N 0.000 claims description 2
- MQSBPWIUYOVKER-UHFFFAOYSA-N 3-fluoro-5-[1-(2-pyrimidin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC1=NC=CC=N1 MQSBPWIUYOVKER-UHFFFAOYSA-N 0.000 claims description 2
- XMPKOXXFXCWCKK-UHFFFAOYSA-N 3-fluoro-5-[1-[2-(3-methylpyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC1=NC=CC=C1C XMPKOXXFXCWCKK-UHFFFAOYSA-N 0.000 claims description 2
- SSYWUXQEVWAUOJ-UHFFFAOYSA-N 3-fluoro-5-[1-[2-(6-methoxypyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC1=NC(=CC=C1)OC SSYWUXQEVWAUOJ-UHFFFAOYSA-N 0.000 claims description 2
- HLGIZZGDYBBSDK-UHFFFAOYSA-N 3-fluoro-5-[1-[2-(6-methylpyridin-2-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC1=NC(=CC=C1)C HLGIZZGDYBBSDK-UHFFFAOYSA-N 0.000 claims description 2
- HDHOKSYAKLYHJG-UHFFFAOYSA-N 3-phenyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1(=CC=CC=C1)N1CC2(CC2C1)C#CC1=NC=CC=C1 HDHOKSYAKLYHJG-UHFFFAOYSA-N 0.000 claims description 2
- FKCBQFJVQSSHAT-UHFFFAOYSA-N 3-phenyl-1-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one Chemical compound C1(=CC=CC=C1)CCC(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 FKCBQFJVQSSHAT-UHFFFAOYSA-N 0.000 claims description 2
- YMKCZBJXPRPWHM-UHFFFAOYSA-N 5-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]-1H-pyrrolo[3,2-b]pyridine Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C1=CC=C2C(=N1)C=CN2 YMKCZBJXPRPWHM-UHFFFAOYSA-N 0.000 claims description 2
- BGSKVWVDJKOOSX-UHFFFAOYSA-N 5-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]pyridine-3-carbonitrile Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C=1C=NC=C(C#N)C=1 BGSKVWVDJKOOSX-UHFFFAOYSA-N 0.000 claims description 2
- BKFNCMLPOXWWPA-UHFFFAOYSA-N 6-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]-1H-benzimidazole Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C1=CC2=C(NC=N2)C=C1 BKFNCMLPOXWWPA-UHFFFAOYSA-N 0.000 claims description 2
- XMCJUZFGBVIQAZ-UHFFFAOYSA-N 6-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]pyridine-2-carbonitrile Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C1=CC=CC(=N1)C#N XMCJUZFGBVIQAZ-UHFFFAOYSA-N 0.000 claims description 2
- KNVJEGFZKYDKOG-UHFFFAOYSA-N N-phenyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane-3-carboxamide Chemical compound C1(=CC=CC=C1)NC(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 KNVJEGFZKYDKOG-UHFFFAOYSA-N 0.000 claims description 2
- UTXXSRYBIHMOEX-UHFFFAOYSA-N N-propyl-1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane-3-carboxamide Chemical compound C(CC)NC(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 UTXXSRYBIHMOEX-UHFFFAOYSA-N 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- ZMXUAIRHMHNJAP-UHFFFAOYSA-N [1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]-pyrrolidin-1-ylmethanone Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C(=O)N1CCCC1 ZMXUAIRHMHNJAP-UHFFFAOYSA-N 0.000 claims description 2
- VFHBDJCTGFMCHH-UHFFFAOYSA-N [1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]-phenylmethanone Chemical compound CC=1SC=C(N=1)C#CC12CN(CC2C1)C(=O)C1=CC=CC=C1 VFHBDJCTGFMCHH-UHFFFAOYSA-N 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- VAHAAQYWELLYKU-UHFFFAOYSA-N cyclopentyl-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound C1(CCCC1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 VAHAAQYWELLYKU-UHFFFAOYSA-N 0.000 claims description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
- CDYBKLVRQVMILH-UHFFFAOYSA-N phenyl-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound C1(=CC=CC=C1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 CDYBKLVRQVMILH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- YIFPYFXMUJGFCQ-UHFFFAOYSA-N pyridin-2-yl-[1-(2-pyridin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound N1=C(C=CC=C1)C(=O)N1CC2(CC2C1)C#CC1=NC=CC=C1 YIFPYFXMUJGFCQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 210000001635 urinary tract Anatomy 0.000 claims description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 6
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- ZRFXAOXSSXSMRI-UHFFFAOYSA-N 2-ethylpentanamide Chemical compound CCCC(CC)C(N)=O ZRFXAOXSSXSMRI-UHFFFAOYSA-N 0.000 claims 1
- HZRPHMRGXSPNRZ-UHFFFAOYSA-N 1-(2-pyridin-2-ylethynyl)-N-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexane-3-carboxamide Chemical compound N1=C(C=CC=C1)C#CC12CN(CC2C1)C(=O)NCC(F)(F)F HZRPHMRGXSPNRZ-UHFFFAOYSA-N 0.000 description 1
- LMNFJRMHHMMNSR-UHFFFAOYSA-N 3-(5-fluoropyridin-3-yl)-1-(2-pyrimidin-2-ylethynyl)-3-azabicyclo[3.1.0]hexane Chemical compound FC=1C=C(C=NC=1)N1CC2(CC2C1)C#CC1=NC=CC=N1 LMNFJRMHHMMNSR-UHFFFAOYSA-N 0.000 description 1
- IKUDBSKONSPSTH-UHFFFAOYSA-N 3-[1-(2-pyrimidin-2-ylethynyl)-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound N1=C(N=CC=C1)C#CC12CN(CC2C1)C=1C=C(C#N)C=CC=1 IKUDBSKONSPSTH-UHFFFAOYSA-N 0.000 description 1
- RRHPYFZXFIMESU-UHFFFAOYSA-N 3-fluoro-5-[1-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)N1CC2(CC2C1)C#CC=1N=C(SC=1)C RRHPYFZXFIMESU-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510713865.7 | 2015-10-28 | ||
| CN201510713865.7A CN106632243B (zh) | 2015-10-28 | 2015-10-28 | 吡咯烷衍生物 |
| PCT/CN2016/102946 WO2017071536A1 (en) | 2015-10-28 | 2016-10-21 | Pyrrolidine derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018532778A JP2018532778A (ja) | 2018-11-08 |
| JP2018532778A5 true JP2018532778A5 (enExample) | 2019-12-05 |
| JP6877771B2 JP6877771B2 (ja) | 2021-05-26 |
Family
ID=58629839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018541471A Active JP6877771B2 (ja) | 2015-10-28 | 2016-10-21 | ピロリジン誘導体 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US10328054B2 (enExample) |
| EP (1) | EP3371163B1 (enExample) |
| JP (1) | JP6877771B2 (enExample) |
| KR (1) | KR102815874B1 (enExample) |
| CN (2) | CN106632243B (enExample) |
| AU (1) | AU2016345244B2 (enExample) |
| BR (1) | BR112018008204B1 (enExample) |
| CA (1) | CA3000794C (enExample) |
| DK (1) | DK3371163T3 (enExample) |
| ES (1) | ES2922978T3 (enExample) |
| HU (1) | HUE058899T2 (enExample) |
| IL (1) | IL258517B (enExample) |
| MX (1) | MX385587B (enExample) |
| RU (1) | RU2740019C1 (enExample) |
| TW (1) | TWI725998B (enExample) |
| WO (1) | WO2017071536A1 (enExample) |
| ZA (1) | ZA201802235B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3052485T3 (pl) | 2013-10-04 | 2022-02-28 | Infinity Pharmaceuticals, Inc. | Związki heterocykliczne i ich zastosowania |
| CA2943075C (en) | 2014-03-19 | 2023-02-28 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
| NZ740616A (en) | 2015-09-14 | 2023-05-26 | Infinity Pharmaceuticals Inc | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| CN106632243B (zh) * | 2015-10-28 | 2019-03-15 | 华领医药技术（上海）有限公司 | 吡咯烷衍生物 |
| KR102740618B1 (ko) * | 2021-11-17 | 2024-12-10 | 유노비아 주식회사 | 아이속사졸 유도체의 제조 방법 및 그의 중간체 |
| CN119569744A (zh) * | 2024-11-19 | 2025-03-07 | 武汉大学人民医院（湖北省人民医院） | 吡喃吡啶酮生物碱类化合物及其制备方法和应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0503646D0 (en) * | 2005-02-22 | 2005-03-30 | Novartis Ag | Organic compounds |
| CN101990536B (zh) * | 2008-01-18 | 2014-09-03 | 上海靶点药物有限公司 | 基于吡咯烷的化合物 |
| TW201116532A (en) * | 2009-08-05 | 2011-05-16 | Merz Pharma Gmbh & Co Kgaa | Metabotropic glutamate receptor modulators |
| US8420661B2 (en) * | 2010-04-13 | 2013-04-16 | Hoffmann-La Roche Inc. | Arylethynyl derivatives |
| WO2012152854A1 (en) * | 2011-05-12 | 2012-11-15 | Merz Pharma Gmbh & Co. Kgaa | Metabotropic glutamate receptor modulators |
| UA110862C2 (uk) * | 2011-10-07 | 2016-02-25 | Ф. Хоффманн-Ля Рош Аг | Похідні етинілу як алостеричні модулятори метаботропного рецептора глутамату mglur 5 |
| CN105121424B (zh) * | 2013-02-18 | 2019-01-22 | 华领医药技术（上海）有限公司 | mGluR调节剂 |
| CN106632243B (zh) * | 2015-10-28 | 2019-03-15 | 华领医药技术（上海）有限公司 | 吡咯烷衍生物 |
-
2015
- 2015-10-28 CN CN201510713865.7A patent/CN106632243B/zh active Active
-
2016
- 2016-10-21 HU HUE16858971A patent/HUE058899T2/hu unknown
- 2016-10-21 AU AU2016345244A patent/AU2016345244B2/en active Active
- 2016-10-21 JP JP2018541471A patent/JP6877771B2/ja active Active
- 2016-10-21 WO PCT/CN2016/102946 patent/WO2017071536A1/en not_active Ceased
- 2016-10-21 CA CA3000794A patent/CA3000794C/en active Active
- 2016-10-21 ES ES16858971T patent/ES2922978T3/es active Active
- 2016-10-21 US US15/771,920 patent/US10328054B2/en active Active
- 2016-10-21 DK DK16858971.1T patent/DK3371163T3/da active
- 2016-10-21 MX MX2018004868A patent/MX385587B/es unknown
- 2016-10-21 EP EP16858971.1A patent/EP3371163B1/en active Active
- 2016-10-21 CN CN201680062993.2A patent/CN108349935B/zh active Active
- 2016-10-21 BR BR112018008204-0A patent/BR112018008204B1/pt active IP Right Grant
- 2016-10-21 KR KR1020187014851A patent/KR102815874B1/ko active Active
- 2016-10-21 RU RU2018119038A patent/RU2740019C1/ru active
- 2016-10-27 TW TW105134694A patent/TWI725998B/zh active
-
2018
- 2018-04-05 IL IL258517A patent/IL258517B/en active IP Right Grant
- 2018-04-05 ZA ZA2018/02235A patent/ZA201802235B/en unknown