JP2017509601A5 - - Google Patents
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- Publication number
- JP2017509601A5 JP2017509601A5 JP2016551806A JP2016551806A JP2017509601A5 JP 2017509601 A5 JP2017509601 A5 JP 2017509601A5 JP 2016551806 A JP2016551806 A JP 2016551806A JP 2016551806 A JP2016551806 A JP 2016551806A JP 2017509601 A5 JP2017509601 A5 JP 2017509601A5
- Authority
- JP
- Japan
- Prior art keywords
- piperidin
- isopropylamino
- pyrazine
- cyano
- difluorophenoxy
- 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
- 150000001875 compounds Chemical class 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 208000018737 Parkinson disease Diseases 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- -1 cyano, hydroxy Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 208000030814 Eating disease Diseases 0.000 claims description 4
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 208000028683 bipolar I disease Diseases 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 235000014632 disordered eating Nutrition 0.000 claims description 4
- 206010013663 drug dependence Diseases 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 208000011117 substance-related disease Diseases 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- RSYHJQQMCPIHCU-UHFFFAOYSA-N 3-cyano-5-(cyclopropylamino)-6-[4-[(2,4-difluorophenyl)methyl]piperazin-1-yl]pyrazine-2-carboxylic acid Chemical compound C(#N)C=1C(=NC(=C(N1)NC1CC1)N1CCN(CC1)CC1=C(C=C(C=C1)F)F)C(=O)O RSYHJQQMCPIHCU-UHFFFAOYSA-N 0.000 claims description 2
- ITPSILGGHCZPDK-UHFFFAOYSA-N 3-cyano-6-(cyclopropylamino)-5-[4-[(2,4-difluorophenyl)methyl]piperazin-1-yl]pyrazine-2-carboxylic acid Chemical compound C(#N)C=1C(=NC(=C(N1)N1CCN(CC1)CC1=C(C=C(C=C1)F)F)NC1CC1)C(=O)O ITPSILGGHCZPDK-UHFFFAOYSA-N 0.000 claims description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- ZXGMCQPQJVWJRW-UHFFFAOYSA-N 3-chloro-6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-5-(propan-2-ylamino)pyrazine-2-carbonitrile Chemical compound ClC=1C(=NC(=C(N1)NC(C)C)N1CCC(CC1)OC1=C(C=C(C=C1)F)F)C#N ZXGMCQPQJVWJRW-UHFFFAOYSA-N 0.000 claims 1
- MKKLGVHYBCYOJR-UHFFFAOYSA-N 3-cyano-5-[4-(2,4-difluorophenoxy)piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound C(#N)C=1C(=NC(=C(N1)N1CCC(CC1)OC1=C(C=C(C=C1)F)F)NC(C)C)C(=O)O MKKLGVHYBCYOJR-UHFFFAOYSA-N 0.000 claims 1
- OPTDUMDJBXAGPL-UHFFFAOYSA-N 3-cyano-5-[4-(2,4-difluorophenoxy)piperidin-1-yl]-N,N-dimethyl-6-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound C(#N)C=1C(=NC(=C(N1)N1CCC(CC1)OC1=C(C=C(C=C1)F)F)NC(C)C)C(=O)N(C)C OPTDUMDJBXAGPL-UHFFFAOYSA-N 0.000 claims 1
- CALGFXLDSDAIDP-QGZVFWFLSA-N 3-cyano-5-[4-[(R)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound C(#N)C=1C(=NC(=C(N1)N1CCC(CC1)[C@@H](F)C1=C(C=C(C=C1)F)F)NC(C)C)C(=O)O CALGFXLDSDAIDP-QGZVFWFLSA-N 0.000 claims 1
- OAIWRIQJKTUCMB-UHFFFAOYSA-N 3-cyano-6-(cyclopropylamino)-5-[4-[(2,4-difluorophenyl)methyl]piperazin-1-yl]-N,N-dimethylpyrazine-2-carboxamide Chemical compound C(#N)C=1C(=NC(=C(N1)N1CCN(CC1)CC1=C(C=C(C=C1)F)F)NC1CC1)C(=O)N(C)C OAIWRIQJKTUCMB-UHFFFAOYSA-N 0.000 claims 1
- DILAMMRHDAEGSY-UHFFFAOYSA-N 3-cyano-6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-5-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound C(#N)C=1C(=NC(=C(N1)NC(C)C)N1CCC(CC1)OC1=C(C=C(C=C1)F)F)C(=O)O DILAMMRHDAEGSY-UHFFFAOYSA-N 0.000 claims 1
- BVTZZYQZJNWAKD-UHFFFAOYSA-N 3-cyano-6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-N,N-dimethyl-5-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound C(#N)C=1C(=NC(=C(N1)NC(C)C)N1CCC(CC1)OC1=C(C=C(C=C1)F)F)C(=O)N(C)C BVTZZYQZJNWAKD-UHFFFAOYSA-N 0.000 claims 1
- MBQWFPGWQKNWSN-QGZVFWFLSA-N 3-cyano-6-[4-[(R)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]-5-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound C(#N)C=1C(=NC(=C(N1)NC(C)C)N1CCC(CC1)[C@@H](F)C1=C(C=C(C=C1)F)F)C(=O)O MBQWFPGWQKNWSN-QGZVFWFLSA-N 0.000 claims 1
- IBRDZKMXHKJPPD-UHFFFAOYSA-N 5-(cyclopropylamino)-6-[4-[(2,4-difluorophenyl)methyl]piperazin-1-yl]pyrazine-2,3-dicarbonitrile Chemical compound C1(CC1)NC=1N=C(C(=NC1N1CCN(CC1)CC1=C(C=C(C=C1)F)F)C#N)C#N IBRDZKMXHKJPPD-UHFFFAOYSA-N 0.000 claims 1
- MEFITDPPFUIGPT-GOSISDBHSA-N 5-(cyclopropylamino)-6-[4-[(R)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]pyrazine-2-carbonitrile Chemical compound C1(CC1)NC=1N=CC(=NC1N1CCC(CC1)[C@@H](F)C1=C(C=C(C=C1)F)F)C#N MEFITDPPFUIGPT-GOSISDBHSA-N 0.000 claims 1
- RPUWWTNVKMGDOT-UHFFFAOYSA-N 5-[4-(2,4-difluorophenoxy)piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2,3-dicarbonitrile Chemical compound FC1=C(OC2CCN(CC2)C=2N=C(C(=NC2NC(C)C)C#N)C#N)C=CC(=C1)F RPUWWTNVKMGDOT-UHFFFAOYSA-N 0.000 claims 1
- PJPUXSYJYLFQDS-UHFFFAOYSA-N 5-[4-(2,4-difluorophenoxy)piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2-carbonitrile Chemical compound FC1=C(OC2CCN(CC2)C=2N=CC(=NC2NC(C)C)C#N)C=CC(=C1)F PJPUXSYJYLFQDS-UHFFFAOYSA-N 0.000 claims 1
- RBSMTSRXWIUZKD-UHFFFAOYSA-N 5-[4-(2,4-difluorophenoxy)piperidin-1-yl]-N,N-dimethyl-6-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound FC1=C(OC2CCN(CC2)C=2N=CC(=NC2NC(C)C)C(=O)N(C)C)C=CC(=C1)F RBSMTSRXWIUZKD-UHFFFAOYSA-N 0.000 claims 1
- QANAFSVJIRJCBJ-UHFFFAOYSA-N 5-[4-(4-chloro-2-fluorophenoxy)piperidin-1-yl]-3-cyano-6-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound ClC1=CC(=C(OC2CCN(CC2)C=2N=C(C(=NC2NC(C)C)C(=O)O)C#N)C=C1)F QANAFSVJIRJCBJ-UHFFFAOYSA-N 0.000 claims 1
- CJRHUDXLQZTVNP-UHFFFAOYSA-N 5-[4-(4-chloro-2-fluorophenoxy)piperidin-1-yl]-3-cyano-N,N-dimethyl-6-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound ClC1=CC(=C(OC2CCN(CC2)C=2N=C(C(=NC2NC(C)C)C(=O)N(C)C)C#N)C=C1)F CJRHUDXLQZTVNP-UHFFFAOYSA-N 0.000 claims 1
- OGSYEOBSSCBGKI-UHFFFAOYSA-N 5-[4-(4-chloro-2-fluorophenoxy)piperidin-1-yl]-6-(cyclopropylamino)pyrazine-2-carbonitrile Chemical compound ClC1=CC(=C(OC2CCN(CC2)C=2N=CC(=NC2NC2CC2)C#N)C=C1)F OGSYEOBSSCBGKI-UHFFFAOYSA-N 0.000 claims 1
- CHDNZVHJOJQCDP-UHFFFAOYSA-N 5-[4-(4-chloro-2-fluorophenoxy)piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2,3-dicarbonitrile Chemical compound ClC1=CC(=C(OC2CCN(CC2)C=2N=C(C(=NC2NC(C)C)C#N)C#N)C=C1)F CHDNZVHJOJQCDP-UHFFFAOYSA-N 0.000 claims 1
- SXGCMIHWZXJJEA-UHFFFAOYSA-N 5-[4-(5-chloro-2-fluorobenzoyl)piperidin-1-yl]-3-cyano-6-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound ClC=1C=CC(=C(C(=O)C2CCN(CC2)C=2N=C(C(=NC2NC(C)C)C(=O)O)C#N)C1)F SXGCMIHWZXJJEA-UHFFFAOYSA-N 0.000 claims 1
- YMTGGBMISZSLFM-UHFFFAOYSA-N 5-[4-(5-chloro-2-fluorobenzoyl)piperidin-1-yl]-3-cyano-N,N-dimethyl-6-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound ClC=1C=CC(=C(C(=O)C2CCN(CC2)C=2N=C(C(=NC=2NC(C)C)C(=O)N(C)C)C#N)C=1)F YMTGGBMISZSLFM-UHFFFAOYSA-N 0.000 claims 1
- KYPYEURSCHOCEQ-UHFFFAOYSA-N 5-[4-(5-chloro-2-fluorobenzoyl)piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2,3-dicarbonitrile Chemical compound ClC=1C=CC(=C(C(=O)C2CCN(CC2)C=2N=C(C(=NC2NC(C)C)C#N)C#N)C1)F KYPYEURSCHOCEQ-UHFFFAOYSA-N 0.000 claims 1
- KYHPFJCEWUIIAD-LJQANCHMSA-N 5-[4-[(R)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2,3-dicarbonitrile Chemical compound FC1=C(C=CC(=C1)F)[C@@H](C1CCN(CC1)C=1N=C(C(=NC1NC(C)C)C#N)C#N)F KYHPFJCEWUIIAD-LJQANCHMSA-N 0.000 claims 1
- QENDOAGTFPJVJN-GOSISDBHSA-N 5-[4-[(R)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]-6-(propan-2-ylamino)pyrazine-2-carbonitrile Chemical compound FC1=C(C=CC(=C1)F)[C@@H](C1CCN(CC1)C=1N=CC(=NC1NC(C)C)C#N)F QENDOAGTFPJVJN-GOSISDBHSA-N 0.000 claims 1
- UUPPUNREICFVIO-UHFFFAOYSA-N 6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-3-morpholin-4-yl-5-(propan-2-ylamino)pyrazine-2-carbonitrile Chemical compound FC1=C(OC2CCN(CC2)C2=C(N=C(C(=N2)C#N)N2CCOCC2)NC(C)C)C=CC(=C1)F UUPPUNREICFVIO-UHFFFAOYSA-N 0.000 claims 1
- OGHPOGBIFGGUDI-UHFFFAOYSA-N 6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-5-(propan-2-ylamino)pyrazine-2-carbonitrile Chemical compound FC1=C(OC2CCN(CC2)C2=C(N=CC(=N2)C#N)NC(C)C)C=CC(=C1)F OGHPOGBIFGGUDI-UHFFFAOYSA-N 0.000 claims 1
- HUJMSSBPGWZSHG-UHFFFAOYSA-N 6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-5-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound FC1=C(OC2CCN(CC2)C2=C(N=CC(=N2)C(=O)O)NC(C)C)C=CC(=C1)F HUJMSSBPGWZSHG-UHFFFAOYSA-N 0.000 claims 1
- ZGTSEKCLSOGFEK-UHFFFAOYSA-N 6-[4-(4-chloro-2-fluorophenoxy)piperidin-1-yl]-3-cyano-5-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound ClC1=CC(=C(OC2CCN(CC2)C2=C(N=C(C(=N2)C(=O)O)C#N)NC(C)C)C=C1)F ZGTSEKCLSOGFEK-UHFFFAOYSA-N 0.000 claims 1
- DOSYINKMPAZWAS-UHFFFAOYSA-N 6-[4-(5-chloro-2-fluorobenzoyl)piperidin-1-yl]-3-cyano-5-(propan-2-ylamino)pyrazine-2-carboxylic acid Chemical compound ClC=1C=CC(=C(C(=O)C2CCN(CC2)C2=C(N=C(C(=N2)C(=O)O)C#N)NC(C)C)C1)F DOSYINKMPAZWAS-UHFFFAOYSA-N 0.000 claims 1
- MWMHIVGWGATOLY-UHFFFAOYSA-N 6-[4-(5-chloro-2-fluorobenzoyl)piperidin-1-yl]-N,N-dimethyl-5-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound ClC=1C=CC(=C(C(=O)C2CCN(CC2)C2=C(N=CC(=N2)C(=O)N(C)C)NC(C)C)C1)F MWMHIVGWGATOLY-UHFFFAOYSA-N 0.000 claims 1
- DJYGHIQUHQRKOQ-GOSISDBHSA-N 6-[4-[(R)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]-N-methyl-5-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound FC1=C(C=CC(=C1)F)[C@@H](C1CCN(CC1)C1=C(N=CC(=N1)C(=O)NC)NC(C)C)F DJYGHIQUHQRKOQ-GOSISDBHSA-N 0.000 claims 1
- DJYGHIQUHQRKOQ-SFHVURJKSA-N 6-[4-[(S)-(2,4-difluorophenyl)-fluoromethyl]piperidin-1-yl]-N-methyl-5-(propan-2-ylamino)pyrazine-2-carboxamide Chemical compound FC1=C(C=CC(=C1)F)[C@H](C1CCN(CC1)C1=C(N=CC(=N1)C(=O)NC)NC(C)C)F DJYGHIQUHQRKOQ-SFHVURJKSA-N 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- RYAJJIYVDSVRMA-UHFFFAOYSA-N [6-[4-(2,4-difluorophenoxy)piperidin-1-yl]-5-(propan-2-ylamino)pyrazin-2-yl]-(3-fluoroazetidin-1-yl)methanone Chemical compound FC1=C(OC2CCN(CC2)C2=C(N=CC(=N2)C(=O)N2CC(C2)F)NC(C)C)C=CC(=C1)F RYAJJIYVDSVRMA-UHFFFAOYSA-N 0.000 claims 1
- 230000003796 beauty Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229960004502 levodopa Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 102100033861 G-protein coupled receptor 6 Human genes 0.000 description 7
- 101001069613 Homo sapiens G-protein coupled receptor 6 Proteins 0.000 description 7
- 238000000034 method Methods 0.000 description 5
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 2
- 208000030990 Impulse-control disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461940294P | 2014-02-14 | 2014-02-14 | |
| US61/940,294 | 2014-02-14 | ||
| PCT/US2015/015841 WO2015123533A1 (en) | 2014-02-14 | 2015-02-13 | Pyrazines modulators of gpr6 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017509601A JP2017509601A (ja) | 2017-04-06 |
| JP2017509601A5 true JP2017509601A5 (https=) | 2018-03-22 |
| JP6484640B2 JP6484640B2 (ja) | 2019-03-13 |
Family
ID=52598823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016551806A Expired - Fee Related JP6484640B2 (ja) | 2014-02-14 | 2015-02-13 | Ｇｐｒ６のピラジンモジュレーター |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US10000468B2 (https=) |
| EP (1) | EP3105216B1 (https=) |
| JP (1) | JP6484640B2 (https=) |
| KR (1) | KR20160122215A (https=) |
| CN (1) | CN106103421B (https=) |
| AU (1) | AU2015218402B2 (https=) |
| BR (1) | BR112016018418A2 (https=) |
| CA (1) | CA2939382A1 (https=) |
| CL (1) | CL2016002043A1 (https=) |
| CR (1) | CR20160428A (https=) |
| DO (1) | DOP2016000211A (https=) |
| EA (1) | EA033861B1 (https=) |
| EC (1) | ECSP16074207A (https=) |
| ES (1) | ES2702205T3 (https=) |
| GE (2) | GEP20186893B (https=) |
| IL (1) | IL247140B (https=) |
| MA (1) | MA39337B1 (https=) |
| MX (1) | MX369857B (https=) |
| MY (1) | MY184366A (https=) |
| PE (1) | PE20170245A1 (https=) |
| PH (1) | PH12016501613B1 (https=) |
| UA (1) | UA117779C2 (https=) |
| WO (1) | WO2015123533A1 (https=) |
| ZA (1) | ZA201606077B (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160122215A (ko) * | 2014-02-14 | 2016-10-21 | 다케다 야쿠힌 고교 가부시키가이샤 | Gpr6의 피라진 조절제 |
| EA202092441A1 (ru) | 2016-06-07 | 2021-05-21 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| KR20240026521A (ko) | 2017-03-23 | 2024-02-28 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| MX390512B (es) * | 2017-03-26 | 2025-03-20 | Takeda Pharmaceuticals Co | Carboxamidas heteroaromáticas sustituidas con piperidinilo y piperazinilo como moduladores de gpr6. |
| JOP20180057A1 (ar) * | 2017-06-15 | 2019-01-30 | Takeda Pharmaceuticals Co | مركبات رابع هيدروبيريدو بيرازين والتي تعمل كمعدلات gpr6 |
| CN112839935A (zh) | 2018-09-26 | 2021-05-25 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| CN115996908B (zh) * | 2020-04-30 | 2026-04-24 | 俄勒冈健康科学大学 | Gpr39蛋白的拮抗剂 |
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