JP2017509601A5 - - Google Patents
Download PDFInfo
- 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 (enExample) | 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 (enExample) |
| EP (1) | EP3105216B1 (enExample) |
| JP (1) | JP6484640B2 (enExample) |
| KR (1) | KR20160122215A (enExample) |
| CN (1) | CN106103421B (enExample) |
| AU (1) | AU2015218402B2 (enExample) |
| BR (1) | BR112016018418A2 (enExample) |
| CA (1) | CA2939382A1 (enExample) |
| CL (1) | CL2016002043A1 (enExample) |
| CR (1) | CR20160428A (enExample) |
| DO (1) | DOP2016000211A (enExample) |
| EA (1) | EA033861B1 (enExample) |
| EC (1) | ECSP16074207A (enExample) |
| ES (1) | ES2702205T3 (enExample) |
| GE (1) | GEP20186893B (enExample) |
| IL (1) | IL247140B (enExample) |
| MA (1) | MA39337B1 (enExample) |
| MX (1) | MX369857B (enExample) |
| MY (1) | MY184366A (enExample) |
| PE (1) | PE20170245A1 (enExample) |
| PH (1) | PH12016501613B1 (enExample) |
| UA (1) | UA117779C2 (enExample) |
| WO (1) | WO2015123533A1 (enExample) |
| ZA (1) | ZA201606077B (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3105216B1 (en) * | 2014-02-14 | 2018-10-10 | Takeda Pharmaceutical Company Limited | Pyrazine modulators of gpr6 |
| EA202092442A3 (ru) | 2016-06-07 | 2021-08-31 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| KR102317480B1 (ko) | 2017-03-23 | 2021-10-25 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| CN110520127B (zh) * | 2017-03-26 | 2023-05-16 | 武田药品工业株式会社 | 作为gpr6的调节剂的经哌啶基取代的杂芳族羧酰胺和经哌嗪基取代的杂芳族羧酰胺 |
| JOP20180057A1 (ar) * | 2017-06-15 | 2019-01-30 | Takeda Pharmaceuticals Co | مركبات رابع هيدروبيريدو بيرازين والتي تعمل كمعدلات gpr6 |
| WO2020063760A1 (en) | 2018-09-26 | 2020-04-02 | Jacobio Pharmaceuticals Co., Ltd. | Novel heterocyclic derivatives useful as shp2 inhibitors |
| KR20230017787A (ko) * | 2020-04-30 | 2023-02-06 | 오레곤 헬스 앤드 사이언스 유니버시티 | Gpr39 단백질의 길항제 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4159331A (en) * | 1978-05-05 | 1979-06-26 | The Upjohn Company | Antihypertensive 4-aminoquinolines |
| US5563142A (en) * | 1989-12-28 | 1996-10-08 | The Upjohn Company | Diaromatic substituted compounds as anti-HIV-1 agents |
| WO2001062765A2 (en) * | 1999-02-26 | 2001-08-30 | Arena Pharmaceuticals, Inc. | Small molecule modulators of g protein-coupled receptor six |
| US6774138B2 (en) | 1999-08-31 | 2004-08-10 | Merck & Co., Inc. | Thiazolyl(pyridyl)ethyne compounds |
| NZ520484A (en) | 2000-02-16 | 2005-03-24 | Neurogen Corp | Substituted arylpyrazines that are modulators of CRF (corticotropin releasing factor) receptor and methods of treatment using them |
| BR0210102A (pt) * | 2001-06-01 | 2004-06-08 | Hoffmann La Roche | Derivados de pirimidina, triazina e pirazina como receptores de glutamato |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| EA006707B1 (ru) | 2002-03-13 | 2006-02-24 | Янссен Фармацевтика Н. В. | Сульфонилпроизводные в качестве новых ингибиторов гистон-деацетилазы |
| JPWO2004054617A1 (ja) * | 2002-12-13 | 2006-04-20 | 協和醗酵工業株式会社 | 中枢疾患の予防および／または治療剤 |
| CN101693697A (zh) | 2003-07-30 | 2010-04-14 | 泽农医药公司 | 哌嗪衍生物和它们作为治疗剂的用途 |
| US20050070718A1 (en) * | 2003-09-30 | 2005-03-31 | Abbott Gmbh & Co. Kg | Heteroaryl-substituted 1,3-dihydroindol-2-one derivatives and medicaments containing them |
| US8580842B2 (en) * | 2003-09-30 | 2013-11-12 | Abbott Gmbh & Co. Kg | Heteroaryl-substituted 1,3-dihydroindol-2-one derivatives and medicaments containing them |
| CN1933838A (zh) * | 2004-02-12 | 2007-03-21 | 默克公司 | 作为代谢型谷氨酸受体－5调节剂的联吡啶酰胺 |
| ATE458730T1 (de) | 2004-04-13 | 2010-03-15 | Icagen Inc | Polycyclische pyrazine als kaliumionenkanal- modulatoren |
| GB0414438D0 (en) * | 2004-06-28 | 2004-07-28 | Syngenta Participations Ag | Chemical compounds |
| US20060199828A1 (en) * | 2005-03-04 | 2006-09-07 | Georg Jaeschke | Pyrazine-2-carboxyamide derivatives |
| BRPI0611439A2 (pt) | 2005-05-13 | 2010-09-08 | Lexicon Pharmaceuticals Inc | compostos multicìclicos e métodos para uso dos mesmos |
| WO2007044085A2 (en) | 2005-05-19 | 2007-04-19 | Xenon Pharmaceuticals Inc. | Heteroaryl compounds and their uses as therapeutic agents |
| US8495335B2 (en) * | 2006-06-16 | 2013-07-23 | Raytheon Company | Data translation system and method |
| AU2009271414A1 (en) | 2008-06-20 | 2010-01-21 | Metabolex, Inc. | Aryl GPR119 agonists and uses thereof |
| WO2011139489A2 (en) | 2010-04-27 | 2011-11-10 | Calcimedica Inc. | Compounds that modulate intracellular calcium |
| MX2012013127A (es) | 2010-05-13 | 2012-11-30 | Amgen Inc | Compuestos heteroariloxiheterociclilo como inhibidores pde10. |
| SG185515A1 (en) * | 2010-05-13 | 2012-12-28 | Amgen Inc | Nitrogen heterocyclic compounds useful as pde10 inhibitors |
| US20120184572A1 (en) | 2011-01-13 | 2012-07-19 | Metabolex, Inc. | Aryl gpr119 agonists and uses thereof |
| US10252984B2 (en) * | 2011-10-27 | 2019-04-09 | Mayo Foundation For Medical Education And Research | Inhibiting G protein coupled receptor 6 kinase polypeptides |
| EP2882722B1 (en) * | 2012-08-13 | 2016-07-27 | Takeda Pharmaceutical Company Limited | Quinoxaline derivatives as gpr6 modulators |
| TR201911140T4 (tr) | 2013-10-21 | 2019-08-21 | Merck Patent Gmbh | Btk inhibitörleri olarak heteroaril bileşikleri ve bunların kullanımları. |
| EP3105216B1 (en) * | 2014-02-14 | 2018-10-10 | Takeda Pharmaceutical Company Limited | Pyrazine modulators of gpr6 |
-
2015
- 2015-02-13 EP EP15707836.1A patent/EP3105216B1/en active Active
- 2015-02-13 PE PE2016001477A patent/PE20170245A1/es unknown
- 2015-02-13 UA UAA201609102A patent/UA117779C2/uk unknown
- 2015-02-13 GE GEAP201514266A patent/GEP20186893B/en unknown
- 2015-02-13 ES ES15707836T patent/ES2702205T3/es active Active
- 2015-02-13 MA MA39337A patent/MA39337B1/fr unknown
- 2015-02-13 AU AU2015218402A patent/AU2015218402B2/en active Active
- 2015-02-13 KR KR1020167025131A patent/KR20160122215A/ko not_active Ceased
- 2015-02-13 EA EA201691632A patent/EA033861B1/ru unknown
- 2015-02-13 CR CR20160428A patent/CR20160428A/es unknown
- 2015-02-13 US US15/118,461 patent/US10000468B2/en not_active Expired - Fee Related
- 2015-02-13 JP JP2016551806A patent/JP6484640B2/ja not_active Expired - Fee Related
- 2015-02-13 MX MX2016010529A patent/MX369857B/es active IP Right Grant
- 2015-02-13 MY MYPI2016702927A patent/MY184366A/en unknown
- 2015-02-13 WO PCT/US2015/015841 patent/WO2015123533A1/en not_active Ceased
- 2015-02-13 CA CA2939382A patent/CA2939382A1/en not_active Abandoned
- 2015-02-13 CN CN201580013589.1A patent/CN106103421B/zh active Active
- 2015-02-13 BR BR112016018418A patent/BR112016018418A2/pt not_active Application Discontinuation
-
2016
- 2016-08-07 IL IL247140A patent/IL247140B/en active IP Right Grant
- 2016-08-12 PH PH12016501613A patent/PH12016501613B1/en unknown
- 2016-08-12 DO DO2016000211A patent/DOP2016000211A/es unknown
- 2016-08-12 CL CL2016002043A patent/CL2016002043A1/es unknown
- 2016-09-01 ZA ZA2016/06077A patent/ZA201606077B/en unknown
- 2016-09-14 EC ECIEPI201674207A patent/ECSP16074207A/es unknown
-
2018
- 2018-05-14 US US15/979,069 patent/US10273225B2/en not_active Expired - Fee Related
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2017509601A5 (enExample) | ||
| PH12019500004A1 (en) | 5,7-dihydro-pyrrolo-pyridine derivatives for treating neurological and neurodegenerative diseases | |
| JP2019517487A5 (enExample) | ||
| PH12020550631A1 (en) | New catecholamine prodrugs for use in the treatment of parkinson`s disease | |
| CN109963854A (zh) | 杂芳基并[4,3-c]嘧啶-5-胺类衍生物、其制备方法及其在医药上的应用 | |
| MX2019015371A (es) | Derivados de dihidro-pirrolo-piridina. | |
| JP2016528301A5 (enExample) | ||
| RU2017121044A (ru) | Производные амидотиадиазола в качестве ингибиторов надфн-оксидазы | |
| MX344308B (es) | Derivados de quinolina carboxamida y quinolina carbonitrilo como moduladores alostericos negativos de mglur2, composiciones y su uso. | |
| CA2856334A1 (en) | Novel trifluoromethyl-oxadiazole derivatives and their use in the treatment of disease | |
| EA201000441A1 (ru) | Водные офтальмологические препараты | |
| TW200600492A (en) | Substituted aryl acylthioureas and related compounds; inhibitors of viral replication | |
| EA025086B9 (ru) | Производные индоламида и родственные соединения для использования при лечении нейродегенеративных заболеваний | |
| JP5916746B2 (ja) | 認知障害を処置するためのピリダジン誘導体、組成物、および方法 | |
| NO20071512L (no) | Terapeutiske kombinasjoner omfattende poly(ADP-ribose)polymeraseinhibitor. | |
| MX2009006947A (es) | Derivados de pirimidona 6-heterociclica 2-sustituida. | |
| JP2019512495A5 (enExample) | ||
| JP2016525104A5 (enExample) | ||
| JP2018507257A5 (enExample) | ||
| TN2020000160A1 (en) | CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGIuR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE | |
| ATE495164T1 (de) | Thiadiazolderivate zur behandlung neurodegenerativer krankheiten | |
| WO2020219486A3 (en) | Collagen peptide-based medicament compositions and devices and methods of production and use thereof | |
| MX2012005695A (es) | Metodos y composiciones para el tratamiento de tumores solidos y otras malignidades. | |
| MX2009007889A (es) | Derivados de 3-cinnolincarboxamida y su uso para el tratamiento del cancer. | |
| JP2024153742A (ja) | Ｃｃｒ３阻害剤を用いて、加齢性機能障害を治療するための方法および組成物 |