JP6484640B2 - Gpr6のピラジンモジュレーター - Google Patents
Gpr6のピラジンモジュレーター Download PDFInfo
- Publication number
- JP6484640B2 JP6484640B2 JP2016551806A JP2016551806A JP6484640B2 JP 6484640 B2 JP6484640 B2 JP 6484640B2 JP 2016551806 A JP2016551806 A JP 2016551806A JP 2016551806 A JP2016551806 A JP 2016551806A JP 6484640 B2 JP6484640 B2 JP 6484640B2
- Authority
- JP
- Japan
- Prior art keywords
- piperidin
- isopropylamino
- pyrazine
- cyano
- chloro
- 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.)
- Expired - Fee Related
Links
- 102100033861 G-protein coupled receptor 6 Human genes 0.000 title description 35
- 101001069613 Homo sapiens G-protein coupled receptor 6 Proteins 0.000 title description 35
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 title 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 223
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- -1 cyano, hydroxy Chemical group 0.000 claims description 50
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 208000018737 Parkinson disease Diseases 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 150000001408 amides Chemical class 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 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 description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 208000028683 bipolar I disease Diseases 0.000 claims description 5
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- 229940079593 drug Drugs 0.000 claims description 5
- 206010013663 drug dependence Diseases 0.000 claims description 5
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 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 description 4
- 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 4
- 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 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 3
- 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 description 3
- 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 description 3
- 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 3
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- 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 description 3
- 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 description 3
- 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 description 3
- 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 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
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
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- 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 description 2
- 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 description 2
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- 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 description 2
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- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
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- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000000534 dopa decarboxylase inhibitor Substances 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 210000004002 dopaminergic cell Anatomy 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
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- QMXSOVCXPDCBMT-UHFFFAOYSA-N methyl 5,6-dichloropyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C(Cl)=N1 QMXSOVCXPDCBMT-UHFFFAOYSA-N 0.000 description 1
- IHBJNSCXVJDJST-UHFFFAOYSA-N methyl 5-bromo-6-oxo-1h-pyrazine-3-carboxylate Chemical compound COC(=O)C1=CN=C(O)C(Br)=N1 IHBJNSCXVJDJST-UHFFFAOYSA-N 0.000 description 1
- BQOISWBADMWTBC-UHFFFAOYSA-N methyl 6-chloro-5-(cyclopropylamino)pyrazine-2-carboxylate Chemical compound ClC1=C(N=CC(=N1)C(=O)OC)NC1CC1 BQOISWBADMWTBC-UHFFFAOYSA-N 0.000 description 1
- TWIIRMSFZNYMQE-UHFFFAOYSA-N methyl pyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=CC=N1 TWIIRMSFZNYMQE-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
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- 239000003208 petroleum Substances 0.000 description 1
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- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical group NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
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- FXYXJKWVTFZJGZ-UHFFFAOYSA-N tert-butyl 4-(2,4-difluorobenzoyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)C1=CC=C(F)C=C1F FXYXJKWVTFZJGZ-UHFFFAOYSA-N 0.000 description 1
- DAWIORDJWWVXOJ-UHFFFAOYSA-N tert-butyl 4-(2,4-difluorophenyl)sulfonylpiperidine-1-carboxylate Chemical compound FC1=C(C=CC(=C1)F)S(=O)(=O)C1CCN(CC1)C(=O)OC(C)(C)C DAWIORDJWWVXOJ-UHFFFAOYSA-N 0.000 description 1
- FCKFRMDTDMXTJI-UHFFFAOYSA-N tert-butyl 4-(2-fluorophenyl)sulfonylpiperidine-1-carboxylate Chemical compound FC1=C(C=CC=C1)S(=O)(=O)C1CCN(CC1)C(=O)OC(C)(C)C FCKFRMDTDMXTJI-UHFFFAOYSA-N 0.000 description 1
- OZNUODLKVJMEIH-UHFFFAOYSA-N tert-butyl 4-(3-fluorophenyl)sulfanylpiperidine-1-carboxylate Chemical compound FC=1C=C(C=CC1)SC1CCN(CC1)C(=O)OC(C)(C)C OZNUODLKVJMEIH-UHFFFAOYSA-N 0.000 description 1
- XGEZZJLFSSPRPI-UHFFFAOYSA-N tert-butyl 4-[(2,4-difluorophenyl)-fluoromethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(F)C1=CC=C(F)C=C1F XGEZZJLFSSPRPI-UHFFFAOYSA-N 0.000 description 1
- ITCQNWXLNZGEHP-UHFFFAOYSA-N tert-butyl 4-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate Chemical compound CON(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1 ITCQNWXLNZGEHP-UHFFFAOYSA-N 0.000 description 1
- WOEQSXAIPTXOPY-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1 WOEQSXAIPTXOPY-UHFFFAOYSA-N 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
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- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
- C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
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 JP2017509601A5 (enExample) | 2018-03-22 |
| JP6484640B2 true 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) |
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| 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 |
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| 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 |
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| 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 |
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