JP2012512255A - ホスホジエステラーゼ10阻害剤としてのアミノピリジンおよびカルボキシピリジン化合物 - Google Patents
ホスホジエステラーゼ10阻害剤としてのアミノピリジンおよびカルボキシピリジン化合物 Download PDFInfo
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- JP2012512255A JP2012512255A JP2011542411A JP2011542411A JP2012512255A JP 2012512255 A JP2012512255 A JP 2012512255A JP 2011542411 A JP2011542411 A JP 2011542411A JP 2011542411 A JP2011542411 A JP 2011542411A JP 2012512255 A JP2012512255 A JP 2012512255A
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- Prior art keywords
- pyridin
- ylamino
- phenoxy
- phenyl
- amine
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- 239000003112 inhibitor Substances 0.000 title claims description 30
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title description 9
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title description 7
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical class OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 title description 5
- 150000003927 aminopyridines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 46
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 38
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 23
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 22
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 16
- -1 tetrahydropyrani Chemical group 0.000 claims description 305
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 168
- 229920006395 saturated elastomer Polymers 0.000 claims description 121
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 117
- 229910052731 fluorine Inorganic materials 0.000 claims description 108
- 229910052794 bromium Inorganic materials 0.000 claims description 105
- 229910052799 carbon Inorganic materials 0.000 claims description 98
- 229910052801 chlorine Inorganic materials 0.000 claims description 95
- 229910052757 nitrogen Inorganic materials 0.000 claims description 88
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 54
- 229910052717 sulfur Inorganic materials 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 101100055332 Pseudomonas oleovorans alkN gene Proteins 0.000 claims description 34
- 229910052760 oxygen Inorganic materials 0.000 claims description 34
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000002950 monocyclic group Chemical group 0.000 claims description 28
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
- 125000004429 atom Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000002619 bicyclic group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
- 206010012289 Dementia Diseases 0.000 claims description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- 208000018737 Parkinson disease Diseases 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 239000011593 sulfur Substances 0.000 claims description 15
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 11
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- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 230000001898 pallidal effect Effects 0.000 claims description 11
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 8
- MMPZKSPHWRDPHY-UHFFFAOYSA-N n-[4-[3-(2-methylpyridin-4-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C1=NC(C)=CC(C=2C(=NC=CC=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 MMPZKSPHWRDPHY-UHFFFAOYSA-N 0.000 claims description 8
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 206010008748 Chorea Diseases 0.000 claims description 7
- MBWWOZAOTCKLFQ-AEFFLSMTSA-N (1s,3r)-3-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]cyclohexan-1-ol Chemical compound C1[C@@H](O)CCC[C@H]1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 MBWWOZAOTCKLFQ-AEFFLSMTSA-N 0.000 claims description 6
- PMNSENSAXPVTRV-UHFFFAOYSA-N 1-[4-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]-3,6-dihydro-2h-pyridin-1-yl]ethanone Chemical compound C1N(C(=O)C)CCC(C=2C(=NC=CC=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 PMNSENSAXPVTRV-UHFFFAOYSA-N 0.000 claims description 6
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 6
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- 239000003085 diluting agent Substances 0.000 claims description 6
- KZJDZHRONGUZNO-UHFFFAOYSA-N n-[4-[3-(oxolan-3-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C1OCCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 KZJDZHRONGUZNO-UHFFFAOYSA-N 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 208000011117 substance-related disease Diseases 0.000 claims description 6
- SZGYRYCRPSFSBT-UHFFFAOYSA-N tert-butyl 4-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C(=NC=CN=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 SZGYRYCRPSFSBT-UHFFFAOYSA-N 0.000 claims description 6
- UMTVKOCJSLGBPV-WBVHZDCISA-N (1s,3r)-3-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]cyclohexan-1-ol Chemical compound C1[C@@H](O)CCC[C@H]1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 UMTVKOCJSLGBPV-WBVHZDCISA-N 0.000 claims description 5
- UMTVKOCJSLGBPV-RDJZCZTQSA-N (1s,3s)-3-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]cyclohexan-1-ol Chemical compound C1[C@@H](O)CCC[C@@H]1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 UMTVKOCJSLGBPV-RDJZCZTQSA-N 0.000 claims description 5
- KFIQHFSOIUFIPH-UHFFFAOYSA-N 1-[4-[3-[2-fluoro-4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC=CN=C1OC(C(=C1)F)=CC=C1NC1=CC=CC=N1 KFIQHFSOIUFIPH-UHFFFAOYSA-N 0.000 claims description 5
- JMWAFGOLTQRKJH-UHFFFAOYSA-N 1-[4-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 JMWAFGOLTQRKJH-UHFFFAOYSA-N 0.000 claims description 5
- MXJQNCCVEAHQCF-UHFFFAOYSA-N 1-[4-[3-[4-[(5-methylpyridin-2-yl)amino]phenoxy]pyrazin-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=C(C)C=N1 MXJQNCCVEAHQCF-UHFFFAOYSA-N 0.000 claims description 5
- GOTUFSIPQGIMRB-UHFFFAOYSA-N 3-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]cyclopent-2-en-1-one Chemical compound O=C1CCC(C=2C(=NC=CC=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 GOTUFSIPQGIMRB-UHFFFAOYSA-N 0.000 claims description 5
- YTSQJSLXKWSKBB-UHFFFAOYSA-N 3-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]cyclopentan-1-ol Chemical compound C1C(O)CCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 YTSQJSLXKWSKBB-UHFFFAOYSA-N 0.000 claims description 5
- KZDALXNTKOJCBC-UHFFFAOYSA-N 3-fluoro-n-[4-[3-(oxan-4-yl)pyrazin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound FC1=CC=CN=C1NC(C=C1)=CC=C1OC1=NC=CN=C1C1CCOCC1 KZDALXNTKOJCBC-UHFFFAOYSA-N 0.000 claims description 5
- ZTJMEDZSQNWSAN-UHFFFAOYSA-N 3-methyl-n-[4-[3-(oxan-4-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound CC1=CC=CN=C1NC(C=C1)=CC=C1OC1=NC=CC=C1C1CCOCC1 ZTJMEDZSQNWSAN-UHFFFAOYSA-N 0.000 claims description 5
- CUGDWPFDKZPNAJ-UHFFFAOYSA-N 5-methyl-n-[4-[3-(oxan-4-yl)pyrazin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound N1=CC(C)=CC=C1NC(C=C1)=CC=C1OC1=NC=CN=C1C1CCOCC1 CUGDWPFDKZPNAJ-UHFFFAOYSA-N 0.000 claims description 5
- RDPSJUJEPIUILE-UHFFFAOYSA-N 5-methyl-n-[4-[3-(oxan-4-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound N1=CC(C)=CC=C1NC(C=C1)=CC=C1OC1=NC=CC=C1C1CCOCC1 RDPSJUJEPIUILE-UHFFFAOYSA-N 0.000 claims description 5
- 206010034719 Personality change Diseases 0.000 claims description 5
- COMCORKQVOAQLV-UHFFFAOYSA-N [4-(3-chloropyrazin-2-yl)oxyphenyl]-pyridin-2-ylmethanone Chemical compound ClC1=NC=CN=C1OC1=CC=C(C(=O)C=2N=CC=CC=2)C=C1 COMCORKQVOAQLV-UHFFFAOYSA-N 0.000 claims description 5
- DMIXVMKHTQBPGM-UHFFFAOYSA-N [4-[3-(2-methylpyridin-4-yl)pyrazin-2-yl]oxyphenyl]-pyridin-2-ylmethanone Chemical compound C1=NC(C)=CC(C=2C(=NC=CN=2)OC=2C=CC(=CC=2)C(=O)C=2N=CC=CC=2)=C1 DMIXVMKHTQBPGM-UHFFFAOYSA-N 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 206010013663 drug dependence Diseases 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- ACFWAHLCVSJSCO-UHFFFAOYSA-N n-[4-[3-(oxan-3-yl)pyrazin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C1CCOCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 ACFWAHLCVSJSCO-UHFFFAOYSA-N 0.000 claims description 5
- WKCXWIVGOHAMBX-UHFFFAOYSA-N n-[4-[3-(oxan-3-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C1CCOCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 WKCXWIVGOHAMBX-UHFFFAOYSA-N 0.000 claims description 5
- OUOCOSQUTDTFOI-UHFFFAOYSA-N n-[4-[3-(oxepan-4-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C1CCOCCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 OUOCOSQUTDTFOI-UHFFFAOYSA-N 0.000 claims description 5
- 230000036961 partial effect Effects 0.000 claims description 5
- 210000002637 putamen Anatomy 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 claims description 4
- NYDBTFLHTFVDII-UHFFFAOYSA-N 1-[4-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 NYDBTFLHTFVDII-UHFFFAOYSA-N 0.000 claims description 4
- JBKGNEWTPLGZFR-UHFFFAOYSA-N 1-[4-[2-[4-[(5-methylpyridin-2-yl)amino]phenoxy]pyridin-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=C(C)C=N1 JBKGNEWTPLGZFR-UHFFFAOYSA-N 0.000 claims description 4
- QTQMKXPIYBIGSW-UHFFFAOYSA-N 1-[4-[3-[2-(pyridine-4-carbonyl)phenoxy]pyrazin-2-yl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C1=NC=CN=C1OC1=CC=CC=C1C(=O)C1=CC=NC=C1 QTQMKXPIYBIGSW-UHFFFAOYSA-N 0.000 claims description 4
- BIIHYKHAFXFPRS-UHFFFAOYSA-N 1-[4-[3-[4-[(5-chloropyridin-2-yl)amino]phenoxy]pyrazin-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=C(Cl)C=N1 BIIHYKHAFXFPRS-UHFFFAOYSA-N 0.000 claims description 4
- BKVOUJAANVLAER-UHFFFAOYSA-N 1-methyl-4-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]piperidin-2-one Chemical compound C1C(=O)N(C)CCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 BKVOUJAANVLAER-UHFFFAOYSA-N 0.000 claims description 4
- ULMXCNUWTRIXHA-UHFFFAOYSA-N 2-[1-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]pyrrolidin-3-yl]propan-2-ol Chemical compound C1C(C(C)(O)C)CCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 ULMXCNUWTRIXHA-UHFFFAOYSA-N 0.000 claims description 4
- OBIWVFIYXKPNBD-UHFFFAOYSA-N 2-methoxy-1-[4-[3-[4-[(5-methylpyridin-2-yl)amino]phenoxy]pyrazin-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)COC)CCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=C(C)C=N1 OBIWVFIYXKPNBD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- PMGLZVXKDHUYHB-UHFFFAOYSA-N 3,5-difluoro-n-[4-[3-(oxan-4-yl)pyridin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound FC1=CC(F)=CN=C1NC(C=C1)=CC=C1OC1=NC=CC=C1C1CCOCC1 PMGLZVXKDHUYHB-UHFFFAOYSA-N 0.000 claims description 4
- OOGYQLSCIDNKTJ-UHFFFAOYSA-N 3-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]prop-2-yn-1-ol Chemical compound OCC#CC1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 OOGYQLSCIDNKTJ-UHFFFAOYSA-N 0.000 claims description 4
- HOSGJQOAQJHUCH-UHFFFAOYSA-N 4-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]cyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 HOSGJQOAQJHUCH-UHFFFAOYSA-N 0.000 claims description 4
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- 206010026749 Mania Diseases 0.000 claims description 4
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- QBHHPAVYYCLELV-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-[4-(pyridin-2-ylamino)phenoxy]pyridine-3-carboxamide Chemical compound C=1C=CN=C(OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C=1C(=O)NCC1CC1 QBHHPAVYYCLELV-UHFFFAOYSA-N 0.000 claims description 4
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- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 4
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- LTPOACJAKSJFPB-UHFFFAOYSA-N [2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]-[3-[3-(trifluoromethyl)phenoxy]azetidin-1-yl]methanone Chemical compound FC(F)(F)C1=CC=CC(OC2CN(C2)C(=O)C=2C(=NC=CC=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 LTPOACJAKSJFPB-UHFFFAOYSA-N 0.000 claims description 2
- WXIPXKBERUARNQ-UHFFFAOYSA-N [2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]-pyrrolidin-1-ylmethanone Chemical compound C=1C=CN=C(OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C=1C(=O)N1CCCC1 WXIPXKBERUARNQ-UHFFFAOYSA-N 0.000 claims description 2
- VWZHTHKFPWBMSB-UHFFFAOYSA-N [3-(4-chlorophenoxy)azetidin-1-yl]-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]methanone Chemical compound C1=CC(Cl)=CC=C1OC1CN(C(=O)C=2C(=NC=CC=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C1 VWZHTHKFPWBMSB-UHFFFAOYSA-N 0.000 claims description 2
- WDQIABDPPBTPTL-UHFFFAOYSA-N [3-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]phenyl]methanol Chemical compound OCC1=CC=CC(C=2C(=NC=CC=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 WDQIABDPPBTPTL-UHFFFAOYSA-N 0.000 claims description 2
- OAFYTJIKNKPOSC-UHFFFAOYSA-N [3-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]phenyl]methanol Chemical compound OCC1=CC=CC(C=2C(=NC=CN=2)OC=2C=CC(NC=3N=CC=CC=3)=CC=2)=C1 OAFYTJIKNKPOSC-UHFFFAOYSA-N 0.000 claims description 2
- FBQOKHKWNUUTHG-UHFFFAOYSA-N [4-(3-morpholin-4-ylpyrazin-2-yl)oxyphenyl]-pyridin-2-ylmethanone Chemical compound C=1C=CC=NC=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1N1CCOCC1 FBQOKHKWNUUTHG-UHFFFAOYSA-N 0.000 claims description 2
- OQWHVLHQKZBAIA-KRWDZBQOSA-N [4-[3-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]pyrazin-2-yl]oxyphenyl]-pyridin-2-ylmethanone Chemical compound COC[C@@H]1CCCN1C1=NC=CN=C1OC1=CC=C(C(=O)C=2N=CC=CC=2)C=C1 OQWHVLHQKZBAIA-KRWDZBQOSA-N 0.000 claims description 2
- VXRLSNNZLSOQSI-UHFFFAOYSA-N [4-[3-[4-(2-hydroxyethyl)piperazin-1-yl]pyrazin-2-yl]oxyphenyl]-pyridin-2-ylmethanone Chemical compound C1CN(CCO)CCN1C1=NC=CN=C1OC1=CC=C(C(=O)C=2N=CC=CC=2)C=C1 VXRLSNNZLSOQSI-UHFFFAOYSA-N 0.000 claims description 2
- PJWFTRKZYKEGCB-UHFFFAOYSA-N azetidin-1-yl-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]methanone Chemical compound C=1C=CN=C(OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C=1C(=O)N1CCC1 PJWFTRKZYKEGCB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 2
- PPPYSZLHBZXEOE-UHFFFAOYSA-N cyclopropyl-[4-[3-[4-[(5-methylpyridin-2-yl)amino]phenoxy]pyrazin-2-yl]piperidin-1-yl]methanone Chemical compound N1=CC(C)=CC=C1NC(C=C1)=CC=C1OC1=NC=CN=C1C1CCN(C(=O)C2CC2)CC1 PPPYSZLHBZXEOE-UHFFFAOYSA-N 0.000 claims description 2
- 125000005959 diazepanyl group Chemical group 0.000 claims description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims description 2
- LRTRDJKXHRFEJI-UHFFFAOYSA-N ethyl 1-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]piperidine-3-carboxylate Chemical compound C1C(C(=O)OCC)CCCN1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 LRTRDJKXHRFEJI-UHFFFAOYSA-N 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005394 methallyl group Chemical group 0.000 claims description 2
- DYYQZFYPGAOIDP-UHFFFAOYSA-N methyl 1-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OC)CCN1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 DYYQZFYPGAOIDP-UHFFFAOYSA-N 0.000 claims description 2
- NGTCMRXABCXPKB-UHFFFAOYSA-N methyl 1-[2-[4-(pyridin-2-ylamino)phenoxy]pyridin-3-yl]pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 NGTCMRXABCXPKB-UHFFFAOYSA-N 0.000 claims description 2
- ZSEKMSKLSQNRSU-UHFFFAOYSA-N methyl 1-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 ZSEKMSKLSQNRSU-UHFFFAOYSA-N 0.000 claims description 2
- QCQONIKODKIMCO-UHFFFAOYSA-N methyl 4-[3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 QCQONIKODKIMCO-UHFFFAOYSA-N 0.000 claims description 2
- VFMWMJGKMIXIDP-UHFFFAOYSA-N n',n'-dimethyl-2-[4-(pyridin-2-ylamino)phenoxy]pyridine-3-carbohydrazide Chemical compound CN(C)NC(=O)C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 VFMWMJGKMIXIDP-UHFFFAOYSA-N 0.000 claims description 2
- SKONCKVWSYBQFX-UHFFFAOYSA-N n-(1-benzylcyclopropyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazine-2-carboxamide Chemical compound N=1C=CN=C(OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C=1C(=O)NC1(CC=2C=CC=CC=2)CC1 SKONCKVWSYBQFX-UHFFFAOYSA-N 0.000 claims description 2
- QATOLQPRBYHATE-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazine-2-carboxamide Chemical compound OCCNC(=O)C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 QATOLQPRBYHATE-UHFFFAOYSA-N 0.000 claims description 2
- UGOYLDLWHYTYLC-UHFFFAOYSA-N n-(2-methoxyethyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound COCCNC1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 UGOYLDLWHYTYLC-UHFFFAOYSA-N 0.000 claims description 2
- KXRMXTHGJCSVAW-UHFFFAOYSA-N n-(2-methylpropyl)-2-[4-(pyridin-2-ylamino)phenoxy]pyridine-3-carboxamide Chemical compound CC(C)CNC(=O)C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 KXRMXTHGJCSVAW-UHFFFAOYSA-N 0.000 claims description 2
- BTEQBLZHCLSRGE-UHFFFAOYSA-N n-(2-methylpropyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound CC(C)CNC1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 BTEQBLZHCLSRGE-UHFFFAOYSA-N 0.000 claims description 2
- GPEIANYLEYGJDE-UHFFFAOYSA-N n-(2-phenylethyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound N=1C=CN=C(OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C=1NCCC1=CC=CC=C1 GPEIANYLEYGJDE-UHFFFAOYSA-N 0.000 claims description 2
- QHNXQDBGQQVWGT-UHFFFAOYSA-N n-(2-piperidin-1-ylethyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound N=1C=CN=C(OC=2C=CC(NC=3N=CC=CC=3)=CC=2)C=1NCCN1CCCCC1 QHNXQDBGQQVWGT-UHFFFAOYSA-N 0.000 claims description 2
- AIVRICGHIVKXLZ-UHFFFAOYSA-N n-(4-pyrazin-2-yloxyphenyl)pyridin-2-amine Chemical compound C=1C=CC=NC=1NC(C=C1)=CC=C1OC1=CN=CC=N1 AIVRICGHIVKXLZ-UHFFFAOYSA-N 0.000 claims description 2
- GLTISMKGQAZAKU-UHFFFAOYSA-N n-(cyclopropylmethyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound C1CC1CNC1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 GLTISMKGQAZAKU-UHFFFAOYSA-N 0.000 claims description 2
- XJXVLWGMXTXAKQ-UHFFFAOYSA-N n-(oxan-4-yl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound C1COCCC1NC1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 XJXVLWGMXTXAKQ-UHFFFAOYSA-N 0.000 claims description 2
- VVSYHEGYISRUIN-UHFFFAOYSA-N n-(oxolan-3-yl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound C1OCCC1NC1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 VVSYHEGYISRUIN-UHFFFAOYSA-N 0.000 claims description 2
- KACUOAXJJTUXOH-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)-3-[4-(pyridin-2-ylamino)phenoxy]pyrazin-2-amine Chemical compound C1CNCCC1CNC1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 KACUOAXJJTUXOH-UHFFFAOYSA-N 0.000 claims description 2
- FXFIHRXDRFMUDB-UHFFFAOYSA-N n-[2-fluoro-4-[3-(2-fluoropyridin-4-yl)pyrazin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C1=NC(F)=CC(C=2C(=NC=CN=2)OC=2C=C(F)C(NC=3N=CC=CC=3)=CC=2)=C1 FXFIHRXDRFMUDB-UHFFFAOYSA-N 0.000 claims description 2
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- BVZWZSBZWRSAIS-UHFFFAOYSA-N n-[2-fluoro-4-[3-(oxan-4-yl)pyrazin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C=1C=C(NC=2N=CC=CC=2)C(F)=CC=1OC1=NC=CN=C1C1CCOCC1 BVZWZSBZWRSAIS-UHFFFAOYSA-N 0.000 claims description 2
- QSMBDCSSADAFTO-UHFFFAOYSA-N n-[4-(3-cyclohexylpyridin-2-yl)oxyphenyl]pyridin-2-amine Chemical compound C1CCCCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 QSMBDCSSADAFTO-UHFFFAOYSA-N 0.000 claims description 2
- VMHICSKJDAGROO-UHFFFAOYSA-N n-[4-(3-cyclopentylpyrazin-2-yl)oxyphenyl]pyridin-2-amine Chemical compound C1CCCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 VMHICSKJDAGROO-UHFFFAOYSA-N 0.000 claims description 2
- NSUFIEDRLXRAPK-UHFFFAOYSA-N n-[4-(3-cyclopentylpyridin-2-yl)oxyphenyl]pyridin-2-amine Chemical compound C1CCCC1C1=CC=CN=C1OC(C=C1)=CC=C1NC1=CC=CC=N1 NSUFIEDRLXRAPK-UHFFFAOYSA-N 0.000 claims description 2
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- ZMEVCFJFTBJUNK-UHFFFAOYSA-N n-[4-(3-pyridin-4-ylpyridin-2-yl)oxyphenyl]quinolin-2-amine Chemical compound C=1C=C2C=CC=CC2=NC=1NC(C=C1)=CC=C1OC1=NC=CC=C1C1=CC=NC=C1 ZMEVCFJFTBJUNK-UHFFFAOYSA-N 0.000 claims description 2
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- RGQUCNBSUPMXAX-UHFFFAOYSA-N n-[4-(3-pyrimidin-4-ylpyridin-2-yl)oxyphenyl]-5-(trifluoromethyl)pyridin-2-amine Chemical compound N1=CC(C(F)(F)F)=CC=C1NC(C=C1)=CC=C1OC1=NC=CC=C1C1=CC=NC=N1 RGQUCNBSUPMXAX-UHFFFAOYSA-N 0.000 claims description 2
- QRCOJBWGNFFJTP-UHFFFAOYSA-N n-[4-(3-pyrimidin-4-ylpyridin-2-yl)oxyphenyl]-6-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)C1=CC=CC(NC=2C=CC(OC=3C(=CC=CN=3)C=3N=CN=CC=3)=CC=2)=N1 QRCOJBWGNFFJTP-UHFFFAOYSA-N 0.000 claims description 2
- VXFGFZRXADIAEG-UHFFFAOYSA-N n-[4-(3-pyrimidin-4-ylpyridin-2-yl)oxyphenyl]pyridin-2-amine Chemical compound C=1C=CC=NC=1NC(C=C1)=CC=C1OC1=NC=CC=C1C1=CC=NC=N1 VXFGFZRXADIAEG-UHFFFAOYSA-N 0.000 claims description 2
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- VQARPLYWKHOQFM-UHFFFAOYSA-N n-[4-[3-(1-benzothiophen-7-yl)pyrazin-2-yl]oxyphenyl]pyridin-2-amine Chemical compound C=1C=C(OC=2C(=NC=CN=2)C=2C=3SC=CC=3C=CC=2)C=CC=1NC1=CC=CC=N1 VQARPLYWKHOQFM-UHFFFAOYSA-N 0.000 claims description 2
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- ZMXIEURKVKVTSL-UHFFFAOYSA-N pyridin-2-yl-[4-(3-pyridin-4-ylpyrazin-2-yl)oxyphenyl]methanone Chemical compound C=1C=CC=NC=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1C1=CC=NC=C1 ZMXIEURKVKVTSL-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
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- 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
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- C07D401/12—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 linked by a chain containing hetero atoms as chain links
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US13844308P | 2008-12-17 | 2008-12-17 | |
| US13843408P | 2008-12-17 | 2008-12-17 | |
| US61/138,434 | 2008-12-17 | ||
| US61/138,443 | 2008-12-17 | ||
| PCT/US2009/068330 WO2010077992A1 (en) | 2008-12-17 | 2009-12-16 | Aminopyridine and carboxypyridine compounds as phosphodiesterase 10 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012512255A true JP2012512255A (ja) | 2012-05-31 |
| JP2012512255A5 JP2012512255A5 (enExample) | 2013-02-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2011542411A Ceased JP2012512255A (ja) | 2008-12-17 | 2009-12-16 | ホスホジエステラーゼ10阻害剤としてのアミノピリジンおよびカルボキシピリジン化合物 |
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| EP (1) | EP2376455B1 (enExample) |
| JP (1) | JP2012512255A (enExample) |
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| AU (1) | AU2009333214B2 (enExample) |
| CA (1) | CA2746307C (enExample) |
| ES (1) | ES2397934T3 (enExample) |
| MX (1) | MX2011006575A (enExample) |
| TW (1) | TW201035051A (enExample) |
| WO (1) | WO2010077992A1 (enExample) |
Cited By (1)
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| JP2020526547A (ja) * | 2017-07-12 | 2020-08-31 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 心不全の治療のためのrockの5員アミノヘテロ環および5,6−または6,6員二環式アミノヘテロ環の阻害剤 |
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| EP2748151B1 (en) * | 2011-08-25 | 2016-03-16 | Merck Sharp & Dohme Corp. | Pyrimidine pde10 inhibitors |
| US8470884B2 (en) | 2011-11-09 | 2013-06-25 | Hoffmann-La Roche Inc. | Alkenyl naphthylacetic acids |
| WO2013148537A1 (en) * | 2012-03-29 | 2013-10-03 | Ning Xi | Substituted spirobicyclic compounds and methods of use |
| MX2014013373A (es) | 2012-05-15 | 2015-08-14 | Novartis Ag | Derivados de benzamida para inhibir la actividad de abl1, abl2 y bcr-abl1. |
| RU2657540C2 (ru) * | 2012-06-26 | 2018-06-14 | Янссен Фармацевтика Нв | Комбинации, содержащие ингибиторы pde 2, такие как 1-арил-4-метил-[1,2,4]триазоло[4,3-а]хиноксалиновые соединения, и ингибиторы pde 10, для применения в лечении неврологических или метаболических расстройств |
| WO2014071044A1 (en) | 2012-11-01 | 2014-05-08 | Allergan, Inc. | Substituted 6,7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (pde10a) |
| US9200016B2 (en) | 2013-12-05 | 2015-12-01 | Allergan, Inc. | Substituted 6, 7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (PDE 10A) |
| US10647675B2 (en) | 2015-09-18 | 2020-05-12 | Kaken Pharmaceutical Co., Ltd. | Biaryl derivative and medicine containing same |
| ES2908801T3 (es) | 2016-06-07 | 2022-05-04 | Jacobio Pharmaceuticals Co Ltd | Nuevos derivados heterocíclicos útiles como inhibidores de SHP2 |
| JP2019534266A (ja) | 2016-10-14 | 2019-11-28 | 江蘇恒瑞医薬股▲ふん▼有限公司 | 5員ヘテロアリール環の架橋した環誘導体、その製造方法およびその医学的使用 |
| DK3601239T3 (da) | 2017-03-23 | 2024-09-30 | Jacobio Pharmaceuticals Co Ltd | Novel heterocyclic derivatives useful as shp2 inhibitors |
| CN108997230B (zh) * | 2018-07-26 | 2020-08-04 | 山东大学 | 具有基质金属蛋白酶抑制活性的喹喔啉衍生物及其制备方法和应用 |
| 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 |
| JP2023553699A (ja) | 2020-12-17 | 2023-12-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | ヘテロ芳香族イソチオシアネート類 |
| JP2025515208A (ja) * | 2022-05-09 | 2025-05-13 | ティーワイケー メディシンズ インコーポレーテッド | 多環式化合物およびその使用 |
| WO2025024688A1 (en) * | 2023-07-25 | 2025-01-30 | The Regents Of The University Of California | Ire1alpha inhibitors and uses thereof |
| WO2025024681A1 (en) * | 2023-07-25 | 2025-01-30 | The Regents Of The University Of California | Ire1alpha inhibitors and uses thereof |
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- 2009-12-16 MX MX2011006575A patent/MX2011006575A/es active IP Right Grant
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020526547A (ja) * | 2017-07-12 | 2020-08-31 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 心不全の治療のためのrockの5員アミノヘテロ環および5,6−または6,6員二環式アミノヘテロ環の阻害剤 |
| JP7234201B2 (ja) | 2017-07-12 | 2023-03-07 | ブリストル-マイヤーズ スクイブ カンパニー | 心不全の治療のためのrockの5員アミノヘテロ環および5,6-または6,6員二環式アミノヘテロ環の阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201035051A (en) | 2010-10-01 |
| MX2011006575A (es) | 2011-10-06 |
| EP2376455B1 (en) | 2012-11-14 |
| AU2009333214A1 (en) | 2011-06-30 |
| CA2746307C (en) | 2013-11-19 |
| US20100160280A1 (en) | 2010-06-24 |
| AR074775A1 (es) | 2011-02-09 |
| WO2010077992A1 (en) | 2010-07-08 |
| US8637500B2 (en) | 2014-01-28 |
| ES2397934T3 (es) | 2013-03-12 |
| EP2376455A1 (en) | 2011-10-19 |
| AU2009333214B2 (en) | 2013-09-26 |
| CA2746307A1 (en) | 2010-07-08 |
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