JP2016514710A5 - - Google Patents
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- JP2016514710A5 JP2016514710A5 JP2016503522A JP2016503522A JP2016514710A5 JP 2016514710 A5 JP2016514710 A5 JP 2016514710A5 JP 2016503522 A JP2016503522 A JP 2016503522A JP 2016503522 A JP2016503522 A JP 2016503522A JP 2016514710 A5 JP2016514710 A5 JP 2016514710A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- amino
- oxo
- dihydro
- pyrazolo
- 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
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- 125000000217 alkyl group Chemical group 0.000 claims 136
- -1 aminocarbonyloxy Chemical group 0.000 claims 43
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 24
- 125000003118 aryl group Chemical group 0.000 claims 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 14
- 125000001072 heteroaryl group Chemical group 0.000 claims 14
- 150000003839 salts Chemical class 0.000 claims 14
- 150000001875 compounds Chemical class 0.000 claims 13
- 125000003282 alkyl amino group Chemical group 0.000 claims 12
- RLZJFTOYCVIYLE-UHFFFAOYSA-N oxane-4-carbonitrile Chemical compound N#CC1CCOCC1 RLZJFTOYCVIYLE-UHFFFAOYSA-N 0.000 claims 12
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 10
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 208000006673 asthma Diseases 0.000 claims 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 5
- 206010003246 arthritis Diseases 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000004404 heteroalkyl group Chemical group 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 claims 3
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims 3
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims 3
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 230000005764 inhibitory process Effects 0.000 claims 3
- 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 claims 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 2
- PHABQEUMBQLONZ-UHFFFAOYSA-N 3-[3-(4-tert-butylsulfonylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxepane-4-carbonitrile Chemical compound C(C)(C)(C)S(=O)(=O)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1COCCCC1C#N PHABQEUMBQLONZ-UHFFFAOYSA-N 0.000 claims 2
- FZZHOXMWASTDDC-UHFFFAOYSA-N 3-[3-[4-(2,6-dimethylmorpholin-4-yl)sulfonylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1CN(CC(C)O1)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 FZZHOXMWASTDDC-UHFFFAOYSA-N 0.000 claims 2
- DATDNGCXBBJWGO-UHFFFAOYSA-N 3-[3-[4-[1-(dimethylamino)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CN(C)C(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)C(F)(F)F DATDNGCXBBJWGO-UHFFFAOYSA-N 0.000 claims 2
- RLLHQSRIRJBRFP-UHFFFAOYSA-N 5-[3-(4-tert-butylsulfonylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxepane-4-carbonitrile Chemical compound C(C)(C)(C)S(=O)(=O)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1C(CCOCC1)C#N RLLHQSRIRJBRFP-UHFFFAOYSA-N 0.000 claims 2
- 208000003456 Juvenile Arthritis Diseases 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- IOXDCCCOLUVQMN-UHFFFAOYSA-N N-tert-butyl-4-[[1-(4-cyanooxan-3-yl)-4-oxo-5H-pyrazolo[4,3-c]pyridin-3-yl]amino]-N-methylbenzenesulfonamide Chemical compound CN(C(C)(C)C)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 IOXDCCCOLUVQMN-UHFFFAOYSA-N 0.000 claims 2
- 125000004442 acylamino group Chemical group 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims 2
- 230000000414 obstructive effect Effects 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004889 1-methylethylamino group Chemical group CC(C)N* 0.000 claims 1
- NWQCVVREYYCLTJ-UHFFFAOYSA-N 3-(3-anilino-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl)oxane-4-carbonitrile Chemical compound O=c1[nH]ccc2n(nc(Nc3ccccc3)c12)C1COCCC1C#N NWQCVVREYYCLTJ-UHFFFAOYSA-N 0.000 claims 1
- DXVXXWQBLURGJX-UHFFFAOYSA-N 3-[3-(3,4-dimethylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound Cc1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1C DXVXXWQBLURGJX-UHFFFAOYSA-N 0.000 claims 1
- CDYRUVDODWFAHB-UHFFFAOYSA-N 3-[3-(4-chloro-3-methylsulfonylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CS(=O)(=O)c1cc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)ccc1Cl CDYRUVDODWFAHB-UHFFFAOYSA-N 0.000 claims 1
- MSLAFAQZAUHBCE-UHFFFAOYSA-N 3-[3-(4-cyano-3-fluoroanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound Fc1cc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)ccc1C#N MSLAFAQZAUHBCE-UHFFFAOYSA-N 0.000 claims 1
- LMBKZSAOJSEFTR-UHFFFAOYSA-N 3-[3-(4-cyanoanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound C(#N)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N LMBKZSAOJSEFTR-UHFFFAOYSA-N 0.000 claims 1
- VCNURNCZJFPRHP-UHFFFAOYSA-N 3-[3-(4-fluoro-3-methoxyanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound COc1cc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)ccc1F VCNURNCZJFPRHP-UHFFFAOYSA-N 0.000 claims 1
- XTMVJGRVZLDCNX-UHFFFAOYSA-N 3-[3-(4-fluoro-3-methylsulfinylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound FC1=C(C=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N)S(=O)C XTMVJGRVZLDCNX-UHFFFAOYSA-N 0.000 claims 1
- DUNNDRSGOPPNJN-UHFFFAOYSA-N 3-[3-(4-methylsulfonylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CS(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 DUNNDRSGOPPNJN-UHFFFAOYSA-N 0.000 claims 1
- LDLPWZKLUCQRQL-UHFFFAOYSA-N 3-[3-(4-tert-butylsulfonylanilino)-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound C(C)(C)(C)S(=O)(=O)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1COCCC1C#N LDLPWZKLUCQRQL-UHFFFAOYSA-N 0.000 claims 1
- FAEYPXVCHWMLMH-UHFFFAOYSA-N 3-[3-[(2-fluoropyridin-4-yl)amino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound Fc1cc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)ccn1 FAEYPXVCHWMLMH-UHFFFAOYSA-N 0.000 claims 1
- VXJWYZRDVLGCKC-UHFFFAOYSA-N 3-[3-[(2-methyl-1,3-benzothiazol-6-yl)amino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1=NC2=CC=C(NC3=NN(C4COCCC4C#N)C4=C3C(=O)NC=C4)C=C2S1 VXJWYZRDVLGCKC-UHFFFAOYSA-N 0.000 claims 1
- UDZITTSXSXGDKJ-UHFFFAOYSA-N 3-[3-[4-(1-amino-2,2,2-trifluoroethyl)anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound NC(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)C(F)(F)F UDZITTSXSXGDKJ-UHFFFAOYSA-N 0.000 claims 1
- LSFCHWZFVUIURS-UHFFFAOYSA-N 3-[3-[4-(2,2-dimethylmorpholin-4-yl)sulfonylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1(C)CN(CCO1)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 LSFCHWZFVUIURS-UHFFFAOYSA-N 0.000 claims 1
- NKAVHSSKHLLZAC-UHFFFAOYSA-N 3-[3-[4-(2,2-dimethylpyrrolidin-1-yl)sulfonylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1(C)CCCN1S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 NKAVHSSKHLLZAC-UHFFFAOYSA-N 0.000 claims 1
- TWFDWXGERBQRFS-UHFFFAOYSA-N 3-[3-[4-(2,3-dimethylbutan-2-ylsulfonyl)anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound O=C1NC=CC2=C1C(=NN2C1COCCC1C#N)NC1=CC=C(C=C1)S(=O)(=O)C(C(C)C)(C)C TWFDWXGERBQRFS-UHFFFAOYSA-N 0.000 claims 1
- XCJUMLLVKNXZCG-UHFFFAOYSA-N 3-[3-[4-(2-aminopropan-2-yl)anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound NC(C)(C)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N XCJUMLLVKNXZCG-UHFFFAOYSA-N 0.000 claims 1
- YWIXRQRPWHUIDZ-UHFFFAOYSA-N 3-[3-[4-(2-methylazetidin-1-yl)sulfonylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1CCN1S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 YWIXRQRPWHUIDZ-UHFFFAOYSA-N 0.000 claims 1
- NSAPRGTZLWOKML-UHFFFAOYSA-N 3-[3-[4-(2-methylbutan-2-ylsulfonyl)anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC(CC)(C)S(=O)(=O)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N NSAPRGTZLWOKML-UHFFFAOYSA-N 0.000 claims 1
- WEHZPWUKUMWGGZ-UHFFFAOYSA-N 3-[3-[4-(2-methylmorpholin-4-yl)sulfonylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1CN(CCO1)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 WEHZPWUKUMWGGZ-UHFFFAOYSA-N 0.000 claims 1
- ZJEWGVXYZXEGSA-UHFFFAOYSA-N 3-[3-[4-(3-methylazetidin-1-yl)sulfonylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1CN(C1)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 ZJEWGVXYZXEGSA-UHFFFAOYSA-N 0.000 claims 1
- FPPBCXXQYOINRJ-UHFFFAOYSA-N 3-[3-[4-(4,4-difluoropiperidine-1-carbonyl)-3-methylanilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound FC1(CCN(CC1)C(=O)C1=C(C=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1COCCC1C#N)C)F FPPBCXXQYOINRJ-UHFFFAOYSA-N 0.000 claims 1
- FPISKLKIWBBDAB-UHFFFAOYSA-N 3-[3-[4-(5,5-dimethyl-3-oxo-2-oxabicyclo[2.2.2]octan-1-yl)anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1(C2C(OC(C1)(CC2)C2=CC=C(C=C2)NC2=NN(C1=C2C(NC=C1)=O)C1COCCC1C#N)=O)C FPISKLKIWBBDAB-UHFFFAOYSA-N 0.000 claims 1
- IDWYKKGXCFTFGK-UHFFFAOYSA-N 3-[3-[4-(azetidin-1-ylsulfonyl)anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound O=c1[nH]ccc2n(nc(Nc3ccc(cc3)S(=O)(=O)N3CCC3)c12)C1COCCC1C#N IDWYKKGXCFTFGK-UHFFFAOYSA-N 0.000 claims 1
- UZFQQJCBGJXNFG-UHFFFAOYSA-N 3-[3-[4-[1-(2,2-dimethylpropylamino)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC(CNC(C(F)(F)F)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1COCCC1C#N)(C)C UZFQQJCBGJXNFG-UHFFFAOYSA-N 0.000 claims 1
- XAILBBYMKDLIKC-UHFFFAOYSA-N 3-[3-[4-[1-(azetidin-1-yl)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound N1(CCC1)C(C(F)(F)F)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1COCCC1C#N XAILBBYMKDLIKC-UHFFFAOYSA-N 0.000 claims 1
- HICWURMPDPCWRE-UHFFFAOYSA-N 3-[3-[4-[1-(cyclobutylamino)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound FC(F)(F)C(NC1CCC1)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 HICWURMPDPCWRE-UHFFFAOYSA-N 0.000 claims 1
- WCMAJBONEJRSME-UHFFFAOYSA-N 3-[3-[4-[1-(cyclopentylamino)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound C1(CCCC1)NC(C(F)(F)F)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N WCMAJBONEJRSME-UHFFFAOYSA-N 0.000 claims 1
- UVJKFXUPMZJTBX-UHFFFAOYSA-N 3-[3-[4-[1-(cyclopropylamino)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound FC(F)(F)C(NC1CC1)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 UVJKFXUPMZJTBX-UHFFFAOYSA-N 0.000 claims 1
- FUGMNWHQRGIZSH-UHFFFAOYSA-N 3-[3-[4-[1-(ethylamino)-2,2,2-trifluoroethyl]anilino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound C(C)NC(C(F)(F)F)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N FUGMNWHQRGIZSH-UHFFFAOYSA-N 0.000 claims 1
- RYCVMXONAHTSQD-UHFFFAOYSA-N 3-[3-[[3-methyl-2-oxo-3-(propan-2-ylamino)-1H-indol-6-yl]amino]-4-oxo-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC(C)NC1(C)C(=O)Nc2cc(Nc3nn(C4COCCC4C#N)c4cc[nH]c(=O)c34)ccc12 RYCVMXONAHTSQD-UHFFFAOYSA-N 0.000 claims 1
- QHEVCBUOBQXHRF-UHFFFAOYSA-N 3-[4-oxo-3-(4-propan-2-ylsulfonylanilino)-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC(C)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 QHEVCBUOBQXHRF-UHFFFAOYSA-N 0.000 claims 1
- XTGCIKKWHWYMIJ-UHFFFAOYSA-N 3-[4-oxo-3-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound O=C1NC=CC2=C1C(=NN2C1COCCC1C#N)NC1=CC=C(C=C1)C(C(F)(F)F)(C)O XTGCIKKWHWYMIJ-UHFFFAOYSA-N 0.000 claims 1
- IFYXHVRGQCIDKX-UHFFFAOYSA-N 3-[4-oxo-3-[4-(2,2,2-trifluoro-1-hydroxy-1-pyridin-2-ylethyl)anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound OC(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)(c1ccccn1)C(F)(F)F IFYXHVRGQCIDKX-UHFFFAOYSA-N 0.000 claims 1
- SBLQVHXFSYAJFC-UHFFFAOYSA-N 3-[4-oxo-3-[4-(2,2,2-trifluoro-1-hydroxy-1-pyridin-4-ylethyl)anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound OC(c1ccncc1)(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)C(F)(F)F SBLQVHXFSYAJFC-UHFFFAOYSA-N 0.000 claims 1
- JEHLIIJLLCMZCZ-UHFFFAOYSA-N 3-[4-oxo-3-[4-(2,2,2-trifluoro-1-piperazin-1-ylethyl)anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound O=C1NC=CC2=C1C(=NN2C1COCCC1C#N)NC1=CC=C(C=C1)C(C(F)(F)F)N1CCNCC1 JEHLIIJLLCMZCZ-UHFFFAOYSA-N 0.000 claims 1
- TVAFKVGYDWDABI-UHFFFAOYSA-N 3-[4-oxo-3-[4-(2,2,2-trifluoro-1-pyrrolidin-1-ylethyl)anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound O=C1NC=CC2=C1C(=NN2C1COCCC1C#N)NC1=CC=C(C=C1)C(C(F)(F)F)N1CCCC1 TVAFKVGYDWDABI-UHFFFAOYSA-N 0.000 claims 1
- QOVQCZIHBVAUAW-UHFFFAOYSA-N 3-[4-oxo-3-[4-[2,2,2-trifluoro-1-(2-methylpropylamino)ethyl]anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound O=C1NC=CC2=C1C(=NN2C2COCCC2C#N)NC2=CC=C(C=C2)C(C(F)(F)F)NCC(C)C QOVQCZIHBVAUAW-UHFFFAOYSA-N 0.000 claims 1
- UNFLXRVOHAFEMD-UHFFFAOYSA-N 3-[4-oxo-3-[4-[2,2,2-trifluoro-1-(2-methylpyrrolidin-1-yl)ethyl]anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC1CCCN1C(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)C(F)(F)F UNFLXRVOHAFEMD-UHFFFAOYSA-N 0.000 claims 1
- NAITXMCGULBVPE-UHFFFAOYSA-N 3-[4-oxo-3-[4-[2,2,2-trifluoro-1-(4-methylpiperazin-1-yl)ethyl]anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CN1CCN(CC1)C(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)C(F)(F)F NAITXMCGULBVPE-UHFFFAOYSA-N 0.000 claims 1
- VJNMTKUCKLBHNN-UHFFFAOYSA-N 3-[4-oxo-3-[4-[2,2,2-trifluoro-1-(propan-2-ylamino)ethyl]anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC(C)NC(c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1)C(F)(F)F VJNMTKUCKLBHNN-UHFFFAOYSA-N 0.000 claims 1
- GNQRXVPCERRFFA-UHFFFAOYSA-N 3-[4-oxo-3-[4-[2-(propan-2-ylamino)propan-2-yl]anilino]-5H-pyrazolo[4,3-c]pyridin-1-yl]oxane-4-carbonitrile Chemical compound CC(C)(NC(C)C)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C2COCCC2C#N GNQRXVPCERRFFA-UHFFFAOYSA-N 0.000 claims 1
- SJDCORZYFJDIGG-UHFFFAOYSA-N 4-[[1-(4-cyanooxan-3-yl)-4-oxo-5H-pyrazolo[4,3-c]pyridin-3-yl]amino]-N,N-dimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)c1ccc(Nc2nn(C3COCCC3C#N)c3cc[nH]c(=O)c23)cc1 SJDCORZYFJDIGG-UHFFFAOYSA-N 0.000 claims 1
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- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 1
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- KMMWOCNAVRZJCV-UHFFFAOYSA-N N-tert-butyl-4-[[1-(4-cyanooxan-3-yl)-4-oxo-5H-pyrazolo[4,3-c]pyridin-3-yl]amino]-N-ethylbenzenesulfonamide Chemical compound C(C)(C)(C)N(S(=O)(=O)C1=CC=C(C=C1)NC1=NN(C2=C1C(NC=C2)=O)C1COCCC1C#N)CC KMMWOCNAVRZJCV-UHFFFAOYSA-N 0.000 claims 1
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- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
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- 125000004122 cyclic group Chemical group 0.000 claims 1
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| PCT/CN2014/000298 WO2014146492A1 (en) | 2013-03-19 | 2014-03-19 | N-(2-cyano heterocyclyl)pyrazolo pyridones as janus kinase inhibitors |
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| JP2016514710A JP2016514710A (ja) | 2016-05-23 |
| JP2016514710A5 true JP2016514710A5 (https=) | 2017-04-13 |
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| WO2014146246A1 (en) * | 2013-03-19 | 2014-09-25 | Merck Sharp & Dohme Corp. | Cycloalkyl nitrile pyrazolo pyridones as janus kinase inhibitors |
| WO2016061751A1 (en) | 2014-10-22 | 2016-04-28 | Merck Sharp & Dohme Corp. | Ethyl n-boc piperidinyl pyrazolo pyridones as janus kinase inhibitors |
| US10766883B2 (en) | 2016-12-14 | 2020-09-08 | Merck Sharp & Dohme Corp. | Aminopyrazoles as janus kinase inhibitors |
| US20220143049A1 (en) | 2019-03-21 | 2022-05-12 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| EP4054579A1 (en) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CN111499592B (zh) * | 2020-03-14 | 2023-06-23 | 江苏省农用激素工程技术研究中心有限公司 | 5-氨甲基糖精的合成方法 |
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| JP2759227B2 (ja) * | 1990-09-28 | 1998-05-28 | 大鵬薬品工業株式会社 | ピラゾロピリジン誘導体 |
| JP2003501429A (ja) | 1999-06-03 | 2003-01-14 | クノール・ゲー・エム・ベー・ハー | ベンゾチアジノンおよびベンゾオキサジノン化合物 |
| RU2004128943A (ru) | 2002-02-28 | 2005-04-20 | Байота, Инк. (Us) | Средства, имитирующие нуклеотиды, и их пролекарственные формы |
| CA2482838A1 (en) * | 2002-05-31 | 2003-12-11 | Eisai Co., Ltd. | Pyrazole compounds and pharmaceutical compositions containing the compound |
| JP4139185B2 (ja) | 2002-10-17 | 2008-08-27 | 京セラ株式会社 | 配線基板の製造方法 |
| CN102532133A (zh) * | 2006-01-17 | 2012-07-04 | 沃泰克斯药物股份有限公司 | 适用作詹纳斯激酶抑制剂的吖吲哚类 |
| EP2123651A4 (en) * | 2007-01-12 | 2011-05-04 | Astellas Pharma Inc | CONDENSED PYRIDINE COMPOUND |
| US9346809B2 (en) | 2009-07-08 | 2016-05-24 | Leo Pharma A/S | Heterocyclic compounds as JAK receptor and protein tyrosine kinase inhibitors |
| PT3354652T (pt) | 2010-03-10 | 2020-07-20 | Incyte Holdings Corp | Derivados de piperidin-4-ilazetidina como inibidores de jak1 |
| WO2012127506A1 (en) | 2011-03-22 | 2012-09-27 | Advinus Therapeutics Limited | Substituted fused tricyclic compounds, compositions and medicinal applications thereof |
| WO2013041042A1 (en) * | 2011-09-22 | 2013-03-28 | Merck Sharp & Dohme Corp. | Pyrazole carboxamides as janus kinase inhibitors |
| WO2013180265A1 (ja) * | 2012-06-01 | 2013-12-05 | 武田薬品工業株式会社 | 複素環化合物 |
| WO2014146246A1 (en) * | 2013-03-19 | 2014-09-25 | Merck Sharp & Dohme Corp. | Cycloalkyl nitrile pyrazolo pyridones as janus kinase inhibitors |
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2014
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- 2014-03-19 WO PCT/CN2014/000298 patent/WO2014146492A1/en not_active Ceased
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- 2014-03-19 CN CN201480016754.4A patent/CN105189497B/zh not_active Expired - Fee Related
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- 2014-03-19 BR BR112015023878A patent/BR112015023878A2/pt not_active Application Discontinuation
- 2014-03-19 RU RU2015144483A patent/RU2669922C2/ru not_active IP Right Cessation
- 2014-03-19 JP JP2016503522A patent/JP6322275B2/ja active Active
- 2014-03-19 MX MX2015013414A patent/MX2015013414A/es unknown
- 2014-03-19 CA CA2901766A patent/CA2901766A1/en not_active Abandoned
- 2014-03-19 AU AU2014234908A patent/AU2014234908B2/en not_active Ceased
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