JP2015519401A5

JP2015519401A5 -

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Publication number: JP2015519401A5
Authority: JP; Japan
Prior art keywords: amino; pyrimidin; carbonyl; pyrazolo; methyl
Prior art date: 2013-06-11
Legal status : Granted

Application number

JP2015517370A

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English (en)

Japanese (ja)

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JP2015519401A (ja

JP6189945B2 (ja

Filing date

2013-06-11

Publication date

2016-08-04

2013-06-11 Application filed filed Critical

2013-06-11 Priority claimed from PCT/US2013/045266 external-priority patent/WO2013191965A1/en

2015-07-09 Publication of JP2015519401A publication Critical patent/JP2015519401A/ja

2016-08-04 Publication of JP2015519401A5 publication Critical patent/JP2015519401A5/ja

2017-08-30 Application granted granted Critical

2017-08-30 Publication of JP6189945B2 publication Critical patent/JP6189945B2/ja

Status Active legal-status Critical Current

2033-06-11 Anticipated expiration legal-status Critical

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-1 amino, monosubstituted amino Chemical group 0.000 claims description 127
239000000203 mixture Substances 0.000 claims description 18
150000001875 compounds Chemical class 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 4
229920000642 polymer Polymers 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 51
125000000217 alkyl group Chemical group 0.000 claims 39
229910052739 hydrogen Inorganic materials 0.000 claims 26
239000001257 hydrogen Substances 0.000 claims 26
150000002431 hydrogen Chemical class 0.000 claims 22
239000007787 solid Substances 0.000 claims 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 17
125000000753 cycloalkyl group Chemical group 0.000 claims 16
125000001424 substituent group Chemical group 0.000 claims 14
238000009472 formulation Methods 0.000 claims 12
125000004438 haloalkoxy group Chemical group 0.000 claims 12
125000005843 halogen group Chemical group 0.000 claims 12
125000001188 haloalkyl group Chemical group 0.000 claims 11
125000000547 substituted alkyl group Chemical group 0.000 claims 11
125000002947 alkylene group Chemical group 0.000 claims 10
125000004093 cyano group Chemical group *C#N 0.000 claims 9
125000002993 cycloalkylene group Chemical group 0.000 claims 9
125000000623 heterocyclic group Chemical group 0.000 claims 9
125000003545 alkoxy group Chemical group 0.000 claims 8
125000001072 heteroaryl group Chemical group 0.000 claims 8
125000003118 aryl group Chemical group 0.000 claims 7
238000000576 coating method Methods 0.000 claims 7
125000001153 fluoro group Chemical group F* 0.000 claims 6
238000002360 preparation method Methods 0.000 claims 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 6
150000003839 salts Chemical class 0.000 claims 6
239000011248 coating agent Substances 0.000 claims 5
239000002702 enteric coating Substances 0.000 claims 5
238000009505 enteric coating Methods 0.000 claims 5
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 4
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 4
125000004414 alkyl thio group Chemical group 0.000 claims 4
125000003710 aryl alkyl group Chemical group 0.000 claims 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
125000004475 heteroaralkyl group Chemical group 0.000 claims 4
125000005842 heteroatom Chemical group 0.000 claims 4
125000004415 heterocyclylalkyl group Chemical group 0.000 claims 4
229910052760 oxygen Inorganic materials 0.000 claims 4
201000004624 Dermatitis Diseases 0.000 claims 3
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 3
125000004476 heterocycloamino group Chemical group 0.000 claims 3
239000008194 pharmaceutical composition Substances 0.000 claims 3
DUOXDOVHDJDYMX-XMMPIXPASA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-piperidin-1-ylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCCCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 DUOXDOVHDJDYMX-XMMPIXPASA-N 0.000 claims 2
BJBBMHJDZCVALB-XMMPIXPASA-N 2-[(2r)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 BJBBMHJDZCVALB-XMMPIXPASA-N 0.000 claims 2
BJBBMHJDZCVALB-DEOSSOPVSA-N 2-[(2s)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 BJBBMHJDZCVALB-DEOSSOPVSA-N 0.000 claims 2
KZMQPYCXSAGLTB-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 KZMQPYCXSAGLTB-HXUWFJFHSA-N 0.000 claims 2
MPMKRFFUACUAAL-LJQANCHMSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)N(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 MPMKRFFUACUAAL-LJQANCHMSA-N 0.000 claims 2
MPMKRFFUACUAAL-IBGZPJMESA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)N(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 MPMKRFFUACUAAL-IBGZPJMESA-N 0.000 claims 2
UFVQLOXPJOGMRI-UHFFFAOYSA-N 3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]-2H-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound NC1=C2C(=NC=N1)NN=C2C2=C(C=C(C=C2)OC2=C(C(=CC=C2)F)F)F UFVQLOXPJOGMRI-UHFFFAOYSA-N 0.000 claims 2
IZUCDIMZZBQYLR-INIZCTEOSA-N 4-amino-N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(=CC(C)(C)N)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 IZUCDIMZZBQYLR-INIZCTEOSA-N 0.000 claims 2
206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims 2
FRMUZCKAJXQYQC-KRWDZBQOSA-N N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4,4-dimethylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(=CC(C)(C)C)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FRMUZCKAJXQYQC-KRWDZBQOSA-N 0.000 claims 2
HAUZZEVZYNEKHM-SFHVURJKSA-N N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-(dimethylamino)-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(=CC(C)(C)N(C)C)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 HAUZZEVZYNEKHM-SFHVURJKSA-N 0.000 claims 2
PTHYZAKMYJLMJF-SFHVURJKSA-N N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-ethoxy-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(C#N)=CC(C)(C)OCC)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 PTHYZAKMYJLMJF-SFHVURJKSA-N 0.000 claims 2
201000004681 Psoriasis Diseases 0.000 claims 2
201000001263 Psoriatic Arthritis Diseases 0.000 claims 2
208000036824 Psoriatic arthropathy Diseases 0.000 claims 2
206010046851 Uveitis Diseases 0.000 claims 2
125000002252 acyl group Chemical group 0.000 claims 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 2
229920006318 anionic polymer Polymers 0.000 claims 2
208000006673 asthma Diseases 0.000 claims 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 2
230000003111 delayed effect Effects 0.000 claims 2
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims 2
229910052736 halogen Inorganic materials 0.000 claims 2
150000002367 halogens Chemical class 0.000 claims 2
PWODFMKTYXDDTQ-KRWDZBQOSA-N n-[(2s)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyano-4-methylpent-2-enamide Chemical compound C12=C(N)N=CN=C2N(C[C@H](C)NC(=O)C(C#N)=CC(C)C)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 PWODFMKTYXDDTQ-KRWDZBQOSA-N 0.000 claims 2
229910052757 nitrogen Inorganic materials 0.000 claims 2
239000000546 pharmaceutical excipient Substances 0.000 claims 2
206010039073 rheumatoid arthritis Diseases 0.000 claims 2
229910052717 sulfur Inorganic materials 0.000 claims 2
208000011580 syndromic disease Diseases 0.000 claims 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
125000004486 1-methylpiperidin-3-yl group Chemical group CN1CC(CCC1)* 0.000 claims 1
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 1
RRADJHOBKOEMGY-UHFFFAOYSA-N 2-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)N(C)C RRADJHOBKOEMGY-UHFFFAOYSA-N 0.000 claims 1
SLYGDRWTJRPLPE-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-chloro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)Cl)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 SLYGDRWTJRPLPE-HXUWFJFHSA-N 0.000 claims 1
QWENXYFISYOVAE-LJQANCHMSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)C(F)(F)CN1C(=O)C(C#N)=CC1CC1 QWENXYFISYOVAE-LJQANCHMSA-N 0.000 claims 1
YVFLIMWHLSVODD-HSZRJFAPSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1[C@@H](CN2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 YVFLIMWHLSVODD-HSZRJFAPSA-N 0.000 claims 1
XNCWOKKBGJRERR-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(3-methyloxetan-3-yl)prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(C)COC1 XNCWOKKBGJRERR-HXUWFJFHSA-N 0.000 claims 1
OTEPSQCCLGCTHS-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCOCC1 OTEPSQCCLGCTHS-JOCHJYFZSA-N 0.000 claims 1
DJFYWYMNPNZOCD-NHCUHLMSSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[(2R)-pyrrolidin-2-yl]prop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=C[C@H]1CCCN1 DJFYWYMNPNZOCD-NHCUHLMSSA-N 0.000 claims 1
VWKLJHJZMCQRTA-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NCC)CC1 VWKLJHJZMCQRTA-OAQYLSRUSA-N 0.000 claims 1
PRRNZFGBGPELQP-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC)CC1 PRRNZFGBGPELQP-HXUWFJFHSA-N 0.000 claims 1
HAPRCXSAULDFHG-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC(C)C)CC1 HAPRCXSAULDFHG-JOCHJYFZSA-N 0.000 claims 1
VILCMHIZGWATBW-XMMPIXPASA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(CN(C)C)CCCC1 VILCMHIZGWATBW-XMMPIXPASA-N 0.000 claims 1
QLFDACIJUUSZFJ-LWMIZPGFSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCNC1 QLFDACIJUUSZFJ-LWMIZPGFSA-N 0.000 claims 1
VXMSFRPFOIGCQU-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCNCC1 VXMSFRPFOIGCQU-JOCHJYFZSA-N 0.000 claims 1
DJFYWYMNPNZOCD-BPGUCPLFSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 DJFYWYMNPNZOCD-BPGUCPLFSA-N 0.000 claims 1
BESYWHDYQFWATR-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 BESYWHDYQFWATR-HXUWFJFHSA-N 0.000 claims 1
FFNPAVVGSXGKFD-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-3-(2-methyl-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C[C@@H]3N(CCC3)C(=O)C(=CC3CC3)C#N)N=2)C(C)=CC=1OC1=CC=CC=C1 FFNPAVVGSXGKFD-JOCHJYFZSA-N 0.000 claims 1
YQBZUMLDZJOWCG-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-3-(3-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=C(F)C(OC=4C=CC=CC=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YQBZUMLDZJOWCG-OAQYLSRUSA-N 0.000 claims 1
UDMBWKPTVSCOHR-HXUWFJFHSA-N 2-[(2R)-2-[[4-amino-3-[2-fluoro-4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=C(F)C=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 UDMBWKPTVSCOHR-HXUWFJFHSA-N 0.000 claims 1
RPLMHDNWGHMMSD-ROPPNANJSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCNC1 RPLMHDNWGHMMSD-ROPPNANJSA-N 0.000 claims 1
ALECKWSRFHPUGK-MUMRKEEXSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 ALECKWSRFHPUGK-MUMRKEEXSA-N 0.000 claims 1
JNAYDXFMMRTTAX-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=C(F)C=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JNAYDXFMMRTTAX-OAQYLSRUSA-N 0.000 claims 1
CHUVQXPESSHLOM-JOCHJYFZSA-N 2-[(2R)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(C[C@@H]2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 CHUVQXPESSHLOM-JOCHJYFZSA-N 0.000 claims 1
XGIYERXTGLEFID-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 XGIYERXTGLEFID-OAQYLSRUSA-N 0.000 claims 1
XLALLISGANRDDC-HSZRJFAPSA-N 2-[(2R)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 XLALLISGANRDDC-HSZRJFAPSA-N 0.000 claims 1
UETBUVYLRUIFIP-OAQYLSRUSA-N 2-[(2R)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 UETBUVYLRUIFIP-OAQYLSRUSA-N 0.000 claims 1
FQEGACSJFGTHBB-HSZRJFAPSA-N 2-[(2R)-2-[[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=C(F)C=4)=CC=3)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 FQEGACSJFGTHBB-HSZRJFAPSA-N 0.000 claims 1
SLYGDRWTJRPLPE-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-chloro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)Cl)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 SLYGDRWTJRPLPE-FQEVSTJZSA-N 0.000 claims 1
QWENXYFISYOVAE-IBGZPJMESA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)C(F)(F)CN1C(=O)C(C#N)=CC1CC1 QWENXYFISYOVAE-IBGZPJMESA-N 0.000 claims 1
YVFLIMWHLSVODD-QHCPKHFHSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1[C@H](CN2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 YVFLIMWHLSVODD-QHCPKHFHSA-N 0.000 claims 1
OTEPSQCCLGCTHS-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCOCC1 OTEPSQCCLGCTHS-QFIPXVFZSA-N 0.000 claims 1
VWKLJHJZMCQRTA-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NCC)CC1 VWKLJHJZMCQRTA-NRFANRHFSA-N 0.000 claims 1
PRRNZFGBGPELQP-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC)CC1 PRRNZFGBGPELQP-FQEVSTJZSA-N 0.000 claims 1
HAPRCXSAULDFHG-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC(C)C)CC1 HAPRCXSAULDFHG-QFIPXVFZSA-N 0.000 claims 1
VILCMHIZGWATBW-DEOSSOPVSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC1(CN(C)C)CCCC1 VILCMHIZGWATBW-DEOSSOPVSA-N 0.000 claims 1
QLFDACIJUUSZFJ-IAXKEJLGSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCNC1 QLFDACIJUUSZFJ-IAXKEJLGSA-N 0.000 claims 1
VXMSFRPFOIGCQU-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCNCC1 VXMSFRPFOIGCQU-QFIPXVFZSA-N 0.000 claims 1
DJFYWYMNPNZOCD-LBAQZLPGSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 DJFYWYMNPNZOCD-LBAQZLPGSA-N 0.000 claims 1
NDLULCUHFGKSRR-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 NDLULCUHFGKSRR-FQEVSTJZSA-N 0.000 claims 1
BESYWHDYQFWATR-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 BESYWHDYQFWATR-FQEVSTJZSA-N 0.000 claims 1
FFNPAVVGSXGKFD-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-(2-methyl-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C[C@H]3N(CCC3)C(=O)C(=CC3CC3)C#N)N=2)C(C)=CC=1OC1=CC=CC=C1 FFNPAVVGSXGKFD-QFIPXVFZSA-N 0.000 claims 1
RYLUGFKKSWCGMS-SFHVURJKSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound N1([C@@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1)C(=O)C(C#N)=CC1(NC)CC1 RYLUGFKKSWCGMS-SFHVURJKSA-N 0.000 claims 1
RPLMHDNWGHMMSD-IJHRGXPZSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCNC1 RPLMHDNWGHMMSD-IJHRGXPZSA-N 0.000 claims 1
ALECKWSRFHPUGK-GGYWPGCISA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CCCN1 ALECKWSRFHPUGK-GGYWPGCISA-N 0.000 claims 1
ZYEDVNPMLFQSQS-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ZYEDVNPMLFQSQS-FQEVSTJZSA-N 0.000 claims 1
JNAYDXFMMRTTAX-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=C(F)C=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JNAYDXFMMRTTAX-NRFANRHFSA-N 0.000 claims 1
YLBOUHDKWPBHCU-FQEVSTJZSA-N 2-[(2S)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=CC=4F)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YLBOUHDKWPBHCU-FQEVSTJZSA-N 0.000 claims 1
YIDJEMDQRXSZRP-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-3-[4-(2-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=CC=CC=4)F)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 YIDJEMDQRXSZRP-NRFANRHFSA-N 0.000 claims 1
HWXKECVQNNJJPE-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-[4-(3,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=C(F)C=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 HWXKECVQNNJJPE-QFIPXVFZSA-N 0.000 claims 1
ODTVIGFDPJLHPJ-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-3-[4-(3-fluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=CC=4)=CC=3)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 ODTVIGFDPJLHPJ-QFIPXVFZSA-N 0.000 claims 1
CHUVQXPESSHLOM-QFIPXVFZSA-N 2-[(2S)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N(C[C@H]2N(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 CHUVQXPESSHLOM-QFIPXVFZSA-N 0.000 claims 1
XGIYERXTGLEFID-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 XGIYERXTGLEFID-NRFANRHFSA-N 0.000 claims 1
UETBUVYLRUIFIP-NRFANRHFSA-N 2-[(2S)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 UETBUVYLRUIFIP-NRFANRHFSA-N 0.000 claims 1
FQEGACSJFGTHBB-QHCPKHFHSA-N 2-[(2S)-2-[[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@H]1CN2C=3N=CN=C(C=3C(C=3C=CC(OC=4C=C(F)C=C(F)C=4)=CC=3)=C2)N)CCN1C(=O)C(C#N)=CC1CC1 FQEGACSJFGTHBB-QHCPKHFHSA-N 0.000 claims 1
DJFYWYMNPNZOCD-LEWJYISDSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-[(2s)-pyrrolidin-2-yl]prop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=C[C@@H]1CCCN1 DJFYWYMNPNZOCD-LEWJYISDSA-N 0.000 claims 1
JVLRCXYMHHEMSN-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C([C@@H]1CN2C=3N=CN=C(C=3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N)CCN1C(=O)C(C#N)=CC1CC1 JVLRCXYMHHEMSN-HXUWFJFHSA-N 0.000 claims 1
NDLULCUHFGKSRR-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 NDLULCUHFGKSRR-HXUWFJFHSA-N 0.000 claims 1
ZUCVBIOQSDKVLU-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound COCCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 ZUCVBIOQSDKVLU-JOCHJYFZSA-N 0.000 claims 1
AWYABWKHBBOMKD-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC(C)(C)NC1CC1 AWYABWKHBBOMKD-JOCHJYFZSA-N 0.000 claims 1
UIAAIUOKBHHXCL-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 UIAAIUOKBHHXCL-OAQYLSRUSA-N 0.000 claims 1
VKBHKMKUFODMAW-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound CCNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 VKBHKMKUFODMAW-OAQYLSRUSA-N 0.000 claims 1
PVBDQCRWZPYKOP-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound CCOC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 PVBDQCRWZPYKOP-OAQYLSRUSA-N 0.000 claims 1
PUFSHOBLKSMSCP-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound CNC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 PUFSHOBLKSMSCP-HXUWFJFHSA-N 0.000 claims 1
CDQOCVPNUKEIQE-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound CC(C)NC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 CDQOCVPNUKEIQE-JOCHJYFZSA-N 0.000 claims 1
NZIQNLGMMJGSQU-HSZRJFAPSA-N 2-[(2r)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCOCC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 NZIQNLGMMJGSQU-HSZRJFAPSA-N 0.000 claims 1
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POGITRIJKUNOCX-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=N1 POGITRIJKUNOCX-HXUWFJFHSA-N 0.000 claims 1
GZOPCCOHXKUGIP-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=CC=C(F)C=3)F)=CC=2)=N1 GZOPCCOHXKUGIP-OAQYLSRUSA-N 0.000 claims 1
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CSUHSJHWBUGLCV-HXUWFJFHSA-N 2-[(2r)-2-[[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=CC=CC=3F)F)=CC=2)=N1 CSUHSJHWBUGLCV-HXUWFJFHSA-N 0.000 claims 1
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OGWLOAWKWZUJRA-JOCHJYFZSA-N 2-[(2r)-2-[[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=C1 OGWLOAWKWZUJRA-JOCHJYFZSA-N 0.000 claims 1
XZYCHOYOFXAVON-AREMUKBSSA-N 2-[(2r)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(diethylamino)-4-methylpent-2-enenitrile Chemical compound CCN(CC)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 XZYCHOYOFXAVON-AREMUKBSSA-N 0.000 claims 1
OEOUGSPJZLNTDO-XMMPIXPASA-N 2-[(2r)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound CCOC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 OEOUGSPJZLNTDO-XMMPIXPASA-N 0.000 claims 1
WBIAKBCGGASHPE-AREMUKBSSA-N 2-[(2r)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCOCC1)N(C1=NC=NC(N)=C11)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WBIAKBCGGASHPE-AREMUKBSSA-N 0.000 claims 1
FPULLUIOKUXKIJ-HSZRJFAPSA-N 2-[(2r)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 FPULLUIOKUXKIJ-HSZRJFAPSA-N 0.000 claims 1
KWBJZFXSWFLQKE-OAQYLSRUSA-N 2-[(2r)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 KWBJZFXSWFLQKE-OAQYLSRUSA-N 0.000 claims 1
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MGOWUKVRTVSTIO-RUZDIDTESA-N 2-[(2r)-2-[[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C MGOWUKVRTVSTIO-RUZDIDTESA-N 0.000 claims 1
CBXYWKLJGUCHPH-IBGZPJMESA-N 2-[(2s)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CC(F)(F)C[C@H]1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 CBXYWKLJGUCHPH-IBGZPJMESA-N 0.000 claims 1
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WBIAKBCGGASHPE-SANMLTNESA-N 2-[(2s)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N1CCOCC1)N(C1=NC=NC(N)=C11)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WBIAKBCGGASHPE-SANMLTNESA-N 0.000 claims 1
FPULLUIOKUXKIJ-QHCPKHFHSA-N 2-[(2s)-2-[[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 FPULLUIOKUXKIJ-QHCPKHFHSA-N 0.000 claims 1
KWBJZFXSWFLQKE-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 KWBJZFXSWFLQKE-NRFANRHFSA-N 0.000 claims 1
BEBHIEGBOKTQIO-QFIPXVFZSA-N 2-[(2s)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 BEBHIEGBOKTQIO-QFIPXVFZSA-N 0.000 claims 1
NEHLIDMTSGJVNM-NRFANRHFSA-N 2-[(2s)-2-[[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound CC(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)=C1 NEHLIDMTSGJVNM-NRFANRHFSA-N 0.000 claims 1
MGOWUKVRTVSTIO-VWLOTQADSA-N 2-[(2s)-2-[[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]methyl]pyrrolidine-1-carbonyl]-4-(dimethylamino)-4-methylpent-2-enenitrile Chemical compound CN(C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1C MGOWUKVRTVSTIO-VWLOTQADSA-N 0.000 claims 1
JZJNGZMDAUNXTF-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 JZJNGZMDAUNXTF-JOCHJYFZSA-N 0.000 claims 1
BTWNIXPKIHIIBT-AREMUKBSSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 BTWNIXPKIHIIBT-AREMUKBSSA-N 0.000 claims 1
SONFNRMAPPWUNU-OAQYLSRUSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 SONFNRMAPPWUNU-OAQYLSRUSA-N 0.000 claims 1
GCYHPPFYYPCIBY-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC)CC1 GCYHPPFYYPCIBY-HXUWFJFHSA-N 0.000 claims 1
UFSIFBMUQNFAPP-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC(C)C)CC1 UFSIFBMUQNFAPP-JOCHJYFZSA-N 0.000 claims 1
AFAVFCVQCOJERG-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(C)C)CCCC1 AFAVFCVQCOJERG-XMMPIXPASA-N 0.000 claims 1
FXSMLAZXJKANGS-LWMIZPGFSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FXSMLAZXJKANGS-LWMIZPGFSA-N 0.000 claims 1
KDXBHDLLRUHOBA-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KDXBHDLLRUHOBA-JOCHJYFZSA-N 0.000 claims 1
KIHVEXSGLLUDHS-BPGUCPLFSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KIHVEXSGLLUDHS-BPGUCPLFSA-N 0.000 claims 1
FXEUQEMBQKIUER-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 FXEUQEMBQKIUER-HXUWFJFHSA-N 0.000 claims 1
JNSZJWMBASVFFG-OAQYLSRUSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)CCC1 JNSZJWMBASVFFG-OAQYLSRUSA-N 0.000 claims 1
XSXRHDHSVBTNAB-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F XSXRHDHSVBTNAB-HXUWFJFHSA-N 0.000 claims 1
NNJAGWVFMOGWLK-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 NNJAGWVFMOGWLK-XMMPIXPASA-N 0.000 claims 1
GGMKESHSVKUWPX-LJQANCHMSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 GGMKESHSVKUWPX-LJQANCHMSA-N 0.000 claims 1
OMCJCDOWQBLMQW-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC)CC1 OMCJCDOWQBLMQW-GOSISDBHSA-N 0.000 claims 1
PMNNGBDRAJTGMU-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC(C)C)CC1 PMNNGBDRAJTGMU-HXUWFJFHSA-N 0.000 claims 1
JSELVWXTZQCPKA-GOSISDBHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JSELVWXTZQCPKA-GOSISDBHSA-N 0.000 claims 1
JCDAJUALOINUEJ-ROPPNANJSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JCDAJUALOINUEJ-ROPPNANJSA-N 0.000 claims 1
GWSGAXGNGOQTFG-HXUWFJFHSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F GWSGAXGNGOQTFG-HXUWFJFHSA-N 0.000 claims 1
YOEWVNKRGSFIBQ-MUMRKEEXSA-N 2-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F YOEWVNKRGSFIBQ-MUMRKEEXSA-N 0.000 claims 1
UQLGRFKOEFQXTK-JOCHJYFZSA-N 2-[(3R)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 UQLGRFKOEFQXTK-JOCHJYFZSA-N 0.000 claims 1
SZZCEUUSTCQTDR-OAQYLSRUSA-N 2-[(3R)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 SZZCEUUSTCQTDR-OAQYLSRUSA-N 0.000 claims 1
UKURDKADUIBPHB-HSZRJFAPSA-N 2-[(3R)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 UKURDKADUIBPHB-HSZRJFAPSA-N 0.000 claims 1
JZJNGZMDAUNXTF-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(oxan-4-yl)prop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CCOCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 JZJNGZMDAUNXTF-QFIPXVFZSA-N 0.000 claims 1
BTWNIXPKIHIIBT-SANMLTNESA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 BTWNIXPKIHIIBT-SANMLTNESA-N 0.000 claims 1
SONFNRMAPPWUNU-NRFANRHFSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 SONFNRMAPPWUNU-NRFANRHFSA-N 0.000 claims 1
UFSIFBMUQNFAPP-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC(C)C)CC1 UFSIFBMUQNFAPP-QFIPXVFZSA-N 0.000 claims 1
AFAVFCVQCOJERG-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-[(dimethylamino)methyl]cyclopentyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(C)C)CCCC1 AFAVFCVQCOJERG-DEOSSOPVSA-N 0.000 claims 1
FXSMLAZXJKANGS-IAXKEJLGSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 FXSMLAZXJKANGS-IAXKEJLGSA-N 0.000 claims 1
KDXBHDLLRUHOBA-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KDXBHDLLRUHOBA-QFIPXVFZSA-N 0.000 claims 1
KIHVEXSGLLUDHS-LBAQZLPGSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KIHVEXSGLLUDHS-LBAQZLPGSA-N 0.000 claims 1
JNSZJWMBASVFFG-NRFANRHFSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)CCC1 JNSZJWMBASVFFG-NRFANRHFSA-N 0.000 claims 1
NNJAGWVFMOGWLK-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(diethylaminomethyl)cyclopentyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(CN(CC)CC)CCCC1 NNJAGWVFMOGWLK-DEOSSOPVSA-N 0.000 claims 1
GGMKESHSVKUWPX-IBGZPJMESA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(ethylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NCC)CC1 GGMKESHSVKUWPX-IBGZPJMESA-N 0.000 claims 1
OMCJCDOWQBLMQW-SFHVURJKSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(methylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC)CC1 OMCJCDOWQBLMQW-SFHVURJKSA-N 0.000 claims 1
PMNNGBDRAJTGMU-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-[1-(propan-2-ylamino)cyclopropyl]prop-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC1(NC(C)C)CC1 PMNNGBDRAJTGMU-FQEVSTJZSA-N 0.000 claims 1
JSELVWXTZQCPKA-SFHVURJKSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JSELVWXTZQCPKA-SFHVURJKSA-N 0.000 claims 1
JCDAJUALOINUEJ-IJHRGXPZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-3-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CNCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F JCDAJUALOINUEJ-IJHRGXPZSA-N 0.000 claims 1
GWSGAXGNGOQTFG-FQEVSTJZSA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-piperidin-4-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CCNCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F GWSGAXGNGOQTFG-FQEVSTJZSA-N 0.000 claims 1
YOEWVNKRGSFIBQ-GGYWPGCISA-N 2-[(3S)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-pyrrolidin-2-ylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2NCCC2)C#N)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F YOEWVNKRGSFIBQ-GGYWPGCISA-N 0.000 claims 1
UQLGRFKOEFQXTK-QFIPXVFZSA-N 2-[(3S)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 UQLGRFKOEFQXTK-QFIPXVFZSA-N 0.000 claims 1
SZZCEUUSTCQTDR-NRFANRHFSA-N 2-[(3S)-3-[4-amino-5-(2-fluoro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 SZZCEUUSTCQTDR-NRFANRHFSA-N 0.000 claims 1
HRTOJHBVIFYGJC-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]-6-methylpyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 HRTOJHBVIFYGJC-DEOSSOPVSA-N 0.000 claims 1
UKURDKADUIBPHB-QHCPKHFHSA-N 2-[(3S)-3-[4-amino-5-[4-(3,5-difluorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C=C1C(C=C1)=CC=C1OC1=CC(F)=CC(F)=C1 UKURDKADUIBPHB-QHCPKHFHSA-N 0.000 claims 1
YVXFHBBAHIDQJL-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidine-1-carbonyl]-3-cyclopropylprop-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CN(CCC2)C(=O)C(=CC2CC2)C#N)C(C)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 YVXFHBBAHIDQJL-DEOSSOPVSA-N 0.000 claims 1
HDRKIVDDSOTVRP-HSZRJFAPSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HDRKIVDDSOTVRP-HSZRJFAPSA-N 0.000 claims 1
OQTDUHVOPVMWPL-JOCHJYFZSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 OQTDUHVOPVMWPL-JOCHJYFZSA-N 0.000 claims 1
OYEWCPLOZQWRTA-JOCHJYFZSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 OYEWCPLOZQWRTA-JOCHJYFZSA-N 0.000 claims 1
DKEBWKMVXXEPHV-OAQYLSRUSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)OCC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 DKEBWKMVXXEPHV-OAQYLSRUSA-N 0.000 claims 1
STNWYIXKAQCFQK-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 STNWYIXKAQCFQK-HXUWFJFHSA-N 0.000 claims 1
IDUOQDBNMAPXQQ-JOCHJYFZSA-N 2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 IDUOQDBNMAPXQQ-JOCHJYFZSA-N 0.000 claims 1
LTAXJGIDEGVGKY-GOSISDBHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 LTAXJGIDEGVGKY-GOSISDBHSA-N 0.000 claims 1
BMHNUHSSZQGNFZ-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BMHNUHSSZQGNFZ-HXUWFJFHSA-N 0.000 claims 1
SOECMCJOWVYWNB-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 SOECMCJOWVYWNB-HXUWFJFHSA-N 0.000 claims 1
YBNBWNZKXLVIFP-LJQANCHMSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)OCC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 YBNBWNZKXLVIFP-LJQANCHMSA-N 0.000 claims 1
ZGHDUMGETQJRHI-GOSISDBHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 ZGHDUMGETQJRHI-GOSISDBHSA-N 0.000 claims 1
GUWMWABHJKWLKX-HXUWFJFHSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 GUWMWABHJKWLKX-HXUWFJFHSA-N 0.000 claims 1
NMPVOGJLOPRRNR-OAQYLSRUSA-N 2-[(3r)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCOCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F NMPVOGJLOPRRNR-OAQYLSRUSA-N 0.000 claims 1
HDRKIVDDSOTVRP-QHCPKHFHSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-3-(1-methylpiperidin-4-yl)prop-2-enenitrile Chemical compound C1CN(C)CCC1C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HDRKIVDDSOTVRP-QHCPKHFHSA-N 0.000 claims 1
KZMQPYCXSAGLTB-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 KZMQPYCXSAGLTB-FQEVSTJZSA-N 0.000 claims 1
OQTDUHVOPVMWPL-QFIPXVFZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 OQTDUHVOPVMWPL-QFIPXVFZSA-N 0.000 claims 1
OYEWCPLOZQWRTA-QFIPXVFZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 OYEWCPLOZQWRTA-QFIPXVFZSA-N 0.000 claims 1
MTMFUKIPDNCURW-NRFANRHFSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 MTMFUKIPDNCURW-NRFANRHFSA-N 0.000 claims 1
DKEBWKMVXXEPHV-NRFANRHFSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)OCC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 DKEBWKMVXXEPHV-NRFANRHFSA-N 0.000 claims 1
STNWYIXKAQCFQK-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 STNWYIXKAQCFQK-FQEVSTJZSA-N 0.000 claims 1
IDUOQDBNMAPXQQ-QFIPXVFZSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 IDUOQDBNMAPXQQ-QFIPXVFZSA-N 0.000 claims 1
KYLMVBZZOSOHLD-QHCPKHFHSA-N 2-[(3s)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCOCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KYLMVBZZOSOHLD-QHCPKHFHSA-N 0.000 claims 1
LTAXJGIDEGVGKY-SFHVURJKSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 LTAXJGIDEGVGKY-SFHVURJKSA-N 0.000 claims 1
BMHNUHSSZQGNFZ-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(2-methoxyethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCCOC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 BMHNUHSSZQGNFZ-FQEVSTJZSA-N 0.000 claims 1
SOECMCJOWVYWNB-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(cyclopropylamino)-4-methylpent-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C(=C(F)C=CC=4)F)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)NC1CC1 SOECMCJOWVYWNB-FQEVSTJZSA-N 0.000 claims 1
SQQLZKRKYFKTLJ-IBGZPJMESA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(ethylamino)-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NCC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 SQQLZKRKYFKTLJ-IBGZPJMESA-N 0.000 claims 1
YBNBWNZKXLVIFP-IBGZPJMESA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-ethoxy-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)OCC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 YBNBWNZKXLVIFP-IBGZPJMESA-N 0.000 claims 1
ZGHDUMGETQJRHI-SFHVURJKSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(methylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 ZGHDUMGETQJRHI-SFHVURJKSA-N 0.000 claims 1
GUWMWABHJKWLKX-FQEVSTJZSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(propan-2-ylamino)pent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)(C)NC(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 GUWMWABHJKWLKX-FQEVSTJZSA-N 0.000 claims 1
NMPVOGJLOPRRNR-NRFANRHFSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-morpholin-4-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCOCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC(F)=C1F NMPVOGJLOPRRNR-NRFANRHFSA-N 0.000 claims 1
VSOCUEJKFRWWRZ-SFHVURJKSA-N 2-[(3s)-3-[4-amino-3-[4-(2,3-difluorophenoxy)-2-fluorophenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1N(C(=O)C(C#N)=CC(C)C)CCC[C@@H]1N1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C(=C(F)C=CC=3)F)=CC=2)F)=N1 VSOCUEJKFRWWRZ-SFHVURJKSA-N 0.000 claims 1
LXMLVOPDJHSYST-UHFFFAOYSA-N 2-[2-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethylsulfonyl]-3-cyclopropylprop-2-enenitrile Chemical compound N1=C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)C=2C(N)=NC=NC=2N1CCS(=O)(=O)C(C#N)=CC1CC1 LXMLVOPDJHSYST-UHFFFAOYSA-N 0.000 claims 1
NDLULCUHFGKSRR-UHFFFAOYSA-N 2-[2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile Chemical compound CC(C)(C)C=C(C#N)C(=O)N1CCCC1CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1 NDLULCUHFGKSRR-UHFFFAOYSA-N 0.000 claims 1
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JP2015517370A 2012-06-18 2013-06-11 癌および自己免疫疾患の治療に有用な可逆性共有結合ピロロ−またはピラゾロピリミジン Active JP6189945B2 (ja)