CA2987054A1 - Inhibitors of bruton's tyrosine kinase - Google Patents

Info

Publication number

CA2987054A1

CA2987054A1 CA2987054A CA2987054A CA2987054A1 CA 2987054 A1 CA2987054 A1 CA 2987054A1 CA 2987054 A CA2987054 A CA 2987054A CA 2987054 A CA2987054 A CA 2987054A CA 2987054 A1 CA2987054 A1 CA 2987054A1

Authority

CA

Canada

Prior art keywords

substituted

unsubstituted

compound

carboxamide

piperidin

Prior art date

2015-06-02

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000003112 inhibitor Substances 0.000 title abstract description 39
• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 title abstract description 38
• 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 title abstract description 38
• 150000001875 compounds Chemical class 0.000 claims abstract description 815
• 238000000034 method Methods 0.000 claims abstract description 98
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 93
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 48
• 201000010099 disease Diseases 0.000 claims abstract description 45
• 201000011510 cancer Diseases 0.000 claims abstract description 40
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 18
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 14
• IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 claims description 356
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 315
• 150000003839 salts Chemical class 0.000 claims description 132
• 239000012453 solvate Substances 0.000 claims description 132
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 117
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 111
• 229940002612 prodrug Drugs 0.000 claims description 110
• 239000000651 prodrug Substances 0.000 claims description 110
• 125000005843 halogen group Chemical group 0.000 claims description 83
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 76
• 229910052736 halogen Inorganic materials 0.000 claims description 71
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 61
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 54
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• 239000000203 mixture Substances 0.000 claims description 49
• 208000035475 disorder Diseases 0.000 claims description 48
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 43
• 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 37
• 150000002367 halogens Chemical class 0.000 claims description 37
• 125000004432 carbon atom Chemical group C* 0.000 claims description 34
• 229910052799 carbon Inorganic materials 0.000 claims description 33
• 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 33
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 31
• 125000004076 pyridyl group Chemical group 0.000 claims description 30
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 26
• 210000003719 b-lymphocyte Anatomy 0.000 claims description 24
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 24
• 125000001424 substituent group Chemical group 0.000 claims description 24
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 23
• 230000002062 proliferating effect Effects 0.000 claims description 21
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 18
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 17
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 16
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 14
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 14
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 13
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
• 201000003444 follicular lymphoma Diseases 0.000 claims description 11
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 10
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 9
• 206010025135 lupus erythematosus Diseases 0.000 claims description 8
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
• UPGMKOOJQCKFAP-MUUNZHRXSA-N 3-[4-(1-cyclopentylpiperidin-4-yl)anilino]-5-[(3R)-3-(3-oxo-1H-isoindol-2-yl)piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CCCC1)N1CCC(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)N1C(C2=CC=CC=C2C1)=O)C(=O)N UPGMKOOJQCKFAP-MUUNZHRXSA-N 0.000 claims description 6
• WKVGPPQKZYTFPL-UKINESCASA-N 3-[[(3R)-1-[(E)-4-[cyclopropyl(methyl)amino]but-2-enoyl]piperidin-3-yl]amino]-5-(4-methylsulfonylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C1(CC1)N(C/C=C/C(=O)N1C[C@@H](CCC1)NC=1N=NC(=C(N1)NC1=CC=C(C=C1)S(=O)(=O)C)C(=O)N)C WKVGPPQKZYTFPL-UKINESCASA-N 0.000 claims description 6
• QOXFMUBWQHGRRX-BIENSFFJSA-N 3-[[(3R)-1-[(E)-4-(dimethylamino)but-2-enoyl]piperidin-3-yl]amino]-5-(4-methylsulfonylanilino)-1,2,4-triazine-6-carboxamide Chemical compound CN(C/C=C/C(=O)N1C[C@@H](CCC1)NC=1N=NC(=C(N1)NC1=CC=C(C=C1)S(=O)(=O)C)C(=O)N)C QOXFMUBWQHGRRX-BIENSFFJSA-N 0.000 claims description 5
• OTPKESFCTVIJSI-CQSZACIVSA-N 3-[[(3R)-1-but-2-ynoylpiperidin-3-yl]amino]-5-(4-methylsulfonylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C(C#CC)(=O)N1C[C@@H](CCC1)NC=1N=NC(=C(N1)NC1=CC=C(C=C1)S(=O)(=O)C)C(=O)N OTPKESFCTVIJSI-CQSZACIVSA-N 0.000 claims description 5
• 208000008585 mastocytosis Diseases 0.000 claims description 5
• PCCUFELXHXGFAW-RUZDIDTESA-N 3-[4-(1-cyclopentylpiperidin-4-yl)anilino]-5-[(3R)-3-(2-oxopyrrolidin-1-yl)piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CCCC1)N1CCC(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)N1C(CCC1)=O)C(=O)N PCCUFELXHXGFAW-RUZDIDTESA-N 0.000 claims description 4
• WTGYQGCIJYXGGH-GDLZYMKVSA-N 3-[4-(1-cyclopropylpiperidin-4-yl)anilino]-5-[(3R)-3-[(6-phenylpyridine-3-carbonyl)amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CC1)N1CCC(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(C1=CN=C(C=C1)C1=CC=CC=C1)=O)C(=O)N WTGYQGCIJYXGGH-GDLZYMKVSA-N 0.000 claims description 4
• 208000006386 Bone Resorption Diseases 0.000 claims description 4
• 208000001132 Osteoporosis Diseases 0.000 claims description 4
• 230000024279 bone resorption Effects 0.000 claims description 4
• 238000007911 parenteral administration Methods 0.000 claims description 4
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
• 238000011200 topical administration Methods 0.000 claims description 4
• YADCPAXRUJZGER-GFCCVEGCSA-N (3R)-3-[[5-carbamoyl-6-[(3-methyl-1,2-thiazol-5-yl)amino]pyrazin-2-yl]amino]-N,N-dimethylazepane-1-carboxamide Chemical compound C(N)(=O)C=1N=CC(=NC1NC1=CC(=NS1)C)N[C@H]1CN(CCCC1)C(=O)N(C)C YADCPAXRUJZGER-GFCCVEGCSA-N 0.000 claims description 3
• VNGLFSKNXAELLE-HHHXNRCGSA-N 3-[4-(1-cyclopentylpiperidin-4-yl)anilino]-5-[(3R)-3-[(4-fluorobenzoyl)amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CCCC1)N1CCC(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(C1=CC=C(C=C1)F)=O)C(=O)N VNGLFSKNXAELLE-HHHXNRCGSA-N 0.000 claims description 3
• CXHZBOWLLILCRJ-AREMUKBSSA-N 3-[4-(1-cyclopentylpiperidin-4-yl)anilino]-5-[(3R)-3-[(5-fluoropyridine-3-carbonyl)amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CCCC1)N1CCC(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(C1=CN=CC(=C1)F)=O)C(=O)N CXHZBOWLLILCRJ-AREMUKBSSA-N 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
• RJVISCHEJZVWGM-OAQYLSRUSA-N 3-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-(4-methylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=NC(=C(N2)NC2=CC=C(C=C2)C)C(=O)N)C=C1 RJVISCHEJZVWGM-OAQYLSRUSA-N 0.000 claims description 2
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• IWFDWNSVJHPEMV-QWDXWUACSA-N 5-[[(3R)-1-[(E)-4-(dimethylamino)but-2-enoyl]piperidin-3-yl]-methylamino]-3-(4-phenoxyanilino)pyrazine-2-carboxamide Chemical compound CN(C/C=C/C(=O)N1C[C@@H](CCC1)N(C=1N=C(C(=NC1)C(=O)N)NC1=CC=C(C=C1)OC1=CC=CC=C1)C)C IWFDWNSVJHPEMV-QWDXWUACSA-N 0.000 claims 2
• NFUGIXXXQFTUTB-RQNOJGIXSA-N C(C)(=O)N[C@@H]1CC[C@H](CC1)NC=1N=C(C(=NC=1CC)C(=O)N)NC1=CC(=C(C=C1)N1CCC(CC1)N1CCN(CC1)C)C Chemical compound C(C)(=O)N[C@@H]1CC[C@H](CC1)NC=1N=C(C(=NC=1CC)C(=O)N)NC1=CC(=C(C=C1)N1CCC(CC1)N1CCN(CC1)C)C NFUGIXXXQFTUTB-RQNOJGIXSA-N 0.000 claims 2
• ANHMZQOQBVHDCM-QGZVFWFLSA-N 3-(cyclopentylamino)-5-[(3R)-3-[[methyl(phenyl)carbamoyl]amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CCCC1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(=O)N(C1=CC=CC=C1)C)C(=O)N ANHMZQOQBVHDCM-QGZVFWFLSA-N 0.000 claims 1
• PNIISZRXSXIOMH-OAHLLOKOSA-N 3-(cyclopropylamino)-5-[(3R)-3-[[methyl(phenyl)carbamoyl]amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CC1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(=O)N(C1=CC=CC=C1)C)C(=O)N PNIISZRXSXIOMH-OAHLLOKOSA-N 0.000 claims 1
• BMOBXUNRUBUXRY-MRXNPFEDSA-N 3-(oxan-4-ylamino)-5-[(3R)-3-(oxan-4-ylcarbamoylamino)piperidin-1-yl]pyrazine-2-carboxamide Chemical compound O1CCC(CC1)NC(N[C@H]1CN(CCC1)C=1N=C(C(=NC1)C(=O)N)NC1CCOCC1)=O BMOBXUNRUBUXRY-MRXNPFEDSA-N 0.000 claims 1
• AXDRKVAYKSVRHT-OAQYLSRUSA-N 3-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-(3-methylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=NC(=C(N2)NC=2C=C(C=CC2)C)C(=O)N)C=C1 AXDRKVAYKSVRHT-OAQYLSRUSA-N 0.000 claims 1
• RZWDONNOUHBZTO-HSZRJFAPSA-N 3-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-(3-pyrimidin-2-ylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=NC(=C(N2)NC2=CC(=CC=C2)C2=NC=CC=N2)C(=O)N)C=C1 RZWDONNOUHBZTO-HSZRJFAPSA-N 0.000 claims 1
• MDQRIUQNZANBTI-HXUWFJFHSA-N 3-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-(4-methylsulfonylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=NC(=C(N2)NC2=CC=C(C=C2)S(=O)(=O)C)C(=O)N)C=C1 MDQRIUQNZANBTI-HXUWFJFHSA-N 0.000 claims 1
• JOAUAXDSUNVTQQ-GOSISDBHSA-N 3-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-[(5-fluoropyridin-3-yl)amino]-1,2,4-triazine-6-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=NC(=C(N2)NC=2C=NC=C(C2)F)C(=O)N)C=C1 JOAUAXDSUNVTQQ-GOSISDBHSA-N 0.000 claims 1
• UCBIZXOMSGKHIB-JOCHJYFZSA-N 3-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-[4-(1,3-oxazol-2-yl)anilino]-1,2,4-triazine-6-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=NC(=C(N2)NC2=CC=C(C=C2)C=2OC=CN2)C(=O)N)C=C1 UCBIZXOMSGKHIB-JOCHJYFZSA-N 0.000 claims 1
• OJKTZJQBFBYXAK-HSZRJFAPSA-N 3-[(3r)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-5-(4-pyrimidin-2-ylanilino)-1,2,4-triazine-6-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)N[C@H]1CN(C=2N=C(NC=3C=CC(=CC=3)C=3N=CC=CN=3)C(C(N)=O)=NN=2)CCC1 OJKTZJQBFBYXAK-HSZRJFAPSA-N 0.000 claims 1
• WHGCLCOZWIDXLS-HXUWFJFHSA-N 3-[4-(1-carbamoylcyclopropyl)anilino]-5-[(3R)-3-[[[3-chloro-5-(trifluoromethyl)phenyl]-methylcarbamoyl]amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C(N)(=O)C1(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(=O)N(C)C1=CC(=CC(=C1)C(F)(F)F)Cl)C(=O)N WHGCLCOZWIDXLS-HXUWFJFHSA-N 0.000 claims 1
• XVVZTURZXRJVBW-RUZDIDTESA-N 3-[4-(1-cyclopropylpiperidin-4-yl)anilino]-5-[(3R)-3-(4,5,6,7-tetrahydro-1-benzothiophene-2-carbonylamino)piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1(CC1)N1CCC(CC1)C1=CC=C(C=C1)NC=1C(=NC=C(N1)N1C[C@@H](CCC1)NC(=O)C1=CC2=C(S1)CCCC2)C(=O)N XVVZTURZXRJVBW-RUZDIDTESA-N 0.000 claims 1
• HBDDRYSVENFBPH-GDLZYMKVSA-N 3-[4-(1-cyclopropylpiperidin-4-yl)anilino]-5-[(3R)-3-(naphthalene-2-carbonylamino)piperidin-1-yl]pyrazine-2-carboxamide Chemical compound C1=C(C=CC2=CC=CC=C12)C(=O)N[C@H]1CN(CCC1)C=1N=C(C(=NC1)C(=O)N)NC1=CC=C(C=C1)C1CCN(CC1)C1CC1 HBDDRYSVENFBPH-GDLZYMKVSA-N 0.000 claims 1
• OGJGLJFSSSDHCU-GOSISDBHSA-N 3-anilino-5-[(3R)-3-[[methyl(phenyl)carbamoyl]amino]piperidin-1-yl]pyrazine-2-carboxamide Chemical compound CN(C(N[C@H]1CN(CCC1)C=1N=C(C(=NC1)C(=O)N)NC1=CC=CC=C1)=O)C1=CC=CC=C1 OGJGLJFSSSDHCU-GOSISDBHSA-N 0.000 claims 1
• LCHGMZINIRROCH-RNWIMVQKSA-N 5-[(2R,3R)-3-benzamido-2-methylpiperidin-1-yl]-3-[4-(1-cyclopentylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound C(C1=CC=CC=C1)(=O)N[C@H]1[C@H](N(CCC1)C=1N=C(C(=NC1)C(=O)N)NC1=CC=C(C=C1)C1CCN(CC1)C1CCCC1)C LCHGMZINIRROCH-RNWIMVQKSA-N 0.000 claims 1
• LCHGMZINIRROCH-MUAVYFROSA-N 5-[(2S,3R)-3-benzamido-2-methylpiperidin-1-yl]-3-[4-(1-cyclopentylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound C(C1=CC=CC=C1)(=O)N[C@H]1[C@@H](N(CCC1)C=1N=C(C(=NC1)C(=O)N)NC1=CC=C(C=C1)C1CCN(CC1)C1CCCC1)C LCHGMZINIRROCH-MUAVYFROSA-N 0.000 claims 1
• IRULKPYXUXYSTC-RUZDIDTESA-N 5-[(3R)-3-(1-benzothiophene-2-carbonylamino)piperidin-1-yl]-3-[4-(1-cyclopropylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound S1C2=C(C=C1C(=O)N[C@H]1CN(CCC1)C=1N=C(C(=NC1)C(=O)N)NC1=CC=C(C=C1)C1CCN(CC1)C1CC1)C=CC=C2 IRULKPYXUXYSTC-RUZDIDTESA-N 0.000 claims 1
• GVPNOZZNVLSCIV-RUZDIDTESA-N 5-[(3R)-3-[(3-chlorobenzoyl)amino]piperidin-1-yl]-3-[4-(1-cyclopropylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound ClC=1C=C(C(=O)N[C@H]2CN(CCC2)C=2N=C(C(=NC2)C(=O)N)NC2=CC=C(C=C2)C2CCN(CC2)C2CC2)C=CC1 GVPNOZZNVLSCIV-RUZDIDTESA-N 0.000 claims 1
• WLRAKZFYCQHVRT-RUZDIDTESA-N 5-[(3R)-3-[(4-chlorobenzoyl)amino]piperidin-1-yl]-3-[4-(1-cyclopropylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound ClC1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=C(C(=NC2)C(=O)N)NC2=CC=C(C=C2)C2CCN(CC2)C2CC2)C=C1 WLRAKZFYCQHVRT-RUZDIDTESA-N 0.000 claims 1
• KJNOYLPRXXIEBI-XMMPIXPASA-N 5-[(3R)-3-[(4-fluorobenzoyl)amino]piperidin-1-yl]-3-[4-(1-methylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound FC1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=C(C(=NC2)C(=O)N)NC2=CC=C(C=C2)C2CCN(CC2)C)C=C1 KJNOYLPRXXIEBI-XMMPIXPASA-N 0.000 claims 1
• CBVUEAAQUJJHEA-HHHXNRCGSA-N 5-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-3-[4-(1-methylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=C(C(=NC2)C(=O)N)NC2=CC=C(C=C2)C2CCN(CC2)C)C=C1 CBVUEAAQUJJHEA-HHHXNRCGSA-N 0.000 claims 1
• ITGUQNXUVZYULD-RUZDIDTESA-N 5-[(3R)-3-[(4-tert-butylbenzoyl)amino]piperidin-1-yl]-3-[4-(4-methylpiperazin-1-yl)anilino]pyrazine-2-carboxamide Chemical compound C(C)(C)(C)C1=CC=C(C(=O)N[C@H]2CN(CCC2)C=2N=C(C(=NC2)C(=O)N)NC2=CC=C(C=C2)N2CCN(CC2)C)C=C1 ITGUQNXUVZYULD-RUZDIDTESA-N 0.000 claims 1
• LUJIAEVVGLFMBH-XMMPIXPASA-N 5-[(3R)-3-[(5-chloropyridine-3-carbonyl)amino]piperidin-1-yl]-3-[4-(1-cyclopropylpiperidin-4-yl)anilino]pyrazine-2-carboxamide Chemical compound ClC=1C=NC=C(C(=O)N[C@H]2CN(CCC2)C=2N=C(C(=NC2)C(=O)N)NC2=CC=C(C=C2)C2CCN(CC2)C2CC2)C1 LUJIAEVVGLFMBH-XMMPIXPASA-N 0.000 claims 1
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