JP2011518219A - タンパク質キナーゼの阻害剤 - Google Patents
タンパク質キナーゼの阻害剤 Download PDFInfo
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- JP2011518219A JP2011518219A JP2011506293A JP2011506293A JP2011518219A JP 2011518219 A JP2011518219 A JP 2011518219A JP 2011506293 A JP2011506293 A JP 2011506293A JP 2011506293 A JP2011506293 A JP 2011506293A JP 2011518219 A JP2011518219 A JP 2011518219A
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- JP
- Japan
- Prior art keywords
- alkylene
- ylamino
- pyrrolo
- pyrimidin
- amino
- 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.)
- Withdrawn
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- 239000003112 inhibitor Substances 0.000 title abstract description 43
- 102000001253 Protein Kinase Human genes 0.000 title description 5
- 108060006633 protein kinase Proteins 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 312
- 238000000034 method Methods 0.000 claims abstract description 88
- 230000000694 effects Effects 0.000 claims abstract description 65
- 150000003839 salts Chemical class 0.000 claims abstract description 65
- 102000042838 JAK family Human genes 0.000 claims abstract description 60
- 108091082332 JAK family Proteins 0.000 claims abstract description 60
- 230000001404 mediated effect Effects 0.000 claims abstract description 52
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims abstract description 16
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 16
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 236
- -1 amino, hydroxy Chemical group 0.000 claims description 225
- 125000000217 alkyl group Chemical group 0.000 claims description 208
- 125000000623 heterocyclic group Chemical group 0.000 claims description 146
- 210000004027 cell Anatomy 0.000 claims description 112
- 125000003118 aryl group Chemical group 0.000 claims description 111
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 103
- 125000003545 alkoxy group Chemical group 0.000 claims description 99
- 125000001072 heteroaryl group Chemical group 0.000 claims description 98
- 229910052799 carbon Inorganic materials 0.000 claims description 93
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 92
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 201000010099 disease Diseases 0.000 claims description 83
- 125000001424 substituent group Chemical group 0.000 claims description 75
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 72
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 70
- 239000000203 mixture Substances 0.000 claims description 69
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 57
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims description 45
- 125000004043 oxo group Chemical group O=* 0.000 claims description 42
- 238000011282 treatment Methods 0.000 claims description 41
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 38
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 35
- 125000000304 alkynyl group Chemical group 0.000 claims description 34
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 27
- 208000023275 Autoimmune disease Diseases 0.000 claims description 26
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 25
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 22
- 230000014509 gene expression Effects 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 208000032839 leukemia Diseases 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 17
- 230000019491 signal transduction Effects 0.000 claims description 17
- 206010020751 Hypersensitivity Diseases 0.000 claims description 16
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 16
- 206010052779 Transplant rejections Diseases 0.000 claims description 16
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 16
- 208000026935 allergic disease Diseases 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 206010025323 Lymphomas Diseases 0.000 claims description 15
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000006356 alkylene carbonyl group Chemical group 0.000 claims description 13
- 201000006417 multiple sclerosis Diseases 0.000 claims description 13
- 125000006361 alkylene amino carbonyl group Chemical group 0.000 claims description 12
- 208000037803 restenosis Diseases 0.000 claims description 12
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 11
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 10
- 208000006673 asthma Diseases 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 208000007056 sickle cell anemia Diseases 0.000 claims description 10
- 208000027930 type IV hypersensitivity disease Diseases 0.000 claims description 10
- 208000006313 Delayed Hypersensitivity Diseases 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 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 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 230000002062 proliferating effect Effects 0.000 claims description 9
- 230000005951 type IV hypersensitivity Effects 0.000 claims description 9
- 208000028622 Immune thrombocytopenia Diseases 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 8
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 7
- 206010062506 Heparin-induced thrombocytopenia Diseases 0.000 claims description 7
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 7
- 125000005001 aminoaryl group Chemical group 0.000 claims description 7
- 208000019622 heart disease Diseases 0.000 claims description 7
- 208000010125 myocardial infarction Diseases 0.000 claims description 7
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- VPQNMDJVVNHZTD-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)anilino]-4-[4-(aminomethyl)piperidin-1-yl]-7h-pyrrolo[2,3-d]pyrimidine-5-carbonitrile Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CN)CC2)=C(C(=CN2)C#N)C2=N1 VPQNMDJVVNHZTD-UHFFFAOYSA-N 0.000 claims description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
- 230000003211 malignant effect Effects 0.000 claims description 6
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000035868 Vascular inflammations Diseases 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 208000014951 hematologic disease Diseases 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- MFMUWALWYSDAIX-INIZCTEOSA-N (3s)-1-[2-(4-piperazin-1-ylanilino)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]pyrrolidin-3-ol Chemical compound C1[C@@H](O)CCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1C=CN2 MFMUWALWYSDAIX-INIZCTEOSA-N 0.000 claims description 4
- ISPIWMLOLHWBJV-UHFFFAOYSA-N 1-[2-(4-piperazin-1-ylanilino)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-3-carboxamide Chemical compound C1C(C(=O)N)CCCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1C=CN2 ISPIWMLOLHWBJV-UHFFFAOYSA-N 0.000 claims description 4
- DSBLPCYZGDBXSG-UHFFFAOYSA-N 1-[2-(4-piperazin-1-ylanilino)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-4-carboxamide Chemical compound C1CC(C(=O)N)CCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1C=CN2 DSBLPCYZGDBXSG-UHFFFAOYSA-N 0.000 claims description 4
- ITBJIOFDMUDQPI-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-fluoropyrimidin-4-yl]piperidine-3-carboxamide Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(F)C(N2CC(CCC2)C(N)=O)=N1 ITBJIOFDMUDQPI-UHFFFAOYSA-N 0.000 claims description 4
- BKSBYMLCXXKXNA-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-3-carboxamide Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CC(CCC2)C(N)=O)=C(C=CN2)C2=N1 BKSBYMLCXXKXNA-UHFFFAOYSA-N 0.000 claims description 4
- QORZSWGMEPAGEF-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-4-carboxamide Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC2)C(N)=O)=C(C=CN2)C2=N1 QORZSWGMEPAGEF-UHFFFAOYSA-N 0.000 claims description 4
- KLNYWORCDSBKLN-UHFFFAOYSA-N 1-[4-[4-[(4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCC2)=C(C=CN2)C2=N1 KLNYWORCDSBKLN-UHFFFAOYSA-N 0.000 claims description 4
- XQNOAAQTRVPEJY-UHFFFAOYSA-N 1-[4-[4-[(4-pyrrolidin-1-yl-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCC2)=C(C=CN2)C2=N1 XQNOAAQTRVPEJY-UHFFFAOYSA-N 0.000 claims description 4
- IMBSTVSBJXHUBW-SFHVURJKSA-N 1-[4-[4-[[4-[(3s)-3-hydroxypyrrolidin-1-yl]-7h-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2C[C@@H](O)CC2)=C(C=CN2)C2=N1 IMBSTVSBJXHUBW-SFHVURJKSA-N 0.000 claims description 4
- UTOCZLMILKVPEA-UHFFFAOYSA-N 1-[4-[4-[[4-[2-(aminomethyl)piperidin-1-yl]-5-fluoropyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(F)C(N2C(CCCC2)CN)=N1 UTOCZLMILKVPEA-UHFFFAOYSA-N 0.000 claims description 4
- AMHCKXVMDFGYGX-UHFFFAOYSA-N 1-[4-[4-[[4-[4-(aminomethyl)piperidin-1-yl]-5-fluoropyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(F)C(N2CCC(CN)CC2)=N1 AMHCKXVMDFGYGX-UHFFFAOYSA-N 0.000 claims description 4
- NSCXCHDGMQTJCY-UHFFFAOYSA-N 1-[4-[4-[[4-[4-(aminomethyl)piperidin-1-yl]-7h-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CN)CC2)=C(C=CN2)C2=N1 NSCXCHDGMQTJCY-UHFFFAOYSA-N 0.000 claims description 4
- IFHNDWIKIZOFSN-UHFFFAOYSA-N 1-[4-[4-[[6-[4-(aminomethyl)piperidin-1-yl]-7h-purin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CN)CC2)=C(N=CN2)C2=N1 IFHNDWIKIZOFSN-UHFFFAOYSA-N 0.000 claims description 4
- QNDRJTWJOGGLGW-UHFFFAOYSA-N 1-[5-fluoro-2-(1h-indazol-6-ylamino)pyrimidin-4-yl]piperidine-3-carboxamide Chemical compound C1C(C(=O)N)CCCN1C1=NC(NC=2C=C3NN=CC3=CC=2)=NC=C1F QNDRJTWJOGGLGW-UHFFFAOYSA-N 0.000 claims description 4
- VMVVFAMYFKESAL-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)anilino]-4-[4-(aminomethyl)piperidin-1-yl]pyrimidine-5-carboxamide Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C(N)=O)C(N2CCC(CN)CC2)=N1 VMVVFAMYFKESAL-UHFFFAOYSA-N 0.000 claims description 4
- WSHBDAVXQWKPGV-UHFFFAOYSA-N 4-[4-(aminomethyl)piperidin-1-yl]-5-fluoro-n-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(F)=CN=2)N2CCC(CN)CC2)=C1 WSHBDAVXQWKPGV-UHFFFAOYSA-N 0.000 claims description 4
- AIOJJUROCPYRGY-UHFFFAOYSA-N 4-[4-(aminomethyl)piperidin-1-yl]-n-(4-piperazin-1-ylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound C1CC(CN)CCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1C=CN2 AIOJJUROCPYRGY-UHFFFAOYSA-N 0.000 claims description 4
- WKIQOCLSDNSELN-UHFFFAOYSA-N 4-[[4-[4-(aminomethyl)piperidin-1-yl]-5-fluoropyrimidin-2-yl]amino]benzamide Chemical compound C1CC(CN)CCN1C1=NC(NC=2C=CC(=CC=2)C(N)=O)=NC=C1F WKIQOCLSDNSELN-UHFFFAOYSA-N 0.000 claims description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims description 4
- 208000007475 hemolytic anemia Diseases 0.000 claims description 4
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 4
- XZZALAYXCNVFOZ-UHFFFAOYSA-N methyl n-[4-[[4-(cyclobutylamino)-7h-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]-n-methylcarbamate Chemical compound C1=CC(N(C)C(=O)OC)=CC=C1NC1=NC(NC2CCC2)=C(C=CN2)C2=N1 XZZALAYXCNVFOZ-UHFFFAOYSA-N 0.000 claims description 4
- RTPBRAGXGHSNGI-UHFFFAOYSA-N n-(4-piperazin-1-ylphenyl)-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound C1CCCCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1C=CN2 RTPBRAGXGHSNGI-UHFFFAOYSA-N 0.000 claims description 4
- LGSSRXTZRZRCGP-UHFFFAOYSA-N n-(4-piperazin-1-ylphenyl)-4-pyrrolidin-1-yl-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound C1CCCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1C=CN2 LGSSRXTZRZRCGP-UHFFFAOYSA-N 0.000 claims description 4
- HQXXUQWPFMATCL-UHFFFAOYSA-N n-[4-[2-(aminomethyl)piperidin-1-yl]-5-fluoropyrimidin-2-yl]-1h-indazol-6-amine Chemical compound NCC1CCCCN1C1=NC(NC=2C=C3NN=CC3=CC=2)=NC=C1F HQXXUQWPFMATCL-UHFFFAOYSA-N 0.000 claims description 4
- LUQJBQPCCBQITJ-UHFFFAOYSA-N n-[4-[4-(aminomethyl)piperidin-1-yl]-5-fluoropyrimidin-2-yl]-1h-indazol-6-amine Chemical compound C1CC(CN)CCN1C1=NC(NC=2C=C3NN=CC3=CC=2)=NC=C1F LUQJBQPCCBQITJ-UHFFFAOYSA-N 0.000 claims description 4
- SMQOSQSCUMJLTB-UHFFFAOYSA-N n-[4-[[4-[4-(aminomethyl)piperidin-1-yl]-5-fluoropyrimidin-2-yl]amino]phenyl]-n-methylacetamide Chemical compound C1=CC(N(C(C)=O)C)=CC=C1NC1=NC=C(F)C(N2CCC(CN)CC2)=N1 SMQOSQSCUMJLTB-UHFFFAOYSA-N 0.000 claims description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- IKMBLWLVMKDJOW-UHFFFAOYSA-N tert-butyl n-[[1-[2-(4-carbamoylanilino)-5-fluoropyrimidin-4-yl]piperidin-4-yl]methyl]carbamate Chemical compound C1CC(CNC(=O)OC(C)(C)C)CCN1C1=NC(NC=2C=CC(=CC=2)C(N)=O)=NC=C1F IKMBLWLVMKDJOW-UHFFFAOYSA-N 0.000 claims description 4
- RJPFULDFMSGSPC-UHFFFAOYSA-N tert-butyl n-[[1-[2-[4-[acetyl(methyl)amino]anilino]-5-fluoropyrimidin-4-yl]piperidin-4-yl]methyl]carbamate Chemical compound C1=CC(N(C(C)=O)C)=CC=C1NC1=NC=C(F)C(N2CCC(CNC(=O)OC(C)(C)C)CC2)=N1 RJPFULDFMSGSPC-UHFFFAOYSA-N 0.000 claims description 4
- TWGVBXWKYXJGIH-UHFFFAOYSA-N tert-butyl n-[[1-[5-fluoro-2-(1h-indazol-6-ylamino)pyrimidin-4-yl]piperidin-2-yl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCCCN1C1=NC(NC=2C=C3NN=CC3=CC=2)=NC=C1F TWGVBXWKYXJGIH-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 3
- 208000002903 Thalassemia Diseases 0.000 claims description 3
- 125000005275 alkylenearyl group Chemical group 0.000 claims description 3
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
- 208000020832 chronic kidney disease Diseases 0.000 claims description 3
- 208000028208 end stage renal disease Diseases 0.000 claims description 3
- 201000000523 end stage renal failure Diseases 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- DTZXUJSOKGXUCS-CYBMUJFWSA-N (2r)-2-[[2-(4-piperazin-1-ylanilino)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]propan-1-ol Chemical compound N=1C=2NC=CC=2C(N[C@@H](CO)C)=NC=1NC(C=C1)=CC=C1N1CCNCC1 DTZXUJSOKGXUCS-CYBMUJFWSA-N 0.000 claims description 2
- DTZXUJSOKGXUCS-ZDUSSCGKSA-N (2s)-2-[[2-(4-piperazin-1-ylanilino)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]propan-1-ol Chemical compound N=1C=2NC=CC=2C(N[C@H](CO)C)=NC=1NC(C=C1)=CC=C1N1CCNCC1 DTZXUJSOKGXUCS-ZDUSSCGKSA-N 0.000 claims description 2
- 125000006636 (C3-C8) cycloalkylcarbonyl group Chemical group 0.000 claims description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
- XZGJAHQTUQUDGB-UHFFFAOYSA-N 1-[2-(4-piperazin-1-ylanilino)-7h-purin-6-yl]piperidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCCN1C1=NC(NC=2C=CC(=CC=2)N2CCNCC2)=NC2=C1N=CN2 XZGJAHQTUQUDGB-UHFFFAOYSA-N 0.000 claims description 2
- SJPPNZACXQFMNM-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-7h-purin-6-yl]piperidine-3-carboxamide Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CC(CCC2)C(N)=O)=C(N=CN2)C2=N1 SJPPNZACXQFMNM-UHFFFAOYSA-N 0.000 claims description 2
- QKXBGQYQXGMLCG-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-7h-purin-6-yl]piperidine-3-carboxylic acid Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CC(CCC2)C(O)=O)=C(N=CN2)C2=N1 QKXBGQYQXGMLCG-UHFFFAOYSA-N 0.000 claims description 2
- XNQDTXPMUWEHIU-UHFFFAOYSA-N 1-[4-(cyclopropylamino)-2-(1h-indazol-6-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]ethanone Chemical compound C=12C(C(=O)C)=CNC2=NC(NC=2C=C3NN=CC3=CC=2)=NC=1NC1CC1 XNQDTXPMUWEHIU-UHFFFAOYSA-N 0.000 claims description 2
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- ZNOASPNIGDFOQH-UHFFFAOYSA-N 1-[4-[4-[[4-(cyclopropylamino)-5-pyridin-4-yl-7h-pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC(NC2CC2)=C(C(=CN2)C=3C=CN=CC=3)C2=N1 ZNOASPNIGDFOQH-UHFFFAOYSA-N 0.000 claims description 2
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| JP2011525192A (ja) * | 2008-06-20 | 2011-09-15 | ジェネンテック, インコーポレイテッド | トリアゾロピリジンjak阻害剤化合物と方法 |
| JP2015524828A (ja) * | 2012-08-14 | 2015-08-27 | シュエンジュウ・ファーマ・カンパニー・リミテッド | 二環性基置換ピリミジン化合物 |
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-
2009
- 2009-04-22 US US12/386,848 patent/US8258144B2/en active Active
- 2009-04-22 EP EP09734422.0A patent/EP2271631B1/en active Active
- 2009-04-22 CA CA2723185A patent/CA2723185A1/en not_active Abandoned
- 2009-04-22 CN CN2013100825419A patent/CN103224497A/zh active Pending
- 2009-04-22 WO PCT/US2009/002512 patent/WO2009131687A2/en not_active Ceased
- 2009-04-22 JP JP2011506293A patent/JP2011518219A/ja not_active Withdrawn
- 2009-04-22 BR BRPI0910668A patent/BRPI0910668A2/pt not_active IP Right Cessation
- 2009-04-22 NZ NZ588830A patent/NZ588830A/xx not_active IP Right Cessation
- 2009-04-22 AU AU2009238590A patent/AU2009238590A1/en not_active Abandoned
- 2009-04-22 CN CN2009801223945A patent/CN102066338A/zh active Pending
-
2010
- 2010-10-14 IL IL208719A patent/IL208719A0/en unknown
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2012
- 2012-06-20 US US13/528,709 patent/US9139581B2/en active Active
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Also Published As
| Publication number | Publication date |
|---|---|
| CN102066338A (zh) | 2011-05-18 |
| WO2009131687A2 (en) | 2009-10-29 |
| BRPI0910668A2 (pt) | 2019-09-24 |
| CN103224497A (zh) | 2013-07-31 |
| EP2271631B1 (en) | 2018-07-04 |
| AU2009238590A1 (en) | 2009-10-29 |
| NZ588830A (en) | 2012-11-30 |
| IL208719A0 (en) | 2010-12-30 |
| WO2009131687A3 (en) | 2010-01-07 |
| US8258144B2 (en) | 2012-09-04 |
| EP2271631A2 (en) | 2011-01-12 |
| US20090298823A1 (en) | 2009-12-03 |
| CA2723185A1 (en) | 2009-10-29 |
| US9139581B2 (en) | 2015-09-22 |
| US20130029944A1 (en) | 2013-01-31 |
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