JP2009538877A - 変性疾患及び炎症性疾患の治療に有用なトリアゾロピラジン化合物 - Google Patents
変性疾患及び炎症性疾患の治療に有用なトリアゾロピラジン化合物 Download PDFInfo
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- JP2009538877A JP2009538877A JP2009512585A JP2009512585A JP2009538877A JP 2009538877 A JP2009538877 A JP 2009538877A JP 2009512585 A JP2009512585 A JP 2009512585A JP 2009512585 A JP2009512585 A JP 2009512585A JP 2009538877 A JP2009538877 A JP 2009538877A
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- JP
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- Prior art keywords
- triazolo
- pyrazin
- substituted
- pyrazol
- compound
- 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.)
- Abandoned
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- 238000011282 treatment Methods 0.000 title claims abstract description 50
- 208000027866 inflammatory disease Diseases 0.000 title claims description 4
- CJGGKSPGRJHZNP-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyrazine Chemical class C1=CN=C2NN=NC2=N1 CJGGKSPGRJHZNP-UHFFFAOYSA-N 0.000 title description 2
- 208000015122 neurodegenerative disease Diseases 0.000 title description 2
- 230000003412 degenerative effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 730
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 230000002265 prevention Effects 0.000 claims abstract description 18
- 206010061218 Inflammation Diseases 0.000 claims abstract description 11
- 230000004054 inflammatory process Effects 0.000 claims abstract description 11
- -1 methylaminoethyl Chemical group 0.000 claims description 172
- 125000000217 alkyl group Chemical group 0.000 claims description 149
- 238000000034 method Methods 0.000 claims description 149
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 65
- 210000004027 cell Anatomy 0.000 claims description 61
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 59
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 55
- 102100028396 MAP kinase-activated protein kinase 5 Human genes 0.000 claims description 52
- 201000010099 disease Diseases 0.000 claims description 49
- 230000014509 gene expression Effects 0.000 claims description 46
- 101710140998 MAP kinase-activated protein kinase 5 Proteins 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 230000000694 effects Effects 0.000 claims description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 239000000651 prodrug Substances 0.000 claims description 29
- 229940002612 prodrug Drugs 0.000 claims description 29
- 238000006731 degradation reaction Methods 0.000 claims description 27
- 230000015556 catabolic process Effects 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 22
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 22
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 22
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 22
- 210000002744 extracellular matrix Anatomy 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 239000011159 matrix material Substances 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 14
- 230000002159 abnormal effect Effects 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 150000003053 piperidines Chemical class 0.000 claims description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 11
- 229910052777 Praseodymium Inorganic materials 0.000 claims description 10
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 102000035195 Peptidases Human genes 0.000 claims description 9
- 108091005804 Peptidases Proteins 0.000 claims description 9
- 230000000155 isotopic effect Effects 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 235000019833 protease Nutrition 0.000 claims description 5
- 150000003230 pyrimidines Chemical class 0.000 claims description 5
- JGGDMMYPOPZHLL-UHFFFAOYSA-N 4-[8-[4-(4-methylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical class C1CN(C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CSC(C(N)=O)=C1 JGGDMMYPOPZHLL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- HBZBAYZNKWTACU-UHFFFAOYSA-N 5-[8-[4-(2-morpholin-4-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C=1C=C2C(=O)NCC2=CC=1C(N1N=CN=C11)=CN=C1NC(C=C1)=CC=C1OCCN1CCOCC1 HBZBAYZNKWTACU-UHFFFAOYSA-N 0.000 claims description 4
- HEAMBSUSRXMHHW-UHFFFAOYSA-N 5-[8-[4-(4-methylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical class C1CN(C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CC=C(C(N)=O)S1 HEAMBSUSRXMHHW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- VBVIHCRFIFYNSO-UHFFFAOYSA-N 2-methoxy-N-[(6-methylpyridin-3-yl)methyl]-4-[[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]amino]benzamide Chemical compound C=1C=C(C(=O)NCC=2C=NC(C)=CC=2)C(OC)=CC=1NC(C1=NC=NN11)=NC=C1C=1C=NNC=1 VBVIHCRFIFYNSO-UHFFFAOYSA-N 0.000 claims description 3
- GIAQJIIDNXNNSY-UHFFFAOYSA-N 3,3-dimethyl-5-[8-[4-(4-propan-2-ylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2h-isoindol-1-one Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CC=C(C(=O)NC2(C)C)C2=C1 GIAQJIIDNXNNSY-UHFFFAOYSA-N 0.000 claims description 3
- FYSTUPGUTFXHBJ-UHFFFAOYSA-N 4-[8-(4-morpholin-4-ylanilino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]furan-2-carboxamide Chemical compound O1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCOCC3)=NC=2)=C1 FYSTUPGUTFXHBJ-UHFFFAOYSA-N 0.000 claims description 3
- SFEDCFUOTZYOEK-UHFFFAOYSA-N 4-[8-(4-morpholin-4-ylanilino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCOCC3)=NC=2)=C1 SFEDCFUOTZYOEK-UHFFFAOYSA-N 0.000 claims description 3
- MDGOPRLPIZCNLF-UHFFFAOYSA-N 4-[8-[(6-morpholin-4-ylpyridin-3-yl)amino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=NC(=CC=3)N3CCOCC3)=NC=2)=C1 MDGOPRLPIZCNLF-UHFFFAOYSA-N 0.000 claims description 3
- YYYGAZMZWJESIR-UHFFFAOYSA-N 4-[8-[4-(1-propan-2-ylpiperidin-4-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical class C1CN(C(C)C)CCC1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CSC(C(N)=O)=C1 YYYGAZMZWJESIR-UHFFFAOYSA-N 0.000 claims description 3
- CBDPFOMIDRBHPG-UHFFFAOYSA-N 4-[8-[4-(2-morpholin-4-ylethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical class S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=CC(OCCN4CCOCC4)=CC=3)=NC=2)=C1 CBDPFOMIDRBHPG-UHFFFAOYSA-N 0.000 claims description 3
- COGVMNOHISNIOE-UHFFFAOYSA-N 4-[8-[4-(4-propan-2-ylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]furan-2-carboxamide Chemical class C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=COC(C(N)=O)=C1 COGVMNOHISNIOE-UHFFFAOYSA-N 0.000 claims description 3
- IIBPKZRWJHPSBG-UHFFFAOYSA-N 4-[8-[4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)C3CCN(CC(F)(F)F)CC3)=NC=2)=C1 IIBPKZRWJHPSBG-UHFFFAOYSA-N 0.000 claims description 3
- SFFPRZBXKZPBER-UHFFFAOYSA-N 4-[8-[4-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCN(CC(F)(F)F)CC3)=NC=2)=C1 SFFPRZBXKZPBER-UHFFFAOYSA-N 0.000 claims description 3
- CEQGCMHVEDNLEF-UHFFFAOYSA-N 4-[8-[4-[4-(cyclopropylmethyl)piperazin-1-yl]anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCN(CC4CC4)CC3)=NC=2)=C1 CEQGCMHVEDNLEF-UHFFFAOYSA-N 0.000 claims description 3
- DSOIXOVZRRVUOU-UHFFFAOYSA-N 4-[8-[[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]amino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound C1CN(C(C)C)CCN1C(N=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CSC(C(N)=O)=C1 DSOIXOVZRRVUOU-UHFFFAOYSA-N 0.000 claims description 3
- NNAAHUUFMAXYRO-UHFFFAOYSA-N 4-[8-[[6-[(2-phenylacetyl)amino]pyridin-3-yl]amino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=NC(NC(=O)CC=4C=CC=CC=4)=CC=3)=NC=2)=C1 NNAAHUUFMAXYRO-UHFFFAOYSA-N 0.000 claims description 3
- AQUIBDVXRAUIFS-UHFFFAOYSA-N 4-[8-[[6-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]pyridin-3-yl]amino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=NC(=CC=3)N3CCN(CC(F)(F)F)CC3)=NC=2)=C1 AQUIBDVXRAUIFS-UHFFFAOYSA-N 0.000 claims description 3
- QBLGZKNTTFTHOK-UHFFFAOYSA-N 4-[8-[[6-[4-(cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl]amino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]thiophene-2-carboxamide Chemical compound S1C(C(=O)N)=CC(C=2N3N=CN=C3C(NC=3C=NC(=CC=3)N3CCN(CC4CC4)CC3)=NC=2)=C1 QBLGZKNTTFTHOK-UHFFFAOYSA-N 0.000 claims description 3
- LCRWIORMRJTMFA-UHFFFAOYSA-N 4-[[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]amino]-N-(pyridin-3-ylmethyl)benzamide Chemical compound C=1C=C(NC=2C3=NC=NN3C(C3=CNN=C3)=CN=2)C=CC=1C(=O)NCC1=CC=CN=C1 LCRWIORMRJTMFA-UHFFFAOYSA-N 0.000 claims description 3
- ACSIJRWNGSUPMS-UHFFFAOYSA-N 5-(5-ethyl-1H-pyrazol-4-yl)-N-(4-morpholin-4-ylphenyl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine Chemical compound N1N=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCOCC3)=NC=2)=C1CC ACSIJRWNGSUPMS-UHFFFAOYSA-N 0.000 claims description 3
- ZDLDULHTZCUMMG-UHFFFAOYSA-N 5-[8-(4-morpholin-4-ylanilino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C=1C=C2C(=O)NCC2=CC=1C(N1N=CN=C11)=CN=C1NC(C=C1)=CC=C1N1CCOCC1 ZDLDULHTZCUMMG-UHFFFAOYSA-N 0.000 claims description 3
- HFFMARMJJSHTDN-UHFFFAOYSA-N 5-[8-(4-morpholin-4-ylanilino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]furan-3-carboxamide Chemical compound NC(=O)C1=COC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCOCC3)=NC=2)=C1 HFFMARMJJSHTDN-UHFFFAOYSA-N 0.000 claims description 3
- ILFSKYBJCHVNJD-UHFFFAOYSA-N 5-[8-[4-(1-propan-2-ylpiperidin-4-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C1CN(C(C)C)CCC1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CC=C(C(=O)NC2)C2=C1 ILFSKYBJCHVNJD-UHFFFAOYSA-N 0.000 claims description 3
- LSIOHAGMVUYTCY-UHFFFAOYSA-N 5-[8-[4-(2-oxo-4-propan-2-ylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound O=C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CC=C(C(=O)NC2)C2=C1 LSIOHAGMVUYTCY-UHFFFAOYSA-N 0.000 claims description 3
- RAJKOVRGWVJRGX-UHFFFAOYSA-N 5-[8-[4-(2-oxopiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C=1C=C2C(=O)NCC2=CC=1C(N1N=CN=C11)=CN=C1NC(C=C1)=CC=C1N1CCNCC1=O RAJKOVRGWVJRGX-UHFFFAOYSA-N 0.000 claims description 3
- VTESFAODZQAOKN-UHFFFAOYSA-N 5-[8-[4-(4-propan-2-ylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CC=C(C(=O)NC2)C2=C1 VTESFAODZQAOKN-UHFFFAOYSA-N 0.000 claims description 3
- OGPDZYDHCXSOGK-UHFFFAOYSA-N 7-fluoro-5-[8-[4-(4-propan-2-ylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C(C=C1F)=CC2=C1C(=O)NC2 OGPDZYDHCXSOGK-UHFFFAOYSA-N 0.000 claims description 3
- XPWKDQHOFGSYMT-UHFFFAOYSA-N N-(2-fluoro-4-morpholin-4-ylphenyl)-5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine Chemical compound FC1=CC(N2CCOCC2)=CC=C1NC(C1=NC=NN11)=NC=C1C=1C=NNC=1 XPWKDQHOFGSYMT-UHFFFAOYSA-N 0.000 claims description 3
- KEJPHZROOKODRB-UHFFFAOYSA-N N-[4-(4-methylpiperazin-1-yl)phenyl]-5-(5-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=C(C)NN=C1 KEJPHZROOKODRB-UHFFFAOYSA-N 0.000 claims description 3
- RPBFPZSBRGQZAF-UHFFFAOYSA-N N-ethyl-3-[[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]amino]benzamide Chemical compound CCNC(=O)C1=CC=CC(NC=2C3=NC=NN3C(C3=CNN=C3)=CN=2)=C1 RPBFPZSBRGQZAF-UHFFFAOYSA-N 0.000 claims description 3
- JFDPEWDADGRRQZ-UHFFFAOYSA-N [2-morpholin-4-yl-5-[[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]amino]phenyl]methanol Chemical compound C=1C=C(N2CCOCC2)C(CO)=CC=1NC(C1=NC=NN11)=NC=C1C=1C=NNC=1 JFDPEWDADGRRQZ-UHFFFAOYSA-N 0.000 claims description 3
- NFPDZRYLXOILPI-UHFFFAOYSA-N [4-[8-(4-morpholin-4-ylanilino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-1H-pyrazol-5-yl]methanol Chemical compound N1N=CC(C=2N3N=CN=C3C(NC=3C=CC(=CC=3)N3CCOCC3)=NC=2)=C1CO NFPDZRYLXOILPI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 230000001668 ameliorated effect Effects 0.000 claims description 3
- WSPYBPVYCFYIRM-UHFFFAOYSA-N chembl1956687 Chemical compound C1COCCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CNN=C1 WSPYBPVYCFYIRM-UHFFFAOYSA-N 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 150000002460 imidazoles Chemical class 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- VSHZLKVKHKMKFB-UHFFFAOYSA-N n-(4-morpholin-4-ylphenyl)-5-(1h-pyrazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine Chemical compound C1COCCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=CC=NN1 VSHZLKVKHKMKFB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 150000003217 pyrazoles Chemical class 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 150000003233 pyrroles Chemical class 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
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- FCYIPZNUCTWQFY-UHFFFAOYSA-N N-[6-[4-(cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl]-5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine Chemical compound C1CN(C=2N=CC(NC=3C4=NC=NN4C(C4=CNN=C4)=CN=3)=CC=2)CCN1CC1CC1 FCYIPZNUCTWQFY-UHFFFAOYSA-N 0.000 claims 1
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
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| US80355206P | 2006-05-31 | 2006-05-31 | |
| US93184407P | 2007-05-25 | 2007-05-25 | |
| US93176407P | 2007-05-25 | 2007-05-25 | |
| US93176307P | 2007-05-25 | 2007-05-25 | |
| US93210007P | 2007-05-29 | 2007-05-29 | |
| PCT/EP2007/055246 WO2007138072A2 (en) | 2006-05-31 | 2007-05-30 | Triazolopyrazine compounds useful for the treatment of degenerative & inflammatory diseases |
Publications (2)
| Publication Number | Publication Date |
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| JP2009538877A true JP2009538877A (ja) | 2009-11-12 |
| JP2009538877A5 JP2009538877A5 (https=) | 2010-08-26 |
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| JP2009512585A Abandoned JP2009538877A (ja) | 2006-05-31 | 2007-05-30 | 変性疾患及び炎症性疾患の治療に有用なトリアゾロピラジン化合物 |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US7501411B2 (https=) |
| JP (1) | JP2009538877A (https=) |
| KR (1) | KR20090026288A (https=) |
| AT (1) | ATE465164T1 (https=) |
| AU (1) | AU2007267121A1 (https=) |
| BR (1) | BRPI0712531A2 (https=) |
| CA (1) | CA2653506A1 (https=) |
| CR (1) | CR10458A (https=) |
| DE (1) | DE602007006010D1 (https=) |
| DK (1) | DK2029602T3 (https=) |
| EA (1) | EA200870592A1 (https=) |
| EC (1) | ECSP088923A (https=) |
| HR (1) | HRP20100378T1 (https=) |
| IL (1) | IL195033A0 (https=) |
| MX (1) | MX2008015057A (https=) |
| NI (1) | NI200800299A (https=) |
| NO (1) | NO20084703L (https=) |
| NZ (1) | NZ573015A (https=) |
| PT (1) | PT2029602E (https=) |
| WO (1) | WO2007138072A2 (https=) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013522222A (ja) * | 2010-03-10 | 2013-06-13 | カリプシス，インク | 疾患の治療のためのヒスタミン受容体の複素環阻害薬 |
| JP2016525072A (ja) * | 2013-06-19 | 2016-08-22 | ガラパゴス・ナムローゼ・フェンノートシャップＧａｌａｐａｇｏｓ Ｎ．Ｖ． | 炎症性障害の治療のための新規化合物及びその医薬組成物 |
| JP2021516695A (ja) * | 2018-03-27 | 2021-07-08 | 北京大学Ｐｅｋｉｎｇ Ｕｎｉｖｅｒｓｉｔｙ | 腫瘍転移の薬物治療における標的、及びその使用 |
| JP2023516893A (ja) * | 2020-02-27 | 2023-04-21 | エスアンドティー バイオメッド カンパニー リミテッド | マトリックスメタロプロテアーゼ１のモノクローナル抗体、その検出キット及び検出方法 |
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| TWI378934B (en) * | 2004-04-02 | 2012-12-11 | Osi Pharm Inc | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| US7893058B2 (en) * | 2006-05-15 | 2011-02-22 | Janssen Pharmaceutica Nv | Imidazolopyrazine compounds useful for the treatment of degenerative and inflammatory diseases |
| PT2029602E (pt) * | 2006-05-31 | 2010-07-08 | Galapagos Nv | Compostos de triazolopirazina uteis para o tratamento de doenãas degenerativas e inflamatërias |
| JP2010511018A (ja) | 2006-12-01 | 2010-04-08 | ガラパゴス・ナムローゼ・フェンノートシャップ | 変性疾患及び炎症性疾患の治療に有用なトリアゾロピリジン化合物 |
| US8148369B2 (en) | 2007-05-10 | 2012-04-03 | Janssen Pharmaceutica Nv | Fused pyrazine compounds useful for the treatment of degenerative and inflammatory diseases |
| US8133895B2 (en) * | 2007-05-10 | 2012-03-13 | Janssen Pharmaceutica N.V. | Fused pyrazine compounds useful for the treatment of degenerative and inflammatory diseases |
| DE102007060172A1 (de) | 2007-12-13 | 2009-06-25 | Bayer Healthcare Ag | Triazolotriazine und Triazolopyrazine und ihre Verwendung |
| DE102008035209A1 (de) | 2008-07-29 | 2010-02-04 | Bayer Schering Pharma Aktiengesellschaft | Triazolotriazine und Triazolopyrazine und ihre Verwendung |
| AR071619A1 (es) * | 2008-05-07 | 2010-06-30 | Galapagos Nv | Compuestos de pirazina fusionados utiles para el tratamiento de enfermedades degenerativas e inflamatorias y composiciones farmaceuticas que los contienen. |
| DE102008023801A1 (de) | 2008-05-15 | 2009-11-19 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Imidazo- und Triazolopyrimidine, Imidazo- und Pyrazolopyrazine und Imidazotriazine |
| TWI453207B (zh) | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶，其組合物及使用其之治療方法 |
| WO2010123792A1 (en) | 2009-04-20 | 2010-10-28 | Osi Pharmaceuticals, Inc. | Preparation of c-pyrazine-methylamines |
| EP2427192A1 (en) * | 2009-05-07 | 2012-03-14 | OSI Pharmaceuticals, LLC | Use of osi-906 for treating adrenocortical carcinoma |
| TW201120043A (en) * | 2009-11-05 | 2011-06-16 | Galapagos Nv | Fused pyrazine compounds as their salts, useful for the treatment of degenerative and inflammatory diseases |
| EP2343297A1 (en) | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Triazolopyridines |
| CN104284896B (zh) | 2012-03-14 | 2016-06-01 | 拜耳知识产权有限责任公司 | 取代的咪唑并哒嗪 |
| RS56034B1 (sr) | 2013-06-11 | 2017-09-29 | Bayer Pharma AG | Derivati prolekova supstituisanih triazolopiridina |
| AU2014375265B2 (en) | 2014-01-03 | 2018-11-01 | Elanco Animal Health Gmbh | Novel pyrazolyl-heteroarylamides as pesticides |
| US9856263B2 (en) | 2014-04-28 | 2018-01-02 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine D1 ligands |
| SG11201710694YA (en) | 2015-06-22 | 2018-01-30 | Sumitomo Dainippon Pharma Co Ltd | Bicyclic heterocyclic amide derivative |
| LT3319959T (lt) | 2015-07-06 | 2021-12-27 | Alkermes, Inc. | Histono deacetilazės hetero-halogeno inhibitoriai |
| EP3319968A1 (en) | 2015-07-06 | 2018-05-16 | Rodin Therapeutics, Inc. | Heterobicyclic n-aminophenyl-amides as inhibitors of histone deacetylase |
| US10898469B2 (en) | 2016-02-26 | 2021-01-26 | Sumitomo Dainippon Pharma Co., Ltd. | Imidazolylamide derivative |
| KR102598895B1 (ko) | 2016-07-12 | 2023-11-07 | 레볼루션 메디슨즈, 인크. | 다른자리 입체성 shp2 억제제로서의 2,5-이치환 3-메틸 피라진 및 2,5,6-3치환 3-메틸 피라진 |
| RS62959B1 (sr) | 2017-01-11 | 2022-03-31 | Alkermes Inc | Biciklični inhibitori histon-deacetilaze |
| MX2019008696A (es) | 2017-01-23 | 2019-09-13 | Revolution Medicines Inc | Compuestos de piridina como inhibidores de shp2 alostericos. |
| MX2019008695A (es) | 2017-01-23 | 2019-09-11 | Revolution Medicines Inc | Compuestos biciclicos como inhibidores alostericos de shp2. |
| CN109206357A (zh) * | 2017-07-04 | 2019-01-15 | 浙江九洲药业股份有限公司 | 一种格列齐特中间体的通式化合物及其制备方法和应用 |
| US11225475B2 (en) | 2017-08-07 | 2022-01-18 | Alkermes, Inc. | Substituted pyridines as inhibitors of histone deacetylase |
| MX2020003579A (es) | 2017-10-12 | 2020-07-22 | Revolution Medicines Inc | Compuestos de piridina, pirazina, y triazina como inhibidores de shp2 alostericos. |
| BR112020009757A2 (pt) | 2017-12-15 | 2020-11-03 | Revolution Medicines, Inc. | compostos policíclicos como inibidores alostéricos de shp2 |
| BR122023024273A2 (pt) | 2018-02-27 | 2024-02-20 | Incyte Corporation | Compostos imidazopirimidinas e triazolopirimidinas, seus usos, método para inibir uma atividade de um receptor de adenosina e composição farmacêutica dos mesmos |
| WO2019222677A1 (en) | 2018-05-18 | 2019-11-21 | Incyte Corporation | Fused pyrimidine derivatives as a2a / a2b inhibitors |
| GEP20237548B (en) | 2018-07-05 | 2023-10-10 | Incyte Corp | Fused pyrazine derivatives as a2a /a2b inhibitors |
| TWI829857B (zh) | 2019-01-29 | 2024-01-21 | 美商英塞特公司 | 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶 |
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| PT2029602E (pt) * | 2006-05-31 | 2010-07-08 | Galapagos Nv | Compostos de triazolopirazina uteis para o tratamento de doenãas degenerativas e inflamatërias |
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- 2007-05-30 JP JP2009512585A patent/JP2009538877A/ja not_active Abandoned
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2008
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- 2008-11-20 NI NI200800299A patent/NI200800299A/es unknown
- 2008-11-25 CR CR10458A patent/CR10458A/es unknown
- 2008-11-28 EC EC2008008923A patent/ECSP088923A/es unknown
-
2009
- 2009-03-08 US US12/399,979 patent/US7915256B2/en not_active Expired - Fee Related
-
2011
- 2011-01-09 US US12/987,129 patent/US20110178067A1/en not_active Abandoned
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013522222A (ja) * | 2010-03-10 | 2013-06-13 | カリプシス，インク | 疾患の治療のためのヒスタミン受容体の複素環阻害薬 |
| JP2016525072A (ja) * | 2013-06-19 | 2016-08-22 | ガラパゴス・ナムローゼ・フェンノートシャップＧａｌａｐａｇｏｓ Ｎ．Ｖ． | 炎症性障害の治療のための新規化合物及びその医薬組成物 |
| JP2021516695A (ja) * | 2018-03-27 | 2021-07-08 | 北京大学Ｐｅｋｉｎｇ Ｕｎｉｖｅｒｓｉｔｙ | 腫瘍転移の薬物治療における標的、及びその使用 |
| JP7138973B2 (ja) | 2018-03-27 | 2022-09-20 | 北京大学 | 腫瘍転移の薬物治療における標的、及びその使用 |
| JP2023516893A (ja) * | 2020-02-27 | 2023-04-21 | エスアンドティー バイオメッド カンパニー リミテッド | マトリックスメタロプロテアーゼ１のモノクローナル抗体、その検出キット及び検出方法 |
| JP7515204B2 (ja) | 2020-02-27 | 2024-07-12 | エスアンドティー バイオメッド カンパニー リミテッド | マトリックスメタロプロテアーゼ１のモノクローナル抗体、その検出キット及び検出方法 |
| JP2024120937A (ja) * | 2020-02-27 | 2024-09-05 | エスアンドティー バイオメッド カンパニー リミテッド | マトリックスメタロプロテアーゼ１のモノクローナル抗体 |
| JP7768598B2 (ja) | 2020-02-27 | 2025-11-12 | エスアンドティー バイオメッド カンパニー リミテッド | マトリックスメタロプロテアーゼ１のモノクローナル抗体 |
| US12595315B2 (en) | 2020-02-27 | 2026-04-07 | S&T Biomed Co., Ltd. | Monoclonal antibody of matrix metalloproteinase-1, detection kit and detection method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ573015A (en) | 2010-11-26 |
| HRP20100378T1 (hr) | 2010-08-31 |
| US20080090818A1 (en) | 2008-04-17 |
| NI200800299A (es) | 2010-05-25 |
| US20100298300A1 (en) | 2010-11-25 |
| IL195033A0 (en) | 2009-08-03 |
| DE602007006010D1 (de) | 2010-06-02 |
| CR10458A (es) | 2009-02-26 |
| CA2653506A1 (en) | 2007-12-06 |
| KR20090026288A (ko) | 2009-03-12 |
| NO20084703L (no) | 2009-02-19 |
| PT2029602E (pt) | 2010-07-08 |
| ECSP088923A (es) | 2009-01-30 |
| DK2029602T3 (da) | 2010-08-09 |
| ATE465164T1 (de) | 2010-05-15 |
| US20110178067A1 (en) | 2011-07-21 |
| US7915256B2 (en) | 2011-03-29 |
| EA200870592A1 (ru) | 2009-08-28 |
| US7501411B2 (en) | 2009-03-10 |
| AU2007267121A1 (en) | 2007-12-06 |
| WO2007138072A3 (en) | 2008-02-14 |
| WO2007138072A2 (en) | 2007-12-06 |
| MX2008015057A (es) | 2008-12-10 |
| BRPI0712531A2 (pt) | 2012-12-25 |
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