CA2536535A1 - Compounds and compositions as protein kinase inhibitors - Google Patents
Compounds and compositions as protein kinase inhibitors Download PDFInfo
- Publication number
- CA2536535A1 CA2536535A1 CA002536535A CA2536535A CA2536535A1 CA 2536535 A1 CA2536535 A1 CA 2536535A1 CA 002536535 A CA002536535 A CA 002536535A CA 2536535 A CA2536535 A CA 2536535A CA 2536535 A1 CA2536535 A1 CA 2536535A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- phenyl
- amide
- pyrimidine
- pyrrolo
- 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
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 115
- 239000000203 mixture Substances 0.000 title description 28
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims abstract description 37
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 230000000694 effects Effects 0.000 claims abstract description 23
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims abstract description 17
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims abstract description 17
- 101100457333 Homo sapiens MAPK11 gene Proteins 0.000 claims abstract description 16
- 101150028321 Lck gene Proteins 0.000 claims abstract description 16
- 108700036166 Mitogen-Activated Protein Kinase 11 Proteins 0.000 claims abstract description 16
- 102100026929 Mitogen-activated protein kinase 11 Human genes 0.000 claims abstract description 16
- 101150046814 SAPK2 gene Proteins 0.000 claims abstract description 16
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 claims abstract description 15
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 claims abstract description 15
- 101150056950 Ntrk2 gene Proteins 0.000 claims abstract description 14
- 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 claims abstract description 13
- 101150036586 FES gene Proteins 0.000 claims abstract description 13
- 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 claims abstract description 13
- 101100272634 Mus musculus Bmx gene Proteins 0.000 claims abstract description 13
- 101000922131 Homo sapiens Tyrosine-protein kinase CSK Proteins 0.000 claims abstract description 11
- 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 claims abstract description 11
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- -1 hydroxy C1-6alkyl Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- GUXRZPJLPDVPJS-UHFFFAOYSA-N 4-chloro-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(Cl)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 GUXRZPJLPDVPJS-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 229910020008 S(O) Inorganic materials 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
- RLWJHNPBSIVWCW-UHFFFAOYSA-N 4-chloro-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(Cl)=C4C=C3)C(C)=CC=2)C=C1 RLWJHNPBSIVWCW-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 230000007170 pathology Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- MQIPQQLXOZJHTP-UHFFFAOYSA-N n-[5-[[3-fluoro-5-(trifluoromethyl)benzoyl]amino]-2-methylphenyl]-4-[3-(1-hydroxyethyl)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(F)C=3)C(F)(F)F)C=2)C)=C1 MQIPQQLXOZJHTP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- TZPPOOXFHQMTSD-UHFFFAOYSA-N 4-(3-acetamidoanilino)-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(=O)NC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1 TZPPOOXFHQMTSD-UHFFFAOYSA-N 0.000 claims description 2
- ZSPBAHOTUQKQOK-UHFFFAOYSA-N 4-(3-bromoanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(Br)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 ZSPBAHOTUQKQOK-UHFFFAOYSA-N 0.000 claims description 2
- PWWKJTCSJICONG-UHFFFAOYSA-N 4-(3-bromoanilino)-n-[3-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound BrC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C=C(C=CC=2)C(=O)NC=2C=CC(=CC=2)N2CCOCC2)=C1 PWWKJTCSJICONG-UHFFFAOYSA-N 0.000 claims description 2
- ATNBRXYGVWYSSS-UHFFFAOYSA-N 4-(3-carbamoylanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C(N)=O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 ATNBRXYGVWYSSS-UHFFFAOYSA-N 0.000 claims description 2
- UADDISIFXJFVJE-UHFFFAOYSA-N 4-(3-carbamoylanilino)-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=C(C=CC=4)C(N)=O)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 UADDISIFXJFVJE-UHFFFAOYSA-N 0.000 claims description 2
- DIAUEZFTEANPKW-UHFFFAOYSA-N 4-(3-carbamoylanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C(N)=O)=C4C=C3)C(C)=CC=2)C=C1 DIAUEZFTEANPKW-UHFFFAOYSA-N 0.000 claims description 2
- WBXFQDNGRMJSEU-UHFFFAOYSA-N 4-(3-chloroanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(Cl)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 WBXFQDNGRMJSEU-UHFFFAOYSA-N 0.000 claims description 2
- SSPBSSSLXNCQBJ-UHFFFAOYSA-N 4-(3-cyanoanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C#N)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 SSPBSSSLXNCQBJ-UHFFFAOYSA-N 0.000 claims description 2
- SQFOGKADMIALOQ-UHFFFAOYSA-N 4-(3-fluoroanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(F)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 SQFOGKADMIALOQ-UHFFFAOYSA-N 0.000 claims description 2
- NMILQUSRDCKFFI-UHFFFAOYSA-N 4-(3-methylanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C)C=CC=5)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 NMILQUSRDCKFFI-UHFFFAOYSA-N 0.000 claims description 2
- ZQFYMEFSGXPSPT-UHFFFAOYSA-N 4-(4-carbamoylanilino)-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=CC(=CC=4)C(N)=O)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 ZQFYMEFSGXPSPT-UHFFFAOYSA-N 0.000 claims description 2
- DDSSBKNEYDTIMA-UHFFFAOYSA-N 4-(4-fluoro-2-methylanilino)-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C(=CC(F)=CC=5)C)=C4C=C3)C(C)=CC=2)C=C1 DDSSBKNEYDTIMA-UHFFFAOYSA-N 0.000 claims description 2
- VPNKGBSMPKBIAY-UHFFFAOYSA-N 4-[3-(1-hydroxyethyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 VPNKGBSMPKBIAY-UHFFFAOYSA-N 0.000 claims description 2
- FWZPOTDOHKDVIT-UHFFFAOYSA-N 4-[3-(1-hydroxyethyl)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1 FWZPOTDOHKDVIT-UHFFFAOYSA-N 0.000 claims description 2
- WOQKHRKDYWZNEG-UHFFFAOYSA-N 4-[3-(2-hydroxypropan-2-yl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)C(C)(C)O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 WOQKHRKDYWZNEG-UHFFFAOYSA-N 0.000 claims description 2
- WPKFPABZEAONQB-UHFFFAOYSA-N 4-[3-(2-methoxyethylcarbamoyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound COCCNC(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 WPKFPABZEAONQB-UHFFFAOYSA-N 0.000 claims description 2
- PJTVXNSVTIVHAJ-UHFFFAOYSA-N 4-[3-(butylsulfamoyl)anilino]-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CCCCNS(=O)(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=CC(CN4CCN(C)CC4)=CC=3)C=2)C)=C1 PJTVXNSVTIVHAJ-UHFFFAOYSA-N 0.000 claims description 2
- VMEAGAJMGGCAEK-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 VMEAGAJMGGCAEK-UHFFFAOYSA-N 0.000 claims description 2
- CGFZWFDOGHQSOP-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1 CGFZWFDOGHQSOP-UHFFFAOYSA-N 0.000 claims description 2
- XQIKPMJOJVFLIQ-UHFFFAOYSA-N 4-[3-(hydroxymethyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(CO)C=CC=5)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 XQIKPMJOJVFLIQ-UHFFFAOYSA-N 0.000 claims description 2
- AYLLCEFPZNBRLH-UHFFFAOYSA-N 4-[3-(hydroxymethyl)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=C(CO)C=CC=4)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 AYLLCEFPZNBRLH-UHFFFAOYSA-N 0.000 claims description 2
- GHHAQSBCUFDLEA-UHFFFAOYSA-N 4-[3-(hydroxymethyl)anilino]-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(CO)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 GHHAQSBCUFDLEA-UHFFFAOYSA-N 0.000 claims description 2
- KWQOKBQJOVNBTN-UHFFFAOYSA-N 4-[3-(methylcarbamoyl)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CNC(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 KWQOKBQJOVNBTN-UHFFFAOYSA-N 0.000 claims description 2
- TWZJCYQRTFJSAF-UHFFFAOYSA-N 4-chloro-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(Cl)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 TWZJCYQRTFJSAF-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- FTVDRSKMAKDXMF-UHFFFAOYSA-N [3-[[7-[[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]carbamoyl]pyrrolo[2,3-d]pyrimidin-4-yl]amino]phenyl]methyl acetate Chemical compound CC(=O)OCC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 FTVDRSKMAKDXMF-UHFFFAOYSA-N 0.000 claims description 2
- KLMBMLLBCGFEKR-UHFFFAOYSA-N [3-[[7-[[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]carbamoyl]-7h-cyclopenta[d]pyrimidin-4-yl]amino]phenyl]methyl acetate Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)C3C4=C(C(=NC=N4)NC=4C=C(COC(C)=O)C=CC=4)C=C3)C(C)=CC=2)C=C1 KLMBMLLBCGFEKR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- LYZOGIUMCBXHNA-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]-4-(3-prop-1-en-2-ylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(=C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 LYZOGIUMCBXHNA-UHFFFAOYSA-N 0.000 claims description 2
- UNZWZIXADXMVCK-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]-4-(3-sulfamoylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)S(N)(=O)=O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 UNZWZIXADXMVCK-UHFFFAOYSA-N 0.000 claims description 2
- UONKBMALFYINMH-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]-4-oxo-1h-pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 UONKBMALFYINMH-UHFFFAOYSA-N 0.000 claims description 2
- BKXFBTKOLQPWBF-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 BKXFBTKOLQPWBF-UHFFFAOYSA-N 0.000 claims description 2
- WRPUNSVNOVIWQJ-UHFFFAOYSA-N n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]-4-(3-sulfamoylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=C(C=CC=4)S(N)(=O)=O)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 WRPUNSVNOVIWQJ-UHFFFAOYSA-N 0.000 claims description 2
- YYGIKXZUPBZOQY-UHFFFAOYSA-N n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]-4-oxo-1h-pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(O)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 YYGIKXZUPBZOQY-UHFFFAOYSA-N 0.000 claims description 2
- MJNMEIBXIFQKEB-UHFFFAOYSA-N n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]-4-(3-methylsulfanylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CSC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=CC(CN4CCN(C)CC4)=CC=3)C=2)C)=C1 MJNMEIBXIFQKEB-UHFFFAOYSA-N 0.000 claims description 2
- DUPNUSWZGRBAFC-UHFFFAOYSA-N n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]-4-(3-sulfamoylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(C=CC=5)S(N)(=O)=O)=C4C=C3)C(C)=CC=2)C=C1 DUPNUSWZGRBAFC-UHFFFAOYSA-N 0.000 claims description 2
- MJGAXHSYLCJQTG-UHFFFAOYSA-N n-[3-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]-4-[3-(trifluoromethyl)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C=C(C=CC=2)C(=O)NC=2C=CC(=CC=2)N2CCOCC2)=C1 MJGAXHSYLCJQTG-UHFFFAOYSA-N 0.000 claims description 2
- WKEFBULGWOHGCS-UHFFFAOYSA-N n-[3-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]-4-[4-(trifluoromethoxy)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=NC=NC2=C1C=CN2C(=O)NC1=CC=CC(C(=O)NC=2C=CC(=CC=2)N2CCOCC2)=C1 WKEFBULGWOHGCS-UHFFFAOYSA-N 0.000 claims description 2
- JLVCZANUGLWQCN-UHFFFAOYSA-N n-[3-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]-4-[4-(trifluoromethyl)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1C=CN2C(=O)NC1=CC=CC(C(=O)NC=2C=CC(=CC=2)N2CCOCC2)=C1 JLVCZANUGLWQCN-UHFFFAOYSA-N 0.000 claims description 2
- SZONEEMLVIFENO-UHFFFAOYSA-N n-[4-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]-4-[4-(trifluoromethyl)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1C=CN2C(=O)NC1=CC=C(C(=O)NC=2C=CC(=CC=2)N2CCOCC2)C=C1 SZONEEMLVIFENO-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 14
- 125000001475 halogen functional group Chemical group 0.000 claims 11
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims 1
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- QQVKTKJYOKUSMW-UHFFFAOYSA-N 4-(3-acetamidoanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CC(=O)NC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=C1 QQVKTKJYOKUSMW-UHFFFAOYSA-N 0.000 claims 1
- DCJUMHHRGCOKRZ-UHFFFAOYSA-N 4-(4-carbamoylanilino)-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=CC(=CC=5)C(N)=O)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 DCJUMHHRGCOKRZ-UHFFFAOYSA-N 0.000 claims 1
- PCDGESIQXPGJGA-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[2-methyl-3-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=CC=2)C)=C1 PCDGESIQXPGJGA-UHFFFAOYSA-N 0.000 claims 1
- XPKOYLFTDURSLS-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C(=CC=C(NC(=O)C=3C=CC(CN4CCN(C)CC4)=CC=3)C=2)C)=C1 XPKOYLFTDURSLS-UHFFFAOYSA-N 0.000 claims 1
- IDWNPBYCXZWKTF-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]-n-[3-[[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]methyl]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(=O)NC=2C=C(CNC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=CC=2)=C1 IDWNPBYCXZWKTF-UHFFFAOYSA-N 0.000 claims 1
- QUOFKSRNXCTMNA-UHFFFAOYSA-N 4-[3-(methanesulfonamido)anilino]-n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(NS(C)(=O)=O)C=CC=5)=C4C=C3)C(C)=CC=2)=CC(C(F)(F)F)=C1 QUOFKSRNXCTMNA-UHFFFAOYSA-N 0.000 claims 1
- LMJBQZWCUKLHJO-UHFFFAOYSA-N 4-[3-(methanesulfonamido)anilino]-n-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(NC=4C=C(NS(C)(=O)=O)C=CC=4)=C3C=C2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 LMJBQZWCUKLHJO-UHFFFAOYSA-N 0.000 claims 1
- 101001005314 Arabidopsis thaliana Ceramide synthase LOH2 Proteins 0.000 claims 1
- BJOGMQOQKRMBFH-UHFFFAOYSA-N n-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]-4-morpholin-4-ylpyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(=C4C=C3)N3CCOCC3)C(C)=CC=2)=CC(C(F)(F)F)=C1 BJOGMQOQKRMBFH-UHFFFAOYSA-N 0.000 claims 1
- GPVGAJHARREYEF-UHFFFAOYSA-N n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]-4-(3-phenoxyanilino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=C(OC=6C=CC=CC=6)C=CC=5)=C4C=C3)C(C)=CC=2)C=C1 GPVGAJHARREYEF-UHFFFAOYSA-N 0.000 claims 1
- FKHFSZVNHQMDEK-UHFFFAOYSA-N n-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]-4-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC(=O)N3C4=NC=NC(NC=5C=NC=CC=5)=C4C=C3)C(C)=CC=2)C=C1 FKHFSZVNHQMDEK-UHFFFAOYSA-N 0.000 claims 1
- ULNVSSYTPKJONX-UHFFFAOYSA-N n-[5-[[3-fluoro-5-(trifluoromethyl)benzoyl]amino]-2-methylphenyl]-4-morpholin-4-ylpyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=C(NC(=O)N2C3=NC=NC(=C3C=C2)N2CCOCC2)C(C)=CC=C1NC(=O)C1=CC(F)=CC(C(F)(F)F)=C1 ULNVSSYTPKJONX-UHFFFAOYSA-N 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 abstract description 10
- 230000004913 activation Effects 0.000 abstract description 9
- 208000035475 disorder Diseases 0.000 abstract description 9
- 230000002074 deregulated effect Effects 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 55
- 239000011347 resin Substances 0.000 description 49
- 229920005989 resin Polymers 0.000 description 49
- 210000004027 cell Anatomy 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 13
- 125000005843 halogen group Chemical group 0.000 description 13
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 11
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- 108700012928 MAPK14 Proteins 0.000 description 9
- 102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 8
- 102000043136 MAP kinase family Human genes 0.000 description 8
- 108091054455 MAP kinase family Proteins 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 150000001204 N-oxides Chemical class 0.000 description 7
- 102000001253 Protein Kinase Human genes 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 230000001413 cellular effect Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 108060006633 protein kinase Proteins 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 6
- 239000012346 acetyl chloride Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 5
- 239000006180 TBST buffer Substances 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 229960002411 imatinib Drugs 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- DYTDVDGSDLVBPF-UHFFFAOYSA-N n-(3-amino-4-methylphenyl)-3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(N)C(C)=CC=2)=CC(C(F)(F)F)=C1 DYTDVDGSDLVBPF-UHFFFAOYSA-N 0.000 description 5
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 5
- GZVFYXQNLUYCES-UHFFFAOYSA-N 4-[3-(dimethylamino)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound CN(C)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(O)=O)=C1 GZVFYXQNLUYCES-UHFFFAOYSA-N 0.000 description 4
- BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 4
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical class CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 229930105110 Cyclosporin A Natural products 0.000 description 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- 208000007766 Kaposi sarcoma Diseases 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 2
- GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 description 2
- JPVKCHIPRSQDKL-UHFFFAOYSA-N 3-aminobenzenesulfonamide Chemical compound NC1=CC=CC(S(N)(=O)=O)=C1 JPVKCHIPRSQDKL-UHFFFAOYSA-N 0.000 description 2
- KASCOCXTXASJAT-UHFFFAOYSA-N 4-(3-carbamoylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound NC(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(O)=O)=C1 KASCOCXTXASJAT-UHFFFAOYSA-N 0.000 description 2
- GDIIPKWHAQGCJF-UHFFFAOYSA-N 4-Amino-2-nitrotoluene Chemical compound CC1=CC=C(N)C=C1[N+]([O-])=O GDIIPKWHAQGCJF-UHFFFAOYSA-N 0.000 description 2
- DAJRDAONMDEBGK-UHFFFAOYSA-N 4-amino-n-(4-morpholin-4-ylphenyl)benzamide Chemical compound C1=CC(N)=CC=C1C(=O)NC1=CC=C(N2CCOCC2)C=C1 DAJRDAONMDEBGK-UHFFFAOYSA-N 0.000 description 2
- RKTIGIFGDFPRNU-UHFFFAOYSA-N 4-chloro-n-[3-[(4-morpholin-4-ylphenyl)carbamoyl]phenyl]pyrrolo[2,3-d]pyrimidine-7-carboxamide Chemical compound C1=CC=2C(Cl)=NC=NC=2N1C(=O)NC(C=1)=CC=CC=1C(=O)NC(C=C1)=CC=C1N1CCOCC1 RKTIGIFGDFPRNU-UHFFFAOYSA-N 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 101100127166 Escherichia coli (strain K12) kefB gene Proteins 0.000 description 2
- 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 2
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000012825 JNK inhibitor Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 2
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 2
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 2
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910008066 SnC12 Inorganic materials 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 231100000024 genotoxic Toxicity 0.000 description 2
- 230000001738 genotoxic effect Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 239000003018 immunosuppressive agent Chemical class 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- FXJLDIHKTIMSKR-UHFFFAOYSA-N n-(3-amino-4-methylphenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(N)C(C)=CC=2)C=C1 FXJLDIHKTIMSKR-UHFFFAOYSA-N 0.000 description 2
- NRYIGJHDUDGENR-UHFFFAOYSA-N n-(3-amino-4-methylphenyl)-n-methyl-4-[(4-methylpiperazin-1-yl)methyl]benzamide Chemical compound C=1C=C(C)C(N)=CC=1N(C)C(=O)C(C=C1)=CC=C1CN1CCN(C)CC1 NRYIGJHDUDGENR-UHFFFAOYSA-N 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Chemical class COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000011369 resultant mixture Substances 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical class C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- ZMKGDQSIRSGUDJ-VSROPUKISA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-30-propyl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,1 Chemical compound CCC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-VSROPUKISA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N 1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthrene-1-carboxylic acid Chemical compound C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- QPKNDHZQPGMLCJ-UHFFFAOYSA-N 1-(3-aminophenyl)ethanol Chemical compound CC(O)C1=CC=CC(N)=C1 QPKNDHZQPGMLCJ-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 1
- IDINUJSAMVOPCM-UHFFFAOYSA-N 15-Deoxyspergualin Natural products NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 description 1
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 1
- ZQOCDOFDUXPNGM-UHFFFAOYSA-N 3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoic acid Chemical compound C1=NC(C)=CN1C1=CC(C(O)=O)=CC(C(F)(F)F)=C1 ZQOCDOFDUXPNGM-UHFFFAOYSA-N 0.000 description 1
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
- BZJPIQKDEGXVFG-UHFFFAOYSA-N 3-n,3-n-dimethylbenzene-1,3-diamine;hydron;dichloride Chemical compound Cl.Cl.CN(C)C1=CC=CC(N)=C1 BZJPIQKDEGXVFG-UHFFFAOYSA-N 0.000 description 1
- RORAMMYKHQADMS-UHFFFAOYSA-N 4-(3-acetamidoanilino)pyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound CC(=O)NC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(O)=O)=C1 RORAMMYKHQADMS-UHFFFAOYSA-N 0.000 description 1
- OTALZDIQWFMHKO-UHFFFAOYSA-N 4-(3-phenoxyanilino)pyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound N1=CN=C2N(C(=O)O)C=CC2=C1NC(C=1)=CC=CC=1OC1=CC=CC=C1 OTALZDIQWFMHKO-UHFFFAOYSA-N 0.000 description 1
- PHDIAPKLPNARHB-UHFFFAOYSA-N 4-(3-sulfamoylanilino)pyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound NS(=O)(=O)C1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(O)=O)=C1 PHDIAPKLPNARHB-UHFFFAOYSA-N 0.000 description 1
- RCOVTJVRTZGSBP-UHFFFAOYSA-N 4-(chloromethyl)benzoyl chloride Chemical compound ClCC1=CC=C(C(Cl)=O)C=C1 RCOVTJVRTZGSBP-UHFFFAOYSA-N 0.000 description 1
- ZOOZXDGDFIQCBS-UHFFFAOYSA-N 4-[3-(methanesulfonamido)anilino]pyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound CS(=O)(=O)NC1=CC=CC(NC=2C=3C=CN(C=3N=CN=2)C(O)=O)=C1 ZOOZXDGDFIQCBS-UHFFFAOYSA-N 0.000 description 1
- VKZOXQNUAHVPBH-UHFFFAOYSA-N 4-chloropyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound N1=CN=C2N(C(=O)O)C=CC2=C1Cl VKZOXQNUAHVPBH-UHFFFAOYSA-N 0.000 description 1
- PHNDZBFLOPIMSM-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCOCC1 PHNDZBFLOPIMSM-UHFFFAOYSA-N 0.000 description 1
- SZJFFFSLLLYELF-UHFFFAOYSA-N 4-morpholin-4-ylpyrrolo[2,3-d]pyrimidine-7-carboxylic acid Chemical compound N1=CN=C2N(C(=O)O)C=CC2=C1N1CCOCC1 SZJFFFSLLLYELF-UHFFFAOYSA-N 0.000 description 1
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 1
- ITZMJCSORYKOSI-AJNGGQMLSA-N APGPR Enterostatin Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N1[C@H](C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CCC1 ITZMJCSORYKOSI-AJNGGQMLSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000032800 BCR-ABL1 positive blast phase chronic myelogenous leukemia Diseases 0.000 description 1
- 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 description 1
- 101150049556 Bcr gene Proteins 0.000 description 1
- 208000004860 Blast Crisis Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 108091071554 Fes family Proteins 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010056328 Hepatic ischaemia Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000935548 Homo sapiens Cytoplasmic tyrosine-protein kinase BMX Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100381978 Mus musculus Braf gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ZMKGDQSIRSGUDJ-UHFFFAOYSA-N NVa2 cyclosporine Natural products CCCC1NC(=O)C(C(O)C(C)CC=CC)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 101150091206 Nfkbia gene Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- BTKMJKKKZATLBU-UHFFFAOYSA-N [2-(1,3-benzothiazol-2-yl)-1,3-benzothiazol-6-yl] dihydrogen phosphate Chemical compound C1=CC=C2SC(C3=NC4=CC=C(C=C4S3)OP(O)(=O)O)=NC2=C1 BTKMJKKKZATLBU-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000009925 apoptotic mechanism Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical class C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 description 1
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Chemical class CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 1
- 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 229950010231 brequinar Drugs 0.000 description 1
- PHEZJEYUWHETKO-UHFFFAOYSA-N brequinar Chemical compound N1=C2C=CC(F)=CC2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PHEZJEYUWHETKO-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940126523 co-drug Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 108010019249 cyclosporin G Proteins 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 230000000431 effect on proliferation Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000001357 hemopoietic progenitor cell Anatomy 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- CZGDYZDUMJDQSD-UHFFFAOYSA-N hydron;4-(trifluoromethyl)aniline;chloride Chemical compound Cl.NC1=CC=C(C(F)(F)F)C=C1 CZGDYZDUMJDQSD-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 108700025907 jun Genes Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 229950000844 mizoribine Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- BLUYEPLOXLPVCJ-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxyethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC[C@H](O)NC(=O)CCCCCCNC(N)=N BLUYEPLOXLPVCJ-INIZCTEOSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 102000005912 ran GTP Binding Protein Human genes 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 201000003896 thanatophoric dysplasia Diseases 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000012443 tonicity enhancing agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 101150025395 trkA gene Proteins 0.000 description 1
- 101150113435 trkA1 gene Proteins 0.000 description 1
- 102000047459 trkC Receptor Human genes 0.000 description 1
- 108010064892 trkC Receptor Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49853203P | 2003-08-28 | 2003-08-28 | |
| US60/498,532 | 2003-08-28 | ||
| PCT/US2004/027997 WO2005039486A2 (en) | 2003-08-28 | 2004-08-27 | Compounds and compositions as protein kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2536535A1 true CA2536535A1 (en) | 2005-05-06 |
Family
ID=34519982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002536535A Abandoned CA2536535A1 (en) | 2003-08-28 | 2004-08-27 | Compounds and compositions as protein kinase inhibitors |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7338957B2 (https=) |
| EP (1) | EP1658290A4 (https=) |
| JP (1) | JP2007504159A (https=) |
| CN (1) | CN100439365C (https=) |
| AU (1) | AU2004283093B2 (https=) |
| BR (1) | BRPI0414049A (https=) |
| CA (1) | CA2536535A1 (https=) |
| MX (1) | MXPA06002347A (https=) |
| WO (1) | WO2005039486A2 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0202873D0 (en) * | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| TW200616974A (en) * | 2004-07-01 | 2006-06-01 | Astrazeneca Ab | Chemical compounds |
| US8183248B2 (en) * | 2005-05-13 | 2012-05-22 | Irm Llc | Substituted pyrrolo[2,3-d]pyrimidines and compositions as protein kinase inhibitors |
| JP5680850B2 (ja) * | 2006-03-30 | 2015-03-04 | ザ・ユニバーシティ・コート・オブ・ザ・ユニバーシティ・オブ・エディンバラＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｃｏｕｒｔ ｏｆ ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ ｏｆ Ｅｄｉｎｂｕｒｇｈ | キナーゼインヒビターを含む培養培地およびその使用 |
| GB0615327D0 (en) | 2006-03-30 | 2006-09-13 | Univ Edinburgh | Culture medium containing kinase inhibitors and uses thereof |
| US20090286803A1 (en) | 2006-04-07 | 2009-11-19 | Manley Paul W | Combination comprising a) a pyrimidylaminobenzamide compound, and b) a thr315lle kinase inhibitor |
| WO2008147831A1 (en) * | 2007-05-23 | 2008-12-04 | Smithkline Beecham Corporation | Anthranilamides |
| WO2009042013A1 (en) | 2007-08-02 | 2009-04-02 | Millennium Pharmaceuticals, Inc. | Process for the synthesis of e1 activating enzyme inhibitors |
| ES2424977T3 (es) * | 2007-08-08 | 2013-10-10 | Glaxosmithkline Intellectual Property Development Limited | Derivados de 2-[(2-{fenilamino}-1H-pirrolo[2,3-D]pirimidin-4-il)amino]benzamida como inhibidores de IGF-1R para el tratamiento del cáncer |
| EA019869B1 (ru) * | 2007-11-28 | 2014-06-30 | Дана Фарбер Кансер Инститьют, Инк. | Низкомолекулярные миристатные ингибиторы тирозинкиназы bcr-abl и способы их применения |
| JP2011510004A (ja) * | 2008-01-22 | 2011-03-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | タンパク質キナーゼ阻害剤及びその使用 |
| MX353308B (es) | 2008-05-21 | 2018-01-08 | Ariad Pharma Inc | Derivados fosforosos como inhibidores de cinasa. |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| SG175929A1 (en) | 2009-05-14 | 2011-12-29 | Millennium Pharm Inc | Hydrochloride salt of ((1s,2s,4r)-4-{4-[(1s)-2,3-dihydro-1h-inden-1-ylamino]-7h-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate |
| US8728763B2 (en) | 2009-08-11 | 2014-05-20 | Response Genetics | Methods, primers, probes and kits useful for the detection of BRAF mutations |
| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| WO2013169401A1 (en) | 2012-05-05 | 2013-11-14 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN104876879B (zh) * | 2015-04-14 | 2018-05-18 | 中国科学院合肥物质科学研究院 | 一种bcr-abl激酶抑制剂 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3290666B2 (ja) * | 1995-06-07 | 2002-06-10 | ファイザー・インコーポレーテッド | 複素環式の縮合環ピリミジン誘導体 |
| ID29028A (id) * | 1998-09-18 | 2001-07-26 | Basf Ag | Pirolopirimidina sebagai penghambat protein kinase |
| CO5271715A1 (es) * | 1999-12-21 | 2003-04-30 | Sugen Inc | 7-aza-indolin-2-onas sustituidas en 4 y su uso como inhibidores de proteiuna quinasa |
| UA76977C2 (en) * | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
| US20040235867A1 (en) * | 2001-07-24 | 2004-11-25 | Bilodeau Mark T. | Tyrosine kinase inhibitors |
-
2004
- 2004-08-26 US US10/927,992 patent/US7338957B2/en not_active Expired - Fee Related
- 2004-08-27 BR BRPI0414049-4A patent/BRPI0414049A/pt not_active IP Right Cessation
- 2004-08-27 CA CA002536535A patent/CA2536535A1/en not_active Abandoned
- 2004-08-27 WO PCT/US2004/027997 patent/WO2005039486A2/en not_active Ceased
- 2004-08-27 MX MXPA06002347A patent/MXPA06002347A/es active IP Right Grant
- 2004-08-27 AU AU2004283093A patent/AU2004283093B2/en not_active Ceased
- 2004-08-27 CN CNB2004800245751A patent/CN100439365C/zh not_active Expired - Fee Related
- 2004-08-27 EP EP04816834A patent/EP1658290A4/en not_active Withdrawn
- 2004-08-27 JP JP2006524903A patent/JP2007504159A/ja active Pending
-
2008
- 2008-01-07 US US11/970,278 patent/US20080108616A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007504159A (ja) | 2007-03-01 |
| US20080108616A1 (en) | 2008-05-08 |
| WO2005039486A3 (en) | 2006-03-16 |
| MXPA06002347A (es) | 2006-05-19 |
| AU2004283093B2 (en) | 2009-02-26 |
| US20050159391A1 (en) | 2005-07-21 |
| US7338957B2 (en) | 2008-03-04 |
| BRPI0414049A (pt) | 2006-10-24 |
| CN100439365C (zh) | 2008-12-03 |
| EP1658290A4 (en) | 2009-04-15 |
| WO2005039486A2 (en) | 2005-05-06 |
| EP1658290A2 (en) | 2006-05-24 |
| CN1842529A (zh) | 2006-10-04 |
| AU2004283093A1 (en) | 2005-05-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20080108616A1 (en) | Compounds and compositions as protein kinase inhibitors | |
| ES2424642T3 (es) | Compuestos y composiciones como inhibidores de la proteína quinasa | |
| CA2583737C (en) | Compounds and compositions as protein kinase inhibitors | |
| ES2358344T3 (es) | Compuestos y composiciones como inhibidores de proteína quinasa. | |
| AU2006227790B2 (en) | Compounds and compositions as protein kinase inhibitors | |
| ES2477878T3 (es) | Compuestos y composiciones de 5-(4-(aloalcoxi)fenil)pirimidin-2-amina como inhibidores de quinasas | |
| AU2008203183A1 (en) | Compounds and compositions as protein kinase inhibitors | |
| US20100324062A1 (en) | Compounds and compositions as protein kinase inhibitors | |
| CA2672101A1 (en) | Compounds and compositions as kinase inhibitors | |
| AU2005258266A1 (en) | Compounds and compositions as protein kinase inhibitors | |
| CN117645598A (zh) | 氮杂二并多元稠环化合物及其药物组合物和应用 | |
| CN101056632B (zh) | 用作蛋白激酶抑制剂的化合物和组合物 | |
| KR100935273B1 (ko) | 단백질 키나제 억제제 화합물 및 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |