ZA200505934B - Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors - Google Patents
Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors Download PDFInfo
- Publication number
- ZA200505934B ZA200505934B ZA200505934A ZA200505934A ZA200505934B ZA 200505934 B ZA200505934 B ZA 200505934B ZA 200505934 A ZA200505934 A ZA 200505934A ZA 200505934 A ZA200505934 A ZA 200505934A ZA 200505934 B ZA200505934 B ZA 200505934B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- product
- alkyl
- radicals
- optionally substituted
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims 10
- 229940043355 kinase inhibitor Drugs 0.000 title claims 2
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical class OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- -1 heterocyclic radical Chemical class 0.000 claims description 332
- 125000000217 alkyl group Chemical group 0.000 claims description 192
- 229910052739 hydrogen Inorganic materials 0.000 claims description 135
- 239000001257 hydrogen Substances 0.000 claims description 135
- 150000003254 radicals Chemical class 0.000 claims description 127
- 229910052760 oxygen Inorganic materials 0.000 claims description 85
- 150000002431 hydrogen Chemical class 0.000 claims description 69
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 62
- 239000011707 mineral Substances 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 59
- 125000004432 carbon atom Chemical group C* 0.000 claims description 58
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 56
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 52
- 239000001301 oxygen Substances 0.000 claims description 52
- 125000001424 substituent group Chemical group 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 48
- 125000001072 heteroaryl group Chemical group 0.000 claims description 47
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 206010028980 Neoplasm Diseases 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- 125000003342 alkenyl group Chemical group 0.000 claims description 33
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 150000007522 mineralic acids Chemical class 0.000 claims description 31
- 150000007524 organic acids Chemical class 0.000 claims description 31
- 235000005985 organic acids Nutrition 0.000 claims description 31
- 150000007530 organic bases Chemical class 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 102000001253 Protein Kinase Human genes 0.000 claims description 21
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 108060006633 protein kinase Proteins 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 125000002837 carbocyclic group Chemical group 0.000 claims description 13
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 12
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 238000002512 chemotherapy Methods 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 5
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 230000035755 proliferation Effects 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 102100037813 Focal adhesion kinase 1 Human genes 0.000 claims description 2
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 2
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 31
- 239000000126 substance Substances 0.000 claims 29
- 238000000034 method Methods 0.000 claims 20
- 229940126601 medicinal product Drugs 0.000 claims 19
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims 17
- 150000001721 carbon Chemical group 0.000 claims 15
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 12
- 125000004193 piperazinyl group Chemical group 0.000 claims 12
- 125000002757 morpholinyl group Chemical group 0.000 claims 11
- 125000005936 piperidyl group Chemical group 0.000 claims 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 7
- 229940080818 propionamide Drugs 0.000 claims 7
- 208000035475 disorder Diseases 0.000 claims 6
- 125000002883 imidazolyl group Chemical group 0.000 claims 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 6
- 239000000651 prodrug Substances 0.000 claims 5
- 229940002612 prodrug Drugs 0.000 claims 5
- 125000000335 thiazolyl group Chemical group 0.000 claims 5
- WUEPMEXUMQVEGN-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;2,2,2-trifluoro-n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethylamino]ethyl]acetamide Chemical compound OC(=O)C(F)(F)F.FC(F)(F)C(=O)NCCNCCNC(=O)C(F)(F)F WUEPMEXUMQVEGN-UHFFFAOYSA-N 0.000 claims 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 4
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000005493 quinolyl group Chemical group 0.000 claims 4
- 125000001544 thienyl group Chemical group 0.000 claims 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims 3
- XIPUIGPNIDKXJU-UHFFFAOYSA-N [CH]1CC1 Chemical compound [CH]1CC1 XIPUIGPNIDKXJU-UHFFFAOYSA-N 0.000 claims 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000003838 furazanyl group Chemical group 0.000 claims 3
- 125000002541 furyl group Chemical group 0.000 claims 3
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
- 206010005949 Bone cancer Diseases 0.000 claims 2
- 208000018084 Bone neoplasm Diseases 0.000 claims 2
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 claims 2
- 206010020751 Hypersensitivity Diseases 0.000 claims 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 206010028289 Muscle atrophy Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 208000017442 Retinal disease Diseases 0.000 claims 2
- 206010038923 Retinopathy Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 2
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 230000007815 allergy Effects 0.000 claims 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- 208000006673 asthma Diseases 0.000 claims 2
- 125000003725 azepanyl group Chemical group 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 2
- 210000004204 blood vessel Anatomy 0.000 claims 2
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 230000003831 deregulation Effects 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 230000003176 fibrotic effect Effects 0.000 claims 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 2
- 125000001041 indolyl group Chemical group 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 206010023841 laryngeal neoplasm Diseases 0.000 claims 2
- 210000004324 lymphatic system Anatomy 0.000 claims 2
- 210000003584 mesangial cell Anatomy 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 210000000653 nervous system Anatomy 0.000 claims 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 2
- 238000001959 radiotherapy Methods 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 210000001625 seminal vesicle Anatomy 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 206010046766 uterine cancer Diseases 0.000 claims 2
- 201000010653 vesiculitis Diseases 0.000 claims 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims 1
- DEIYDPRULONZAB-UHFFFAOYSA-N 5-[[4-[[5,5-dimethyl-2,4-dioxo-3-[4-(trifluoromethylsulfanyl)phenyl]imidazolidin-1-yl]methyl]pyridin-2-yl]amino]pyridine-2-carboxylic acid Chemical compound O=C1N(C=2C=CC(SC(F)(F)F)=CC=2)C(=O)C(C)(C)N1CC(C=1)=CC=NC=1NC1=CC=C(C(O)=O)N=C1 DEIYDPRULONZAB-UHFFFAOYSA-N 0.000 claims 1
- 101100329003 Arabidopsis thaliana COV1 gene Proteins 0.000 claims 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 claims 1
- 101100342473 Drosophila melanogaster Raf gene Proteins 0.000 claims 1
- 101150017750 FGFRL1 gene Proteins 0.000 claims 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 claims 1
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 claims 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims 1
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 claims 1
- 102100026149 Fibroblast growth factor receptor-like 1 Human genes 0.000 claims 1
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 claims 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims 1
- 108091008611 Protein Kinase B Proteins 0.000 claims 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims 1
- 101100523543 Rattus norvegicus Raf1 gene Proteins 0.000 claims 1
- 108091008605 VEGF receptors Proteins 0.000 claims 1
- 101100523549 Xenopus laevis raf1 gene Proteins 0.000 claims 1
- 101150037250 Zhx2 gene Proteins 0.000 claims 1
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims 1
- 238000004113 cell culture Methods 0.000 claims 1
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims 1
- 229940047889 isobutyramide Drugs 0.000 claims 1
- 239000003909 protein kinase inhibitor Substances 0.000 claims 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
- 125000003831 tetrazolyl group Chemical group 0.000 claims 1
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 26
- 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 24
- 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 24
- 108091000080 Phosphotransferase Proteins 0.000 description 9
- 102000020233 phosphotransferase Human genes 0.000 description 9
- 230000002018 overexpression Effects 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 6
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 230000012010 growth Effects 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 108091007960 PI3Ks Proteins 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 102000006495 integrins Human genes 0.000 description 3
- 108010044426 integrins Proteins 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 2
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 2
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 108091006082 receptor inhibitors Proteins 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 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 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 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 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150012716 CDK1 gene Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229940124783 FAK inhibitor Drugs 0.000 description 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010091824 Focal Adhesion Kinase 1 Proteins 0.000 description 1
- 102000004315 Forkhead Transcription Factors Human genes 0.000 description 1
- 108090000852 Forkhead Transcription Factors Proteins 0.000 description 1
- 102100029974 GTPase HRas Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 102100033067 Growth factor receptor-bound protein 2 Human genes 0.000 description 1
- 108091009389 Growth factor receptor-bound protein 2 Proteins 0.000 description 1
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 1
- 101001077604 Homo sapiens Insulin receptor substrate 1 Proteins 0.000 description 1
- 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
- 101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 1
- 101000798007 Homo sapiens RAC-gamma serine/threonine-protein kinase Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108700012441 IGF2 Proteins 0.000 description 1
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000008636 Neoplastic Processes Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108010058765 Oncogene Protein pp60(v-src) Proteins 0.000 description 1
- 102000018546 Paxillin Human genes 0.000 description 1
- ACNHBCIZLNNLRS-UHFFFAOYSA-N Paxilline 1 Natural products N1C2=CC=CC=C2C2=C1C1(C)C3(C)CCC4OC(C(C)(O)C)C(=O)C=C4C3(O)CCC1C2 ACNHBCIZLNNLRS-UHFFFAOYSA-N 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 101710113459 RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
- 102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 1
- 102100032314 RAC-gamma serine/threonine-protein kinase Human genes 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 108700031954 Tgfb1i1/Leupaxin/TGFB1I1 Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 1
- 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 1
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 210000001650 focal adhesion Anatomy 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 230000005853 oncogenic activation Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- ACNHBCIZLNNLRS-UBGQALKQSA-N paxilline Chemical compound N1C2=CC=CC=C2C2=C1[C@]1(C)[C@@]3(C)CC[C@@H]4O[C@H](C(C)(O)C)C(=O)C=C4[C@]3(O)CC[C@H]1C2 ACNHBCIZLNNLRS-UBGQALKQSA-N 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009396 radiation induced apoptosis Effects 0.000 description 1
- 102000016914 ras Proteins Human genes 0.000 description 1
- 108010014186 ras Proteins Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000025915 regulation of apoptotic process Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material 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)
- Diabetes (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0301098A FR2850652B1 (fr) | 2003-01-31 | 2003-01-31 | Nouveaux derives d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200505934B true ZA200505934B (en) | 2007-06-27 |
Family
ID=32696243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200505934A ZA200505934B (en) | 2003-01-31 | 2005-07-22 | Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors |
Country Status (24)
| Country | Link |
|---|---|
| EP (1) | EP1599464B1 (de) |
| JP (1) | JP4604020B2 (de) |
| KR (1) | KR20050098286A (de) |
| CN (1) | CN1768054A (de) |
| AR (1) | AR042936A1 (de) |
| AT (1) | ATE482207T1 (de) |
| AU (1) | AU2004209319A1 (de) |
| BR (1) | BRPI0407091A (de) |
| CA (1) | CA2513631A1 (de) |
| DE (1) | DE602004029236D1 (de) |
| FR (1) | FR2850652B1 (de) |
| HR (1) | HRP20050679A2 (de) |
| MA (1) | MA27651A1 (de) |
| ME (1) | MEP22608A (de) |
| MX (1) | MXPA05007407A (de) |
| NO (1) | NO20054006L (de) |
| NZ (1) | NZ541270A (de) |
| PE (1) | PE20040808A1 (de) |
| PL (1) | PL377811A1 (de) |
| RS (1) | RS20050657A (de) |
| RU (1) | RU2341523C2 (de) |
| TW (1) | TW200505898A (de) |
| WO (1) | WO2004070050A2 (de) |
| ZA (1) | ZA200505934B (de) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007504171A (ja) | 2003-08-29 | 2007-03-01 | ザ ブライハム アンド ウイメンズ ホスピタル， インコーポレイテッド | 細胞壊死インヒビター |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7700603B2 (en) | 2003-12-15 | 2010-04-20 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| CA2550447A1 (en) | 2003-12-19 | 2005-07-07 | The Regents Of The University Of California | Methods and materials for assessing prostate cancer therapies |
| AU2005232526B2 (en) | 2004-02-24 | 2011-06-23 | The Regents Of The University Of California | Methods and materials for assessing prostate cancer therapies and compounds |
| EP1621535A1 (de) * | 2004-07-27 | 2006-02-01 | Aventis Pharma S.A. | Cyclische Substituirte Harnstoffderivate, Verfahren zu ihrer Herstellung, und ihre pharmazeutische Verwendung als Kinase Inhibitoren |
| EP1621536A1 (de) * | 2004-07-27 | 2006-02-01 | Aventis Pharma S.A. | Amino zyklische Urea-Derivaten, ihre Herstellung und deren pharmazeutische Verwendungen als Kinase Inhibitoren |
| EP1893196B2 (de) | 2005-05-13 | 2015-07-29 | The Regents of The University of California | Diarylhydantoin-verbindung |
| US7709517B2 (en) | 2005-05-13 | 2010-05-04 | The Regents Of The University Of California | Diarylhydantoin compounds |
| US7709516B2 (en) * | 2005-06-17 | 2010-05-04 | Endorecherche, Inc. | Helix 12 directed non-steroidal antiandrogens |
| FR2896503B1 (fr) * | 2006-01-23 | 2012-07-13 | Aventis Pharma Sa | Nouveaux derives soufres d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
| FR2896504B1 (fr) * | 2006-01-23 | 2012-07-13 | Aventis Pharma Sa | Nouveaux derives d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
| SI2368550T1 (sl) * | 2006-03-27 | 2013-11-29 | The Regents Of The University Of California | Modulator androgenskih receptorjev za zdravljenje raka prostate in bolezni, povezanih z androgenskimi receptorji |
| MX2008012492A (es) | 2006-03-29 | 2008-12-12 | Univ California | Compuestos de diariltiohidantoina. |
| WO2008017381A1 (de) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituierte imidazolidin-2,4-dione, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und ihre verwendung |
| AU2007332754A1 (en) | 2006-12-12 | 2008-06-19 | Schering Corporation | Aspartyl protease inhibitors |
| JP5535925B2 (ja) | 2007-10-26 | 2014-07-02 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | アンドロゲン受容体調節物質としてのジアリールヒダントイン化合物 |
| US20120122889A1 (en) | 2008-12-23 | 2012-05-17 | President And Fellows Of Harvard College | Small molecule inhibitors of necroptosis |
| DK3124481T3 (en) | 2010-02-16 | 2018-05-07 | Aragon Pharmaceuticals Inc | ANDROGEN RECEPTOR MODULATORS AND APPLICATIONS THEREOF |
| US8685256B2 (en) * | 2010-12-21 | 2014-04-01 | Cytec Technology Corp. | Microdispersions of hydroxamated polymers and methods of making and using them |
| US8492556B2 (en) * | 2011-11-10 | 2013-07-23 | Allergan, Inc. | 2,5-Dioxoimidazolidin-1-yl-3-phenylurea derivatives as formyl peptide receptor like-1 (FPRL-1) receptor modulators |
| IL312316A (en) | 2012-09-26 | 2024-06-01 | Aragon Pharmaceuticals Inc | Antiandrogens for the treatment of castration-resistant prostate cancer without metastases |
| JOP20200097A1 (ar) | 2013-01-15 | 2017-06-16 | Aragon Pharmaceuticals Inc | معدل مستقبل أندروجين واستخداماته |
| US9725452B2 (en) | 2013-03-15 | 2017-08-08 | Presidents And Fellows Of Harvard College | Substituted indoles and pyrroles as RIP kinase inhibitors |
| GB201312492D0 (en) * | 2013-07-12 | 2013-08-28 | Syngenta Ltd | Herbicidal compounds |
| US10202373B2 (en) | 2014-01-14 | 2019-02-12 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| KR20160122736A (ko) | 2014-01-14 | 2016-10-24 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 헤테로아릴 및 이의 용도 |
| WO2016094846A1 (en) | 2014-12-11 | 2016-06-16 | President And Fellows Of Harvard College | Inhibitors of cellular necrosis and related methods |
| TWI726969B (zh) | 2016-01-11 | 2021-05-11 | 比利時商健生藥品公司 | 用作雄性激素受體拮抗劑之經取代之硫尿囊素衍生物 |
| CN107619388A (zh) * | 2016-07-13 | 2018-01-23 | 南京天印健华医药科技有限公司 | 作为fgfr抑制剂的杂环化合物 |
| HRP20211868T1 (hr) * | 2016-07-20 | 2022-03-04 | Novartis Ag | Derivati aminopiridina i njihova uporaba kao selektivnih inhibitora za alk-2 |
| KR20200070334A (ko) | 2017-10-16 | 2020-06-17 | 아라곤 파마슈티컬스, 인코포레이티드 | 비-전이성 거세-저항성 전립선암의 치료를 위한 항-안드로겐 |
| EP3705474A4 (de) * | 2017-10-31 | 2021-06-09 | Pelemed Co., Ltd. | Pharmazeutische zusammensetzung zur vorbeugung oder behandlung von akuter myeloischer leukämie oder metastatischem brustkrebs |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2329276A1 (fr) * | 1975-10-29 | 1977-05-27 | Roussel Uclaf | Nouvelles imidazolidines substituees, procede de preparation, application comme medicament et compositions les renfermant |
| DE4228717A1 (de) * | 1992-08-28 | 1994-03-03 | Cassella Ag | Imidazolidin-Derivate |
| DE19540027A1 (de) * | 1995-10-27 | 1997-04-30 | Gruenenthal Gmbh | Substituierte Imidazolidin-2,4-dion-Verbindungen als pharmazeutische Wirkstoffe |
| WO1998039303A1 (en) * | 1997-03-03 | 1998-09-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Small molecules useful in the treatment of inflammatory disease |
| DE19732928C2 (de) * | 1997-07-31 | 2000-05-18 | Gruenenthal Gmbh | Verwendung substituierter Imidazolidin-2,4-dion-Verbindungen als Schmerzmittel |
| FR2796945B1 (fr) * | 1999-07-30 | 2002-06-28 | Sod Conseils Rech Applic | Nouveaux derives d'hydantoines, de thiohydantoines, de pyrimidinediones et de thioxopyrimidinones, leurs procedes de preparation et leur application a titre de medicaments |
| EP1284973B1 (de) * | 2000-05-31 | 2007-06-27 | Tanabe Seiyaku Co., Ltd. | Inhibitoren der alpha-l beta-2 vermittelten zelladhäsion |
| CA2486090C (en) * | 2002-05-16 | 2011-07-05 | Bayer Cropscience Gmbh | Pyridine carboxamide derivatives and their use as pesticides |
-
2003
- 2003-01-31 FR FR0301098A patent/FR2850652B1/fr not_active Expired - Fee Related
-
2004
- 2004-01-22 PE PE2004000090A patent/PE20040808A1/es not_active Application Discontinuation
- 2004-01-27 AR ARP040100233A patent/AR042936A1/es unknown
- 2004-01-28 KR KR1020057014096A patent/KR20050098286A/ko not_active Application Discontinuation
- 2004-01-28 EP EP04705838A patent/EP1599464B1/de not_active Expired - Lifetime
- 2004-01-28 RU RU2005127335/04A patent/RU2341523C2/ru not_active IP Right Cessation
- 2004-01-28 ME MEP-226/08A patent/MEP22608A/xx unknown
- 2004-01-28 DE DE602004029236T patent/DE602004029236D1/de not_active Expired - Lifetime
- 2004-01-28 CA CA002513631A patent/CA2513631A1/fr not_active Abandoned
- 2004-01-28 MX MXPA05007407A patent/MXPA05007407A/es active IP Right Grant
- 2004-01-28 PL PL377811A patent/PL377811A1/pl not_active Application Discontinuation
- 2004-01-28 JP JP2006502123A patent/JP4604020B2/ja not_active Expired - Fee Related
- 2004-01-28 BR BR0407091-7A patent/BRPI0407091A/pt not_active IP Right Cessation
- 2004-01-28 CN CNA2004800088356A patent/CN1768054A/zh active Pending
- 2004-01-28 AU AU2004209319A patent/AU2004209319A1/en not_active Abandoned
- 2004-01-28 NZ NZ541270A patent/NZ541270A/en unknown
- 2004-01-28 RS YUP-2005/0657A patent/RS20050657A/sr unknown
- 2004-01-28 WO PCT/FR2004/000188 patent/WO2004070050A2/fr active Application Filing
- 2004-01-28 AT AT04705838T patent/ATE482207T1/de not_active IP Right Cessation
- 2004-01-30 TW TW093102064A patent/TW200505898A/zh unknown
-
2005
- 2005-07-22 ZA ZA200505934A patent/ZA200505934B/en unknown
- 2005-07-29 MA MA28417A patent/MA27651A1/fr unknown
- 2005-07-29 HR HR20050679A patent/HRP20050679A2/xx not_active Application Discontinuation
- 2005-08-29 NO NO20054006A patent/NO20054006L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0407091A (pt) | 2006-01-24 |
| NO20054006L (no) | 2005-10-13 |
| DE602004029236D1 (de) | 2010-11-04 |
| NZ541270A (en) | 2008-11-28 |
| MEP22608A (en) | 2010-06-10 |
| JP2006517569A (ja) | 2006-07-27 |
| FR2850652B1 (fr) | 2008-05-30 |
| ATE482207T1 (de) | 2010-10-15 |
| WO2004070050A2 (fr) | 2004-08-19 |
| HRP20050679A2 (en) | 2006-12-31 |
| EP1599464B1 (de) | 2010-09-22 |
| WO2004070050A3 (fr) | 2005-02-17 |
| RU2005127335A (ru) | 2006-09-10 |
| JP4604020B2 (ja) | 2010-12-22 |
| AU2004209319A1 (en) | 2004-08-19 |
| PE20040808A1 (es) | 2004-12-31 |
| MXPA05007407A (es) | 2005-09-12 |
| RS20050657A (en) | 2007-06-04 |
| RU2341523C2 (ru) | 2008-12-20 |
| MA27651A1 (fr) | 2005-12-01 |
| KR20050098286A (ko) | 2005-10-11 |
| CA2513631A1 (fr) | 2004-08-19 |
| AR042936A1 (es) | 2005-07-06 |
| PL377811A1 (pl) | 2006-02-20 |
| EP1599464A2 (de) | 2005-11-30 |
| NO20054006D0 (no) | 2005-08-29 |
| CN1768054A (zh) | 2006-05-03 |
| TW200505898A (en) | 2005-02-16 |
| FR2850652A1 (fr) | 2004-08-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200505934B (en) | Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors | |
| US20240139194A1 (en) | Preparation and methods of use for ortho-aryl 5-membered heteroaryl-carboxamide containing multi-targeted kinase inhibitors | |
| US7642278B2 (en) | Indazole benzimidazole compounds | |
| US7064215B2 (en) | Indazole benzimidazole compounds | |
| US7186716B2 (en) | 3-Pyrrol-pyridopyrazoles and 3-pyrrolyl-indazoles as novel kinase inhibitors | |
| KR101675984B1 (ko) | 티에노디아제핀 유도체 또는 이의 약학적으로 허용가능한 염, 및 이를 유효성분으로 포함하는 약학적 조성물 | |
| BR112019008061A2 (pt) | métodos de uso de indazol-3-carboxamidas e seu uso como inibidores da via de sinalização de wnt/b-catenina | |
| CN113646307B (zh) | 具有蛋白激酶抑制活性的吡啶并[3,4-d]嘧啶-8-酮衍生物及其药物组合物 | |
| WO2014004863A2 (en) | Compounds, compositions, and therapeutic uses thereof | |
| EP3010503A2 (de) | Neuartige bicyclische bromdomänenhemmer | |
| JP2001508800A (ja) | 血管形成阻害活性を有するフタラジン | |
| JP2016520116A (ja) | イミダゾピロリジノン誘導体および疾患の処置におけるその使用 | |
| JP2015514802A (ja) | Ｒａｆキナーゼ媒介疾患用の方法及び組成物 | |
| TW200303863A (en) | Substituted indazoles, compositions comprising them, manufacturing process and use | |
| US11304929B2 (en) | Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors | |
| JP2016537384A (ja) | ピロロピロロン誘導体およびｂｅｔ阻害剤としてのその使用 | |
| WO2016115869A1 (zh) | Flt3激酶的新型抑制剂及其用途 | |
| JP7285249B2 (ja) | Ｃｄｋ８／ｃｄｋ１９阻害剤としての新規な［１，６］ナフチリジン化合物及び誘導体 | |
| RU2780168C1 (ru) | Новое производное пиридо [3,4-d] пиримидин-8-она, обладающее ингибирующей протеинкиназы активностью, и фармацевтическая композиция для предупреждения, облегчения или лечения рака, содержащее указанное выше | |
| TWI759829B (zh) | 作為第iii型受體酪胺酸激酶抑制劑之雜環吡唑衍生物 | |
| US20240217968A1 (en) | Pharmaceutical compound | |
| EP4377304A1 (de) | Srpk-hemmer | |
| AU2010319382A1 (en) | Kinase inhibitors |