ZA200300489B - Indole, azaindole and indazole derivatives having VEGF inhibiting activities. - Google Patents
Indole, azaindole and indazole derivatives having VEGF inhibiting activities. Download PDFInfo
- Publication number
- ZA200300489B ZA200300489B ZA200300489A ZA200300489A ZA200300489B ZA 200300489 B ZA200300489 B ZA 200300489B ZA 200300489 A ZA200300489 A ZA 200300489A ZA 200300489 A ZA200300489 A ZA 200300489A ZA 200300489 B ZA200300489 B ZA 200300489B
- Authority
- ZA
- South Africa
- Prior art keywords
- salkyl
- group
- 4alkyl
- ring
- compound
- Prior art date
Links
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 14
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 title description 10
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 title description 10
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 title description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title description 9
- 150000002473 indoazoles Chemical class 0.000 title 1
- 230000002401 inhibitory effect Effects 0.000 title 1
- -1 N- methylpiperazinyl Chemical group 0.000 claims description 116
- 229910052739 hydrogen Inorganic materials 0.000 claims description 98
- 239000001257 hydrogen Substances 0.000 claims description 98
- 125000001424 substituent group Chemical group 0.000 claims description 82
- 150000002431 hydrogen Chemical group 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
- 125000005843 halogen group Chemical group 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 125000004043 oxo group Chemical group O=* 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
- 125000005842 heteroatom Chemical group 0.000 claims description 37
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 125000003386 piperidinyl group Chemical group 0.000 claims description 35
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 34
- 125000002393 azetidinyl group Chemical group 0.000 claims description 33
- 125000004122 cyclic group Chemical group 0.000 claims description 29
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 29
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 29
- 125000004193 piperazinyl group Chemical group 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000001041 indolyl group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 230000008728 vascular permeability Effects 0.000 claims description 10
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- 230000001772 anti-angiogenic effect Effects 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
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 230000001603 reducing effect Effects 0.000 claims description 6
- 150000002475 indoles Chemical group 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical group C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 2
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical group C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 8
- 239000000126 substance Substances 0.000 claims 6
- 238000006243 chemical reaction Methods 0.000 claims 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- BKJGIMPOVHBHEG-UHFFFAOYSA-N 1-(1h-indol-6-yloxy)-4-(pyridin-4-ylmethyl)phthalazine Chemical compound N=1N=C(OC=2C=C3NC=CC3=CC=2)C2=CC=CC=C2C=1CC1=CC=NC=C1 BKJGIMPOVHBHEG-UHFFFAOYSA-N 0.000 claims 1
- OCZMXALKTWARIX-UHFFFAOYSA-N 1-[(2-methyl-1h-indol-6-yl)oxy]-4-(pyridin-4-ylmethyl)phthalazine Chemical compound C1=C2NC(C)=CC2=CC=C1OC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 OCZMXALKTWARIX-UHFFFAOYSA-N 0.000 claims 1
- LFIBOSVBSATXIS-UHFFFAOYSA-N 1-[(4-fluoro-1h-indol-5-yl)oxy]-4-(pyridin-4-ylmethyl)phthalazine Chemical compound C1=CC=2NC=CC=2C(F)=C1OC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 LFIBOSVBSATXIS-UHFFFAOYSA-N 0.000 claims 1
- JOWQCTXBMHNGDA-UHFFFAOYSA-N 1-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-4-(pyridin-4-ylmethyl)phthalazine Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 JOWQCTXBMHNGDA-UHFFFAOYSA-N 0.000 claims 1
- OMLKXRBYJHLIIA-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]thieno[3,2-d]pyrimidine Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC1=NC=NC2=C1SC=C2 OMLKXRBYJHLIIA-UHFFFAOYSA-N 0.000 claims 1
- 229940125377 Selective β-Amyloid-Lowering Agent Drugs 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 235000008001 rakum palm Nutrition 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 description 11
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 9
- 125000004848 alkoxyethyl group Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 7
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 101150021185 FGF gene Proteins 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 241000282412 Homo Species 0.000 description 3
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 101100372761 Mus musculus Flt1 gene Proteins 0.000 description 2
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 201000011066 hemangioma Diseases 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 206010051113 Arterial restenosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 101150009958 FLT4 gene Proteins 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 101150048336 Flt1 gene Proteins 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- 206010025282 Lymphoedema Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 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
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 208000002502 lymphedema Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000004614 tumor growth Effects 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
- 210000002700 urine Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000029663 wound healing Effects 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
- C07D401/14—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
-
- 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
- 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
- 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
-
- 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
- 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
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00402257 | 2000-08-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200300489B true ZA200300489B (en) | 2004-04-19 |
Family
ID=8173808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200300489A ZA200300489B (en) | 2000-08-09 | 2003-01-17 | Indole, azaindole and indazole derivatives having VEGF inhibiting activities. |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20030207878A1 (fr) |
| EP (1) | EP1311500A2 (fr) |
| JP (1) | JP2004505965A (fr) |
| KR (1) | KR20030029812A (fr) |
| CN (1) | CN1245402C (fr) |
| AU (2) | AU7993801A (fr) |
| BR (1) | BR0113078A (fr) |
| CA (1) | CA2416525A1 (fr) |
| IL (1) | IL154034A0 (fr) |
| MX (1) | MXPA03000874A (fr) |
| NO (1) | NO20030628L (fr) |
| NZ (1) | NZ523987A (fr) |
| WO (1) | WO2002012227A2 (fr) |
| ZA (1) | ZA200300489B (fr) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2262935C2 (ru) | 1999-02-10 | 2005-10-27 | Астразенека Аб | Производные хиназолина в качестве ингибиторов ангиогенеза |
| NZ518028A (en) | 1999-11-05 | 2004-03-26 | Astrazeneca Ab | Quinazoline derivatives as VEGF inhibitors |
| JP2003525897A (ja) | 2000-03-06 | 2003-09-02 | アストラゼネカ アクチボラグ | 治 療 |
| IL151626A0 (en) * | 2000-04-07 | 2003-04-10 | Astrazeneca Ab | Quinazoline compounds |
| PT1474420E (pt) | 2002-02-01 | 2012-05-10 | Astrazeneca Ab | Compostos de quinazolina |
| TW200400034A (en) | 2002-05-20 | 2004-01-01 | Bristol Myers Squibb Co | Pyrazolo-pyrimidine aniline compounds useful as kinase inhibitors |
| US6933386B2 (en) * | 2002-07-19 | 2005-08-23 | Bristol Myers Squibb Company | Process for preparing certain pyrrolotriazine compounds |
| TWI329112B (en) * | 2002-07-19 | 2010-08-21 | Bristol Myers Squibb Co | Novel inhibitors of kinases |
| WO2004030635A2 (fr) * | 2002-10-03 | 2004-04-15 | Targegen, Inc. | Agents vasculo-statiques et procedes d'utilisation de ceux-ci |
| PL215161B1 (pl) | 2002-11-04 | 2013-10-31 | Astrazeneca Ab | Pochodne chinazoliny, sposób ich wytwarzania, kompozycje farmaceutyczne je zawierajace oraz ich zastosowanie |
| PT1625121E (pt) | 2002-12-20 | 2010-03-11 | Pfizer Prod Inc | Derivados de piridina para o tratamento de crescimento celular anormal |
| US7109337B2 (en) | 2002-12-20 | 2006-09-19 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| EP1601348A4 (fr) | 2003-02-28 | 2008-12-10 | Oxigene Inc | Compositions et methodes presentant une activite therapeutique amelioree |
| US20040266688A1 (en) * | 2003-05-14 | 2004-12-30 | Nayak Nihar R | Methods for modulating endometrium |
| BRPI0511132A (pt) | 2004-05-14 | 2007-11-27 | Pfizer Prod Inc | derivados de pirimidina e composição farmacêutica compreendendo os mesmos |
| BRPI0510963A (pt) | 2004-05-14 | 2007-11-20 | Pfizer Prod Inc | derivados pirimidina para o tratamento do crescimento anormal de células |
| MXPA06013164A (es) | 2004-05-14 | 2007-02-13 | Pfizer Prod Inc | Derivados de pirimidina para el tratamiento de crecimiento de celulas anormal. |
| CL2007003158A1 (es) * | 2006-11-02 | 2008-05-16 | Astrazeneca Ab | Procedimiento de preparacion de compuestos derivados de quinazolina o sus sales farmaceuticamente aceptables; compuestos intermediarios; procedimiento de preparacion. |
| US20080190689A1 (en) * | 2007-02-12 | 2008-08-14 | Ballard Ebbin C | Inserts for engine exhaust systems |
| CN104945311A (zh) | 2009-01-19 | 2015-09-30 | Abbvie公司 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| AU2010216263A1 (en) | 2009-02-23 | 2011-07-14 | Merck Sharp & Dohme Corp. | Pyrazolo [4,3-c] cinnolin-3-one M1 receptor positive allosteric modulators |
| US8653079B2 (en) | 2011-08-15 | 2014-02-18 | Merck Sharp & Dohme Corp. | Pyrazolo [4,3-C] cinnolin-3-one M1 receptor positive allosteric modulators |
| CA2952857A1 (fr) * | 2014-06-19 | 2015-12-23 | Merial, Inc. | Compositions parasiticides comprenant des derives d'indole, leurs procedes et leurs utilisations |
| WO2021254529A1 (fr) * | 2020-07-14 | 2021-12-23 | 江苏先声药业有限公司 | Composé bicyclique |
| TW202309022A (zh) | 2021-04-13 | 2023-03-01 | 美商努法倫特公司 | 用於治療具egfr突變之癌症之胺基取代雜環 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3987332A (en) * | 1975-10-09 | 1976-10-19 | Varian Associates | Gang tuner for multi-cavity klystron |
| US5480883A (en) * | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5237629A (en) * | 1992-03-19 | 1993-08-17 | The United States Of America As Represented By The United States Department Of Energy | Digitally controlled distributed phase shifter |
| US5440270A (en) * | 1992-07-14 | 1995-08-08 | Linear Technology Corporation | Linear-phase filter having high gain selectivity |
| SE9302453L (sv) * | 1993-07-20 | 1994-10-17 | Telia Ab | Förfarande och anordning för synkronisering i digitalt transmissionssystem av typen OFDM |
| TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| US5639757A (en) * | 1995-05-23 | 1997-06-17 | Pfizer Inc. | 4-aminopyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors |
| US6395733B1 (en) * | 1995-06-07 | 2002-05-28 | Pfizer Inc | Heterocyclic ring-fused pyrimidine derivatives |
| GB9604361D0 (en) * | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| JP3727406B2 (ja) * | 1996-03-07 | 2005-12-14 | 株式会社日立国際電気 | 関数変換演算器 |
| HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| ATE300521T1 (de) * | 1996-09-25 | 2005-08-15 | Astrazeneca Ab | Chinolin-derivate die den effekt von wachstumsfaktoren wie vegf vezögern |
| CO4950519A1 (es) * | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| US6162804A (en) * | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| UA72881C2 (uk) * | 1997-11-11 | 2005-05-16 | Пфайзер Продактс Інк. | Похідні тієнопіридину, фармацевтична композиція з використанням таких сполук (варіанти), проміжна сполука |
| JPH11259454A (ja) * | 1998-03-09 | 1999-09-24 | Sharp Corp | フーリエ変換装置 |
| AU5620299A (en) * | 1998-08-11 | 2000-03-06 | Novartis Ag | Isoquinoline derivatives with angiogenesis inhibiting activity |
| US20030162795A1 (en) * | 1998-10-22 | 2003-08-28 | Pfizer Inc. | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
| KR200212866Y1 (ko) * | 1998-12-26 | 2001-02-15 | 서평원 | 선왜곡 방식 전력증폭기용 능동 왜곡신호 발생회로 |
| RU2331640C2 (ru) * | 1999-05-21 | 2008-08-20 | Бристол-Маерс Сквибб Ко. | Пирролтриазиновые ингибиторы киназ |
| US6982265B1 (en) * | 1999-05-21 | 2006-01-03 | Bristol Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
| DOP2000000070A (es) * | 1999-09-28 | 2002-02-28 | Bayer Healthcare Llc | Piridinas y piridacinas sustituidas con actividad de inhibición de angiogénesis |
| TR200402656T4 (tr) * | 2000-06-06 | 2004-11-22 | Pfizer Products Inc. | Antikanser ajanları olarak faydalı tiyofen türevleri |
-
2001
- 2001-08-08 NZ NZ523987A patent/NZ523987A/en unknown
- 2001-08-08 IL IL15403401A patent/IL154034A0/xx unknown
- 2001-08-08 WO PCT/GB2001/003561 patent/WO2002012227A2/fr active IP Right Grant
- 2001-08-08 KR KR10-2003-7001852A patent/KR20030029812A/ko not_active Application Discontinuation
- 2001-08-08 BR BR0113078-1A patent/BR0113078A/pt not_active IP Right Cessation
- 2001-08-08 CA CA002416525A patent/CA2416525A1/fr not_active Abandoned
- 2001-08-08 AU AU7993801A patent/AU7993801A/xx active Pending
- 2001-08-08 AU AU2001279938A patent/AU2001279938B2/en not_active Ceased
- 2001-08-08 JP JP2002518202A patent/JP2004505965A/ja active Pending
- 2001-08-08 EP EP01958210A patent/EP1311500A2/fr not_active Withdrawn
- 2001-08-08 MX MXPA03000874A patent/MXPA03000874A/es not_active Application Discontinuation
- 2001-08-08 US US10/343,236 patent/US20030207878A1/en not_active Abandoned
- 2001-08-08 CN CNB018166962A patent/CN1245402C/zh not_active Expired - Fee Related
-
2003
- 2003-01-17 ZA ZA200300489A patent/ZA200300489B/en unknown
- 2003-02-07 NO NO20030628A patent/NO20030628L/no not_active Application Discontinuation
-
2006
- 2006-02-16 US US11/355,006 patent/US20060148819A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1311500A2 (fr) | 2003-05-21 |
| NO20030628L (no) | 2003-04-08 |
| US20060148819A1 (en) | 2006-07-06 |
| NO20030628D0 (no) | 2003-02-07 |
| MXPA03000874A (es) | 2003-06-06 |
| NZ523987A (en) | 2004-10-29 |
| BR0113078A (pt) | 2003-07-01 |
| AU2001279938B2 (en) | 2007-01-25 |
| JP2004505965A (ja) | 2004-02-26 |
| US20030207878A1 (en) | 2003-11-06 |
| CN1468230A (zh) | 2004-01-14 |
| CA2416525A1 (fr) | 2002-02-14 |
| AU7993801A (en) | 2002-02-18 |
| WO2002012227A3 (fr) | 2002-08-01 |
| CN1245402C (zh) | 2006-03-15 |
| IL154034A0 (en) | 2003-07-31 |
| WO2002012227A2 (fr) | 2002-02-14 |
| KR20030029812A (ko) | 2003-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200300489B (en) | Indole, azaindole and indazole derivatives having VEGF inhibiting activities. | |
| ZA200106340B (en) | Quinazoline derivatives as angiogenesis inhibitors. | |
| ZA200405908B (en) | Quinazoline compounds | |
| AU2015360360B2 (en) | Substituted 2-anilinopyrimidine derivatives as EGFR modulators | |
| ZA200601025B (en) | Quinazoline derivatives as angiogenesis inhibitors | |
| EP1178965B1 (fr) | Derives de la quinoleine utilises comme inhibiteurs des enzymes mek | |
| ES2622138T3 (es) | Nuevos derivados de pirimidina condensados para la inhibición de la actividad tirosina quinasa | |
| NO324471B1 (no) | Kinazolinforbindelser samt anvendelse og fremgangsmate for fremstilling derav og farmasoytisk sammensetning | |
| US20100029673A1 (en) | Therapeutic agents comprising an anti-angiogenic agent in combination with an src-inhibitor and their therapeutic use | |
| EP1178966B1 (fr) | Derives de quinoline inhibiteurs des enzymes mek | |
| NZ523358A (en) | Quinoline derivatives having VEGF inhibiting activity | |
| RU2001124816A (ru) | Производные хиназолина в качестве ингибиторов ангиогенеза | |
| WO2002016348A1 (fr) | Derives bicycliques antiangiogeniques | |
| NZ523388A (en) | Cinnoline compounds | |
| JP2007510667A (ja) | 癌の治療法 | |
| ZA200601030B (en) | Quinazoline derivatives as inhibitors of VEGF receptor tyrosine kinases | |
| CN106916112B (zh) | 嘧啶衍生物及其制备方法和在医药上的应用 | |
| CA3147649A1 (fr) | Derive de pyrazole et son utilisation | |
| US20240024324A1 (en) | Kinase inhibitor combinations for cancer treatment | |
| US20080177068A1 (en) | Quinazole derivatives | |
| ZA200207382B (en) | Quinazoline compounds. | |
| MXPA01011361A (en) | Quinoline derivatives as inhibitors of mek enzymes | |
| DE112005003498T5 (de) | Herstellungsverfahren für Chinazolinderivate und Anwendung zur Herstellung zur Behandlung von Tumorerkrankungen |