ES2206729T3 - Compuestos heteroaromaticos biciclicos como inhibidores de la proteina tirosina quinasa. - Google Patents
Compuestos heteroaromaticos biciclicos como inhibidores de la proteina tirosina quinasa.Info
- Publication number
- ES2206729T3 ES2206729T3 ES97930518T ES97930518T ES2206729T3 ES 2206729 T3 ES2206729 T3 ES 2206729T3 ES 97930518 T ES97930518 T ES 97930518T ES 97930518 T ES97930518 T ES 97930518T ES 2206729 T3 ES2206729 T3 ES 2206729T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- group
- pyrimidin
- benzyl
- indazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 title claims abstract description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 239000003112 inhibitor Substances 0.000 title abstract description 9
- 102000004169 proteins and genes Human genes 0.000 title abstract description 5
- 108090000623 proteins and genes Proteins 0.000 title abstract description 5
- 150000002390 heteroarenes Chemical class 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 238000000034 method Methods 0.000 claims abstract description 79
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 238000002360 preparation method Methods 0.000 claims abstract description 24
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 8
- 201000011510 cancer Diseases 0.000 claims abstract description 8
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 207
- 125000000217 alkyl group Chemical group 0.000 claims description 100
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 55
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 239000000376 reactant Substances 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 239000012453 solvate Substances 0.000 claims description 31
- 125000003282 alkyl amino group Chemical group 0.000 claims description 28
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 28
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 25
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 21
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 20
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- QNDFCSITSCMNGP-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QNDFCSITSCMNGP-UHFFFAOYSA-N 0.000 claims description 18
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000004175 fluorobenzyl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
- 125000001589 carboacyl group Chemical group 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 150000003852 triazoles Chemical class 0.000 claims description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- YUSMWODGNWPEBC-UHFFFAOYSA-N n-morpholin-4-ylacetamide Chemical compound CC(=O)NN1CCOCC1 YUSMWODGNWPEBC-UHFFFAOYSA-N 0.000 claims description 8
- PDUSWJORWQPNRP-UHFFFAOYSA-N n-propan-2-ylacetamide Chemical compound CC(C)NC(C)=O PDUSWJORWQPNRP-UHFFFAOYSA-N 0.000 claims description 8
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 8
- DYYZXRCFCVDSKD-UHFFFAOYSA-N N6,N6-dimethyl-N4-[1-(phenylmethyl)-5-indazolyl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 DYYZXRCFCVDSKD-UHFFFAOYSA-N 0.000 claims description 7
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical compound NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-UHFFFAOYSA-N 0.000 claims description 7
- JCMRKIPIHJRILY-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 JCMRKIPIHJRILY-UHFFFAOYSA-N 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 6
- 150000003536 tetrazoles Chemical class 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- JFXFEXXASOCJBR-UHFFFAOYSA-N 4-n-(1-benzylindazol-5-yl)-6-n-ethyl-6-n-methylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)CC)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 JFXFEXXASOCJBR-UHFFFAOYSA-N 0.000 claims description 5
- BMIOWXJYLRLVHA-UHFFFAOYSA-N 4-n-(1-benzylindazol-5-yl)-6-n-methylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(NC)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 BMIOWXJYLRLVHA-UHFFFAOYSA-N 0.000 claims description 5
- RLCKHNKPUUYNQD-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 RLCKHNKPUUYNQD-UHFFFAOYSA-N 0.000 claims description 5
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 5
- 150000004702 methyl esters Chemical class 0.000 claims description 5
- HKNPEKHQRROZPD-UHFFFAOYSA-N 4-n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC(F)=C1 HKNPEKHQRROZPD-UHFFFAOYSA-N 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- MLLMAIJXIZOSFS-UHFFFAOYSA-N n,n-dimethylpyrrolidine-2-carboxamide Chemical compound CN(C)C(=O)C1CCCN1 MLLMAIJXIZOSFS-UHFFFAOYSA-N 0.000 claims description 4
- GIZAHSJRRRUFEE-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(1,3-dioxolan-2-yl)furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)C=3OC(=CC=3)C3OCCO3)=CC=C2N1CC1=CC=CC=C1 GIZAHSJRRRUFEE-UHFFFAOYSA-N 0.000 claims description 4
- YCPVGYFQXXTANI-UHFFFAOYSA-N n-(2-benzyl-3h-benzimidazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1N=2)=CC=C1NC=2CC1=CC=CC=C1 YCPVGYFQXXTANI-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 229910052721 tungsten Inorganic materials 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- XJKWUSYIOHJDIM-UHFFFAOYSA-N 2-[[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]-methylamino]ethanol Chemical compound N1=CN=C2C=NC(N(CCO)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 XJKWUSYIOHJDIM-UHFFFAOYSA-N 0.000 claims description 3
- XKGUJMPYDBMSDA-UHFFFAOYSA-N 4-n-(1-benzyl-3-methylindazol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C(C)=N2)=CC=C1N2CC1=CC=CC=C1 XKGUJMPYDBMSDA-UHFFFAOYSA-N 0.000 claims description 3
- YZZIGXZRNAEFCP-UHFFFAOYSA-N 4-n-(1-benzylindol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2CC1=CC=CC=C1 YZZIGXZRNAEFCP-UHFFFAOYSA-N 0.000 claims description 3
- BIQOFKWYWPJGNB-UHFFFAOYSA-N 4-n-[1-(benzenesulfonyl)indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 BIQOFKWYWPJGNB-UHFFFAOYSA-N 0.000 claims description 3
- HBOLGDVBJIQIQE-UHFFFAOYSA-N 4-n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1F HBOLGDVBJIQIQE-UHFFFAOYSA-N 0.000 claims description 3
- MQNRGKYCHYKEMO-UHFFFAOYSA-N 4-n-[1-[(4-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=C(F)C=C1 MQNRGKYCHYKEMO-UHFFFAOYSA-N 0.000 claims description 3
- OCCGRAZNBVMQAO-UHFFFAOYSA-N 4-n-[3-(benzenesulfonyl)-1h-indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C12)=CC=C1NC=C2S(=O)(=O)C1=CC=CC=C1 OCCGRAZNBVMQAO-UHFFFAOYSA-N 0.000 claims description 3
- VKPHMHJHCQWKKV-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-2-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=N1 VKPHMHJHCQWKKV-UHFFFAOYSA-N 0.000 claims description 3
- USTNKMJFNDVPLS-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-3-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CN=C1 USTNKMJFNDVPLS-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- UZXVIZOKQMXWKF-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(3-methylimidazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CN1C=NC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 UZXVIZOKQMXWKF-UHFFFAOYSA-N 0.000 claims description 3
- NEHINJYPPQYUQH-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-imidazol-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3C=NC=C3)=CC=C2N1CC1=CC=CC=C1 NEHINJYPPQYUQH-UHFFFAOYSA-N 0.000 claims description 3
- OEYOUMHPXUXUIQ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-piperidin-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3CCCCC3)=CC=C2N1CC1=CC=CC=C1 OEYOUMHPXUXUIQ-UHFFFAOYSA-N 0.000 claims description 3
- WVIYDZAMWSNDDO-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-pyrrolidin-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3CCCC3)=CC=C2N1CC1=CC=CC=C1 WVIYDZAMWSNDDO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- SDNXQWUJWNTDCC-UHFFFAOYSA-N 2-methylsulfonylethanamine Chemical compound CS(=O)(=O)CCN SDNXQWUJWNTDCC-UHFFFAOYSA-N 0.000 claims description 2
- UUVCADJIKORGBL-UHFFFAOYSA-N CS(CCCNC(NCCCS(C)(=O)=O)N(CC(N)=O)NCCNS(C)(=O)=O)=O Chemical compound CS(CCCNC(NCCCS(C)(=O)=O)N(CC(N)=O)NCCNS(C)(=O)=O)=O UUVCADJIKORGBL-UHFFFAOYSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052770 Uranium Inorganic materials 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 2
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 2
- OXLINNZBULSARQ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(1,2,4-triazol-1-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3N=CN=C3)=CC=C2N1CC1=CC=CC=C1 OXLINNZBULSARQ-UHFFFAOYSA-N 0.000 claims description 2
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- 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 1
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- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
- OGYWKJKAIAEDQX-UHFFFAOYSA-N tributyl-(3-methylimidazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=CN1C OGYWKJKAIAEDQX-UHFFFAOYSA-N 0.000 description 1
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- JUDXOKKZTISQDJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 JUDXOKKZTISQDJ-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
-
- 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
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9614763.2A GB9614763D0 (en) | 1996-07-13 | 1996-07-13 | Heterocyclic compounds |
| GB9614763 | 1996-07-13 | ||
| GB9625492 | 1996-12-07 | ||
| GBGB9625492.5A GB9625492D0 (en) | 1996-12-07 | 1996-12-07 | Heterocyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2206729T3 true ES2206729T3 (es) | 2004-05-16 |
Family
ID=26309694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97930518T Expired - Lifetime ES2206729T3 (es) | 1996-07-13 | 1997-07-11 | Compuestos heteroaromaticos biciclicos como inhibidores de la proteina tirosina quinasa. |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US6174889B1 (Direct) |
| EP (2) | EP1304110A3 (Direct) |
| JP (1) | JP2000514445A (Direct) |
| KR (1) | KR20000023812A (Direct) |
| CN (1) | CN1230187A (Direct) |
| AP (1) | AP9901434A0 (Direct) |
| AR (1) | AR007856A1 (Direct) |
| AT (1) | ATE249458T1 (Direct) |
| AU (1) | AU3443997A (Direct) |
| BR (1) | BR9710359A (Direct) |
| CA (1) | CA2260061A1 (Direct) |
| CZ (1) | CZ8999A3 (Direct) |
| DE (1) | DE69724789T2 (Direct) |
| EA (1) | EA199900022A1 (Direct) |
| ES (1) | ES2206729T3 (Direct) |
| HR (1) | HRP970371A2 (Direct) |
| ID (1) | ID19403A (Direct) |
| IL (1) | IL127796A0 (Direct) |
| IS (1) | IS4939A (Direct) |
| NO (1) | NO990124L (Direct) |
| PE (1) | PE91198A1 (Direct) |
| PL (1) | PL331221A1 (Direct) |
| TR (1) | TR199900049T2 (Direct) |
| WO (1) | WO1998002438A1 (Direct) |
| YU (1) | YU1099A (Direct) |
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| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (Direct) | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| SK281724B6 (sk) | 1994-11-14 | 2001-07-10 | Warner-Lambert Company | 6-arylpyrido[2,3-d]pyrimidíny, ich použitie a farmaceutické prostriedky na ich báze |
| GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| AR004010A1 (es) * | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
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| EP0912559B1 (en) | 1996-07-13 | 2002-11-06 | Glaxo Group Limited | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
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1997
- 1997-07-08 HR HR9625492.5A patent/HRP970371A2/hr not_active Application Discontinuation
- 1997-07-11 ES ES97930518T patent/ES2206729T3/es not_active Expired - Lifetime
- 1997-07-11 ID IDP972412A patent/ID19403A/id unknown
- 1997-07-11 US US09/214,270 patent/US6174889B1/en not_active Expired - Fee Related
- 1997-07-11 CA CA002260061A patent/CA2260061A1/en not_active Abandoned
- 1997-07-11 WO PCT/EP1997/003674 patent/WO1998002438A1/en not_active Ceased
- 1997-07-11 EA EA199900022A patent/EA199900022A1/ru unknown
- 1997-07-11 YU YU1099A patent/YU1099A/sr unknown
- 1997-07-11 EP EP02080417A patent/EP1304110A3/en not_active Withdrawn
- 1997-07-11 BR BR9710359A patent/BR9710359A/pt not_active Application Discontinuation
- 1997-07-11 EP EP97930518A patent/EP0912570B1/en not_active Expired - Lifetime
- 1997-07-11 PL PL97331221A patent/PL331221A1/xx unknown
- 1997-07-11 AT AT97930518T patent/ATE249458T1/de not_active IP Right Cessation
- 1997-07-11 PE PE1997000611A patent/PE91198A1/es not_active Application Discontinuation
- 1997-07-11 AR ARP970103102A patent/AR007856A1/es unknown
- 1997-07-11 CN CN97197876A patent/CN1230187A/zh active Pending
- 1997-07-11 CZ CZ9989A patent/CZ8999A3/cs unknown
- 1997-07-11 AP APAP/P/1999/001434A patent/AP9901434A0/en unknown
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- 1997-07-11 IL IL12779697A patent/IL127796A0/xx unknown
- 1997-07-11 AU AU34439/97A patent/AU3443997A/en not_active Abandoned
- 1997-07-11 JP JP10505598A patent/JP2000514445A/ja not_active Ceased
- 1997-07-11 TR TR1999/00049T patent/TR199900049T2/xx unknown
-
1998
- 1998-12-31 IS IS4939A patent/IS4939A/is unknown
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1999
- 1999-01-12 NO NO990124A patent/NO990124L/no not_active Application Discontinuation
- 1999-01-13 KR KR1019997000298A patent/KR20000023812A/ko not_active Withdrawn
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2000
- 2000-06-30 US US09/608,971 patent/US6723726B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| BR9710359A (pt) | 1999-08-17 |
| KR20000023812A (ko) | 2000-04-25 |
| US6174889B1 (en) | 2001-01-16 |
| CN1230187A (zh) | 1999-09-29 |
| EA199900022A1 (ru) | 1999-08-26 |
| DE69724789D1 (de) | 2003-10-16 |
| IS4939A (is) | 1998-12-31 |
| EP0912570A1 (en) | 1999-05-06 |
| PL331221A1 (en) | 1999-07-05 |
| DE69724789T2 (de) | 2004-07-01 |
| AP9901434A0 (en) | 1999-03-31 |
| EP1304110A2 (en) | 2003-04-23 |
| TR199900049T2 (xx) | 1999-04-21 |
| EP0912570B1 (en) | 2003-09-10 |
| ID19403A (id) | 1998-07-09 |
| HRP970371A2 (en) | 1998-08-31 |
| IL127796A0 (en) | 1999-10-28 |
| WO1998002438A1 (en) | 1998-01-22 |
| CZ8999A3 (cs) | 1999-06-16 |
| PE91198A1 (es) | 1999-01-15 |
| AU3443997A (en) | 1998-02-09 |
| CA2260061A1 (en) | 1998-01-22 |
| YU1099A (en) | 1999-11-22 |
| ATE249458T1 (de) | 2003-09-15 |
| NO990124D0 (no) | 1999-01-12 |
| NO990124L (no) | 1999-03-11 |
| EP1304110A3 (en) | 2003-12-17 |
| AR007856A1 (es) | 1999-11-24 |
| US6723726B1 (en) | 2004-04-20 |
| JP2000514445A (ja) | 2000-10-31 |
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