ZA200405025B - 3-Cyanoquinolines as inhibitors of EGF-R and Her2 kinases - Google Patents
3-Cyanoquinolines as inhibitors of EGF-R and Her2 kinases Download PDFInfo
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- ZA200405025B ZA200405025B ZA200405025A ZA200405025A ZA200405025B ZA 200405025 B ZA200405025 B ZA 200405025B ZA 200405025 A ZA200405025 A ZA 200405025A ZA 200405025 A ZA200405025 A ZA 200405025A ZA 200405025 B ZA200405025 B ZA 200405025B
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- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 title description 9
- 239000003112 inhibitor Substances 0.000 title description 8
- 108091000080 Phosphotransferase Proteins 0.000 title description 7
- 102000020233 phosphotransferase Human genes 0.000 title description 7
- 101150029707 ERBB2 gene Proteins 0.000 title description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 329
- 150000001875 compounds Chemical class 0.000 claims description 109
- -1 nitro, carboxy Chemical group 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
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- 239000000203 mixture Substances 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 13
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 13
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- 239000000126 substance Substances 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 125000004970 halomethyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 150000001721 carbon Chemical class 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 230000012010 growth Effects 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 229930192474 thiophene Natural products 0.000 claims description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 5
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 5
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- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000035984 Colonic Polyps Diseases 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
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- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 210000003238 esophagus Anatomy 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 210000000867 larynx Anatomy 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
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- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 2
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 2
- ICMFXKPVTNHUTG-UHFFFAOYSA-N 2,2-bis(dimethylamino)butanamide Chemical compound CCC(N(C)C)(N(C)C)C(N)=O ICMFXKPVTNHUTG-UHFFFAOYSA-N 0.000 claims description 2
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
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- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 claims description 2
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- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 2
- KHPIRECQOJCDSH-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-3-(dimethylamino)butanamide Chemical compound C=12C=C(NC(=O)CC(C)N(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 KHPIRECQOJCDSH-UHFFFAOYSA-N 0.000 claims description 2
- ZOQGOOXQXUTMMX-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-methoxyquinolin-6-yl]-3,4-bis(3-hydroxypyrrolidin-1-yl)butanamide Chemical compound C=12C=C(NC(=O)CC(CN3CC(O)CC3)N3CC(O)CC3)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 ZOQGOOXQXUTMMX-UHFFFAOYSA-N 0.000 claims description 2
- RPXQGRBJRFCZNX-UHFFFAOYSA-N n-[4-(3-chloro-4-phenylmethoxyanilino)-3-cyano-7-ethoxyquinolin-6-yl]-3,6-bis(dimethylamino)hexanamide Chemical compound C=12C=C(NC(=O)CC(CCCN(C)C)N(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 RPXQGRBJRFCZNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- HBHMXHFTLOCNKM-UHFFFAOYSA-N n-[4-(3-chloro-4-phenylmethoxyanilino)-3-cyano-7-ethoxyquinolin-6-yl]-3,4-dipyrrolidin-1-ylbutanamide Chemical compound C=12C=C(NC(=O)CC(CN3CCCC3)N3CCCC3)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 HBHMXHFTLOCNKM-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 208000014081 polyp of colon Diseases 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 230000011664 signaling Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 208000005057 thyrotoxicosis Diseases 0.000 description 1
- 238000001685 time-resolved fluorescence spectroscopy Methods 0.000 description 1
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- 238000000844 transformation Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- 238000001262 western blot Methods 0.000 description 1
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- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US33356801P | 2001-11-27 | 2001-11-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200405025B true ZA200405025B (en) | 2006-12-27 |
Family
ID=23303345
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200405025A ZA200405025B (en) | 2001-11-27 | 2004-06-24 | 3-Cyanoquinolines as inhibitors of EGF-R and Her2 kinases |
Country Status (24)
Country | Link |
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US (1) | US6821988B2 (uk) |
EP (1) | EP1448531B1 (uk) |
JP (1) | JP2005514384A (uk) |
KR (1) | KR20050044599A (uk) |
CN (1) | CN1659145A (uk) |
AR (1) | AR037438A1 (uk) |
AT (1) | ATE370123T1 (uk) |
AU (1) | AU2002359489B2 (uk) |
BR (1) | BR0214485A (uk) |
CA (1) | CA2467573A1 (uk) |
CO (1) | CO5580828A2 (uk) |
DE (1) | DE60221886D1 (uk) |
EC (1) | ECSP045122A (uk) |
HU (1) | HUP0402228A2 (uk) |
IL (1) | IL161921A0 (uk) |
MX (1) | MXPA04004969A (uk) |
NO (1) | NO20042634L (uk) |
NZ (1) | NZ533118A (uk) |
PL (1) | PL370137A1 (uk) |
RU (1) | RU2309150C2 (uk) |
TW (1) | TW200300348A (uk) |
UA (1) | UA77469C2 (uk) |
WO (1) | WO2003050090A1 (uk) |
ZA (1) | ZA200405025B (uk) |
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EP1670473A1 (en) * | 2003-09-15 | 2006-06-21 | Wyeth a Corporation of the State of Delaware | Substituted quinolines as protein tyrosine kinase enzyme inhibitors |
US7399865B2 (en) * | 2003-09-15 | 2008-07-15 | Wyeth | Protein tyrosine kinase enzyme inhibitors |
US7365203B2 (en) * | 2003-09-15 | 2008-04-29 | Wyeth | Process for the synthesis of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-ethoxy-quinoline-3-carbonitrile |
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US7781591B2 (en) | 2006-06-13 | 2010-08-24 | Wyeth Llc | Substituted 3-cyanopyridines as protein kinase inhibitors |
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TW200616612A (en) * | 2004-10-08 | 2006-06-01 | Wyeth Corp | Method for the teatment of polycystic kidney disease field of invention |
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JP4989476B2 (ja) | 2005-08-02 | 2012-08-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質の効果を検定する方法 |
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KR101513326B1 (ko) | 2007-11-09 | 2015-04-17 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 혈관 신생 저해 물질과 항종양성 백금 착물의 병용 |
WO2009151910A2 (en) * | 2008-05-25 | 2009-12-17 | Wyeth | Combination product of receptor tyrosine kinase inhibitor and fatty acid synthase inhibitor for treating cancer |
KR20130088908A (ko) | 2008-06-17 | 2013-08-08 | 와이어쓰 엘엘씨 | Hki-272 및 비노렐빈을 함유하는 항신생물성 조합물 |
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WO2017117474A1 (en) * | 2015-12-30 | 2017-07-06 | Dana-Farber Cancer Institute, Inc. | Bifunctional compounds for her3 degradation and methods of use |
CN115057861A (zh) * | 2016-03-01 | 2022-09-16 | 上海医药集团股份有限公司 | 一种含氮杂环化合物、制备方法、中间体、组合物和应用 |
MD3658552T2 (ro) | 2017-07-28 | 2024-02-29 | Yuhan Corp | Procedeu de obținere a N-(5-((4-(4-((dimetilamino)metil)-3-fenil-1H-pirazol-1-il)pirimidin-2-il)amino)-4-metoxi-2-morfolinofenil)acrilamidei prin prin reacţia aminei corespunzătoare cu clorură de 3-halo-propionil |
CN110452232A (zh) * | 2019-09-17 | 2019-11-15 | 北京振东光明药物研究院有限公司 | 阿法替尼杂质化合物及其制备方法与应用 |
CN111995618B (zh) * | 2020-09-02 | 2021-06-11 | 重庆医科大学 | 一种来那替尼杂质g的制备方法 |
CN111943933B (zh) * | 2020-09-02 | 2021-05-28 | 重庆医科大学 | 一种来那替尼杂质d的制备方法 |
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SK285141B6 (sk) * | 1996-02-13 | 2006-07-07 | Astrazeneca Uk Limited | Použitie chinazolínového derivátu, chinazolínový derivát, spôsob jeho prípravy a farmaceutická kompozícia, ktorá ho obsahuje |
UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
US6235740B1 (en) * | 1997-08-25 | 2001-05-22 | Bristol-Myers Squibb Co. | Imidazoquinoxaline protein tyrosine kinase inhibitors |
ES2457396T3 (es) * | 1998-09-29 | 2014-04-25 | Wyeth Holdings Llc | 3-Cianoquinolinas sustituidas como inhibidores de las proteínas tirosina quinasas |
JP4548642B2 (ja) * | 1998-09-29 | 2010-09-22 | アメリカン・サイアナミド・カンパニー | プロテインチロシンキナーゼインヒビターとしての置換3−シアノキノリン |
GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
DK1242382T3 (da) * | 1999-12-29 | 2007-05-07 | Wyeth Corp | Tricycliske proteinkinaseinhibitorer |
AU2002210714A1 (en) | 2000-11-02 | 2002-06-11 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
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- 2002-11-26 KR KR1020047007951A patent/KR20050044599A/ko not_active Application Discontinuation
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PL370137A1 (en) | 2005-05-16 |
DE60221886D1 (de) | 2007-09-27 |
UA77469C2 (en) | 2006-12-15 |
NO20042634L (no) | 2004-06-23 |
CA2467573A1 (en) | 2003-06-19 |
MXPA04004969A (es) | 2004-08-11 |
EP1448531B1 (en) | 2007-08-15 |
ECSP045122A (es) | 2004-07-23 |
US20030149056A1 (en) | 2003-08-07 |
RU2004119414A (ru) | 2006-02-27 |
CO5580828A2 (es) | 2005-11-30 |
BR0214485A (pt) | 2004-09-14 |
EP1448531A1 (en) | 2004-08-25 |
JP2005514384A (ja) | 2005-05-19 |
ATE370123T1 (de) | 2007-09-15 |
KR20050044599A (ko) | 2005-05-12 |
AR037438A1 (es) | 2004-11-10 |
AU2002359489A1 (en) | 2003-06-23 |
HUP0402228A2 (hu) | 2005-02-28 |
CN1659145A (zh) | 2005-08-24 |
IL161921A0 (en) | 2005-11-20 |
AU2002359489B2 (en) | 2008-10-30 |
WO2003050090A1 (en) | 2003-06-19 |
RU2309150C2 (ru) | 2007-10-27 |
US6821988B2 (en) | 2004-11-23 |
NZ533118A (en) | 2006-07-28 |
TW200300348A (en) | 2003-06-01 |
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