UA77469C2 - 3-cyanoquinolines as egf-r and her2 kinase inhibitors - Google Patents
3-cyanoquinolines as egf-r and her2 kinase inhibitors Download PDFInfo
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- UA77469C2 UA77469C2 UA20040605019A UA20040605019A UA77469C2 UA 77469 C2 UA77469 C2 UA 77469C2 UA 20040605019 A UA20040605019 A UA 20040605019A UA 20040605019 A UA20040605019 A UA 20040605019A UA 77469 C2 UA77469 C2 UA 77469C2
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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 7
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 title 1
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 157
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 208000030761 polycystic kidney disease Diseases 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 390
- -1 nitro, carboxy Chemical group 0.000 claims description 80
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
- 206010028980 Neoplasm Diseases 0.000 claims description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
- 125000000304 alkynyl group Chemical group 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical group 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 150000001721 carbon Chemical group 0.000 claims description 19
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 19
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 150000003254 radicals Chemical class 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 125000004970 halomethyl group Chemical group 0.000 claims description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 15
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 14
- 125000004429 atom Chemical group 0.000 claims description 13
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 13
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 13
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 10
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 10
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 10
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 9
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 230000003993 interaction Effects 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 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
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-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
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- QNXSIUBBGPHDDE-UHFFFAOYSA-N alpha-indanone Natural products C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
- 229930192474 thiophene Natural products 0.000 claims description 6
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 5
- 235000018417 cysteine Nutrition 0.000 claims description 5
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 5
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 4
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 4
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 4
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000003302 alkenyloxy group Chemical group 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
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 4
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 4
- 239000012964 benzotriazole Substances 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 210000002429 large intestine Anatomy 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 4
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 claims description 4
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 3
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 3
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- KGLPWQKSKUVKMJ-UHFFFAOYSA-N 2,3-dihydrophthalazine-1,4-dione Chemical compound C1=CC=C2C(=O)NNC(=O)C2=C1 KGLPWQKSKUVKMJ-UHFFFAOYSA-N 0.000 claims description 3
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 3
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 210000003238 esophagus Anatomy 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 3
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 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
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
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- 210000001672 ovary Anatomy 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
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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
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- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 claims description 2
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- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33356801P | 2001-11-27 | 2001-11-27 | |
| PCT/US2002/037918 WO2003050090A1 (en) | 2001-11-27 | 2002-11-26 | 3-cyanoquinolines as inhibitors of egf-r and her2 kinases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA77469C2 true UA77469C2 (en) | 2006-12-15 |
Family
ID=23303345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20040605019A UA77469C2 (en) | 2001-11-27 | 2002-11-26 | 3-cyanoquinolines as egf-r and her2 kinase inhibitors |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6821988B2 (zh) |
| EP (1) | EP1448531B1 (zh) |
| JP (1) | JP2005514384A (zh) |
| KR (1) | KR20050044599A (zh) |
| CN (1) | CN1659145A (zh) |
| AR (1) | AR037438A1 (zh) |
| AT (1) | ATE370123T1 (zh) |
| AU (1) | AU2002359489B2 (zh) |
| BR (1) | BR0214485A (zh) |
| CA (1) | CA2467573A1 (zh) |
| CO (1) | CO5580828A2 (zh) |
| DE (1) | DE60221886D1 (zh) |
| EC (1) | ECSP045122A (zh) |
| HU (1) | HUP0402228A2 (zh) |
| IL (1) | IL161921A0 (zh) |
| MX (1) | MXPA04004969A (zh) |
| NO (1) | NO20042634L (zh) |
| NZ (1) | NZ533118A (zh) |
| PL (1) | PL370137A1 (zh) |
| RU (1) | RU2309150C2 (zh) |
| TW (1) | TW200300348A (zh) |
| UA (1) | UA77469C2 (zh) |
| WO (1) | WO2003050090A1 (zh) |
| ZA (1) | ZA200405025B (zh) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1415987B1 (en) | 2000-10-20 | 2007-02-28 | Eisai R&D Management Co., Ltd. | Nitrogenous aromatic ring compounds as anti cancer agents |
| EP2277867B1 (en) | 2002-07-15 | 2012-12-05 | Symphony Evolution, Inc. | Compounds, pharmaceutical compositions thereof and their use in treating cancer |
| CN1832757A (zh) * | 2003-08-01 | 2006-09-13 | 惠氏控股公司 | 表皮生长因子受体激酶抑制剂与细胞毒性剂组合在治疗和抑制癌症中的用途 |
| US7399865B2 (en) * | 2003-09-15 | 2008-07-15 | Wyeth | Protein tyrosine kinase enzyme inhibitors |
| MXPA06002846A (es) * | 2003-09-15 | 2006-06-14 | Wyeth Corp | Quinolinas sustituidas como inhibidores de la enzima de la proteina tirosina cinasa. |
| 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 |
| DK2392564T3 (da) * | 2003-09-26 | 2014-01-13 | Exelixis Inc | c-Met-modulatorer og anvendelsesfremgangsmåder |
| US7781591B2 (en) | 2006-06-13 | 2010-08-24 | Wyeth Llc | Substituted 3-cyanopyridines as protein kinase inhibitors |
| CN101337930B (zh) | 2003-11-11 | 2010-09-08 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
| AU2005272815A1 (en) | 2004-08-13 | 2006-02-23 | Genentech, Inc. | Thiazole based inhibitors of ATP-utilizing enzymes |
| EP1797881B1 (en) | 2004-09-17 | 2009-04-15 | Eisai R&D Management Co., Ltd. | Medicinal composition with improved stability and reduced gelation properties |
| TW200616612A (en) * | 2004-10-08 | 2006-06-01 | Wyeth Corp | Method for the teatment of polycystic kidney disease field of invention |
| CN102886045A (zh) | 2005-02-03 | 2013-01-23 | 综合医院公司 | 治疗吉非替尼耐药性癌症的方法 |
| GB0509227D0 (en) * | 2005-05-05 | 2005-06-15 | Chroma Therapeutics Ltd | Intracellular enzyme inhibitors |
| US7624279B2 (en) * | 2005-06-29 | 2009-11-24 | Lenovo Singapore Pte. Ltd. | System and method for secure O.S. boot from password-protected HDD |
| EP2281901B1 (en) | 2005-08-02 | 2013-11-27 | Eisai R&D Management Co., Ltd. | Anti-tumour pharmaceutical composition with angiogenesis inhibitors |
| KR101354828B1 (ko) | 2005-11-04 | 2014-02-18 | 와이어쓰 엘엘씨 | ｍＴＯＲ 저해자, 헤르셉틴, 및/또는 ＨＫＩ-272의항신생물성 조합 |
| EP2036557B1 (en) | 2006-05-18 | 2015-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| BRPI0712737A2 (pt) * | 2006-06-13 | 2012-05-08 | Wyeth Corp | composto; composição farmacêutica; método e tratamento ou inibição de uma condição ou transtorno patológico mediado por uma proteìna quinase em um mamìfero; e uso do composto |
| KR101472600B1 (ko) | 2006-08-28 | 2014-12-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암에 대한 항종양제 |
| JP5319306B2 (ja) | 2007-01-29 | 2013-10-16 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 未分化型胃癌治療用組成物 |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| US8952035B2 (en) | 2007-11-09 | 2015-02-10 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| WO2009151910A2 (en) * | 2008-05-25 | 2009-12-17 | Wyeth | Combination product of receptor tyrosine kinase inhibitor and fatty acid synthase inhibitor for treating cancer |
| EP3135285B1 (en) | 2008-06-17 | 2018-08-15 | Wyeth LLC | Antineoplastic combinations containing hki-272 and vinorelbine |
| EP2326329B1 (en) | 2008-08-04 | 2017-01-11 | Wyeth LLC | Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine |
| ITMI20082336A1 (it) * | 2008-12-29 | 2010-06-30 | Univ Parma | Composti inibitori irreversibili di egfr con attivita' antiproliferativa |
| SG173014A1 (en) | 2009-01-16 | 2011-08-29 | Exelixis Inc | Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quin0lin-4-yl] oxy}phenyl)-n' - (4 -fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer |
| DK3000467T3 (da) | 2009-04-06 | 2023-03-27 | Wyeth Llc | Behandling med neratinib mod brystkræft |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| ES2729677T3 (es) | 2009-11-09 | 2019-11-05 | Wyeth Llc | Esferoides de fármacos recubiertos y sus usos para eliminar o reducir condiciones, como la emesis y la diarrea |
| WO2011153942A1 (zh) * | 2010-06-09 | 2011-12-15 | 天津和美生物技术有限公司 | 氰基喹啉衍生物 |
| CN102958523B (zh) | 2010-06-25 | 2014-11-19 | 卫材R&D管理有限公司 | 使用具有激酶抑制作用的组合的抗肿瘤剂 |
| EA025451B1 (ru) * | 2010-08-26 | 2016-12-30 | Симфони Эволюшн, Инк. | Модулятор киназы рецепторного типа и способы лечения поликистозной болезни почек |
| AU2010363329A1 (en) | 2010-11-07 | 2013-05-09 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| CN102675287A (zh) * | 2011-03-11 | 2012-09-19 | 江苏恒瑞医药股份有限公司 | (e)-n-[4-[[3-氯-4-(2-吡啶基甲氧基)苯基]氨基]-3-氰基-7-乙氧基-6-喹啉基]-3-[(2r)-1-甲基吡咯烷-2-基]丙-2-烯酰胺的可药用的盐、其制备方法及其在医药上的应用 |
| WO2012144463A1 (ja) | 2011-04-18 | 2012-10-26 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| US9945862B2 (en) | 2011-06-03 | 2018-04-17 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| BR112015009004A8 (pt) | 2012-12-21 | 2021-07-20 | Eisai R&D Man Co Ltd | forma amorfa de derivado de quinolina e método de produção da mesma |
| CN103214489B (zh) * | 2013-02-25 | 2016-10-26 | 中国人民解放军第二军医大学 | 一类具有抗肿瘤活性的多靶点激酶抑制剂及其制备方法 |
| MX368099B (es) | 2013-05-14 | 2019-09-19 | Eisai R&D Man Co Ltd | Biomarcadores para predecir y evaluar el grado de respuesta de sujetos con cancer de endometrio a compuestos de tipo lenvatinib. |
| CN103304494B (zh) * | 2013-06-20 | 2015-05-27 | 河北大学 | 茚(1,2-b)喹喔啉-11-酮肟衍生物及其制备方法和用途 |
| HRP20221047T1 (hr) | 2014-08-28 | 2022-11-11 | Eisai R&D Management Co., Ltd. | Derivat kinolina visoke čistoće i postupak za njegovu proizvodnju |
| CN107427505A (zh) | 2015-02-25 | 2017-12-01 | 卫材R&D管理有限公司 | 用于抑制喹啉衍生物的苦味的方法 |
| WO2016140717A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
| US11369623B2 (en) | 2015-06-16 | 2022-06-28 | Prism Pharma Co., Ltd. | Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor |
| WO2016210345A1 (en) | 2015-06-25 | 2016-12-29 | The California Institute For Biomedical Research | Composition and methods for inhibiting mammalian sterile 20-like kinase 1 |
| WO2017117474A1 (en) * | 2015-12-30 | 2017-07-06 | Dana-Farber Cancer Institute, Inc. | Bifunctional compounds for her3 degradation and methods of use |
| WO2017148391A1 (zh) * | 2016-03-01 | 2017-09-08 | 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 |
| RS64654B1 (sr) | 2017-07-28 | 2023-10-31 | Yuhan Corp | Proces za pripremu n-(5-((4-(4-((dimetilamino)metil)-3-fenil-1h-pirazol-1-il)pirimidin-2-il)amino)-4-metoksi-2- morfolinofenil)akrilamida reakcijom odgovarajućeg amina sa 3-halo-propionil hloridom |
| 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 |
| 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 |
| 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 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL125686A (en) * | 1996-02-13 | 2002-11-10 | Zeneca Ltd | Quinazoline derivatives, processes for their preparation, pharmaceutical preparations containing them and their use in the manufacture of a drug with an anti-angiogenic effect and / or an effect of reducing vascular permeability |
| US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| US6235740B1 (en) * | 1997-08-25 | 2001-05-22 | Bristol-Myers Squibb Co. | Imidazoquinoxaline protein tyrosine kinase inhibitors |
| AU763669B2 (en) * | 1998-09-29 | 2003-07-31 | Wyeth Holdings Corporation | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
| BR9914164A (pt) * | 1998-09-29 | 2001-06-26 | American Cyanamid Co | Composto, método para o tratamento, inibição do crescimento de, ou erradiacação de um neoplasma, e de doença de rim policìstico, em um mamìfero em necessidade do mesmo, composição farmacêutica, e, processo para preparar um composto |
| GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| AU2464601A (en) * | 1999-12-29 | 2001-07-09 | Wyeth | Tricyclic protein kinase inhibitors |
| WO2002044166A1 (en) * | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
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2002
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- 2002-11-26 IL IL16192102A patent/IL161921A0/xx unknown
- 2002-11-26 AT AT02794031T patent/ATE370123T1/de not_active IP Right Cessation
- 2002-11-26 TW TW091134370A patent/TW200300348A/zh unknown
- 2002-11-26 CN CN028275381A patent/CN1659145A/zh active Pending
- 2002-11-26 NZ NZ533118A patent/NZ533118A/en unknown
- 2002-11-26 RU RU2004119414/04A patent/RU2309150C2/ru not_active IP Right Cessation
- 2002-11-26 JP JP2003551115A patent/JP2005514384A/ja not_active Ceased
- 2002-11-26 EP EP02794031A patent/EP1448531B1/en not_active Expired - Lifetime
- 2002-11-26 AR ARP020104543A patent/AR037438A1/es not_active Application Discontinuation
- 2002-11-26 WO PCT/US2002/037918 patent/WO2003050090A1/en active IP Right Grant
- 2002-11-26 KR KR1020047007951A patent/KR20050044599A/ko not_active Application Discontinuation
- 2002-11-26 PL PL02370137A patent/PL370137A1/xx not_active Application Discontinuation
- 2002-11-26 MX MXPA04004969A patent/MXPA04004969A/es active IP Right Grant
- 2002-11-26 BR BR0214485-9A patent/BR0214485A/pt not_active IP Right Cessation
- 2002-11-26 CA CA002467573A patent/CA2467573A1/en not_active Abandoned
- 2002-11-26 DE DE60221886T patent/DE60221886D1/de not_active Expired - Lifetime
- 2002-11-26 UA UA20040605019A patent/UA77469C2/uk unknown
- 2002-11-26 AU AU2002359489A patent/AU2002359489B2/en not_active Ceased
- 2002-11-26 HU HU0402228A patent/HUP0402228A2/hu unknown
-
2004
- 2004-05-25 CO CO04048181A patent/CO5580828A2/es not_active Application Discontinuation
- 2004-05-26 EC EC2004005122A patent/ECSP045122A/es unknown
- 2004-06-23 NO NO20042634A patent/NO20042634L/no not_active Application Discontinuation
- 2004-06-24 ZA ZA200405025A patent/ZA200405025B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20030149056A1 (en) | 2003-08-07 |
| MXPA04004969A (es) | 2004-08-11 |
| RU2004119414A (ru) | 2006-02-27 |
| EP1448531B1 (en) | 2007-08-15 |
| ATE370123T1 (de) | 2007-09-15 |
| US6821988B2 (en) | 2004-11-23 |
| NO20042634L (no) | 2004-06-23 |
| AU2002359489A1 (en) | 2003-06-23 |
| BR0214485A (pt) | 2004-09-14 |
| WO2003050090A1 (en) | 2003-06-19 |
| ECSP045122A (es) | 2004-07-23 |
| CO5580828A2 (es) | 2005-11-30 |
| KR20050044599A (ko) | 2005-05-12 |
| AR037438A1 (es) | 2004-11-10 |
| TW200300348A (en) | 2003-06-01 |
| AU2002359489B2 (en) | 2008-10-30 |
| CN1659145A (zh) | 2005-08-24 |
| PL370137A1 (en) | 2005-05-16 |
| EP1448531A1 (en) | 2004-08-25 |
| RU2309150C2 (ru) | 2007-10-27 |
| IL161921A0 (en) | 2005-11-20 |
| DE60221886D1 (de) | 2007-09-27 |
| HUP0402228A2 (hu) | 2005-02-28 |
| ZA200405025B (en) | 2006-12-27 |
| JP2005514384A (ja) | 2005-05-19 |
| CA2467573A1 (en) | 2003-06-19 |
| NZ533118A (en) | 2006-07-28 |
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