ZA200102729B - Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors. - Google Patents
Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors. Download PDFInfo
- Publication number
- ZA200102729B ZA200102729B ZA200102729A ZA200102729A ZA200102729B ZA 200102729 B ZA200102729 B ZA 200102729B ZA 200102729 A ZA200102729 A ZA 200102729A ZA 200102729 A ZA200102729 A ZA 200102729A ZA 200102729 B ZA200102729 B ZA 200102729B
- Authority
- ZA
- South Africa
- Prior art keywords
- carbon atoms
- acceptable salt
- pharmaceutically acceptable
- phenyl
- methoxy
- Prior art date
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- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title description 20
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title description 20
- 239000003112 inhibitor Substances 0.000 title description 13
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 title description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 859
- 150000003839 salts Chemical class 0.000 claims description 195
- -1 nitro, carboxy Chemical group 0.000 claims description 191
- 150000001875 compounds Chemical class 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 74
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- 125000003342 alkenyl group Chemical group 0.000 claims description 55
- 125000000304 alkynyl group Chemical group 0.000 claims description 55
- 229910052799 carbon Inorganic materials 0.000 claims description 49
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 41
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- 150000003254 radicals Chemical group 0.000 claims description 39
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 38
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 38
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 37
- 125000003282 alkyl amino group Chemical group 0.000 claims description 36
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical group 0.000 claims description 36
- 125000004970 halomethyl group Chemical group 0.000 claims description 36
- 125000004414 alkyl thio group Chemical group 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 32
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 31
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 31
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 30
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 30
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 26
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 23
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 22
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 20
- 150000001721 carbon Chemical class 0.000 claims description 20
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 10
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 10
- 229930192474 thiophene Natural products 0.000 claims description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 9
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 230000012010 growth Effects 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 9
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 8
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-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
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 6
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 6
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 6
- 150000003536 tetrazoles Chemical class 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 5
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 5
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 5
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 5
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-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
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 3
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- QNXSIUBBGPHDDE-UHFFFAOYSA-N alpha-indanone Natural products C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 3
- 230000008569 process Effects 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 2
- OARGFWQSVACNCO-UHFFFAOYSA-N 1-oxidoquinoxalin-1-ium Chemical compound C1=CC=C2[N+]([O-])=CC=NC2=C1 OARGFWQSVACNCO-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 2
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 claims description 2
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical compound C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 2
- 239000012964 benzotriazole Substances 0.000 claims description 2
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 claims description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 2
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 claims description 2
- TYLGVQVJCVFREB-UHFFFAOYSA-N pyrido[3,4-b]pyrazine Chemical compound C1=NC=CC2=NC=CN=C21 TYLGVQVJCVFREB-UHFFFAOYSA-N 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 19
- 239000000126 substance Substances 0.000 claims 8
- 229910019567 Re Re Inorganic materials 0.000 claims 5
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 claims 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims 2
- 210000001072 colon Anatomy 0.000 claims 2
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims 2
- 210000003238 esophagus Anatomy 0.000 claims 2
- 210000003734 kidney Anatomy 0.000 claims 2
- 210000000867 larynx Anatomy 0.000 claims 2
- 210000004072 lung Anatomy 0.000 claims 2
- 210000000214 mouth Anatomy 0.000 claims 2
- 210000001672 ovary Anatomy 0.000 claims 2
- 210000002784 stomach Anatomy 0.000 claims 2
- 210000003932 urinary bladder Anatomy 0.000 claims 2
- HLVUTYRQJVXXMA-AATRIKPKSA-N (e)-n-[4-(3-chloro-4-pyridin-4-yloxyanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OC1=CC=NC=C1 HLVUTYRQJVXXMA-AATRIKPKSA-N 0.000 claims 1
- PPCBUZPEORQZEG-UHFFFAOYSA-N 1,3-dioxolane;oxane Chemical compound C1COCO1.C1CCOCC1 PPCBUZPEORQZEG-UHFFFAOYSA-N 0.000 claims 1
- MXBVNILGVJVVMH-UHFFFAOYSA-N 1,7-naphthyridine Chemical compound C1=NC=CC2=CC=CN=C21 MXBVNILGVJVVMH-UHFFFAOYSA-N 0.000 claims 1
- ZEMCGIDMAMIJLF-UHFFFAOYSA-N 1-benzyl-2-phenylhydrazine Chemical compound C=1C=CC=CC=1CNNC1=CC=CC=C1 ZEMCGIDMAMIJLF-UHFFFAOYSA-N 0.000 claims 1
- NLHOVYMVGLRDPF-UHFFFAOYSA-N 1-oxidoquinazolin-1-ium Chemical compound C1=CC=C2[N+]([O-])=CN=CC2=C1 NLHOVYMVGLRDPF-UHFFFAOYSA-N 0.000 claims 1
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims 1
- YQZZJSAAELHVAX-UHFFFAOYSA-N 2-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=C(NC=2C=C3NN=CC3=CC=2)C2=CC(OC)=CC=C2N=C1OCCN1CCN(CCO)CC1 YQZZJSAAELHVAX-UHFFFAOYSA-N 0.000 claims 1
- MXFNTSRVTMCEIX-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2OCOC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 MXFNTSRVTMCEIX-UHFFFAOYSA-N 0.000 claims 1
- DJBSYXCQXWSUGR-UHFFFAOYSA-N 4-(1,3-benzothiazol-6-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2N=CSC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 DJBSYXCQXWSUGR-UHFFFAOYSA-N 0.000 claims 1
- TVXVKHGYFDHAET-UHFFFAOYSA-N 4-(1h-indazol-5-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C2NN=CC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OC)OC)=C1 TVXVKHGYFDHAET-UHFFFAOYSA-N 0.000 claims 1
- RHKJQRDAZXRLRK-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-5,8-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C(OC)=CC=C(C3=NC=C2C#N)OC)=C1 RHKJQRDAZXRLRK-UHFFFAOYSA-N 0.000 claims 1
- DCIGBUYSYRJHIJ-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-5-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C(C#N)=CN=C3C=CC=C(C=23)OC)=C1 DCIGBUYSYRJHIJ-UHFFFAOYSA-N 0.000 claims 1
- ZOESNMKXJDKRGQ-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6,7,8-trimethoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=C(C(=C(OC)C3=NC=C2C#N)OC)OC)=C1 ZOESNMKXJDKRGQ-UHFFFAOYSA-N 0.000 claims 1
- ABKSPJGBRHIABU-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6,7-bis(2-methoxyethoxy)quinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCCOC)OCCOC)=C1 ABKSPJGBRHIABU-UHFFFAOYSA-N 0.000 claims 1
- ZFEGVOZAULXMAI-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OC)OC)=C1 ZFEGVOZAULXMAI-UHFFFAOYSA-N 0.000 claims 1
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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|---|---|---|---|---|
| HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
-
1999
- 1999-09-22 EP EP99948410A patent/EP1117659B1/en not_active Expired - Lifetime
- 1999-09-22 CA CA2344169A patent/CA2344169C/en not_active Expired - Lifetime
- 1999-09-22 IL IL14212199A patent/IL142121A0/xx active IP Right Grant
- 1999-09-22 WO PCT/US1999/022054 patent/WO2000018761A1/en not_active Application Discontinuation
- 1999-09-22 JP JP2000572221A patent/JP4548642B2/ja not_active Expired - Lifetime
- 1999-09-22 SK SK413-2001A patent/SK284846B6/sk not_active IP Right Cessation
- 1999-09-22 CZ CZ20011038A patent/CZ303899B6/cs not_active IP Right Cessation
- 1999-09-22 KR KR1020017003892A patent/KR100705142B1/ko active IP Right Grant
- 1999-09-22 PL PL346934A patent/PL201475B1/pl unknown
- 1999-09-22 EA EA200100411A patent/EA004436B1/ru not_active IP Right Cessation
- 1999-09-22 BR BRPI9914167-1A patent/BR9914167B1/pt not_active IP Right Cessation
- 1999-09-22 HU HU0103520A patent/HUP0103520A3/hu unknown
- 1999-09-22 CN CNB998113697A patent/CN1165532C/zh not_active Expired - Lifetime
- 1999-09-22 AT AT99948410T patent/ATE255575T1/de active
- 1999-09-22 UA UA2001042929A patent/UA72749C2/uk unknown
- 1999-09-22 ES ES99948410T patent/ES2211175T3/es not_active Expired - Lifetime
- 1999-09-22 AU AU61593/99A patent/AU763669B2/en not_active Expired
- 1999-09-22 DE DE69913364T patent/DE69913364T2/de not_active Expired - Lifetime
- 1999-09-22 NZ NZ510551A patent/NZ510551A/xx not_active IP Right Cessation
- 1999-09-22 PT PT99948410T patent/PT1117659E/pt unknown
- 1999-09-22 DK DK99948410T patent/DK1117659T3/da active
- 1999-09-28 AR ARP990104884A patent/AR035155A1/es active IP Right Grant
- 1999-09-29 TW TW088116630A patent/TWI233437B/zh not_active IP Right Cessation
-
2001
- 2001-03-20 IL IL142121A patent/IL142121A/en not_active IP Right Cessation
- 2001-03-28 NO NO20011575A patent/NO324563B1/no not_active IP Right Cessation
- 2001-04-03 ZA ZA200102729A patent/ZA200102729B/en unknown
- 2001-08-17 HK HK01105823A patent/HK1035188A1/xx not_active IP Right Cessation
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