BG108325A - Нови 4-анилинохинолин-3-карбоксамиди - Google Patents
Нови 4-анилинохинолин-3-карбоксамиди Download PDFInfo
- Publication number
- BG108325A BG108325A BG108325A BG10832503A BG108325A BG 108325 A BG108325 A BG 108325A BG 108325 A BG108325 A BG 108325A BG 10832503 A BG10832503 A BG 10832503A BG 108325 A BG108325 A BG 108325A
- Authority
- BG
- Bulgaria
- Prior art keywords
- methoxy
- quinol
- amino
- quinolinecarboxamide
- dimethoxy
- Prior art date
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- MOXCMUMGZFALMQ-UHFFFAOYSA-N 4-anilinoquinoline-3-carboxamide Chemical class NC(=O)C1=CN=C2C=CC=CC2=C1NC1=CC=CC=C1 MOXCMUMGZFALMQ-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 184
- 238000000034 method Methods 0.000 claims abstract description 54
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims abstract 3
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims abstract 3
- -1 tetrahydronaphenyl Chemical group 0.000 claims description 239
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 45
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 22
- BLTDCIWCFCUQCB-UHFFFAOYSA-N quinoline-3-carboxamide Chemical compound C1=CC=CC2=CC(C(=O)N)=CN=C21 BLTDCIWCFCUQCB-UHFFFAOYSA-N 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical group CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 claims description 6
- TWOJJUGTAYVRLD-UHFFFAOYSA-N 7-[3-(dimethylamino)propoxy]-4-(2-ethylanilino)-6-methoxyquinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCCN(C)C)=C(OC)C=C12 TWOJJUGTAYVRLD-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 5
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 150000003852 triazoles Chemical class 0.000 claims description 5
- BSBSTIVGBSMVCU-UHFFFAOYSA-N 4-(2-ethylanilino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCCN3CCOCC3)=C(OC)C=C12 BSBSTIVGBSMVCU-UHFFFAOYSA-N 0.000 claims description 4
- ZENSQDUJTCHDDE-UHFFFAOYSA-N 4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC(CO)=C1C ZENSQDUJTCHDDE-UHFFFAOYSA-N 0.000 claims description 4
- SKUPLWYPPZPCAH-UHFFFAOYSA-N 7-methoxy-4-(2-methylanilino)-6-(2-morpholin-4-ylethylamino)quinoline-3-carboxamide Chemical compound C=12C=C(NCCN3CCOCC3)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC=C1C SKUPLWYPPZPCAH-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- BEGKILNSQXLQLG-UHFFFAOYSA-N 4-(2-bromoanilino)-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC=C1Br BEGKILNSQXLQLG-UHFFFAOYSA-N 0.000 claims description 3
- FLMXLIKYEZKKPG-UHFFFAOYSA-N 4-(2-ethylanilino)-6-methoxy-7-(4-morpholin-4-ylbutoxy)quinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCCCN3CCOCC3)=C(OC)C=C12 FLMXLIKYEZKKPG-UHFFFAOYSA-N 0.000 claims description 3
- CBIHUXHQURLZPD-UHFFFAOYSA-N 4-(2-ethylanilino)-6-methoxy-7-[2-(methylamino)ethoxy]quinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCNC)=C(OC)C=C12 CBIHUXHQURLZPD-UHFFFAOYSA-N 0.000 claims description 3
- GYKIPVJRUKQQIF-UHFFFAOYSA-N 4-(2-ethylanilino)-6-methoxy-7-[3-[methyl(pyridin-4-yl)amino]propoxy]quinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCCN(C)C=3C=CN=CC=3)=C(OC)C=C12 GYKIPVJRUKQQIF-UHFFFAOYSA-N 0.000 claims description 3
- ZBFPEUSSTBRUCM-UHFFFAOYSA-N 4-[3-(2-amino-2-oxoethyl)-2-methylanilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CC(N)=O)=C1C ZBFPEUSSTBRUCM-UHFFFAOYSA-N 0.000 claims description 3
- CWKPWMFANIDKFU-UHFFFAOYSA-N 4-[3-(cyanomethyl)-2-methylanilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CC#N)=C1C CWKPWMFANIDKFU-UHFFFAOYSA-N 0.000 claims description 3
- DQXKJJFICWXPTI-UHFFFAOYSA-N 4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-7-(3-thiomorpholin-4-ylpropoxy)quinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(OCCCN3CCSCC3)C(OC)=CC2=C1NC1=CC=CC(CO)=C1C DQXKJJFICWXPTI-UHFFFAOYSA-N 0.000 claims description 3
- NSEIFVLEVTZPMT-UHFFFAOYSA-N 4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxy-6-phenylmethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OCC=3C=CC=CC=3)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CO)=C1C NSEIFVLEVTZPMT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- CAGYKCOTGKSBER-UHFFFAOYSA-N 6-hydroxy-4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxyquinoline-3-carboxamide Chemical compound C=12C=C(O)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CO)=C1C CAGYKCOTGKSBER-UHFFFAOYSA-N 0.000 claims description 3
- ARWACSHHZKMUQQ-UHFFFAOYSA-N 6-methoxy-4-(2-methylanilino)-7-(2-morpholin-4-ylethoxy)quinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(OCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC=C1C ARWACSHHZKMUQQ-UHFFFAOYSA-N 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- HVWLKCYOKFESKQ-UHFFFAOYSA-N methyl 4-[3-carbamoyl-6-methoxy-4-(2-methylanilino)quinolin-7-yl]oxybutanoate Chemical compound C=12C=C(OC)C(OCCCC(=O)OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC=C1C HVWLKCYOKFESKQ-UHFFFAOYSA-N 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- HPQRQAOVNXWEEQ-UHFFFAOYSA-N quinoline-8-carboxamide Chemical compound C1=CN=C2C(C(=O)N)=CC=CC2=C1 HPQRQAOVNXWEEQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims description 2
- IRQKVVCDXXXGGC-UHFFFAOYSA-N 3-[(3-carbamoyl-6,7-dimethoxyquinolin-4-yl)amino]-2-methylbenzoic acid Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(C(O)=O)=C1C IRQKVVCDXXXGGC-UHFFFAOYSA-N 0.000 claims description 2
- DKCWUFZIMRNLTO-UHFFFAOYSA-N 4-(1h-indol-4-ylamino)-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC2=C1C=CN2 DKCWUFZIMRNLTO-UHFFFAOYSA-N 0.000 claims description 2
- ZHFNYOIDMCEWMM-UHFFFAOYSA-N 4-(1h-indol-4-ylamino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carboxamide Chemical compound COC1=CC2=C(NC=3C=4C=CNC=4C=CC=3)C(C(N)=O)=CN=C2C=C1OCCCN1CCOCC1 ZHFNYOIDMCEWMM-UHFFFAOYSA-N 0.000 claims description 2
- JIFNRRKQAHLEAX-UHFFFAOYSA-N 4-(2-ethylanilino)-7-(2-imidazol-1-ylethoxy)-6-methoxyquinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCN3C=NC=C3)=C(OC)C=C12 JIFNRRKQAHLEAX-UHFFFAOYSA-N 0.000 claims description 2
- QZVCPJMBGNCFMQ-UHFFFAOYSA-N 4-(2-ethylanilino)-7-(3-hydroxypropoxy)-6-methoxyquinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OCCCO)=C(OC)C=C12 QZVCPJMBGNCFMQ-UHFFFAOYSA-N 0.000 claims description 2
- RWSDZEDXPXJFII-UHFFFAOYSA-N 4-(3-hydroxy-2-methylanilino)-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(O)=C1C RWSDZEDXPXJFII-UHFFFAOYSA-N 0.000 claims description 2
- XZGGOZYDAVVFDA-UHFFFAOYSA-N 4-(4-bromo-2-methylanilino)-7-methoxyquinoline-3-carboxamide Chemical compound NC(=O)C=1C=NC2=CC(OC)=CC=C2C=1NC1=CC=C(Br)C=C1C XZGGOZYDAVVFDA-UHFFFAOYSA-N 0.000 claims description 2
- PDRUYGJKOGAVPR-UHFFFAOYSA-N 4-(4-fluoro-2-methylanilino)-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=C(F)C=C1C PDRUYGJKOGAVPR-UHFFFAOYSA-N 0.000 claims description 2
- RVBZWKPLUQOMRM-UHFFFAOYSA-N 4-[(2-ethylpyrazol-3-yl)amino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound CCN1N=CC=C1NC1=C(C(N)=O)C=NC2=CC(OC)=C(OC)C=C12 RVBZWKPLUQOMRM-UHFFFAOYSA-N 0.000 claims description 2
- VYMIAEOEKQAWIO-UHFFFAOYSA-N 4-[(3-carbamoyl-6,7-dimethoxyquinolin-4-yl)amino]-3-methylbenzoic acid Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=C(C(O)=O)C=C1C VYMIAEOEKQAWIO-UHFFFAOYSA-N 0.000 claims description 2
- ACMPEYKTPKISHO-UHFFFAOYSA-N 4-[2-bromo-3-(hydroxymethyl)anilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CO)=C1Br ACMPEYKTPKISHO-UHFFFAOYSA-N 0.000 claims description 2
- KSJAGHWRPJQMKX-UHFFFAOYSA-N 4-[2-ethyl-3-(hydroxymethyl)anilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound CCC1=C(CO)C=CC=C1NC1=C(C(N)=O)C=NC2=CC(OC)=C(OC)C=C12 KSJAGHWRPJQMKX-UHFFFAOYSA-N 0.000 claims description 2
- YXPFYTWMQZCLTM-UHFFFAOYSA-N 4-[3-(2-hydroxyethyl)-2-methylanilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CCO)=C1C YXPFYTWMQZCLTM-UHFFFAOYSA-N 0.000 claims description 2
- QENMIGZJVOHRKF-UHFFFAOYSA-N 4-[3-(hydroxymethyl)-2-methylanilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CO)=C1C QENMIGZJVOHRKF-UHFFFAOYSA-N 0.000 claims description 2
- SMRAKASSXKAARV-UHFFFAOYSA-N 4-[4-(hydroxymethyl)-2-methylanilino]-6,7-dimethoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=C(CO)C=C1C SMRAKASSXKAARV-UHFFFAOYSA-N 0.000 claims description 2
- IJUKVWFZVBJPEH-UHFFFAOYSA-N 6,7-dimethoxy-4-[2-methyl-3-(2-methylpropoxymethyl)anilino]quinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(COCC(C)C)=C1C IJUKVWFZVBJPEH-UHFFFAOYSA-N 0.000 claims description 2
- KWOLJAYNNJXSJD-UHFFFAOYSA-N 6-[2-(dimethylamino)ethoxy]-4-(2-ethylanilino)-7-methoxyquinoline-3-carboxamide Chemical compound CCC1=CC=CC=C1NC1=C(C(N)=O)C=NC2=CC(OC)=C(OCCN(C)C)C=C12 KWOLJAYNNJXSJD-UHFFFAOYSA-N 0.000 claims description 2
- CLWXFIFHPNQPDK-UHFFFAOYSA-N 6-[2-(dimethylamino)ethoxy]-4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxyquinoline-3-carboxamide Chemical compound C=12C=C(OCCN(C)C)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CO)=C1C CLWXFIFHPNQPDK-UHFFFAOYSA-N 0.000 claims description 2
- FMTQFMGKMOIBQK-UHFFFAOYSA-N 6-[2-(ethylamino)ethoxy]-4-(2-ethylanilino)-7-methoxyquinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(OC)C(OCCNCC)=CC2=C1NC1=CC=CC=C1CC FMTQFMGKMOIBQK-UHFFFAOYSA-N 0.000 claims description 2
- CPCBRGLQMGIAIL-UHFFFAOYSA-N 6-methoxy-4-(2-methylanilino)-7-(2-morpholin-4-ylethylamino)quinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(NCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC=C1C CPCBRGLQMGIAIL-UHFFFAOYSA-N 0.000 claims description 2
- FWMVDBIKONGVAR-UHFFFAOYSA-N 6-methoxy-4-(2-methylanilino)-7-(3-morpholin-4-ylpropoxy)quinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC=C1C FWMVDBIKONGVAR-UHFFFAOYSA-N 0.000 claims description 2
- FNHYWWXDZCYOND-UHFFFAOYSA-N 6-methoxy-4-(2-methylsulfanylanilino)-7-(3-morpholin-4-ylpropoxy)quinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC=C1SC FNHYWWXDZCYOND-UHFFFAOYSA-N 0.000 claims description 2
- MKBIMGXETBEZIJ-UHFFFAOYSA-N 7-[3-(ethylamino)propoxy]-4-(2-ethylanilino)-6-methoxyquinoline-3-carboxamide Chemical compound C=12C=C(OC)C(OCCCNCC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC=C1CC MKBIMGXETBEZIJ-UHFFFAOYSA-N 0.000 claims description 2
- ZYVXCKUAQAKLLQ-UHFFFAOYSA-N 7-hydroxy-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxyquinoline-3-carboxamide Chemical compound NC(=O)C1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=CC(CO)=C1C ZYVXCKUAQAKLLQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- LTUDISCZKZHRMJ-UHFFFAOYSA-N potassium;hydrate Chemical compound O.[K] LTUDISCZKZHRMJ-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Chemical class 0.000 description 1
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- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
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- QZZYYBQGTSGDPP-ZQBYOMGUSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC([14C]#N)=CN=C21 QZZYYBQGTSGDPP-ZQBYOMGUSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000600 sorbitol Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- ZTBNOFSSMFDTHM-UHFFFAOYSA-N tert-butyl n-[(2-aminophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC=C1N ZTBNOFSSMFDTHM-UHFFFAOYSA-N 0.000 description 1
- RNACIMILHGHUIR-UHFFFAOYSA-N tert-butyl n-[(3-amino-2-methylphenyl)methyl]carbamate Chemical compound CC1=C(N)C=CC=C1CNC(=O)OC(C)(C)C RNACIMILHGHUIR-UHFFFAOYSA-N 0.000 description 1
- DCQZFTBPBAFBJK-UHFFFAOYSA-N tert-butyl n-[[3-[(3-carbamoyl-6,7-dimethoxyquinolin-4-yl)amino]-2-methylphenyl]methyl]carbamate Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C(N)=O)C=1NC1=CC=CC(CNC(=O)OC(C)(C)C)=C1C DCQZFTBPBAFBJK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
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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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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- 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
-
- 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
-
- 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
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—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
- 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
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0101675A SE0101675D0 (sv) | 2001-05-11 | 2001-05-11 | Novel composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG108325A true BG108325A (bg) | 2004-11-30 |
Family
ID=20284085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG108325A BG108325A (bg) | 2001-05-11 | 2003-11-07 | Нови 4-анилинохинолин-3-карбоксамиди |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US7037925B2 (cs) |
| EP (1) | EP1387830A1 (cs) |
| JP (1) | JP2004533452A (cs) |
| KR (1) | KR20040007547A (cs) |
| CN (1) | CN1286815C (cs) |
| AR (1) | AR037489A1 (cs) |
| BG (1) | BG108325A (cs) |
| BR (1) | BR0209431A (cs) |
| CA (1) | CA2446717A1 (cs) |
| CZ (1) | CZ20033034A3 (cs) |
| EE (1) | EE200300544A (cs) |
| HU (1) | HUP0401339A2 (cs) |
| IL (1) | IL158517A0 (cs) |
| IS (1) | IS7016A (cs) |
| MX (1) | MXPA03010207A (cs) |
| MY (1) | MY134136A (cs) |
| NO (1) | NO20034992D0 (cs) |
| NZ (1) | NZ529302A (cs) |
| PL (1) | PL366766A1 (cs) |
| RU (1) | RU2281940C2 (cs) |
| SE (1) | SE0101675D0 (cs) |
| SK (1) | SK13712003A3 (cs) |
| UA (1) | UA76142C2 (cs) |
| WO (1) | WO2002092571A1 (cs) |
| ZA (1) | ZA200308350B (cs) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7576074B2 (en) | 2002-07-15 | 2009-08-18 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| SE0301373D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Novel compounds |
| TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
| WO2005009971A1 (ja) * | 2003-07-24 | 2005-02-03 | Astellas Pharma Inc. | キノロン誘導体又はその塩 |
| EP2210607B1 (en) | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
| GB0322722D0 (en) * | 2003-09-27 | 2003-10-29 | Glaxo Group Ltd | Compounds |
| JP2007518823A (ja) * | 2004-01-23 | 2007-07-12 | アムゲン インコーポレイテッド | キノリン、キナゾリン、ピリジン、及びピリミジン化合物と炎症、血管新生、及び癌に対する治療におけるそれら化合物の用途 |
| SE0400284D0 (sv) * | 2004-02-10 | 2004-02-10 | Astrazeneca Ab | Novel compounds |
| AU2005237254B2 (en) * | 2004-05-03 | 2010-02-04 | Novartis Ag | Combinations comprising a S1P receptor agonist and a JAK3 kinase inhibitor |
| BRPI0516093A (pt) | 2004-10-12 | 2008-08-19 | Astrazeneca Ab | derivado de quinazolina, processo para a preparação do mesmo, composição farmacêutica, uso de um derivado de quinazolina, e, método para tratamento de distúrbios proliferativos celulares em um animal de sanque quente |
| MX2007004465A (es) * | 2004-10-19 | 2007-05-07 | Hoffmann La Roche | Derivados de quinolina. |
| JP2009513615A (ja) | 2005-10-28 | 2009-04-02 | アストラゼネカ アクチボラグ | 癌の治療においてチロシンキナーゼ阻害剤として使用するための4−(3−アミノピラゾール)ピリミジン誘導体 |
| WO2007099323A2 (en) * | 2006-03-02 | 2007-09-07 | Astrazeneca Ab | Quinoline derivatives |
| UY30183A1 (es) * | 2006-03-02 | 2007-10-31 | Astrazeneca Ab | Derivados de quinolina |
| CA2645376C (en) | 2006-03-13 | 2017-06-20 | Activx Biosciences, Inc. | Aminoquinolones as gsk-3 inhibitors |
| KR20080112380A (ko) * | 2006-04-14 | 2008-12-24 | 아스트라제네카 아베 | Csf-1r 키나제 억제제로서의 4-아닐리노퀴놀린-3-카르복스아미드 |
| WO2007139496A1 (en) * | 2006-05-30 | 2007-12-06 | Clanotech Ab | Quinoline derivatives acting as tyrosine kinase inhibitors |
| TW200829555A (en) * | 2006-11-10 | 2008-07-16 | Astrazeneca Ab | Chemical compounds |
| CL2008000191A1 (es) * | 2007-01-25 | 2008-08-22 | Astrazeneca Ab | Compuestos derivados de 4-amino-cinnotina-3-carboxamida; inhibidores de csf-1r quinasa; su proceso de preparacion; y su uso para tratar el cancer. |
| CN102351880B (zh) * | 2007-09-11 | 2014-11-12 | 杏林制药株式会社 | 作为gsk-3 抑制剂的氰基氨基喹诺酮和四唑并氨基喹诺酮 |
| US8476261B2 (en) | 2007-09-12 | 2013-07-02 | Kyorin Pharmaceutical Co., Ltd. | Spirocyclic aminoquinolones as GSK-3 inhibitors |
| US8063058B2 (en) | 2008-04-16 | 2011-11-22 | Portola Pharmaceuticals, Inc. | Inhibitors of syk and JAK protein kinases |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| JP2011520804A (ja) * | 2008-05-07 | 2011-07-21 | アストラゼネカ アクチボラグ | 化合物 |
| EP2361902A4 (en) * | 2008-11-21 | 2012-04-25 | Astellas Pharma Inc | 4,6-DIAMINONICOTINSÄUREAMIDVERBINDUNG |
| NZ779754A (en) | 2009-01-16 | 2023-04-28 | Exelixis Inc | Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl] oxy} phenyl)-n’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer |
| MX2011009414A (es) | 2009-03-11 | 2011-10-19 | Kyorin Seiyaku Kk | 7-cicloalquiloaminoquinolonas como inhibidores de gsk-3. |
| US8367689B2 (en) | 2009-05-06 | 2013-02-05 | Portola Pharmaceuticals, Inc. | Inhibitors of JAK |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| CA2806332C (en) | 2010-07-30 | 2017-11-14 | Oncotherapy Science, Inc. | Quinoline derivatives and melk inhibitors containing the same |
| UY33549A (es) * | 2010-08-10 | 2012-01-31 | Glaxo Group Ltd | Quinolil aminas como agentes inhibidores de las quinasas |
| EP2975027A1 (en) | 2010-11-01 | 2016-01-20 | Portola Pharmaceuticals, Inc. | Nicotinamides as jak kinase modulators |
| US9604963B2 (en) | 2011-03-04 | 2017-03-28 | Glaxosmithkline Intellectual Property Development Limited | Amino-quinolines as kinase inhibitors |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| MX363551B (es) | 2011-11-23 | 2019-03-27 | Portola Pharmaceuticals Inc Star | Compuestos derivados de pirazina como inhibidores de cinasa. |
| AR092529A1 (es) | 2012-09-13 | 2015-04-22 | Glaxosmithkline Llc | Compuesto de aminoquinazolina, composicion farmaceutica que lo comprende y uso de dicho compuesto para la preparacion de un medicamento |
| TW201425307A (zh) | 2012-09-13 | 2014-07-01 | Glaxosmithkline Llc | 作為激酶抑制劑之胺基-喹啉類 |
| EP2956138B1 (en) | 2013-02-15 | 2022-06-22 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| MX368903B (es) | 2013-02-20 | 2019-10-21 | Kala Pharmaceuticals Inc | Compuestos terapéuticos y sus usos en el tratamiento de enfermedades proliferativas. |
| CA2902132C (en) | 2013-02-21 | 2020-09-22 | Glaxosmithkline Intellectual Property Development Limited | Quinazolines as kinase inhibitors |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| US9458169B2 (en) | 2013-11-01 | 2016-10-04 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| WO2016125187A1 (en) * | 2015-02-03 | 2016-08-11 | Council Of Scientific & Industrial Research | Novel quinoline derivatives and preparation thereof |
| AU2017324713B2 (en) | 2016-09-08 | 2020-08-13 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| US10336767B2 (en) | 2016-09-08 | 2019-07-02 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| EP3509423A4 (en) | 2016-09-08 | 2020-05-13 | Kala Pharmaceuticals, Inc. | CRYSTALLINE FORMS OF THERAPEUTIC COMPOUNDS AND USES THEREOF |
| CN109496212B (zh) * | 2016-10-18 | 2020-08-14 | 北京康辰药业股份有限公司 | 一种喹啉基取代的羧酸化合物或其药学上可接受的盐、其药物组合物及应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3037925A (en) * | 1958-04-09 | 1962-06-05 | Smith Corp A O | Cathodically protected structure and method of making same |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| KR20010089171A (ko) * | 1998-08-21 | 2001-09-29 | 추후제출 | 퀴나졸린 유도체 |
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- 2002-05-06 SK SK13712003A patent/SK13712003A3/sk unknown
- 2002-05-06 HU HU0401339A patent/HUP0401339A2/hu unknown
- 2002-05-06 EE EEP200300544A patent/EE200300544A/xx unknown
- 2002-05-06 EP EP02733657A patent/EP1387830A1/en not_active Withdrawn
- 2002-05-06 JP JP2002589457A patent/JP2004533452A/ja active Pending
- 2002-05-06 CZ CZ20033034A patent/CZ20033034A3/cs unknown
- 2002-05-06 WO PCT/SE2002/000875 patent/WO2002092571A1/en not_active Ceased
- 2002-05-06 RU RU2003131679/04A patent/RU2281940C2/ru not_active IP Right Cessation
- 2002-05-06 US US10/477,254 patent/US7037925B2/en not_active Expired - Fee Related
- 2002-05-06 CN CNB02809722XA patent/CN1286815C/zh not_active Expired - Fee Related
- 2002-05-06 IL IL15851702A patent/IL158517A0/xx unknown
- 2002-05-06 NZ NZ529302A patent/NZ529302A/en unknown
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- 2002-05-06 BR BR0209431-2A patent/BR0209431A/pt not_active IP Right Cessation
- 2002-05-06 MX MXPA03010207A patent/MXPA03010207A/es unknown
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- 2002-05-06 PL PL02366766A patent/PL366766A1/xx unknown
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| IS7016A (is) | 2003-11-05 |
| AR037489A1 (es) | 2004-11-17 |
| WO2002092571A1 (en) | 2002-11-21 |
| US20060173034A1 (en) | 2006-08-03 |
| BR0209431A (pt) | 2004-08-03 |
| JP2004533452A (ja) | 2004-11-04 |
| CN1507434A (zh) | 2004-06-23 |
| CZ20033034A3 (en) | 2004-06-16 |
| NZ529302A (en) | 2004-08-27 |
| SE0101675D0 (sv) | 2001-05-11 |
| NO20034992D0 (no) | 2003-11-10 |
| EP1387830A1 (en) | 2004-02-11 |
| PL366766A1 (en) | 2005-02-07 |
| RU2281940C2 (ru) | 2006-08-20 |
| HUP0401339A2 (hu) | 2004-12-28 |
| UA76142C2 (en) | 2006-07-17 |
| MXPA03010207A (es) | 2004-03-10 |
| IL158517A0 (en) | 2004-05-12 |
| SK13712003A3 (en) | 2004-10-05 |
| KR20040007547A (ko) | 2004-01-24 |
| US7037925B2 (en) | 2006-05-02 |
| RU2003131679A (ru) | 2005-05-10 |
| MY134136A (en) | 2007-11-30 |
| US20040248923A1 (en) | 2004-12-09 |
| CN1286815C (zh) | 2006-11-29 |
| HU0401339D0 (en) | 2004-08-30 |
| ZA200308350B (en) | 2005-01-27 |
| EE200300544A (et) | 2004-02-16 |
| CA2446717A1 (en) | 2002-11-21 |
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