CA2495603A1 - Benzonaphthyridines with pde 3/4 inhibiting activity - Google Patents
Benzonaphthyridines with pde 3/4 inhibiting activity Download PDFInfo
- Publication number
- CA2495603A1 CA2495603A1 CA002495603A CA2495603A CA2495603A1 CA 2495603 A1 CA2495603 A1 CA 2495603A1 CA 002495603 A CA002495603 A CA 002495603A CA 2495603 A CA2495603 A CA 2495603A CA 2495603 A1 CA2495603 A1 CA 2495603A1
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- CA
- Canada
- Prior art keywords
- alkyl
- alkoxy
- methyl
- phenyl
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 230000002401 inhibitory effect Effects 0.000 title description 10
- BJVCSICIEDHBNI-UHFFFAOYSA-N benzo[b][1,8]naphthyridine Chemical class N1=CC=CC2=CC3=CC=CC=C3N=C21 BJVCSICIEDHBNI-UHFFFAOYSA-N 0.000 title description 5
- 101100135867 Caenorhabditis elegans pde-3 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 186
- -1 1-4C-alkyl Chemical group 0.000 claims description 584
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 153
- 229910052739 hydrogen Inorganic materials 0.000 claims description 151
- 239000001257 hydrogen Substances 0.000 claims description 150
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 124
- 229910052736 halogen Inorganic materials 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 74
- 150000002367 halogens Chemical group 0.000 claims description 64
- 150000003254 radicals Chemical group 0.000 claims description 63
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 50
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 34
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 28
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 27
- 150000001204 N-oxides Chemical class 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 239000011737 fluorine Substances 0.000 claims description 22
- 125000001153 fluoro group Chemical group F* 0.000 claims description 22
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 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 14
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 13
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 12
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 12
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 11
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical compound C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 8
- JYNZIOFUHBJABQ-UHFFFAOYSA-N allyl-{6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl-}-methyl-amin Chemical group C=1OC2=CC(OCCCCCCN(C)CC=C)=CC=C2C=1C1=CC=C(Br)C=C1 JYNZIOFUHBJABQ-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 125000004544 purin-8-yl group Chemical group N1=CN=C2N=C(NC2=C1)* 0.000 claims description 8
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 8
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 7
- RFEBDZANCVHDLP-UHFFFAOYSA-N 3-[(4-cyanophenyl)methylamino]-6-(trifluoromethyl)quinoxaline-2-carboxylic acid Chemical group OC(=O)C1=NC2=CC=C(C(F)(F)F)C=C2N=C1NCC1=CC=C(C#N)C=C1 RFEBDZANCVHDLP-UHFFFAOYSA-N 0.000 claims description 7
- LFMFPKKYRXFHHZ-UHFFFAOYSA-N R24 Chemical compound C1=C(Cl)C(C)=CC=C1NC1=NC(N)=C(C=CC=C2)C2=N1 LFMFPKKYRXFHHZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000017520 skin disease Diseases 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 5
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- PXCBFHNABYEDMU-DHIUTWEWSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino(thiomorpholin-4-yl)methylidene]benzamide Chemical compound CCOc1cc2[C@H]3CN(C)CC[C@H]3N=C(c3ccc(cc3)C(=O)N=C(N)N3CCSCC3)c2cc1OC PXCBFHNABYEDMU-DHIUTWEWSA-N 0.000 claims description 2
- NMCVBHGCGQCGTA-FQLXRVMXSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino-(4-phenylpiperazin-1-yl)methylidene]benzamide Chemical compound NC(N1CCN(CC1)C1=CC=CC=C1)=NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O NMCVBHGCGQCGTA-FQLXRVMXSA-N 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 8
- VAHBCEWLPQSTOM-NHCUHLMSSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-(1-methyl-4-oxoimidazolidin-2-ylidene)benzamide Chemical compound C(C)OC1=CC2=C(C(=N[C@@H]3CCN(C[C@H]23)C)C2=CC=C(C(=O)NC=3N(CC(N3)=O)C)C=C2)C=C1OC VAHBCEWLPQSTOM-NHCUHLMSSA-N 0.000 claims 1
- ZEVNGXMSXKCTGA-PQUUEDNTSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-(3,4,4a,5-tetrahydro-1H-isoquinoline-2-carboximidoyl)benzamide Chemical compound C1N(CCC2CC=CC=C12)C(=N)NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O ZEVNGXMSXKCTGA-PQUUEDNTSA-N 0.000 claims 1
- MZIOFBWJQAQWBK-DNQXCXABSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-(3,5-dimethylpyrazole-1-carboximidoyl)benzamide Chemical compound CC1=NN(C(=C1)C)C(=N)NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O MZIOFBWJQAQWBK-DNQXCXABSA-N 0.000 claims 1
- PTUONTLZUVQGNT-JWQCQUIFSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-(4-acetylpiperazine-1-carboximidoyl)benzamide Chemical compound C(C)(=O)N1CCN(CC1)C(N)=NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O PTUONTLZUVQGNT-JWQCQUIFSA-N 0.000 claims 1
- RPUTVKWGOZEXIX-KAYWLYCHSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[N'-[2-(3,4-dimethoxyphenyl)ethyl]carbamimidoyl]benzamide Chemical compound CCOc1cc2[C@H]3CN(C)CC[C@H]3N=C(c3ccc(cc3)C(=O)NC(=N)NCCc3ccc(OC)c(OC)c3)c2cc1OC RPUTVKWGOZEXIX-KAYWLYCHSA-N 0.000 claims 1
- ZSYZVBSWYMMVEL-LOYHVIPDSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino-(4-benzylpiperazin-1-yl)methylidene]benzamide Chemical compound NC(N1CCN(CC1)CC1=CC=CC=C1)=NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O ZSYZVBSWYMMVEL-LOYHVIPDSA-N 0.000 claims 1
- AUPZCBBRPGYOAX-FIRIVFDPSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino-(4-benzylpiperidin-1-yl)methylidene]benzamide Chemical compound CCOc1cc2[C@H]3CN(C)CC[C@H]3N=C(c3ccc(cc3)C(=O)N=C(N)N3CCC(Cc4ccccc4)CC3)c2cc1OC AUPZCBBRPGYOAX-FIRIVFDPSA-N 0.000 claims 1
- COEFGZZFDBPVFM-FQLXRVMXSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino-(4-cyclohexylpiperazin-1-yl)methylidene]benzamide Chemical compound NC(N1CCN(CC1)C1CCCCC1)=NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O COEFGZZFDBPVFM-FQLXRVMXSA-N 0.000 claims 1
- FQXQCGJTGJJWDJ-VSGBNLITSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino-[4-(2-methoxyphenyl)piperazin-1-yl]methylidene]benzamide Chemical compound CCOc1cc2[C@H]3CN(C)CC[C@H]3N=C(c3ccc(cc3)C(=O)N=C(N)N3CCN(CC3)c3ccccc3OC)c2cc1OC FQXQCGJTGJJWDJ-VSGBNLITSA-N 0.000 claims 1
- BOWWBAUOPMWYBN-KAYWLYCHSA-N 4-[(4aR,10bS)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1H-benzo[c][1,6]naphthyridin-6-yl]-N-[amino-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]methylidene]benzamide Chemical compound NC(N1CCN(CC1)CCOCCO)=NC(C1=CC=C(C=C1)C1=N[C@@H]2CCN(C[C@@H]2C2=C1C=C(C(=C2)OCC)OC)C)=O BOWWBAUOPMWYBN-KAYWLYCHSA-N 0.000 claims 1
- BLOXCQJLLFAOPS-FGZHOGPDSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[(e)-n'-(4-methyl-1,3-thiazol-2-yl)carbamimidoyl]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C(C=C1)=CC=C1C(=O)N\C(N)=N\C1=NC(C)=CS1 BLOXCQJLLFAOPS-FGZHOGPDSA-N 0.000 claims 1
- IQJVESWCXAEULU-FIRIVFDPSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[[4-(4-acetylphenyl)piperazin-1-yl]-aminomethylidene]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C(C=C1)=CC=C1C(=O)N=C(N)N(CC1)CCN1C1=CC=C(C(C)=O)C=C1 IQJVESWCXAEULU-FIRIVFDPSA-N 0.000 claims 1
- KBQIZRVBKBVLBH-JWQCQUIFSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino(anilino)methylidene]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C(C=C1)=CC=C1C(=O)N=C(N)NC1=CC=CC=C1 KBQIZRVBKBVLBH-JWQCQUIFSA-N 0.000 claims 1
- OSDITUJPDREPII-CLJLJLNGSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino(azocan-1-yl)methylidene]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C(C=C1)=CC=C1C(=O)N=C(N)N1CCCCCCC1 OSDITUJPDREPII-CLJLJLNGSA-N 0.000 claims 1
- DUBIPMHMELWMDP-DHIUTWEWSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-(1h-benzimidazol-2-ylamino)methylidene]benzamide Chemical compound C1=CC=C2NC(NC(N)=NC(=O)C3=CC=C(C=C3)C3=N[C@@H]4CCN(C)C[C@@H]4C=4C=C(C(=CC=43)OC)OCC)=NC2=C1 DUBIPMHMELWMDP-DHIUTWEWSA-N 0.000 claims 1
- AUVVMOHYFDVDJQ-VSGBNLITSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)methylidene]benzamide Chemical compound C1CC2=CC(OC)=C(OC)C=C2CN1C(N)=NC(=O)C(C=C1)=CC=C1C1=N[C@@H]2CCN(C)C[C@@H]2C2=C1C=C(OC)C(OCC)=C2 AUVVMOHYFDVDJQ-VSGBNLITSA-N 0.000 claims 1
- KYVKZRRUECDXCK-WOJBJXKFSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-(cyanoamino)methylidene]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C1=CC=C(C(=O)N=C(N)NC#N)C=C1 KYVKZRRUECDXCK-WOJBJXKFSA-N 0.000 claims 1
- NYFHYIHORPMRGI-XRKRLSELSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-(naphthalen-1-ylamino)methylidene]benzamide Chemical compound C1=CC=C2C(NC(N)=NC(=O)C3=CC=C(C=C3)C3=N[C@@H]4CCN(C)C[C@@H]4C=4C=C(C(=CC=43)OC)OCC)=CC=CC2=C1 NYFHYIHORPMRGI-XRKRLSELSA-N 0.000 claims 1
- ASFYKLUBNAMNGE-FQLXRVMXSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]methylidene]benzamide Chemical compound C1=C2OCOC2=CC(CN2CCN(CC2)C(N)=NC(=O)C2=CC=C(C=C2)C2=N[C@@H]3CCN(C)C[C@@H]3C=3C=C(C(=CC=32)OC)OCC)=C1 ASFYKLUBNAMNGE-FQLXRVMXSA-N 0.000 claims 1
- UKAOXXMANKNUNB-FQLXRVMXSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methylidene]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C(C=C1)=CC=C1C(=O)N=C(N)N(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 UKAOXXMANKNUNB-FQLXRVMXSA-N 0.000 claims 1
- YNKBHOPWFHOJGV-JWQCQUIFSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[amino-[bis(2-methoxyethyl)amino]methylidene]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C1=CC=C(C(=O)N=C(N)N(CCOC)CCOC)C=C1 YNKBHOPWFHOJGV-JWQCQUIFSA-N 0.000 claims 1
- NAMFPJABTYKEOL-JWQCQUIFSA-N 4-[(4ar,10bs)-9-ethoxy-8-methoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]-n-[n'-(2-morpholin-4-ylethyl)carbamimidoyl]benzamide Chemical compound N([C@@H]1CCN(C)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C(C=C1)=CC=C1C(=O)NC(N)=NCCN1CCOCC1 NAMFPJABTYKEOL-JWQCQUIFSA-N 0.000 claims 1
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Inverter Devices (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02018529.4 | 2002-08-17 | ||
| EP02018529 | 2002-08-17 | ||
| PCT/EP2003/008996 WO2004018465A2 (en) | 2002-08-17 | 2003-08-13 | Benzonaphthyridines with pde 3/4 inhibiting activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2495603A1 true CA2495603A1 (en) | 2004-03-04 |
Family
ID=31896838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002495603A Abandoned CA2495603A1 (en) | 2002-08-17 | 2003-08-13 | Benzonaphthyridines with pde 3/4 inhibiting activity |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20060113968A1 (enExample) |
| EP (1) | EP1581533A2 (enExample) |
| JP (1) | JP2005537313A (enExample) |
| AU (1) | AU2003263216A1 (enExample) |
| CA (1) | CA2495603A1 (enExample) |
| HR (1) | HRP20050227A2 (enExample) |
| IS (1) | IS7729A (enExample) |
| PL (1) | PL373598A1 (enExample) |
| RS (1) | RS20050117A (enExample) |
| WO (1) | WO2004018465A2 (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20050293A2 (en) | 2002-09-04 | 2006-07-31 | Altana Pharma Ag | Novel benzonaphthyridines |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| HRP20130828T1 (en) | 2004-03-03 | 2013-09-30 | Takeda Gmbh | Novel hydroxy-6-heroarylphenanthridines and their use as pde4 inhibitors |
| WO2005090345A1 (en) * | 2004-03-17 | 2005-09-29 | Altana Pharma Ag | Novel n- (alkoxyalkyl) carbamoyl - substituted 6-phenyl-benzonaphthyridine derivatives and their use as pde3/4 inhibitors |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| NZ560268A (en) | 2005-03-02 | 2010-12-24 | Nycomed Gmbh | Novel salts of 6-heterocyclyl substituted hexahydrophenanthridine derivatives |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| DE102005047551A1 (de) * | 2005-09-30 | 2007-04-12 | Siemens Ag | Erregereinrichtung für eine elektrische Maschine |
| JP5006330B2 (ja) | 2005-10-21 | 2012-08-22 | ノバルティス アーゲー | Ｉｌ１３に対するヒト抗体および治療的使用 |
| GB0526244D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| HRP20120494T1 (hr) | 2006-04-21 | 2012-08-31 | Novartis Ag | Derivati purina za uporabu kao agonista adenozin a2a receptora |
| KR20090073121A (ko) | 2006-09-29 | 2009-07-02 | 노파르티스 아게 | Ｐｉ3ｋ 지질 키나제 억제제로서의 피라졸로피리미딘 |
| US20100041662A1 (en) | 2006-10-30 | 2010-02-18 | Sandrine Ferrand | Heterocyclic compounds as antiinflammatory agents |
| TWI618544B (zh) | 2006-12-26 | 2018-03-21 | 藍瑟斯醫學影像公司 | 使心臟神經分布顯像之配位體 |
| CA2673803A1 (en) | 2007-01-10 | 2008-07-17 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| ES2361595T3 (es) | 2007-05-07 | 2011-06-20 | Novartis Ag | Compuestos orgánicos. |
| KR101578235B1 (ko) | 2007-12-10 | 2015-12-16 | 노파르티스 아게 | 유기 화합물 |
| WO2009087224A1 (en) | 2008-01-11 | 2009-07-16 | Novartis Ag | Pyrimidines as kinase inhibitors |
| AU2009256645A1 (en) | 2008-06-10 | 2009-12-17 | Novartis Ag | Pyrazine derivatives as epithelial sodium channel blockers |
| TW201031406A (en) | 2009-01-29 | 2010-09-01 | Novartis Ag | Substituted benzimidazoles for the treatment of astrocytomas |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| CN102573846B (zh) | 2009-08-17 | 2015-10-07 | 因特利凯公司 | 杂环化合物及其用途 |
| MX2012002179A (es) | 2009-08-20 | 2012-03-16 | Novartis Ag | Compuestos heterociclicos de oxima. |
| AU2010310449A1 (en) | 2009-10-22 | 2012-05-03 | Vertex Pharmaceuticals Incorporated | Compositions for treatment of cystic fibrosis and other chronic diseases |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| JP5992399B2 (ja) | 2010-05-11 | 2016-09-14 | ランセウス メディカル イメージング， インコーポレイテッド | 造影剤の合成および使用のための組成物、方法およびシステム |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| US9127000B2 (en) | 2011-02-23 | 2015-09-08 | Intellikine, LLC. | Heterocyclic compounds and uses thereof |
| JP5959541B2 (ja) | 2011-02-25 | 2016-08-02 | ノバルティス アーゲー | Ｔｒｋ阻害剤としてのピラゾロ［１，５−ａ］ピリジン |
| EP2549638A1 (de) * | 2011-07-19 | 2013-01-23 | AEG Power Solutions B.V. | Stromversorgungsanordnung für einen Reaktor zur Polysiliciumherstellung mit einem Frequenzumrichter |
| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| EP2755976B1 (en) | 2011-09-15 | 2018-07-18 | Novartis AG | 6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyridines as c-met tyrosine kinase inhibitors |
| US9056867B2 (en) | 2011-09-16 | 2015-06-16 | Novartis Ag | N-substituted heterocyclyl carboxamides |
| EP2755967B1 (en) | 2011-09-16 | 2015-10-21 | Novartis AG | Heterocyclic compounds for the treatment of cystic fibrosis |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| ES2894830T3 (es) | 2012-04-03 | 2022-02-16 | Novartis Ag | Productos combinados con inhibidores de tirosina·cinasa y su uso |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| CN105246482A (zh) | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| JP6404944B2 (ja) | 2014-04-24 | 2018-10-17 | ノバルティス アーゲー | ホスファチジルイノシトール３−キナーゼ阻害薬としてのピラジン誘導体 |
| EP3134397A1 (en) | 2014-04-24 | 2017-03-01 | Novartis AG | Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| EA201692140A1 (ru) | 2014-04-24 | 2017-04-28 | Новартис Аг | Производные аминопиридина в качестве ингибиторов фосфатидилинозитол 3-киназы |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| KR20170036037A (ko) | 2014-07-31 | 2017-03-31 | 노파르티스 아게 | 조합 요법 |
| WO2018069210A1 (en) | 2016-10-10 | 2018-04-19 | Takeda Gmbh | Tetrahydrofuro[3,4-c]isoquinolines as inhibitors of pde4 |
| EP3980121A1 (en) | 2019-06-10 | 2022-04-13 | Novartis AG | Pyridine and pyrazine derivative for the treatment of cf, copd, and bronchiectasis |
| CN114341132A (zh) | 2019-08-28 | 2022-04-12 | 诺华股份有限公司 | 经取代的1,3-苯基杂芳基衍生物及其在治疗疾病中的用途 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9027055D0 (en) * | 1990-12-13 | 1991-02-06 | Sandoz Ltd | Organic compounds |
| ATE234300T1 (de) * | 1996-11-11 | 2003-03-15 | Altana Pharma Ag | Benzonaphthyridine als bronchialtherapeutika |
| WO1998040382A1 (en) * | 1997-03-07 | 1998-09-17 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Novel tetrazoles |
| DE59904535D1 (de) * | 1998-05-05 | 2003-04-17 | Altana Pharma Ag | Neue Benzonaphtyridin-N-oxide |
| US6436952B1 (en) * | 1998-08-31 | 2002-08-20 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Benzonaphthyridine-N-oxides comprising a PDE3 and PDE4 inhibiting activity |
| US6924292B2 (en) * | 2000-03-23 | 2005-08-02 | Takeda Chemical Industries, Ltd. | Furoisoquinoline derivatives, process for producing the same and use thereof |
| PT1377574E (pt) * | 2001-02-21 | 2005-05-31 | Byk Gulden Lomberg Chem Fab | 6-fenilbenzonaftiridinas |
-
2003
- 2003-08-13 JP JP2004530142A patent/JP2005537313A/ja not_active Withdrawn
- 2003-08-13 WO PCT/EP2003/008996 patent/WO2004018465A2/en not_active Ceased
- 2003-08-13 US US10/524,638 patent/US20060113968A1/en not_active Abandoned
- 2003-08-13 HR HR20050227A patent/HRP20050227A2/hr not_active Application Discontinuation
- 2003-08-13 CA CA002495603A patent/CA2495603A1/en not_active Abandoned
- 2003-08-13 RS YUP-2005/0117A patent/RS20050117A/sr unknown
- 2003-08-13 AU AU2003263216A patent/AU2003263216A1/en not_active Abandoned
- 2003-08-13 EP EP03792314A patent/EP1581533A2/en not_active Withdrawn
- 2003-08-13 PL PL03373598A patent/PL373598A1/xx not_active Application Discontinuation
-
2005
- 2005-03-08 IS IS7729A patent/IS7729A/is unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RS20050117A (sr) | 2007-06-04 |
| HRP20050227A2 (en) | 2006-06-30 |
| WO2004018465A2 (en) | 2004-03-04 |
| WO2004018465A9 (en) | 2005-09-15 |
| JP2005537313A (ja) | 2005-12-08 |
| US20060113968A1 (en) | 2006-06-01 |
| PL373598A1 (en) | 2005-09-05 |
| EP1581533A2 (en) | 2005-10-05 |
| IS7729A (is) | 2005-03-08 |
| WO2004018465A3 (en) | 2004-05-27 |
| AU2003263216A1 (en) | 2004-03-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |