HRP20050083A2 - Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs - Google Patents
Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs Download PDFInfo
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- HRP20050083A2 HRP20050083A2 HR20050083A HRP20050083A HRP20050083A2 HR P20050083 A2 HRP20050083 A2 HR P20050083A2 HR 20050083 A HR20050083 A HR 20050083A HR P20050083 A HRP20050083 A HR P20050083A HR P20050083 A2 HRP20050083 A2 HR P20050083A2
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- Prior art keywords
- alkyl
- carbon atoms
- pyridylmethyl
- substituted
- halogen
- Prior art date
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- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 title claims description 184
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 title description 237
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 13
- 150000001448 anilines Chemical class 0.000 title description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 345
- -1 cyano, hydroxy Chemical group 0.000 claims description 304
- 125000004432 carbon atom Chemical group C* 0.000 claims description 297
- 229910052736 halogen Inorganic materials 0.000 claims description 244
- 150000001875 compounds Chemical class 0.000 claims description 231
- 150000002367 halogens Chemical class 0.000 claims description 230
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 167
- 238000000034 method Methods 0.000 claims description 151
- 125000003545 alkoxy group Chemical group 0.000 claims description 145
- 125000003118 aryl group Chemical group 0.000 claims description 134
- 125000004043 oxo group Chemical group O=* 0.000 claims description 113
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 104
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 92
- 239000000203 mixture Substances 0.000 claims description 88
- 125000004429 atom Chemical group 0.000 claims description 81
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 70
- 229920006395 saturated elastomer Polymers 0.000 claims description 68
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 62
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 47
- 125000003282 alkyl amino group Chemical group 0.000 claims description 45
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 41
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 40
- 125000002837 carbocyclic group Chemical group 0.000 claims description 38
- 229910052760 oxygen Inorganic materials 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 37
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 35
- 125000002252 acyl group Chemical group 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 34
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 34
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 33
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 33
- 125000004414 alkyl thio group Chemical group 0.000 claims description 33
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 32
- 208000026139 Memory disease Diseases 0.000 claims description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 24
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 21
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 20
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 20
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- 206010027175 memory impairment Diseases 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 15
- 201000000980 schizophrenia Diseases 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000005389 trialkylsiloxy group Chemical group 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- 208000027866 inflammatory disease Diseases 0.000 claims description 11
- QLRBNEZOQPLERN-UHFFFAOYSA-N (sulfonylamino)benzene Chemical compound O=S(=O)=NC1=CC=CC=C1 QLRBNEZOQPLERN-UHFFFAOYSA-N 0.000 claims description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 10
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 10
- 208000023105 Huntington disease Diseases 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 10
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 10
- 230000000172 allergic effect Effects 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- 208000000044 Amnesia Diseases 0.000 claims description 9
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 9
- 206010019196 Head injury Diseases 0.000 claims description 9
- 206010021143 Hypoxia Diseases 0.000 claims description 9
- 208000026935 allergic disease Diseases 0.000 claims description 9
- 230000019771 cognition Effects 0.000 claims description 9
- 230000007954 hypoxia Effects 0.000 claims description 9
- 208000023060 memory loss Diseases 0.000 claims description 9
- 208000031886 HIV Infections Diseases 0.000 claims description 8
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 8
- 206010039966 Senile dementia Diseases 0.000 claims description 8
- 201000004810 Vascular dementia Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 8
- 230000032683 aging Effects 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 230000002490 cerebral effect Effects 0.000 claims description 8
- 230000002255 enzymatic effect Effects 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 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 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 230000006984 memory degeneration Effects 0.000 claims description 6
- ZIZIJHBSNITYBE-UHFFFAOYSA-N 3-[3-hydroxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound C1=C(O)C(OC)=CC=C1N(C=1C=C(C=CC=1)C(O)=O)CC1=CC=CN=C1 ZIZIJHBSNITYBE-UHFFFAOYSA-N 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- WUPPXHSCTGNONT-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzamide Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(N)=O)C=C1OC1CCCC1 WUPPXHSCTGNONT-UHFFFAOYSA-N 0.000 claims description 4
- XQVMANRSBUNGSR-UHFFFAOYSA-N 4-[3-(cyclopropylmethoxy)-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=CC(=CC=2)C(O)=O)C=C1OCC1CC1 XQVMANRSBUNGSR-UHFFFAOYSA-N 0.000 claims description 4
- IKYOLUBQNJKMBC-UHFFFAOYSA-N 2-acetamido-5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(NC(C)=O)=CC=2)C(O)=O)C=C1OC1CCCC1 IKYOLUBQNJKMBC-UHFFFAOYSA-N 0.000 claims description 3
- GVESADABUIVATI-UHFFFAOYSA-N 2-chloro-4-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(Cl)C(C(O)=O)=CC=2)C=C1OC1CCCC1 GVESADABUIVATI-UHFFFAOYSA-N 0.000 claims description 3
- JBOHJDIOSKJSEP-UHFFFAOYSA-N 2-chloro-5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(Cl)=CC=2)C(O)=O)C=C1OC1CCCC1 JBOHJDIOSKJSEP-UHFFFAOYSA-N 0.000 claims description 3
- JOHMSZBFSOCBHW-UHFFFAOYSA-N 3-[3-(2-cyclopropylethoxy)-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OCCC1CC1 JOHMSZBFSOCBHW-UHFFFAOYSA-N 0.000 claims description 3
- YQMXJQLDUFDCSG-UHFFFAOYSA-N 3-[3-(cyclobutylmethoxy)-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OCC1CCC1 YQMXJQLDUFDCSG-UHFFFAOYSA-N 0.000 claims description 3
- BPAMXLJNRKSMEZ-UHFFFAOYSA-N 3-[3-cyclobutyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OC1CCC1 BPAMXLJNRKSMEZ-UHFFFAOYSA-N 0.000 claims description 3
- PVIZKCDYYHQHFS-UHFFFAOYSA-N 3-[3-cycloheptyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OC1CCCCCC1 PVIZKCDYYHQHFS-UHFFFAOYSA-N 0.000 claims description 3
- FKBXEXYECLAJEG-UHFFFAOYSA-N 3-[3-cyclohexyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OC1CCCCC1 FKBXEXYECLAJEG-UHFFFAOYSA-N 0.000 claims description 3
- ZQVJRONONNYCSU-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-(difluoromethoxy)-n-(pyridin-3-ylmethyl)anilino]-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(N(CC=2C=NC=CC=2)C=2C=C(OC3CCCC3)C(OC(F)F)=CC=2)=C1 ZQVJRONONNYCSU-UHFFFAOYSA-N 0.000 claims description 3
- OIOJVANAGFBYFG-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-5-fluorobenzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=C(F)C=2)C(O)=O)C=C1OC1CCCC1 OIOJVANAGFBYFG-UHFFFAOYSA-N 0.000 claims description 3
- GFAOXAVMWZPBOM-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(N(CC=2C=NC=CC=2)C=2C=C(OC3CCCC3)C(OC)=CC=2)=C1 GFAOXAVMWZPBOM-UHFFFAOYSA-N 0.000 claims description 3
- YJKRSUSXIRYJEJ-UHFFFAOYSA-N 3-[3-cyclopentyloxy-n-[(2,6-difluorophenyl)methyl]-4-methoxyanilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C(=CC=CC=2F)F)C=2C=C(C=CC=2)C(O)=O)C=C1OC1CCCC1 YJKRSUSXIRYJEJ-UHFFFAOYSA-N 0.000 claims description 3
- GHVNTTDGOXVIHP-UHFFFAOYSA-N 3-[3-cyclopentyloxy-n-[(5-fluoropyridin-3-yl)methyl]-4-methoxyanilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=C(F)C=NC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OC1CCCC1 GHVNTTDGOXVIHP-UHFFFAOYSA-N 0.000 claims description 3
- RVSHDISGIWENMA-UHFFFAOYSA-N 3-[4-methoxy-3-(2h-pyran-4-yloxy)-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OC1=CCOC=C1 RVSHDISGIWENMA-UHFFFAOYSA-N 0.000 claims description 3
- LLLNMSCNJYWDEY-UHFFFAOYSA-N 3-chloro-n-(3-cyclopentyloxy-4-methoxyphenyl)-n-(pyridin-3-ylmethyl)-4-(2h-tetrazol-5-yl)aniline Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(Cl)C(C3=NNN=N3)=CC=2)C=C1OC1CCCC1 LLLNMSCNJYWDEY-UHFFFAOYSA-N 0.000 claims description 3
- GAJOCFUTGRDBFY-UHFFFAOYSA-N 4-[3,4-dimethoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1N(C=1C=CC(=CC=1)C(O)=O)CC1=CC=CN=C1 GAJOCFUTGRDBFY-UHFFFAOYSA-N 0.000 claims description 3
- ONHDAUIJKHRUGL-UHFFFAOYSA-N 4-[3-cyclobutyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=CC(=CC=2)C(O)=O)C=C1OC1CCC1 ONHDAUIJKHRUGL-UHFFFAOYSA-N 0.000 claims description 3
- UTBGICCEGURIGQ-UHFFFAOYSA-N 4-[3-cyclohexyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=CC(=CC=2)C(O)=O)C=C1OC1CCCCC1 UTBGICCEGURIGQ-UHFFFAOYSA-N 0.000 claims description 3
- JWKWDLKITOJRJB-UHFFFAOYSA-N 4-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-fluorobenzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(F)C(C(O)=O)=CC=2)C=C1OC1CCCC1 JWKWDLKITOJRJB-UHFFFAOYSA-N 0.000 claims description 3
- HKYAIVSQNSOYRR-UHFFFAOYSA-N 4-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-methylbenzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C)C(C(O)=O)=CC=2)C=C1OC1CCCC1 HKYAIVSQNSOYRR-UHFFFAOYSA-N 0.000 claims description 3
- NSHPFJPSUOYGMY-UHFFFAOYSA-N 4-[3-cyclopentyloxy-4-methoxy-n-(pyridin-4-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=CN=CC=2)C=2C=CC(=CC=2)C(O)=O)C=C1OC1CCCC1 NSHPFJPSUOYGMY-UHFFFAOYSA-N 0.000 claims description 3
- DOGXBUWLYGJKNK-UHFFFAOYSA-N 4-[3-cyclopentyloxy-n-[(5-fluoropyridin-3-yl)methyl]-4-methoxyanilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=C(F)C=NC=2)C=2C=CC(=CC=2)C(O)=O)C=C1OC1CCCC1 DOGXBUWLYGJKNK-UHFFFAOYSA-N 0.000 claims description 3
- HZIWYCZYZJMOGR-UHFFFAOYSA-N 4-[3-ethoxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound C1=C(OC)C(OCC)=CC(N(CC=2C=NC=CC=2)C=2C=CC(=CC=2)C(O)=O)=C1 HZIWYCZYZJMOGR-UHFFFAOYSA-N 0.000 claims description 3
- LMQAGPUCDCQDLE-UHFFFAOYSA-N 4-[4-methoxy-3-propan-2-yloxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound C1=C(OC(C)C)C(OC)=CC=C1N(C=1C=CC(=CC=1)C(O)=O)CC1=CC=CN=C1 LMQAGPUCDCQDLE-UHFFFAOYSA-N 0.000 claims description 3
- JMJJYMSXMIJWNY-UHFFFAOYSA-N 5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-fluorobenzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(F)=CC=2)C(O)=O)C=C1OC1CCCC1 JMJJYMSXMIJWNY-UHFFFAOYSA-N 0.000 claims description 3
- PICQSMOKJUFJKD-UHFFFAOYSA-N 5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-methoxybenzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(OC)=CC=2)C(O)=O)C=C1OC1CCCC1 PICQSMOKJUFJKD-UHFFFAOYSA-N 0.000 claims description 3
- QMCMGKPINZXINN-UHFFFAOYSA-N 5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-methylbenzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(C)=CC=2)C(O)=O)C=C1OC1CCCC1 QMCMGKPINZXINN-UHFFFAOYSA-N 0.000 claims description 3
- XHJXUEDZZHWKIT-UHFFFAOYSA-N methyl 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoate Chemical compound COC(=O)C1=CC=CC(N(CC=2C=NC=CC=2)C=2C=C(OC3CCCC3)C(OC)=CC=2)=C1 XHJXUEDZZHWKIT-UHFFFAOYSA-N 0.000 claims description 3
- SRUNVORPVAFPQR-UHFFFAOYSA-N n-cyclohexyl-3-cyclopentyloxy-4-methoxyaniline Chemical compound C1=C(OC2CCCC2)C(OC)=CC=C1NC1CCCCC1 SRUNVORPVAFPQR-UHFFFAOYSA-N 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- ONQYIIVOAHLMJC-OZAIVSQSSA-N 2-chloro-5-[2-[(3R)-4-methoxyoxolan-3-yl]oxy-N-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1[C@@H](COC1)OC1=C(N(CC=2C=NC=CC=2)C2=CC(=C(C=C2)Cl)C(=O)O)C=CC=C1 ONQYIIVOAHLMJC-OZAIVSQSSA-N 0.000 claims description 2
- WWYNKQTWLCQREJ-OZAIVSQSSA-N 3-[2-[(3R)-4-methoxyoxolan-3-yl]oxy-N-(pyridin-4-ylmethyl)anilino]benzoic acid Chemical compound COC1[C@@H](COC1)OC1=C(N(CC2=CC=NC=C2)C2=CC(=CC=C2)C(=O)O)C=CC=C1 WWYNKQTWLCQREJ-OZAIVSQSSA-N 0.000 claims description 2
- CDUIOUDOCKFVCV-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-n-(2-methylphenyl)sulfonylbenzamide Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)C=C1OC1CCCC1 CDUIOUDOCKFVCV-UHFFFAOYSA-N 0.000 claims description 2
- LBKFHDGISJQJFO-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-n-methylsulfonylbenzamide Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(=O)NS(C)(=O)=O)C=C1OC1CCCC1 LBKFHDGISJQJFO-UHFFFAOYSA-N 0.000 claims description 2
- WOJYWTBANNNKLV-UHFFFAOYSA-N 3-[3-cyclopentyloxy-n-[(5-fluoropyridin-3-yl)methyl]-4-methoxyanilino]-n-(4-fluorophenyl)sulfonylbenzamide Chemical compound COC1=CC=C(N(CC=2C=C(F)C=NC=2)C=2C=C(C=CC=2)C(=O)NS(=O)(=O)C=2C=CC(F)=CC=2)C=C1OC1CCCC1 WOJYWTBANNNKLV-UHFFFAOYSA-N 0.000 claims description 2
- GBOMDBPTDBFTII-UHFFFAOYSA-N 3-cyclopentyloxy-4-methoxy-n-(3-morpholin-4-ylsulfonylphenyl)-n-(pyridin-3-ylmethyl)aniline Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)S(=O)(=O)N2CCOCC2)C=C1OC1CCCC1 GBOMDBPTDBFTII-UHFFFAOYSA-N 0.000 claims description 2
- PHMBUKGEPZESLG-UHFFFAOYSA-N 3-cyclopentyloxy-4-methoxy-n-(4-morpholin-4-ylsulfonylphenyl)-n-(pyridin-3-ylmethyl)aniline Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)C=C1OC1CCCC1 PHMBUKGEPZESLG-UHFFFAOYSA-N 0.000 claims description 2
- PHBRPGFKBJGQPE-UHFFFAOYSA-N 3-cyclopentyloxy-4-methoxy-n-[3-(4-methylpiperazin-1-yl)sulfonylphenyl]-n-(pyridin-3-ylmethyl)aniline Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1OC1CCCC1 PHBRPGFKBJGQPE-UHFFFAOYSA-N 0.000 claims description 2
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- QPZVBTVTPZSAPL-UHFFFAOYSA-N tert-butyl 3-[3-ethoxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoate Chemical compound C1=C(OC)C(OCC)=CC(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(=O)OC(C)(C)C)=C1 QPZVBTVTPZSAPL-UHFFFAOYSA-N 0.000 description 1
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- RRRMWDRCBKKNAL-UHFFFAOYSA-N tert-butyl 4-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-fluorobenzoate Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(F)C(C(=O)OC(C)(C)C)=CC=2)C=C1OC1CCCC1 RRRMWDRCBKKNAL-UHFFFAOYSA-N 0.000 description 1
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- QQRGWEGLTDGINU-UHFFFAOYSA-N tert-butyl 4-[3-cyclopentyloxy-4-methoxy-n-(pyridin-4-ylmethyl)anilino]benzoate Chemical compound COC1=CC=C(N(CC=2C=CN=CC=2)C=2C=CC(=CC=2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 QQRGWEGLTDGINU-UHFFFAOYSA-N 0.000 description 1
- QBKGCLWVZGDHEC-UHFFFAOYSA-N tert-butyl 4-[3-cyclopentyloxy-n-[(5-fluoropyridin-3-yl)methyl]-4-methoxyanilino]benzoate Chemical compound COC1=CC=C(N(CC=2C=C(F)C=NC=2)C=2C=CC(=CC=2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 QBKGCLWVZGDHEC-UHFFFAOYSA-N 0.000 description 1
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- OTZJLXISKPTOJH-UHFFFAOYSA-N tert-butyl 4-[3-hydroxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoate Chemical compound C1=C(O)C(OC)=CC=C1N(C=1C=CC(=CC=1)C(=O)OC(C)(C)C)CC1=CC=CN=C1 OTZJLXISKPTOJH-UHFFFAOYSA-N 0.000 description 1
- GSWWWJZOMIGYOK-UHFFFAOYSA-N tert-butyl 4-[4-methoxy-3-propan-2-yloxy-n-(pyridin-3-ylmethyl)anilino]benzoate Chemical compound C1=C(OC(C)C)C(OC)=CC=C1N(C=1C=CC(=CC=1)C(=O)OC(C)(C)C)CC1=CC=CN=C1 GSWWWJZOMIGYOK-UHFFFAOYSA-N 0.000 description 1
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- KNKIQBLPOBBXTJ-UHFFFAOYSA-N tert-butyl 5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-methylbenzoate Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(C)=CC=2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 KNKIQBLPOBBXTJ-UHFFFAOYSA-N 0.000 description 1
- DXMWZHHOIWMGMA-UHFFFAOYSA-N tert-butyl 5-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]-2-nitrobenzoate Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C(=CC=2)[N+]([O-])=O)C(=O)OC(C)(C)C)C=C1OC1CCCC1 DXMWZHHOIWMGMA-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- ZZKQYNAFDWPSPY-UHFFFAOYSA-N tert-butyl-(2-methoxy-5-nitrophenoxy)-dimethylsilane Chemical compound COC1=CC=C([N+]([O-])=O)C=C1O[Si](C)(C)C(C)(C)C ZZKQYNAFDWPSPY-UHFFFAOYSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
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- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000001806 thionaphthenyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
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- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tri(ortho-tolyl)phosphine Substances CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 125000002348 vinylic group Chemical group 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having 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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- C07—ORGANIC CHEMISTRY
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
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- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/88—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to a carbon atom of a ring other than a six-membered aromatic ring
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/92—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the nitrogen atom of at least one of the amino groups being further bound to a carbon atom of a six-membered aromatic ring
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- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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US39672502P | 2002-07-19 | 2002-07-19 | |
PCT/US2003/022543 WO2004009552A1 (en) | 2002-07-19 | 2003-07-21 | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
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US (1) | US7405230B2 (ja) |
EP (1) | EP1539697A1 (ja) |
JP (1) | JP2006504656A (ja) |
CN (1) | CN1688545A (ja) |
AU (1) | AU2003256616B2 (ja) |
BR (1) | BR0312999A (ja) |
CA (1) | CA2492907A1 (ja) |
CO (1) | CO5680399A2 (ja) |
HR (1) | HRP20050083A2 (ja) |
IL (1) | IL166163A0 (ja) |
MX (1) | MXPA05000827A (ja) |
NO (1) | NO20050870L (ja) |
NZ (1) | NZ537724A (ja) |
RU (1) | RU2368604C2 (ja) |
WO (1) | WO2004009552A1 (ja) |
ZA (1) | ZA200500488B (ja) |
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-
2003
- 2003-07-21 AU AU2003256616A patent/AU2003256616B2/en not_active Ceased
- 2003-07-21 CN CNA038223546A patent/CN1688545A/zh active Pending
- 2003-07-21 EP EP03765748A patent/EP1539697A1/en not_active Withdrawn
- 2003-07-21 BR BR0312999-3A patent/BR0312999A/pt not_active IP Right Cessation
- 2003-07-21 MX MXPA05000827A patent/MXPA05000827A/es active IP Right Grant
- 2003-07-21 WO PCT/US2003/022543 patent/WO2004009552A1/en active Application Filing
- 2003-07-21 CA CA002492907A patent/CA2492907A1/en not_active Abandoned
- 2003-07-21 NZ NZ537724A patent/NZ537724A/en unknown
- 2003-07-21 RU RU2005104819/04A patent/RU2368604C2/ru not_active IP Right Cessation
- 2003-07-21 US US10/622,833 patent/US7405230B2/en not_active Expired - Fee Related
- 2003-07-21 JP JP2004523585A patent/JP2006504656A/ja active Pending
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2005
- 2005-01-05 IL IL16616305A patent/IL166163A0/xx unknown
- 2005-01-18 ZA ZA200500488A patent/ZA200500488B/xx unknown
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- 2005-01-26 HR HR20050083A patent/HRP20050083A2/hr not_active Application Discontinuation
- 2005-02-18 NO NO20050870A patent/NO20050870L/no unknown
Also Published As
Publication number | Publication date |
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CN1688545A (zh) | 2005-10-26 |
AU2003256616B2 (en) | 2009-08-27 |
CO5680399A2 (es) | 2006-09-29 |
RU2368604C2 (ru) | 2009-09-27 |
RU2005104819A (ru) | 2005-10-10 |
BR0312999A (pt) | 2005-06-07 |
EP1539697A1 (en) | 2005-06-15 |
IL166163A0 (en) | 2006-01-15 |
US20050119225A1 (en) | 2005-06-02 |
JP2006504656A (ja) | 2006-02-09 |
CA2492907A1 (en) | 2004-01-29 |
NZ537724A (en) | 2006-10-27 |
WO2004009552A1 (en) | 2004-01-29 |
ZA200500488B (ja) | 2006-06-28 |
MXPA05000827A (es) | 2005-08-29 |
NO20050870L (no) | 2005-03-31 |
US7405230B2 (en) | 2008-07-29 |
AU2003256616A1 (en) | 2004-02-09 |
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