AU2002303078B2 - Aniline derivatives useful as phosphodiesterase 4 inhibitors - Google Patents
Aniline derivatives useful as phosphodiesterase 4 inhibitors Download PDFInfo
- Publication number
- AU2002303078B2 AU2002303078B2 AU2002303078A AU2002303078A AU2002303078B2 AU 2002303078 B2 AU2002303078 B2 AU 2002303078B2 AU 2002303078 A AU2002303078 A AU 2002303078A AU 2002303078 A AU2002303078 A AU 2002303078A AU 2002303078 B2 AU2002303078 B2 AU 2002303078B2
- Authority
- AU
- Australia
- Prior art keywords
- pyridylmethyl
- methoxy
- cyclopentyloxy
- diphenylamine
- substituted
- 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.)
- Ceased
Links
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 18
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 title 1
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims description 483
- -1 cyano, hydroxy Chemical group 0.000 claims description 394
- 125000000217 alkyl group Chemical group 0.000 claims description 285
- 229940035422 diphenylamine Drugs 0.000 claims description 241
- 125000004432 carbon atom Chemical group C* 0.000 claims description 230
- 150000001875 compounds Chemical class 0.000 claims description 220
- 229910052736 halogen Inorganic materials 0.000 claims description 210
- 150000002367 halogens Chemical class 0.000 claims description 202
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 155
- 125000003545 alkoxy group Chemical group 0.000 claims description 127
- 125000004043 oxo group Chemical group O=* 0.000 claims description 109
- 125000006413 ring segment Chemical group 0.000 claims description 99
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 96
- 125000003118 aryl group Chemical group 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 86
- 239000000203 mixture Substances 0.000 claims description 85
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 72
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- 239000002253 acid Substances 0.000 claims description 64
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 57
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 56
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 54
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- 125000003282 alkyl amino group Chemical group 0.000 claims description 42
- 229920006395 saturated elastomer Polymers 0.000 claims description 41
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 37
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000002837 carbocyclic group Chemical group 0.000 claims description 33
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 32
- 125000002252 acyl group Chemical group 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 30
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 29
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 29
- 125000004414 alkyl thio group Chemical group 0.000 claims description 29
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 26
- 125000004434 sulfur atom Chemical group 0.000 claims description 26
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 25
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 24
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 24
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 24
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 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 19
- 150000001412 amines Chemical class 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
- 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 16
- 206010027175 memory impairment Diseases 0.000 claims description 16
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000005389 trialkylsiloxy group Chemical group 0.000 claims description 13
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 11
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 10
- 230000015654 memory Effects 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- PNIUJOQYAGLPHM-UHFFFAOYSA-N 3-[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=CC=2)C(O)=O)C=C1OC1CCCC1 PNIUJOQYAGLPHM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 230000000172 allergic effect Effects 0.000 claims description 5
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- 230000019771 cognition Effects 0.000 claims description 5
- 230000007423 decrease Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- LLJRXVHJOJRCSM-UHFFFAOYSA-N 3-pyridin-4-yl-1H-indole Chemical group C=1NC2=CC=CC=C2C=1C1=CC=NC=C1 LLJRXVHJOJRCSM-UHFFFAOYSA-N 0.000 claims description 4
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- QDAUEZSAGQJRSN-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-(difluoromethoxy)-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC(N(CC=2C=NC=CC=2)C=2C=C(OC3CCCC3)C(OC(F)F)=CC=2)=C1 QDAUEZSAGQJRSN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- PFNVGWKABOYUIG-UHFFFAOYSA-N 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=CC(=CC=2)C(O)=O)C=C1OC1CCCC1 PFNVGWKABOYUIG-UHFFFAOYSA-N 0.000 claims description 3
- 102000009346 Adenosine receptors Human genes 0.000 claims description 3
- 108050000203 Adenosine receptors Proteins 0.000 claims description 3
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 3
- 206010019196 Head injury Diseases 0.000 claims description 3
- 206010021143 Hypoxia Diseases 0.000 claims description 3
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims description 3
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 239000000480 calcium channel blocker Substances 0.000 claims description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- DCWIRBQULCICSN-UHFFFAOYSA-N n-[3-cyclopentyloxy-4-(difluoromethoxy)phenyl]-n-(pyridin-3-ylmethyl)pyridin-3-amine Chemical compound FC(F)OC1=CC=C(N(CC=2C=NC=CC=2)C=2C=NC=CC=2)C=C1OC1CCCC1 DCWIRBQULCICSN-UHFFFAOYSA-N 0.000 claims description 3
- KLXOLDSVEVCINI-UHFFFAOYSA-N n-[[4-methoxy-3-(2-phenoxyethoxy)-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound COC1=CC=NCC1(OCCOC=1C=CC=CC=1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 KLXOLDSVEVCINI-UHFFFAOYSA-N 0.000 claims description 3
- BOIVZFFQBGEXFX-UHFFFAOYSA-N n-[[4-methoxy-3-(2-pyridin-2-ylethoxy)-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound COC1=CC=NCC1(OCCC=1N=CC=CC=1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 BOIVZFFQBGEXFX-UHFFFAOYSA-N 0.000 claims description 3
- 239000008177 pharmaceutical agent Substances 0.000 claims description 3
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
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- 230000007278 cognition impairment Effects 0.000 claims description 2
- LEHYXDMZGBGISK-UHFFFAOYSA-N n-(3-cyclopentyloxy-4-methoxyphenyl)-n-(pyridin-3-ylmethyl)isoquinolin-4-amine Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C3=CC=CC=C3C=NC=2)C=C1OC1CCCC1 LEHYXDMZGBGISK-UHFFFAOYSA-N 0.000 claims description 2
- VGTXHUFPGAREKA-UHFFFAOYSA-N n-(3-cyclopentyloxy-4-methoxyphenyl)-n-(pyridin-3-ylmethyl)pyridin-2-amine Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2N=CC=CC=2)C=C1OC1CCCC1 VGTXHUFPGAREKA-UHFFFAOYSA-N 0.000 claims description 2
- WZWGSXNVMJZJQG-UHFFFAOYSA-N n-(3-cyclopentyloxy-4-methoxyphenyl)-n-(pyridin-3-ylmethyl)pyridin-3-amine Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=NC=CC=2)C=C1OC1CCCC1 WZWGSXNVMJZJQG-UHFFFAOYSA-N 0.000 claims description 2
- OUMUNOWUXDBYMX-UHFFFAOYSA-N n-[[3-(cyclopropylmethoxy)-4-(difluoromethoxy)-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound FC(F)OC1=CC=NCC1(OCC1CC1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 OUMUNOWUXDBYMX-UHFFFAOYSA-N 0.000 claims description 2
- XWVICXGHYZVQSD-UHFFFAOYSA-N n-[[3-(cyclopropylmethoxy)-4-methoxy-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound COC1=CC=NCC1(OCC1CC1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 XWVICXGHYZVQSD-UHFFFAOYSA-N 0.000 claims description 2
- AWSQSUXLWVZOFC-UHFFFAOYSA-N n-[[3-[2-(4-chlorophenyl)ethenoxy]-4-methoxy-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound COC1=CC=NCC1(OC=CC=1C=CC(Cl)=CC=1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 AWSQSUXLWVZOFC-UHFFFAOYSA-N 0.000 claims description 2
- JXVLOHDJDYJPIM-UHFFFAOYSA-N n-[[3-cyclopentyloxy-4-(difluoromethoxy)-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound FC(F)OC1=CC=NCC1(OC1CCCC1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 JXVLOHDJDYJPIM-UHFFFAOYSA-N 0.000 claims description 2
- UCIWLVLLCTUEAB-UHFFFAOYSA-N n-[[4-methoxy-3-(2-methoxyethoxy)-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound C=1C=CC=CC=1N(C=1C=CC=CC=1)CC1(OCCOC)CN=CC=C1OC UCIWLVLLCTUEAB-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 8
- XXUJMEYKYHETBZ-UHFFFAOYSA-N ethyl 4-nitrophenyl ethylphosphonate Chemical compound CCOP(=O)(CC)OC1=CC=C([N+]([O-])=O)C=C1 XXUJMEYKYHETBZ-UHFFFAOYSA-N 0.000 claims 3
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 3
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 claims 2
- WNAODSRZKOTLRD-UHFFFAOYSA-N 3-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC(N(CC=2C=NC=CC=2)C=2C=C(OCC3CC3)C(OC(F)F)=CC=2)=C1 WNAODSRZKOTLRD-UHFFFAOYSA-N 0.000 claims 2
- VTFYMSNCTVOXOQ-UHFFFAOYSA-N 3-[4-methoxy-3-(oxolan-3-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=C1OC1CCOC1 VTFYMSNCTVOXOQ-UHFFFAOYSA-N 0.000 claims 2
- 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 2
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- RULLGLRZJAUWJC-UHFFFAOYSA-N 3-[3-(2,3-dihydro-1h-inden-2-yloxy)-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound C1=C(OC2CC3=CC=CC=C3C2)C(OC)=CC=C1N(C=1C=C(C=CC=1)C(O)=O)CC1=CC=CN=C1 RULLGLRZJAUWJC-UHFFFAOYSA-N 0.000 claims 1
- GXVCOVKPAQZYDG-UHFFFAOYSA-N 3-[4-methoxy-3-(2-pyridin-2-ylethoxy)-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=C1OCCC1=CC=CC=N1 GXVCOVKPAQZYDG-UHFFFAOYSA-N 0.000 claims 1
- JRJOWCAFOMTANO-UHFFFAOYSA-N 4-methoxy-3-[(n-phenylanilino)methyl]-2h-pyridin-3-ol Chemical compound COC1=CC=NCC1(O)CN(C=1C=CC=CC=1)C1=CC=CC=C1 JRJOWCAFOMTANO-UHFFFAOYSA-N 0.000 claims 1
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- LKEMHOKFBVYBFR-VQCQRNETSA-N N-[2-[(3R)-4-(difluoromethoxy)oxolan-3-yl]oxyphenyl]-N-(pyridin-3-ylmethyl)pyridin-3-amine Chemical compound FC(OC1[C@@H](COC1)OC1=C(C=CC=C1)N(CC=1C=NC=CC=1)C=1C=NC=CC=1)F LKEMHOKFBVYBFR-VQCQRNETSA-N 0.000 claims 1
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- XUBZIFGHZVFJEN-UHFFFAOYSA-N ethyl 3-[3-hydroxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoate Chemical compound CCOC(=O)C1=CC=CC(N(CC=2C=NC=CC=2)C=2C=C(O)C(OC)=CC=2)=C1 XUBZIFGHZVFJEN-UHFFFAOYSA-N 0.000 claims 1
- OSNHRDBNKUEDPF-UHFFFAOYSA-N n-(3-cyclopentyloxy-4-methoxyphenyl)-n-(pyridin-3-ylmethyl)pyrimidin-5-amine Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=NC=NC=2)C=C1OC1CCCC1 OSNHRDBNKUEDPF-UHFFFAOYSA-N 0.000 claims 1
- KMMWYQNGITYSFV-UHFFFAOYSA-N n-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-n-(pyridin-3-ylmethyl)pyridin-3-amine Chemical compound FC(F)OC1=CC=C(N(CC=2C=NC=CC=2)C=2C=NC=CC=2)C=C1OCC1CC1 KMMWYQNGITYSFV-UHFFFAOYSA-N 0.000 claims 1
- NHUAZXDSSJLSSR-UHFFFAOYSA-N n-[[3,4-bis(difluoromethoxy)-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound FC(F)OC1=CC=NCC1(OC(F)F)CN(C=1C=CC=CC=1)C1=CC=CC=C1 NHUAZXDSSJLSSR-UHFFFAOYSA-N 0.000 claims 1
- QVHODOMCMPUSNN-UHFFFAOYSA-N n-[[3-(2,3-dihydro-1h-inden-1-yloxy)-4-methoxy-2h-pyridin-3-yl]methyl]-n-phenylaniline Chemical compound COC1=CC=NCC1(OC1C2=CC=CC=C2CC1)CN(C=1C=CC=CC=1)C1=CC=CC=C1 QVHODOMCMPUSNN-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D213/04—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D213/73—Unsubstituted amino or imino radicals
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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
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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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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C217/92—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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- 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
- C07D213/04—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- 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
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26265101P | 2001-01-22 | 2001-01-22 | |
US60/262,651 | 2001-01-22 | ||
US26719601P | 2001-02-08 | 2001-02-08 | |
US60/267,196 | 2001-02-08 | ||
US30614001P | 2001-07-19 | 2001-07-19 | |
US60/306,140 | 2001-07-19 | ||
PCT/US2002/001508 WO2002074726A2 (en) | 2001-01-22 | 2002-01-22 | Aniline derivatives useful as phosphodiesterase 4 inhibitors |
Publications (2)
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AU2002303078A1 AU2002303078A1 (en) | 2003-03-27 |
AU2002303078B2 true AU2002303078B2 (en) | 2007-08-30 |
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Application Number | Title | Priority Date | Filing Date |
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AU2002303078A Ceased AU2002303078B2 (en) | 2001-01-22 | 2002-01-22 | Aniline derivatives useful as phosphodiesterase 4 inhibitors |
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EP (1) | EP1353907A2 (sh) |
JP (1) | JP4223287B2 (sh) |
KR (1) | KR100856622B1 (sh) |
CN (1) | CN100378075C (sh) |
AU (1) | AU2002303078B2 (sh) |
BG (1) | BG108003A (sh) |
BR (1) | BR0206943A (sh) |
CA (1) | CA2435847A1 (sh) |
CL (1) | CL2004001165A1 (sh) |
CZ (1) | CZ20031986A3 (sh) |
EE (1) | EE05362B1 (sh) |
HK (1) | HK1066215A1 (sh) |
HR (1) | HRP20030662A2 (sh) |
HU (1) | HUP0302793A3 (sh) |
IL (1) | IL156958A0 (sh) |
MA (1) | MA25996A1 (sh) |
MX (1) | MXPA03006519A (sh) |
NO (1) | NO329548B1 (sh) |
NZ (1) | NZ527081A (sh) |
PL (1) | PL373301A1 (sh) |
SK (1) | SK9152003A3 (sh) |
WO (1) | WO2002074726A2 (sh) |
YU (1) | YU57603A (sh) |
ZA (1) | ZA200305623B (sh) |
Cited By (1)
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AU2003256616B2 (en) * | 2002-07-19 | 2009-08-27 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs |
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US7153871B2 (en) | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
ES2328795T3 (es) * | 2001-02-14 | 2009-11-18 | Karo Bio Ab | Moduladores del receptor glucocorticoide. |
CN100381425C (zh) | 2002-07-19 | 2008-04-16 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的6-氨基-1h-吲唑及其药物组合物和用途 |
CN100513397C (zh) * | 2002-11-19 | 2009-07-15 | 记忆药物公司 | 磷酸二酯酶4抑制剂 |
WO2004047836A1 (en) * | 2002-11-22 | 2004-06-10 | Merck Frosst Canada & Co. | Use of phosphodiesterase-4 inhibitors as enhancers of cognition |
DK1578740T3 (da) * | 2002-12-27 | 2007-07-30 | Lundbeck & Co As H | 1,2,4-triaminobenzenderivater, der er egnede til behandling af lidelser i centralnervesystemet |
FR2856595B1 (fr) * | 2003-06-27 | 2008-05-30 | Exonhit Therapeutics Sa | Methodes et compositions pour le traitement de deficits cognitifs. |
MXPA06002521A (es) | 2003-09-05 | 2006-06-20 | Altana Pharma Ag | Uso de inhibidores de pde4 para el tratamiento de diabetes mellitus. |
MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
RU2392278C2 (ru) | 2004-07-15 | 2010-06-20 | Джапан Тобакко Инк. | Конденсированное производное бензамида и ингибитор активности подтипа 1 рецептора ваниллоида (vr1) |
CA2585210A1 (en) * | 2004-10-28 | 2006-05-11 | Merck & Co., Inc. | Pyrimidine and quinoline potentiators of metabotropic glutamate receptors |
BRPI0609371A2 (pt) | 2005-03-08 | 2010-03-30 | Nycomed Gmbh | usos de roflumilast na produção de composições farmacêuticas para o tratamento de diabetes mellitus |
EP1888528A2 (en) * | 2005-06-10 | 2008-02-20 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
AR057455A1 (es) * | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
US7906508B2 (en) | 2005-12-28 | 2011-03-15 | Japan Tobacco Inc. | 3,4-dihydrobenzoxazine compounds and inhibitors of vanilloid receptor subtype 1 (VRI) activity |
EP2121633A2 (en) | 2007-02-12 | 2009-11-25 | Merck & Co., Inc. | Piperazine derivatives for treatment of ad and related conditions |
EP2110375A1 (en) | 2008-04-14 | 2009-10-21 | CHIESI FARMACEUTICI S.p.A. | Phosphodiesterase-4 inhibitors belonging to the tertiary amine class |
US8461389B2 (en) | 2008-04-18 | 2013-06-11 | University College Dublin, National University Of Ireland, Dublin | Psycho-pharmaceuticals |
WO2010041449A1 (ja) * | 2008-10-09 | 2010-04-15 | 国立大学法人 岡山大学 | Rxr作動性物質を有効成分とする抗アレルギー剤 |
US10253020B2 (en) | 2009-06-12 | 2019-04-09 | Abivax | Compounds for preventing, inhibiting, or treating cancer, AIDS and/or premature aging |
MX2019008390A (es) * | 2009-06-12 | 2019-09-09 | Abivax | Compuestos utiles para tratar cancer. |
RU2567752C2 (ru) | 2009-06-12 | 2015-11-10 | Абивакс | Соединения, пригодные для лечения рака |
WO2011099305A1 (en) | 2010-02-12 | 2011-08-18 | Raqualia Pharma Inc. | 5-ht4 receptor agonists for the treatment of dementia |
JP6124351B2 (ja) | 2012-02-09 | 2017-05-10 | 塩野義製薬株式会社 | 複素環および炭素環誘導体 |
CN102603676B (zh) * | 2012-02-20 | 2014-02-12 | 徐江平 | 一种能避免呕吐反应的磷酸二酯酶4抑制剂 |
CA2859842C (en) * | 2012-03-14 | 2016-11-08 | Sinochem Corporation | Substitute diphenylamine compounds use thereof as antitumor agents |
EP2757161A1 (en) | 2013-01-17 | 2014-07-23 | Splicos | miRNA-124 as a biomarker of viral infection |
ES2898385T3 (es) | 2013-07-05 | 2022-03-07 | Abivax | Compuestos bicíclicos útiles para el tratamiento de enfermedades causadas por retrovirus |
TW201540301A (zh) | 2013-08-16 | 2015-11-01 | Takeda Gmbh | 以pde4抑制劑治療認知損傷 |
EP2974729A1 (en) | 2014-07-17 | 2016-01-20 | Abivax | Quinoline derivatives for use in the treatment of inflammatory diseases |
EP3669873A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Quinoline derivatives for use ine the traeatment of inflammation diseases |
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WO1996021435A1 (en) * | 1995-01-10 | 1996-07-18 | Euro-Celtique, S.A. | Compounds for and method of inhibiting phosphodiesterase iv |
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EP0700389A1 (en) | 1993-05-27 | 1996-03-13 | Smithkline Beecham Laboratoires Pharmaceutiques | Anti-arrhythmic n-substituted 3-benzazepines or isoquinolines |
JPH07206789A (ja) * | 1993-09-01 | 1995-08-08 | Taisho Pharmaceut Co Ltd | コンブレタスタチン類縁化合物 |
FR2729142A1 (fr) * | 1995-01-06 | 1996-07-12 | Smithkline Beecham Lab | Nouvelles amines heterocycliques, leur procede de preparation et leur utilisation en tant que medicaments et notamment en tant qu'agents anti-arythmiques |
CA2295106C (en) * | 1997-06-24 | 2007-03-13 | Nikken Chemicals Co., Ltd. | 3-anilino-2-cycloalkenone derivatives |
MXPA01011832A (es) * | 1999-05-21 | 2002-06-21 | Squibb Bristol Myers Co | Inhibidores de cinasas, de pirrolotriazina. |
ES2254077T3 (es) * | 1999-12-18 | 2006-06-16 | Wella Aktiengesellschaft | Derivados 2-aminoalquil-1,4-diaminobenceno y su utilizacion para el teñido de fibras. |
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2002
- 2002-01-22 NZ NZ527081A patent/NZ527081A/xx unknown
- 2002-01-22 BR BR0206943-1A patent/BR0206943A/pt not_active Application Discontinuation
- 2002-01-22 EP EP02731078A patent/EP1353907A2/en not_active Withdrawn
- 2002-01-22 CZ CZ20031986A patent/CZ20031986A3/cs unknown
- 2002-01-22 PL PL02373301A patent/PL373301A1/xx not_active Application Discontinuation
- 2002-01-22 JP JP2002573735A patent/JP4223287B2/ja not_active Expired - Fee Related
- 2002-01-22 AU AU2002303078A patent/AU2002303078B2/en not_active Ceased
- 2002-01-22 WO PCT/US2002/001508 patent/WO2002074726A2/en active Application Filing
- 2002-01-22 KR KR1020037009624A patent/KR100856622B1/ko not_active IP Right Cessation
- 2002-01-22 HU HU0302793A patent/HUP0302793A3/hu unknown
- 2002-01-22 EE EEP200300347A patent/EE05362B1/xx not_active IP Right Cessation
- 2002-01-22 YU YU57603A patent/YU57603A/sh unknown
- 2002-01-22 CA CA002435847A patent/CA2435847A1/en not_active Abandoned
- 2002-01-22 IL IL15695802A patent/IL156958A0/xx unknown
- 2002-01-22 SK SK915-2003A patent/SK9152003A3/sk unknown
- 2002-01-22 CN CNB028070100A patent/CN100378075C/zh not_active Expired - Fee Related
- 2002-01-22 MX MXPA03006519A patent/MXPA03006519A/es active IP Right Grant
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2003
- 2003-07-18 BG BG108003A patent/BG108003A/bg unknown
- 2003-07-21 ZA ZA2003/05623A patent/ZA200305623B/en unknown
- 2003-07-21 NO NO20033288A patent/NO329548B1/no not_active IP Right Cessation
- 2003-07-22 MA MA27246A patent/MA25996A1/fr unknown
- 2003-08-20 HR HR20030662A patent/HRP20030662A2/hr not_active Application Discontinuation
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2004
- 2004-05-20 CL CL200401165A patent/CL2004001165A1/es unknown
- 2004-11-17 HK HK04109061A patent/HK1066215A1/xx not_active IP Right Cessation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1996021435A1 (en) * | 1995-01-10 | 1996-07-18 | Euro-Celtique, S.A. | Compounds for and method of inhibiting phosphodiesterase iv |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003256616B2 (en) * | 2002-07-19 | 2009-08-27 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs |
Also Published As
Publication number | Publication date |
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CN1498211A (zh) | 2004-05-19 |
HK1066215A1 (en) | 2005-03-18 |
CL2004001165A1 (es) | 2005-04-15 |
NO329548B1 (no) | 2010-11-08 |
CN100378075C (zh) | 2008-04-02 |
ZA200305623B (en) | 2005-01-26 |
KR100856622B1 (ko) | 2008-09-03 |
JP2005507365A (ja) | 2005-03-17 |
CZ20031986A3 (cs) | 2003-12-17 |
WO2002074726A3 (en) | 2003-03-13 |
WO2002074726A2 (en) | 2002-09-26 |
JP4223287B2 (ja) | 2009-02-12 |
SK9152003A3 (en) | 2004-04-06 |
CA2435847A1 (en) | 2002-09-26 |
BG108003A (bg) | 2004-09-30 |
EE200300347A (et) | 2003-12-15 |
NZ527081A (en) | 2006-03-31 |
KR20040064606A (ko) | 2004-07-19 |
HUP0302793A3 (en) | 2006-01-30 |
HUP0302793A2 (hu) | 2003-11-28 |
NO20033288D0 (no) | 2003-07-21 |
NO20033288L (no) | 2003-09-22 |
PL373301A1 (en) | 2005-08-22 |
EE05362B1 (et) | 2010-12-15 |
HRP20030662A2 (en) | 2005-06-30 |
IL156958A0 (en) | 2004-02-08 |
EP1353907A2 (en) | 2003-10-22 |
MXPA03006519A (es) | 2004-10-15 |
YU57603A (sh) | 2006-08-17 |
BR0206943A (pt) | 2006-01-24 |
MA25996A1 (fr) | 2003-12-31 |
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