JP2006508987A - ホスホジエステラーゼ４阻害剤 - Google Patents
ホスホジエステラーゼ４阻害剤 Download PDFInfo
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- JP2006508987A JP2006508987A JP2004553941A JP2004553941A JP2006508987A JP 2006508987 A JP2006508987 A JP 2006508987A JP 2004553941 A JP2004553941 A JP 2004553941A JP 2004553941 A JP2004553941 A JP 2004553941A JP 2006508987 A JP2006508987 A JP 2006508987A
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- Prior art keywords
- alkyl
- substituted
- pyridylmethyl
- oxy
- compound
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- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title description 14
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 14
- -1 nitroxide compounds Chemical class 0.000 claims abstract description 515
- 150000001875 compounds Chemical class 0.000 claims abstract description 288
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims abstract description 113
- 230000005764 inhibitory process Effects 0.000 claims abstract description 18
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims abstract 3
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims description 204
- 125000004432 carbon atom Chemical group C* 0.000 claims description 164
- 229910052736 halogen Inorganic materials 0.000 claims description 137
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 133
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 128
- 150000002367 halogens Chemical class 0.000 claims description 126
- 125000003545 alkoxy group Chemical group 0.000 claims description 96
- 125000003118 aryl group Chemical group 0.000 claims description 95
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 78
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 68
- 239000005711 Benzoic acid Substances 0.000 claims description 64
- 235000010233 benzoic acid Nutrition 0.000 claims description 64
- 125000004043 oxo group Chemical group O=* 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 125000006413 ring segment Chemical group 0.000 claims description 45
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 42
- 229920006395 saturated elastomer Polymers 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 33
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 28
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 27
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 26
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 25
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 23
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002252 acyl group Chemical group 0.000 claims description 21
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 20
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 19
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000004434 sulfur atom Chemical group 0.000 claims description 19
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 19
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 18
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 18
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
- 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 17
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- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
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- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 208000023105 Huntington disease Diseases 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 11
- 102000004190 Enzymes Human genes 0.000 claims description 11
- 108090000790 Enzymes Proteins 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- HFZZTHJMXZSGFP-UHFFFAOYSA-N 1-benzofuran-2-amine Chemical compound C1=CC=C2OC(N)=CC2=C1 HFZZTHJMXZSGFP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 150000003254 radicals Chemical class 0.000 claims description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
- 125000003944 tolyl group Chemical group 0.000 claims description 8
- 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 7
- 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
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 7
- 239000004305 biphenyl Chemical group 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000005389 trialkylsiloxy group Chemical group 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
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- 208000001089 Multiple system atrophy Diseases 0.000 claims description 6
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
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- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 5
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- 208000028683 bipolar I disease Diseases 0.000 claims description 5
- 230000002490 cerebral effect Effects 0.000 claims description 5
- 230000006999 cognitive decline Effects 0.000 claims description 5
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 5
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
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- 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
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- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 230000007954 hypoxia Effects 0.000 claims description 4
- 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 claims description 4
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- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
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- YUCFVHQCAFKDQG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH] YUCFVHQCAFKDQG-UHFFFAOYSA-N 0.000 claims description 3
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Landscapes
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Applications Claiming Priority (2)
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| US42722102P | 2002-11-19 | 2002-11-19 | |
| PCT/US2003/036986 WO2004046113A2 (en) | 2002-11-19 | 2003-11-19 | Pyridine n-oxide compounds as phosphodiesterase 4 inhibitors |
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| JP2006508987A true JP2006508987A (ja) | 2006-03-16 |
| JP2006508987A5 JP2006508987A5 (enExample) | 2007-02-15 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007513957A (ja) * | 2003-12-11 | 2007-05-31 | メモリー ファーマシューティカルス コーポレーション | Ｎ−置換ジアリールアミン類縁体を含む，ホスホジエステラーゼ４阻害剤本出願は，参照によりその全開示がここに導入されている２００３年１２月１１日に提出した米国仮出願番号６０／５２８，４８６の利益を請求するものである。 |
| WO2008105386A1 (ja) * | 2007-02-27 | 2008-09-04 | National University Corporation Okayama University | アルコキシ基を有するレキシノイド化合物 |
| 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 |
| JP2011517687A (ja) * | 2008-04-14 | 2011-06-16 | シエシー ファルマセウティチィ ソシエタ ペル アチオニ | ホスホジエステラーゼ−４阻害剤としての第３アミン誘導体 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007513957A (ja) * | 2003-12-11 | 2007-05-31 | メモリー ファーマシューティカルス コーポレーション | Ｎ−置換ジアリールアミン類縁体を含む，ホスホジエステラーゼ４阻害剤本出願は，参照によりその全開示がここに導入されている２００３年１２月１１日に提出した米国仮出願番号６０／５２８，４８６の利益を請求するものである。 |
| WO2008105386A1 (ja) * | 2007-02-27 | 2008-09-04 | National University Corporation Okayama University | アルコキシ基を有するレキシノイド化合物 |
| JPWO2008105386A1 (ja) * | 2007-02-27 | 2010-06-03 | 国立大学法人 岡山大学 | アルコキシ基を有するレキシノイド化合物 |
| JP4691619B2 (ja) * | 2007-02-27 | 2011-06-01 | 国立大学法人 岡山大学 | アルコキシ基を有するレキシノイド化合物 |
| US8389538B2 (en) | 2007-02-27 | 2013-03-05 | National University Corporation Okayama University | Rexinoid compound having alkoxy group |
| JP2011517687A (ja) * | 2008-04-14 | 2011-06-16 | シエシー ファルマセウティチィ ソシエタ ペル アチオニ | ホスホジエステラーゼ−４阻害剤としての第３アミン誘導体 |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05005345A (es) | 2005-08-26 |
| WO2004046113A3 (en) | 2005-03-24 |
| DE60334243D1 (de) | 2010-10-28 |
| US20100173942A1 (en) | 2010-07-08 |
| EP1569908B1 (en) | 2010-09-15 |
| RU2356893C2 (ru) | 2009-05-27 |
| ZA200503995B (en) | 2006-08-30 |
| EP1569908A2 (en) | 2005-09-07 |
| WO2004046113A2 (en) | 2004-06-03 |
| NZ540138A (en) | 2008-07-31 |
| KR20050075430A (ko) | 2005-07-20 |
| BR0315705A (pt) | 2005-09-06 |
| CN1714081A (zh) | 2005-12-28 |
| AU2003295656B2 (en) | 2010-11-11 |
| US20040152902A1 (en) | 2004-08-05 |
| AU2003295656A2 (en) | 2005-06-30 |
| US20060211865A1 (en) | 2006-09-21 |
| NO20052976L (no) | 2005-08-18 |
| AU2003295656A1 (en) | 2004-06-15 |
| CN100513397C (zh) | 2009-07-15 |
| ATE481387T1 (de) | 2010-10-15 |
| CA2506297A1 (en) | 2004-06-03 |
| US7700631B2 (en) | 2010-04-20 |
| RU2005119627A (ru) | 2006-01-27 |
| NO20052976D0 (no) | 2005-06-17 |
| US7087625B2 (en) | 2006-08-08 |
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