JP2002507204A - ネガティブホルモン活性および/または拮抗薬活性を有するレチノイド化合物の合成と使用 - Google Patents
ネガティブホルモン活性および/または拮抗薬活性を有するレチノイド化合物の合成と使用Info
- Publication number
- JP2002507204A JP2002507204A JP50499899A JP50499899A JP2002507204A JP 2002507204 A JP2002507204 A JP 2002507204A JP 50499899 A JP50499899 A JP 50499899A JP 50499899 A JP50499899 A JP 50499899A JP 2002507204 A JP2002507204 A JP 2002507204A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- mmol
- dimethyl
- rar
- solution
- 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.)
- Granted
Links
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Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
- C07C57/50—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
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- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
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- C07C233/00—Carboxylic acid amides
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- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/87—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
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- C07C245/10—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems
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- C07C63/74—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings containing halogen having unsaturation outside the aromatic rings
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- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/19—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups having unsaturation outside the aromatic ring
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- C07C65/28—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups having unsaturation outside the aromatic rings
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- C07C65/38—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups having unsaturation outside the aromatic rings
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式: [式中、 Xは、C(R1)2、またはOであり; R1は、H、または炭素原子数1〜6のアルキルであり; R2は、炭素原子数1〜6の低級アルキル、F、Cl、Br、I、CF3、炭素 原子数1〜6のフルオロ置換アルキル、OH、SH、炭素原子数1〜6のアルコ キシ、または炭素原子数1〜6のアルキルチオであり; mは、0〜3の整数であり; R3は、炭素原子数1〜6の低級アルキル、またはFであり; oは、0〜3の整数であり; sは、1〜3の整数であり; R8は、炭素原子数1〜10のアルキル基もしくはトリメチルシリルアルキル (ここでアルキル基は1〜10の炭素原子を有する)、または炭素原子数5〜1 0のシクロアルキル基、あるいはR8は、フェニルまたは低級アルキルフェニル であり; R15は、同一または異なって、H、F、Cl、Br、I、NO2、N(R8)2、 COR8、NR8CON(R8)2、OCOR8、OR8、CN、炭素原子数1〜10の アルキル基、炭素原子数1〜10のフルオロ置換アルキル基、炭素原子数1〜1 0で1〜3の二重結合を有するアルケニル基、炭素原子数1〜10で1〜3の三 重結合を有するアルキニル基、またはトリアルキルシリルもしくはトリアルキル シリルオキシ基(ここでアルキル基は同一または異なって1〜6の炭素原子を有 する)であり; rは、0〜5の整数であり; CONH基は、ベンゾピランの6または7位に、また、ジヒドロナフタレン環 の2または3位に存在する。] で示される化合物、または薬学的に許容し得るその塩。 2.XがC(R1)2であり、R1がCH3である請求項1記載の化合物。 3.rが1であり、R15が低級アルキルである請求項2記載の化合物。 4.R15が4−メチルである請求項3記載の化合物。 5.oが0である請求項2記載の化合物。 6.mが0である請求項2記載の化合物。 7.XがOである請求項1記載の化合物。 8.rが1であり、R15が低級アルキルである請求項7記載の化合物。 9.R15が4−メチルである請求項8記載の化合物。 10.R3がCH3であり、oが2であり、これら置換基CH3がベンゾピラン 環の2位に存在する請求項7記載の化合物。 11.R2がBrであり、mが1であり、このブロモ置換基がベンゾピラン環 の8位に存在する請求項7記載の化合物。 12.式: [式中、 Xは、C(CH3)2、またはOであり; R2は、H、またはBrであり; R2’およびR2”は、同一または異なって、H、またはFであり; R3は、H、またはCH3であり; R8は、H、炭素原子数1〜6の低級アルキルである。] で示される化合物、または薬学的に許容し得るその塩。 13.XがC(CH3)2であり、R3がHである請求項12記載の化合物。 14.R2がHである請求項13記載の化合物。 15.R2’がFであろ請求項14記載の化合物。 16.R8がHまたはエチルである請求項15記載の化合物または薬学的に許 容し得るその塩。 17.R2”がFである請求項15記載の化合物。 18.R8がHまたはエチルである請求項17記載の化合物または薬学的に許 容し得るその塩。 19.XがOであり、R3がCH3である請求項12記載の化合物。 20.R2がBrである請求項19記載の化合物。 21.R2’がHであり、R2”がHである請求項20記載の化合物。 22.R8がHまたはエチルである請求項21記載の化合物または薬学的に許 容し得るその塩。 23.R2’がFであり、R2”がHである請求項20記載の化合物。 24.R8がHまたはエチルである請求項23記載の化合物または薬学的に許 容し得るその塩。 25.R2’がFであり、R2”がFである請求項20記載の化合物。 26.R8がHまたはエチルである請求項25記載の化合物または薬学的に許 容し得るその塩。 27.哺乳動物の病態を処置する方法であって、該病態はレチノイン酸受容体 活性に関連するものであり、該方法はRARα、RARβおよびRARγからな る群より選択されるレチノイン酸受容体亜型に結合することのできるレチノイド 拮抗薬またはネガティブホルモンを哺乳動物に投与することを含んで成り、該拮 抗薬またはネガティブホルモンは哺乳動物の前記病態に対し処置効果をもたらす 薬学的有効量で投与し、該拮抗薬またはネガティブホルモンは請求項1記載の化 合物である方法。 28.病態はレチノイド化合物を哺乳動物に投与することから生じる毒性また は望ましくない副作用であり、処置効果は該毒性または望ましくない副作用の防 止または改善である請求項27記載の方法。 29.レチノイド薬剤またはビタミンAもしくはビタミンA前駆体を哺乳動物 が摂取することにより引き起こされた予め存在する病態を治療または改善するた めにレチノイド拮抗薬またはネガティブホルモンを投与する請求項27記載の方 法。 30.処置目的で投与するレチノイド薬剤による望ましくない局所副作用を防 止または改善するためにレチノイド拮抗薬またはネガティブホルモンを局所投与 ずる請求項27記載の方法。 31.処置目的で全身的に投与するレチノイド薬剤による望ましくない局所副 作用を防止または改善するためにレチノイド拮抗薬またはネガティブホルモンを 局所投与する請求項27記載の方法。 32.レチノイド薬剤またはビタミンAにより引き起こされた予め存在する病 態または副作用を処置するためにレチノイド拮抗薬またはネガティブホルモンを 局所投与する請求項27記載の方法。 33.レチノイド薬剤またはビタミンAにより引き起こされた予め存在する病 態または副作用を処置するためにレチノイド拮抗薬またはネガティブホルモンを 全身的に投与する請求項27記載の方法。 34.レチノイド薬剤またはビタミンAの同時投与により引き起こされる骨毒 性を防止または改善するためにレチノイド拮抗薬またはネガティブホルモンを全 身的に投与する請求項27記載の方法。
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US08/880,823 | 1997-06-24 | ||
PCT/US1998/013065 WO1998058922A1 (en) | 1997-06-24 | 1998-06-24 | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
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- 1998-06-24 KR KR10-1999-7012229A patent/KR100512058B1/ko not_active IP Right Cessation
- 1998-06-24 CN CNB988082950A patent/CN1142928C/zh not_active Expired - Fee Related
- 1998-06-24 WO PCT/US1998/013065 patent/WO1998058922A1/en active IP Right Grant
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- 1998-06-24 DE DE69829183T patent/DE69829183T2/de not_active Expired - Fee Related
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JP2007518719A (ja) * | 2003-12-26 | 2007-07-12 | アラーガン インコーポレイテッド | RARγレチノイド受容体アンタゴニスト活性を有する二置換カルコンオキシム |
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ATE289998T1 (de) | 2005-03-15 |
CA2294601A1 (en) | 1998-12-30 |
AU8261998A (en) | 1999-01-04 |
CN1268130A (zh) | 2000-09-27 |
EP0991636A1 (en) | 2000-04-12 |
KR20010020505A (ko) | 2001-03-15 |
WO1998058922A1 (en) | 1998-12-30 |
EP1535919A3 (en) | 2005-10-26 |
BR9810340A (pt) | 2000-09-19 |
DE69829183D1 (de) | 2005-04-07 |
JP4295361B2 (ja) | 2009-07-15 |
DE69829183T2 (de) | 2006-04-06 |
EP1535919A2 (en) | 2005-06-01 |
AU729140B2 (en) | 2001-01-25 |
US5877207A (en) | 1999-03-02 |
CN1142928C (zh) | 2004-03-24 |
EP0991636B1 (en) | 2005-03-02 |
KR100512058B1 (ko) | 2005-09-02 |
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