发明公开
EP0566142A1 Inclusion complexes of optically active and racemic 1,4-dihydro pyridines with cyclodextrin derivates
失效
Inklusion-Komplexe von optisch aktiven und racmischen 1,4-Dihydropyridinederivate mit Zyklodextrin。
- 专利标题： Inclusion complexes of optically active and racemic 1,4-dihydro pyridines with cyclodextrin derivates
- 专利标题（中）： Inklusion-Komplexe von optisch aktiven und racmischen 1,4-Dihydropyridinederivate mit Zyklodextrin。
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申请号： EP93106236.8申请日： 1993-04-16
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公开(公告)号： EP0566142A1公开(公告)日： 1993-10-20
- 发明人: Fercej-Temeljotov, Darja, Mag.-Ing. , Zmitek, Janko, Dr.-Ing. , Husu-Kovacevic, Breda, Mag.-Ing. , Kotnik, Sonja, Dipl.-Ing. , Jerala-Strukelj, Zdenka, Dipl.-Ing.
- 申请人： LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d.
- 申请人地址： Verovskova 57 SI-61107 Ljubljana SI
- 专利权人： LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d.
- 当前专利权人： LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d.
- 当前专利权人地址： Verovskova 57 SI-61107 Ljubljana SI
- 代理机构： Steil, Christian, Dipl.Ing.
- 优先权： AT795/92 19920416
- 主分类号： A61K47/48
- IPC分类号： A61K47/48 ; A61K31/44
摘要：
Novel inclusion complexes of racemic 1,4-dihydropyridines and enantiomers thereof of the formula
wherein
R represents a phenyl group, substituted with nitro, trifluoromethyl, difluoromethoxy group or with one or two halo atoms (especially chlorine),
R₁ and R₂, if the same, represent methyl groups and if one of them has the meaning of a 2-aminoethoxymethyl or cyano group, the other represents a methyl group,
R₃ and R₄, if different, stand each time for a hydrogen, linear or branched C₁-C₆-alkyl, 2-methoxyethyl, 1-(phenylmethyl)-3-piperidinylphenyl, styryl, furyl, piperidino, 4-diphenylmethyl-1-piperazinylethyl, 5-phenyl-3-pirazolyloxy, 1-phenyl-methyl-3-pyrrolidinyl group or a group of the formula
or, if the same, stand each time C₁-C₄ alkyl group,
and of acid addition salts thereof with methyl-β-cyclodextrin, hydroxy-ethyl-β-cyclodextrin or hydroxypropyl-β-cyclodextrin, with the exception of inclusion complexes of racemic dihydropyridines with HP-β-CD, or, in case of amlodipine and enantiomeric nicardipine, also with β-cyclodextrin, are disclosed.
Whilst inclusion complexes of racemic dihydropyridines with the cited cyclodextrins are prepared in a well-known manner disclosed in the literature, enantiomerically pure dihydropyridines and inclusion complexes thereof with cyclodextrins are prepared in a novel way by means of preparative column chromatography.
The invention also relates to a pharmaceutical formulation containing novel inclusion complexes and to the use thereof as calcium antagonists for the treatment of hypertension, angina pectoris and cerebrovascular disorders.
wherein
R represents a phenyl group, substituted with nitro, trifluoromethyl, difluoromethoxy group or with one or two halo atoms (especially chlorine),
R₁ and R₂, if the same, represent methyl groups and if one of them has the meaning of a 2-aminoethoxymethyl or cyano group, the other represents a methyl group,
R₃ and R₄, if different, stand each time for a hydrogen, linear or branched C₁-C₆-alkyl, 2-methoxyethyl, 1-(phenylmethyl)-3-piperidinylphenyl, styryl, furyl, piperidino, 4-diphenylmethyl-1-piperazinylethyl, 5-phenyl-3-pirazolyloxy, 1-phenyl-methyl-3-pyrrolidinyl group or a group of the formula
or, if the same, stand each time C₁-C₄ alkyl group,
and of acid addition salts thereof with methyl-β-cyclodextrin, hydroxy-ethyl-β-cyclodextrin or hydroxypropyl-β-cyclodextrin, with the exception of inclusion complexes of racemic dihydropyridines with HP-β-CD, or, in case of amlodipine and enantiomeric nicardipine, also with β-cyclodextrin, are disclosed.
Whilst inclusion complexes of racemic dihydropyridines with the cited cyclodextrins are prepared in a well-known manner disclosed in the literature, enantiomerically pure dihydropyridines and inclusion complexes thereof with cyclodextrins are prepared in a novel way by means of preparative column chromatography.
The invention also relates to a pharmaceutical formulation containing novel inclusion complexes and to the use thereof as calcium antagonists for the treatment of hypertension, angina pectoris and cerebrovascular disorders.
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