STEREOCHEMICAL STUDIES OF CHIRAL H-1 ANTAGONISTS OF HISTAMINE - THE RESOLUTION, CHIRAL ANALYSIS, AND BIOLOGICAL EVALUATION OF 4 ANTIPODAL PAIRS

被引：73
作者：
CASY, AF
DRAKE, AF
GANELLIN, CR
MERCER, AD
UPTON, C
机构：
[1] UNIV BATH,SCH PHARM & PHARMACOL,BATH BA2 7AY,AVON,ENGLAND
[2] UNIV LONDON BIRKBECK COLL,DEPT CHEM,LONDON WC1E 7HX,ENGLAND
[3] UNIV LONDON UNIV COLL,DEPT CHEM,LONDON WC1E 6BT,ENGLAND
来源：
CHIRALITY | 1992年 / 4卷 / 06期
关键词：
H-1; ANTIHISTAMINES; CHIRAL HPLC; BETA-CYCLODEXTRIN-INCLUSION COMPLEXES; NMR; CIRCULAR DICHROISM; AFFINITY CONSTANTS;
D O I：
10.1002/chir.530040606
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The resolution of the H-1 antihistamines chloropheniramine, dimethindene, carbinoxamine, and mebrophenhydramine is described. The optical purity of antipodal products is investigated by chiral HPLC (use of alpha1-acid glycoprotein and beta-cyclodextrin columns) and NMR (spectra of beta-cyclodextrin inclusion complexes). Configurational relationships among the group are reviewed and assignments are confirmed and extended by circular dichroism evidence. Affinity constants of antipodal pairs for guinea pig ileum and cerebellum sites, determined by gut bath and binding experiments respectively, are reported together with some in vivo tests in man for central effects. Results are discussed in terms of configurational requirements for activity and variations in antipodal potency ratios within the group.
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页码：356 / 366
页数：11
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