Stereochemical studies of chiral H-1 antagonists of histamine: the resolution, chiral analysis, and biological evaluation of four antipodal pairs.

Article Details

Citation

Casy AF, Drake AF, Ganellin CR, Mercer AD, Upton C

Stereochemical studies of chiral H-1 antagonists of histamine: the resolution, chiral analysis, and biological evaluation of four antipodal pairs.

Chirality. 1992;4(6):356-66. doi: 10.1002/chir.530040606.

PubMed ID
1360248 [ View in PubMed
]
Abstract

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 alpha 1-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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CarbinoxamineHistamine H1 receptorProteinHumans
Yes
Antagonist
Details
ChlorpheniramineHistamine H1 receptorProteinHumans
Yes
Antagonist
Details
DimetindeneHistamine H1 receptorProteinHumans
Yes
Antagonist
Details
DiphenhydramineHistamine H1 receptorProteinHumans
Yes
Antagonist
Details