Stereochemical studies of chiral h‐1 antagonists of histamine: The resolution, chiral analysis, and biological evaluation of four antipodal pairs

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.

Asymmetric Nucleophilic Substitution of Acetals

“…Chiral diarylmethanols are constituents of biologically active compounds such as clemastine, [26] neobenodine, [27] and chloropheniramine. [28Ϫ30] Enantioselective syntheses of diarylmethanols use either asymmetric catalytic hydrogenation of diarylketones [31,32] or enantioselective addition of arylzinc reagents to benzaldehydes in the presence of chiral catalysts.…”

Bio-analytical chiral chromatography method for the enantioselective separation of carbinoxamine maleate in human plasma

“…Ethanolamine class of H 1 antihistamines were proven to show stereoselectivity in binding to the receptors (Casy et al 1992). Doxylamine which is a similar kind of molecule to that of carbinoxamine showed that its (d) or (+) form has more binding affinity compared to its antipode (Tadiboyina et al 2015).…”

Development of Efficient Catalytic Arylation of Aldehydes with Thioether-Imidazolinium Carbene Ligands

“…[13][14][15] Due to the advantages of organoboron reagents such as low toxicity, superior stability, and widespread availability, [16][17][18] and the significance of adducts as intermediates for the synthesis of biologically active compounds, [19][20][21] several types of active catalysts have been developed for this kind of reaction, such as palladium, 22) nickel, 23) and copper 24) complexes in addition to recently found effective metal species following our report. [25][26][27][28] However, they did not achieve adequate level performance and high catalyst loading was usually required to obtain sufficient results.…”