Structural studies of antihistamines. The crystal structure ofH _{4aH 9a} -cis-H ₉,H _9a-trans-2-methyl-9-phenyl-2, 3,4,4_a,9,9_a-hexahydro-1H-indeno[2,1-c]pyridine hydrochloride

Abstract

The crystal and molecular structure ofH _4a ,H _9a -cis-H ₉,H _9a -trans-2-methyl-9-phenyl-2, 3,4,4 _a ,9,9 _a -hexahydro-1H-indeno[2,1-c]pyridine hydrochloride was determined. The compound crystallizes in the orthorhombic space groupPbca, with eight molecules in the unit cell of dimensionsa = 10.461(2),b = 20.141(10), andc = 15.469(3) Å. Intensity data were measured using Mo radiation and a θ−θ scan method. The structure was solved by direct methods and refined by least-squares techniques to a finalR of 4.6%. Thecis-trans isomer has higher antihistamine activity compared to thecis-cis isomer but is less active than phenindamine, the 2,3,4,9-tetrahydro derivative. The bond distances in thecis-trans andcis-cis derivatives are identical so that the differences in activity must be related to differences in conformation. The difference in the conformation is discussed from a receptor-site view of the two molecules.