Molecular and crystal structures of MDL27,467A hydrochloride and quinapril hydrochloride, two ester derivatives of potent angiotensin converting enzyme inhibitors.

The molecular structures of MDL27,467A hydrochloride, [4 alpha,7 alpha(R*),12b beta]-7-[[1-(ethoxycarbonyl)-3-phenyl-propyl] amino]-1,2,3,4,6,7,12a,12b-octahydro-6-oxopyrido[2,1- a][2]benzazepine-4-carboxylic acid diphenylmethyl ester hydrochloride, and quinapril hydrochloride, [3S-[2[R*(R*)],3R]]-2-[2[[1- (ethoxycarbonyl)-3-phenylpropyl]-amino]-1-oxopropyl]-1,2,3,4- tetrahydro-3-isoquinolinecarboxylic acid hydrochloride, were determined by X-ray diffraction methods. The modified, C-terminal dipeptide portions and the phenylpropyl fragments in both crystal structures adopt similar conformations. The binding positions for several pharmacophores are defined by the constraint of the tricyclic system in the crystallographic structure of MDL27,467A hydrochloride. Conformational energy calculations show that the phenyl ring of the tetrahydro-3-isoquinoline system of quinapril does not fit into the S2 hydrophobic pocket of angiotensin converting enzyme.