Configuration and preferential solid-state conformations of perindoprilat (S-9780). Comparison with the crystal structures of other ACE inhibitors and conclusions related to structure-activity relationships.
The conformation of perindoprilat, an antihypertensive drug, is studied in the solid state by X-ray analysis. The resolution of its structure reveals important analogies between its observed conformation and that of several ACE inhibitors of the same family. This comparison points out a constant relative orientation of the functional groups, regardless of the molecular environment. This angular constancy appears to us as not being accidental and is a good argument for the spatial design of the ACE binding site. Although ACE is a carboxydipeptidase, the binding site may not contain two but one unique hydrophobic pocket receiving the C-terminal end of the inhibitors.
Pascard
C
C
Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France.
Guilhem
J
J
Vincent
M
M
Rémond
G
G
Portevin
B
B
Laubie
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors; D001665:Binding Sites; D003461:Crystallography; D007211:Indoles; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C053500:perindoprilat