Synthesis of novel keto-ACE analogues as domain-selective angiotensin I-converting enzyme inhibitors.
Novel analogues of the angiotensin I-converting enzyme (ACE) inhibitor keto-ACE were synthesized via a facile Horner-Emmons olefination of a phosphonoketone precursor with ethyl glyoxylate. Introduction of a bulky aromatic tryptophan at the P(2)(') position of keto-ACE resulted in a significant increase in C-domain-selectivity.
Nchinda
Aloysius T
AT
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
Chibale
Kelly
K
Redelinghuys
Pierre
P
Sturrock
Edward D
ED
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A