RESUMO
The synthesis and some of the spectral properties of N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (lisinopril, MK-521) are described. This compound inhibits angiotensin-converting enzyme with an IC50 of 1.2 X 10(-9) M.
Assuntos
Dipeptídeos/síntese química , Isótopos de Carbono , Fenômenos Químicos , Química , Lisinopril , Espectroscopia de Ressonância MagnéticaRESUMO
Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study.
