New renin inhibitors containing pseudodipeptidic units in P3-P2 and P1-P1' positions.
A series of four non-peptidic renin inhibitors have been designed and synthesized. All of them contain in their molecule (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA), a hydrophobic portion at the C-terminus and a second dipeptide-like transition state analog or unnatural dipeptidic fragment at the N-terminus. Inhibitory activity of the compounds was measured in vitro by high performance liquid chromatography (HPLC). Their IC50 (M/l) values were: <10(-3) (12), 1.0 x 10(-6) (19), 4.0 x 10(-4) (23) and 1.0 x 10(-6) (29), respectively. All the compounds are stable against chymotrypsin.
Paruszewski
Ryszard
R
Department of Drug Chemistry, Medical University, Poland. rpbw@farm.amwaw.edu.pl
Jaworski
Paweł
P
Bodnar
Magdalena
M
Dudkiewicz-Wilczyńska
Jadwiga
J
Roman
Iza
I
D000818:Animals; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D015394:Molecular Structure; D008970:Molecular Weight; D012083:Renin / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine; D000092502:Renin Inhibitors
D004151:Dipeptides; D004791:Enzyme Inhibitors; D012083:Renin; D000092502:Renin Inhibitors