N-[2(S)-hydroxy-4-methylpentyl] tripeptide derivatives as inhibitors of renin

The following N-2(S)-hydroxy-4-methylpentyl derivatives of GlyValPheOMe and LeuValPheOMe were designed as analogues of the transition state of the renin-angiotensinogen reaction: N-[2(S)-hydroxy-4-methylpentyl] GlyValPheOMe 2 and N-[2(S-hydroxy-4-methylpentyl] LeuValPheOMe 3. Once synthesized they were tested for their abilities to inhibit hog kidney renin. The two compounds were found to have comparable activity to the known tetrapeptide inhibitors LeuGlyValPheOMe and LeuLeuValPheOMe. The type of kinetic behavior for each of the synthesized compounds was the same as that of the respective parent tetrapeptide; being competitive in the case of 2 and non-competitive in the case of 3.