Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.


The desire to replace the amide backbone of renin inhibitors with a new scaffold led us to explore vinylogous amides (enaminones). An initial attempt proved unsuccessful, a result explained after the fact via docking experiments. Based on this lesson, we designed a different vinylogous amide scaffold which incorporated one or more pyrrolinone rings into the backbone. Three of the four compounds gave IC50S in the 0.6 to 18 microM range. These compounds did not inhibit HIV-1 protease. Taken together, the results reported herein provide insights into the role of hydrogen bonding and steric interactions for binding to renin.

Cite this paper

@article{Smith1995DesignAS, title={Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.}, author={Amos B. Smith and Ryuichiro Akaishi and David R. Jones and T. P. Keenan and Mark C Guzman and Ron Holcomb and Paul A. Sprengeler and Jonathan Wood and Ralph F Hirschmann and M. Katharine Holloway}, journal={Biopolymers}, year={1995}, volume={37 1}, pages={29-53} }