1. Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.
- Author
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Smith AB 3rd, Akaishi R, Jones DR, Keenan TP, Guzman MC, Holcomb RC, Sprengeler PA, Wood JL, Hirschmann R, and Holloway MK
- Subjects
- Drug Design, Hydrogen Bonding, Protein Conformation, Peptides chemical synthesis, Renin antagonists & inhibitors
- Abstract
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.
- Published
- 1995
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