title: Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.
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.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia 19104.
authors.forename: A B
authors.initials: AB
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Akaishi
authors.forename: D R
authors.initials: DR
authors.lastname: Jones
authors.forename: T P
authors.initials: TP
authors.lastname: Keenan
authors.forename: M C
authors.initials: MC
authors.lastname: Guzman
authors.forename: R C
authors.initials: RC
authors.lastname: Holcomb
authors.forename: P A
authors.initials: PA
authors.lastname: Sprengeler
authors.forename: J L
authors.initials: JL
authors.lastname: Wood
authors.forename: R
authors.initials: R
authors.lastname: Hirschmann
authors.forename: M K
authors.initials: MK
authors.lastname: Holloway
mesh_terms: D015195:Drug Design; D006860:Hydrogen Bonding; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D000092502:Renin Inhibitors
chemical_list: D010455:Peptides; D000092502:Renin Inhibitors