Structure-activity relationship studies of functionalized aromatic peptidomimetics as neurolysin activators.

ABSTRACT: Modulating peptidase neurolysin (Nln) has been identified as a potential cerebroprotective target for the development of therapeutics for ischemic stroke. Continued structure-activity relationship studies on peptidomimetic small molecule activators of Nln bearing electron-donating and electron- withdrawing functionalized phenyls are explored. Incorporation of fluorine or trifluoromethyl groups produces Nln activators with enhanced A₅₀, while methoxy substitution produces derivatives with enhanced A_max. Selected activators containing methoxy or trifluoromethyl substitution are selective for Nln over related peptidases and possess increased blood-brain barrier penetrability than initial hits.

SUBMITTER: Rahman MS 

PROVIDER: S-EPMC8985228 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature