Synthesis and Biological Evaluation of Lysophosphatidic Acid Analogues Using Conformational Restriction and Bioisosteric Replacement Strategies.

ABSTRACT: Lysophosphatidic acid (LPA) is a key player in many physiological and pathophysiological processes. The biological activities of LPA are mediated through interactions with-at least-six subtypes of G-protein-coupled receptors (GPCRs) named LPA_1-6. Developing a pharmacological tool molecule that activates LPA subtype receptors selectively will allow a better understanding of their specific physiological roles. Here, we designed and synthesized conformationally restricted 25 1-oleoyl LPA analogues MZN-001 to MZN-025 by incorporating its glycerol linker into dihydropyran, tetrahydropyran, and pyrrolidine rings and variating the lipophilic chain. The agonistic activities of these compounds were evaluated using the TGFα shedding assay. Overall, the synthesized analogues

SUBMITTER: Abdelwahid MAS 

PROVIDER: S-EPMC10753746 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature