The Role of Orthosteric Building Blocks of Bitopic Ligands for Muscarinic M1 Receptors.

ABSTRACT: The muscarinic M₁ acetylcholine receptor is an important drug target for the treatment of various neurological disorders. Designing M₁ receptor-selective drugs has proven challenging, mainly due to the high conservation of the acetylcholine binding site among muscarinic receptor subtypes. Therefore, less conserved and topographically distinct allosteric binding sites have been explored to increase M₁ receptor selectivity. In this line, bitopic ligands, which target orthosteric and allosteric binding sites simultaneously, may provide a promising strategy. Here, we explore the allosteric, M₁-selective BQCAd scaffold derived from BQCA as a starting point for the design, synthesis, and pharmacological evaluation of a series of novel bitopic ligands i

SUBMITTER: Volpato D 

PROVIDER: S-EPMC7745449 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature