Novel 1-Amidino-4-Phenylpiperazines as Potent Agonists at Human TAAR1 Receptor: Rational Design, Synthesis, Biological Evaluation and Molecular Docking Studies.

ABSTRACT: Targeting trace amine-associated receptor 1 (TAAR1) receptor continues to offer an intriguing opportunity to develop innovative therapies in different pharmacological settings. Pursuing our endeavors in the search for effective and safe human TAAR1 (hTAAR1) ligands, we synthesized a new series of 1-amidino-4-phenylpiperazine derivatives (1-16) based on the application of a combined pharmacophore model/scaffold simplification strategy for an in-house series of biguanide-based TAAR1 agonists. Most of the novel compounds proved to be more effective than their prototypes, showing nanomolar EC₅₀ values in functional activity at hTAAR1 and low general cytotoxicity (CC₅₀ > 80 µM) when tested on the Vero-76 cell line. In this new series, the main d

SUBMITTER: Francesconi V 

PROVIDER: S-EPMC7697893 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature