The Identification of GPR52 Agonist HTL0041178, a Potential Therapy for Schizophrenia and Related Psychiatric Disorders

  • ACS Med Chem Lett. 2023 Mar 14;14(4):499-505. doi: 10.1021/acsmedchemlett.3c00052.
Simon Poulter  1 ,  Nigel Austin  1 ,  Rachel Armstrong  1 ,  Matt Barnes  1 ,  Sarah Joanne Bucknell  1 ,  Alicia Higueruelo  1 ,  Joydeep Banerjee  2 ,  Andy Mead  1 ,  Richard Mould  1 ,  Cliona MacSweeney  1 ,  M Alistair O'Brien  1 ,  Lisa Alice Stott  1 ,  Stephen P Watson  1  2
Affiliations
  • 1. Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge CB21 6DG, United Kingdom.
  • 2. Syngene International, Biocon Park, Bommasandra, Bangalore 560099, India.
Abstract

HTL0041178 (1), a potent GPR52 agonist with a promising pharmacokinetic profile and exhibiting oral activity in preclinical models, has been identified. This molecule was the outcome of a judicious molecular property-based optimization approach, focusing on balancing potency against metabolic stability, solubility, permeability, and P-gp efflux.

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