Thyrotropin-releasing hormone (TRH) analogues that exhibit selectivity to TRH receptor subtype 2

  • J Med Chem. 2005 Sep 22;48(19):6162-5. doi: 10.1021/jm0505462.
Navneet Kaur  1 ,  Xinping Lu ,  Marvin C Gershengorn ,  Rahul Jain
Affiliations
  • 1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar--160 062, Punjab, India.
PMID: 16162016 DOI: 10.1021/jm0505462
Abstract

Thyrotropin-releasing hormone (TRH) analogues in which the C-2 position of the imidazole ring of the centrally placed histidine residue is substituted with various alkyl groups were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). Several analogues were found to be selective agonists for TRH-R2 exhibiting no activation of TRH-R1. For example, analogue 4 (R= c-C3H5) was found to activate TRH-R2 with a potency (EC50) of 0.41 microM but did not activate TRH-R1 (potency > 100 microM). This study describes the first discovery of TRH-R2-specific agonists and provides impetus to design predominately CNS-effective TRH peptides.