title: Thyrotropin-releasing hormone (TRH) analogues that exhibit selectivity to TRH receptor subtype 2.
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.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar--160 062, Punjab, India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Kaur
authors.forename: Xinping
authors.initials: X
authors.lastname: Lu
authors.forename: Marvin C
authors.initials: MC
authors.lastname: Gershengorn
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D002460:Cell Line; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000819:agonists*; D013329:Structure-Activity Relationship; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D002491:Central Nervous System Agents; D007093:Imidazoles; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone