33208-87-6Relevant academic research and scientific papers
Synthesis, receptor binding, and activation studies of N(1)-alkyl-l-histidine containing thyrotropin-releasing hormone (TRH) analogues
Kaur, Navneet,Monga, Vikramdeep,Josan, Jatinder S.,Lu, Xinping,Gershengorn, Marvin C.,Jain, Rahul
, p. 5981 - 5988 (2006)
Thyrotropin-releasing hormone (TRH) analogues in which the N(1)-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). Analogue 3 (R = C2H5) exhibited binding affinity (Ki) of 0.012 μM to TRH-R1 that is about 1.1-fold higher than that of TRH. Several analogues were found to selectively activate TRH-R2 with greater potency than TRH-R1. The most selective agonist of the series 5 [R = CH(CH3)2] was found to activate TRH-R2 with a potency (EC50) of 0.018 μM but could only activate TRH-R1 at EC50 value of 1.6 μM; that is, exhibited 88-fold greater potency for TRH-R2 versus TRH-R1. The results of this study indicate that modulation of central histidine residue is important for designing analogues which were selective agonist at TRH receptor subtypes.
