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 ...