Potential thyroliberin affinity labels. 1. Chloroacetyl-substituted phenylalanylpyrrolidines

Six analogues of thyroliberin (TRH) that have a chloroacetyl substituent at the amino terminus have been prepared as potential affinity labels for the TRH receptor. These compounds are N-(chloroacetyl)-L-alanyl-L-phenylalanylpyrrolidine (ClAc-Ala-Phe-Pyrr; 14), N-[m-(chloroacetyl)benzoyl]-L-phenylalanylpyrrolidine (m-ClAcBz-Phe-Pyrr; 11a), N-[m-(chloroacetyl)benzoyl]-L-alanyl-L-phenylalanylpyrrolidine (m-ClAcBz-Ala-Phe-Pyrr; 15a), N-[p-(chloroacetyl)benzoyl]-L-phenylalanylpyrrolidine (p-ClAcBz-Phe-Pyrr; 11b), and N-[p-(chloroacetyl)benzoyl]-L-alanyl-L-phenylalanylpyrrolidine (p-ClAcBz-Ala-Phe-Pyrr; 15b). Pyroglutamyl-L-phenylalanylpyrrolidine was also synthesized as a model agonist. Weak agonist activity was observed for 11a, 11b, and 15b. These three analogues do not contain the amide group of the pyroglutamyl moiety that was previously thought to be essential for intrinsic activity. No significant antagonist activity was observed for these compounds at the doses tested.