1-Benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diols as novel affinity and photoaffinity probes for beta-adrenoceptor subtypes

Trimetoquinol (TMQ, 1) is a potent non-selective beta-adrenoceptor (beta-AR) agonist possessing a tetrahydroisoquinoline (THI) structure. The binding site for 1-trimethoxybenzyl group of 1, which distinguishes it from classical catecholamines, is unknown. Affinity and photoaffinity labeled compounds are good tools to determine the exact interaction between a ligand and a specific amino acid(s) in a receptor. In this study, we designed and synthesized a series of affinity 6, 12, 18, and photoaffinity 24, 29 labeled analogues of TMQ. All of these compounds were full agonists and demonstrated an equal or greater binding affinity and functional activity as compared to TMQ on beta1-, beta2-, and beta3-AR. Washout experiments on Chinese hamster ovary (CHO) cells expressing hu beta2-AR were helpful in identifying the isothiocyanate 18 and the azide 24 as very effective affinity and photoaffinity labels at this receptor subtype.