1-Pentanoyl-N-{[2’-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-pyrrolidine-2-carboxamide: Investigation of Structural Variations

We recently reported a series of 1-acyl-N-(biphenyl-4-ylmethyl)pyrrolidine- 2-carboxamides as AT1 receptor ligands. The most potent compound of the series, 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}- pyrrolidine-2-carboxamide, showed an interesting affinity for the receptor. To investigate the influence of structure variations on affinity, the synthesis of additional compounds belonging to this series has been performed. Biological tests run on the newly synthesized compounds on CHO-hAT 1 cells stably expressing the human AT1 receptor confirm our previous hypothesis, i.e. that, within this series, the length of the acyl chain, the substitution of the amidic group and the nature of the acidic one are crucial for the receptor interaction, being a valeric chain, a secondary amidic function and the tetrazole moiety, respectively, the optimal ones. New 1-acyl-N-(biphenyl-4- ylmethyl)pyrrolidine-2-carboxamides have been designed by enlarging our previously reported series in order to clarify the requirements for AT1 receptor interaction.