Fig. 2.
Chemical structures of propranolol, esmolol, and the carboxylic acid metabolite of esmolol. The discovery of the ultrashort-acting β-blocker esmolol, described in a 1982 publication, was based on replacing the lipophilic naphthalene ring of propranolol with the aryl methyl propionate group in esmolol.3 Rapid hydrolysis of esmolol’s methyl ester by blood esterases produces the esmolol carboxylic acid metabolite which is significantly less active at antagonizing the β-adrenergic receptor. This soft drug medicinal chemistry approach was similarly applied to the discovery of remifentanil.