Benzylphosphonic acid inhibitors of human prostatic acid phosphatase

A series of α-substituted benzylphosphonic acids is described as inhibitors of human prostatic acid phosphatase, an enzyme which has been used as a model to study aryl phosphatases. The most potent inhibitors in this series are 2-trifluoromethylbenzhydrylphosphonic acid (9 μM), and α-(2-phenylethyl)benzylphosphonic acid (14 μM). The structure-activity studies suggest that bulk tolerance beyond the phosphate binding area limits the steric or hydrophobic contribution to inhibitor potency achieved through α-carbon substitution.