Synthesis and Renal Vasodilator Activity of 2-Chlorodopamine and N-Substituted Derivatives

Article abstract of DOI:10.1021/jm00159a005

A four-step synthesis of 2-chlorodopamine (2b) is presented as well as methods for the syntheses of the N-methyl, ethyl, and n-propyl analogues (2c-e).Compounds 2b and 2c were essentially equipotent to dopamine for increasing renal blood flow in anesthesized dogs that had been treated with the α-adrenergic antagonist phenoxybenzamine.The increases in renal blood flow were blocked by the DA₁ antagonist (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine.Compounds 2d and 2e were significantly less potent than dopamine in the same model; the increases in renal blood flow were attenuated by propanolol and blocked by a combination of propanolol and (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine.The significance of an o-chloro substituent on dopamine analogues for the activation of the DA₁ receptor is briefly discussed.