Synthesis and pharmacological evaluation of N,N-di-n-propyldopamine congeners containing phenolic bioisosteres

A series of analogues of N,N-di-n-propyldopamine (DPDA) in which the 3-hydroxyl group was replaced by bioisosteric groups was prepared and evaluated for D1- and D2-receptor affinity. The 3-methane-sulfonamide analogue (18) had a higher affinity for the D2 receptor than DPDA and was more selective for the D2 receptor. The 3-formamide derivative (15) also retained significant D2 affinity. Both of these compounds demonstrated in vivo cardiovascular and renal profiles in an anesthetized rat model that were consistent with selective D2-receptor agonism.