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.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005559:Formamides; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010636:Phenols; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides
D005559:Formamides; D010636:Phenols; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013449:Sulfonamides; C036871:methanesulfonamide; C031066:formamide; C020895:N,N-di-n-propyldopamine; D004298:Dopamine