Synthesis and renal vasodilator activity of 2-chlorodopamine and N-substituted derivatives.
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 anesthetized dogs that had been treated with the alpha-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 propranolol and blocked by a combination of propranolol 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.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000098:blood supply; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects*
D001552:Benzazepines; C050034:2-chlorodopamine; D011433:Propranolol; D004298:Dopamine