Clonidine and related analogues. Quantitative correlations.
Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the critical role of the steric effect in the ortho positions. On the other hand, attempted quantitative correlations between physicochemical parameters and central hypotensive activity were unsuccessful. These results are discussed in the light of the postulated mechanism of action of clonidine.
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003000:Clonidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D008433:Mathematics; D051381:Rats; D013329:Structure-Activity Relationship
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D003000:Clonidine