Synthesis and dopamine autoreceptor activity of a 5-(methylmercapto)methyl-substituted derivative of (+/-)-3-PPP (3-(3-hydroxyphenyl)-1-n-propylpiperidine).
In an attempt to enhance the potency of the dopamine autoreceptor agonist 3-PPP, racemic cis-3-(3-hydroxyphenyl)-5-[(methylmercapto)methyl]-N-n-propylpiperidine has been prepared in a stereoselective synthesis. NMR studies of 3 show a diequatorial conformation for the 3- and 5-substituents, which gives compound 3 an intriguing overlap with the ergoline derivative pergolide. Pharmacological testing revealed that 3, which is a 5-(methylmercapto)methyl derivative of racemic 3-PPP does not show the anticipated potency increase as a dopamine autoreceptor agonist. In vitro (inhibition of tyrosine hydroxylation) 3 and 1 have similar potency, and the in vivo potency (inhibition of GBL accelerated dopamine synthesis) of 3 is inferior to that of 1.
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013329:Structure-Activity Relationship
D010880:Piperidines; D011954:Receptors, Dopamine; D004295:Dihydroxyphenylalanine; C046495:3-(3-hydroxyphenyl)-5-((methylmercapto)methyl)-N-n-propylpiperidine; C026539:preclamol; D015107:4-Butyrolactone; D004298:Dopamine