Synthesis and evaluation of N,N-di-n-propyltetrahydrobenz[f]indol-7-amine and related congeners as dopaminergic agonists.
An evaluation of 6-[2-(di-n-propylamino)ethyl]indole (4), its rigid analogue N,N-di-n-propyl-5,6,7,8-tetrahydrobenz[f]indol-7-amine (5), and some related congeners, for ability to suppress serum prolactin in reserpinized rats, revealed modest biological activity in this in vivo model of dopaminergic activity. Although the indole N-H in these compounds can be considered to be oriented "meta" with respect to the ethylamine side chain, compounds with the indole N-H located in the other "meta" position (i.e. 4-[2-(di-n-propylamino)ethyl]indole (2) or its rigid benz[e]indole analogue 3) were much more potent dopamine agonists. The results argue for a particular orientation of the indole N-H vector. In addition, relatively potent dopamine agonists also resulted when the pyrrole portion of the indole ring was replaced by a methanesulfonamido function, supporting the idea that the indole N-H serves as a hydrogen-bond donor.
Nichols
D E
DE
Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana 47907.
Cassady
J M
JM
Persons
P E
PE
Yeung
M C
MC
Clemens
J A
JA
Smalstig
E B
EB
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006900:Hydroxylation; D007211:Indoles / Q000138:chemical synthesis*; D008297:Male; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D007211:Indoles; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C060959:6-(2-(di-n-propylamino)ethyl)indole; C060960:N,N-di-n-propyl-5,6,7,8-tetrahydrobenz(f)indol-7-amine; D011388:Prolactin