Synthesis and dopamine receptor modulating activity of unsubstituted and substituted triproline analogues of L-prolyl-L-leucyl-glycinamide (PLG).
Triprolines Pro-Pro-Pro-NH2 (4), Pro-Pro-D-Pro-NH2 (5), Pro-Pro(trans-3-Me)-D-Pro-NH2 (6), and Pro-Pro(cis-3-Me)-D-Pro-NH2 (7) were made as conformationally constrained analogues of Pro-Leu-Gly-NH2. Triprolines 4-6 produced significant increases in the high- and low-affinity state ratio (RH/RL) of the dopamine receptor, but only 4 was found to increase apomorphine induced rotations in 6-hydroxydopamine-lesioned rats.
Baures
P W
PW
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455, USA.
Pradhan
A
A
Ojala
W H
WH
Gleason
W B
WB
Mishra
R K
RK
Johnson
R L
RL
D000818:Animals; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*
D011954:Receptors, Dopamine; D009075:MSH Release-Inhibiting Hormone