Synthesis and dopamine receptor modulating activity of unsubstituted and substituted triproline analogues of L-prolyl-L-leucyl-glycinamide (PLG)

Abstract Triprolines Pro-Pro-Pro-NH 2 ( 4 ), Pro-Pro- d -Pro-NH 2 ( 5 ), Pro-Pro (trans-3- Me)- d -Pro-NH 2 ( 6 ), and Pro-Pro (cis-3- Me)- d -Pro-NH 2 ( 7 ) were made as conformationally constrained analogues of Pro-Leu-Gly-NH 2 . Triprolines 4–6 produced significant increases in the high- and low-affinity state ratio ( R H R L ) of the dopamine receptor, but only 4 was found to increase apomorphine induced rotations in 6-hydroxydopamine-lesioned rats.