Study of the structural requirements for dopa potentiation and oxotremorine antagonism by L-propyl-L-leucylglycinamide

Article abstract of DOI:10.1021/jm00200a004

A number of analogues of the tripeptide L-prolyl-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetronitrile, amino-2-propanone, semicarbazide, or β-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide and L-propyl-L-leucyl-(+)-thiazolidine-2-carboxamide showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-prolyl-L-leucyl-L-prolinamide, on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotinin potentiation test.