Design of μ selective opioid dipeptide antagonists

We have recently designed potent 5 selective opioid antagonist dipeptides on the basis of a simple conformational analysis. Following a similar procedure we found a \i selective dipeptide antagonist, 2,6-dimethyl-Tyr-D-Phe-NH2. Although its selectivity is not as high as those of the quoted S selective dipeptides it has good in vitro activity and looks very promising for further development since the 2,6-dimethyl-Tyr-D-Phe message, like the 8 selective 2,6-dimethyl-Tyr-l,2,3,4-tetrahydroisoquinoline- 3-carboxylic acid counterpart, seems able to impart antagonism to longer peptides.