Pseudoreceptor and QSAR analysis of new class of analgesics

An introductory prognosis of activity and selectivity of the series of cycl ic enkephalin analogs in which ring formation was achieved via ureido group incorporating the side-chain amino groups of diamino acids is presented. T he aim of our investigations was to construct activity model of new cyclic opioid peptide analogs, and, on the basis of the model, predicting of biolo gical activity of array of analogs to their possible synthesis. As a refere nce set of molecules 28 cyclic peptide analogs were chosen. All of them wer e flexibly fitted to the model of mu-selective receptor pharmacophore based on mu-selective opiates. Subsequent QSAR analysis was conducted using Rece ptor Surface Analysis and Molecular Field Analysis modules in Cerius(2) pac kage. Statistical analysis based on Genetic Function Approximation revealed several QSAR models. Furthermore, CoMFA method from SYBYL package was used as an additional study to check validity of models created by previous too ts. Ten new compounds with known activities but not included in the model w ere used to verify the created models. Those models with accepted predictab ility were used to predict activities of trial molecules.