Maxdo and RDF55v are Crucial Molecular Descriptors Governing the Cannabinoid Receptor 1(CB1) Modulator Activity of N, N'-diphenyl Urea Analogs and 1H-Indole-2-carboxamides

Abstract

CB1 allosteric modulators such as synthetic cannabinoids are promising therapeutic agents. Among the various CB1 receptor modulators, indole-2-carboxamides, and N, N'-diphenyl urea derivatives are continuously explored for their potency and selectivity towards the receptor. In the present computational work, QSAR models were generated using Drug Theoretics and Chemoinformatics (DTC tools) tools to analyze the influence of molecular features of these modulators (one hundred and fourteen compounds) on the activity. A statistically significant three-parameter model (SPMin2_Bhm, maxdO, and minssN) was derived that displayed R2 and Q2 values of 0.66 and 0.62, respectively. SPMin2_Bhm and maxdO negatively correlated with the activity, whereas minssN has a positive connection. A seven-parameter model (maxdO, minsssN, RDF55v, VE3_D, minHBint10, SpMin5_Bhs, and CrippenLogP) was also obtained with R2 and Q2 values of 0.76 and 0.70, respectively. The findings might assist in the design and development of novel CB1 modulators based on the structures of indole-2-carboxamides and N, N'-diphenyl urea