3D-QSAR Studies on the Biological Activity of Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor Antagonists

Background: Human immunodeficiency virus type 1 (HIV-1) infection ultimately leading to acquired immunodeficiency syndrome (AIDS), remains a significant problem. CCR5 is a member of the chemokine receptor family that is utilized in the early stage of the replication cycle by the most commonly transmitted M-tropic strains of HIV-1. In this study, we developed 3D-QSAR models using CoMFA and CoMSIA methods on a series of 71 imidazolidinylpiperidinylbenzoic acid CCR5 antagonists, in order to better understand the substituent requirements and get more potent antagonists of CCR5. Methods: The research of 3D-QSAR modeling of imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 (CCR5) antagonists was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Results: For this study, a dataset containing 71 imidazolidinyl-piperidinyl-benzoic acids was divided into a training set of 22 compounds and a test set of 49 compounds. The results obtained from the CoMFA/CoMSIA model exhibited a statistical significance r 2 of 0.996 (0.984) with an estimated standard error of 0.109 (0.209). Conclusion: Both CoMFA and CoMSIA models provided valuable insight into the structural requirements for improving the activity of then CCR5 antagonists.