Geldenhuys, Werner J.Novotny, NicholasMalan, Sarel F.Van der Schyf, Cornelis J.2018-01-102018-01-102013Geldenhuys, W.J. et al. (2013). 3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (σ1) receptor. Bioorganic & Medicinal Chemistry Letters, 23: 1707 – 17110968-0896http://dx.doi.org/10.1016/j.bmcl.2013.01.069http://hdl.handle.net/10566/3370Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure–activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (r1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q2) regression value of 0.6, and a non-cross validatedr2 of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of atest set with an r2 >0.7. We also describe here the docking of the PCU-derivedcompounds into a homology model of the sigma-1 (r1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [3H]pentazocine binding assay anoxa-PCU, NGP1-01 (IC50 = 1.78 lM) and its phenethyl derivative (IC50 = 1.54 lM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(r1)enThis is the author-version of the article published online at: http://dx.doi.org/10.1016/j.bmcl.2013.01.069PentacycloundecylaminesSigma-1 receptorCoMFAGlaucomatous neurodegenerationHomology modelingArticle