Conformational analysis of HIV gp41 inhibitors

ORGN 77

Sarah M. Remmert, sarah.remmert@richmond.edu1, Carol A. Parish, cparish@richmond.edu1, and Inmaculada Robina, robina@us.es2. (1) Department of Chemistry, University of Richmond, 28 Westhampton Way, University of Richmond, VA 23173, (2) Department of Organic Chemistry. Faculty of Chemistry, University of Seville, P.O. Box 553, 41071-Seville, Spain
Nine potential inhibitors of HIV viral membrane protein gp41 were characterized by classical mechanical conformational searching techniques using the Schrödinger software package. Mixed low mode and Monte Carlo searching techniques were performed to exhaustively sample the OPLS2005/GBSA(water) potential energy surface of trisubstituted cyclohexane and benzene derivatives of C3 symmetry. Geometric structure, molecular length, and hydrogen bonding patterns were analyzed. Non-aromatic compounds exhibited exclusively chair conformation geometry at low energies, with a preference for axial or equatorial substituent positions depending upon the presence of additional ring substituent methyl groups. Increasing chain length often resulted in overall shorter molecular length, due to additional chain flexibility. These results were consistent with two dimensional temperature dependent NMR studies.
 

Process R&D, Physical Organic Chemistry, Heterocycles, Aromatics, Metal-Mediated Reactions
8:00 PM-10:00 PM, Sunday, March 25, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Organic Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007