W0402

Molecular Interactions and Methanesulfonanilides. P.W. Codding¹ and P.I. Lario², ¹Univ. of Victoria, Victoria, Canada; ²Univ. of British Columbia, Vancouver, Canada.

Crystal structure analyses of methanesulfonanilides show that a specific intramolecular interaction reduces the geometric possibilities for hydrogen bond formation between the sulfonyl and NH groups and other molecules. This finding has implications for the utility of methanesulfonilides in drug design particularly in the use of this fragment as a bioisostere for more constrained moieties like cyano, imidazole and nitro groups. Databases of fragment intermolecular interactions are often used to predict molecular interactions and may need mechanisms for incorporating the presence of strong intramolecular interactions to allow accurate prediction of the geometry of the assembly. In the sulfonylanilides the intramolecular interaction arises from steric interactions between phenyl hydrogen atoms and the NH group and from an intramolecular C-H···O hydrogen bond. Progress in evaluating the relative importance of these two forces and developing methods to combine fragment information will be presented.