A Consensus Neural Network-Based Technique for Discriminating Soluble and Poorly Soluble Compounds

Abstract

BCUT [Burden, CAS, and University of Texas] descriptors, defined as eigenvalues of modified connectivity matrices, have traditionally been applied to drug design tasks such as defining receptor relevant subspaces to assist in compound selections. In this paper we present studies of consensus neural networks trained on BCUTs to discriminate compounds with poor aqueous solubility from those with reasonable solubility. This level was set at 0.1 mg/mL on advice from drug formulation and drug discovery scientists. By applying strict criteria to the insolubility predictions, approximately 95% of compounds are classified correctly. For compounds whose predictions have a lower level of confidence, further parameters are examined in order to flag those considered to possess unsuitable biopharmaceutical and physicochemical properties. This approach is not designed to be applied in isolation but is intended to be used as a filter in the selection of screening candidates, compound purchases, and the application of synthetic priorities to combinatorial libraries.