Comprehensive sampling of diverse chemistry space: A key driver for primary screening libraries


Ying Zhang, Jean Patterson, Libing Yu, and Carmen M. Baldino. Department of Chemistry, ArQule, Inc, 19 Presidential Way, Woburn, MA 01801
Diversity-oriented synthesis (DOS) provides an efficient strategy for accessing an almost infinite amount of diverse chemistry space with complex and functionally dense natural product-like structures. However, the challenge of rapidly developing the required chemical methods to synthesize these high value libraries still remains. Herein, we describe our standardized chemistry development approach that leverages the systematic sampling of the desired chemistry space to provide much needed efficiencies. Application of this strategy has afforded the efficient development of high throughput chemistry protocols delivering significant collections of purified screening libraries that embody the desired balance of physicochemical properties to support early stage drug discovery programs.