Distributed Drug Discovery (D3) (J. Comb. Chem.2009,   11, 3-13) employs simple yet powerful synthetic procedures, inexpensive equipment and distributed resources to enable scientists world-wide to readily and reproducibly synthesize new biomimetic molecules as potential drug leads. Molecules to be made using particular D3 based synthetic procedures (e.g. Scheme) are chosen either for their inherent biomimetic nature or through computational analysis of virtual D3 catalogs enumerated from proven D3 synthetic protocols and accessible reagents. D3 molecules have been submitted to the NIH small molecule repository and have been tested in a variety of NIH high-throughput screens. Several hits have been identified through these screens. The flexible nature of D3 protocols permitted the rapid re-synthesis of these hits, with the simultaneous replicated synthesis of analogs. Examples are given for molecules reported to be potentiators at the oxytocin receptor or to cause delayed death in malarial parasites.The ability of D3 accessible biomimetic molecules to lead to marketed drugs will be demonstrated through a retrospective analysis of the discovery of nateglinide, a drug for type II diabetes. A molecule made through the D3 process solely because of its biomimetic nature was found in the literature to be a key part of the SAR that led to nateglinide. This validates the potential for molecules in the biomimetic class represented by D3 virtual catalogs to be synthesized and lead to the discovery of drugs.

Distributed drug discovery (D3): Virtual D3 biomimetic catalogs, tested molecules, hit follow-up, drugs

246th National Meeting (2013)

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