Target-oriented and diversity-oriented organic synthesis in drug discovery

Modern drug discovery often involves screening small molecules for their ab ility to bind to a preselected protein target. Target-oriented syntheses of these small molecules, individually or as collections (focused Libraries), can be planned effectively with retrosynthetic analysis. Drug discovery ca n also involve screening small molecules for their ability to modulate a bi ological pathway in cells or organisms, without regard for any particular p rotein target. This process is Likely to benefit in the future from an evol ving forward analysis of synthetic pathways, used in diversity-oriented syn thesis, that Leads to structurally complex and diverse small molecules. One goal of diversity-oriented syntheses is to synthesize efficiently a collec tion of small molecules capable of perturbing any disease-related biologica l pathway, Leading eventually to the identification of therapeutic protein targets capable of being modulated by small molecules. Several synthetic pl anning principles for diversity-oriented synthesis and their role in the dr ug discovery process are presented in this review.