title: Strategies and tactics for optimizing the Hit-to-Lead process and beyond--a computational chemistry perspective.
abstract: The Hit-to-Lead-to-Candidate process continues to evolve rapidly, and while technological advances offer much potential, the reality often pales to the promise. Conversely, strategies and tactics implementing existing technologies may result in more benefit in the end. This article focuses on some of the thinking and approaches that may improve the efficiency and effectiveness of the beginnings of the drug discovery path. From the perspective of computational chemists, different types of strategy and philosophy of approach will be treated including: considerations of early lead choices, strategies for improving poor leads, multivariate optimization, opportunities for informatics, and engineering good decisions.
authors.affiliation: Neurogen Corporation, 35 N.E. Industrial Road, Branford, CT 06405, United States. cmanly@yahoo.com
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Manly
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Chandrasekhar
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Ochterski
authors.forename: Jack D
authors.initials: JD
authors.lastname: Hammer
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Warfield
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D003657:Decision Making; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D011340:Problem Solving; D013678:Technology, Pharmaceutical / Q000379:methods*