Drug discovery structure-activity relationships

The Negishi cross-coupling reactions have been showcased as key steps in the synthesis of many natural products and in structure-activity relationship drug discovery programmes. 

The early empirical structure-activity relationships promoted discovery of second-generation anticancer drugs such as complexes 2 and 3. However, analogs of these drugs usually display similar clinical profiles to the parent drugs. Therefore new classes of platinum complexes are required with distinct properties. 

Mechanism-based inactivation of cytochrome P450 enzymes Structure-activity relationships and discovery strategies to mitigate drug—drug interaction risks 12JMC4896. 

Johns DG, Duffy J, Fisher T, Hubbard BK, Forrest MJ (2012) On- and off-target pharmacology of torcetrapib current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors. Drugs 72 491-507... 

Kubinyi H 1995. The Quantitative Analysis of Structure-Activity Relationships. In Wolff M E (Editor) Burger s Medicinal Chemistry and Drug Discovery. 5th Edition, Volume 1. New York, John Wiley Sons, pp. 497-571. 

Considerable progress has been made in understanding the chemical principles in Pt-nucleic acid interactions since the discovery of Pt antitumor drugs. At the same time, however, new questions have been raised upon development of novel drugs that violate the early structure-activity relationships. A common feature for various Pt drugs is that their initial binding to nucleic acid fragments seems to be controlled by the... 

Abraham, D.J. (Ed.). History of quantitative structure activity relationships. In Burger s Medicinal Chemistry and Drug Discovery, Volume 3. John Wiley Sons, Hoboken, NJ, 2003, 1-48. Chapters by Selassie, C.D. Tropsha, a. Recent trends in quantitative stmcture-activity relationships, 49-76 Marshall, G.R. Beusen, D.D. Molecular modeling in drug design, 77-168 ... 

Frye SV. (1999) Structure-activity relationship homology (SARAH) A conceptual framework for drug discovery in the genomic era. Chem. Biol. 6 R3-R7. 

Abstract Inhibitors of the kinases controlling the cell cycle have emerged as an important therapeutic modality for the treatment of cancer. Drug discovery efforts have focused on inhibitors of the cyclin-dependent kinases, the Aurora kinases, and Polo-like kinases. Agents for each kinase are now advancing in human clinical trials. In this review we will summarize the work in this area with special emphasis on the structural biology and structure-activity relationships developed for the many chemotypes explored. 

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