Structure-activity relationships for the design of small-molecule inhibitors.
One of the most important stages of the drug discovery process is the generation of lead compounds. Structure-activity relationships (SAR) are well-integrated in modern drug discovery and have been largely used for the finding of new leads, scaffold generation, the optimization of receptor or enzyme affinity, as well as of pharmacokinetic and physicochemical properties. This review highlights some SAR approaches that can be used to optimize leads through a continuous, multi-step process based on knowledge gained at each stage, thus exploiting SAR in the design of selective, potent, small-molecule drug candidates.
Centro de Biotecnologia Molecular Estrutural-CBME, Instituto de Física de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao-carlense, 400, 13560-970 Sao Carlos-SP, Brazil. aandrico@if.sc.usp.br
Adriano D
AD
Andricopulo
Carlos A
CA
Montanari
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins; D010600:Pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011955:Receptors, Drug; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases