Drug design bioisosteric replacement

Various bioisosteric replacements for a phenolic hydroxyl have been explored. One such, a lactam NH, is incorporated into the design of the 3-adrenergic blocker, carteolol O)- The fundamental synthon is carbostyril derivative K This is reacted in the usual manner with epichlorohydrin to give which is in turn reacted with t-butylamine to complete the synthesis of carteolol (3 ), a drug that appears to have relatively reduced nonspecific myocardial depressant action. Carrying this de-... 

Devereux, M. and Popelier, P.LA. (2010) In silico techniques for the identification of bioisosteric replacements for drug design. Current Topics in Medicinal Chemistry, 10, 657-668. 

Database a web-based tool using quantum chemical topology to predict bioisosteric replacements for drug design. Journal of Chemical Information and Modeling, 49 (6), 1497-1513. 

While bioisosterism had been comprehensively treated in several printed reviews dealing with common replacements used in analogue design, computer databases allowing (sub)structure searches were slow to appear. Toshio Fujita was the first to tackle this problem and, in the early 1990s, developed EMIL (Example-Mediated Innovation for Lead Evolution), an expert system built around a knowledge base of thousands of consecutive structural modification patterns for several drug and pesticide classes described in the literature [12, 13]. ... 

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