Screening, biological

Computer-aided inhibitor design is a relatively new and powerful approach for the development of novel, potentially potent, nonsubstrate-analogue enzyme inhibitors. Computer-aided methods and biological screening can each lead to new classes of novel inhibitors. However, computer-aided design methods can focus the search for inhibitors, thereby circumventing much of the time-consuming synthetic and natural product purification procedures for those compounds they find unlikely to function as inhibitors. 

Coe et al. reported an efficient modification for the preparation of /-substituted indole analogs for biology screening in good yield. The intermediate P-nitrostyrene 44, prepared from the condensation of 43 with DMFDMA, underwent methanolysis and reduction to provide the aniline acetal intermediate 45. Alkylation of amine 45 was carried out employing standard conditions of reductive alkylation to provide A-alkyl analogs represented by 46. The indole 47 was generated by formation of the oxonium ion (from 46) under acidic conditions, followed by cyclization, accompanied by loss of methanol. 

Considering a median value of 106"1 possible structures in chemical space clearly indicates that the number of possible structures available is far too large for complete coverage by chemical synthesis and biological screening. It has been... 

Desbrow, C., Routledge, E.J., and Brighty, G.C. et al. (1998). Identification of estrogenic chemicals in STW effluent. 1. Chemical fractionation and in vitro biological screening. Environmental Science and Technology 32, 1549-1558. 

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