Retrosynthetic Combinatorial Analysis Procedure

Lewell XQ, Judd DB, Watson SP, Hann MM. RECAP—retrosynthetic combinatorial analysis procedure a powerful new techniqne for identifying privileged molecular fragments with useful applications in combinatorial chemistry. J Chem Inf Comput Sci 1998 38 511-22. 

Figure 8.12 Retrosynthetic combinatorial analysis procedure (RECAP).

Another way to obtain a library of fragments is to decompose a known database of drug- or lead-like molecules by /j gMifo-retrosynthetic rules like RECAP (Retrosynthetic Combinatorial Analysis Procedure).The RECAP bond cleavage procedure consists of eleven bond cleavage types shown in Figure 7.3. This approach has several advantages ... 

In a similar effort, researchers from the same company used AstraZeneca data and ADMET properties, namely, solubility, plasma protein binding, and lipophilicity (log D) from a pool of 50000 molecules in total [16]. In particular, a set of approximately 9000 side chains was identified by applying the fragmentation rules proposed in Retrosynthetic Combinatorial Analysis Procedure (RECAP) [26]. The MMPs were then generated easily by identifying compounds that contain any of the aforementioned predetermined Ust of side chains. The authors reported the most frequent side chain replacements, as well as the replacements that lead to an increase of the average property value, although their statistics were based on relatively low numbers of observations for each replacement (11-77). 

Lewell, X.Q., Judd, D.B., Watson, S.P., and Harm, M.M. (1998) RECAP— Retrosynthetic Combinatorial Analysis Procedure a powerfid new technique for identifying privileged molecular fragments with usefid applications in combinatorial chemistry. Journal of Chemical Information and Computer Sciences, 38 (3), 511-522. 

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