Ester lability steric effects

Ester functions present in molecules tend to be considered labile although steric effects etc. may be utilized to produce drugs without inherent chemical or metabolic problems due to ester lability. For instance a series of antimuscarinic compounds which had selectivity for the M3 receptor (Figure 7.18) were stabilized by the incorporation of a hydroxy ethyl side chain or a cyclic ring system at positions surrounding the ester function. Presumably the proximity of these groups to the ester function (carbonyl) prevents close approach of the attacking nucleophile, in this case probably a serine hydroxyl. 

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