Direct Structure-Efficacy Correlation

As compared to the natural ligand ACh, the conformation of anatoxin is relatively rigid, with only one rotatable bond as compared to four in ACh. This simplifies the ability to correlate the structural conformation of the ligand to efficacy, and, consequently, attention has been directed toward determining the active conformation through the use of sterically constrained analogs of the s-ds and s-trans conformers of anatoxin-a [19,40-44]). Although current evidence leans toward s-trans as the active conformation, condusive evidence, such as a crystal structure of (+)-anatoxin-a in complex with an nACh receptor, is still needed. 

This remarkable efficacy could be directly correlated to calculated properties of the compounds by means of a novel, quantitative structure-activity relationship model. 

The aromatic amines phenothiazine, phenoxa-cine, and iminostUbene (formula [276]) proved to be about two orders of magnitude more effective than common phenolic antioxidants in their protective activity against oxidative nerve cell death (Moosmann et al. 2001). This remarkable efficacy could be directly correlated to calculated properties of the compound by means of a novel, quantitative structure-activity relationship model. 

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