Conformational Analysis and the Olfactophore Approach

The models can be tested using inactive molecules. These, in theory, should not be able to satisfy the proposed biophore. However, inactivity can be the result of other factors. For example, a molecule that can fulfil the distance geometry requirements may, in fact, be inactive because it cannot reach the site of detection. The latter will be determined by physicochemical properties such as hydrophobicity, solubility and volatility. 

In fact, the main criticism of the olfactophore approach is that it does not take into account these types of properties. 

Since the identification of olfactophores is best suited to sets of compounds with a limited amount of conformational flexibility, this technique has mostly been applied to the following odour areas  

Pelzer s analysis of 73 alcohols produced the following rules for olfactophore 1. 

1) Cl is substituted by one to three alkyl groups, ideally three, provided that the hydroxyl group is not overshadowed too strongly by steric hindrance. 

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