Application of the computer automated structure evaluation methodology to a QSAR study of chemoreception. Aromatic musky odorants

Eighty-seven nitro-free aromatic musks and 65 of their odorless structural analogs were studied using the computer automated structure evaluation (CASE) methodology. A QSAR equation relating the strength of musky odor to 23 structural descriptors and (Log f12 was obtained. Lipophilicity appears to be less important than structural features for the strength of musky odor. A hierarchical MultiCASE analysis identified nine structural determinants responsible for the musky smell as well as seven dearomatizing fragments. This allowed speculations about the spatial requirements for interaction between a musk molecule and a hypothetical musky odor receptor. In random testing the (Multi-)CASE model was able to predict a priori 9 of 10 musky odorants and 8 of 9 odorless chemicals correctly. Forty-six nitrated musks were analyzed. Overlap was found between the structural requirements for musky odor in nitrated and nitro-free musks.

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