Open-chain Compounds versus Ring Systems

Open-chain Compounds versus Ring Systems 

There are numerous examples of isosterism between open-chain and ring systems among bioactive molecules [68]. In comparison to the corresponding five-and six-membered ring systems (Chapters 29.2.2 and 29.2.3, respectively), the open-chain compounds exhibit similar broad insecticidal activity, forming a so-called quasi-cyclic conformation when binding to the insect nAChR [69]. 

Generally, the open-chain neonicotinoids are less lipophilic than the corresponding neonicotinoids with a ring structure (Chapters 29.2.2 and 29.2.3). Based on CoMFA results, a binding model for imidacloprid (11) has been described. 

On the other hand, the sterically forbidden regions beyond the imidazolidine 3-nitrogen atom of 11 is important for binding [72]. The area around the 6 hloro atom of the CPM moiety was described as a sterically permissible region. Apparently, the steric interactions were more important for open-chain neonicotinoids than ring systems. 

Finally, it was also shown that the open-chain neonicotinoids bind to the nAChR recognition site in a similar manner to ring structures like 11, and that the electrostatic properties of the open hain neonicotinoids and cyclic imidazolidine structures affected their binding affinity. 

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Open-chain Compounds versus Ring Systems... 

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