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The concept of so-called "privileged structures" was initially proposed by scientists at Merck in 1980s (see ref. Journal of Medicinal Chemistry, 31, 2235-2246, 1988). They observed in their research at Merck that certain type of structures were preferred by certain class of receptors (proteins). For example, Spiro-based structures are preferred by GPCR receptors, while purine-based structures are preferred by kinases.
Privileged structures are usually rigid, hetero-cycle based structures. The following structures are some examples of privileged structures: |
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Currently on the market, a significant amount of drugs contain a privileged structure in their molecules. For example, the following drugs, Atorvastatin, Sildenafil, and Erlotinib.
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all contain a privileged structure in their molecules: |
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Atorvastatin |
Sildenafil |
Erlotinib |
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It appears that the main function of the privileged structure in a drug molecule is to position those functional groups that are attached to it in a right direction and help them interact with the receptor properly. Therefore, it's logical to think that by replacing the privileged structure of a drug molecule while keeping those functional groups unchanged, we might find a better drug. For example, Erlotinib is a drug for the treatment of cancer. By replacing its privileged structure with other privileged structures, we can potentially design and synthesize the following novel analogs ( 1 - 5 ): |
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The most convincing successful example of privileged structure-based drug discovery has been the development of Levitra by Bayer and GSK. The structural similarity of both drugs is striking: |
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At SSCT, we have designed over 500 novel and drug-like privileged structures and some of them are currently in stock. Please feel free to contact us for your drug discovery needs and we are happy to help you design and synthesize any novel privileged structures to speed up your drug discovery process.
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