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Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral absorption. Reviewing the syntheses of bRo5 drugs approved since 1990 highlights synthetic chemistry's contribution to drug discovery in this space. Initially, bRo5 drugs were mainly natural products and semi‐synthetic derivatives. Later, peptidomimetics...
Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites, with most of those approved since 1990 belonging to seven major classes. Initially, drugs in this space were natural products, or semi‐synthetic derivatives prepared by selective functional group manipulations in compounds with complex structures. Later, peptidomimetics and de novo designed compounds...
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