This book reviews macrocycles in drug discovery both those of natural origin and semi synthetic derivatives of natural products and those designed and synthesized based on principles of medicinal chemistry the medicinal chemistry of macrocyclic natural products is interesting in itself but lessons learned from these compounds in terms of the relationship between structure and desirable physicochemical properties are now informing the design of fully synthetic macrocyclic drug . Macrocycles in drug discovery have been defined as a ring system consisting of 12 or more atoms opinions differ on the definition of macrocycles based on ring size but this option usefully captures the qualitative differences in behavior between large macrocyclic rings 12 atoms and medium rings 8 11 atoms. Returning to one of the primary drivers for the pursuit of macrocycles in drug discovery the potential to address intractable targets such as ppi the unique and versatile nature of the macrocyclic framework again has been demonstrated with increasing reports of successful modulation of this target class with these molecules although such applications are still too early stage to gauge their clinical impact 30 interestingly in a comprehensive analysis of how drug molecules bind to their . Macrocycles in new drug discovery the use of drug like macrocycles is emerging as an exciting area of medicinal chemistry with several recent examples highlighting the favorable changes in biological and physicochemical properties that macrocyclization can afford
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