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Complexity‐to‐Diversity and Pseudo‐Natural Product Strategies as Powerful Platforms for Deciphering Next Generation Therapeutics

Von Wiley-VCH zur Verfügung gestellt

Stereochemical and skeletal complexity are particularly important vis-à-vis the cross-talks between a small molecule and a complementary active site of a biological target. This intricate harmony is known to increase selectivity, reduce toxicity, and increase the success rate in clinical trials. Therefore, the development of novel strategies for establishing underrepresented chemical space that is rich in stereochemical, and skeletal diversity represents an important milestone in a drug discovery campaign. In this review, we aim to discuss the evolution of interdisciplinary synthetic methodologies utilized in chemical biology and drug discovery that has revolutionized the discovery of first-in-class molecules over the last decade with an emphasis on Complexity-to-Diversity (CtD) and Pseudo-Natural product strategies as a remarkable toolbox for deciphering the next generation therapeutics. We also report on how these approaches dramatically revolutionized the discovery of novel chemical probes that target underrepresented biological space. We also highlight selected applications and discuss key opportunities offered by these tools and important synthetic strategies utilized for the construction of chemical spaces that are rich in skeletal and stereochemical diversity. We also gave our insight on how the integration of these protocols will strategically hold a promise of changing the landscape of the drug discovery (DD).

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