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• W4240848402 startingPage "13742" @default.
• W4240848402 abstract "Activity-directed synthesis (ADS), a novel discovery approach in which bioactive molecules emerge in parallel with associated syntheses, was exploited to develop a weakly binding fragment into novel androgen receptor agonists. Harnessing promiscuous intermolecular reactions of carbenoid compounds enabled highly efficient exploration of chemical space. Four substrates were prepared, yet exploited in 326 reactions to explore diverse chemical space; guided by bioactivity alone, the products of just nine of the reactions were purified to reveal diverse novel agonists with up to 125-fold improved activity. Remarkably, one agonist stemmed from a novel enantioselective transformation; this is the first time that an asymmetric reaction has been discovered solely on the basis of the biological activity of the product. It was shown that ADS is a significant addition to the lead generation toolkit, enabling the efficient and rapid discovery of novel, yet synthetically accessible, bioactive chemotypes." @default.
• W4240848402 created "2022-05-12" @default.
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• W4240848402 date "2015-09-11" @default.
• W4240848402 modified "2023-09-26" @default.
• W4240848402 title "Activity-Directed Synthesis with Intermolecular Reactions: Development of a Fragment into a Range of Androgen Receptor Agonists" @default.
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• W4240848402 doi "https://doi.org/10.1002/ange.201506944" @default.
• W4240848402 hasPublicationYear "2015" @default.
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