Synthesis and biological evaluation of (2‐aminosulfonylpyridin‐6‐yl)pyrazolopyrimidinone derivatives as Wee1 inhibitors for cancer treatment
Yeon Ju Kim,
Myoung Eun Jung,
Ju Yeong Lee
et al.
Abstract:For an analog‐based design of novel Wee1 inhibitors, we profiled in vitro ADMET and in vivo PK properties of adavosertib. Based on the properties of adavosertib, we aimed to improve its metabolic stability by designing a novel target compound 1a with an aminosulfonyl group instead of the 2‐hydroxypropan‐2‐yl moiety in adavosertib. Derivatives of target compound 1a were synthesized and evaluated for Wee1 enzyme inhibition and liver microsomal phase I stability. We identified compound 1a as a sub‐nanomolar Wee1 … Show more
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