-transparent.png){kind=logo}
Discovery of 5,7-Dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ones as Highly Selective CDK2 Inhibitors. 2022
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-off, Wilmington, Delaware 19803, United States.
A series of exceptionally selective CDK2 inhibitors are described. Starting from an HTS hit, we successfully scaffold hopped to a 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one core structure, which imparted a promising initial selectivity within the CDK family. Extensive further SAR identified additional factors that drove selectivity to above 200× for CDKs 1/4/6/7/9. General kinome selectivity was also greatly improved. Finally, use of in vivo metabolite identification allowed us to pinpoint sulfonamide dealkylation as the primary metabolite, which was ameliorated through the deuterium effect.
| UI | MeSH Term | Description | Entries |
|---|
Related Publications
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
November 2019,
Bioorganic chemistry,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
January 2019,
Biological & pharmaceutical bulletin,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
November 2021,
Archiv der Pharmazie,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
March 2013,
Bioorganic & medicinal chemistry,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
December 2022,
Journal of enzyme inhibition and medicinal chemistry,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
August 2002,
Bioorganic & medicinal chemistry letters,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
July 2011,
Drug and chemical toxicology,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
April 1979,
Il Farmaco; edizione scientifica,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
May 2018,
Bioorganic & medicinal chemistry letters,
Alexander Sokolsky, and
Sarah Winterton, and
Keith Kennedy, and
Katherine Drake, and
Kristine Stump, and
Lu Huo, and
Yvonne Lo, and
Min Ye, and
Maryanne Covington, and
Sharon Diamond, and
Yan-Ou Yang, and
Sunkyu Kim, and
Swamy Yeleswaram, and
Liangxing Wu, and
Wenqing Yao
October 2016,
ACS medicinal chemistry letters,
