2. Academic Validation
  3. Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2-ones as potent and selective mTOR kinase inhibitors

Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2-ones as potent and selective mTOR kinase inhibitors

  • Bioorg Med Chem Lett. 2011 Nov 15;21(22):6793-9. doi: 10.1016/j.bmcl.2011.09.035.
Deborah S Mortensen 1,  Sophie M Perrin-Ninkovic,  Roy Harris,  Branden G S Lee,  Graziella Shevlin,  Matt Hickman,  Gody Khambatta,  Rene R Bisonette,  Kimberly E Fultz,  Sabita Sankar
Affiliations

Affiliation

  • 1 Medicinal Chemistry, Celgene Corporation, 4550 Towne Centre Court, San Diego, CA 92121, USA. dmortens@celgene.com
PMID: 21978683 DOI: 10.1016/j.bmcl.2011.09.035
Abstract

We report here the discovery of a novel series of selective mTOR kinase inhibitors. A series of imidazo[4,5-b]pyrazin-2-ones, represented by screening hit 1, was developed into lead compounds with excellent mTOR potency and exquisite kinase selectivity. Potent compounds from this series show >1000-fold selectivity over the related PI3Kα lipid kinase. Further, compounds such as 2 achieve mTOR pathway inhibition, blocking both mTORC1 and mTORC2 signaling, in PC3 Cancer cells as measured by inhibition of pS6 and pAkt (S473).

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z