原创力文档discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (atr)：（发现pyrazolopyrimidine衍生品的新型抑制剂共济失调毛细管扩张和rad3相关蛋白(atr)）.pdfVIP
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discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (atr)：（发现pyrazolopyrimidine衍生品的新型抑制剂共济失调毛细管扩张和rad3相关蛋白(atr)）
Bioorganic Medicinal Chemistry Letters 27 (2017) 750–754
Contents lists available at ScienceDirect
Bioorganic Medicinal Chemistry Letters
journal homepage: www.else /locate/bmcl
Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia
telangiectasia and rad3 related protein (ATR)
Sreekanth A. Ramachandran a, Pradeep S. Jadhavar a, Manvendra P. Singh a, Ankesh Sharma a,
Gaurav N. Bagle a, Kevin P. Quinn b, Po-yin Wong b, Andrew A. Protter b,c, Roopa Rai b, Son M. Pham b,⇑,
Jeffrey N. Lindquist b,⇑
a Integral BioSciences, Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh, 201306, India
b Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States
c Current address: Palo Alto Pharmaceutical Consulting Service, United States
a r t i c l e i n f o a b s t r a c t
Article history: The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly prolifer-
Received 20 December 2016 ating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression.
Accepted 13 January 2017 Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic
Available online 16 January 2017
repurposing of compounds targeting PI3K.
2017 Elsevier Ltd. All rights reserved.
Keywords:
ATR
Pyrazolopyrimidine
DNA damage
PI3K
HTS
Damage to cellular DNA, from intrinsic and extrinsi
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