title: Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR).
abstract: The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.
authors.affiliation: Integral BioSciences, Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh, 201306, India.
authors.forename: Sreekanth A
authors.initials: SA
authors.lastname: Ramachandran
authors.affiliation: Integral BioSciences, Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh, 201306, India.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Jadhavar
authors.affiliation: Integral BioSciences, Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh, 201306, India.
authors.forename: Manvendra P
authors.initials: MP
authors.lastname: Singh
authors.affiliation: Integral BioSciences, Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh, 201306, India.
authors.forename: Ankesh
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Integral BioSciences, Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh, 201306, India.
authors.forename: Gaurav N
authors.initials: GN
authors.lastname: Bagle
authors.affiliation: Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Quinn
authors.affiliation: Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States.
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Wong
authors.affiliation: Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States; Current address: Palo Alto Pharmaceutical Consulting Service, United States.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Protter
authors.affiliation: Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States.
authors.forename: Roopa
authors.initials: R
authors.lastname: Rai
authors.affiliation: Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States.
authors.forename: Son M
authors.initials: SM
authors.lastname: Pham
authors.affiliation: Medivation, Now Pfizer Inc., 525 Market Street, 36th Floor, San Francisco, CA 94105, United States. Electronic address: pham.sm@gmail.com.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Lindquist
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; C000621046:1-(4-(methylsulfonyl)phenyl)-3-(1H-pyrrolo(2,3-b)pyridin-5-yl)-1H-pyrazolo(3,4-d)pyrimidin-4-amine; C118531:pyrazolopyridine
keywords: ATR; DNA damage; HTS; PI3K; Pyrazolopyrimidine