4FA6

Design and Synthesis of a Novel Pyrrolidinyl Pyrido Pyrimidinone Derivative as a Potent Inhibitor of PI3Ka and mTOR

Summary for 4FA6

• Entry DOI: 10.2210/pdb4fa6/pdb
• Related: 4FAD
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 2-amino-8-cyclopentyl-4-methyl-6-(1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidin-7(8H)-one (3 entities in total)
• Functional Keywords: phosphoinositide kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P48736
• Total number of polymer chains: 1
• Total formula weight: 111037.46

Authors

Pannifer, A.,Greasley, S.E. (deposition date: 2012-05-21, release date: 2013-04-03, Last modification date: 2024-02-28)

Primary citation

Le, P.T.,Cheng, H.,Ninkovic, S.,Plewe, M.,Huang, X.,Wang, H.,Bagrodia, S.,Sun, S.,Knighton, D.R.,LaFleur Rogers, C.M.,Pannifer, A.,Greasley, S.,Dalvie, D.,Zhang, E.
Design and synthesis of a novel pyrrolidinyl pyrido pyrimidinone derivative as a potent inhibitor of PI3Kalpha and mTOR
Bioorg.Med.Chem.Lett., 22:5098-5103, 2012

PubMed Abstract: Lead optimization efforts that employed structure base drug design and physicochemical property based optimization leading to the discovery of a novel series of 4-methylpyrido pyrimidinone (MPP) are discussed. Synthesis and profile of 1, a PI3Kα/mTOR dual inhibitor, is highlighted.

PubMed: 22749419
DOI: 10.1016/j.bmcl.2012.05.100

Experimental method

X-RAY DIFFRACTION (2.7 Å)