3PS6

Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.

Summary for 3PS6

• Entry DOI: 10.2210/pdb3ps6/pdb
• Related: 3ML8 3ML9 3OAW 3PRE 3PRZ
• Descriptor: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 4-amino-N-(6-methoxypyridin-3-yl)-2-methylquinazoline-8-carboxamide (2 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: 111036.43

Authors

Knighton, D.R.,Greasley, S.E.,Rogers, C.M.-L. (deposition date: 2010-11-30, release date: 2011-02-09, Last modification date: 2024-02-21)

Primary citation

Liu, K.K.,Huang, X.,Bagrodia, S.,Chen, J.H.,Greasley, S.,Cheng, H.,Sun, S.,Knighton, D.,Rodgers, C.,Rafidi, K.,Zou, A.,Xiao, J.,Yan, S.
Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.
Bioorg.Med.Chem.Lett., 21:1270-1274, 2011

PubMed Abstract: Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3-D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs.

PubMed: 21269826
DOI: 10.1016/j.bmcl.2010.12.026

Experimental method

X-RAY DIFFRACTION (2.6 Å)