Structural highlights
Evolutionary Conservation
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Publication Abstract from PubMed
We discovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran- 3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3Kalpha. An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3Kgamma revealed the key hydrogen bonding interactions.
Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran- 3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR).,Tsou HR, MacEwan G, Birnberg G, Grosu G, Bursavich MG, Bard J, Brooijmans N, Toral-Barza L, Hollander I, Mansour TS, Ayral-Kaloustian S, Yu K Bioorg Med Chem Lett. 2010 Apr 1;20(7):2321-5. Epub 2010 Feb 2. PMID:20188552[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tsou HR, MacEwan G, Birnberg G, Grosu G, Bursavich MG, Bard J, Brooijmans N, Toral-Barza L, Hollander I, Mansour TS, Ayral-Kaloustian S, Yu K. Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran- 3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Bioorg Med Chem Lett. 2010 Apr 1;20(7):2321-5. Epub 2010 Feb 2. PMID:20188552 doi:10.1016/j.bmcl.2010.01.135
