Journal of Medicinal Chemistry
ARTICLE
4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-trispho-
sphate; RTK, receptor protein tyrosine kinase; PTEN, phos-
phatase and tensin homologue; SAR, structure-activity
relationships; ATP, adenosine-50-triphosphate; MTT, 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; GSK3,
glycogen synthase kinase 3; HUVEC, human umbilical vein
endothelial cells; DMF, N,N-dimethylformamide; DIPE, diiso-
propyl ether
Preparation of 2-aminobenzothiazole derivatives as phosphoinositide
3-kinase (PI3 kinase) modulators. PCT Int. Appl. WO 2009017822,
2009. (c) Bo, Y. Y.; Booker, S.; Bryan, M.; Deak, H. L.; Liu, L.; Andrews,
K.; Nishimura, N.; Norman, M. H.; Panter, K.; Schenkel, L.; Siegmund,
A. C.; Tamayo, N. A.; Yang, K. Heteroarylpyridine derivatives as
inhibitors of PI3 kinase and their preparation and use in the treatment
of cancer. PCT Int. Appl. WO 2009155121, 2009. (d) Hamblin, J. N.;
Jones, P. S.; Keeling, S. E.; Le, J.; Mitchell, C. J.; Parr, N. J. Preparation of
oxazole-substituted indazole derivatives for use as PI3-kinase inhibitors.
PCT Int. Appl. WO 2010125082. 2010. (e) Knight, S. D.; Adams, N. D.;
Burgess, J. L.; Chaudhari, A. M.; Darcy, M. G.; Donatelli, C. A.; Luengo,
J. I.; Newlander, K. A.; Parrish, C. A.; Ridgers, L. H.; Sarpong, M. A.;
Schmidt, S. J.; Van Aller, G. S.; Carson, J. D.; Diamond, M. A.; Elkins,
P. A.; Gardiner, C. M.; Garver, E.; Gilbert, S. A.; Gontarek, R. R.;
Jackson, J. R.; Kershner, K. L.; Luo, L.; Raha, K.; Sherk, C. S.; Sung,
C. M.; Sutton, D.; Tummino, P. J.; Wegrzyn, R. J.; Auger, K. R.; Dhanak,
D. Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the
Mammalian Target of Rapamycin. ACS Med. Chem. Lett. 2010, 1, 39–43.
(f) Hong, S.; Lee, S.; Kim, B.; Lee, H.; Hong, S.-S.; Hong, S. Discovery of
new azaindole-based PI3KR inhibitors: apoptotic and antiangiogenic
effect on cancer cells. Bioorg. Med. Chem. Lett. 2010, 20, 7212–7215.(g)
Adams, N. D.; Darcy, M. G.; Johnson, N. W.; Kasparec, J.; Knight, S. D.;
Newlander, K. A.; Peng, X.; Ridgers, L. H. Pyridosulfonamide derivatives
as PI3 kinase inhibitors. PCT Int. Appl. WO2009055418A1 2009.
(10) (a) Barile, E; De, S. K.; Carlson, C. B.; Chen, V.; Knutzen, C.;
Riel-Mehan, M.; Yang, L.; Dahl, R.; Chiang, G.; Pellecchia, M. Design,
Synthesis, and Structure-Activity Relationships of 3-Ethynyl-1H-inda-
zoles as Inhibitors of the Phosphatidylinositol 3-Kinase Signaling Path-
way. J. Med. Chem. 2010, 53, 8368–8375. (b) Kim, D.; Jun, H.; Lee, H.;
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