GSK 2636771

Company: GlaxoSmithKline
Meant to treat: tumors with loss-of-function in the tumor suppressor protein PTEN (phosphatase and tensin homolog)- 2nd most inactivated tumor suppressor after p53- cancers where this is often the case include prostate and endometrial
Mode of action: inhibitor of phosphoinositide 3-kinase-beta (PI3K-beta). Several lines of evidence suggest that proliferation in certain PTEN-deficient tumor cell lines is driven primarily by PI3K-beta.
Medicinal chemistry tidbits: The GSK team seemed boxed in because in 3 out of 4 animals used in preclinical testing, promising drug candidates had high clearance. It turned out that a carbonyl group that they thought was critical for interacting with the back pocket of the PI3K-beta enzyme wasn’t so critical after all. When they realized they could replace the carbonyl with a variety of functional groups, GSK2636771 eventually emerged. GSK2636771B (shown) is the tris salt of GSK2636771.
Status in the pipeline: Phase I clinical trials..........http://cenblog.org/the-haystack/2012/03/liveblogging-first-time-disclosures-from-acssandiego/
CARMEN
Posted By Carmen Drahl on Mar 24, 2012

Phone: 202-872-4502

Fax: 202-872-8727 or -6381

1372540-25-4
1H-​Benzimidazole-​4-​carboxylic acid, 2-​methyl-​1-​[[2-​methyl-​3-​(trifluoromethyl)​phenyl]​methyl]​-​6-​(4-​morpholinyl)​-
2-Methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid
GSK2636771 is a potent, orally bioavailable, PI3Kβ-selective inhibitor, sensitive to PTEN null cell lines.
Formula:C₂₂H_22F3N₃O₃
M.Wt:433.43
SEE AT
http://newdrugapprovals.org/2015/03/19/gsk-2636771/
 ............

WO2012047538

http://www.google.com/patents/WO2012047538A1?cl=en
Example 31

Preparation of 2-methyl- 1 - { [2-methyl-3-(trifluoromethyl)phenyllmethyl| -6-(4-morpholiny0- 1 H-benzimidazole-4-carboxylic acidAn aqueous solution of 2 N LiOH (1.2 mL) was added to a solution of methyl 2-methyl- 1- {[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-lH-benzimidazole-4- carboxylate, prepared as described in Example 30 (180 mg, 0.4 mmol) in THF (10 mL) and stirred at 50° C for 1 h. When TLC showed no starting material remaining, the mixture was cooled to rt and THF was removed under reduced pressure. The pH of the mixture was acidified to pH 3. The suspension was filtered and the filtrate was collected, and washed with water (lOmL) to give the product as a white solid (152 mg, yield 88%).
1H NMR (300 MHz,DMSO-d₆):
δ ppm 2.46 (s, 3H), 2.54 (s, 3H), 3.10 (t, 4H, J=4.8 Hz), 3.73 (t, 4H, J=4.8 Hz), 5.63 (s, 2H), 6.37 (d, IH, J=7.8 Hz), 7.26 (t, IH, J=7.8 Hz), 7.35 (d, IH, J=2.4 Hz), 7.44 (d, IH, J=2.4 Hz), 7.62 (d, IH, J=7.8 Hz);
LC-MS: m/e = 434 [M+l]


SEE AT
http://newdrugapprovals.org/2015/03/19/gsk-2636771/





SEE AT
http://newdrugapprovals.org/2015/03/19/gsk-2636771/









SEE AT
http://newdrugapprovals.org/2015/03/19/gsk-2636771/