Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1-ones as novel selective TRIM24/BRPF1 bromodomain inhibitors
TRIM24 (tripartite motif-containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are epigenetics “readers” and potential therapeutic targets for cancer and other diseases. Here we describe the structure-guided design of 1-(indolin-1-yl)ethan-1-ones as novel TRIM24/BRPF1 bromodomain inhibitors. The representative compound 20l (Y08624) is a new TRIM24/BRPF1 dual inhibitor, with IC50 values of 0.98 and 1.16 μM, respectively. Cellular activity of 20l was validated by viability assay in prostate cancer (PC) cell lines. In PC xenograft models, 20l suppressed tumor growth (50 mg/kg/day, TGI = 53%) without exhibiting noticeable toxicity. Compound 20l represents a versatile starting point for the development of more potent TRIM24/BRPF1 inhibitors.
3-AZABICYCLO [3.1.0] HEXANE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
The present invention relates to 3-azabicyclo[3.1.0]hexane derivatives, which are useful as vanilloid receptor (VR) ligands, methods of treating diseases, conditions and/or disorders modulated by vanilloid receptors with them, and processes for preparing them.
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Page/Page column 34-35
(2009/08/16)
Synthesis of 2-aryl- and 2,5-diarylfurans and thiophenes by Suzuki-Miyaura reactions using potassium trifluoroborate salts and heteroaryltellurides
The Suzuki-Miyaura cross-coupling reaction of 2-(butyltellanyl) or 2,5-bis-(butyltellanyl)furans and thiophenes with potassium aryltrifluoroborate salts catalyzed by palladium afforded 2-aryl- or 2,5-diaryl-furans and thiophenes in moderate to good yields.
Botteselle, Giancarlo V.,Hough, Thomas L. S.,Venturoso, Raphael C.,Cella, Rodrigo,Vieira, Adriano S.,Stefani, Helio A.
experimental part
p. 870 - 873
(2009/04/11)
SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 6- AND 7--1-ETHYL-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXYLIC ACIDS
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Glushkov, R. G.,Adamskaya, E. V.,Oleinik, A. F.,Silin, V. A.,Padeiskaya, E. N.,Solov'eva N. P.
p. 200 - 203
(2007/10/02)
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