161599-56-0Relevant academic research and scientific papers
Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl} phenylsulfamate: Synthesis, SAR, crystal structure, and in vitro and in vivo activities
Wood, Paul M.,Woo, L. W. Lawrence,Labrosse, Jean-Robert,Thomas, Mark P.,Mahon, Mary F.,Chander, Surinder K.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
, p. 1577 - 1593 (2011/12/01)
The design and synthesis of a series of bicyclic ring containing dual aromatase-sulfatase inhibitors (DASIs) based on the aromatase inhibitor (AI) 4-[(4-bromobenzyl)(4H-1,2,4-triazol-4-yl)amino] benzonitrile are reported. Biological evaluation with JEG-3 cells revealed structure-activity relationships. The X-ray crystal structure of sulfamate 23 was determined, and selected compounds were docked into the aromatase and steroid sulfatase (STS) crystal structures. In the sulfamate-containing series, compounds containing a naphthalene ring are both the most potent AI (39, IC50AROM=0.25 nm) and the best STS inhibitor (31, IC50STS=26 nm). The most promising DASI is 39 (IC50AROM= 0.25 nm, IC50STS=205 nm), and this was evaluated orally in vivo at 10 mgkg-1, showing potent inhibition of aromatase (93%) and STS (93%) after 3 h. Potent aromatase and STS inhibition can thus be achieved with a DASI containing a bicyclic ring system; development of such a DASI could provide an attractive new option for the treatment of hormone-dependent breast cancer.
ALPHA SUBSTITUTED CARBOXYLIC ACID AS PPAR MODULATORS
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Page 115, (2010/02/09)
Alpha substituted carboxylic acids of formula (I): wherein R' and R2 are as defined in the specification and R3 is A) formula (II); B) formula (III); C) formula (IV); and D) formula (V); wherein Y, Art, Are, AP, R4, R5, R6, R7, R6, R9, R9a, R10, R", R12, R17, ring A, and p are as defined in the specification; pharmaceutical compositions containing effective amounts of said compounds or their salts are useful for treating PPAR, specifically PPAR α/y related disorders, such as diabetes, dyslipidemia, obesity and inflammatory disorders.
