113336-22-4Relevant academic research and scientific papers
Aminoisoxazoles as Potent Inhibitors of Tryptophan 2,3-Dioxygenase 2 (TDO2)
Pei, Zhonghua,Mendonca, Rohan,Gazzard, Lewis,Pastor, Richard,Goon, Leanne,Gustafson, Amy,Vanderporten, Erica,Hatzivassiliou, Georgia,Dement, Kevin,Cass, Robert,Yuen, Po-Wai,Zhang, Yamin,Wu, Guosheng,Lin, Xingyu,Liu, Yichin,Sellers, Benjamin D.
, p. 417 - 421 (2018)
Tryptophan 2,3-dioxygenase 2 (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers; therefore, TDO inhibition may be a useful therapeutic intervention for
Solvent-free synthesis and structural characterization of azolyl-substituted pyrimidines
De la Hoz, Antonio,Blasco, Hector,Diaz-Ortiz, Angel,Elguero, Jose,Foces-Foces, Concepcion,Moreno, Andres,Sanchez-Migallon, Ana,Valiente, Gema
, p. 926 - 932 (2002)
Base-catalyzed trimerization of N-cyanomethylazoles under pressure and in solvent-free conditions afforded 4-amino-2,6-bis(azol-1-ylmethyl)-5-(azol-1-yl)pyrimidines (1-3) in 33-67% yields. The structures of these compounds was determined by a combination of NMR techniques and X-ray crystallography. The 4-amino groups show a restricted rotation around the C-N bond; the free energy of activation for this process was determined by variable temperature experiments. In the crystal structure of the pyrazol-1-yl derivative, the amino group shows a distorted planar geometry in both independent molecules and acts as a double hydrogen bond donor towards two of the three pyrazole rings, forming ribbons of R22(10) rings.
PYRIMIDONE CARBOXAMIDE COMPOUNDS AS PDE2 INHIBITORS
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Page/Page column 46; 47, (2015/07/15)
Disclosed are pyrimidine carboxamide compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2), pharmaceutical compositions and uses thereof.
Design of reversible, cysteine-targeted michael acceptors guided by kinetic and computational analysis
Krishnan, Shyam,Miller, Rand M.,Tian, Boxue,Mullins, R. Dyche,Jacobson, Matthew P.,Taunton, Jack
supporting information, p. 12624 - 12630 (2015/01/16)
Electrophilic probes that covalently modify a cysteine thiol often show enhanced pharmacological potency and selectivity. Although reversible Michael acceptors have been reported, the structural requirements for reversibility are poorly understood. Here, we report a novel class of acrylonitrile-based Michael acceptors, activated by aryl or heteroaryl electron-withdrawing groups. We demonstrate that thiol adducts of these acrylonitriles undergo β-elimination at rates that span more than 3 orders of magnitude. These rates correlate inversely with the computed proton affinity of the corresponding carbanions, enabling the intrinsic reversibility of the thiol-Michael reaction to be tuned in a predictable manner. We apply these principles to the design of new reversible covalent kinase inhibitors with improved properties. A cocrystal structure of one such inhibitor reveals specific noncovalent interactions between the 1,2,4-triazole activating group and the kinase. Our experimental and computational study enables the design of new Michael acceptors, expanding the palette of reversible, cysteine-targeted electrophiles.
KINASE INHIBITORS
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Paragraph 0466; 0467, (2013/03/26)
Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.
NOVEL OXAZOLIDINONE COMPOUNDS AS ANTIINFECTIVE AGENTS
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Page/Page column 54, (2009/01/20)
The present invention relates to novel oxazolidinone compounds of formula (I) with antibacterial activity, their pharmaceutically acceptable salts, their stereoisomers, their prodrugs, pharmaceutical compositions comprising the same and to their use as therapeutic agents
