958633-52-8Relevant academic research and scientific papers
Potent and selective inhibitors of human reticulocyte 12/15-lipoxygenase as anti-stroke therapies
Rai, Ganesha,Joshi, Netra,Jung, Joo Eun,Liu, Yu,Schultz, Lena,Yasgar, Adam,Perry, Steve,Diaz, Giovanni,Zhang, Qiangli,Kenyon, Victor,Jadhav, Ajit,Simeonov, Anton,Lo, Eng H.,Van Leyen, Klaus,Maloney, David J.,Holman, Theodore R.
supporting information, p. 4035 - 4048 (2014/06/09)
A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC 50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke.
Microwave-mediated synthesis and manipulation of a 2-substituted-5- aminooxazole-4-carbonitrile library
Spencer, John,Patel, Hiren,Amin, Jahangir,Callear, Samantha K.,Coles, Simon J.,Deadman, John J.,Furman, Christophe,Mansouri, Roxane,Chavatte, Philippe,Millet, Régis
supporting information; experimental part, p. 1656 - 1659 (2012/04/17)
A 2-substituted-5-aminooxazole-4-carbonitrile library has been synthesised and modified via microwave-mediated and flow chemistries. One synthesised compound, 5-(1H-pyrrol-1-yl)-4-(1H-tetrazol-5-yl)-2-(thien-2-yl)oxazole, contains three distinct heterocyc
Synthesis and friedlaender reactions of 5-amino-4-cyano-1,3-oxazoles
Carreiras, M. Carmo,Eleuterio, Ana,Dias, Catarina,Brito, M. Alexandra,Brites, Dora,Marco-Contelles,Gomez-Sanchez, Eiena
, p. 2249 - 2262 (2008/09/17)
The synthesis of 2-substituted 5-amino-4-cyano-l,3-oxazoles (1-4, 6-11) and the Friedaender-type reaction of compounds 1, 3, 4 is described. Compounds 13-17 are tacrine (18) analogues provided by the Friedlaender reaction. The anti-cholinesterase activity
