916765-76-9Relevant articles and documents
Discovery and Optimization of Pyrazole Amides as Inhibitors of ELOVL1
Andreassi, John,Bonanno, Kenneth C.,Boucher, Christina,Bunnage, Mark E.,Chakilam, Ananthisrinivas,Charifson, Paul S.,Clark, Michael P.,Coll, Joyce,Come, Jon H.,Considine, Tony,Court, John J.,Crawford, Dan,Doyle, Elisabeth,Engtrakul, Juntyma,Furey, Brinley,Gagnon, Kevin J.,Gale-Day, Zachary,Gan, Lu,Gao, Hong,Gu, Wenxin,Huang, Yulin,Iyer, Ganesh,Jackson, Katrina L.,Kemper, Raymond,Kramer, Tal,Krueger, Elaine,Liang, Jianglin,Lu, Fan,Magavi, Sanjay S.,Maltais, Francois,Mohanty, Arun K.,Moody, Cameron S.,Morris, Mark,Nanthakumar, Suganthini,O'Dowd, Hardwin,Phillips, Jonathan,Sanders, Martin,Senter, Timothy J.,Song, Bin,Swett, Rebecca,Taylor, William,Vought, Bryan,Winquist, Ray,Zuccola, Harmon
, (2021/11/24)
Accumulation of very long chain fatty acids (VLCFAs) due to defects in ATP binding cassette protein D1 (ABCD1) is thought to underlie the pathologies observed in adrenoleukodystrophy (ALD). Pursuing a substrate reduction approach based on the inhibition of elongation of very long chain fatty acid 1 enzyme (ELOVL1), we explored a series of thiazole amides that evolved into compound 27─a highly potent, central nervous system (CNS)-penetrant compound with favorable in vivo pharmacokinetics. Compound 27 selectively inhibits ELOVL1, reducing C26:0 VLCFA synthesis in ALD patient fibroblasts, lymphocytes, and microglia. In mouse models of ALD, compound 27 treatment reduced C26:0 VLCFA concentrations to near-wild-type levels in blood and up to 65% in the brain, a disease-relevant tissue. Preclinical safety findings in the skin, eye, and CNS precluded progression; the origin and relevance of these findings require further study. ELOVL1 inhibition is an effective approach for normalizing VLCFAs in models of ALD.
N-arylacetyl thiosemicarbazide urease inhibitor and preparation method and application thereof
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Paragraph 0028; 0029-0031; 0033; 0077, (2019/01/14)
N-arylacetyl thiosemicarbazide compounds have a structural formula as shown in the specification, have great inhibiting effects on urease and can be used for preparation of medicines for treating gastritis, gastric ulcer, lithangiuria and the like. The in
