684236-02-0Relevant academic research and scientific papers
4-((2-HYDROXY-3-METHOXYBENZYL)AMINO) BENZENESULFONAMIDE DERIVATIVES AS 12-LIPOXYGENASE INHIBITORS
-
Paragraph 0190; 0198; 0219, (2015/04/28)
Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molec
Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase
Luci, Diane K.,Jameson, J. Brian,Yasgar, Adam,Diaz, Giovanni,Joshi, Netra,Kantz, Auric,Markham, Kate,Perry, Steve,Kuhn, Norine,Yeung, Jennifer,Kerns, Edward H.,Schultz, Lena,Holinstat, Michael,Nadler, Jerry L.,Taylor-Fishwick, David A.,Jadhav, Ajit,Simeonov, Anton,Holman, Theodore R.,Maloney, David J.
, p. 495 - 506 (2014/02/14)
Human lipoxygenases (LOXs) are a family of iron-containing enzymes which catalyze the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Our group has taken a particular interest in platelet-type 12-(S)-LOX (12-LOX) because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Herein, we report the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino) benzenesulfonamide-based scaffold. Top compounds, exemplified by 35 and 36, display nM potency against 12-LOX, excellent selectivity over related lipoxygenases and cyclooxygenases, and possess favorable ADME properties. In addition, both compounds inhibit PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells.
