764708-20-5Relevant articles and documents
UREA, AMIDE, AND SUBSTITUTED HETEROARYL COMPOUNDS FOR CBL-B INHIBITION
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Paragraph 0443, (2021/02/05)
Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells invivo, in vitro, or ex vivo.
INHIBITORS OF CBL-B AND METHODS OF USE THEREOF
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Paragraph 1445, (2019/08/12)
Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.
Synthesis of celecoxib analogs that possess a N-hydroxypyrid-2(1H)one 5-lipoxygenase pharmacophore: Biological evaluation as dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity
Chowdhury, Morshed Alam,Abdellatif, Khaled R.A.,Dong, Ying,Das, Dipankar,Suresh, Mavanur R.,Knaus, Edward E.
experimental part, p. 6138 - 6141 (2009/06/30)
A hitherto unknown class of celecoxib analogs was designed for evaluation as dual inhibitors of the 5-lipoxygenase/cyclooxygenase-2 (5-LOX/COX-2) enzymes. These compounds possess a SO2Me (11a), or SO2NH2 (11b) COX-2 pharmacophore at the para-position of the N1-phenyl ring in conjunction with a 5-LOX N-hydroxypyrid-2(1H)one iron-chelating moiety in place of the celecoxib C-5 tolyl group. The title compounds 11a-b are weak inhibitors of the COX-1 and COX-2 isozymes (IC50 = 7.5-13.2 μM range). In contrast, the SO2Me (11a, IC50 = 0.35 μM), and SO2NH2 (11b, IC50 = 4.9 μM), compounds are potent inhibitors of the 5-LOX enzyme comparing favorably with the reference drug caffeic acid (5-LOX IC50 = 3.47 μM). The SO2Me (11a, ED50 = 66.9 mg/kg po), and SO2NH2 (11b, ED50 = 99.8 mg/kg po) compounds exhibited excellent oral anti-inflammatory (AI) activities being more potent than the non-selective COX-1/COX-2 inhibitor drug aspirin (ED50 = 128.9 mg/kg po) and less potent than the selective COX-2 inhibitor celecoxib (ED50 = 10.8 mg/kg po). The N-hydroxypyridin-2(1H)one moiety constitutes a novel pharmacophore for the design of cyclic hydroxamic mimetics capable of chelating 5-LOX iron for exploitation in the design of 5-LOX inhibitory AI drugs.
