CAS: 1594-58-7; N-Hydroxynicotinimidamide

上下游产品

pyridine-3-carbonitrile 3-Bromopyridine 3-pyridinylacetonitrile (D,L)-5-(2-phenyl-1-tert-butyloxycarbonylaminoethyl)-3-(3-pyridyl)-1,2,4-oxadiazole ethyl [3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]carboxylate Pyridyl-4,5-dihydro-1.2.4-oxadiazolon-(5)3-3Pyridyl-4,5-dihydro-1.2.4-oxadiazolon-(5) 3-(3-(pyridine-3-yl)-1,2,4-oxadiazol-5-yl)benzonitrile

3-氰基吡啶置于盐酸羟胺,Potassium Carbonate体系中,用 乙醇 用作溶剂,化学反应 12.0H,以48.6%的收率获得3-吡啶基偕胺肟
参考文献:具有1,2,4-恶二唑核心的新型nrf2激活剂的结构-活性和结构-性质关系及其对乙酰氨基酚(apap)诱导的急性肝损伤的治疗作用
标题:具有1,2,4-恶二唑核心的新型nrf2激活剂的结构-活性和结构-性质关系及其对乙酰氨基酚(apap)诱导的急性肝损伤的治疗作用
摘要:Nrf2诱导的抗氧化功能可保护肝脏免受损害.我们通过先前报道的化合物1的结构修饰发现了一种名为化合物25的新型nrf2活化剂.在体外,化合物25通过激活nrf2-Are信号通路,诱导nrf2转运到细胞核中,并保护肝细胞l02细胞免受apap诱导的细胞毒性作用.在体内,通过上调nrf2依赖性抗氧化酶和下调血清中的肝损伤标记物,在对乙酰氨基酚(apap)诱发的急性肝损伤的小鼠模型中,有25种药物具有治疗作用.在一起,这些结果表明25是有效的nrf2 / Are激活剂体外和体内.化合物25的类药物特性进一步揭示了其作为治疗急性肝损伤的治疗药物的潜力.
Doi:10.1016/j.Ejmech.2018.08.071

专利信息

专利号:US-9878999-B2
优先权日:2011-03-24
标题 :Proteasome chymotrypsin-like inhibition using PI-1833 analogs
发明人：LAWRENCE HARSHANI R; SEBTI SAID M; OZCAN SEVIL
权利人:H LEE MOFFITT CANCER CT & RES
摘要:Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).