📜3,6-二氯哒嗪,苯乙腈置于sodium Amide体系中,用 苯 作为反应溶剂,以54%的收率获得产物6-氯-α-苯基-3-哒嗪乙酰腈 参考文献:Studies On New Antiulcer Agents. I. Synthesis And Antisecretory Activity Of Pyridazine Derivatives. 标题:Studies On New Antiulcer Agents. I. Synthesis And Antisecretory Activity Of Pyridazine Derivatives. 摘要:本研究的首要化合物2-苯基-2-(2-吡啶基)硫代乙酰胺(ia)的吡啶环被吡嗪环替换,以期获得更具效力和更低毒性,且作用持久的药物,并合成了一系列2-苯基-2-(3-吡嗪基)硫代乙酰胺衍生物(II),这些衍生物是从卤代吡嗪(iii)和苯基乙腈通过关键中间体2-苯基-2-(3-吡嗪基)乙腈衍生物(iv)合成的.根据核磁共振(NMR)和紫外(uv)光谱数据,Ii的化学结构似乎在吡嗪形式和吡嗪酮-美特形式之间处于平衡状态.对ii的抗分泌活性和急性毒性进行了研究,并讨论了结构-活性关系.在测试的化合物中,2-苯基-2-(3-吡嗪基)硫代乙酰胺(iia)和2-(6-甲基-3-吡嗪基)-2-苯基硫代乙酰胺(iib)在以20 Mg/kg剂量给药给大鼠时表现出持久而强效的活性.iia和iib的急性毒性约为ia在小鼠中毒性的半至三分之一. DOI:10.1248/cpb.29.3433
参考标题:The Discovery Of Vx-745: A Novel And Selective P38α Kinase Inhibitor 作者:John P. Duffy,Edmund M. Harrington,Francesco G. Salituro,John E. Cochran,Jeremy Green,Huai Gao,Guy W. Bemis,Ghotas Evindar,Vincent P. Galullo,Pamella J. Ford,Ursula A. Germann,Keith P. Wilson,Steven F. Bellon,Guanging Chen,Paul Taslimi,Peter Jones,Cassey Huang,S. Pazhanisamy,Yow-Ming Wang,Mark A. Murcko,Michael S.S. Su |发布日期:2011.10.13 摘要:The Synthesis Of Novel, Selective, Orally Active 2,5-Disubstituted 6H-Pyrimido[1,6-B]Pyridazin-6-One P38Alpha Inhibitors Is Described. Application Of Structural Information From Enzyme-Ligand Complexes Guided The Selection Of Screening Compounds, Leading To The Identification Of A Novel Class Of P38Alpha Inhibitors Containing A Previously Unreported Bicyclic Heterocycle Core. Advancing The Sar Of This
合成参考文献
摘要:Haider, N.; Holzer, W., Science of Synthesis, (2004) 16, 198. 摘要:Haider, N.; Holzer, W., Science of Synthesis, (2004) 16, 196.