口服活性吲哚N-氧化物磷酸二酯酶4抑制剂。
Orally active indole N-oxide PDE4 inhibitors.
作者信息
Hulme C, Mathew R, Moriarty K, Miller B, Ramanjulu M, Cox P, Souness J, Page K M, Uhl J, Travis J, Labaudiniere R, Huang F, Djuric S W
机构信息
Rhône-Poulenc Rorer Central Research, Collegeville, PA 19426, USA.
出版信息
Bioorg Med Chem Lett. 1998 Nov 3;8(21):3053-8. doi: 10.1016/s0960-894x(98)00572-1.
This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-alpha levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.
本通讯描述了一系列新型强效磷酸二酯酶IV型（PDE4）抑制剂的合成及其体外和体内评价。所展示的几种化合物对PDE4抑制具有低纳摩尔IC50值，并且在抑制脂多糖攻击的小鼠（小鼠内毒素血症模型）中TNF-α水平方面具有优异的体内活性。展示了最有效的PDE4抑制剂在催吐研究（犬）和链球菌细胞壁（SCW）关节炎模型中的疗效。
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