取代菲咪唑类化合物作为强效、选择性且口服活性的mPGES-1抑制剂。
Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors.
作者信息
Côté Bernard, Boulet Louise, Brideau Christine, Claveau David, Ethier Diane, Frenette Richard, Gagnon Marc, Giroux André, Guay Jocelyne, Guiral Sébastien, Mancini Joseph, Martins Evelyn, Massé Frédéric, Méthot Nathalie, Riendeau Denis, Rubin Joel, Xu Daigen, Yu Hongping, Ducharme Yves, Friesen Richard W
机构信息
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que., Canada.
出版信息
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6816-20. doi: 10.1016/j.bmcl.2007.10.033. Epub 2007 Oct 17.
Phenanthrene imidazole 3 (MF63) has been identified as a novel potent, selective, and orally active mPGES-1 inhibitor. This new series was developed by lead optimization of a hit from an internal HTS campaign. Compound 3 is significantly more potent than the previously reported indole carboxylic acid 1 with an A549 whole cell IC(50) of 0.42 microM (50% FBS) and a human whole blood IC(50) of 1.3 microM. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model when orally dosed at 30 and 100mg/kg.
菲咯啉咪唑3（MF63）已被鉴定为一种新型强效、选择性且口服活性的mPGES-1抑制剂。这个新系列是通过对内部高通量筛选活动中获得的一个先导化合物进行优化而开发的。化合物3比先前报道的吲哚羧酸1的活性显著更高，在含50%胎牛血清的A549全细胞中的半数抑制浓度（IC50）为0.42微摩尔，在人全血中的IC50为1.3微摩尔。当以30和100毫克/千克的剂量口服给药时，它在豚鼠痛觉过敏模型中表现出显著的镇痛作用。
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