Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors
Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors
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DOI：
10.1016/j.bmcl.2009.08.085
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发表时间：
2009-10-15
影响因子：
2.7
通讯作者：
Friesen, Richard W.
中科院分区：
文献类型：
--
作者：
Giroux, Andre;Boulet, Louise;Friesen, Richard W.
菲咪唑26和44已被鉴定为新型有效的、选择性的和口服活性的mPGES-1抑制剂。这些抑制剂比以前报道的氯菲咪唑1（MF 63）明显更有效，人全血IC 50分别为0.20和0.14 μ M。在豚鼠痛觉过敏模型中，口服剂量低至14 mg/kg时，其表现出显著的镇痛作用。活性和选择性mPGES-1抑制剂（26和44）具有相对不同的药代动力学特征，适合临床开发。皇冠版权所有（C）2009由爱思唯尔有限公司出版。保留所有权利。
Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC50 of 0.20 and 0.14 mu M, respectively. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model at oral doses as low as 14 mg/kg. Both active and selective mPGES-1 inhibitors (26 and 44) have a relatively distinct pharmacokinetic profile and are suitable for clinical development. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.