Ranatunge Ramani R, Garvey David S, Janero David R, Letts L Gordon, Martino Allison M, Murty Madhavi G, Richardson Stewart K, Young Delano V, Zemetseva Irina S
NitroMed Inc, 12 Oak Park Drive, Bedford, MA 01730, USA.
Bioorg Med Chem. 2004 Mar 15;12(6):1357-66. doi: 10.1016/j.bmc.2004.01.012.
Novel series of pyrazolo[5,1-b]1,3-oxazolidines, pyrazolo[5,1-b]1,3-oxazines and imidazolidino[1,2-d]pyrazoles were synthesized. These compounds were evaluated in vitro for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human whole blood (HWB). Several of the compounds were found to be novel and selective COX-2 inhibitors, the most potent and selective being 1-(5-cyclohexyl (2H,3H-pyrazolo[5,1-b]-1,3-oxazolidin-6-yl)-4-(methylsulfonyl)benzene, 7a (IC(5o) for COX-1>100 microM; for COX-2=1.3 microM).
合成了一系列新型的吡唑并[5,1 - b]1,3 - 恶唑烷、吡唑并[5,1 - b]1,3 - 恶嗪和咪唑并[1,2 - d]吡唑。对这些化合物在体外抑制人全血（HWB）中环氧化酶 - 1（COX - 1）和环氧化酶 - 2（COX - 2）的能力进行了评估。发现其中几种化合物是新型的选择性COX - 2抑制剂，最有效和选择性最强的是1 - (5 - 环己基(2H,3H - 吡唑并[5,1 - b] - 1,3 - 恶唑烷 - 6 - 基)-4 - (甲基磺酰基)苯，7a（COX - 1的IC(50)>100微摩尔；COX - （此处原文有误，推测应为COX - 2）2 = 1.3微摩尔）。
