Synthesis and evaluation of carbaborane derivatives of indomethacin as cyclooxygenase inhibitors.
Synthesis and evaluation of carbaborane derivatives of indomethacin as cyclooxygenase inhibitors.
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DOI：
10.1016/j.bmc.2011.03.054
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发表时间：
2011-05-15
影响因子：
3.5
通讯作者：
Hey-Hawkins E
中科院分区：
文献类型：
--
作者：
Scholz M;Blobaum AL;Marnett LJ;Hey-Hawkins E
非甾体抗炎药（NSAIDs）通过抑制环氧化酶（考克斯）-1和考克斯-2发挥其药理学活性。先前的研究表明，非选择性抑制剂如吲哚美辛的酯和酰胺对考克斯-2具有选择性，COX-2是治疗相关的同种型。结构-活性分析表明，取代的苯环作为酯组分是耐受的。在本研究中，探讨了引入无机的邻位和间位碳硼烷部分，目的是创建考克斯-2抑制剂，更重要的是研究使用这些硼簇作为药物实体的有效性。有趣的是，只有邻-碳硼烷酯是活性的，而Meta异构体不是。当在酯官能团中引入碳硼烷上的金刚烷基取代基或亚烷基间隔基时，观察到类似的抑制效力缺乏。
Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological activities by inhibiting cyclooxygenase (COX)-1 and COX-2. Previous studies have shown that esters and amides of non-selective inhibitors such as indomethacin are selective against COX-2, which is the therapeutically relevant isoform. Structure-activity analysis indicates that substituted phenyl rings are tolerated as ester components. In the present study, the introduction of inorganic ortho- and meta-carbaborane moieties was explored with the aim to create COX-2 inhibitors and more importantly to investigate the validity of using these boron clusters as drug entities. Interestingly, only the ortho-carbaborane ester was active whereas the meta isomer was not. A similar lack of inhibitory potency was observed when an adamantyl substituent or alkylene spacers at the carbaborane were introduced in the ester functionality.
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影响因子：
15
作者：
KISTENMA.TJ;MARSH, RE
通讯作者：
MARSH, RE
影响因子：
4
作者：
Armstrong, Andrea F.;Valliant, John F.
通讯作者：
Valliant, John F.
DOI：
10.1073/pnas.97.2.925
发表时间：
2000-01-18
影响因子：
11.1
作者：
Kalgutkar, AS;Crews, BC;Marnett, LJ
通讯作者：
Marnett, LJ
影响因子：
3.5
作者：
Goto, T;Ohta, K;Endo, Y
通讯作者：
Endo, Y
影响因子：
7.3
作者：
Beer, Michael L.;Lemon, Jennifer;Valliant, John F.
通讯作者：
Valliant, John F.