Chen H, Ji Z, Wong L K, Siuda J F, Narayanan V L
Shenyang College of Pharmacy, People's Republic of China.
Pharm Res. 1996 Oct;13(10):1482-7. doi: 10.1023/a:1016067210281.
A series of 2-substituted-2-dimethylaminomethyl-5-(E)-arylidene cyclopentanones, 4 were synthesized. The main objective of this investigation was to explore the structural parameters necessary for antiinflammatory activity in this series of compounds, while keeping cytotoxic action to a minimum.
The target compounds were synthesized in two steps commencing with 2-alkyl-cyclopentanones. Antiinflammatory, analgesic and cytotoxic activities were determined in rats. Cytotoxic results were examined in human cell lines.
Eight of the eighteen synthetic substances possessed significant antiinflammatory activity and twelve showed appreciable analgesic action. Cytotoxicity was minimal or non-existent for most of the compounds. The stability of one of the compounds, 4b in both aqueous and non-aqueous media, and an amine exchange reaction with aniline were used to explain the observed antiinflammatory and cytotoxic activities.
Unlike monosubstituted aminomethyl groups (Mannich bases) at the 2-position of 5-arylidene-2-cyclopentanones, a second substituent at the 2-position increases stability of the Mannich base and significantly decreases cytotoxic activity. Antiinflammatory and analgesic action is retained in many of the compounds, thus strongly indicating that these desired pharmacological results can be obtained without untoward damage to cells.
合成了一系列2-取代-2-二甲基氨基甲基-5-(E)-亚芳基环戊酮（4）。本研究的主要目的是探索该系列化合物中产生抗炎活性所需的结构参数，同时将细胞毒性作用降至最低。
以2-烷基环戊酮为起始原料，分两步合成目标化合物。在大鼠身上测定抗炎、镇痛和细胞毒性活性。在人细胞系中检测细胞毒性结果。
18种合成物质中有8种具有显著的抗炎活性，12种显示出明显的镇痛作用。大多数化合物的细胞毒性极小或不存在。利用其中一种化合物4b在水性和非水性介质中的稳定性以及与苯胺的胺交换反应来解释观察到的抗炎和细胞毒性活性。
与5-亚芳基-2-环戊酮2位上的单取代氨基甲基基团（曼尼希碱）不同，2位上的第二个取代基增加了曼尼希碱的稳定性并显著降低了细胞毒性活性。许多化合物保留了抗炎和镇痛作用，因此有力地表明，在不对细胞造成不良损害的情况下可以获得这些理想的药理结果。
