Bhandari Kalpana, Srivastava Shipra, Shankar Girija, Nath Chandishwar
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
Bioorg Med Chem. 2006 Apr 15;14(8):2535-44. doi: 10.1016/j.bmc.2005.11.032. Epub 2005 Dec 5.
Several 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes (7-21) as conformationally rigid analogues of fluoxetine were synthesized and evaluated for their anorexigenic and antidepressant activities. For SAR studies the related acyclic analogues (22-27) were also prepared. Out of the 21 synthesized compounds, 10 compounds (9, 10, 11, 15, 16, 18, 21, 22, 23 and 27) exhibited significant anorexigenic activity (at 75 micromol/kg). Interestingly, all the compounds (7-20, 22-26) were devoid of antidepressant effect, except for compounds 21 and 27 in which the antidepressant activity was retained. Compound 16 emerged as the most active compound of the series with better anorexigenic activity (97.92%) compared to fluoxetine (76.25%) and even with a clinically used drug sibutramine, thus providing a new structural lead for appetite suppressants.
合成了几种作为氟西汀构象刚性类似物的1-芳氧基-2-取代氨甲基四氢萘（7-21），并对其厌食和抗抑郁活性进行了评估。为了进行构效关系研究，还制备了相关的开链类似物（22-27）。在合成的21种化合物中，有10种化合物（9、10、11、15、16、18、21、22、23和27）表现出显著的厌食活性（在75微摩尔/千克时）。有趣的是，除了保留抗抑郁活性的化合物21和27外，所有化合物（7-20、22-26）均无抗抑郁作用。化合物16是该系列中活性最高的化合物，与氟西汀（76.25%）甚至与临床使用的药物西布曲明相比，具有更好的厌食活性（97.92%），从而为食欲抑制剂提供了新的结构先导。
