Wardakhan Wagnat W, Abdel-Salam Omar M E, Elmegeed Gamal A
National Organization for Drug Control and Research, P.O. 29 Cairo, Egypt.
Acta Pharm. 2008 Mar;58(1):1-14. doi: 10.2478/v10007-007-0041-5.
This study was aimed at the synthesis of fused benzothiophene derivatives containing heterocyclic moiety. The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with ethoxycarbonylisothiocyanate afforded the thiourea derivatives 2a,b. Cyclization of the latter products gave the annulated benzo[b]thienopyrimidine derivatives 3a,b. Compounds 2a,b and 3a underwent a series of heterocyclization reactions through the reaction with some chemical reagents to give the new benzo[b]thienopyrimidine derivatives 5a,b to 8a-c. Also, this work was extended to study the potential role of the novel synthesized thiourea derivative 2a and benzo[b]thienopyrimidine derivatives 3a, 5b, 6a and 8b as antidepressant, sedative or analgesic agents at two doses (15 or 30 mg kg(-1) body mass). Some compounds (2a, 3a and 5b) showed mild antidepressant activity in the forced-swimming test. No compound showed sedative effect. Visceral pain evoked by i.p. injection of acetic acid in mice was significantly inhibited by all compounds at a high doses.
本研究旨在合成含杂环部分的稠合苯并噻吩衍生物。四氢苯并[b]噻吩衍生物1a、b与乙氧基羰基异硫氰酸酯反应得到硫脲衍生物2a、b。后者产物的环化反应得到稠合苯并[b]噻吩并嘧啶衍生物3a、b。化合物2a、b和3a通过与一些化学试剂反应进行了一系列杂环化反应，得到新的苯并[b]噻吩并嘧啶衍生物5a、b至8a - c。此外，本研究还扩展到研究新合成的硫脲衍生物2a以及苯并[b]噻吩并嘧啶衍生物3a、5b、6a和8b在两种剂量（15或30 mg kg(-1)体重）下作为抗抑郁、镇静或镇痛剂的潜在作用。一些化合物（2a、3a和5b）在强迫游泳试验中显示出轻度抗抑郁活性。没有化合物显示出镇静作用。所有化合物在高剂量时均能显著抑制小鼠腹腔注射醋酸引起的内脏疼痛。
