Acta Pharm. 58 (2008) 1-14

full paper

Original research paper

 

Screening for antidepressant, sedative and analgesic activities of novel fused thiophene derivatives

 

WAGNAT W. WARDAKHAN, OMAR M. E. ABDEL-SALAM and GAMAL A. ELMEGEED

wagnatward@hotmail.com

National Organization for Drug Control & Research, P.O. 29, Cairo, Egypt

Pharmacology Department, Hormone Department, National Research Centre, Dokki, Cairo, Egypt

Accepted February 1, 2008

 

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.

 

Keywords: tetrahydrobenzo[b]thiophene, pyrimidine, thiourea, antidepressant, sedative, analgesic