Synthesis and pharmacological evaluation of 4,4a,5,6-tetrahydro-2H-thieno(2,3-h)cinnolin-3-ones bioisosters of antihypertensive and antithrombotic benzo(h)cinnolinones

The 8-acetylamino-4,4a,5,6-tetrahydro-2H-thieno[2,3-h]cinnolin-3-one (2b) has been synthesized and tested for its pharmacological profile in comparison with the bioisoster 8-acetylamino-4,4a,5,6-tetrahydrobenzo(h)cinnolin-3(2H)one (1b), which we reported to be a potent antihypertensive and antithrombotic agent. The new compound retained antithrombotic properties which were higher than those of acetylsalycilic acid but without significant antihypertensive activity. Conformational analysis performed by molecular mechanic calculations suggests that the lack of activity could be due to a different orientation of the acetylamino group in the 2 compounds. In addition, the unsubstituted term 2a was found to be comparable to ASA as an antithrombotic agent.