Khalimova O. Analgesic properties of derivatives of 3-substituted 1,2-di-hydro-3Н-1,4-benzodiazepin-2-ones

The thesis is devoted to the study of analgesic action of novel 3-arylidene-3-alkoxy and 3-arylamino 1,2-dihydro-3H-1,4-benzodiazepin-2-ones. These compounds (102 representatives) were shown to possess high analgesic activity (ED50 0,007-6,600 mg/kg) in the "acetic acid writhing" test in mice, which exceeded the activity of standard preparation diclofenac sodium.For the most active derivatives, in the test of rat paw carrageenan-induced oedema were found anti-inflammatory activity values, compared to that for diclofenac. It was determined the ability of compounds-leaders to inhibit animals pain behaviour in first (pain) and second (inflammatory) phases of formalin test, exceeding the effect of diclofenac in this test 3 times. It was defined that LD50 values exceeded 1000 mg/kg, what allows considering the compounds-leaders as low toxic.It is shown that neither flumazenil, benzodiazepine receptor antagonist, nor naloxone, opioid receptor antagonist, did not abolish the analgesic action of compound- leadrs 3-propanoxi-7-bromo-5-(2'-chloro)phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one.In tenzometric experiments on inhibition of bradykinin-induced rat gastric smooth muscle contractions, it was established the presence of functional anti- bradykinin activity for given above compound-leader. That allows to predict the bradykinin-antagonist properties of 3-substituted 1,2-dihydro-3H-1,4-benzodiazepin-2-ones.