SYNTHESIS OF NEW 2-[3-BROMO-1-(1,1-DIOXOTHIETAN-3-YL)- 1,2,4-TRIAZOLYL-5-THIO]ACETIC ACID DERIVATIVES WITH ANTIDEPRESSANT ACTIVITY

The incidence of psychiatric and behavioral disturbances has increased dramatically in the last decades so the development of novel 2-[3-bromo-1-(1,1-dioxothietanyl-3)-1,2,4-triazolyl-5-thio]acetic acid derivatives with a potential antidepressant activity is crucial. Ether of 2-[1-(1,1-dioxothietanyl-3)-3-bromo-1,2,4-triazolyl-5-thio]acetic acid IIIb was treated with hydrazine which results in 2- [1-(1,1-dioxothietanyl-3)-3-bromo-1,2,4-triazolyl-5-thio]acetic acid hydrazide IV. A series of novel 2-[3-bromo-1-(1,1-dioxothietanyl- 3)-1,2,4-triazolyl-5-thio]acetic acid arylmethylidenehydrazides Va-i were synthesized by reacting hydrazide IV with various substituted aromatic aldehydes and ketones. The target compounds Va-i were obtained in 57 – 97% yields. The formation of the compounds was established considering the output obtained from spectral analysis. The computational studies indicated that the synthesized compounds are in agree the rule of five Lipinsky, and supposed to be non-mutagenic, non-irritant with no reproductive effects. Ethers IIIc (2 mg/kg), IIId (2 and 20 mg/kg) and arylmethylidenehydrazides Va (2 and 20 mg/kg), Vb (2 and 20 mg/kg), Vf (2 and 20 mg/kg), Vi (2 and 20 mg/kg) with single intraperitoneal administration of male mice have demonstrated the antidepressant like activity.