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

Issue: 
12
Year: 
2017

E.E. Klen
Dr.Sc. (Pharm.), Professor, Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry,
Bashkir State Medical University (Ufa)
E-mail: klen_elena@yahoo.com
I.L. Nikitina
Dr.Sc. (Med.), Professor, Department of Farmacology N 1, Bashkir State Medical University (Ufa)
E-mail: irennixleo@gmail.com
O.A. Ivanova
Ph.D. (Med.), Associate Professor, Department of Farmacology N 1, Bashkir State Medical University (Ufa)
E-mail: pharma1olga@yandex.ru
N.N. Makarova
Ph.D. (Pharm.), Associate Professor, Department of Farmacology N 2, Bashkir State Medical University (Ufa)
E-mail: nnm16@yandex.ru
F.A. Khaliullin
Dr.Sc. (Pharm.), Professor, Head of Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry,
Bashkir State Medical University (Ufa)
E-mail: khaliullin_ufa@yahoo.com

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.

Keywords: 
Key words: thietane 1
1-dioxide
1
2
4-triazole
thioglycolic acid
hydrazide
arylmethylidenehedrazide
antidepressant like activity
the rule of five Lipinsky
tail suspension test
forced swim test
mice.