Scientific Online Resource System

Scripta Scientifica Pharmaceutica

Synthesis of 5-substituted 1,3,4-thiadiazol-2-yl-sulfanylacetic acid derivatives

Igor Sych, Lina Perekhoda, Tetiana Tsapko

Abstract

The study is devoted to the design and synthesis of new 2,5-disubstituted 1,3,4-thiadiazoles 3a-k as a promising multi-targeted pharmacological scaffold. Heterocyclization of acylated thiosemicarbazides 1a-i with carbon disulfide lead to the intermediate 5-R-carbonylamino-1,3,4-thiadiazol-2-thioles 2a-i. Further S-alkylation of compounds 2a-i with chloroacetic acid amides and ethyl ester allowed to obtain the target 5-R-carbonylamino-1,3,4-thiadiazol-2-yl-sulfanylacetic acid derivatives 3a-k. The developed method could be used for producing of molecular diversity of disubstituted 5-amino-1,3,4-thiadiazol-2-thiols via variation of substituents on both functional groups. Synthesized compounds are discussed as prospective anticonvulsants and antiproliferative agents.


Keywords

5-amino-1,3,4-thiadiazole-2-thioles; S-alkylation; chloroacetic acid derivatives

Full Text


References

Hu Y, Li CY, Wang XM, Yang YH, Zhu HL. 1,3,4-Thiadiazole: synthesis, reactions, and applications in medicinal, agricultural, and materials chemistry. Chem Rev. 2014;114 (10): 5572–610.

Dogan HN, Duran A, Rollas S, Sener G, Uysal MK, Gülen D. Synthesis of new 2,5-disubstituted-1,3,4-thiadiazoles and preliminary evaluation of anticonvulsant and antimicrobial activities. Bioorg Med Chem. 2002;10(9):2893–8.

Rajak H, Behera CK, Pawar RS, Singour PK, Kharya MD. A novel series of 2,5-disubstituted 1,3,4-thiadiazoles as potential anticonvulsant agent. Chinese Chem Lett. 2010;21(10):1149-52.

Masi HH, Gajjar AK, Savjani JK, Masi IA. Synthesis and anticonvulsant activity of novel 2,5-disubstituted 1,3,4-thiadiazole derivatives. Int J PharmTech Res. 2011; 3(4):2017-24.

Wei MX, Feng L, Li XQ, Zhou XZ, Shao ZH. Synthesis of new chiral 2,5-disubstituted 1,3,4-thiadiazoles possessing γ-butenolide moiety and preliminary evaluation of in vitro anticancer activity. Eur J Med Chem. 2009;44(8):3340–4.

Barbuceanu SF, Saramet G, Almajan GL, Draghici C, Barbuceanu F, Bancescu G. New heterocyclic compounds from 1,2,4-triazole and 1,3,4-thiadiazole class bearing diphenylsulfone moieties. Synthesis, characterization and antimicrobial activity evaluation. Eur J Med Chem. 2012;49:417-23.

Ameen HA, Qasir AJ. Synthesis and preliminary antimicrobial study of 2-amino-5-mercapto-1,3,4-thiadiazole derivatives. Iraqi J Pharm Sci. 2012;21(1):98-104.

Sharma R, Misra GP, Sainy J, Chaturvedi SC. Synthesis and biological evaluation of 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives as antidepressant, anxiolytics and anticonvulsant agents. Med Chem Res. 2011;20(2):245-53.

Yusuf M, Khan RA, Khan M, Ahmed B. An interactive human carbonic anhydrase-II (hCA-II) receptor--pharmacophore molecular model & anti-convulsant activity of the designed and synthesized 5-amino-1,3,4-thiadiazole-2-thiol conjugated imine derivatives. Chem Biol Drug Des. 2013;81(5):666-73.

Harish KP, Mohana KN, Mallesha L. Synthesis of new 2,5-disubstituted-1,3,4-thiadiazole derivatives and theirs in vivo anticonvulsant activity. Bioorg Khim. 2014;40(1):108-16.

Yusuf M, Khan RA, Ahmed B. Syntheses and anti-depressant activity of 5-amino-1,3,4-thiadiazole-2-thiol imines and thiobenzyl derivatives. Bioorg Med Chem. 2008;17:8029-34.

Can OD, Altintop MD, Ozkay UD, Uçel UI, Doğruer B, Kaplancikli ZA. Synthesis of thiadiazole derivatives bearing hydrazone moieties and evaluation of their pharmacological effects on anxiety, depression, and nociception parameters in mice. Arch Pharm Res. 2012;35(4):659-69.

Datar PA, Deokule TA. Development of thiadiazole as an antidiabetic agent – a review. Mini Rev Med Chem. 2014;14(2):136-53.

Rezki N, Al-Yahyawi AM, Bardaweel SK, Al-Blewi FF, Aouad MR. Synthesis of novel 2,5-disubstituted-1,3,4-thiadiazoles clubbed 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and/or schiff base as potential antimicrobial and antiproliferative agents. Molecules. 2015;20(9):16048-67.

Alwan SM. Synthesis and preliminary antimicrobial activities of new arylideneamino-1,3,4-thiadiazole-(thio/dithio)-acetamido cephalosporanic acids. Molecules. 2012;17(1):1025-38.

Mistry JK, Dawes R, Choudhury A, Van De Mark MR. 5-Mercapto-1,3,4-thiadiazole-2(3H)-thione: synthesis and structure of alkylated derivatives. J Heterocyclic Chem. 2014;51(3):747–54.

Shaker R.M. The chemistry of mercapto- and thione-substituted 1,2,4-triazoles and their utility in heterocyclic synthesis. Arkivoc. 2006;9:59-112.

Semenov VE, Krylova ES, Galyametdinova IV, Chernova AV, Kharlamov SV, Latypov SK, et al. Synthesis and reactivity of acyclic and macrocyclic uracils bridged with five-membered heterocycles. Tetrahedron. 2011;67(38):7370–8.

Cho NS, Hong SI, Suh IH, Kang SK. Crystal structures of macrocyclic compounds containing two 5-mercapto-3H-1,3,4-thiadiazolin-2-one groups. Bull Korean Chem Soc. 2009;30(10):2425-8.

Available from: www.pharmaexpert.ru/passonline.

Carragher NO. Calpain inhibition: a therapeutic strategy targeting multiple disease states. Curr Pharm Des. 2006;12(5):615-38.

Rebhandl S, Huemer M, Greil R, Geisberger R. AID/APOBEC deaminases and cancer. Oncoscience. 2015;2(4):320-33.

Yue P, Turkson J. Targeting STAT3 in cancer: how successful are we? Expert Opin Investig Drugs. 2009;18(1):45–56.

Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798-809.

Ebner FH, Mariotto S, Darra E, Suzuki H, Cavalieri E. Use of STAT1 inhibitors in the treatment of brain I/R injury and neurodegenerative diseases. Cent Nerv Syst Agents Med Chem. 2011;11(1):2-7.

Raj V, Rai A, Singh M, Kumar A, Kumar V, Sharma SK. Recent update on 1,3,4-thiadiazole derivatives: as anticonvulsant agents. EC Pharmaceutical Science. 2015;2(1):202-29.

Perekhoda LO, Georgiyants VA, Taran AV. Synthesis and anticonvulsive properties of anilides 5-R-phenylamino-1,3,4-thiadiazol-2-yl-thioacetic acid. J Org Pharm Chem. 2012;10(4):50-53.




DOI: http://dx.doi.org/10.14748/ssp.v2i2.1404

Refbacks

Article Tools
Email this article (Login required)
About The Authors

Igor Sych
Kharkiv Research Institute of Forensic Sciences, Kharkiv, Ukraine
Ukraine

Lina Perekhoda
National University of Pharmacy, Kharkiv
Ukraine

Tetiana Tsapko
National University of Pharmacy, Kharkiv, Ukraine
Ukraine

Font Size


|