Skip to main content

Synthesis of Novel Bi-Heterocycles as Valuable Anti-Diabetic Agents: 2-({5-((2-Amino-1,3-Thiazol-4-yl)methyl)-1,3,4-Oxadiazol-2-yl}sulfanyl)-N-(Substituted)acetamides


The synthesis of a new series of S-substituted acetamides derivatives of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol were synthesized and evaluated for enzyme inhibition study along with cytotoxic behavior. Ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate was converted to corresponding acid hydrazide by hydrazine hydrate in ethanol. The reflux of acid hydrazide with carbon disulfide resulted to 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol. Different electrophiles were synthesized by the reaction of respective anilines (one in each reaction) and 2-bromoacetylbromide in an aqueous medium. The targeted bi-heterocyclic compounds were synthesized by stirring nucleophilic 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol with different acetamides electrophiles (one after another), in DMF using LiH as base and activator. The proposed structures of newly synthesized compounds were deduced by spectroscopic techniques such as 1H NMR, 13C NMR, EI MS and elemental analysis. These novel bi-heterocycles were tested for their anti-diabetic potential via the in vitro inhibition of \(\alpha \)-glucosidase enzyme. The in silico study of these molecules was also coherent with their enzyme inhibition data. Furthermore, these molecules were analyzed for their cytotoxic behavior against brine shrimps. It was inferred from the results that most of them exhibited very potent inhibitory potential against the studied enzyme and can be utilized as valuable anti-diabetic agent.

This is a preview of subscription content, access via your institution.

Fig. 1.


  1. Pasqualotto, A.C., Thiele, K.O., and Goldani, L.Z., Eur. J. Med. Chem., 2010, vol. 11, pp. 165–169.

    CAS  Google Scholar 

  2. Knadler, M.P., Bergstrom, R.F., Callaghan, J.T., and Rubin, A., Asian J. Chem., 1986, vol. 14, pp. 175–187.

    CAS  Google Scholar 

  3. Foroumadi, A., Mansouri, S., Kiani, Z., and Rahmani, A., Eur. J. Med. Chem., 2003, vol. 38, pp. 851–857.

    CAS  PubMed  Google Scholar 

  4. Yatin, J.M., Arun, M.I., Shridhar, M., Shrikrishna, I., and Hoong-Kun, F., Arab. J. Chem., 2013, vol. 6, pp. 177–184.

    Google Scholar 

  5. Cihan-ustundag, G., Simsek, B., Ilhan, E., and Capan, G., Lett. Drug Design Disc., 2014, vol. 11, pp. 290–296.

    CAS  Google Scholar 

  6. Holla, B.S., Veerendra, B., Shivananda, M.K., and Poojary, B., Eur. J. Med. Chem., 2003, vol. 38, pp.759–765.

    Google Scholar 

  7. Abdel-Rahman F., Erik, D.C., and Elkashef, H., Arkivoc, 2006, pp. 137–141.

  8. Li, Z., Zhan, P., and Liu, X., Mini. Rev. Med. Chem., 2011, vol. 11, pp. 1130–1142.

    CAS  PubMed  Google Scholar 

  9. Joshi, D. and Parikh, K.S., Med. Chem. Res., 2014, vol. 23, pp. 1855–1864.

    CAS  Google Scholar 

  10. Bondock, S., Adel, S., Etman, H.A., and Badria, F.A., Eur. J. Med. Chem., 2012, vol. 48, pp. 192–199.

    CAS  PubMed  Google Scholar 

  11. Patel, K.N., Jadhav, N.C., Jagadhane, P.B., and Telvekar, V.N., Synlett., 2012, vol. 23, pp. 1970–1972.

    CAS  Google Scholar 

  12. Gupta, A., Kashaw, S.K., Jain, N., Rajak, H., Soni, A., Stables, J.P., Med. Chem. Res., 2011, vol. 20, pp. 1638–1642.

    CAS  Google Scholar 

  13. Sanchit, S. and Pandeya, S.N., Int. J. Res. Ayurv. Pharm., 2011, vol. 2, pp. 459–468.

    Google Scholar 

  14. Coppo, F.T., Evans, K.A., Graybill, T.L., and Burton, G., Tetrahedron Lett., 2004, vol. 45, pp. 3257–3260.

    CAS  Google Scholar 

  15. Yang, S.J., Lee, S.H., Kwak, H.J., and Gong, Y.D., J. Org. Chem., 2013, vol. 78, pp. 438–444.

    CAS  PubMed  Google Scholar 

  16. Brain, C.T., Paul, J.M., Loong, Y., and Oakley, P., Tetrahedron Lett., 1999, vol. 40, pp. 3275–3278.

    CAS  Google Scholar 

  17. Park, Y.-D., Kim, J.-J., Chung, H.-A., Kweon, D.-H., Cho, S.-D., Lee, S.-G., and Yoon, Y.J., Synthesis, 2003, vol. 4, pp. 560–564.

    Google Scholar 

  18. Patel, R.V., Kumari, P., and Chikhalia, K.H., Med. Chem., 2013, vol. 9, pp. 596–607.

    CAS  PubMed  Google Scholar 

  19. Oliveira, C.S., Lira, B.F., Barbosa-Filho, J.M., Lorenzo, J.G., and Athayde-Filho, P.F., Molecules, 2012, vol. 17, pp. 10 192–10 231.

    Google Scholar 

  20. Kitchen, D.B., Decornez, H., Furr, J.R., and Bajorath, J., Nat. Rev. Drug Discov., 2004, vol. 3, pp. 935–949.

    CAS  PubMed  Google Scholar 

  21. Sama, K., Murugesan, K., and Sivaraj, R., AsianJ. Plant Sci. Res., 2012, vol. 2, pp. 550–553.

    Google Scholar 

  22. Abbasi, M.A., Ramzan, M.S., Aziz-ur-Rehman, Siddiqui, S.Z., Hassan, M., Raza, H., Shah, S.A.A., Mirza, B., and Seo, S.-Y., J. Serb. Chem. Soc., 2019, vol. 84, pp. 649–661.

    CAS  Google Scholar 

  23. Abbasi, M.A., Ramzan, M.S., Aziz-ur-Rehman, Siddiqui, S.Z., Shah, S.A.A., Hassan, M., Seo, S.-Y., Ashraf, M., Mirza, B., and Ismail, H., Russ. J. Bioorg. Chem., 2018, 44, pp. 801–811.

    CAS  Google Scholar 

  24. Butt, A.R.S., Abbasi, M.A., Aziz-ur-Rehman, Siddiqui, S.Z., Hassan, M., Raza, H., Shah, S.A.A., and Seo, S.-Y., Bioorg. Chem. 2019, vol. 86, pp. 197–209.

    CAS  PubMed  Google Scholar 

  25. Ellman, G.L., Courtney, K.D., Andres, V., Featherstone, R.M., Bio Pharm., 1961, vol. 7, pp. 88–95.

    CAS  Google Scholar 

  26. Tan, K., Tesar, C., Wilton, R., Keigher, L., Babnigg, G., Joachimiak, A., FASEB J., 2010, vol. 24, pp. 3939–3949.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Boström, J., Greenwood, J.R., and Gottfries, J., Mol. Graph. Model., 2003, vol. 21, pp. 449–462.

    Google Scholar 

  28. Jensen, E.C., Ogg, C., Nickerson, K., App. Biochem. Microb., 1992, vol. 58, pp. 2505–2508.

    CAS  Google Scholar 

Download references


The Higher Education Commission (HEC) of Pakistan is highly acknowledged by the authors for financial support regarding purchasing of chemicals and spectral study.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Muhammad Athar Abbasi.

Ethics declarations


This article does not contain any studies involving animals or human participants performed by any of the authors.

Conflict of Interests

The authors declare that they have no conflict of interests.

Additional information

Corresponding author: phone: (+92)-42-111000010; e-mail:;

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Muhammad Athar Abbasi, Ramzan, M.S., Aziz-ur-Rehman et al. Synthesis of Novel Bi-Heterocycles as Valuable Anti-Diabetic Agents: 2-({5-((2-Amino-1,3-Thiazol-4-yl)methyl)-1,3,4-Oxadiazol-2-yl}sulfanyl)-N-(Substituted)acetamides. Russ J Bioorg Chem 46, 590–598 (2020).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • : ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate
  • 1,3,4-oxadiazole
  • acetamide
  • enzyme inhibition
  • molecular docking
  • cytotoxicity