Skip to main content
SpringerLink
Log in

External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A new route to 5-amino-1,2,4-thiadiazole derivatives via reaction of N-chloroamidines with isothiocyanates has been proposed. The advantages of this method are high product yields (up to 93%), the column chromatography-free workup procedure, scalability and the absence of additive oxidizing agents or transition metal catalysts. The 28 examples of 5-amino-1,2,4-thiadiazole derivatives obtaining via the proposing protocol were evaluated in vitro against ESKAPE pathogens strains (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae). It was found that compounds 5ba, 5bd, 6a, 6d and 6c have potent antibacterial activity (MIC values 0.09–1.5 μg mL−1), which is superior to the activity of commercial antibiotics such as pefloxacin (MIC 4–8 μg mL−1) and streptomycin (MIC 2–32 μg mL−1). The additional cytotoxic assay of hit compounds on PANC-1 cell line demonstrated the low or non-cytotoxicity activity at the same level of concentrations. Thus, these 5 compounds are promising starting point for further antimicrobial drug development.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Scheme 3
Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dwivedi J, Kaur N, Kishore D, Kumari S, Sharma S (2016) Synthetic and biological aspects of thiadiazoles and their condensed derivatives: an overview. Curr Top Med Chem 16(26):2884–2920. https://doi.org/10.2174/1568026616666160506144859

    Article  CAS  PubMed  Google Scholar 

  2. Frija LMT, Pombeiro AJL (2017) Kopylovich MN (2017) Building 1,2,4-thiadiazole: ten years of progress. Eur J Org Chem 19:2670–2682. https://doi.org/10.1002/ejoc.201601642

    Article  CAS  Google Scholar 

  3. Li Y, Geng J, Liu Y, Yu S, Zhao G (2013) Thiadiazole-a promising structure in medicinal chemistry. ChemMedChem 8(1):27–41. https://doi.org/10.1002/cmdc.201200355

    Article  CAS  PubMed  Google Scholar 

  4. Surov AO, Churakov AV, Proshin AN, Dai X-L, Lu T, Perlovich GL (2018) Cocrystals of a 1,2,4-thiadiazole-based potent neuroprotector with gallic acid: solubility, thermodynamic stability relationships and formation pathways. Phys Chem Chem Phys 20(21):14469–14481. https://doi.org/10.1039/C8CP02532K

    Article  CAS  PubMed  Google Scholar 

  5. Volkova TV, Terekhova IV, Silyukov OI, Proshin AN, Bauer-Brandl A, Perlovich GL (2017) Towards the rational design of novel drugs based on solubility, partitioning/distribution, biomimetic permeability and biological activity exemplified by 1,2,4-thiadiazole derivatives. Medchemcomm 8(1):162–175. https://doi.org/10.1039/C6MD00545D

    Article  CAS  PubMed  Google Scholar 

  6. Surov AO, Voronin AP, Vasilev NA, Ilyukhin AB, Perlovich GL (2021) Novel cocrystals of the potent 1,2,4-thiadiazole-based neuroprotector with carboxylic acids: virtual screening, crystal structures and solubility performance. New J Chem 45(6):3034–3047. https://doi.org/10.1039/D0NJ05644H

    Article  CAS  Google Scholar 

  7. Perlovich GL, Proshin AN, Volkova TV, Petrova LN, Bachurin SO (2012) Novel 1,2,4-Thiadiazole derivatives as potent neuroprotectors: approach to creation of bioavailable drugs. Mol Pharm 9(8):2156–2167. https://doi.org/10.1021/mp300011r

    Article  CAS  PubMed  Google Scholar 

  8. Makhaeva GF, Kovaleva NV, Boltneva NP, Makhaeva GF, Kovaleva NV, Boltneva NP, Lushchekina SV, Rudakova EV, Stupina TS, Terentiev AA, Serkov IV, Proshin AN, Radchenko EV, PalyulinVV BSO, Richardson RJ (2020) Conjugates of tacrine and 1,2,4-thiadiazole derivatives as new potential multifunctional agents for Alzheimer’s disease treatment: synthesis, quantum-chemical characterization, molecular docking, and biological evaluation. Bioorg Chem 94:103387. https://doi.org/10.1016/j.bioorg.2019.103387

    Article  CAS  PubMed  Google Scholar 

  9. Pomeislová A, Otmar M, Rubešová P, Benýˇsek J, Matouˇsov ́M, Mertlíkov ́ a-Kaiserov ́ H, Pohl R, Poˇstov ́ a Slavˇetínsk ́ L, Pomeisl K, Kreˇcmerov ́M, (2021) 1,2,4-Thiadiazole acyclic nucleoside phosphonates as inhibitors of cysteine dependent enzymes cathepsin K and GSK-3β. Bioorg Med Chem 32:115998. https://doi.org/10.1016/j.bmc.2021.115998

    Article  CAS  PubMed  Google Scholar 

  10. Pragathi YJ, Sreenivasulu R, Veronica D, Raju RR (2021) Design, Synthesis, and biological evaluation of 1,2,4-Thiadiazole-1,2,4-Triazole derivatives bearing amide functionality as anticancer agents. Arab J Sci Eng 46(1):225–232. https://doi.org/10.1007/s13369-020-04626-z

    Article  CAS  PubMed  Google Scholar 

  11. Proshin AN, Trofimova TP, Zefirova ON, Zhirkina IV, Skvortsov DA, Bachurin SO (2021) Screening of a series of 3,5-disubstituted 1,2,4-thiadiazoles for selectivity of cytotoxic action to cancer cells. Russ Chem Bull 70(3):510–514. https://doi.org/10.1007/s11172-021-3116-4

    Article  CAS  Google Scholar 

  12. Shahinshavali S, Sreenivasulu R, Guttikonda VR, Kolli D, Rao MVB (2019) Synthesis and anticancer activity of amide derivatives of 1,2-isoxazole combined 1,2,4-Thiadiazole. Russ J Gen Chem 89(2):324–329. https://doi.org/10.1134/S1070363219020257

    Article  CAS  Google Scholar 

  13. Khachatoorian R, Micewicz ED, Micewicz A, French SW, Ruchala P (2019) Optimization of 1,3-disubstituted urea-based inhibitors of Zika virus infection. Bioorg Med Chem Lett 29(20):126626. https://doi.org/10.1016/j.bmcl.2019.126626

    Article  CAS  PubMed  Google Scholar 

  14. Hinklin RJ, Baer BR, Boyd SA, Chicarelli MD, Condroski KR, DeWolf WE Jr, Fischer J, Frank M, Hingorani GP, Lee PA, Neitzel NA, Pratt SA, Singh A, Sullivan FX, Turner T, Voegtli WC, Wallace EM, Williams L, Aicher TD (2020) Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator. Bioorg Med Chem 28(1):115232. https://doi.org/10.1016/j.bmc.2019.115232

    Article  CAS  PubMed  Google Scholar 

  15. Khadse SC, Amnerkar ND, Dighole KS, Dhote AM, Patil VR, Lokwani DK, Ugale VG, Charbe NB, Chatpalliwar VA (2020) Hetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: design, synthesis, molecular docking and in-silico ADME evaluation. J Mol Struct 1222:128916. https://doi.org/10.1016/j.molstruc.2020.128916

    Article  CAS  Google Scholar 

  16. Kono M, Matsumoto T, Kawamura T et al (2013) Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors. Bioorg Med Chem 21(1):28–41. https://doi.org/10.1016/j.bmc.2012.11.006

    Article  CAS  PubMed  Google Scholar 

  17. Duplessis C, Crum-Cianflone NF (2011) Ceftaroline: a new cephalosporin with activity against methicillin-resistant staphylococcus aureus (MRSA). Clin Med Rev Ther 3:1–17. https://doi.org/10.4137/CMRT.S1637

    Article  Google Scholar 

  18. Srisuknimit V, Qiao Y, Schaefer K, Kahne D, Walker S (2017) Peptidoglycan cross-linking preferences of staphylococcus aureus penicillin-binding proteins have implications for treating MRSA infections. J Am Chem Soc 139(29):9791–9794. https://doi.org/10.1021/jacs.7b04881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagace·-Wiens PRS, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch 3rd JP, Karlowsky JA (2014) Ceftolozane/Tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs 74(1): 31-51 https://doi.org/10.1007/s40265-013-0168-2

  20. Scheeren TW (2015) Ceftobiprole medocaril in the treatment of hospital-acquired pneumonia. Future Microbiol 10(12):1913–1928. https://doi.org/10.2217/fmb.15.115

    Article  CAS  PubMed  Google Scholar 

  21. Tam T, Leung-Toung R, Li W, Spino M, Karimian K (2005) Medicinal chemistry and properties of 1,2,4-Thiadiazoles. Mini-Rev Med Chem 5(4):367–379. https://doi.org/10.2174/1389557053544056

    Article  CAS  PubMed  Google Scholar 

  22. Yoshizawa H, Kubota T, Itani H, Minami K, Miwa H, Nishitani Y (2004) New broad-spectrum parenteral cephalosporins exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa Part 3: 7β-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido] cephalosporins bearin. Bioorg Med Chem 12(15):4221–4231. https://doi.org/10.1016/j.bmc.2004.05.021

    Article  CAS  PubMed  Google Scholar 

  23. Rineh A, Soren O, McEwan T et al (2020) Discovery of cephalosporin-3′-diazeniumdiolates that show dual antibacterial and antibiofilm effects against pseudomonas aeruginosa clinical cystic fibrosis isolates and efficacy in a murine respiratory infection model. ACS Infect Dis 6(6):1460–1479. https://doi.org/10.1021/acsinfecdis.0c00070

    Article  CAS  PubMed  Google Scholar 

  24. Doğan H, Doğan ŞD, Gündüz MG, Krishna VS, Lherbet C, Sriram D, S ̧ ahin O, Sarıpınar E, (2020) Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors. Eur J Med Chem 188:112035. https://doi.org/10.1016/j.ejmech.2020.112035

    Article  CAS  PubMed  Google Scholar 

  25. Shetnev A, Baykov S, Kalinin S, Belova A, Sharoyko V, Rozhkov A, Zelenkov L, Tarasenko M, Sadykov E, Korsakov M, Krasavin M (2019) 1,2,4-Oxadiazole/2-imidazoline hybrids: multi-target-directed compounds for the treatment of infectious diseases and cancer. Int J Mol Sci 20(7):1699. https://doi.org/10.3390/ijms20071699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tarasenko MV, Presnukhina SI, Baikov SV, Shetnev AA (2020) Synthesis and evaluation of antibacterial activity of 1,2,4-oxadiazole-containing biphenylcarboxylic acids. Russ J Gen Chem 90(9):1611–1619. https://doi.org/10.1134/S1070363220090042

    Article  CAS  Google Scholar 

  27. Tarasenko M, Sidneva V, Belova A, Romanycheva A, Sharonova T, Baykov S, Shetnev A, Kofanov E, Kuznetsov MA (2018) An efficient synthesis and antimicrobial evaluation of 5-alkenyl- and 5-styryl-1,2 4-oxadiazoles. Arkivoc https://doi.org/10.24820/ark.5550190.p010.760

  28. Yang L, Song L, Tang S, Li L, Li H, Yuan B (2019) Yang G (2019) Co-Catalyzed Intramolecular S-N bond formation in water for 1,2-benzisothiazol-3(2H )-ones and 1,2,4-Thiadiazoles synthesis. Eur J Org Chem 6:1281–1285. https://doi.org/10.1002/ejoc.201801642

    Article  CAS  Google Scholar 

  29. Kim H-Y, Kwak SH, Lee G-H, Gong Y-D (2014) Copper-catalyzed synthesis of 3-substituted-5-amino-1,2,4-thiadiazoles via intramolecular N-S bond formation. Tetrahedron 70(45):8737–8743. https://doi.org/10.1016/j.tet.2014.09.023

    Article  CAS  Google Scholar 

  30. Mariappan A, Rajaguru K, Merukan Chola N, Muthusubramanian S, Bhuvanesh N (2016) Hypervalent Iodine(III) mediated synthesis of 3-substituted 5-Amino-1,2,4-thiadiazoles through Intramolecular oxidative S-N bond formation. J Org Chem 81(15):6573–6579. https://doi.org/10.1021/acs.joc.6b01199

    Article  CAS  PubMed  Google Scholar 

  31. Wang B, Meng Y, Zhou Y, Ren L, Wu J, Yu W, Chang J (2017) Synthesis of 5-Amino and 3,5-Diamino substituted 1,2,4-Thiadiazoles by I 2 -mediated oxidative N-S bond formation. J Org Chem 82(11):5898–5903. https://doi.org/10.1021/acs.joc.7b00814

    Article  CAS  PubMed  Google Scholar 

  32. Yang Z, Zhang J, Hu L, Li L, Liu K, Yang T, Zhou C (2020) Electrochemical oxidative intramolecular N-S bond formation: synthesis of 3-substituted 5-amino-1,2,4-Thiadiazoles. J Org Chem 85(5):3358–3363. https://doi.org/10.1021/acs.joc.9b03155

    Article  CAS  PubMed  Google Scholar 

  33. Tumula N, Palakodety RK, Balasubramanian S, Nakka M (2018) Hypervalent Iodine(III)-mediated solvent-free, regioselective synthesis of 3,4-disubstituted 5-imino-1,2,4-thiadiazoles and 2-aminobenzo[d ]thiazoles. Adv Synth Catal 360(15):2806–2812. https://doi.org/10.1002/adsc.201800353

    Article  CAS  Google Scholar 

  34. Yang Z, Cao T, Liu S, Li A, Liu K, Yang T, Zhou C (2019) Transition-metal-free S-N bond formation: synthesis of 5-amino-1,2,4-thiadiazoles from isothiocyanates and amidines. New J Chem 43(17):6465–6468. https://doi.org/10.1039/C9NJ01419E

    Article  CAS  Google Scholar 

  35. Zhong Q, Sheng S, Chen J (2020) External oxidant-free electrooxidative intramolecular S-N bond formation for one-pot synthesis for 3,5-disubstituted 1,2,4-thiadiazoles. Phosphorus Sulfur Silicon Relat Elem 195(12):988–993. https://doi.org/10.1080/10426507.2020.1768093

    Article  CAS  Google Scholar 

  36. Yu W, Huang Y, Li J, Tang X, Wu W, Jiang H (2018) Copper-Catalyzed aerobic oxidative [3+2] annulation for the synthesis of 5-amino/imino-substituted 1,2,4-thiadiazoles through c-n/n–s bond formation. J Org Chem 83(16):9334–9343. https://doi.org/10.1021/acs.joc.8b01292

    Article  CAS  PubMed  Google Scholar 

  37. Li J, Xie X, Yang P et al (2020) Electrochemical synthesis of 1,2,4-thiadiazoles through intermolecular dehydrogenative S-N coupling. Adv Synth Catal 362(4):771–775. https://doi.org/10.1002/adsc.201901290

    Article  CAS  Google Scholar 

  38. Chen J-Y, Selvaraju M, Lin Y-T, Dhole S, Lin C-Y, Sun C-M (2020) Molecular iodine-promoted [3 + 2] oxidative cyclization for the synthesis of heteroarene-fused [1,2,4] thiadiazoles/selenadiazoles. J Org Chem 85(8):5570–5579. https://doi.org/10.1021/acs.joc.0c00421

    Article  CAS  PubMed  Google Scholar 

  39. Jatangi N, Tumula N, Palakodety RK, Nakka M (2018) I 2 -mediated oxidative C-N and N–S bond formation in water: a metal-free synthesis of 4,5-disubstituted/n-fused 3-amino-1,2,4-triazoles and 3-substituted 5-amino-1,2,4-thiadiazoles. J Org Chem 83(10):5715–5723. https://doi.org/10.1021/acs.joc.8b00753

    Article  CAS  PubMed  Google Scholar 

  40. Prieto A, Uzel A, Bouyssi D, Monteiro N (2017) Thiocyanation of N, N-dialkylhydrazonoyl bromides: an entry to sulfur-containing 1,2,4-triazole derivatives. Eur J Org Chem 2017:4201–4204. https://doi.org/10.1002/ejoc.201700819

    Article  CAS  Google Scholar 

  41. Li Y, Huang Z, Mo G, Jiang W, Zheng C, Feng P, Ruan Z (2020) Direct electrochemical synthesis of sulfur-containing triazolium inner salts. Chin J Chem 39:942–946. https://doi.org/10.1002/cjoc.202000586

    Article  CAS  Google Scholar 

  42. Kai Y, Chiku S (1994) Synthesis of [14C]E1077, a novel parenteral cephalosporin antibiotic. J Label Compd Radiopharm 34(11):1069–1073. https://doi.org/10.1002/jlcr.2580341110

    Article  CAS  Google Scholar 

  43. Haruki E, Inaike T, Imoto E (1968) Some reactions of N -haloamidines. Bull Chem Soc Jpn 41(6):1361–1367. https://doi.org/10.1246/bcsj.41.1361

    Article  CAS  Google Scholar 

  44. Fuchigami T, Odo K (1976) N -Halogen Compounds of Cyanamide Derivatives. VI. The preparation and reaction of 2-carbonimidoyl-3-imino- Δ 4 -1,2,4-thiadiazolines. Bull Chem Soc Jpn 49(11):3165–3169. https://doi.org/10.1246/bcsj.49.3165

  45. Judkins BD, Allen DG, Cook TA, Evans B, Sardharwala TE (1996) A versatile synthesis of amidines from nitriles via amidoximes. Synth Commun 26(23):4351–4367. https://doi.org/10.1080/00397919608003838

    Article  CAS  Google Scholar 

  46. Hervé G, Jacob G, Latypov N (2005) The reactivity of 1,1-diamino-2,2-dinitroethene (FOX-7). Tetrahedron 61(28):6743–6748. https://doi.org/10.1016/j.tet.2005.05.010

    Article  CAS  Google Scholar 

  47. Vo TT, Zhang J, Parrish DA, Twamley B, Shreeve JM (2013) New Roles for 1,1-Diamino-2,2-dinitroethene (FOX-7): halogenated FOX-7 and Azo-bis(diahaloFOX) as energetic materials and oxidizers. J Am Chem Soc 135(32):11787–11790. https://doi.org/10.1021/ja406629g

    Article  CAS  PubMed  Google Scholar 

  48. Zhou A-N, Li B, Ruan L, Wang Y, Duan G, Li J (2017) An improved and practical route for the synthesis of enzalutamide and potential impurities study. Chinese Chem Lett 28(2):426–430. https://doi.org/10.1016/j.cclet.2016.09.007

    Article  CAS  Google Scholar 

  49. Baykov S, Tarasenko M, Zelenkov LE, Kasatkina S, Savko P (2019) Shetnev A (2019) Diastereoselective opening of bridged anhydrides by amidoximes providing access to 1,2,4-Oxadiazole/Norborna(e)ne Hybrids. Eur J Org Chem 33:5685–5693. https://doi.org/10.1002/ejoc.201900843

    Article  CAS  Google Scholar 

  50. Baykov S, Semenov A, Tarasenko M, Boyarskiy VP (2020) Application of amidoximes for the heterocycles synthesis. Tetrahedron Lett 61(42):152403. https://doi.org/10.1016/j.tetlet.2020.152403

    Article  CAS  Google Scholar 

  51. Pankrat’eva VE, Sharonova TV, Tarasenko MV, Baikov SV, Kofanov ER, (2018) One-Pot Synthesis of 3,5-disubstituted 1,2,4-oxadiazoles using catalytic system NaOH-DMSO. Russ J Org Chem 54(8):1250–1255. https://doi.org/10.1134/S1070428018080213

    Article  Google Scholar 

  52. Hudson R, Bizier NP, Esdale KN, Katz JL (2015) Synthesis of indoles, benzofurans, and related heterocycles via an acetylene-activated SNAr/intramolecular cyclization cascade sequence in water or DMSO. Org Biomol Chem 13(8):2273–2284. https://doi.org/10.1039/C4OB02549K

    Article  CAS  PubMed  Google Scholar 

  53. Baykov S, Sharonova T, Shetnev A, Rozhkov S, Kalinin S, Smirnov AV (2017) The first one-pot ambient-temperature synthesis of 1,2,4-oxadiazoles from amidoximes and carboxylic acid esters. Tetrahedron 73(7):945–951. https://doi.org/10.1016/j.tet.2017.01.007

    Article  CAS  Google Scholar 

  54. Pandey R, Mishra SK, Shrestha A (2021) Characterisation of ESKAPE pathogens with special reference to multidrug resistance and biofilm production in a nepalese hospital. Infect Drug Resist 14:2201–2212. https://doi.org/10.2147/IDR.S306688

    Article  PubMed  PubMed Central  Google Scholar 

  55. Mulani MS, Kamble EE, Kumkar SN, Tawre MS, Pardesi KR (2019) Emerging strategies to combat ESKAPE pathogens in the era of antimicrobial resistance: a review. Front Microbiol 2019:10. https://doi.org/10.3389/fmicb.2019.00539

    Article  Google Scholar 

  56. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  57. Krasavin M, Shetnev A, Baykov S, Kalinin S, Nocentini A, Sharoyko V, Poli G, Tuccinardi T, Tennikova TB, Supuran CT (2019) Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines. Eur J Med Chem 168:301–314. https://doi.org/10.1016/j.ejmech.2019.02.044

    Article  CAS  PubMed  Google Scholar 

  58. Krasavin M, Shetnev A, Sharonova T, Baykov S, Kalinin S, Nocentini A, Sharoyko V, Poli G, Tuccinardi T, Presnukhina S, Tennikova TB, Supuran CT (2019) Continued exploration of 1,2,4-oxadiazole periphery for carbonic anhydrase-targeting primary arene sulfonamides: discovery of subnanomolar inhibitors of membrane-bound hCA IX isoform that selectively kill cancer cells in hypoxic environment. Eur J Med Chem 164:92–105. https://doi.org/10.1016/j.ejmech.2018.12.049

    Article  CAS  PubMed  Google Scholar 

  59. Zhang L, Xu L, Zhang F, Vlashi E (2017) Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer. Cell Cycle 16(8):737–745. https://doi.org/10.1080/15384101.2016.1241929

    Article  CAS  PubMed  Google Scholar 

  60. Martinu T, Dailey WP (2006) Reactivity of 1-Chloro-3-phenyldiazirines. J Org Chem 71:5012–5015. https://doi.org/10.1021/jo060341g

    Article  CAS  PubMed  Google Scholar 

  61. Herve G, Jacob G, Latypov N (2005) The reactivity of 1,1-diamino-2,2-dinitroethene (FOX-7). Tetrahedron 61:6743–6748. https://doi.org/10.1016/j.tet.2005.05.010

    Article  CAS  Google Scholar 

  62. Yu W, Huang Y, Li J, Tang X, Wu W, Jiang H (2018) Copper-Catalyzed aerobic oxidative [3+2] annulation for the synthesis of 5-amino/imino-substituted 1,2,4-thiadiazoles through c-n/n–s bond formation. J Org Chem 83:9334–9343. https://doi.org/10.1021/acs.joc.8b01292

    Article  CAS  PubMed  Google Scholar 

  63. Chen D, Errey JC, Heitman LH, Marshall FH, IJzerman, A. P., Siegal, G. (2012) Fragment screening of GPCRs using biophysical methods: identification of ligands of the adenosine A2A receptor with novel biological activity. ACS Chem Biol 7:2064–2073. https://doi.org/10.1021/cb300436c

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Russian Foundation for Basic Research (grant 19-33-60064). Physicochemical studies were performed at the Magnetic Resonance Research Centre, Centre for X-ray Diffraction Studies, Chemical Analysis and Materials Research Centre (all belong to Saint Petersburg State University).

Author information

Authors and Affiliations

  1. Pharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named After K.D. Ushinsky, Yaroslavl, Russian Federation, 150000

    Anton Shetnev, Marina Tarasenko & Valentina Kotlyarova

  2. Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, Saint Petersburg, Russian Federation, 199034

    Sergey Baykov, Kirill Geyl, Svetlana Kasatkina, Nikolina Sibinčić & Vladimir Sharoyko

  3. Department of General and Bioorganic Chemistry, Pavlov First Saint Petersburg State Medical University, 6–8 L’va Tolstogo Street, Saint Petersburg, Russian Federation, 197022

    Vladimir Sharoyko

  4. Saint Petersburg Pasteur Institute, 14 Mira Street, Saint Petersburg, Russian Federation, 197101

    Elizaveta V. Rogacheva & Liudmila A. Kraeva

Authors
  1. Anton Shetnev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina Tarasenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valentina Kotlyarova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sergey Baykov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kirill Geyl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Svetlana Kasatkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nikolina Sibinčić
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vladimir Sharoyko
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Elizaveta V. Rogacheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Liudmila A. Kraeva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anton Shetnev.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 4149 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shetnev, A., Tarasenko, M., Kotlyarova, V. et al. External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains. Mol Divers 27, 651–666 (2023). https://doi.org/10.1007/s11030-022-10445-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-022-10445-1

Keywords

Search

Navigation