Synthesis and hypoglycemic activity of new nicotinonitrile-furan molecular hybrids

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Abstract

New hybrid molecules bearing 4-(2-furyl)-1,4-dihydronicotinonitrile and 4-(2-furyl)-1,4,5,6-tetrahydronico- tinonitrile fragments were prepared starting from cyanothioacetamide and furfural. The hypoglycemic activity in dexamethasone-induced diabetes mellitus was investigated in vivo in senile rats. Some compounds revealed hypoglycemic effects superior to that of the reference drug (metformin).

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About the authors

D. A. Tilchenko

Lugansk State Medical University named after St. Luke; Belgorod State National Research University

Email: victor_dotsenko_@mail.ru
Russian Federation, 91045, Lugansk, kv. 50 let Oborony Luganska, 1g; 308015, Belgorod, ul. Pobedy, 85

E. Yu. Bibik

Lugansk State Medical University named after St. Luke; Belgorod State National Research University

Email: victor_dotsenko_@mail.ru
Russian Federation, 91045, Lugansk, kv. 50 let Oborony Luganska, 1g; 308015, Belgorod, ul. Pobedy, 85

V. V. Dotsenko

Kuban State University; North Caucasus Federal University

Author for correspondence.
Email: victor_dotsenko_@mail.ru
Russian Federation, 350040, Krasnodar, ul. Stavropolskaya, 149; 355009, Stavropol, ul. Pushkina, 1

S. G. Krivokolysko

Lugansk State Medical University named after St. Luke; Vladimir Dahl Lugansk State University

Email: victor_dotsenko_@mail.ru
Russian Federation, 91045, Lugansk, kv. 50 let Oborony Luganska, 1g; 91034, Lugansk, kv. Molodezhny, 20A

K. A. Frolov

Lugansk State Medical University named after St. Luke; Vladimir Dahl Lugansk State University

Email: victor_dotsenko_@mail.ru
Russian Federation, 91045, Lugansk, kv. 50 let Oborony Luganska, 1g; 91034, Lugansk, kv. Molodezhny, 20A

N. A. Aksenov

North Caucasus Federal University

Email: victor_dotsenko_@mail.ru
Russian Federation, 355009, Stavropol, ul. Pushkina, 1

I. V. Aksenova

North Caucasus Federal University

Email: victor_dotsenko_@mail.ru
Russian Federation, 355009, Stavropol, ul. Pushkina, 1

References

  1. Bérubé G. // Expert Opin. Drug Discov. 2016. V. 11. P. 281–305. https://doi.org/10.1517/17460441.2016.1135125
  2. Soltan O.M., Shoman M.E., Abdel-Aziz S.A., Narumi A., Konno H., Abdel-Aziz M. // Eur. J. Med. Chem. 2021. V. 225. P. 113768. https://doi.org/10.1016/j.ejmech.2021.113768
  3. Singh A.K., Kumar A., Singh H., Sonawane P., Paliwal H., Thareja S., Pathak P., Grishina M., Jaremko M., Em- was A.H., Yadav J.P., Verma A., Khalilullah H., Kumar P. // Pharmaceuticals. 2022. V. 15. P. 1071. https://doi.org/10.3390/ph15091071
  4. Ivasiv V., Albertini C., Gonçalves A.E., Rossi M., Bolognesi M.L. // Curr. Top. Med. Chem. 2019. V. 19. P. 1694–1711. https://doi.org/10.2174/1568026619666190619115735
  5. Prasher P., Sharma M., Aljabali A.A.A., Gupta G., Negi P., Kapoor D.N., Singh I., Zacconi F.C., de Jesus Andreoli Pinto T., da Silva M.W., Bakshi H.A., Chellappan D.K., Tambuwala M.M., Dua K. // Drug Dev. Res. 2020. V. 81. P. 837–858. https://doi.org/10.1002/ddr.21704
  6. Alarcón-Espósito J., Mallea M., Rodríguez-Lavado J. // Curr. Neuropharmacol. 2021. V. 19. P. 832–867. https://doi.org/10.2174/1570159X18666200914155951
  7. González J.F., Alcántara A.R., Doadrio A.L., Sánchez-Montero J.M. // Exp. Opin. Drug Discov. 2019. V. 14. P. 879–891. https://doi.org/10.1080/17460441.2019.1623201
  8. Auti P.S., George G., Paul A.T. // RSC Adv. 2020. V. 10. P. 41353–41392. https://doi.org/10.1039/d0ra06642g
  9. Shaveta, Mishra S., Singh P. // Eur. J. Med. Chem. 2016. V. 124. P. 500–536. https://doi.org/10.1016/j.ejmech.2016.08.039
  10. Anusionwu C.G., Aderibigbe B.A., Mbianda X.Y. // Mini Rev. Med. Chem. 2019. V. 19. P. 450–464. https://doi.org/10.2174/1389557519666181210162003
  11. Mehta K., Khambete M., Abhyankar A., Omri A. // Pharmaceuticals. 2023. V. 16. P. 377. https://doi.org/10.3390/ph16030377
  12. Design of hybrid molecules for drug development / Ed. Decker M. Amsterdam: Elsevier, 2017. 338 pp.
  13. Oliveira R., Miranda D., Magalhães J., Capela R., Perry M.J., O’Neill P.M., Moreira R., Lopes F. // Bioorg. Med. Chem. 2015. V. 23. P. 5120–5130. https://doi.org/10.1016/j.bmc.2015.04.017
  14. Chauhan S.S., Sharma M., Chauhan P.M.S. // Drug News Perspect. 2010. V. 23. P. 632–646. https://doi.org/10.1358/dnp.2010.23.10.1468390
  15. Leite D.I., de Castro Bazan Moura S., da Conceição Avelino Dias M., Costa C.C.P., Machado G.P., Pimentel L.C.F., Branco F.S.C., Moreira R., Bastos M.M., Boechat N. // Molecules. 2023. V. 28. P. 3342. https://doi.org/10.3390/molecules28083342
  16. Краузе А.А., Одынец А.Г., Веррева А.А., Германе С.К., Кожухов А.Н., Дубур Г.Я. // Хим.-фарм. журн. 1991. Т. 25. С. 40–43. [Krauze A.A., Odynets A.G., Verreva A.A., Germane S.K., Kozhukhov A.N., Dubur G.Ya. // Pharm. Chem. J. 1991. V. 25. P. 477–481.] https://doi.org/10.1007/BF00772003
  17. Fernandes M.A., Santos M.S., Moreno A.J., Chernova L., Krauze A., Duburs G., Vicente J.A. // Toxicol. In Vitro. 2009. V. 23. P. 1333–1341. https://doi.org/10.1016/j.tiv.2009.07.002
  18. Osolodkin D.I., Kozlovskaya L.I., Dueva E.V., Dotsenko V.V., Rogova Y.V., Frolov K.A., Krivokolysko S.G., Romanova E.G., Morozov A.S., Karganova G.G., Palyulin V.A., Pentkovski V.M., Zefirov N.S. // ACS Med. Chem. Lett. 2013. V. 4. P. 869–874. https://doi.org/10.1021/ml400226s
  19. Bibik E.Yu., Saphonova A.A., Yeryomin A.V., Frolov K.A., Dotsenko V.V., Krivokolysko S.G. // Res. Results Pharmacol. 2017. V. 3. P. 20–25. https://doi.org/10.18413/2313-8971-2017-3-4-20-25
  20. Бибик Е.Ю., Ярошевская О.Г., Девдера А.В., Де- менко А.В., Захаров В.В., Фролов К.А., Доценко В.В., Кривоколыско С.Г. // Хим.-фарм. журн. 2017. Т. 51. С. 16–19. [Bibik E.Yu., Yaroshevskaya O.G., Dev- dera A.V., Demenko A.V., Zakharov V.V., Frolov K.A., Dotsenko V.V., Krivokolysko S.G. // Pharm. Chem. J. 2017. V. 51. P. 648–651.] https://doi.org/10.1007/s11094-017-1669-1
  21. Бибик Е.Ю., Некраса И.А., Деменко А.В., Фролов К.А., Доценко В.В., Кривоколыско С.Г. // Бюлл. сиб. мед. 2019. Т. 18. С. 21–28. [Bibik E.Yu., Nekrasa I.A., Demenko A.V., Frolov K.A., Dotsenko V.V., Krivokolysko S.G. // Bull. Sib. Med. 2019. V. 18. P. 21–28.] https://doi.org/10.20538/1682-0363-2019-3-21-28
  22. Бибик И.В., Бибик Е.Ю., Доценко В.В., Фролов К.А., Кривоколыско С.Г., Аксенов Н.А., Аксенова И.В., Щербаков С.В., Овчаров С.Н. // ЖОХ. 2021. Т. 91. С. 190–204. [Bibik I.V., Bibik E.Yu., Dotsenko V.V., Frolov K.A., Krivokolysko S.G., Aksenov N.A., Aksenova I.V., Shcherbakov S.V., Ovcharov S.N. // Russ. J. Gen. Chem. 2021. V. 91. P. 154–166.] https://doi.org/10.1134/S107036322102002X
  23. Rice W.G., Turpin J.A., Schaeffer C.A., Graham L., Clanton D., Buckheit R.W., Zaharevitz D., Summers M.F., Wallqvist A., Covell D.G. // J. Med. Chem. 1996. V. 39. P. 3606–3616. https://doi.org/10.1021/jm960375o
  24. Norman D.D., Ibezim A., Scott W.E., White S., Parrill A.L., Baker D.L. // Bioorg. Med. Chem. 2013. V. 21. P. 5548–5560. https://doi.org/10.1016/j.bmc.2013.05.061
  25. Abbas H.A., El Sayed W.A., Fathy N.M. // Eur. J. Med. Chem. 2010. V. 45. P. 973–982. https://doi.org/10.1016/j.ejmech.2009.11.039
  26. Orlov A.A., Eletskaya A.A., Frolov K.A., Golinets A.D., Palyulin V.A., Krivokolysko S.G., Kozlovskaya L.I., Dotsenko V.V., Osolodkin D.I. // Arch. Pharm. 2018. V. 351. P. e1700353. https://doi.org/10.1002/ardp.201700353
  27. Литвинов В.П. // Изв. АН. Сер. хим. 1998. № 11. С. 2123–2141. [Litvinov V.P. // Russ. Chem. Bull. 1998. V. 47. P. 2053–2073.] https://doi.org/10.1007/BF02494257
  28. Литвинов В.П., Кривоколыско С.Г., Дяченко В.Д. // Химия гетероциклич. соед. 1999. № 5. С. 579–609. [Litvinov V.P., Krivokolysko S.G., Dyachenko V.D. // Chem. Heterocycl. Compd. 1999. V. 35. P. 509–540.] https://doi.org/10.1007/BF02324634
  29. Литвинов В.П. // Усп. химии. 2006. Т. 75. № 7. С. 645–668. [Litvinov V.P. // Russ. Chem. Rev. 2006. V. 75. P. 577–599.] https://doi.org/10.1070/RC2006v075n07ABEH003619
  30. Gouda M.A., Berghot M.A., Abd El Ghani G.E., Khalil A.E.G.M. // Synth. Commun. 2014. V. 44. P. 297–330. https://doi.org/10.1080/00397911.2013.823549
  31. Salem M.A., Helel M.H., Gouda M.A., Ammar Y.A., El-Gaby M.S.A. // Synth. Commun. 2018. V. 48. P. 345–374. https://doi.org/10.1080/00397911.2017.1394468
  32. Gouda M.A., Hussein B.H., Helal M.H., Salem M.A. // J. Heterocycl. Chem. 2018. V. 55. P. 1524–1553. https://doi.org/10.1002/jhet.3188
  33. Gouda M.A., Attia E., Helal M.H., Salem M.A. // J. Heterocycl. Chem. 2018. V. 55. P. 2224–2250. https://doi.org/10.1002/jhet.3298
  34. Shamroukh A.H., Kotb E.R., Anwar M.M., Sharaf M. // Egypt. J. Chem. 2021. V. 64. P. 4509–4529. https://doi.org/10.21608/EJCHEM.2021.64971.3392
  35. Hassan H., Hisham M., Osman M., Hayallah A. // J. Adv. Biomed. Pharm. Sci. 2023. V. 6. P. 1–11. https://doi.org/10.21608/jabps.2022.162396.1166
  36. Лукевиц Э., Демичева Л. // Химия гетероциклич. соед. 1993. С. 291–321. [Lukevits É, Demicheva L. // Chem. Heterocycl. Compds. 1993. V. 29. P. 243–267.] https://doi.org/10.1007/BF00531499
  37. Alizadeh M., Jalal M., Khodaei Hamed A.S., Kheirouri S., Tabrizi F.P.F., Kamari N. // J. Inflam. Res. 2020. V. 13. P. 451–463. https://doi.org/10.2147/JIR.S262132
  38. Кривоколыско Д.С., Доценко В.В., Бибик Е.Ю., Самокиш А.А., Венидиктова Ю.С., Фролов К.А., Кривоколыско С.Г., Василин В.К., Панков А.А., Аксенов Н.А., Аксенова И.В. // ЖОХ. 2021. Т. 91. С. 1359–1374. [Krivokolysko D.S., Dotsenko V.V., Bibik E.Yu., Samokish A.A., Venidiktova Yu.S., Frolov K.A., Krivokolysko S.G., Vasilin V.K., Pankov A.A., Aksenov N.A., Aksenova I.V. // Russ. J. Gen. Chem. 2021. V. 91. P. 1646–1660.] https://doi.org/10.1134/S1070363221090073
  39. Бибик И.В., Бибик Е.Ю., Фролов К.А., Доценко В.В., Кривоколыско С.Г. // Бюлл. мед. науки. 2023. № 1 (29). С. 5–15. [Bibik I.V., Bibik E.Yu., Frolov K.A., Dotsenko V.V., Krivokolysko S.G. // Bull. Med. Sci. 2023. № 1 (29). P. 5–15.] https://doi.org/10.31684/25418475-2023-1-5
  40. Бибик Е.Ю., Олейник И.С., Панков А.А., Фролов К.А., Доценко В.В., Кривоколыско С.Г. // Кубан. науч. мед. вестн. 2023. Т. 30. С. 64–75. https://doi.org/10.25207/1608-6228-2023-30-2-64-75
  41. Кривоколыско Д.С., Доценко В.В., Бибик Е.Ю., Самокиш А.А., Венидиктова Ю.С., Фролов К.А., Кривоколыско С.Г., Панков А.А., Аксенов Н.А., Аксенова И.В. // Биоорг. хим. 2022. Т. 48. С. 486–494. [Krivokolysko D.S., Dotsenko V.V., Bibik E.Yu., Samo- kish A.A., Venidiktova Yu.S., Frolov K.A., Krivokolysko S.G., Pankov A.A., Aksenov N.A., Aksenova I.V. // Russ. J. Bioorg. Chem. 2022. V. 48. P. 628–635.] https://doi.org/10.1134/S1068162022030104
  42. Кривоколыско Д.С., Доценко В.В., Бибик Е.Ю., Мязина А.В., Кривоколыско С.Г., Василин В.К., Пан- ков А.А., Аксенов Н.А., Аксенова И.В. // ЖОХ. 2022. Т. 92. С. 72–91. [Krivokolysko D.S., Dotsenko V.V., Bi- bik E.Yu., Myazina A.V., Krivokolysko S.G., Vasilin V.K., Pankov A.A., Aksenov N.A., Aksenova I.V. // Russ. J. Gen. Chem. 2021. V. 91. P. 2588–2605.] https://doi.org/10.1134/S1070363221120306
  43. Bibik E.Yu., Kurbanov L.I., Grygoryan S.A., Krivokolysko D.S., Kudrina M.A., Pankov A.A., Frolov K.A., Dotsenko V.V., Krivokolysko S.G. // J. Siber. Med. Sci. 2021. № 3. P. 45–55. https://doi.org/10.31549/2542-1174-2021-3-45-55
  44. Бибик Е.Ю., Кривоколыско Д.С., Батищева Г.А., Самокиш А.А., Венидиктова Ю.С., Мязина А.В., Панков А.А., Фролов К.А., Доценко В.В., Кривоко- лыско С.Г. // Кубан. науч. мед. вестн. 2022. Т. 29. С. 77–95. https://doi.org/10.25207/1608-6228-2022-29-1-77-95
  45. Фролов К.А., Доценко В.В., Кривоколыско С.Г. // Химия гетероциклич. соед. 2013. № 8. C. 1232– 1236. [Frolov K.A., Dotsenko V.V., Krivokolysko S.G. // Chem. Heterocycl. Compd. 2013. V. 49. P. 1146–1150.] https://doi.org/10.1007/s10593-013-1356-4
  46. Sanders M.P., Roumen L., van der Horst E., Lane J.R., Vischer H.F., van Offenbeek J., de Vries H., Verhoe- ven S., Chow K.Y., Verkaar F., Beukers M.W., McGuire R., Leurs R., IJzerman A.P., de Vlieg J., de Esch I.J.P., Za- man G.J.R., Klomp J.P.G., Bender A., de Graaf C. // J. Med. Chem. 2012. V. 55. P. 5311–5325. https://doi.org/10.1021/jm300280e
  47. Pang J.P., Hu X.P., Wang Y.X., Liao J.N., Chai X., Wang X.W., Shen C., Wang J.J., Zhang L.L., Wang X.Y., Zhu F., Weng Q.J., Xu L., Hou T.J., Li D. // Acta Pharmacol. Sin. 2022. V. 43. P. 2429–2438. https://doi.org/10.1038/s41401-021-00855-6
  48. Michels M., Briem H., Vakalopoulos A., Zimmermann K., Teusch N. // Patent WO2011061157A1, published 26.05.2011. https://worldwide.espacenet.com/patent/search/family/043619076/publication/WO2011061157A1?q=pn%3DWO2011061157
  49. Zhang Y., Zhang S., Xu G., Yan H., Pu Y., Zuo Z. // Mol. BioSyst. 2016. V. 12. P. 3734–3742. https://doi.org/10.1039/c6mb00661b
  50. Jadhav A., Ferreira R.S., Klumpp C., Mott B.T., Austin C.P., Inglese J., Thomas C.J., Maloney D.J., Shoichet B.K., Simeonov A. // J. Med. Chem. 2010. V. 53. P. 37–51. https://doi.org/10.1021/jm901070c
  51. Alqasoumi S.I., Al-Taweel A.M., Alafeefy A.M., Ghorab M.M., Noaman E. // Eur. J. Med. Chem. 2010. V. 45. P. 1849–1853. https://doi.org/10.1016/j.ejmech.2010.01.022
  52. Alqasoumi S.I., Al-Taweel A.M., Alafeefy A.M., Ha- med M.M., Noaman E., Ghorab M.M. // Bioorg. Med. Chem. Lett. 2009. V. 19. P. 6939–6942. https://doi.org//10.1016/j.bmcl.2009.10.065
  53. Azzam R.A., Mohareb R.M. // Chem. Pharm. Bull. 2015. V. 63. P. 1055–1064. https://doi.org/10.1248/cpb.c15-00685
  54. Ahmed M.H., El-Hashash M.A., Marzouk M.I., El-Naggar A.M. // J. Heterocycl. Chem. 2019. V. 56. P. 114–123. https://doi.org/10.1002/jhet.3380
  55. Yang J., Kwon S., Bae S.H., Park K.M., Yoon C., Lee J.H., Seok C. // J. Chem. Inf. Model. 2020. V. 60. P. 3246–3254. https://doi.org/10.1021/acs.jcim.0c00104
  56. GalaxyWEB. A web server for protein structure prediction, refinement, and related methods // Computational Biology Lab, Department of Chemistry, Seoul National University, S. Korea. https://galaxy.seoklab.org/index.html
  57. Ko J., Park H., Heo L., Seok C. // Nucleic Acids Res. 2012. V. 40. Iss. W1. P. W294–W297. https://doi.org/10.1093/nar/gks493
  58. Daina A., Michielin O., Zoete V. // Nucleic Acids Res. 2019. V. 47. Iss. W1. P. W357–W364. https://doi.org/10.1093/nar/gkz382
  59. Тюренков И.Н., Озеров А.А., Куркин Д.В., Логви- нова Е.О., Бакулин Д.А., Волотова Е.В., Бородин Д.Д. // Усп. химии. 2018. Т. 87. С. 151–166. [Tyurenkov I.N., Ozerov A.A., Kurkin D.V., Logvinova E.O., Bakulin D.A., Volotova E.V., Borodin D.D. // Russ. Chem. Rev. 2018. V. 87. P. 151–166.] https://doi.org/10.1070/rcr4737
  60. Lin H.V., Efanov A.M., Fang X., Beavers L.S., Wang X., Wang J., Gonzalez Valcarcel I.C., Ma T. // PLoS One. 2016. V. 11. P. e0157298. https://doi.org/10.1371/journal.pone.0157298
  61. Ueda Y., Iwakura H., Bando M., Doi A., Ariyasu H., Inaba H., Morita S., Akamizu T. // PLoS One. 2018. V. 13. P. e0198762. https://doi.org/10.1371/journal.pone.0198762
  62. Cohen P., Goedert M. // Nat. Rev. Drug. Discov. 2003. V. 3. P. 479–487. https://doi.org/10.1038/nrd1415
  63. Спасов А.А., Косолапов В.А., Бабков Д.А., Майка О.Ю. // Пробл. эндокринол. 2018. Т. 64. С. 180–187. https://doi.org/10.14341/probl8747
  64. Matschinsky F.M., Wilson D.F. // Front. Physiol. 2019. V. 10. P. 148. https://doi.org/10.3389/fphys.2019.00148
  65. Ashcroft F.M., Lloyd M., Haythorne E.A. // Trends Endocrinol. Metab. 2023. V. 34. P. 119–130. https://doi.org/10.1016/j.tem.2022.12.007
  66. Jay M.A., Ren J. // Curr. Diabetes Rev. 2007. V. 3. P. 33–39. https://doi.org/10.2174/157339907779802067
  67. Chandra A., Kaur P., Sahu S.K., Mittal A. // Chem. Biol. Drug Design. 2022. V. 100. P. 947–967. https://doi.org/10.1111/cbdd.14020
  68. Sharma N., Bhagat S., Singh Chundawat T. // Mini Rev. Med. Chem. 2017. V. 17. P. 947–958. https://doi.org/10.2174/1389557517666170120152917
  69. Li Z., Xu X., Huang W., Qian H. // Med. Res. Rev. 2018. V. 38. P. 381–425. https://doi.org/10.1002/med.21441
  70. Доценко В.В., Лебедева И.А., Кривоколыско С.Г., Повстяной М.В., Повстяной В.М., Костырко Е.О. // Химия гетероциклич. соед. 2012. Т. 48. С. 492–499. [Dotsenko V.V., Lebedeva I.A., Krivokolysko S.G., Povstyanoi M.V., Povstyanoi V.M., Kostyrko E.O. // Chem. Heterocycl. Compd. 2012. V. 48. P. 462–469.]
  71. Dotsenko V.V., Frolov K.A., Pekhtereva T.M., Papaianina O.S., Suikov S.Yu., Krivokolysko S.G. // ACS Comb. Sci. 2014. V. 16. P. 543–550. https://doi.org/10.1021/co5000807
  72. Dotsenko V.V., Bushmarinov I.S., Goloveshkin A.S., Chigorina E.A., Frolov K.A., Krivokolysko S.G. // Phosphorus Sulfur Silicon Relat. Elem. 2017. V. 192. P. 47–52. https://doi.org/10.1080/10426507.2016.1224877
  73. Чуканова Г.Н., Дворацк М., Искаков С.С., Курмам- баев Е.Ж. // Наука и здравоохранение. 2014. № 4. С. 4–8.
  74. Рыболовлев Ю.Р., Рыболовлев Р.С. // Докл. АН СССР. 1979. Т. 247. С. 1513–1516.
  75. Song Q.Q., Xie W.Y., Tang Y.J., Zhang J., Liu J. // Pharmacogenomics. 2017. V. 18. P. 293–316. https://doi.org/10.2217/pgs-2016-0151
  76. García-Menaya J.M., Cordobés-Durán C., García-Martín E., Agúndez J.A. // Front. Pharmacol. 2019. V. 10. Р. 520. https://doi.org/10.3389/fphar.2019.00520
  77. Тильченко Д.А., Бибик Е.Ю., Фролов К.А., Доценко В.В., Кривоколыско С.Г., Батищева Г.А., Кетова Е.С. // J. Siber. Med. Sci. 2023. Т. 7. С. 118–131. https://doi.org/10.31549/2542-1174-2023-7-1-118-131
  78. Дяченко В.Д., Дяченко И.В., Ненайденко В.Г. // Усп. химии. 2018. Т. 87. С. 1–27. https://doi.org/10.1070/RCR4760

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Biologically active 1,4-dihydro nicotinonitriles.

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3. Fig. 2. Biologically active hybrid molecules with 2-furyl and 1,4-dihydronicotinonitrile fragments.

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4. Scheme 1. Synthesis of compounds (XX) and (XXI).

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5. Scheme 2. Synthesis of compounds (XXII) and (XXIII).

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6. Fig. 3. Dynamics of changes in body weight of rats against the background of modeling dexamethasone diabetes mellitus with subsequent pharmacocorrection with compounds (XX–XXIII) and the reference drug metformin. The differences in the values in the experimental, control and reference groups are significant in comparison with the intact group (p ≤ 0.05).

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