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Synthesis of Biologically Active 6-(Tolylhydrazinylidene)Pyrazolo[1,5-a]Pyrimidinones

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Chemistry of Heterocyclic Compounds Aims and scope

New pyrazolo[1,5-a]pyrimidinones functionalized with the tolylhydrazone fragment were obtained as a result of cyclization of 3-oxo-2-(tolylhydrazinylidene) esters with 3-aminopyrazoles. In this case, methyl- and trifluoromethyl-containing derivatives regioselectively form pyrazolo[1,5-a]pyrimidin-7-ones, while cyclization of polyfluoroalkyl-substituted analogs can take place competitively with the formation of dihydropyrazolo[1,5-a]pyrimidin-5-ones, for which ring-chain isomerism is characteristic in solution. It was found that 6-(tolylhydrazinylidene)pyrazolo[1,5-a]pyrimidin-7-ones have a pronounced analgesic activity. The trifluoromethyl-containing analog selectively inhibits carboxylesterase in micromolar concentration.

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References

  1. Cherukupalli, S.; Karpoormath, R.; Chandrasekaran, B.; Hampannavar, G. A.; Thapliyal, N.; Palakollu, V. N. Eur. J. Med. Chem.2017, 126, 298.

    Article  CAS  Google Scholar 

  2. Tabrizi, A. M.; Baraldi, P. G.; Saponaro, G.; Moorman, A. R.; Romagnoli, R.; Preti, D.; Baraldi, S.; Ruggiero, E.; Tintori, C.; Tuccinardi, T.; Vincenzi, F.; Borea, P. A.; Varani, K. J. Med. Chem.2013, 56, 4482.

    Article  Google Scholar 

  3. Selleri, S.; Bruni, F.; Costagli, C.; Costanzo, A.; Guerrini, G.; Ciciani, G.; Gratteri, P.; Bonaccini, C.; Aiello, P. M.; Besnard, F.; Renard, S.; Costa, B.; Martini, C. J. Med. Chem.2003, 46, 310.

    Article  CAS  Google Scholar 

  4. Qi, J.; Zhang, F.; Mi, Y.; Fu, Y.; Xu, W.; Zhang, D.; Wu, Y.; Du, X.; Jia, Q.; Wang, K.; Zhang, H. Eur. J. Med. Chem.2011, 46, 934.

    Article  CAS  Google Scholar 

  5. Jia, C.; Qi, J.; Zhang, F.; Mi, Y.; Zhang, X.; Chen, X.; Liu, L.; Du, X.; Zhang, H. Pharmacology2011, 87, 297.

    Article  CAS  Google Scholar 

  6. Lin, H.; Moore, M. L.; Qu, J.; Rivero, R. A.; Tedesco, R.; Yu, H.; Luengo, J. I. WO Patent 2013028263A1.

  7. Gehling, V. S.; Bellon, S. F.; Harmange, J.-C.; LeBlanc, Y.; Poy, F.; Odate, S.; Buker, S.; Lan, F.; Arora, S.; Williamson, K. E.; Sandy, P.; Cummings, R. T.; Bailey, C. M.; Bergeron, L.; Mao, W.; Gustafson, A.; Liu, Y.; VanderPorten, E.; Audia, J. E.; Trojer, P.; Albrecht, B. K. Bioorg. Med. Chem. Lett.2016, 26, 4350.

    Article  CAS  Google Scholar 

  8. Liang, J.; Zhang, B.; Labadie, S.; Ortwine, D. F.; Vinogradova, M.; Kiefer, J. R.; Gehling, V. S.; Harmange, J.- C.; Cummings, R.; Lai, T.; Liao, J.; Zheng, X.; Liu, Y.; Gustafson, A.; Van der Porten, E.; Mao, W.; Liederer, B. M.; Deshmukh, G.; Classon, M.; Trojer, P.; Dragovich, P. S.; Murray, L. Bioorg. Med. Chem. Lett.2016, 26, 4036.

  9. Vazquez-Rodriguez, S.; Wright, M.; Rogers, C. M.; Cribbs, A. P.; Velupillai, S.; Philpott, M.; Lee, H.; Dunford, J. E.; Huber, K. V. M.; Robers, M. B.; Vasta, J. D.; Thezenas, M.-L.; Bonham, S.; Kessler, B.; Bennett, J.; Fedorov, O.; Raynaud, F.; Donovan, A.; Blagg, J.; Bavetsias, V.; Oppermann, U.; Bountra, C.; Kawamura, A.; Brennan, P. E. Angew. Chem., Int. Ed. Engl.2019, 58, 515.

  10. Metwally, N. H.; Mohamed, M. S.; Ragb, E. A. Bioorg. Chem.2019, 88, 102929.

    Article  CAS  Google Scholar 

  11. Senga, K.; Novinson, T.; Wilson, H. R.; Robins, R. K. J. Med. Chem.1981, 24, 610.

    Article  CAS  Google Scholar 

  12. Modi, P.; Patel, S.; Chhabria, M. Bioorg. Chem.2019, 87, 240.

    Article  CAS  Google Scholar 

  13. El-Sayed, E. H.; Mohamed, K. S. Polycyclic Aromat. Compd.2019, 39, 1.

    Article  Google Scholar 

  14. Barton, N. P.; Bertrand, S. M.; Down, K.; Gray, M. WO Patent 2019141694A1.

  15. Lançois, D. F. A.; Guillemont, J. É. G.; Raboisson, P. J.-M. B.; Roymans, D. A. E.; Rigaux, P.; Michaut, A. B.; Mercey, G. J. M. WO Patent 2019106004.

  16. Naidu, B. N.; Patel, M.; D'andrea, S.; Zheng, Z. B.; Connolly, T. P.; Langley, D. R.; Peese, K.; Wang, Z.; Walker, M. A.; Kadow, J. F. WO Patent 2014028384.

  17. Babaoglu, K.; Boojamra, C. G.; Eisenberg, E. J.; Hui, H. C.; Mackman, R. L.; Parrish, J. P.; Sangi, M.; Saunders, O. L.; Siegel, D.; Sperandio, D.; Yang, H. WO Patent 2011163518A1.

  18. Gu, B.; Block, T.; Cuconati, A. WO Patent 2007005541A2.

  19. Griffith, D. A. WO Patent 2005103052A1.

  20. Binch, H.; Grootenhuis, P. D. J.; Pierce, A.; Fanning, L. T. D. WO Patent 2009076593A1.

  21. Ndubaku, C. O.; Katibah, G. E.; Roberts, T. C.; Sung, L.; Ciblat, S.; Raeppel, F.; Ly, V. L.; Ramtohul, Y. K.; Rybak, T.; Zaky, M.; Gillard, L.; Ismaili, H. WO Patent 2019055750A1.

  22. Ivachtchenko, A. V.; Golovina, E. S.; Kadieva, M. G.; Kysil, V. M.; Mitkin, O. D.; Tkachenko, S. E.; Okun, I. M. J. Med. Chem.2011, 54, 8161.

    Article  CAS  Google Scholar 

  23. Paruch, K.; Dwyer, M. P.; Alvarez, C.; Brown, C.; Chan, T.-Y.; Doll, R. J.; Keertikar, K.; Knutson, C.; McKittrick, B.; Rivera, J.; Rossman, R.; Tucker, G.; Fischmann, T. O.; Hruza, A.; Madison, V.; Nomeir, A. A.; Wang, Y.; Lees, E.; Parry, D.; Sgambellone, N.; Seghezzi, W.; Schultz, L.; Shanahan, F.; Wiswell, D.; Xu, X.; Zhou, Q.; James, R. A.; Paradkar, V. M.; Park, H.; Rokosz, L. R.; Stauffer, T. M.; Guzi, T. J. Bioorg. Med. Chem. Lett.2007, 17, 6220.

    Article  CAS  Google Scholar 

  24. Labroli, M.; Paruch, K.; Dwyer, M. P.; Alvarez, C.; Keertikar, K.; Poker, C.; Rossman, R.; Duca, J. S.; Fischmann, T. O.; Madison, V.; Parry, D.; Davis, N.; Seghezzi, W.; Wiswell, D.; Guzi, T. J. Bioorg. Med. Chem. Lett.2011, 21, 471.

    Article  CAS  Google Scholar 

  25. Hwang, J. Y.; Windisch, M. P.; Jo, S.; Kim, K.; Kong, S.; Kim, H. C.; Kim, S.; Kim, H.; Lee, M. E.; Kim, Y.; Choi, J.; Park, D.-S.; Park, E.; Kwon, J.; Nam, J.; Ahn, S.; Cechetto, J.; Kim, J.; Liuzzi, M.; No, Z.; Lee, J. Bioorg. Med. Chem. Lett.2012, 22, 7297.

    Article  CAS  Google Scholar 

  26. Li, J.; Zhao, Y. F.; Zhao, X. L.; Yuan, X. Y.; Gong, P. Arch. Pharm.2006, 339, 593.

    Article  CAS  Google Scholar 

  27. Kelada, M.; Walsh, J. M. D.; Devine, R. W.; McArdle, P.; Stephens, J. C. Beilstein J. Org. Chem.2018, 14, 1222.

    CAS  Google Scholar 

  28. Azeredo, L. F. S. P.; Coutinho, J. P.; Jabor, V. A. P.; Feliciano, P. R.; Nonato, M. C.; Kaiser, C. R.; Menezes, C. M. S.; Hammes, A. S. O.; Caffarena, E. R.; Hoelz, L. V. B.; de Souza, N. B.; Pereira, G. A. N.; Cerávolo, I. P.; Krettli, A. U.; Boechat, N. Eur. J. Med. Chem.2017, 126, 72.

    Article  CAS  Google Scholar 

  29. Kosugi, T.; Mitchell, D. R.; Fujino, A.; Imai, M.; Kambe, M.; Kobayashi, S.; Makino, H.; Matsueda, Y.; Oue, Y.; Komatsu, K.; Imaizumi, K.; Sakai, Y.; Sugiura, S.; Takenouchi, O.; Unoki, G.; Yamakoshi, Y.; Cunliffe, V.; Frearson, J.; Gordon, R.; Harris, C. J.; Kalloo-Hosein, H.; Le, J.; Patel, G.; Simpson, D. J.; Sherborne, B.; Thomas, P. S.; Suzuki, N.; Takimoto -Kamimura, M.; Kataoka, K. J. Med. Chem.2012, 55, 6700.

  30. Khudina, O. G.; Shchegol'kov, E. V.; Burgart, Y. V.; Kodess, M. I.; Saloutin, V. I.; Kazheva, O. N.; Shilov, G. V.; D'yachenko, O. A.; Grishina, M. A.; Potemkin, V. A.; Chupakhin, O. N. Russ. J. Org. Chem.2007, 43, 380. [Zh. Org. Khim.2007, 43, 381.]

  31. Khudina, O. G.; Burgart, Y. V.; Shchegol'kov, E. V.; Saloutin, V. I.; Kazheva, O. N.; Chekhlov, A. N.; D'yachenko, O. A. Russ. J. Org. Chem.2009, 45, 801. [Zh. Org. Khim.2009, 45, 819.]

  32. Shchegol'kov, E. V.; Ivanova, A. E.; Burgart, Y. V.; Saloutin, V. I. J. Heterocycl. Chem.2013, 50, E80.

    Article  CAS  Google Scholar 

  33. Shchegol'kov, E. V.; Sadchikova, E. V.; Burgart, Y. V.; Saloutin, V. I. Russ. J. Org. Chem. 2009, 45, 572. [Zh. Org. Khim.2009, 45, 586.]

  34. Khudina, O. G.; Shchegol'kov, E. V.; Burgart, Y. V.; Kodess, M. I.; Kazheva, O. N.; Chekhlov, A. N.; Shilov, G. V.; Dyachenko, O. A.; Saloutin, V. I.; Chupakhin, O. N. J. Fluorine Chem.2005, 126, 1230.

    Article  CAS  Google Scholar 

  35. Shchegol'kov, E. V.; Sadchikova, E. V.; Burgart, Y. V.; Saloutin, V. I. Russ. Chem. Bull., Int. Ed.2008, 57, 612. [Izv. Akad. Nauk, Ser. Khim.2008, 599.]

  36. Shchegol'kov, E. V.; Khudina, O. G.; Ivanova, A. E.; Burgart, Y. V.; Sadchikova, E. V.; Kravchenko, M. A.; Saloutin, V. I. Pharm. Chem. J.2014, 48, 383. [Khim. Farm. Zh.2014, 48(6), 29.]

  37. Guidelines for preclinical studies of drugs. Part I [in Russian]; Mironov, A. N., Ed.; Moscow: Grif i K, 2012.

  38. OECD Guideline for Testing of Chemicals; 423: Acute Oral Toxicity – Acute Toxic Class Method; Paris, 2001.

  39. Gein, V. L.; Popov, A. V.; Kolla, V. E.; Popova, N. A.; Potemkin, K. D. Pharm. Chem. J.1993, 27, 343. [Khim. Farm. Zh.1993, 27(5), 42.]

  40. Inoue, M.; Okamura, T.; Shoji, Y.; Hashimoto, K.; Ohara, M.; Yasuda, T. WO Patent 1997011946A1.

  41. 41.Boltneva, N. P.; Makhaeva, G. F.; Kovaleva, N. V.; Lushchekina, S. V.; Burgart, Y. V.; Shchegol'kov, E. V.; Saloutin, V. I.; Chupakhin, O. N. Dokl. Biochem. Biophys.2015, 465, 381. [Dokl. Akad. Nauk2015, 465, 367.]

  42. Boltneva, N. P.; Makhaeva, G. F.; Shchegol'kov, E. V.; Burgart, Y. V.; Saloutin, V. I. Biomed. Chem. Res. Methods2018, 1, e00026.

    Article  Google Scholar 

  43. Shchegol'kov, E. V.; Makhaeva, G. F.; Boltneva, N. P.; Lushchekina, S. V.; Serebryakova, O. G.; Rudakova, E. V.; Kovaleva, N. V.; Burgart, Y. V.; Saloutin, V. I.; Chupakhin, O. N.; Bachurin, S. O.; Richardson, R. J. Bioorg. Med. Chem.2017, 25, 3997.

    Article  CAS  Google Scholar 

  44. Makhaeva, G. F.; Elkina, N. A.; Shchegolkov, E. V.; Boltneva, N. P.; Lushchekina, S. V.; Serebryakova, O. G.; Rudakova, E. V.; Kovaleva, N. V.; Radchenko, E. V.; Palyulin, V. A.; Burgart, Y. V.; Saloutin, V. I.; Bachurin, S. O.; Richardson, R. J. Bioorg. Chem.2019, 91, 103097.

    Article  CAS  Google Scholar 

  45. Makhaeva, G. F.; Rudakova, E. V.; Kovaleva, N. V.; Lushchekina, S. V.; Boltneva, N. P.; Proshin, A. N.; Shchegolkov, E. V.; Burgart, Y. V.; Saloutin, V. I. Russ. Chem. Bull., Int. Ed.2019, 68, 967. [Izv. Akad. Nauk, Ser. Khim.2019, 967.]

  46. Makhaeva, G. F.; Radchenko, E. V.; Palyulin, V. A.; Rudakova, E. V.; Aksinenko, A. Y.; Sokolov, V. B.; Zefirov, N. S.; Richardson, R. J. Chem.-Biol. Interact.2013, 203, 231.

  47. Makhaeva, G. F.; Boltneva, N. P.; Lushchekina, S. V.; Serebryakova, O. G.; Stupina, T. S.; Terentiev, A. A.; Serkov, I. V.; Proshin, A. N.; Bachurin, S. O.; Richardson, R. J. Bioorg. Med. Chem.2016, 24, 1050.

    Article  CAS  Google Scholar 

  48. Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Free Radical Biol. Med.1999, 26, 1231.

    Article  CAS  Google Scholar 

  49. Shchegolkov, E. V; Burgart, Y. V; Khudina, O. G.; Saloutin, V. I.; Chupakhin, O. N. Russ. Chem. Rev.2010, 79, 31. [Usp. Khim.2010, 79, 33.]

  50. Politanskaya, L. V; Selivanova, G. A.; Panteleeva, E. V.; Tretyakov, E. V.; Platonov, V. E.; Nikul'shin, P. V.; Vinogradov, A. S.; Zonov, Y. V; Karpov, V. M.; Mezhenkova, T. V; Vasilyev, A. V.; Koldobskii, A. B.; Shilova, O. S.; Morozova, S. M.; Burgart, Ya. V.; Shchegolkov, E. V.; Saloutin, V. I.; Sokolov, V. B.; Aksinenko, A. Yu.; Nenajdenko, V. G.; Moskalik, M. Yu.; Astakhova, V. V.; Shainyan, B. A.; Tabolin, A. A.; Ioffe, S. L.; Muzalevskiy, V. M.; Balenkova, E. S.; Shastin, A. V.; Tyutyunov, A. A.; Boiko, V. E.; Igumnov, S. M.; Dilman, A. D.; Adonin, N. Y.; Bardin, V. V.; Masoud, S. M.; Vorobyeva, D. V.; Osipov, S. N.; Nosova, E. V.; Lipunova, G. N.; Charushin, V. N.; Prima, D. O.; Makarov, A. G.; Zibarev, A. V.; Trofimov, B. A.; Sobenina, L. N.; Belyaeva, K. V.; Sosnovskikh, V. Y.; Obydennov, D. L.; Usachev, S. A. Russ. Chem. Rev.2019, 88,425. [Usp. Khim.2019, 88, 425.]

  51. Sheldrick, G. M. Acta Crystallogr, Sect. C: Struct. Chem.2015, 71, 3.

  52. Burgart, Y. V.; Agafonova, N. A.; Shchegolkov, E. V.; Maslova, V. V.; Triandafilova, G. A.; Solodnikov, S. Y.; Krasnykh, O. P.; Saloutin, V. I. Chem. Heterocycl. Compd.2019, 55, 52. [Khim. Geterotsikl. Soedin.2019, 55, 52.]

  53. Agafonova, N.; Shchegolkov, E.; Burgart, Y.; Saloutin, V.; Trefilova, A.; Triandafilova, G.; Solodnikov, S.; Maslova, V.; Krasnykh, O.; Borisevich, S.; Khursan, S. Med. Chem.2019, 15, 521.

    Article  CAS  Google Scholar 

  54. Makhaeva, G. F.; Sokolov, V. B.; Shevtsova, E. F.; Kovaleva, N. V.; Lushchekina, S. V.; Boltneva, N. P.; Rudakova, E. V.; Aksinenko, A. Y.; Shevtsov, P. N.; Neganova, M. E.; Dubova, L. G.; Bachurin, S. O. Pure Appl. Chem.2017, 89, 1167.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22 S. Kovalevskoi / 20 Akademicheskaya St, Yekaterinburg, 620108, Russia

    Yanina V. Burgart, Natalia А. Elkina, Evgeny V. Shchegolkov & Victor I. Saloutin

  2. Ural Federal University named after the first President of Russia B. N. Yeltsin, 19 Mira St, Yekaterinburg, 620002, Russia

    Yanina V. Burgart, Evgeny V. Shchegolkov & Victor I. Saloutin

  3. Perm National Research Polytechnic University, 29 Komsomolsky Ave, Perm, 614990, Russia

    Olga P. Krasnykh, Vera V. Maslova, Galina A. Triandafilova & Sergey Yu. Solodnikov

  4. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severnyi Proezd, Chernogolovka, 142432, Russia

    Galina F. Makhaeva, Olga G. Serebryakova & Elena V. Rudakova

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  1. Yanina V. Burgart
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  2. Natalia А. Elkina
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Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(2), 199–207

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Burgart, Y.V., Elkina, N.А., Shchegolkov, E.V. et al. Synthesis of Biologically Active 6-(Tolylhydrazinylidene)Pyrazolo[1,5-a]Pyrimidinones. Chem Heterocycl Comp 56, 199–207 (2020). https://doi.org/10.1007/s10593-020-02652-1

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