Synthesis 2020; 52(16): 2347-2356
DOI: 10.1055/s-0040-1707948
paper
© Georg Thieme Verlag Stuttgart · New York

Regioselective Synthesis of Pyrazolyl-pyrimidine Hybrids of Pharmacological Interest

Adriano F. Camargo
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
,
Mário A. Marangoni
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
,
Paulo A. de Moraes
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
,
Pablo A. Nogara
b  Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
,
Blessing A. Afolabi
b  Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
,
Carlos E. Bencke
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
,
João B. T. Rocha
b  Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
,
Helio G. Bonacorso
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
,
Marcos A. P. Martins
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
,
a  Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil   Email: nilo.zanatta@ufsm.br
› Author Affiliations
The authors are grateful for financial support from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS/CNPq – PRONEX, grant No. 16/2551-0000477-3), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant no. 407898/2018-2).
Further Information

Publication History

Received: 27 February 2020

Accepted after revision: 11 April 2020

Publication Date:
12 May 2020 (online)


Abstract

The regioselective synthesis of twenty novel [3-substituted 5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl][6-aryl-(2-methylthio)pyrimidin-4-yl]methanones from the cyclocondensation reactions of new 6-aryl-2-(methylthio)pyrimidine-4-carbohydrazides with 4-substituted 1,1,1-trifluorobut-3-en-2-ones is reported. Human acetylcholinesterase (HsAChE) and butyrylcholinesterase (HsBChE) inhibition tests were performed on selected products in order to explore the possible pharmacological applications of these compounds. Two compounds showed significant and selective inhibitory activity for BChE.

Supporting Information

 
  • References

  • 1 Agarwal A, Srivastava K, Puri SK, Chauhana PM. S. Bioorg. Med. Chem. 2005; 13: 4645
  • 2 Bailey JP, Giles MB, Pass M. WO 2006005914, 2006
  • 3 Rotili D, Tarantino D, Artico M, Nawrozkij MB, Ortega EG, Clotet B, Samuele A, Esté JA, Maga G, Mail A. J. Med. Chem. 2011; 54: 3091
  • 4 Agarwal A, Srivastava K, Puri SK, Sinha S, Chauhana PM. S. Bioorg. Med. Chem. Lett. 2005; 15: 5218
  • 5 da Silva AM. P. W, da Silva FM, Nogara PA, Dutra EJ. M, Serres JD. S, Saraiva RA, Piccoli BC, Oliveira CS, Schetinger MR. C, Morsch VM. M, Rocha JB. T, Bonacorso HG, Martins MA. P, Zanatta N. Chem. Biol. Drug Des. 2017; 90: 1161
  • 6 Lobo MM, Zanatta N, Martins MA. P, Bonacorso HG, Santos JM, Oliveira MS, Brusco I, Machado P, Timmers FS. M. L, Canova B, Silva VF. T. Eur. J. Med. Chem. 2015; 102: 143
  • 7 Bekhit AA, Abdel-Aziem T. Bioorg. Med. Chem. 2004; 12: 1935
  • 8 Zanatta N, Flores DC, Madruga CC, Faoro D, Flores AF. C, Bonacorso HG, Martins MA. P. Synthesis 2003; 894
  • 9 Petricci E, Mugnaini C, Radi M, Togninelli A, Bernardi C, Manetti F, Parlato MC, Renzulli ML, Alongi M, Falciani C, Corelli F, Botta M. ARKIVOC 2006; (vii): : 452
  • 10 Bolli M, Lescop C, Mathys B, Mueller C, Nayler O, Steiner B. WO2009057079A2, 2009 .
    • 11a Shcherbatiuk AV, Shyshlyk OS, Yarmoliuk DV, Shishkin OV, Shishkina SV, Starova VS, Zaporozhets OA, Zozulya S, Moriev R, Kravchuk O, Manoilenko O, Tolmachev AA, Mykhailiuk PK. Tetrahedron 2013; 69: 3796
    • 11b Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
    • 12a Bonacorso HG, Oliveira MR, Costa MB, Silva LB, Zanatta N, Martins MA. P, Flores AF. C. J. Braz. Chem. Soc. 2005; 16: 868
    • 12b Bonacorso HG, Cavinatto S, Moraes MC, Pittaluga EP, Peroza LR, Venturini T, Alves SH, Stefanello ST, Soares FA. A, Martins MA. P, Zanatta N, Frizzo CP. J. Braz. Chem. Soc. 2015; 26: 2346
    • 12c Bonacorso HG, Cechinel CA, Navarini J, Andrighetto R, Martins MA. P, Zanatta N. Monatsh. Chem. 2011; 142: 277
    • 12d Bonacorso HG, Rodrigues MB, Rosa WC, Silva LB, Frizzo CP, Zanatta N, Martins MA. P. J. Fluorine Chem. 2015; 178: 296
  • 13 Zanatta N, Fortes SA, Bencke EC, Marangoni MA, Fantinel AC, Camargo FA, Martins MA. P, Bonacorso HG. Synthesis 2015; 47: 827
  • 14 Budesinsky Z, Roubínek F. Collect. Czech. Chem. Commum. 1961; 26: 2871
  • 15 Bonacorso HG, Nogara AP, Silva DA. F, Rosa CW, Wiethan WC, Rocha BT, Zanatta N, Martins MA. P. J. Fluorine Chem. 2016; 190: 31
  • 16 Zanatta N, Amaral SS, dos Santos JM, da Silva AM. P. W, Schneider JM. F. M, Fernandes LS, Bonacorso HG, Martins MA. P. Tetrahedron Lett. 2013; 54: 4076
    • 17a Bonacorso HG, Paim GR, Guerra CZ, Sehnem RC, Cechinel CA, Porte LM. F, Martins MA. P, Zanatta N. J. Braz. Chem. Soc. 2009; 20: 509
    • 17b Bonacorso HG, Pittaluga EP, Alves SH, Schaffer LF, Cavinatto S, Porte LM. F, Paim GR, Martins MA. P, Zanatta N. ARKIVOC 2012; (viii): : 62
    • 18a Krátký M, Štěpánková S, Vorčáková K, Švarcová M, Vinšová J. Molecules 2016; 21: 191
    • 18b Giacobini E. Drugs Aging 2001; 18: 891
    • 19a Nordberg A., Ballard C., Bullock R., Darreh-Shori T., Somogyi M.; Primary Care Companion CNS Disord.; 2013, DOI: 10.4088/PCC.12r01412
    • 19b Dighe SN, Deora GS, De la Mora E, Nachon F, Chan S, Parat M.-O, Brazzolotto X, Ross BP. J. Med. Chem. 2016; 59: 7683
    • 20a Mohamed T, Rao PP. N. Bioorg. Med. Chem. Lett. 2010; 20: 3606
    • 20b Unsal-Tan O, Küçükkılınç TT, Ayazgök B, Balkan A, Ozadali-Sari K. MedChemComm 2019; 10: 1018
    • 20c Chigurupati S, Selvaraj M, Mani V, Selvarajan KK, Mohammad JI, Kaveti B, Bera H, Palanimuthu VR, Teh LK, Salleh MZ. Bioorg. Chem. 2016; 67: 9
  • 21 Bruker, APEX2 (Version 2.1), COSMO (Version 1.56) BIS (Version 2.0.1.9), SAINT (Version 7.3A), SADABS (Version 2004/1), and XPREP9 (Version2005/4), Bruker AXS Inc., Madison, WI, USA, 2006.
  • 22 Farrugia LJ. J. Appl. Crystallogr. 1999; 32: 837
  • 23 Worek F, Mast U, Kiderlen D, Diepold C, Eyer P. Clin. Chim. Acta 1999; 288: 73
  • 24 Bjerrum PJ. J. Membr. Biol. 1979; 48: 43
  • 25 Ellman GL, Courtney KD, Andres V, Featherstone RM. Biochem. Pharmacol. 1961; 7: 88
  • 26 Dixon M. Biochem. J. 1953; 55: 170
  • 27 Punekar NS. Enzymes: Catalysis, Kinetics and Mechanisms . Springer Nature Singapore; Singapore: 2018
  • 28 Trott O, Olson A. J. Comput. Chem. 2010; 31: 455
  • 29 Babkov DA, Chizhov AO, Khandazhinskaya AL, Corona A, Esposito F, Tramontano E, Seley-Radtke KL, Novikov MS. Synthesis 2015; 47: 1413
  • 30 Nogara P. A., Saraiva R. D. A., Caeran Bueno D., Lissner L. J., Corte C. L. D., Braga M. M., Rosemberg D. B., Rocha J. B. T.; BioMed Res. Int.; 2015, DOI: org/10.1155/2015/870389
  • 31 Nicolet Y, Lockridge O, Masson P, Fontecilla-Camps JC, Nachon C. J. Biol. Chem. 2003; 278: 41141
  • 32 Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. J. Comput. Chem. 2004; 25: 1605
  • 33 Hanwell M. D., Curtis D. E., Lonie D. C., Vandermeersch T., Zurek E., Hutchison G. R.; J. Cheminf.; 2012, DOI: org/10.1186/1758-2946-4-17
  • 34 Stewart JJ. P. J. Mol. Model. 2007; 13: 1173
  • 35 Rossi S, Annunziata R, Cozzi F, Raimondi LM. Synthesis 2015; 47: 2113
  • 36 Stewart J. MOPAC . Stewart Computational Chemistry; Colorado Springs: 2016. ; http://openmopac.net/
  • 37 Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ. J. Comput. Chem. 1998; 19: 1639
  • 38 D.S. BIOVIA. Accelrys Discovery Studio (now Dassault Systèmes BIOVIA), 2017. https://www.3dsbiovia.com/.