Synthesis, characterization and anthelmintic activity evaluation of pyrimidine derivatives bearing carboxamide and sulphonamide moieties

David Izuchukwu Ugwu, Uchechukwu C. Okoro, Narendra Kumar Mishra

Abstract


Pyrimidines, sulphonamides and carboxamides have shown a large number of pharmacological properties against different types of diseases inc­luding helminthiasis. Seventeen new pyrimidine derivatives bearing sulphon­amide and carboxamide were synthesized and investigated for their in vitro anthelmintic properties. Substituted benzenesulphonyl chlorides 15ac were treated with various amino acids (16ah) to obtain benzenesulphonamide derivatives 17al. Compounds 17af were subsequently treated with benzoyl chloride to obtain the N-benzoylated derivatives 19af. Further reactions of compounds 19af and 17gl with 4- or 2-aminopyrimidine (20) using boric acid as a catalyst gave the required sulphonamide carboxamide derivatives 21aq in excellent yields. The compounds were isolated in their analytical grade and characterized using FTIR, 1H-NMR, 13C-NMR and HRMS. The in vitro anthel­mintic studies showed that all the synthesized compounds possessed anthel­mintic property. Compounds 21ac, e, g, m and p showed mean paralyzing times of 15, 19, 14, 18, 19, 19 and 18 min, respectively, at 100 mg mL-1 compared to 10 min for albendazole. Compounds 21a–c, g and m had mean death times of 18, 24, 16, 20 and 25 min, respectively, at 100 mg mL-1 compared to 13 min for albendazole.

Keywords


catalysis; anthelmintics; synthesis; carboxamides; sulphonamides

References


M. Albonico, H. Allen, L, Chitsulo, D. Engles, A. F. Gabrielli, L. Savioli, S. Brooker, PLOS Negletted Tropical Diseases, 2(3), (2008) 126.

A. K. Young-Joon, Y. J. K. Min, B. Sang-Ji, J. Econ. Entomol., 86 (1993) 1338.

S. El-Zemity, M. E. Badawy, M. M. Khattab, A. E. Marei, Int. J. Agric. Bio., 8(5) (2006) 665.

C. T. Supuran, H. Scozzafava, A. Casini, Med. Res. Rev., 23(2) (2003) 189.

J. A. Eussell, Annu. Rev. Biochem., 14, (1945) 309.

Shinogi, US Patent, 2 888 455, (1959).

L. MacDonald, P. Kazanijan, Formulary, 31 (1996) 470.

M. S. L. Kwee, L. M. L. Stolk, Pharm. Weekbl., 6 (1984) 104.

H. Mitsuya, Proc. Natl. Acad. Sci. 82 (1985) 7096.

F. C. Coalpaert, T. F. Meert, C. J. E. Niemegens, P. A. J. Janssen, Psychopharmacology, 86, (1985) 45.

M. J. Arnaud, Products of metabolism of caffein. In Caffein, Perspectives from Recent Research (ed. Dews, P. B.), SpringerVerlag, New York, 1984, p. 3.

Abott, US Patent, 2 153 729, (1939).

E. Honkanen, A. Pipuri, P. Kairisalo, P. Nore, H. Karppaness, I. Paakari, J. Med. Chem., 26 (1983) 143.

B. Gauthier, Ann. Pharm. Fr. 21, (1963) 655.

J. Tani, J. Med. Chem., 22, (1979) 95.

E. F. Gale, E. Cundliffe, P. E. Reynolds, M. H. Richmond, M. J. Waring, The Molecular Basis of Antibiotic Action, Wiley and Sons, 1981, 2nd edn, pp. 500–502.

A. Polak, H. J. Scholer, Chemotherapy 21 (1975) 113.

E. A. Brown, R. Griffith, C. A. Harvey, D. D. A. Owen, Brit. J. Pharmacol., 87, (1986) 569.

B. D. Clarkson, Cancer 5, (1970) 227.

F. Hunziker, Helv. Chim. Acta, 50 (1967) 1588.

S. J. Raul, A. H. More, S. S. Mahajan, Intl. J. of Research in Pharmacy and Chemistry 1(4), (2011), 991.

R. Vardanyan, V. Hruby, (2006) Synthesis of Essential Drugs. Amsterdam: Elsevier 8

M. Asif, Am. J. Curr. Org. Chem., 1, (2014) 59.

M. J. Yelland, C. J. Nikles, N. McNairn, C. B. Del Mar, P. J. Schluter, Rheumatology 46 (2007), 140.

Z. G. Jiao, H. Q. He, C. C. Zeng, J. J. Tan, L. M. Hu, C. X. Wang, Molecules 15 (2010) 1917.

F. C. Hans, E. Jawetz, Basic and Chemical Pharmacology (1998), Katzung, B.G (ed) Appletonlange 763.

P. Verhaeghe, N. Azas, M. Gasquet, S. Hutter, C. Ducros, Bioorg. Med. Chem. Lett. 18, (2008) 401.

H. H. Mrozik, N. J. Matawan US, 3987199 (1976) 28.

N. R. Mohan, S. Sreenivasa, K. E. Manojkumar, T. M. C. Rao, B. S. Thippeswamy, P. A. Suchetan, J. Braz. Chem. Soc. 25(6) (2014) 1020.

J. Vijaya, E. Jayachandran, S. Ravi, K. Patel, G. M. Sreenivasa, Int. J. Pharma Biosciences 1(3) (2010) 8.

R. Kumar, G. K. Sharma, D. Pathak, Int. J. Pharm. Rev. Res. 27(1) (2014) 60.

I. S. Babu, S. Selankumar, Der Pharma Chemica 5(4) (2013) 206.

R. Kumar, Y. C. Joshi, J. Serb. Chem. Soc. 73(10) (2008) 943.

P. W. Tang, Org. Synth., 81 (2005) 262.

L. C. Garg, C. K. Atal, Ind. J. Pharm. Sci., 59 (1963) 245.




DOI: https://doi.org/10.2298/JSC170127109U

Copyright (c) 2017 J. Serb. Chem. Soc.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

IMPACT FACTOR 0.822 (131 of 166 journals)
5 Year Impact Factor 1.015 (118 of 166 journals)