European Journal of Chemistry

Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues

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Published: Dec 31, 2014
DOI: https://doi.org/10.5155/eurjchem.5.4.588-594.1109
Keywords:
Pyrimidines, Anti-HIV activity, Sodium hypochlorite, Molecular modeling study, Structure activity relationship, Non-nucleoside reverse transcriptase inhibitors
Section
Research Article
Issue
Vol. 5 No. 4 (2014): December 2014
Dates
Received 2014-06-15
Accepted 2014-07-08
Published 2014-12-31


Main Article Content

Yossra Abood Marich
Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
Niran Jassim Al-Salihi
Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
Najim Aboud Al-Masoudi
Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq

Abstract

A new series of 2,6-diamino-5-arylazo-4-chloropyrimidine analogues (6-13) were synthesized from the pyrimidine scaffold 5, via diazotization with various amines. Nucleophilic displacement of compound 5 by ethanethiolate or arylthio nucleophiles, afforded the 4-alkylthio analogues (14-16). Treatment of compound 17 or 18 with thiourea under MWI gave the 4-thione derivatives 19 and 20, respectively. On treatment of compound 20 with 2-mercaptoacetic acid furnished the 4-thio analogue (21). Reaction of compound 19 or 20 with sodium hypochlorite followed by ammonium hydroxide afforded the 4-aminothio analogues 22 and 23, respectively. Oxidation of compound 23 with H2O2 led to the 4-sulphonamide derivative 24. All new compounds were evaluated for their in vitro antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. Compounds 14-16 and 21 showed an EC50 values of > 2.12, 1.99, 1.80 and 1.92 μg/mL, respectively. In addition, preliminary structure-activity relationship and molecular modeling of compound 15 has been studied.


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Marich, Y. A.; Al-Salihi, N. J.; Al-Masoudi, N. A. Synthesis, Anti-HIV Activity and Molecular Modeling Study of Some New Pyrimidine Analogues. Eur. J. Chem. 2014, 5, 588-594.

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References

[1]. Cocco, M. T.; Congiu, C.; Lilliu, V. Bioorg. Med. Chem. 2006, 14, 366-372.
http://dx.doi.org/10.1016/j.bmc.2005.08.012

[2]. Heidelberger, C.; Chaudhuri, N. K.; Danneberg, P.; Mooren, D.; Griesbach, L.; Duschinsky, R.; Schnitzer, R. J.; Pleven, E.; Scheiner, J. Nature 1957, 179, 663-666.
http://dx.doi.org/10.1038/179663a0

[3]. Beattie, J. F.; Breault, G. A.; Ellston, R. P. A.; Green, S.; Jewsbury, P. J.; Midgley, C. J.; Naven, R. T.; Minshull, C. A.; Pauptit, R. A.; Tucker, J. A.; Pease, J. E. Bioorg. Med. Chem. Lett. 2003, 13, 2955-2960.
http://dx.doi.org/10.1016/S0960-894X(03)00202-6

[4]. Kimura, H.; Katoh, T.; Kajimoto, T.; Node, M.; Hisaki, M.; Sugimoto, Y.; Majima, T.; Uehara, Y.; Yamori, T. Anticancer Res. 2006, 26, 91-97.

[5]. Lagoja, I. M. Chem. Biodiver. 2005, 2, 1-50.
http://dx.doi.org/10.1002/cbdv.200490173

[6]. Dudhea, R.; Sharmab, P. K.; Vermae, P.; Chaudhary, A. J. Adv. Sci. Res. 2011, 2, 10-17.

[7]. Patel, D. H.; Mistry, B. D.; Desai, K. R Indian J. Hetero. Chem. 2003, 13, 179-80

[8]. Bantawal, S. H.; Manjathuru, M.; Mari, K. S.; Padiyath, K. M. Bioorg. Med. Chem. 2006, 14, 2040-2047.
http://dx.doi.org/10.1016/j.bmc.2005.10.053

[9]. Sharma, P.; Rane, N.; Gurram, V. K. Bioorg. Med. Chem. Lett. 2004, 14, 4185-4190.
http://dx.doi.org/10.1016/j.bmcl.2004.06.014

[10]. Adnan, A. B.; Hesham, T. Z.; Sherif, A. F.; Azza, M. B. Eur. J. Med. Chem. 2003, 38, 27-36.
http://dx.doi.org/10.1016/S0223-5234(02)00009-0

[11]. Russell, R. K.; Press, J. B.; Rampulla, R. A.; McNally, J. J.; Falotico, R.; Keiser, J. A.; J. Med. Chem. 1988, 31, 1786-1793.
http://dx.doi.org/10.1021/jm00117a019

[12]. Fillios, L. C.; Naito, C.; Andrews, S.; Roach, A. M. Circ. Res. 1960, 8, 71-77.
http://dx.doi.org/10.1161/01.RES.8.1.71

[13]. Kappe, C. O. Tetrahedron 1993, 49, 6937-6963.
http://dx.doi.org/10.1016/S0040-4020(01)87971-0

[14]. Kreutzberger, A.; Burgwitz, K. Arch. Pharm. 1981, 314, 394-398.
http://dx.doi.org/10.1002/ardp.19813140504

[15]. Monge, A.; Martinez-Merino, V.; Sanmartin, C.; Fernandez, F. J.; Ochoa, M. C.; Bellver, C. Artigas, P. Arznei-Forschung. 1990, 40, 1230-1233.

[16]. Yamazi, Y.; Takahashi, M.; Todome, Y. Proc. Soc. Exp. Biol. Med. 1970, 133, 674-677.
http://dx.doi.org/10.3181/00379727-133-34542

[17]. Prichard, M. N.; Quenelle, D. C.; Hartline, C. B.; Harden, E. A.; Jefferson, G.; Frederick, S. L.; Daily, S. L.; Whitley, R. J.; Tiwari, K. N.; Maddry, J. A.; Secrist, J. A.; Kern, E. R. Antimicrob. Agents Chemother. 2009, 53, 5251-5285.
http://dx.doi.org/10.1128/AAC.00417-09

[18]. Miyasaka, T.; Tanaka, H.; Baba, M.; Hayakawa, H.; Walker, R. T.; Balzarini, J.; De Clercq, E. J. Med. Chem. 1989, 32, 2507-2509.
http://dx.doi.org/10.1021/jm00132a002

[19]. Tanaka, H.; Takashima, H.; Ubasawa, M.; Sekiya, K.; Nitta, I.; Baba, M.; Shigeta, S.; Walker, R. T.; De Clercq, E.; Miyasaka, T. J. Med. Chem. 1992, 35, 337-345.
http://dx.doi.org/10.1021/jm00080a020

[20]. Balzarini, J.; Baba, M.; De Clercq, E. Antimicrob. Agents Chemother. 1995, 39, 998-1002.
http://dx.doi.org/10.1128/AAC.39.4.998

[21]. Janssen, P. A. J.; Lewi, P. J.; Arnold, E.; Daeyaert, F.; de Jonge, M.; Heeres, J.; Koymans, L.; Vinkers, M.; Guillemont, J.; Pasquier, E.; Kukla, M.; Ludovici, D.; Andries, K.; de Béthune, M. -P.; Pauwels, R.; Das, K.; Clark Jr., A. D.; Frenkel, Y. V.; Hughes, S. H.; Medaer, B.; De Knaep, F.; Bohets, H.; De Clerck, F.; Lampo, A.; Williams, P.; Stoffels, P. J. Med. Chem. 2005, 48, 1901-1909.
http://dx.doi.org/10.1021/jm040840e

[22]. Ludovici, D. W.; de Corte, B. L.; Kukla, M. J.; Ye, H.; Ho, C. Y.; Lichtenstein, M. A.; Kavash, R. W.; Andries, K.; de Bethune, M. P.; Azijn, H.; Pauwels, R.; Lewi, P. J.; Heeres, J.; Koymans, L. M.; de Jonge, M. R.; Aken, K. J. V.; Daeyaert, F. F.; Das, K.; Arnold, E.; Janssen, P. A. Bioorg. Med. Chem. 2001, 11, 2235-2239.
http://dx.doi.org/10.1016/S0960-894X(01)00412-7

[23]. Das, K.; Clark, A. D.; Lewi, P. J.; Heeres, J.; de Jonge, M. R.; Koymans, L. M. H.; Vinkers, H. M.; Daeyaert, F.; Ludovici, D. W.; Kukla, M. J.; De Corte, B.; Kavash, R. W.; Ho, C. Y.; Ye, H.; Lichtenstein, M. A.; Andries, K.; Pauwels, R.; de Béthune, M. -P.; Boyer, P. L.; Clark, P.; Hughes, S. H.; Janssen, P. A. J.; Arnold, E. J. Med. Chem. 2004, 47, 2550-2560.
http://dx.doi.org/10.1021/jm030558s

[24]. Yan, Z. H.; Wu, H. Q.; Chen, W. X.; Piao, H. R.; He, Q. Q.; Chen, F. E.; De Clercq, E.; Pannecouque, C. Bioorg. Med. Chem. 2014, 22, 3220-3226.
http://dx.doi.org/10.1016/j.bmc.2014.03.020

[25]. Pindola, V. K.; Zarowitz, B. J. Pharmacother. 2002, 22, 1249-1265.
http://dx.doi.org/10.1592/phco.22.15.1249.33482

[26]. Gong, B.; Hong, F.; Kohm, K.; Jenkins, S.; Tulinsky, J.; Bhatt, R.; de Vries, P.; Singer, J. W.; Klein, P. P. Bioorg. Med. Chem. Lett. 2004, 14, 2303-2308.
http://dx.doi.org/10.1016/j.bmcl.2004.01.104

[27]. Mayer, T. U.; Kapoor, T. M.; Haggarty, S. J.; King, R. W.; Schreiber, S. L.; Mitchison, T. J. Science 1999, 286, 971-974.
http://dx.doi.org/10.1126/science.286.5441.971

[28]. Sharp, D. J.; Rogers, G. C.; Scholey, J. M. Nature 2000, 407, 41-47.
http://dx.doi.org/10.1038/35024000

[29]. Yoon, Y. A.; Park, C. S.; Cha, M. H.; Choi, H.; Sim, J. Y.; Kim, J. G. Biooorg. Med. Chem. Lett. 2010, 20, 5735-5738.
http://dx.doi.org/10.1016/j.bmcl.2010.08.007

[30]. Jain, K. S.; Chitre, T. S.; Miniyar, P. B.; Kathiravan, M. K.; Bendre, V. S.; Veer, V. S.; Shahane, S. R.; Shishoo, C. J. Curr. Sci. 2006, 90, 793-803.

[31]. Al-Masoudi, N. A.; Jafar, N. N. A.; Baqir, S. J.; Pannecouque, C.; Leyssen, P.; Neyts, J. Antivir. Chem. Chemother. 2012, 23, 103-112.
http://dx.doi.org/10.3851/IMP2400

[32]. Al-Masoudi, N. A.; Kassim, A. G.; Abdul-Reda, N. A. Nucleos. Nucleot. Nucl. 2014, 33, 141-161.
http://dx.doi.org/10.1080/15257770.2014.880475

[33]. Al-Masoudi, N. A.; Marich, Y. A.; Al-Salihi, N. J.; Saeed, B. Z. Naturforsch. 2014, 69b, 913-923.
http://dx.doi.org/10.5560/ZNB.2014-4107

[34]. Davis, A. L.; Keeler, J.; Laue, E. D.; Moskau, D. J. Magn. Reson. 1992, 98, 207-216.

[35]. Lawson, A.; Tinkler, R. B. Chem. Rev. 1970, 70, 593-618.
http://dx.doi.org/10.1021/cr60267a004

[36]. Xu, Y.; Yang, H.; Hu, J.; Wang, X. W; Liu, J. Y. J. Chinese Pharm. Sci. 2007, 16, 125-127.

[37]. Iijima, I.; Rice, K. C. J. Heterocycl. Chem. 1978, 15, 1527-1528.
http://dx.doi.org/10.1002/jhet.5570150863

[38]. Davis, A. L.; Keeler, J.; Laue, E. D.; Moskau, D. J. Magn. Reson. 1992, 98, 207-216.

[39]. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. J. Virol. Methods 1988, 20, 309-321.
http://dx.doi.org/10.1016/0166-0934(88)90134-6

[40]. Hargrave, K. D.; Proudfoot, J. R.; Grozinger, K. G.; Cullen, E.; Kapadia, S. R.; Patel, U. R.; Fuchs, V. U.; Mauldin, S. C.; Vitous, J.; Behnke, M. L.; Klunder, J. M.; Pal, K.; Skiles, J. W.; McNeil, D. W.; Rose, J. M.; Chow, G. C.; Skoog, M. T.; Wu, J. C.; Schmidt, G.; Engel, W. W.; Eberlein, W. G.; Saboe, T. D.; Campbell, S. J.; Rosenthal, A. S.; Adams, J. J. Med. Chem. 1991, 34, 2231-2241.
http://dx.doi.org/10.1021/jm00111a045

[41]. Mitsuya, H.; Weinhold, K. J.; Furman, P. A.; Clair, M. H. St.; Lehrmann, S. N.; Gallo, R.; Bolognesi, D.; Barry, D. W.; Broder, S. Proc. Natl. Acad. Sci. USA 1985, 82, 7096-7100.
http://dx.doi.org/10.1073/pnas.82.20.7096

[42]. Seeliger, S.; de Groot, B. L. J. Comput. Aid. Mol. Des. 2010, 24, 417-422.
http://dx.doi.org/10.1007/s10822-010-9352-6

[43]. Zhan, P.; Liu, X.; Li, Z.; Fang, Z.; Pannecouque, C.; De Clercq, E. Chem. Biodivers. 2010, 7, 1717-1727.
http://dx.doi.org/10.1002/cbdv.200900197

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