European Journal of Chemistry

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



Main Article Content

Yossra Abood Marich
Niran Jassim Al-Salihi
Najim Aboud Al-Masoudi

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.


icon graph This Abstract was viewed 1403 times | icon graph Article PDF downloaded 794 times

How to Cite
(1)
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.

Article Details

Share
Crossref - Scopus - Google - European PMC
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

Supporting Agencies

Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
Most read articles by the same author(s)
TrendMD

Dimensions - Altmetric - scite_ - PlumX

Downloads and views

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...
License Terms

License Terms

by-nc

Copyright © 2024 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at https://www.eurjchem.com/index.php/eurjchem/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (https://www.eurjchem.com/index.php/eurjchem/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).