European Journal of Chemistry 2014, 5(4), 588-594 | doi: https://doi.org/10.5155/eurjchem.5.4.588-594.1109 | Get rights and content






  OPEN ACCESS | PEER-REVIEWED | RESEARCH ARTICLE | DOWNLOAD PDF | VIEW FULL-TEXT PDF | TOTAL VIEWS

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


Yossra Abood Marich (1) , Niran Jassim Al-Salihi (2) , Najim Aboud Al-Masoudi (3,*)

(1) Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
(2) Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
(3) Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
(*) Corresponding Author

Received: 15 Jun 2014 | Accepted: 08 Jul 2014 | Published: 31 Dec 2014 | Issue Date: December 2014

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.


Keywords


Pyrimidines; Anti-HIV activity; Sodium hypochlorite; Molecular modeling study; Structure activity relationship; Non-nucleoside reverse transcriptase inhibitors

Full Text:

PDF /    /


DOI: 10.5155/eurjchem.5.4.588-594.1109

Links for Article


| | | | | | |

| | | | | | |

| |

Related Articles




Article Metrics

This Abstract was viewed 672 times | PDF Article downloaded 321 times

Funding information


Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq

Citations

/


[1]. Mohammed Abed Al-Hussein Salman, Nabeel Abed Abdul-Rida
Synthesis of new derivatives of aryl-clonazepam via Suzuki Cross-coupling reaction
European Journal of Chemistry  7(2), 152, 2016
DOI: 10.5155/eurjchem.7.2.152-155.1403
/


[2]. Nabeel A. Abdul-Rida, Tiba I. Mohammed, Najim A. Al-Masoudi, Martin Frotscher
Synthesis, anti-17β-HSD and antiproliferative activity of new substituted 5-nitrosopyrimidine analogs
Medicinal Chemistry Research  26(4), 830, 2017
DOI: 10.1007/s00044-017-1795-z
/


[3]. Ajaz Hussain, Muhammad Usman Khan, Muhammad Ibrahim, Muhammad Khalid, Akbar Ali, Shafqat Hussain, Muhammad Saleem, Naseeb Ahmad, Shabbir Muhammad, Abdullah G. Al-Sehemi, Ayesha Sultan
Structural parameters, electronic, linear and nonlinear optical exploration of thiopyrimidine derivatives: A comparison between DFT/TDDFT and experimental study
Journal of Molecular Structure  1201, 127183, 2020
DOI: 10.1016/j.molstruc.2019.127183
/


[4]. Marcin Stolarczyk, Iwona Bryndal, Agnieszka Matera-Witkiewicz, Tadeusz Lis, Karolina Królewska-Golińska, Marcin Cieślak, Julia Kaźmierczak-Barańska, Jerzy Cieplik
Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives
Acta Crystallographica Section C Structural Chemistry  74(10), 1138, 2018
DOI: 10.1107/S2053229618012706
/


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

How to cite


Marich, Y.; Al-Salihi, N.; Al-Masoudi, N. Eur. J. Chem. 2014, 5(4), 588-594. doi:10.5155/eurjchem.5.4.588-594.1109
Marich, Y.; Al-Salihi, N.; Al-Masoudi, N. Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues. Eur. J. Chem. 2014, 5(4), 588-594. doi:10.5155/eurjchem.5.4.588-594.1109
Marich, Y., Al-Salihi, N., & Al-Masoudi, N. (2014). Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues. European Journal of Chemistry, 5(4), 588-594. doi:10.5155/eurjchem.5.4.588-594.1109
Marich, Yossra, Niran Jassim Al-Salihi, & Najim Aboud Al-Masoudi. "Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues." European Journal of Chemistry [Online], 5.4 (2014): 588-594. Web. 25 Nov. 2020
Marich, Yossra, Al-Salihi, Niran, AND Al-Masoudi, Najim. "Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues" European Journal of Chemistry [Online], Volume 5 Number 4 (31 December 2014)

The other citation formats (EndNote | Reference Manager | ProCite | BibTeX | RefWorks) for this article can be found online at: How to cite item


DOI Link: https://doi.org/10.5155/eurjchem.5.4.588-594.1109

| | | | | | | |

| | | | | |

Save to Zotero Save to Mendeley



European Journal of Chemistry 2014, 5(4), 588-594 | doi: https://doi.org/10.5155/eurjchem.5.4.588-594.1109 | Get rights and content

Refbacks

  • There are currently no refbacks.




Copyright (c)




© Copyright 2010 - 2020  Atlanta Publishing House LLC All Right Reserved.

The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.

Copyright 2010-2020 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 2850 Smith Ridge Trce Peachtree Cor GA 30071-2636, USA. Registered in USA.