Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from  5-Aminopyrazole and Study Biological Activity and Cytotoxicity

Wedad M. Al-Adiwish; Maryam A. S. Abubakr; Naowara M. Alarafi

doi:doi:10.11648/j.cb.20170505.11

| Peer-Reviewed

Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity

Wedad M. Al-Adiwish, Maryam A. S. Abubakr, Naowara M. Alarafi

Published in Cell Biology (Volume 5, Issue 5)

Received: 27 December 2016 Accepted: 9 January 2017 Published: 2 August 2017

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Treatment of 2-[bis(methylthio)methylene]malononitrile 1 with p-Chloroaniline afforded 2-[(4-chlorophenylamino) (methylthio) methylene] malononitrile 2a, of which upon reaction with hydrazine hydrate yielded 5-amino-3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile 3. This compound was utilized as a key intermediate for the synthesis of pyrazolo [5, 1-c] [1, 2, 4] triazines by diazotization of 3 with nitrous acid at low temperature afforded 3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile-5-diazonium chloride 3', in which coupling with active methylene of acetylacetone and malononitrile in the presence of pyridine gave the hydrazone derivatives, which cyclized directly upon addition of acetic acid to produce respective pyrazolo [5, 1-c] [1, 2, 4] triazine derivatives 7 and 8. Finally, treatment of 3 with acetic anhydride gave the acetyl amide derivative 9. The antibacterial and antifungal activities, as well cytotoxicity against Breast cancer cells (MCF7) of some selected compounds are also reported.

Published in	Cell Biology (Volume 5, Issue 5)
DOI	10.11648/j.cb.20170505.11
Page(s)	45-52
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Pyrazolo [5, 1-c] [1, 2, 4] triazines, p-Chloroaniline, 5-Aminopyrazole, Antibacterial Activity, Antifungal Activity, Cytotoxicity

References

[1]	M. Mojzych; A. Rykowski, J. Wierzchowski, Pyrazolo [4, 3-e] [1, 2, 4] triazines: Purine analogues with electronic absorption in the visible region, Molecules, 10 (2005) 1298-1306.
[2]	W. B. Parker, J. A. Secrist, W. R. Waud, Purine nucleoside antimetabolites in development for the treatment of cancer. Curr. Op. Invest. Drugs 5 (2004) 592-596.
[3]	B. Zacharie, T. P. Connolly, R. Rej, G. Attardo, C. L. Penney, A short synthesis of 4-substituted 1-(hydroxyalkyl)-1H-pyrazolo [3, 4-d] pyrimidines, Tetrahedron, 52 (1996) 2271-2278.
[4]	C. R. Petrie III, H. B. Cottam, P. A. McKernan, R. K. Robins, G. R Revankar. Synthesis and biological activity of 6-azacadeguomycin and certain 3, 4, 6-trisubstituted pyrazolo [3, 4-d] pyrimidine ribonucleosides, J. Med. Chem. 28 (1985) 1010-1016.
[5]	G. A Bhat, J. G. Montero, R. P. Panzica, L. L. Worting, L. B. Towsend, pyrazolopyrimidine nucleosides. 12. Synthesis and biological activity of certain pyrazolo [3, 4-d]-pyrimidine nucleosides related to adenosine. J. Med. Chem. 24 (1981) 1165-1172.
[6]	M. A. Gouda, M. A. Berghot, A. I. Shoeib, A. M. Khalil, Synthesis and antimicrobial activity of new anthraquinone derivatives incorporating pyrazole moiety, Eur. J. Med. Chem. 45 (2010) 1843–1848.
[7]	M. A. Gouda, A. I. Berghot, E. A. Ghada, A. M. Khalil, Synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4, 5, 6, 7-tetrahydrobenzothiophene moiety, Eur. J. Med. Chem. 45 (2010) 1338–1345.
[8]	Wedad M. Al-Adiwish, M. I. M. Tahir, Siti-Noor-Adnalizawati A., Siti Farah Hashim, Nazlina Ibrahim and W. A. Yaacob. 2013. Synthesis, Antibacterial Activity and Cytotoxicity of New Fused Pyrazolo [1, 5-a] pyrimidine and Pyrazolo [5, 1-c] [1, 2, 4] triazine Derivatives from New 5-Aminopyrazoles. European Journal of Medicinal Chemistry 64: 464-476.
[9]	M. A. Elnagdi, M. R. H. Elmoghayer, G. H. Elgemeie, Chemistry of pyrazolopyrimidines, Adv. Heterocyclic Chem. 41 (1987) 320–367. J. D. Anderson, H. B. Cottam, S. B. Larson, L. D. Nord, G. R. Revankar, R. K. Robins, Synthesis of certain pyrazolo [3, 4-d] pyrimidin-3-one nucleosides, J. Heterocyclic Chem. 27 (1990) 439-453.
[10]	J. L. Avila, M. A. Polegre, A. R. Avila, K. Robins, Action of pyrazolopyrimidine derivatives on american Leiishmania SPP Promastigotes, Comp. Biochem. Physiol. 83C (1986) 285-289.
[11]	J. Salimon, N. Salih, Synthesis, characterization and biological activity of some new 1, 2, 4-triazine derivatives. Int. J. Pharm. Tech. Res. 2 (2010) 1041-1045.
[12]	M. Mariusz, Antiviral activity evaluation of pyrazolo [4, 3-e] [1, 2, 4] triazines, J. Chem. Soc. Pak. 33 (2011).
[13]	M. Yokoyama, H. Togo, S. Kondo, Synthesis of heterocycles from ketene dithioacetals, Sulfur Rep. 10 (1990) 23–47.
[14]	M. A. Zaharan, A. M. Sh. El-Sharief, M. S. A. El-Gaby, Y. A. Ammar, U. H. El-Said, Some reactions with ketene dithioacetals Part I: Synthesis of antimicrobial pyrazolo [1, 5-a] pyrimidines via the reaction of ketene dithioacetals and 5-aminopyrazoles, Il Farmaco 56 (2001) 277–283.
[15]	Clinical and Laboratory Standards Institute, Performance Standards for Antimicrobial Disk Susceptibility Test. Approved Standard, ninth ed., CLSI, Wayne, PA, USA, 2006.
[16]	Mosmann T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. Journal of Immunology Methods 1983; 65: 55-63.
[17]	F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen, R. J. Taylor, Table of bond lengths determined by X-ray and neutron diffraction. Part 1. Bond lengths in organic compounds, Chem. Soc. Perkin Trans. 2. (1987), S1±S19.
[18]	CCDC 1033262 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, fax: +44 1223 336033, e-mail: deposit@ccdc.cam.ac.uk).
[19]	M. A. Gouda, M. A. Berghot, A. I. Shoeib, A. M. Khalil, Synthesis and antimicrobial activity of new anthraquinone derivatives incorporating pyrazole moiety, Eur. J. Med. Chem. 45 (2010) 1843–1848.
[20]	M. A. Gouda, A. I. Berghot, E. A. Ghada, A. M. Khalil, Synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4, 5, 6, 7-tetrahydrobenzothiophene moiety, Eur. J. Med. Chem. 45 (2010) 1338–1345.
[21]	Chandrashekar, G. J., Gopal, M. And Byregowda, S. M. 2011. Cytotoxic activity of Tragia involucrate. Linn. Extract. American-Eurasian Journal of Toxicological Sciences. 3 (2): 6769.

Cite This Article

Plain Text BibTeX RIS

APA Style

Wedad M. Al-Adiwish, Maryam A. S. Abubakr, Naowara M. Alarafi. (2017). Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity. Cell Biology, 5(5), 45-52. https://doi.org/10.11648/j.cb.20170505.11

Copy | Download

ACS Style

Wedad M. Al-Adiwish; Maryam A. S. Abubakr; Naowara M. Alarafi. Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity. Cell Biol. 2017, 5(5), 45-52. doi: 10.11648/j.cb.20170505.11

Copy | Download

AMA Style

Wedad M. Al-Adiwish, Maryam A. S. Abubakr, Naowara M. Alarafi. Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity. Cell Biol. 2017;5(5):45-52. doi: 10.11648/j.cb.20170505.11

Copy | Download

@article{10.11648/j.cb.20170505.11,
  author = {Wedad M. Al-Adiwish and Maryam A. S. Abubakr and Naowara M. Alarafi},
  title = {Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from  5-Aminopyrazole and Study Biological Activity and Cytotoxicity},
  journal = {Cell Biology},
  volume = {5},
  number = {5},
  pages = {45-52},
  doi = {10.11648/j.cb.20170505.11},
  url = {https://doi.org/10.11648/j.cb.20170505.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cb.20170505.11},
  abstract = {Treatment of 2-[bis(methylthio)methylene]malononitrile 1 with p-Chloroaniline afforded 2-[(4-chlorophenylamino) (methylthio) methylene] malononitrile 2a, of which upon reaction with hydrazine hydrate yielded 5-amino-3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile 3. This compound was utilized as a key intermediate for the synthesis of pyrazolo [5, 1-c] [1, 2, 4] triazines by diazotization of 3 with nitrous acid at low temperature afforded 3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile-5-diazonium chloride 3', in which coupling with active methylene of acetylacetone and malononitrile in the presence of pyridine gave the hydrazone derivatives, which cyclized directly upon addition of acetic acid to produce respective pyrazolo [5, 1-c] [1, 2, 4] triazine derivatives 7 and 8. Finally, treatment of 3 with acetic anhydride gave the acetyl amide derivative 9. The antibacterial and antifungal activities, as well cytotoxicity against Breast cancer cells (MCF7) of some selected compounds are also reported.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from  5-Aminopyrazole and Study Biological Activity and Cytotoxicity
AU  - Wedad M. Al-Adiwish
AU  - Maryam A. S. Abubakr
AU  - Naowara M. Alarafi
Y1  - 2017/08/02
PY  - 2017
N1  - https://doi.org/10.11648/j.cb.20170505.11
DO  - 10.11648/j.cb.20170505.11
T2  - Cell Biology
JF  - Cell Biology
JO  - Cell Biology
SP  - 45
EP  - 52
PB  - Science Publishing Group
SN  - 2330-0183
UR  - https://doi.org/10.11648/j.cb.20170505.11
AB  - Treatment of 2-[bis(methylthio)methylene]malononitrile 1 with p-Chloroaniline afforded 2-[(4-chlorophenylamino) (methylthio) methylene] malononitrile 2a, of which upon reaction with hydrazine hydrate yielded 5-amino-3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile 3. This compound was utilized as a key intermediate for the synthesis of pyrazolo [5, 1-c] [1, 2, 4] triazines by diazotization of 3 with nitrous acid at low temperature afforded 3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile-5-diazonium chloride 3', in which coupling with active methylene of acetylacetone and malononitrile in the presence of pyridine gave the hydrazone derivatives, which cyclized directly upon addition of acetic acid to produce respective pyrazolo [5, 1-c] [1, 2, 4] triazine derivatives 7 and 8. Finally, treatment of 3 with acetic anhydride gave the acetyl amide derivative 9. The antibacterial and antifungal activities, as well cytotoxicity against Breast cancer cells (MCF7) of some selected compounds are also reported.
VL  - 5
IS  - 5
ER  -

Copy | Download

Author Information

Wedad M. Al-Adiwish

Chemistry Department, Faculty of Science, Azawia University, Az Zawiyah, Libya
Maryam A. S. Abubakr

Department of Botany, Faculty of Science, Azawia University, Az Zawiyah, Libya
Naowara M. Alarafi

Chemistry Department, Faculty of Science, Benghazi University, Benghazi, Libya

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Wedad M. Al-Adiwish, Maryam A. S. Abubakr, Naowara M. Alarafi. (2017). Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity. Cell Biology, 5(5), 45-52. https://doi.org/10.11648/j.cb.20170505.11

Copy | Download

ACS Style

Wedad M. Al-Adiwish; Maryam A. S. Abubakr; Naowara M. Alarafi. Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity. Cell Biol. 2017, 5(5), 45-52. doi: 10.11648/j.cb.20170505.11

Copy | Download

AMA Style

Wedad M. Al-Adiwish, Maryam A. S. Abubakr, Naowara M. Alarafi. Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity. Cell Biol. 2017;5(5):45-52. doi: 10.11648/j.cb.20170505.11

Copy | Download

@article{10.11648/j.cb.20170505.11,
  author = {Wedad M. Al-Adiwish and Maryam A. S. Abubakr and Naowara M. Alarafi},
  title = {Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from  5-Aminopyrazole and Study Biological Activity and Cytotoxicity},
  journal = {Cell Biology},
  volume = {5},
  number = {5},
  pages = {45-52},
  doi = {10.11648/j.cb.20170505.11},
  url = {https://doi.org/10.11648/j.cb.20170505.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cb.20170505.11},
  abstract = {Treatment of 2-[bis(methylthio)methylene]malononitrile 1 with p-Chloroaniline afforded 2-[(4-chlorophenylamino) (methylthio) methylene] malononitrile 2a, of which upon reaction with hydrazine hydrate yielded 5-amino-3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile 3. This compound was utilized as a key intermediate for the synthesis of pyrazolo [5, 1-c] [1, 2, 4] triazines by diazotization of 3 with nitrous acid at low temperature afforded 3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile-5-diazonium chloride 3', in which coupling with active methylene of acetylacetone and malononitrile in the presence of pyridine gave the hydrazone derivatives, which cyclized directly upon addition of acetic acid to produce respective pyrazolo [5, 1-c] [1, 2, 4] triazine derivatives 7 and 8. Finally, treatment of 3 with acetic anhydride gave the acetyl amide derivative 9. The antibacterial and antifungal activities, as well cytotoxicity against Breast cancer cells (MCF7) of some selected compounds are also reported.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from  5-Aminopyrazole and Study Biological Activity and Cytotoxicity
AU  - Wedad M. Al-Adiwish
AU  - Maryam A. S. Abubakr
AU  - Naowara M. Alarafi
Y1  - 2017/08/02
PY  - 2017
N1  - https://doi.org/10.11648/j.cb.20170505.11
DO  - 10.11648/j.cb.20170505.11
T2  - Cell Biology
JF  - Cell Biology
JO  - Cell Biology
SP  - 45
EP  - 52
PB  - Science Publishing Group
SN  - 2330-0183
UR  - https://doi.org/10.11648/j.cb.20170505.11
AB  - Treatment of 2-[bis(methylthio)methylene]malononitrile 1 with p-Chloroaniline afforded 2-[(4-chlorophenylamino) (methylthio) methylene] malononitrile 2a, of which upon reaction with hydrazine hydrate yielded 5-amino-3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile 3. This compound was utilized as a key intermediate for the synthesis of pyrazolo [5, 1-c] [1, 2, 4] triazines by diazotization of 3 with nitrous acid at low temperature afforded 3-(4-chlorophenylamino)-1H-pyrazole-4-carbonitrile-5-diazonium chloride 3', in which coupling with active methylene of acetylacetone and malononitrile in the presence of pyridine gave the hydrazone derivatives, which cyclized directly upon addition of acetic acid to produce respective pyrazolo [5, 1-c] [1, 2, 4] triazine derivatives 7 and 8. Finally, treatment of 3 with acetic anhydride gave the acetyl amide derivative 9. The antibacterial and antifungal activities, as well cytotoxicity against Breast cancer cells (MCF7) of some selected compounds are also reported.
VL  - 5
IS  - 5
ER  -

Copy | Download