Efficient three-component synthesis of N-alkyl-3, 6-diaryl-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]triazin-7-amines under solvent-free condition

Article abstract of DOI:10.24820/ark.5550190.p010.175

A simple, efficient and environment-friendly approach is described for the synthesis of N-alkyl-3, 6-diaryl-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]triazin-7-amines based on three-component reaction between 5-aryl-4H-1, 2, 4-triazole-3, 4-diamine, isocyanide and aldeyhde under solvent-free condition. The products are obtained in moderate to good yields and are in a state of high purity.

Full text of DOI:10.24820/ark.5550190.p010.175

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Organic Chemistry
Arkivoc 2017, part v, 293-300
Efficient three-component synthesis of N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-
b][1,2,4]triazin-7-amines under solvent-free condition
Sara Azimi,a Mehdi Soheilizad,b Afsaneh Zonouzi,a* and Mohammad Mahdavib*
a School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
b Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran 14176, Iran
Email: Mahdavi_chem@yahoo.com, zonouzi@khayam.ut.ac.ir
Received 05-18-2017
Accepted 09-22-2017
Published on line 11-19-2017
Abstract
A simple, efficient and environment-friendly approach is described for the synthesis of N-alkyl-3,6-diaryl-
[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines based on three-component reaction between 5-aryl-4H-1,2,4-
triazole-3,4-diamine, isocyanide and aldeyhde under solvent-free condition. The products are obtained in
moderate to good yields and are in a state of high purity.
Keywords: Three-component reaction, N-Alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines, 5-aryl-
4H-1,2,4-triazole-3,4-diamine, isocyanide, aldehyde
DOI: https://doi.org/10.24820/ark.5550190.p010.175
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Introduction
The development of eco-friendly synthetic approaches is a major challenge for synthetic chemists. One of the
most promising approaches is the solvent-free organic synthesis. These reactions may provide greater
selectivity, precede with enhanced reaction rates, give cleaner products, and involve simple manipulation.[1-6]
Nitrogen-containing heterocyclic compounds and their analogous are pharmaceutically attractive scaffolds
and widely exist in naturally occurring and synthetic biologically active molecules.[7-11] Among them, fused
polycyclic nitrogen-containing heteroaromatics have received much synthetic attention because of their high
therapeutic values. These N-fused polycycles displayed a wide range of biological activities such as anticancer,
antibacterial, antifungal, antiplasmodial, antineoplastic and DNA intercalators.[12-16] For instance, diverse
compounds derived from 1,2,4-triazoles are well known as antibacterial, antifungal, antiviral,
antiinflammatory, antihypertensive, and hypoglycemic agents.[17-23] They also show herbicidal and
antimicrobial activities making them a popular target for new drug development.[24-26] Another example of N-
containing biologically active heterocycles is 1,2,4-triazine-based derivatives which have been reported to
possess anti-AIDS, antitumoural, anticancer, antiviral and antimicrobial activities.[27-31]
Owing to this broad range of properties of N-containing triazole and triazine heterocycles, it is also reasonable
to expect that fused triazole-triazine derivatives have significant biological activity. So, in this paper, we intend
to describe an efficient and eco-friendly approach for the synthesis of N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-
b][1,2,4]triazin-7-amines under solvent-free condition. To date, this is the first report on the synthesis of this
fused N-containing heterocyclic compounds.
Results and Discussion
In continuation of our researches on preparation of N-containing organic compounds,[32-37] herein, we report a
novel and efficient approach for the green synthesis of N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-
amines 4a–h, via three-component reaction of 5-aryl-4H-1,2,4-triazole-3,4-diamine 1, isocyanide 2, and
aldeyhde 3, under solvent-free condition at 150 C (Scheme 1). The reactions went to completion within 4
hours and the corresponding products 4 were obtained in 68–82% yields. All the products were characterized
1
by H and 13C NMR spectral data. No product other than 4 could be detected by NMR spectroscopy. The
results are summarized in the Table 1.
Scheme 1. Three-component synthesis of the N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines.
The 5-aryl-4H-1,2,4-triazole-3,4-diamines 1 were prepared based on four-step procedure reported by Gupta[38]
shown in Scheme 2.
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Scheme 2. Three-component synthesis of the N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines.
Table 1. Synthesis of N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines
Product
4a
4b
4c
4d
4e
4f
4g
4h
Ar
Ar׳
C6H5
R
t-Bu
t-Bu
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Yield (%)a
4-NO2-C6H4
4-Cl-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-NO2-C6H4
3,4-Cl2-C6H3
72
75
82
85
78
74
80
78
2-CH3-C6H4
3-NO2-C6H4
C6H5
3-NO2-C6H4
2-Cl-C6H4
2-Cl-C6H4
3-NO2-C6H4
a Yield of isolated products.
To explain the formation of N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines 4, a plausible
reaction mechanism is proposed in Scheme 3. Initially, due to the stronger nucleophilicity of the amino group
at position 4 of the five-member ring in contrast to the amino group at position 3,[39,40] it is reasonable to
assume that imine intermediate 5 is formed by condensation of 5-aryl-4H-1,2,4-triazole-3,4-diamine 1 with
aldehyde 3. Then, the nucleophilic addition of isocyanide 2 to this intermediate results in formation of
intermediate 6, which undergoes the intramolecular cyclization of amino group with triple bond followed by
tautomerization and aerobic oxidation affords the N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-
amines 4 (Scheme 2).
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Scheme 3. Plausible mechanism for synthesis of the N-alkyl-3,6-diaryl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines.
Conclusions
In conclusion, a straightforward and eco-friendly approach for the synthesis of N-alkyl-3,6-diaryl-
[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amines based on three-component reaction between 5-aryl-4H-1,2,4-
triazole-3,4-diamine, isocyanide and aldeyhde under solvent-free condition is described. The simplicity of
starting materials, moderate to good yields of the products and use of solvent-free conditions are the main
advantages of this method.
Experimental Section
General. All chemicals were purchased from Merck and Fluka companies. All yields refer to isolated products.
1
IR spectra were recorded on a Shimadzu IR-460 spectrometer. H and 13C NMR spectra were recorded on a
Brucker, Rheinstetten, Germany (at 500 and 400 MHz) NMR spectrometer using tetramethylsilane (TMS) as
internal standard. Elemental analyses for C, H and N were performed using a Heraeus CHN-O-Rapid analyzer.
Melting points were determined in a capillary tube and are not corrected. The progress of reaction was
followed with TLC using silica gel SILG/UV 254 and 365 plates. All products are known compounds and their
structures were deduced by 1H and 13C NMR spectroscopy as well as elemental analysis.
General procedure for the preparation of products 4a–4h. A mixture of appropriate 5-aryl-4H-1,2,4-triazole-
3,4-diamine 1 (1.0 mmol), isocyanide 2 (1.0 mmol), and aldeyhde 3 (1.0 mmol) was stirred in a sealed vessel at
150 °C under solvent-free condition for 4–9 h. After reaction completion (TLC), the reaction mixture was
cooled to room temperature and the crude product was purified by column chromatography on silica gel using
hexane–EtOAc (4:1) as eluent to afford products 4a–4h (Table 1).
N-(tert-butyl)-3-(4-nitrophenyl)-6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4a). White solid, mp
1
218–220 °C; IR (KBr): 3379, 2936, 2875, 1628, 1500, 1548, 1423, 1366cm-1. H NMR (DMSO-d6, 500 MHz): δ
0.99 (s, 9H), 4.65 (s, 1H), 7.19–7.22 (m, 3H), 7.51 (d, J 9.0 Hz), 8.05 (d, J 8.0 Hz), 8.51 (d, J 8.0 Hz) ppm; 13C NMR
(DMSO-d6, 125 MHz): δ 29.9, 59.9, 118.2, 121.5, 121.7, 124.3, 124.5, 127.5, 127.6, 128.4, 128.5, 132.0, 136.3,
149.3 ppm; Anal. Calcd for C20H19N7O2: C, 61.69; H, 4.92; N, 25.18. Found: C, 61.61; H, 4.90; N, 25.16.
N-(tert-butyl)-3-(4-chlorophenyl)-6-(2-tolyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4b): White solid,
mp224–226 °C; IR (KBr): 3370, 2930, 2852, 1601, 1570, 1565, 1489, 1382 cm-1. 1H NMR (DMSO-d6, 500 MHz):
δ 0.99 (s, 9H), 2.32 (s, 1H), 4.56 ( s, 1H), 6.85 (t, J 7.0 Hz), 7.15 (t, J 7.0 Hz), 7.19 (d, J 8.0 Hz, 2H), 7.44 (d, J 7.0
Hz, 1H), 8.05 (d, J 8.0 Hz, 2H), 8.38 (d, J 7.0 Hz, 1H) ppm; 13C NMR (DMSO-d6, 125 MHz): δ 20.8, 30.0, 55.6,
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116.3, 123.5, 123.8, 123.9, 124.0, 127.5, 127.6, 128.3, 128.4, 129.2, 132.4, 135.9, 137.9, 140.8 ppm; Anal.
Calcd for C21H21ClN6: C, 64.20; H, 5.39; Cl, 9.02; N, 21.39. Found: C, 64.11; H, 5.30; Cl, 8.96; N, 21.23.
N-cyclohexyl-3-(4-methoxyphenyl)-6-(3-nitrophenyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4c): Pale
1
yellow solid, mp 188–190 °C; IR (KBr): 3277, 2944, 2856, 1654, 1527, 1530, 1428, 1338 cm-1. H NMR (DMSO-
d6, 500 MHz): δ 1.08–1.70 (m, 10H), 2.81–2.84 (m, 1H), 4.00 (s, 3H), 4.79 (d, J 6.0 Hz, 1H), 7.17 (d, J 7.5 Hz, 1H),
7.28 (d, J 7.5 Hz, 1H), 7.40 (t, J 7.5 Hz, 1H), 7.51 (d, J 8.0 Hz, 2H), 8.13 (t, J 7.5 Hz, 1H), 8.33 (s, 1H) ppm; 13C
NMR (DMSO-d6, 125 MHz): δ 24.3, 25.3, 33.4, 49.8, 56.2, 111.3, 111.5, 116.2, 123.2, 123.9, 124.9, 125.3,
127.7, 129.6, 130.0, 130.6, 134.2, 136.6, 143.1, 157.1 ppm; Anal. Calcd for C23H23N7O3: C, 62.01; H, 5.20; N,
22.01; Found: C, 61.92; H, 5.12; N, 21.93.
3-(4-chlorophenyl)-N-cyclohexyl-6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4d): White solid, mp
1
212–214 °C; IR (KBr): 3294, 2973, 2844, 1600, 1528, 1483, 1351cm-1. H NMR (DMSO-d6, 500 MHz): δ 0.91–
1.59 (m, 10H), 2.68–2.73 (m, 1H), 4.53 (s, 1H), 7.16 (m, 2H), 7.39–7.44 (m, 2H), 7.50–7.58 (m, 3H), 8.43 (d, J 8.0
13
Hz, 2H) ppm; C NMR (DMSO-d6, 125 MHz): δ 24.0, 25.2, 32.9, 54.5, 118.6, 120.5, 120.7, 123.5, 126.5, 126.7,
127.4, 129.3, 132.3, 132.9, 133.8, 137.9 ppm; Anal. Calcd for C22H21ClN6: C, 65.26; H, 5.23; Cl, 8.76; N, 20.76.
Found: C, 65.21; H, 5.15; Cl, 8.70; N, 20.71.
3-(4-chlorophenyl)-N-cyclohexyl-6-(3-nitrophenyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4e): White
1
solid, mp 185–187 °C; IR (KBr): 3270, 2900, 2810, 1628, 1544, 1525, 1489, 1366cm-1. H NMR (DMSO-d6, 500
MHz): δ 1.09–1.71 (m, 10H), 2.80–2.82 (m, 1H), 4.78 (d, J =6.0 Hz, 1H), 7.09 (d, J 7.5 Hz, 1H), 7.18–7.31 (m, 3H),
7.34 (d, J 7.5 Hz, 1H), 7.51 (d, J 8.0 Hz, 2H), 8.13 (d, J 7.5 Hz, 1H), 8.33 (s, 1H) ppm; 13C NMR (DMSO-d6, 125
MHz): δ 24.4, 25.3, 33.4, 52.8, 114.5, 117.2, 118.5, 120.8, 124.3, 124.6, 124.6, 127.7, 127.9, 128.1, 128.7,
157.3, 160.0 ppm; ; Anal. Calcd for C22H20ClN7O2: C, 58.73; H, 4.48; Cl, 7.88; N, 21.79. Found: C, 58.66; H, 4.41;
Cl, 7.80; N, 21.71.
6-(2-chlorophenyl)-3-(4-chlorophenyl)-N-cyclohexyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4f): Yellow
1
solid, mp 190–192 °C; IR (KBr): 3230, 2917, 2860, 1625, 1587, 1555, 1364 cm-1. H NMR (DMSO-d6, 500 MHz):
δ 1.09–1.72 (m, 10H), 2.79 (m, 1H), 4.68 (d, J 6.0 Hz, 1H), 6.84 (t, J 7.5 Hz, 1H), 7.07 (d, J 7.5 Hz, 1H), 7.14 (t, J
7.5 Hz, 1H), 7.27 (d, J 8.0 Hz, 2H), 7.42 (d, J 7.5 Hz, 1H), 7.87 (d, J 8.0 Hz, 1H) ppm; 13C NMR (DMSO-d6, 125
MHz): δ 24.4, 25.3, 33.4, 52.0, 111.0, 114.4, 116.4, 121.3, 123.1, 123.4, 124.6, 127.7, 130.1, 131.6, 135.3,
140.3, 157.1 ppm; Anal. Calcd for C22H20Cl2N6: C, 60.14; H, 4.59; Cl, 16.14; N, 19.13. Found: C, 60.04; H, 4.43;
Cl, 16.01; N, 19.02.
6-(2-chlorophenyl)-N-cyclohexyl-3-(4-nitrophenyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine (4g): White
1
solid, mp 202–204 °C; IR (KBr): 3285, 2900, 2827, 1615, 1577, 1515, 1479, 1365 cm-1. H NMR (DMSO-d6, 500
MHz): δ 1.12–1.79 (m, 10H), 2.85–2.90 (m, 1H), 4.98 (s, 1H), 7.23 (t, J 7.5 Hz, 1H), 7.52 (d, J 7.5 Hz, 1H), 7.73 (t,
J 7.5 Hz, 1H), 8.11 (d, J 8.0 Hz, 2H), 8.36 (d, J 7.5 Hz, 1H), 8.66 (d, J 8.0 Hz, 2H) ppm; 13C NMR (DMSO-d6, 125
MHz): δ 24.4, 25.3, 33.5, 56.7, 116.8, 117.0, 121.1, 121.1, 123.5, 123.6, 124.4, 124.6, 129.7, 132.0, 132.2,
136.3, 140.7, 148.1 ppm; Anal. Calcd for C22H20ClN7O2: C, 58.73; H, 4.48; Cl, 7.88; N, 21.79. Found: C, 58.67; H,
4.40; Cl, 7.74; N, 21.68.
N-cyclohexyl-3-(3,4-dichlorophenyl)-6-(3-nitrophenyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-amine
(4h):
White solid, mp 217–219 °C; IR (KBr): 3280, 2925, 2847, 1615, 1577, 1535, 1479, 1360 cm-1. H NMR (DMSO-
d6, 500 MHz): δ 1.11–1.78 (m, 10H), 2.84–2.88 (m, 1H), 5.05 (s, 1H), 7.26 (d, J 9.5 Hz, 1H), 7.58 (d, J 9.5 Hz, 1H),
7.74 (t, J 8.0 Hz, 1H), 8.14 (d, J 8.0 Hz, 1H), 8.57 (s, 1H), 8.63 (d, J 8.0 Hz, 1H) 9.09 (d, J 8.0 Hz, 1H) ppm; 13C
NMR (DMSO-d6, 125 MHz): δ 24.5, 25.2, 33.5, 56.9, 119.0, 120.3, 120.6, 121.2, 121.3, 125.1, 127.8, 129.8,
132.0, 132.1, 132.7, 135.9, 139.0, 148.1 ppm; Anal. Calcd for C22H19Cl2N7O2: C, 54.56; H, 3.95; Cl, 14.64; N,
20.24. Found: C, 54.48; H, 3.83; Cl, 14.53; N, 20.17.
1
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Acknowledgements
This research was supported by a grant from Iran National Science Foundation (INSF).
Supplementary Material
General information, General procedure for the preparation of products 4a-4h, Characterization data for
compounds 4a-4h, Copies of 1H and 13C NMR Spectra.
References
1. Tanaka, K., Ed.; Solvent-Free Organic Synthesis; Wiley-VCH: Weinheim, 2004.
2. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
https://doi.org/10.1021/cr940089p
3. Singh, M. S.; Chowdhury, S. RSC Adv. 2012, 2, 4547.
https://doi.org/10.1039/c2ra01056a
4. Zhao, Y. N.; Li, J.; Li, C. J.; Yin, K.; Ye, D. Y.; Jia, X. S. Green Chem. 2010, 12, 1370.
https://doi.org/10.1039/c0gc00158a
5. Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Buriol, L.; Machado, P. Chem. Rev. 2009, 109, 4140.
https://doi.org/10.1021/cr9001098
6. Franklin, E. C. Chem. Rev. 1935, 16, 305.
https://doi.org/10.1021/cr60055a001
7. Bergstrom, F. W. Chem. Rev. 1944, 35, 77.
https://doi.org/10.1021/cr60111a001
8. Lichtenthaler, F. W. Acc. Chem. Res. 2002, 35, 728.
https://doi.org/10.1021/ar010071i
9. Khalili, S. B.; Sardarian, A. R. Monatsh. Chem. 2012, 143, 841.
https://doi.org/10.1007/s00706-011-0647-7
10. Litvinov, V. P. Russ. Chem. Rev. 2003, 72, 69.
https://doi.org/10.1070/RC2003v072n01ABEH000764
11. Xu, Y.; Guo, Q.-X. Heterocycles 2004, 63, 903.
https://doi.org/10.3987/REV-03-574
12. Reitz, A. B.; Gauthier, D. A.; Ho, W.; Maryanoff, B. E. Tetrahedron 2000, 56, 8809.
https://doi.org/10.1016/S0040-4020(00)00874-7
13. Katritzky, A. R.; Tymoshenko, D. O.; Monteux, D.; Vvedensky, V.; Nikonov, G.; Cooper, C. B.; Deshpande,
M. J. Org. Chem. 2000, 65, 8059.
https://doi.org/10.1021/jo000946r
14. Maryanoff, B. E.; McComsey, D. F.; Ho, W.; Shank, R. P.; Dubinsky, B. Bioorg. Med. Chem. Lett. 1996, 6,
333.
https://doi.org/10.1016/0960-894X(96)00025-X
15. Rida, S. M.; Soliman, F. S. G.; Badawey, E.; Kappe, T. J. Heterocycl. Chem. 1988, 25, 1725.
https://doi.org/10.1002/jhet.5570250622
Page 298
©ARKAT USA, Inc

Arkivoc 2017, v, 293-300
Azimi, S. et al.
16. Badawey, E.; Kappe, T. Eur. J. Med. Chem. 1995, 30, 327.
https://doi.org/10.1016/0223-5234(96)88241-9
17. Dumaitre, B.; Dodic, N.; J. Med. Chem. 1996, 39, 1635.
https://doi.org/10.1021/jm950812j
18. Shankar, U. R.; Jain, S.; Sinha, N.; Kishore, N.; Chandra, R.; Arora, S. K.; Eur. J. Med. Chem. 2004, 39, 579.
https://doi.org/10.1016/j.ejmech.2004.03.004
19. Longley, N.; Muzoora, C.; Taseera, K.; Mwesigye, J.; Rwebembera, J.; Chakera, A.; Wall, E.; Andia, I.;
Jaffar, S.; Harrison, T. S. Clin. Infect. Dis. 2008, 47, 1556.
https://doi.org/10.1086/593194
20. Eweiss, N. F.; Bahajaj, A. A.; Elsherbini, E. A. J. Heterocyclic Chem. 1986, 23, 1451.
https://doi.org/10.1002/jhet.5570230540
21. Demirbs, N.; Demirbas, A. U. Bioorg. Med. Chem. 2002, 10, 3717.
https://doi.org/10.1016/S0968-0896(02)00420-0
22. Emilsson, H.; Salender, H.; Gaarder, J. Eur. J. Med. Chem. Chim. Ther. 1985, 21, 333.
23. Rhaimini, A. E.; Mornet, R. Indian.
https://doi.org/10.1002/jhet.5570290632
J. Heterocyclic Chem. 1992, 29, 1561.
24. Joung, J. K.; Ramm, E. I.; Pabo, C. O. P. Natl. Acad. Sci. USA. 2000, 97, 7382.
https://doi.org/10.1073/pnas.110149297
25. Banfi, E., Scialino, G., Zampieri, D., Mamolo, M.G., Vio, L., Ferrone, M., Fermeglia, M., Paneni, M.S., Pricl,
S. J. Antimicrob. Chemother. 2006, 58, 76.
https://doi.org/10.1093/jac/dkl182
26. Ulusoy, N., Gürsoy, A., Otük, G. Farmaco. 2001, 56, 947.
https://doi.org/10.1016/S0014-827X(01)01128-4
27. Abdel-Rahman, R. M.; Seada, M.; Fawzy, M.; El-Baz, I. Farmaco 1993, 48, 397.
28. Sztanke, K.; Pasternak, K.; Rzymowska, J.; Sztanke, M.; Szerszen. M. K. Eur. J. Med. Chem., 2008, 43, 1085.
https://doi.org/10.1016/j.ejmech.2007.07.009
29. El-Gendy, Z.; Morsy, J. M.; Allimony, H.; Abdel-Monem, W. R.; Abdel-Rahman, R. M. Pharmazie 2001, 56,
376.
30. Sidwell, R.W.; Dixon, G. J.; Sellers, S. M.; Schable, F. M. Appl Microbiol 1968, 16, 370.
31. Wittman, M. D.; Carboni, J. M.; Yahg, Z.; Lee, F. Y.; Attar, R.; Baliman, P.; Vyas, D. M. J. Med. Chem., 2009,
52, 7360.
https://doi.org/10.1021/jm900786r
32. Noushini, S.; Mahdavi, M.; Firoozpour, L.; Moghimi, S.; Shafiee, A.; Foroumadi, A. Tetrahedron, 2015, 71,
6272.
https://doi.org/10.1016/j.tet.2015.06.060
33. Goli-Garmroodi, F.; Omidi, M.; Saeedi, M.; Sarrafzadeh, F.; Rafinejad, A.; Mahdavi, M.; Bardajee, G. R.;
Akbarzadeh, T.; Firoozpour, L.; Shafiee, A.; Foroumadi, A. Tetrahedron Lett., 2015, 56, 743.
https://doi.org/10.1016/j.tetlet.2014.12.099
34. Rahmani-Nezhad, S.; Safavi, M.; Pordeli, M.; Ardestani, S. K; Khosravani, L.; Pourshojaei, Y.; Mahdavi, M.;
Emami, S.; Foroumadi, A.; Shafiee, A. Eur. J. Med. Chem. 2014, 86, 562.
https://doi.org/10.1016/j.ejmech.2014.09.017
35. Saeedi, M.; Mahdavi, M.; Foroumadi, A.; Shafiee, A. Tetrahedron, 2013, 69, 3506.
https://doi.org/10.1016/j.tet.2013.02.023
Page 299
©ARKAT USA, Inc

Arkivoc 2017, v, 293-300
Azimi, S. et al.
36. Hosseini-Zare, M. S.; Mahdavi, M.; Saeedi, M.; Asadi, M.; Javanshir, S.; Shafiee, A.; Foroumadi, A.
Tetrahedron Lett., 2012, 53, 3448.
https://doi.org/10.1016/j.tetlet.2012.04.088
37. Tahghighi, A.; Razmi, S.; Mahdavi. M.; Foroumadi, P.; Ardestani, S. K.; Emami, S.; Kobarfard, F.;
Dastmalchi, S.; Shafiee, A.; Foroumadi, A. Eur. J. Med. Chem. 2012, 50, 124.
https://doi.org/10.1016/j.ejmech.2012.01.046
38. Gupta, M. Bioorg. Med. Chem. Lett. 2011, 21, 4919.
https://doi.org/10.1016/j.bmcl.2011.06.007
39. Emilsson, H.; Luthman, K.; Selander,H. Eur. J. Med. Chem., 1986, 21, 235
40. Emilsson, H. J. Heterocycl. Chem., 1989, 26, 1077.
https://doi.org/10.1002/jhet.5570260431
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