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</svg>-D-glucopyranosyl)thiosemicarbazide

Dinh Thanh, Nguyen; Giang, Nguyen Thi Kim

doi:https://doi.org/10.1155/2013/237058

Journal of Chemistry

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Abstract Introduction Experimental Results and Discussion Conclusion References Copyright Related Articles

Research Article | Open Access

Volume 2013 | Article ID 237058 | https://doi.org/10.1155/2013/237058

Reaction of N-alkylisatins with 4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl)thiosemicarbazide

Nguyen Dinh Thanh¹and Nguyen Thi Kim Giang¹

Academic Editor: Nicolas Joly

Received26 Jun 2012

Revised20 Jul 2012

Accepted22 Jul 2012

Published16 Aug 2012

Abstract

Some N-alkylisatins were converted to corresponding thiosemicarbazones by reaction with 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazide using microwave-assisted heating method. The structure of products have been confirmed by IR, NMR, and mass spectra.

1. Introduction

Isatin-β-thiosemicarbazone and N-methylisatin-β-thiosemicarbazone (methisazone, marboran) are extensively studied thiosemicarbazones that demonstrate an inhibitory effect against the replication of poxviruses [1]. Methisazone has also been used in the clinical treatment of smallpox [2]. This drug plays an important role as a smallpox chemoprophylactic agent. The spectrum of antiviral activity of this drug has been extended by additional in vitro studies to include other groups of viruses, such as adenovirus, herpesvirus, picornavirus, reovirus, arbovirus, myxo- and paramyxovirus, and retrovirus [3]. N-alkylation of isatin reduces the lability of the isatin nucleus towards bases, while maintaining its typical reactivity. Thus, N-substituted isatins have been frequently used as intermediates and synthetic precursors for the preparation of a wide variety of heterocyclic compounds [4, 5]. In addition, properly functionalized N-alkyl isatins present different biological activities [4], and in recent years compounds showing potent cytotoxicity in vitro [6], antiviral activity [7], and potent and selective caspase inhibition [8] have been reported, among others. Thiosemicarbazides exhibit various biological activities and are extensively applied in medicine, particularly in the treatment of tuberculosis [9, 10]. Numerous compounds with a thiosemicarbazone moiety also exhibit biological activity [11, 12]. Several peracetylated glucopyranosyl thiosemicarbazones were synthesized [13, 14].

Some tetra-O-acetyl-β-D-glucopyranosyl thiosemicarbazones containing isatin ring were synthesized in good yields by the reactions of substituted isatins with tetra-O-acetyl-β-D-glucopyranosyl thiosemicarbazide in our lab [15]. Continuing our works on glucopyranosyl thiosemicarbazones [16, 17], we report herein the synthesis of some N-alkylisatin 4-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones.

2. Experimental

Melting points were measured on STUART SMP3 (BIBBY STERILIN-UK). The FTIS spectra were recorded on Impact 410 FT-IR Spectrometer (Nicolet, USA) in form of KBr. The ¹H NMR and ¹³C NMR spectra were recorded on an Avance Spectrometer AV500 (Bruker, Germany) at 500.13 MHz and 125.77 MHz, respectively, using DMSO- as solvent and TMS as an internal reference. MS spectra were recorded on mass spectrometer AutoSpec Premier (Water, USA) using EI method. All other solvents and reagents were used as received or purified by standard protocols. 4-(Tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazide using our method [9].

General Procedure for Synthesis of N-alkylisatins 2a-h. To a solution of isatin 1 (0.03 mol) in DMF (7 mL) corresponding alkyl halide (0.03 mol) and K₂CO₃ (0.042 mol, 6.20 g) were added. Reaction mixture was irradiated for appropriate time and then cooled to room temperature and mixed thoroughly with ice water. The product recrystallized from the suitable solvent. Reaction time, yield, melting point, and recrystallization solvents for these N-alkylisatins are following: N-methylisatin (2a), 2 min, 84%, 130-131°C (96% ethanol), [18, 19]: 130–133°C; N-ethylisatin (2b), 3 min, 71%, 86-87°C (96% ethanol), [18, 19]: 88-89°C; N-n-propylisatin (2c), 3 min, 75%, 196-197°C (96% ethanol), [18]: 198°C; N-n-butylisatin (2d), 4 min, 63%, 34–36°C (diethyl ether), [20]: 36°C; N-allylisatin (2f), 2 min, 72%, 90-91°C (96% ethanol), [18]: 88-89°C; N-benzylisatin (2g), 3 min, 88%, 129-130°C (96% ethanol), [18]: 131-132°C. Compounds 2e and 2h were prepared similarly and used for synthesis of corresponding thiosemicarbazones: N-isobutylisatin (2e), 5 min, 74%, 88-89°C (96% ethanol); N-phenethylisatin (2 h), 4 min, 90%, 110–112°C (96% ethanol).

General Procedure for Synthesis of N-alkylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones 3a-h. To a solution of 4-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazide (1 mmol) in 99% ethanol (10 mL) N-alkylisatin 2 (1 mmol) was added. Glacial acetic acid (0.5 mL) as catalyst was added dropwise with stirring. The obtained mixture was then irradiated in microwave oven for 8–20 min; cooled to room temperature and the separated precipitate was filtered and recrystallized from 96% ethanol to yield the title compounds 3.

N-Methylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3a). Yellow solid, mp 208-209°C (from 96% ethanol), yield 82%; IR (KBr) /cm⁻¹: 3320, 1755, 1610, 1228, 1040, 1370; ¹H NMR (DMSO-) δ (ppm): 12.71 (s, 1H, NH-2), 9.61 (d, 1H, Hz, NH-4), 7.75 (d, 1H, Hz, H-7′), 7.48 (t, 1H, Hz, H-5′), 7.19 (t, 1H, Hz, H-6′), 7.16 (d, 1H, Hz, H-4′), 6.01 (t, 1H, Hz, H-1), 5.46 (t, 1H, Hz, H-3), 5.34 (t, 1H, Hz, H-2), 4.99 (t, 1H, Hz, H-4), 4.24 (t, 1H, , 5.0 Hz, H-6a), 4.18 (m, 1H, H-5), 4.00 (dd, 1H, Hz, H-6b), 3.21 (s, 3H, CH₃, N-methyl), 2.01–1.93 (s, 12H, 4 × CH₃CO); ¹³C NMR (DMSO-) δ (ppm): 179.0 (C=S), 169.3–169.9 (COCH₃), 160.7 (C=O isatin), 144.0 (C-3′), 132.5 (C-4′), 131.6 (C-4′a), 122.9 (C-5′), 121.0 (C-6′), 119.0 (C-7′), 109.9 (C-7′a), 81.9 (C-1), 70.9 (C-2), 72.7 (C-3), 67.7 (C-4), 72.4 (C-5), 61.7 (C-6), 25.7 (CH₃, N-methyl), 20.5–20.3 (4 × CH₃CO); EI-HRMS: C₂₄H₂₈N₄O₁₀S, calc. for Da, found: 564.1533.

N-Ethylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3b). Yellow solid, mp 152-153°C (from 96% ethanol), yield 81%; IR (KBr) /cm⁻¹: 3350, 1751, 1614, 1367, 1232, 1039; ¹H NMR (DMSO-) δ (ppm): 12.72 (s, 1H, NH-2), 9.61 (d, 1H, Hz, NH-4), 7.76 (d, 1H, Hz, H-7′), 7.72 (d, 1H, Hz, H-4′), 7.46 (t, 1H, Hz, H-6′), 7.19 (t, 1H, Hz, H-5′), 6.01 (t, 1H, Hz, H-1), 5.46 (t, 1H, Hz, H-3), 5.34 (t, 1H, Hz, H-2), 4.98 (t, 1H, Hz, H-4), 4.24 (dd, 1H, , 4.5 Hz, H-6a), 4.17 (ddd, 1H, , 4.5, 2.0 Hz, H-5), 4.00 (dd, 1H, , 1.5 Hz, H-6b), 3.77 (t, 2H, CH₂, N-ethyl; 2.01-1.93 (s, 12H, 4 × CH₃CO), 1.20 (t, 3H, CH₃, N-ethyl); ¹³C NMR (DMSO-) δ (ppm): 179.0 (C=S), 169.9–169.3 (4 × COCH₃), 160.3 (C=O isatin), 142.9 (C-3′), 132.6 (C-4′), 131.7 (C-4′a), 122.8 (C-5′), 121.3 (C-6′), 119.2 (C-7′), 110.0 (C-7′a), 81.9 (C-1), 70.9 (C-2), 72.7 (C-3), 67.7 (C-4), 72.4 (C-5), 61.7 (C-6), 34.1 (CH₂, N-ethyl), 20.5–18.5 (4 × CH₃CO), 12.5 (CH₃, N-ethyl); EI-HRMS: C₂₅H₃₀N₄O₁₀S, calc. for = 578.1682 Da, found: 578.1692.

N-n-Propylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3c). Yellow solid, mp 187–189°C (from 96% ethanol), yield 93%; IR (KBr) /cm⁻¹: 3294, 1743, 1615, 1367, 1235, 1035; ¹H NMR (DMSO-) δ (ppm): 12.73 (s, 1H, NH-2), 9.62 (d, 1H, Hz, NH-4), 7.77 (d, 1H, Hz, H-7′), 7.21 (t, 1H, Hz, H-4′), 7.46 (t, 1H, Hz, H-6′), 7.19 (t, 1H, Hz, H-5′), 6.01 (t, 1H, Hz, H-1), 5.46 (t, 1H, Hz, H-3), 5.34 (t, 1H, Hz, H-2), 4.98 (t, 1H, .75 Hz, H-4), 4.24 (dd, 1H, , 4.75 Hz, H-6a), 4.17 (ddd, 1H, , 4.5, 2.0 Hz, H-5), 4.00 (d, 1H, , H-6b), 3.71 (t, 2H, Hz, NCH₂, N-propyl; 2.01–1.93 (4 × CH₃CO), 1.65 (sextet, 2H, Hz, CH₂, N-propyl), 0.89 (t, 3H, Hz, CH₃, N-propyl); EI-HRMS: C₂₆H₃₂N₄O₁₀S, calc. for Da, found: 592.1852.

N-n-Butylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3d). Yellow solid, mp 186–189°C (from 96% ethanol), yield 91%; IR (KBr) /cm⁻¹: 3346, 1749, 1612, 1376, 1227, 1043; ¹H NMR (DMSO-) δ (ppm): 12.73 (s, 1H, NH-2), 9.61 (d, 1H, Hz, NH-4), 7.77 (d, 1H, Hz, H-7′), 7.46 (t, 1H, Hz, H-6′), 7.20 (d, 1H, Hz, H-4′), 7.19 (t, 1H, Hz, H-5′), 6.01 (t, 1H, Hz, H-1), 5.46 (t, 1H, Hz, H-3), 5.34 (t, 1H, Hz, H-2), 4.98 (t, 1H, Hz, H-4), 4.24 (dd, 1H, , 4.5 Hz, H-6a), 4.17 (dt, 1H, , 2.0 Hz, H-5), 4.00 (d, 1H, Hz, H-6b), 3.74 (t, 2H, Hz, CH₂, N-butyl), 2.07 (m, 1H, CH, N-butyl); 2.01–1.93 (s, 12H, 4 × CH₃CO), 1.61 (m, 2H, CH₂, N-butyl), 1.61 (m, 2H, CH₂, N-butyl), 0.90 (t, 3H, Hz, CH₃, N-butyl); EI-HRMS: C₂₇H₃₄N₄O₁₀S, calc. for Da, found: 606.2008.

N-Isobutylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3e). Yellow solid, mp 190–193°C (from 96% ethanol), yield 86%; IR (KBr) /cm⁻¹: 3287, 1747, 1617, 1370, 1230, 1040; ¹H NMR (DMSO-) δ (ppm): 12.73 (s, 1H, NH-2), 9.63 (d, 1H, Hz, NH-4), 7.77 (d, 1H, Hz, H-7′), 7.45 (t, 1H, Hz, H-6′), 7.20 (d, 1H, Hz, H-4′), 7.19 (t, 1H, Hz, H-5′), 6.01 (t, 1H, Hz, H-1), 5.46 (t, 1H, Hz, H-3), 5.34 (t, 1H, Hz, H-2), 4.98 (t, 1H, Hz, H-4), 4.24 (dd, 1H, , 4.5 Hz, H-6a), 4.17 (ddd, 1H, , 4.75, 2.0 Hz, H-5), 3.98 (dd, 1H, , 1.5 Hz, H-6b), 3.55 (d, 2H, CH₂, N-isobutyl), 2.07 (m, 1H, CH, N-isobutyl); 2.01–1.93 (s, 12H, 4 × CH₃CO), 0.91 [d, 6H, (CH₃)₂, N-isobutyl]; ¹³C NMR (DMSO-) δ (ppm): 179.0 (C=S), 170.0–169.3 (4 × COCH₃), 161.0 (C=O isatin), 143.6 (C-3′), 132.4 (C-4′), 131.6 (C-4′a), 122.8 (C-5′), 121.1 (C-6′), 119.0 (C-7′), 110.4 (C-7′a), 81.8 (C-1), 70.9 (C-2), 72.7 (C-3), 67.7 (C-4), 72.4 (C-5), 61.7 (C-6), 46.6 (CH₂, N-isobutyl), 26.8 (CH, N-isobutyl), 20.5–18.3 (4 × CH₃CO); 19.9 [(CH₃)₂, N-isobutyl]; EI-HRMS: C₂₇H₃₄N₄O₁₀S, calc. for Da, found: 606.2011.

N-Allylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3f). Yellow solid, mp 150-151°C (from 96% ethanol), yield 88%; IR (KBr) /cm⁻¹: 3303, 1747, 1611, 1373, 1229, 1037; ¹H NMR (DMSO-) δ (ppm): 12.68 (s, 1H, NH-2), 9.64 (d, 1H, Hz, NH-4), 7.78 (d, 1H, Hz, H-7′), 7.44 (t, 1H, Hz, H-6′), 7.19 (t, 1H, Hz, H-5′), 7.09 (d, 1H, Hz, H-4′), 6.02 (t, 1H, J=9.0; 9.0 Hz, H-1), 5.46 (t, 1H, J=9.5 Hz, H-3), 5.35 (t, 1H, Hz, H-2), 5.88 (m, 1H, N–CH₂–CH=CH₂), 5.21 (m, 2H, N–CH₂–CH=CH₂), 4.37 (m, 2H, N-CH₂–CH=CH₂), 4.99 (t, 1H, Hz, H-4), 4.24 (dd, 1H, , 5.0 Hz, H-6a), 4.17 (ddd, 1H, , 4.5, 2.0 Hz, H-5), 4.00 (dd, 1H, J=11.75, 1.5 Hz, H-6b), 2.01-1.93 (s, 12H, 4 × CH₃CO); ¹³C NMR (DMSO-) δ (ppm): 179.00 (C=S), 169.3–167.0 (4 × COCH₃), 160.4 (C=O isatin), 143.0 (C-3′), 132.3 (C-4′), 131.5 (C-4′a), 131.3 (N–CH₂–CH=CH₂), 122.9 (C-5′), 121.2 (C-6′), 119.1 (C-7′), 110.4 (C-7′a), 117.4 (N–CH₂–CH=CH₂), 81.9 (C-1), 70.9 (C-2), 72.7 (C-3), 67.7 (C-4), 72.4 (C-5), 61.7 (C-6), 41.3 (N–CH₂–CH=CH₂), 20.5–20.3 (4 × CH₃CO); EI-HRMS: C₂₇H₃₄N₄O₁₀S, calc. for Da, found: m/z 590.1692.

N-Benzylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3g). Yellow solid, mp 195-196°C (from 96% ethanol), yield 90%; IR (KBr) ν/cm⁻¹: 3341, 1750, 1608, 1370, 1229, 1064; ¹H NMR (DMSO-) δ (ppm): 12.72 (s, 1H, NH-2), 9.67 (d, 1H, Hz, NH-4), 7.79 (d, 1H, Hz, H-7′), 7.33 (t, 1H, Hz, H-6′), 7.39–7.32 (5H, C₆H₅, N-benzyl), 7.17 (t, 1H, Hz, H-5′), 7.04 (d, 1H, Hz, H-4′), 6.04 (t, 1H, Hz, H-1), 5.47 (t, 1H, Hz, H-3), 5.36 (t, 1H, Hz, H-2), 5.00 (t, 1H, Hz, H-4), 4.98 (s, 2H, CH₂, N-benzyl), 4.24 (dd, 1H, , 5.0 Hz, H-6a), 4.19 (ddd, 1H, , 4.75, 1.5 Hz, H-5), 4.01 (dd, 1H, Hz, H-6b), 2.01–1.93 (s, 12H, 4 × CH₃CO); ¹³C NMR (DMSO-) δ (ppm): ¹³C NMR (DMSO-) δ (ppm): 179.0 (C=S), 169.9–169.3 (4 × COCH₃), 160.7 (C=O (isatin), 142.9 (C-3′), 135.6 (C-1′′, N-benzyl), 132.2 (C-4′), 131.5 (C-4′′, N-benzyl), 128.8 (C-4′a), 128.6 (C-3′′ and C-5′′, N-benzyl), 127.4 (C-2′′ and C-6′′, N-benzyl), 123.0 (C-5′), 121.2 (C-6′), 119.2 (C-7′), 110.4 (C-7′a), 81.9 (C-1), 70.9 (C-2), 72.7 (C-3), 67.7 (C-4), 72.4 (C-5), 61.7 (C-6), 42.6 (CH₂, N-benzyl), 20.5–20.3 (4 × CH₃CO); EI-HRMS: C₂₇H₃₂N₄O₁₀S, calc. for Da, found: 640.1850.

N-Phenethylisatin 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazone (3h). Yellow solid, mp 200–203°C (from 96% ethanol), yield 73%; IR (KBr) /cm⁻¹: 3290, 1735, 1614, 1367, 1234, 1040; ¹H NMR (DMSO-) δ (ppm): 12.66 (s, 1H, NH-2), 9.62 (d, 1H, Hz, NH-4), 7.75 (d, 1H, Hz, H-7′), 7.42 (t, 1H, Hz, H-6′), 7.28–7.21 (5H, C₆H₅, N-phenethyl), 7.19–7.16 (m, 2H, H-4′ and H-5′), 6.00 (t, 1H, Hz, H-1), 5.46 (t, 1H, Hz, H-3), 5.33 (t, 1H, Hz, H-2), 4.98 (t, 1H, Hz, H-4), 4.34 (t, 2H, Hz, CH₂, N-phenethyl), 4.24 (dd, 1H, , 4.75 Hz, H-6a), 4.17 (ddd, 1H, , 4.5, 1.5 Hz, H-5), 4.02 (d, 1H, Hz, H-6b), 3.46–3.41 (m, 2H, CH₂, N-phenethyl), 2.08–1.93 (s, 12H, 4 × CH₃CO); EI-HRMS: C₃₁H₃₄N₄O₁₀S, calc. for Da, found: 654.2007.

3. Results and Discussion

Alkylation reaction in isatin 1 using corresponding alkyl bromide in the presence of potassium carbonate as base in DMF under microwave-assisted heating method gave required N-alkylisatins 2a-h [21]. Condensation of N-alkylisatins 2a-h with 4-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazide was carried out on refluxing in the presence of glacial acetic acid as catalyst. These reactions were executed under microwave-assisted heating method. Reaction products usually separated as color solid after cooling to room temperature. The products are soluble in common organic solvents, such as toluene, ethanol, methanol, DMF, acetone, and ethyl acetate (Scheme 1).

The structure of these thiosemicarbazones was first confirmed using IR spectroscopic method. IR spectra show the characteristic absorption bands at 3462–3313 and 3331–3212 cm⁻¹ (), 1752–1747 cm⁻¹ ( ester), 1697–1688 ( in isatin), 1618–1610 cm⁻¹ (), 1228–1218 and 1060–1049 cm⁻¹( ester), and 1092–1090 cm⁻¹ (), some bands at 1597–1490 cm⁻¹ ( aromatic). The evidence that confirms the success of reactions is the absence of C=O band (that belong to isatin) in IR spectra at 1780–1745 cm⁻¹ and chemical shifts of NH and NH₂ (in thiosemicarbazide) at δ = 9.32, 8.08, and 4.63 ppm, respectively, that belong to thiosemicarbazide link, NHCSNHNH₂, of 4-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazide (in ¹H NMR spectra). Other evidence is the appearance of C=S signals at δ = 179.6–177.5 ppm and of C=N signals at δ = 138.0–127.9 ppm.

The assignments of ¹H and ¹³C were confirmed using HMBC and HSQC methods in case of compound 3a (R=Me). The ¹H NMR spectra of the N-methylisatin 4-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones (3a-h) showed resonance signals for proton NH-2 in range at δ = 12.75–12.67 ppm (singlet) and for proton NH-4 at δ = 9.71–9.62 ppm (doublet) with coupling constants = 8.5–9.0 Hz. Protons in glucopyranose ring have resonance signals in range at δ = 5.97–4.07 ppm. Methyl groups in acetate ester have chemical shifts in range at δ = 2.17–1.95 ppm. The β anomeric configuration of 3a-h was confirmed on the basis of the coupling constant –9.0 Hz in agreement with the 1,2-trans-diaxial relationships between protons H-1 and H-2. The ¹³C NMR spectrum of compound 3a-h showed resonance signals at δ = 179.6–179.1 ppm (carbon atom in C=S group), δ = 170.5–169.3 ppm (carbon atoms in C=O bond of acetyl groups), and δ = 82.8–61.3 ppm (protons in glucopyranose ring).

Antibacterial activity was done by the paper-disc plate method. The nutrient agar medium (peptone, beef extract, NaCl, and agar-agar) and 5-mm diameter paper discs (Whatman No. 1) were used. The compounds were dissolved in DMSO in 50, 100, and 150 μg/mL concentrations. The filterpaper discs were soaked in different solutions of the compounds, dried, and then placed in the petri dishes previously seeded with the test organisms (Escherichia coli and Candida albicans). The plates were incubated for 24 h at 28 ± 2°C and the inhibition zone around each disc was measured. All these thiosemicarbazones have antibacterial activities on E. coli and C. albicans. The diameter of inhibition zone is 15–21 mm and 10–30 mm for E. coli and C. albicans, respectively. The antibacterial activities on C. albicans are somewhat higher than on E. coli.

4. Conclusion

In summary, an efficient method for synthesis of N-alkylisatin 4-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones under microwave-assisted refluxing conditions has been performed. Reaction yields were 73–93%.

Acknowledgment

Financial support for this work was provided by Vietnam’s National Foundation for Science and Technology Development (NAFOSTED).

References

M. C. Pirrung, S. V. Pansare, K. Das Sarma, K. A. Keith, and E. R. Kern, “Combinatorial optimization of isatin-β-thiosemicarbazones as anti-poxvirus agents,” Journal of Medicinal Chemistry, vol. 48, no. 8, pp. 3045–3050, 2005.
View at: Publisher Site | Google Scholar
G. G. Heiner, N. Fatima, P. K. Russell et al., “Field trials of methisazone as a prophylactic agent against smallpox,” American Journal of Epidemiology, vol. 94, no. 5, pp. 435–449, 1971.
View at: Google Scholar
M. D. Hall, N. K. Salam, J. L. Hellawell et al., “Synthesis, activity, and pharmacophore development for isatin-β- thiosemicarbazones with selective activity toward multidrug-resistant cells,” Journal of Medicinal Chemistry, vol. 52, no. 10, pp. 3191–3204, 2009.
View at: Publisher Site | Google Scholar
L. Somogyi, “Synthesis of spiro[indoline-3,2′(3′H)-[1,3,4] thiadiazolinel-4-ones by acetylation of isatin-β-thiosemicarbazones,” Liebigs Annalen der Chemie, vol. 1993, no. 8, pp. 931–934, 1993.
View at: Google Scholar
M. H. Shih and C. L. Wu, “Efficient syntheses of thiadiazoline and thiadiazole derivatives by the cyclization of 3-aryl-4-formylsydnone thiosemicarbazones with acetic anhydride and ferric chloride,” Tetrahedron, vol. 61, no. 46, pp. 10917–10925, 2005.
View at: Publisher Site | Google Scholar
K. L. Vine, J. M. Locke, M. Ranson, S. G. Pyne, and J. B. Bremner, “An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins,” Journal of Medicinal Chemistry, vol. 50, no. 21, pp. 5109–5117, 2007.
View at: Publisher Site | Google Scholar
L. Zhou, Y. Liu, W. Zhang et al., “Isatin compounds as noncovalent SARS coronavirus 3C-like protease inhibitors,” Journal of Medicinal Chemistry, vol. 49, no. 12, pp. 3440–3443, 2006.
View at: Publisher Site | Google Scholar
W. Chu, J. Rothfuss, A. D'Avignon et al., “Isatin sulfonamide analogs containing a Michael addition acceptor: a new class of caspase 3/7 inhibitors,” Journal of Medicinal Chemistry, vol. 50, no. 15, pp. 3751–3755, 2007.
View at: Publisher Site | Google Scholar
H. K. Shuka, N. C. Desia, R. R. Astik, and K. A. Thaker, “The uses of phenylthiosemecarbazide in heterocyclic syntheses,” Journal of Indian Chemical Society, vol. 61, pp. 168–175, 1984.
View at: Google Scholar
M. U. Yamaguchi, A. P. B. Da Silva, T. Ueda-Nakamura, B. P. D. Filho, C. C. Da Silva, and C. V. Nakamura, “Effects of a thiosemicarbazide camphene derivative on Trichophyton mentagrophytes,” Molecules, vol. 14, no. 5, pp. 1796–1807, 2009.
View at: Publisher Site | Google Scholar
R. Singh, P. S. Mishra, and R. Mishra, “Synthesis and evaluation of biological activities of thiosemicarbazones derivatives,” Biomirror, vol. 2, no. 11, pp. 1–4, 2011.
View at: Google Scholar
P. Tarasconi, S. Capacchi, G. Pelosi et al., “Synthesis, spectroscopic characterization and biological properties of new natural aldehydes thiosemicarbazones,” Bioorganic and Medicinal Chemistry, vol. 8, no. 1, pp. 157–162, 2000.
View at: Publisher Site | Google Scholar
A. C. Tenchiu (Deleanu), I. D. Kostas, D. Kovala-Demertzi, and A. Terzis, “Synthesis and characterization of new aromatic aldehyde/ketone 4-(β-d-glucopyranosyl)thiosemicarbazones,” Carbohydrate Research, vol. 344, no. 11, pp. 1352–1364, 2009.
View at: Publisher Site | Google Scholar
S. Ghosh, A. K. Misra, G. Bhatia, M. M. Khan, and A. K. Khanna, “Syntheses and evaluation of glucosyl aryl thiosemicarbazide and glucosyl thiosemicarbazone derivatives as antioxidant and anti-dyslipidemic agents,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 2, pp. 386–389, 2009.
View at: Publisher Site | Google Scholar
N. D. Thanh and N. T. K. Giang, “Microwave-assisted synthesis of novel tetra-o-acetyl-β-d- glucopyranosyl thiosemicarbazones of substituted isatins,” Letters in Organic Chemistry, vol. 8, no. 7, pp. 500–503, 2011.
View at: Publisher Site | Google Scholar
N. D. Thanh and H. T. K. Van, “Synthesis of some novel substituted benzaldehyde (hepta-O-acetyl-β- maltosyl)thiosemicarbazones,” Asian Journal of Chemistry, vol. 23, no. 10, pp. 4263–4267, 2011.
View at: Google Scholar
N. D. Thanh, N. T. K. Giang, and T. le Hoai, “Microwave-assisted synthesis of acetophenone (per-O-acetylated-β-D-glucopyranosyl)-thiosemicarbazones,” E-Journal of Chemistry, vol. 7, no. 3, pp. 899–907, 2010.
View at: Google Scholar
T. Aboul-Fadl, F. A. H. Mohammed, and E. A. S. Hassan, “Synthesis, antitubercular activity and pharmacokinetic studies of some Schiff bases derived from 1-alkylisatin and isonicotinic acid hydrazide (INH),” Archives of Pharmacal Research, vol. 26, no. 10, pp. 778–784, 2003.
View at: Google Scholar
A. A. Esmaili and A. Bodaghi, “New and efficient one-pot synthesis of functionalized γ-spirolactones mediated by vinyltriphenylphosphonium salts,” Tetrahedron, vol. 59, no. 8, pp. 1169–1171, 2003.
View at: Publisher Site | Google Scholar
D. J. Bauer and P. W. Sadler, “1-Substituted isatin-thiosemicarbazones, their preparation and pharmaceutical preparations containing them,” Britain Patent 975357, 1964, Chemical Abstracts, vol. 62, no. 6462c, 1965.
View at: Google Scholar
M. S. Shmidt, A. M. Reverdito, L. Kremenchuzky, I. A. Perillo, and M. M. Blanco, “Simple and efficient microwave assisted N-alkylation of isatin,” Molecules, vol. 13, no. 4, pp. 831–840, 2008.
View at: Publisher Site | Google Scholar

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Copyright © 2013 Nguyen Dinh Thanh and Nguyen Thi Kim Giang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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