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(Ar), 129.1 (Ar), 132.9 (Ar), 134.9 (Ar), 152.2 (C]O), 159.5 (CH] NH), 8.01 (s, 1H, CH]N). 13C NMR (75.5 MHz, DMSO-d6), d
N), 170.1 (C]O). Elemental analysis – EAtheor: N 11.96%; C (ppm): 11.2 (CH3), 17.1 (CH3), 25.8 (CH2), 33.3 (CH), 45.9 (CH3O),
64.95%; H 4.88%; EAexp: N 11.83%; C 64.90%; H 5.04%.
58.5 (CH), 135.0 (Ar), 123.6 (Ar), 168.1 (C]O), 170.1 (C]O).
(Z)-2-(1,3-Dioxoisoindolin-2-yl)-N0-(4-methoxybenzylidene)-3- Elemental analysis – EAtheor: N 10.56%; C 63.40%; H 5.07%;
phenylpropanehydrazide (7b). Chemical formula: C25H21N3O4. EAexp: N 10.72%; C 63.51%; H 5.11%.
MW: 427.45 g. Yield: 49.12%. Rf: 0.3 (Hex/AcEt: 9/1). M.p.: 169–
(Z)-N0-(3,4-Dichlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)-
170 ꢀC. IR (KBr, cmꢂ1): 1620 (C]N); 1602 (C]O). 1H NMR (300 propanehydrazide (9a). Chemical formula: C18H13Cl2N3O3. MW:
MHz, DMSO-d6), d (ppm): 2.61 (m, 1H, CH), 4.11 (s, 3H, OCH3), 390.22 g. Yield: 45.76%. Rf: 0.7 (Hex/AcEt: 9/1). M.p.: 170–172 ꢀC.
4.34 (m, 1H, CH), 7.12 and 7.49 (2 br, 2H, NH2), 7.10–7.52 IR (KBr, cmꢂ1): 3442 (NH2), 2997 (C–H), 1710 (C]O), 1627 (C]N)
(m, 8H, Ar), 7.86–7.87 (m, 4H, Ar), 7.99 (s, 1H, NH), 8.01 (s, 1H, cmꢂ1. 1H NMR (300 MHz, DMSO-d6), d (ppm): 1.11 (d, 3H, CH3),
CH]N). 13C NMR (75.5 MHz, DMSO-d6), d (ppm): 25.8 (CH2), 2.49 (m, 1H, CH), 4.11 (s, 3H, CH3), 7.51–7.63 (4H, Ar), 7.85–8.05
33.3 (CH), 45.9 (CH3O), 58.5 (CH), 123.6 (Ar), 125.0 (Ar), 126.5 (m, 4H, Ar), 8.19 (s, 1H, CH]N). 13C NMR (75.5 MHz, DMSO-d6),
(Ar), 131.0 (Ar), 135.0 (Ar), 168.1 (C]O), 170.1 (C]O). 7b – d (ppm): 15.4 (CH3), 20.8 (CH), 125.5 (Ar), 128.6 (Ar), 129.1 (Ar),
elemental analysis – EAtheor: N 9.83%; C 70.25%; H 4.95%; 132.9 (Ar), 134.9 (Ar), 147.9 (Ar, C–Cl), 152.2 (C]O), 159.5 (CH]
EAexp: N 10.02%; C 70.13%; H 4.98%.
(Z)-2-(1,3-Dioxoisoindolin-2-yl)-N0-(4-methoxybenzylidene)-3- 55.40%; H 3.36%; EAexp: N 10.67%; C 55.46%; H 3.25%.
methylpentanehydrazide (7c). Chemical formula: C22H23N3O4.
(Z)-N0-(3,4-Dichlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)-
MW: 393.44 g. Yield: 48.75%. Rf: 0.2 (Hex/AcEt: 9/1). M.p.: 169– 3-phenylpropanehydrazide (9b). Chemical formula:
171 ꢀC. IR (KBr, cmꢂ1): 1661 (C]N); 1623 (C]O). 1H NMR (300
24H17Cl2N3O3. MW: 466.32 g. Yield: 46.82%. Rf: 0.7 (Hex/AcEt:
N), 170.1 (C]O). Elemental analysis – EAtheor: N 10.77%; C
C
MHz, DMSO-d6), d (ppm): 0.77 (m, 3H, CH3), 0.91 (m, 2H, CH2), 9/1). M.p.: 171–173 ꢀC. IR (KBr, cmꢂ1): 3442 (NH2), 2997 (C–H),
0.98 (m, 2H, CH3), 2.51 (m, 1H, CH), 4.11 (s, 3H, OCH3), 4.34 1700 (C]O), 1687 (C]N) cmꢂ1. 1H NMR (300 MHz, DMSO-d6),
(m, 1H, CH), 7.12 and 7.49 (2 br, 2H, NH2), 7.19–7.32 (m, 4H, d (ppm): 2.49 (m, 1H, CH), 4.11 (s, 3H, CH3), 7.10–7.52 (m, 8H,
Ar), 7.87–7.86 (m, 4H, Ar), 7.99 (s, 1H, NH), 8.01 (s, 1H, CH]N). Ar), 7.85–8.05 (m, 4H, Ar), 8.19 (s, 1H, CH]N). 13C NMR (75.5
13C NMR (75.5 MHz, DMSO-d6), d (ppm): 11.2 (CH3), 17.1 (CH3), MHz, DMSO-d6), d (ppm): 25.8 (CH2), 33.3 (CH), 58.5 (CH), 125.0
25.8 (CH2), 33.3 (CH), 45.9 (CH3O), 58.5 (CH), 123.6 (Ar), 135.0 (Ar), 126.5 (Ar), 131.0 (Ar), 135.0 (Ar), 143.6 (Ar), 168.1 (C]O),
(Ar), 168.1 (C]O), 170.1 (C]O). Elemental analysis – EAtheor: N 170.1 (C]O). Elemental analysis – EAtheor: N 9.01%; C 61.82%;
10.68%; C 67.16%; H 5.89%. EAexp: N 10.85%; C 67.30%; H H 3.67%; EAexp: N 9.24%; C 61.74%; H 3.46%.
5.69%.
(Z)-N0-(3,4-Dichlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)-
(Z)-N0-(4-Chlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)pro- propanehydrazide (9c). Chemical formula: C21H19Cl2N3O3. MW:
panehydrazide (8a). Chemical formula: C18H14ClN3O3. MW: 432.30 g. Yield: 50.02%. Rf: 0.7 (Hex/AcEt: 9/1). M.p.: 178–
355.78 g. Yield: 60.04%. Rf: 0.7 (Hex/AcEt: 9/1). M.p.: 209– 180 C. IR (KBr, cmꢂ1): 3442 (NH2), 2997 (C–H), 1700 (C]O),
ꢀ
210 ꢀC. IR (KBr, cmꢂ1): 1660 (C]N); 1624 (C]O). 1H NMR (300 1687 (C]N) cmꢂ1. 1H NMR (300 MHz, DMSO-d6), d (ppm): 1.11
MHz, DMSO-d6), d (ppm): 1.11 (d, 3H, CH3), 2.49 (m, 1H, CH), (d, 3H, CH3), 2.49 (m, 1H, CH), 4.11 (s, 3H, CH3), 7.51–7.63
4.11 (s, 3H, CH3), 7.51–7.72 (m, 4H, Ar), 7.85–8.05 (m, 4H, Ar), (m, 2H, Ar), 7.85–8.05 (m, 4H, Ar), 8.19 (s, 1H, CH]N). 13C NMR
8.09 (s, 1H, CH]N). 13C NMR (75.5 MHz, DMSO-d6), d (ppm): (75.5 MHz, DMSO-d6), d (ppm): 15.4 (CH3), 20.8 (CH), 125.5 (Ar),
15.4 (CH3), 20.8 (CH), 123.6 (Ar), 125.5 (Ar), 128.6, 129.1 (Ar), 128.6 (Ar), 129.1 (Ar), 132.9 (Ar), 134.9 (Ar), 147.9 (Ar, C–Cl),
132.9 (Ar), 134.9 (Ar), 147.9 (Ar, C–Cl), 152.2 (C]O), 159.5 (CH] 152.2 (C]O), 159.5 (CH]N), 170.1 (C]O). Elemental analysis –
N), 170.1 (C]O). Elemental analysis – EAtheor: N 11.81%; C EAtheor: N 9.72%; C 58.35%; H 4.43%; EAexp: N 9.60%; C 58.27%;
60.77%; H 3.97%; EAexp: N 11.72%; C 60.68%; H 3.89%.
(Z)-N0-(4-Chlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)-3-phe-
nylpropanehydrazide (8b). Chemical formula: C24H18ClN3O3.
H 4.67%.
Biological in vitro evaluation
MW: 431.87 g. Yield: 50.25%. Rf: 0.7 (Hex/AcEt: 9/1). M.p.: 210–
1
211 C. IR (KBr, cmꢂ1): 1658 (C]N); 1624 (C]O). H NMR (300
TNF-a and IL-1 levels. Mice peritoneal macrophages were
ꢀ
MHz, DMSO-d6), d (ppm): 2.51 (m, 2H, CH2), 4.34 (m, 1H, CH), placed into 96 well plates at a cell density of 2 ꢁ 106 cells per mL
6
ꢀ
7.10–7.52 (m, 8H, Ar), 7.87–7.86 (m, 4H, Ar), 7.99 (s, 1H, NH), 8.01 and incubated for 2 h at 37 C and 5% CO2. Cells at 2 ꢁ 10
(s, 1H, CH]N). 13C NMR (75.5 MHz, DMSO-d6), d (ppm): 25.8 concentration were suspended in RPMI 1640 with 5% FBS, 100
(CH2), 33.3 (CH), 45.9 (CH3O), 58.5 (CH), 123.6 (Ar), 125.0 (Ar), UI mLꢂ1 of penicillin, 100 mg mLꢂ1 of streptomycin and 50 mM
126.5 (Ar), 131.0 (Ar), 135.0 (Ar), 168.1 (C]O), 170.1 (C]O). 2-mercaptoethanol. 100 mL of suspension and 100 mL of samples
Elemental analysis – AEteor: N 9.73%; C 66.75%; H 4.20%; AEexp: N were incubated with LPS 2 mg mLꢂ1 (positive control) or with the
9.92%; C 66.83%; H 4.47%.
test compounds in different concentrations. Aer 24 h, the
(Z)-N0-(4-Chlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)-3- supernatants were removed and kept at ꢂ80 C until the eval-
methylpentanehydrazide (8c). Chemical formula: C21H20ClN3O3. uation of cytokine levels (TNF and IL-1). The doses of cytokines
MW: 397.86 g. Yield: 55.54%. Rf: 0.7 (Hex/AcEt: 9/1). M.p.: 210– in the exudates were assayed by sandwich ELISA, using mono-
211 ꢀC. IR (KBr, cmꢂ1): 1660 (C]N); 1624 (C]O). 1H NMR (300 clonal antibodies specic to the detection of cytokines.
ꢀ
MHz, DMSO-d6), d (ppm): 0.77 (m, 3H, CH3), 0.91 (m, 2H, CH2),
TNF-a, cell death and apoptosis inhibition. The effect of
0.98 (m, 2H, CH3), 2.51 (m, 1H, CH), 4.11 (s, 3H, OCH3), 4.34 (m, each compound on inhibiting TNF expression and decreasing
1H, CH), 7.19–7.32 (m, 4H, Ar), 7.87–7.86 (m, 4H, Ar), 7.99 (s, 1H, cell viability was determined using the cell line FRT-Jurkat TNF.
764 | Med. Chem. Commun., 2014, 5, 758–765
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