AARJANE ET AL.
9 of 10
|
114.38, 100.23, 42.20, 41.22. HRMS (ESI) m/z [M+H]+ calcd. for
CH‐isoxazole), 5.69 (s, 2H, CH2), 2.50 (s, 3H, CH3). 13C NMR
(75 MHz, CDCl3, 25°C, TMS): 13C NMR (75 MHz, CDCl3) δ 177.98,
167.89, 161.97, 141.85, 136.47, 134.42, 129.23, 128.19, 128.10,
126.72, 122.85, 122.23, 114.32, 100.92, 43.56. HRMS (ESI) m/z [M
+H]+ calcd. for C24H17ClN2O2: 401.1040, found: 401.1050.
C
25H21N3O: 396.1683, found: 396.1687.
2‐Methyl‐10‐[(3‐phenyl‐1,2‐oxazol‐5‐yl)methyl]acridin‐9‐one (4g)
White solid; yield: 77%, mp = 229°C. IR (KBr): 3015 (m) (C–H), 2964
(w) (C–H), 1636 (s) (C═O), 1617 (m) (C═N), 1596 (s) (C═C) cm−1 1H
.
NMR (300 MHz, DMSO‐d6, 25°C, TMS): 8.40 (dd, J = 8.0, 1.6 Hz, 1H,
Ar–H), 8.19 (s, 1H, Ar–H), 7.93–7.76 (m, 5H, Ar–H), 7.67 (dd, J = 8.9,
2.3 Hz, 1H, Ar–H), 7.52–7.41 (m, 3H, Ar–H), 7.37 (td, J = 7.9, 6.5,
1.2 Hz, 1H, Ar–H), 7.01 (s, 1H, CH‐isoxazole), 6.04 (s, 2H, CH2), 2.45
(s, 3H, CH3). 13C NMR (75 MHz, DMSO‐d6, 25°C, TMS): 176.53,
168.69, 161.99, 141.61, 139.86, 135.62, 134.17, 131.05, 130.29,
129.01, 128.08, 126.76, 126.60, 125.99, 121.75, 121.73, 121.53,
115.97, 115.80, 101.11, 42.06, 20.16. HRMS (ESI) m/z [M+H]+ calcd.
for C24H18N2O2: 367.1398, found: 367.1404.
2‐Methyl‐10‐{[3‐(4‐nitrophenyl)‐1,2‐oxazol‐5‐yl]methyl}acridin‐9‐
one (4k)
White solid; yield: 65%, mp = 276°C. IR (KBr): 3000 (m) (C–H), 2970
(m) (C–H), 1638 (s) (C═O), 1610 (m) (C═N), 1598 (s) (C═C) cm−1
.
1H NMR (300 MHz, DMSO‐d6, 25°C, TMS): 8.40 (dd, J = 8.0, 1.5 Hz,
1H, Ar–H), 8.33–8.25 (m, 2H, Ar–H), 8.19 (s, 1H, Ar–H), 8.15–8.07
(m, 2H, Ar–H), 7.96–7.75 (m, 3H, Ar–H), 7.68 (dd, J = 8.9, 2.3 Hz, 1H,
Ar–H), 7.38 (td, J = 7.9, 6.3, 1.5 Hz, 1H, Ar–H), 7.15 (s, 1H, CH‐
isoxazole), 6.08 (s, 2H, CH2), 2.46 (s, 3H, CH3). 13C NMR (75 MHz,
DMSO‐d6, 25°C, TMS): 176.54, 169.70, 160.62, 148.35, 141.59,
139.83, 135.67, 134.23, 134.11, 131.12, 127.95, 126.79, 126.02,
124.19, 121.77, 121.59, 115.94, 115.76, 101.54, 42.09, 20.16. HRMS
(ESI) m/z [M+H]+ calcd. for C24H18N3O4: 412.1239, found: 412.1239.
10‐{[3‐(4‐Methoxyphenyl)‐1,2‐oxazol‐5‐yl]methyl}‐2‐methylacridin‐
9‐one (4h)
White solid; yield: 79%, mp = 263°C. IR (KBr): 3011 (m) (C–H), 2987
(w) (C–H), 1637 (s) (C═O), 1616 (m) (C═N), 1598 (s) (C═C) cm−1
.
1H NMR (300 MHz, CDCl3, 25°C, TMS): 8.63 (dd, J = 8.0, 1.7 Hz, 1H,
Ar–H), 8.39 (s, 1H, Ar–H), 7.81–7.64 (m, 3H, Ar–H), 7.54–7.44
(m, 2H, Ar–H), 7.39 (td, J = 7.9, 6.9, 0.9 Hz, 2H, Ar–H), 6.93
(d, J = 8.9 Hz, 2H, Ar–H), 6.32 (s, 1H, CH‐isoxazole), 5.70 (s, 2H, CH2),
3.85 (s, 3H, CH3), 2.50 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3, 25°C,
TMS): 178.06, 167.19, 162.52, 161.27, 141.94, 134.40, 128.26,
128.16, 122.85, 122.18, 120.69, 114.43, 114.34, 100.82, 55.34,
43.67, 20.15. HRMS (ESI) m/z [M+H]+ calcd. for C25H20N2O3:
397.1473, found: 397.1507.
10‐({3‐[4‐(Dimethylamino)phenyl]‐1,2‐oxazol‐5‐yl}methyl)‐2‐
methylacridin‐9‐one (4l)
Yellow solid; yield: 63%, mp = 255°C. IR (KBr): 3014 (m) (C–H), 2975
(w) (C–H), 1635 (s) (C═O), 1616 (m) (C═N), 1597 (s) (C═C) cm−1
.
1H NMR (300 MHz, CDCl3, 25°C, TMS): 8.60 (dd, J = 8.0, 1.7 Hz, 1H,
Ar–H), 8.38 (s, 1H, Ar–H), 7.76–7.65 (m, 2H, Ar–H), 7.55 (td, J = 8.5,
5.5, 3.5 Hz, 2H, Ar–H), 7.40 (m, 2H, Ar–H), 7.03 (d, J = 8.5 Hz, 1H,
Ar–H), 6.67 (d, J = 8.8 Hz, 2H, Ar–H), 6.27 (s, 1H, CH‐isoxazole), 5.65
(s, 2H, CH2), 2.99 (s, 6H, CH3), 2.49 (s, 3H, CH3). 13C NMR (75 MHz,
CDCl3, 25°C, TMS): 177.97, 167.68, 161.64, 152.01, 141.72, 139.89,
135.71, 131.91, 129.18, 128.10, 127.80, 127.43, 125.85, 122.63,
122.18, 121.15, 119.79, 115.54, 114.54, 111.87, 100.72, 43.34,
40.12, 20.59. HRMS (ESI) m/z [M+H]+ calcd. for C26H23N3O2:
410.1820, found: 410.1829.
10‐{[3‐(4‐Hydroxy‐3‐methoxyphenyl)‐1,2‐oxazol‐5‐yl]methyl}‐2‐
methylacridin‐9‐one (4i)
Yellow solid; yield: 40%, mp = 214°C. IR (KBr): 3420 (s) (O–H), 3014
(m) (C–H), 2970 (m) (C–H), 1644 (s) (C═O), 1615 (m) (C═N), 1595 (s)
(C═C) cm−1 1H NMR (300 MHz, DMSO‐d6, 25°C, TMS): 9.50 (s, 1H,
.
OH), 8.41 (dd, J = 8.1, 1.7 Hz, 1H, Ar–H), 7.78 (d, J = 1.9 Hz, 1H,
Ar–H), 7.48–7.41 (m, 1H, Ar–H), 7.33–7.27 (m, 2H, Ar–H), 7.24
(d, J = 8.4 Hz, 1H, Ar–H), 7.22–7.12 (m, 3H, Ar–H), 6.89 (s, 1H, CH‐
isoxazole), 6.80 (td, J = 7.3, 1.3 Hz, 1H, Ar–H), 6.01 (s, 2H, CH2), 3.88
(s, 3H, CH3), 2.40 (s, 3H, CH3). 13C NMR (75 MHz, DMSO‐d6, 25°C,
TMS): 178.76, 168.83, 158.04, 148.70, 147.80, 141.36, 140.06,
134.16, 132.19, 131.78, 126.88, 124.21, 123.35, 121.79, 121.64,
121.50, 116.05, 115.83, 114.86, 110.50, 100.95, 56.14, 45.78, 20.85.
HRMS (ESI) m/z [M+H]+ calcd. for C25H20N2O4: 399.1266, found:
399.1265.
|
4.2
Antibacterial activity
The novel isoxazoles (4a–l) were evaluated for their in vitro anti-
bacterial activity by the disk‐diffusion method. The active com-
pounds were subjected to the determination of the MIC, using the
broth microdilution method. The microorganisms used for the test
were E. coli, S. aureus, P. putida, and K. pneumoniae. They were col-
lected from clinical isolates. Bacterial inoculums were prepared by
subculturing microorganisms into MHB at 37°C for 18 h and were
diluted to approximately 106 CFU/ml. Initial solution with con-
centration 0.5 mg/ml of the compounds 4a–l was prepared in DMF,
further serial dilutions were made in the microplates, and 100 μl of
MHB containing each test microorganism was added to the micro-
plate,[33,34] then incubated at 36°C for 24 h. After incubation, 20 μl of
tetrazolium chloride (TTC; 0.04 mg/ml) was added to each micro-
plate. The color changes of TTC from colorless to red were accepted
10‐{[3‐(4‐Chlorophenyl)‐1,2‐oxazol‐5‐yl]methyl}‐2‐methylacridin‐9‐
one (4j)
Yellow solid; yield: 73%, mp = 240°C. IR (KBr): 3010 (m) (C–H), 2974
(w) (C–H), 1640 (s) (C═O), 1616 (m) (C═N), 1598 (s) (C═C) cm−1
.
1H NMR (300 MHz, CDCl3, 25°C, TMS): 8.62 (dd, J = 7.9, 1.6 Hz, 1H,
Ar–H), 8.39 (s, 1H, Ar–H), 7.74 (m, 3H, Ar–H), 7.57 (dd, J = 8.7,
2.3 Hz, 2H, Ar–H), 7.50–7.31 (m, 4H, Ar–H), 6.34 (s, 1H,