JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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derivatives were synthesized. Their anti-inflammatory activity was 113.6, 69.1. HRMS C30H23N3O5, m/z: (calcd.), 506.1708 [M þ H]þ
also evaluated.
(505.5207).
Experimental section
5c
(1E,3E,4E)-1–(4-chlorophenyl)-5–(2-(3-methylbenzyloxy)phenyl)penta-
1,4-dien-3-one O-nicotinoyl oxime, Yellow solids, yield, 48.2%, m.p.
1 2 7–129 ꢁC; IR (KBr, cmꢂ1) ꢀmax: 3101, 2837, 1749, 1590, 1489,
1419, 1343, 1236, 1081, 1015, 971, 915, 813, 777, 758. 1H NMR
(500 MHz, DMSO-d6, ppm) d 9.14 (dd, J1 ¼ 2.2 Hz, J2 ¼ 0.8 Hz, 1H,
PyH), 8.81 (dd, J1 ¼ 4.8 Hz, J2 ¼ 1.7 Hz, 1H, PyH), 8.30 (d, J ¼ 6.4 Hz,
1H, PyH), 7.84–7.81(m, 1H, PyH), 7.73–7.70 (m, 2H, ArH), 7.66–7.59
(m, 2H, ArH), 7.57–7.51 (m, 1H, ArH), 7.47–7.44 (m, 2H, ArH), 7.38
(d, J ¼ 10.1 Hz, 1H, ArH), 7.37 (d, J ¼ 5.9 Hz,1H, ArH), 7.26–7.22 (m,
1H, ArH), 7.19–7.13 (m, 3H, Ar-C ¼ CH, ArH), 7.02 (dd, J1 ¼ 11.4 Hz,
J2 ¼ 9.8 Hz, 2H, Ar-CH¼, Ar-C ¼ CH), 6.95 (d, J ¼ 5.6 Hz, 1H, Ar-CH¼),
5.13 (s, 2H, CH2), 2.12 (s, 3H, CH3).13 C NMR (125 MHz, DMSO-d6,
ppm) d 162.6, 157.4, 154.5, 150.6, 138.1, 137.7, 137.5, 137.1, 135.0,
134.3, 132.0, 129.9, 129.4, 128.8, 128.3, 125.1, 124.8, 124.6, 124.4,
121.9, 121.7, 117.5, 113.8, 70.4, 21.3. HRMS C31H25ClN2O3, m/z:
(calcd.), 509.8852 [M þ H]þ (508.9948).
Chemistry
The reactions were monitored by thin layer chromatography (TLC)
on pre-coated silica GF254 plates. Melting points were determined
on a XT4MP apparatus (Taike Corp., Beijing, China), and are uncor-
rected. The infrared spectra were determined by IR-960 (Shimadzu,
Japan). 1H and 13 C NMR spectra were recorded on a Brucker AM-
500 (500 MHz) spectrometer with CDCl3 or DMSO-d6 as the solvent.
High-resolution electron impact mass spectra (HR-MS) were
recorded under electron impact using a MicroMass GCT CA 055
instrument, USA.
General procedure for the synthesis of title compound 5a
(1E,3E,4E)-1–(4-chlorophenyl)-5–(2-(3-methylbenzyloxy)phenyl)-
penta-1,4-dien-3-one oxime (compound 4a) (10 mmol) and
potassium carbonate (15 mmol) were dissolved in acetone (10 ml)
at room temperature. After 10 min, benzoyl chloride (12 mmol)
was slowly drip under the ice bath. The mixture was reacted for
5 h at 0–5 ꢁC.
The reaction was monitored by TLC (PE/EA ¼3/1), a large yel-
low solid was obtained. The mixture was cooled and collected by
filtration, then the crude residue was purified by recrystallization
with ethyl acetate to give title compound 5a (Scheme 1) as yellow
solids. According to the same way, compounds 5b–5k were
synthesized.
5d
(1E,3Z,4E)-1–(2-(4-nitrobenzyloxy)phenyl)-5-(pyridin-2-yl)penta-1,4-
dien-3-one O-cinnamoyl oxime, Light yellow solids, yield, 75.0%,
m.p0.1 6 2–164 ꢁC; IR (KBr, cmꢂ1) ꢀmax: 3039, 2853, 1749, 1518,
1487, 1451, 1347, 1301, 1242, 1119, 976, 893, 760. 1H NMR
(500 MHz, CDCl3, ppm) d 8.65 (d, J ¼ 6.1 Hz, 1H, PyH), 8.07 (dd,
J1¼13.1 Hz, J2 ¼ 5.2 Hz, 2H, PyH), 7.88 (d, J ¼ 16.0 Hz, 1H, PyH),
7.77–7.69 (m, 3H, Py-CH¼, ArH), 7.63–7.53 (m, 5H, ArH, Ar-CH¼),
7.47–7.33 (m, 7H, ArH), 7.27 (d, J ¼ 8.7 Hz, 1H, ArH), 7.09 (d,
J ¼ 9.6 Hz, 1H, CH ¼ C), 6.93 (d, J ¼ 8.7 Hz, 1H, Py-C ¼ CH), 6.61 (d,
J ¼ 6.1 Hz, 1H, Ar-C ¼ CH), 5.25 (s, 2H, CH2). 13 C NMR (125 MHz,
CDCl3, ppm) d 164.7, 160.8, 156.4, 154.2, 150.1, 147.6, 146.7, 144.0,
137.9, 136.9, 135.2, 134.3, 131.3, 130.8, 129.1, 128.4, 127.8, 127.4,
125.0, 124.8, 124.0, 123.6, 123.2, 121.9, 117.3, 115.6, 112.5, 69.1.
HRMS C32H25N3O5, m/z: (calcd.), 532.1865 [M þ H]þ (531.5580).
5a
(1E,3E,4E)-1–(4-chlorophenyl)-5–(2-(3-methylbenzyloxy)phenyl)penta-
1,4-dien-3-one O-benzoyl oxime, Yellow solids, yield, 65.8%, m.p. 1
4 3–145 ꢁC; IR (KBr, cmꢂ1) ꢀmax: 3058, 2851, 1745, 1613, 1593,
1536, 1490, 1452, 1237, 1173, 1053, 1023, 916, 814, 757. 1H NMR
(500 MHz, DMSO-d6, ppm) d 7.99 (dt, J ¼ 7.8, 3.8 Hz, 2H, ArH), 7.78
(dd, J1 ¼ 7.7 Hz, J2 ¼ 1.5 Hz, 1H, PyH), 7.73–7.68 (m, 2H, ArH), 7.65
(d, J ¼ 9.8 Hz, 1H, Ar-CH¼), 7.57 (dd, J1¼16.2 Hz, J2¼10.1 Hz, 2H,
ArH), 7.52–7.47 (m, 2H, ArH), 7.44 (d, J ¼ 8.5 Hz, 2H, PyH), 7.37 (d,
J ¼ 12.5 Hz, 1H, Py-CH¼), 7.34–7.30 (m, 1H, ArH), 7.23 (d,
J ¼ 16.2 Hz, 1H, PyH), 7.19–7.13 (m, 3H, ArH), 7.05–6.96 (m, 3H, Ar-
C ¼ CH, Py-C ¼ CH, ArH), 5.16 (s, 2H, CH2), 2.08 (s, 3H, CH3). 13 C
NMR (125 MHz, DMSO-d6, ppm) d 167.9, 163.4, 162.2, 157.4, 155.4,
138.1, 137.4, 137.2, 136.8, 135.0, 134.3, 131.9, 129.8, 129.5, 129.2,
128.9, 128.2, 124.8, 124.5, 122.1, 121.7, 117.6, 113.8, 70.3, 21.3.
5e
(1E,3Z,4E)-1–(4-(3-fluorobenzyloxy)phenyl)-5-(pyridin-2-yl)penta-1,4-
dien-3-one O-cinnamoyl oxime, Light yellow solids, yield, 69.8%,
m.p0.1 4 2–144 ꢁC; IR (KBr, cmꢂ1) ꢀmax: 3087, 2951, 1734, 1601,
1508, 1470, 1430, 1378, 1304, 1239, 1175, 1112, 977, 808, 781, 762.
1H NMR (500 MHz, CDCl3, ppm) d 8.67 (d, J ¼ 25.6 Hz, 1H, PyH),
7.90 (d, J ¼ 15.9 Hz, 1H, ArH), 7.70 (t, J ¼ 7.5 Hz, 1H, PyH), 7.56 (m,
5H, Ar-CH¼, Py-CH¼, ArH), 7.45 (m, 7H, PyH, ArH), 7.31 (m, 4H,
ArH), 7.23 (d, J ¼ 7.9 Hz, 1H, Ar-C ¼ CH), 6.98 (m, 2H, Py-C ¼ CH,
ArH), 6.65 (d, J ¼ 16.0 Hz, 1H, Ar-C ¼ CH), 5.07 (s, 2H, CH2). 13 C
NMR (125 MHz, CDCl3, ppm) d 164.8, 160.3, 159.9, 154.2, 149.9,
146.6, 140.0, 138.7, 137.3, 136.9, 134.7, 134.4, 130.8, 130.1, 129.5,
129.1, 128.8, 128.4, 127.5, 125.5, 124.4, 123.5, 115.7, 115.3, 114.9,
69.3. HRMS C32H25FN2O3, m/z: (calcd.), 527.6256 [M þ Na]þ
(504.5509).
5b
(1E,3Z,4E)-1–(2-(4-nitrobenzyloxy)phenyl)-5-(pyridin-2-yl)penta-1,4-
dien-3-one O-benzoyl oxime, Light yellow solids, yield, 61.2%,
m.p. 1 8 4–86 ꢁC; IR (KBr, cmꢂ1) ꢀmax: 3061, 3005, 2857, 1740,
1598, 1520, 1485, 1452, 1347, 1308, 1239, 1173, 1080, 1060,
1025, 971, 920, 833, 780, 748. 1H NMR (500 MHz, DMSO-d6,
ppm) d 8.84 (d, J ¼ 5.2 Hz, 1H, PyH), 8.36 (t, J ¼ 7.3 Hz, 1H, ArH),
8.27 (d, J ¼ 7.7 Hz, 1H, ArH), 8.12–8.00 (m, 5H, ArH), 7.79 (m, 8H,
ArH, PyH), 7.55–7.49 (m, 2H, Ar-CH¼, Py-CH¼), 7.48–7.42
(m, 1H, PyH), 7.23 (d, J ¼ 8.3 Hz 1H, Ar-C ¼ CH), 7.13
5f
(1E,3Z,4E)-1–(4-(3-fluorobenzyloxy)phenyl)-5-(pyridin-2-yl)penta-1,4-
dien-3-one O-4-fluorobenzoyl oxime, Yellow solids, yield, 69.2%,
m.p0.1 5 3–155 ꢁC; IR (KBr, cmꢂ1) ꢀmax: 3089, 3003, 2851, 1731,
(d, J ¼ 7.4 Hz, 1H, Py-C ¼ CH), 5.43 (s, 2H, CH2).13
C NMR
(125 MHz, DMSO-d6, ppm) d 163.2, 160.9, 157.1, 150.6, 147.3, 1586, 1513, 1474, 1426, 1272, 1171, 1069, 1011, 945, 907, 843, 746.
145.5, 145.1, 143.0, 137.5, 134.2, 132.1, 130.1, 129.7, 129.4, 1H NMR (500 MHz, DMSO-d6, ppm) d 8.73 (d, J ¼ 7.2 Hz,1H, PyH),
128.7, 128.4, 125.9, 125.5, 124.4, 123.9, 123.1, 121.9, 117.6, 8.24–8.11 (m, 3H, ArH), 8.07 (d, J ¼ 8.5 Hz, 1H, PyH), 7.77 (m, 3H,