J. Yang et al.
Bioorganic Chemistry 114 (2021) 105043
1-(3-(4-hydroxyphenyl)-5-(4-(trifluoromethyl)phenyl)-4,5-dihydro-
160.38, 156.07, 142.86, 129.05, 127.57, 125.78, 98.17, 96.28, 92.02,
57.79, 56.02, 46.96, 22.15 . ESI-MS: m/z calcd for C18H18N2O4 (M + H+)
327.1, found 327.1.
1H-pyrazol-1-yl)ethan-1-one (compound 30)
White solid, yield: 57%. 1H NMR (400 MHz, DMSO‑d6) δ 10.00 (s,
1H), 7.66 (dd, J = 29.8, 8.1 Hz, 4H), 7.41 (d, J = 8.0 Hz, 2H), 6.84 (d, J
= 8.4 Hz, 2H), 5.60 (dd, J = 11.9, 4.7 Hz, 1H), 3.84 (dd, J = 18.0, 11.9
Hz, 1H), 3.12 (dd, J = 18.0, 4.7 Hz, 1H), 2.30 (s, 3H).13C NMR (101
MHz, DMSO‑d6) δ 167.61, 160.00, 154.65, 147.51, 128.89, 126.80,
125.99, 122.22, 115.98, 59.26, 42.38, 22.03 . ESI-MS: m/z calcd for
C18H15F3N2O2 (M + H+) 349.1, found 349.1.
1-(5-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-4-(tri-
fluoromethyl)phenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one (com-
pound 37)
White solid, yield: 44%. 1H NMR (400 MHz, DMSO‑d6) δ 10.72 (s,
1H), 8.92 (s, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.25 (d, J = 7.7 Hz, 2H), 6.80
(s, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 5.44 (dd, J =
11.6, 4.3 Hz, 1H), 3.92 (dd, J = 18.4, 11.9 Hz, 1H), 3.75 (s, 3H), 3.30 –
3.24 (m, 1H), 2.30 (s, 3H).13C NMR (101 MHz, DMSO‑d6) δ 167.72,
157.13, 154.33, 147.98, 146.19, 133.51, 130.43, 121.27, 117.95,
116.17, 115.86, 110.49, 59.22, 56.03, 44.41, 22.25 . ESI-MS: m/z calcd
for C19H17F3N2O4 (M + H+) 395.1, found 395.1.
1-(3-(2-hydroxy-4-methoxyphenyl)-5-(4-hydroxyphenyl)-4,5-dihy-
dro-1H-pyrazol-1-yl)ethan-1-one (compound 31)
White solid, yield: 73%. 1H NMR (400 MHz, DMSO‑d6) δ 7.47 (d, J =
8.6 Hz, 1H), 6.99 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 8.4 Hz, 2H), 6.58 –
6.44 (m, 2H), 5.38 (dd, J = 11.5, 3.9 Hz, 1H), 3.85 (dd, J = 18.2, 11.6
Hz, 1H), 3.77 (s, 3H), 3.21 (d, J = 14.2 Hz, 1H), 2.25 (s, 3H).13C NMR
(101 MHz, DMSO‑d6) δ 166.89, 162.66, 159.38, 157.03, 156.39, 132.91,
130.56, 127.10, 115.66, 109.72, 106.74, 101.66, 58.01, 55.73, 43.83,
22.24 . ESI-MS: m/z calcd for C18H18N2O4 (M + H+) 327.1, found 327.1.
1-(3-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxy-4-methox-
1-(3-(4-hydroxyphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyr-
azol-1-yl)ethan-1-one (compound 38)
White solid, yield: 55%. 1H NMR (400 MHz, DMSO‑d6) δ 9.98 (s, 1H),
8.17 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.84 (d, J = 8.2 Hz,
1H), 7.61 (h, J = 7.1 Hz, 4H), 7.44 (t, J = 7.7 Hz, 1H), 7.12 (d, J = 7.1
Hz, 1H), 6.81 (d, J = 8.5 Hz, 2H), 6.25 (dd, J = 11.6, 4.0 Hz, 1H), 4.05
(dd, J = 17.6, 11.9 Hz, 1H), 2.99 (dd, J = 17.7, 4.3 Hz, 1H), 2.40 (s,
3H).13C NMR (101 MHz, DMSO‑d6) δ 167.59, 159.93, 137.60, 134.14,
129.16, 128.83, 127.87, 126.74, 126.24, 125.94, 123.79, 115.96, 57.03,
42.47, 22.16 . ESI-MS: m/z calcd for C21H18N2O2 (M + H+) 331.1, found
331.1.
yphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one (compound 32)
White solid, yield: 74%. 1H NMR (400 MHz, DMSO‑d6) δ 10.38 (s,
1H), 8.91 (s, 1H), 7.46 (s, 1H), 6.74 (d, J = 36.6 Hz, 2H), 6.54 (d, J = 6.4
Hz, 3H), 5.39 (dd, J = 11.4, 3.7 Hz, 1H), 3.86 (dd, J = 18.1, 11.7 Hz,
1H), 3.76 (d, J = 15.7 Hz, 6H), 3.23 (dd, J = 18.2, 3.9 Hz, 1H), 2.27 (s,
3H).13C NMR (101 MHz, DMSO‑d6) δ 167.03, 162.67, 158.90, 156.37,
147.96, 146.15, 133.52, 130.69, 117.86, 115.86, 110.54, 107.02,
101.58, 58.24, 56.04, 55.79, 43.74, 22.26 . ESI-MS: m/z calcd for
General procedure for synthesis of compound 39–40
Compound 39–40 were synthesized as follow: (E)-1-(2-hydroxy-4-
methoxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (0.37 mmol) and
urea (3.71 mmol) were added in hydrochloric acid 1,4-dioxane (4 mL).
The mixture was heated and refluxed for 12 h. After the reaction,
saturated aqueous solution of NaHCO3 was added in to adjust pH to 7.
The mixture liquor were extracted with ethyl acetate in three times, 10
mL for each. The organic layer was dried with anhydrous Na2SO4 and
concentrated under reduced pressure. The residue was purified on a
silica gel column (petroleum ether/ethyl acetate elute) to provide
compound.
C
19H20N2O5 (M + H+) 357.1, found 357.1.
1-(5-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-4-methox-
yphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one (compound 33)
White solid, yield: 68%. 1H NMR (400 MHz, DMSO‑d6) δ 10.38 (s,
1H), 8.95 (d, J = 27.1 Hz, 1H), 7.45 (d, J = 8.3 Hz, 1H), 6.89 – 6.76 (m,
1H), 6.71 (d, J = 8.0 Hz, 1H), 6.63 – 6.50 (m, 3H), 5.51 – 5.23 (m, 1H),
3.87 (dd, J = 13.7, 4.9 Hz, 1H), 3.76 (d, J = 14.9 Hz, 6H), 3.29 – 3.15 (m,
1H), 2.27 (s, 3H).13C NMR (101 MHz, DMSO‑d6) δ 167.03, 162.70,
158.91, 156.37, 133.52, 130.69, 117.86, 116.64, 115.87, 113.02,
110.54, 109.58, 107.01, 101.58, 58.24, 56.04, 55.78, 43.72, 22.26 . ESI-
MS: m/z calcd for C19H20N2O5 (M + H+) 357.1, found 357.1.
1-(3-(2-hydroxy-4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-
dihydro-1H-pyrazol-1-yl)ethan-1-one(compound 34)
4-(2-hydroxy-4-methoxyphenyl)-6-(3-hydroxy-4-methoxyphenyl)-
5,6-dihydropyrimidin-2(1H)-one (compound 39)
White solid, yield: 42%. 1H NMR (400 MHz, Chloroform-d) δ 7.90 (d,
J = 8.8 Hz, 1H), 7.00 (d, J = 14.4 Hz, 3H), 6.69 – 6.60 (m, 1H), 6.52 (s,
1H), 5.73 (d, J = 8.6 Hz, 1H), 5.41 (dd, J = 13.3, 2.3 Hz, 1H), 3.96 (s,
3H), 3.86 (s, 3H), 3.08 (dd, J = 16.8, 13.4 Hz, 1H), 2.83 (dd, J = 16.8,
2.7 Hz, 1H).13C NMR (101 MHz, Chloroform-d) δ 190.69, 166.11,
163.47, 146.68, 146.09, 130.60, 128.70, 119.57, 114.76, 114.47,
110.16, 108.74, 100.88, 80.05, 55.95, 55.59, 44.28 . ESI-MS: m/z calcd
for C18H18N2O5 (M + H+) 343.1, found 343.1.
White solid, yield: 82%. 1H NMR (400 MHz, DMSO‑d6) δ 10.36 (s,
1H), 7.45 (d, J = 9.3 Hz, 1H), 6.60 – 6.45 (m, 4H), 5.42 (dd, J = 11.6,
4.6 Hz, 1H), 3.93 – 3.85 (m, 1H), 3.78 (s, 3H), 3.74 (s, 6H), 3.64 (s, 3H),
3.25 (dd, J = 18.2, 4.7 Hz, 1H), 2.30 (s, 3H).13C NMR (101 MHz,
DMSO‑d6) δ 167.33, 162.69, 158.88, 156.26, 153.46, 138.39, 136.97,
130.70, 109.60, 107.00, 102.98, 101.58, 60.32, 58.69, 56.29, 55.78,
43.85, 22.23 . ESI-MS: m/z calcd for C21H24N2O6 (M + H+) 401.1, found
401.1.
4-(2-hydroxy-4-methoxyphenyl)-6-(4-hydroxyphenyl)-5,6-dihy-
dropyrimidin-2(1H)-one (compound 40)
1-(3-([1,1′-biphenyl]-4-yl)-5-(4-hydroxy-3-methoxyphenyl)-4,5-
dihydro-1H-pyrazol-1-yl)ethan-1-one (compound 35)
White solid, yield: 44%. 1H NMR (400 MHz, DMSO‑d6) δ 9.57 (s, 1H),
7.72 (d, J = 8.8 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.5 Hz,
2H), 6.66 (dd, J = 8.8, 2.3 Hz, 1H), 6.60 (d, J = 2.2 Hz, 1H), 5.50 (dd, J
= 13.0, 2.5 Hz, 1H), 3.81 (s, 3H), 3.18 (dd, J = 16.8, 13.0 Hz, 1H), 2.67
(dd, J = 16.8, 2.9 Hz, 1H).13C NMR (101 MHz, DMSO‑d6) δ 190.76,
166.02, 163.65, 158.06, 129.53, 128.70, 128.38, 115.53, 114.82,
110.24, 101.38, 79.60, 56.20, 43.50. ESI-MS: m/z calcd for C17H16N2O4
(M + H+) 313.1, found 313.1.
White solid, yield: 72%. 1H NMR (400 MHz, DMSO‑d6) δ 8.92 (s, 1H),
7.87 (d, J = 8.1 Hz, 2H), 7.75 (dd, J = 19.5, 7.9 Hz, 4H), 7.50 (t, J = 7.5
Hz, 2H), 7.41 (t, J = 7.2 Hz, 1H), 6.79 (s, 1H), 6.72 (d, J = 8.1 Hz, 1H),
6.57 (d, J = 7.9 Hz, 1H), 5.48 (dd, J = 11.5, 4.1 Hz, 1H), 3.83 (dd, J =
17.9, 11.8 Hz, 1H), 3.75 (s, 3H), 3.17 (dd, J = 17.9, 4.2 Hz, 1H), 2.33 (s,
3H).13C NMR (101 MHz, DMSO‑d6) δ 167.76, 154.23, 133.79, 129.44,
128.36, 127.62, 127.33, 127.08, 117.90, 115.89, 110.51, 60.16, 56.02,
42.53, 22.21 . ESI-MS: m/z calcd for C24H22N2O3 (M + H+) 387.1, found
387.1.
4.2. Biology assays
1-(3-(2,4-dihydroxy-6-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-
pyrazol-1-yl)ethan-1-one (compound 36)
4.2.1. Preparation of peritoneal macrophage
Peritoneal macrophage were obtained by peritoneal lavage from 6 to
8 week old C57BL/6 mice (purchased from the Laboratory Animal
Center of Southern Medical University) 4d after i.p injection of 3 mL 4%
sterile thioglycollate. Cells were washed with PBS three times and
cultured in RPMI 1640 [supplemented with 10% FBS, penicillin (100 U/
ml), and streptomycin (100 mg/ml)]. The cells were used in subsequent
White solid, yield: 44%. 1H NMR (400 MHz, DMSO‑d6) δ 11.19 (s,
1H), 10.08 (s, 1H), 7.34 (t, J = 7.3 Hz, 2H), 7.23 (dd, J = 24.6, 7.3 Hz,
3H), 6.01 (d, J = 4.2 Hz, 2H), 5.41 (dd, J = 11.6, 3.9 Hz, 1H), 3.95 (dd, J
= 18.8, 11.7 Hz, 1H), 3.70 (s, 3H), 3.21 (dd, J = 18.8, 4.1 Hz, 1H), 2.24
(s, 3H).13C NMR (101 MHz, DMSO‑d6) δ 166.67, 161.68, 160.98,
11