Carboxylated Chalcones
J ournal of Medicinal Chemistry, 1997, Vol. 40, No. 7 1087
petroleum ether (40-60)/acetic acid (10:10:1); recrystallisation
129.26 (t, C5), 130.22 (t, C7-quinoline), 132.92 (t, C4′ or C6′),
133.80 (t, C4′ or C6′), 134.66 (t, Câ), 134.98 (q), 136.59 (q),
1
from methanol; yield 5%; mp 226.0-228.2 °C; H NMR (400
3
MHz, 300 K, DMSO) δ 7.24 (d, 1H, J ) 8.7 Hz, H3′), 7.54-
137.55 (t, C4-quinoline), 143.23 (t, C-olefin), 145.67 (q), 154.68
7.59 (m, 2H, H5, H6-quinoline), 7.66 (d, 1H, 3J ) 16.4 Hz, HR),
7.75-7.79 (m, 1H, H7-quinoline), 7.85-7.91 (m, 3H, H4, H6,
H3-quinoline), 7.89 (d, 1H, 3J ) 15.7 Hz, PhCHdCH-quino-
(q), 159.51 (q), 169.41 (q), 189.90 (q); MS m/ z 455 (M+ for
-
35
Cl). Anal. (C27H18ClNO4) C, H, N, Cl.
5′-Br om o-3′-car boxy-2′-h ydr oxy-3-[2-(2-qu in olin yl)eth e-
n yl)]ch a lcon e (52): recrystallization from DMF; yield 34%;
mp 264.1-266.0 °C; 1H NMR (400 MHz, 335 K, DMSO) δ 7.53
(t, 1H, 3J ) 7.8 Hz, H5), 7.59 (d, 1H, 3J ) 16.4 Hz, HR), 7.58-
7.62 (m, 1H, H6-quinoline), 7.69 (d, 1H, 3J ) 15.9 Hz,
PhCHdCH-quinoline), 7.75-7.82 (m, 3H, H4, H6, H7-quino-
3
3
line), 7.90 (d, 1H, J ) 16.4 Hz, Hâ), 7.96 (d, 1H, J ) 7.7 Hz,
H5-quinoline), 8.00 (d, 1H, 3J ) 8.5 Hz, H8-quinoline), 8.05
3
3
(d, 1H, J ) 15.6 Hz, PhCHdCH-quinoline), 8.17 (dd, 1H, J
) 8.7 Hz, 4J ) 2.1 Hz, H4′), 8.30 (s, 1H, H2), 8.38 (d, 1H, 3J )
8.5 Hz, H4-quinoline), 8.66 (d, 1H, 4J ) 2.1 Hz, H6′), 12.39
(br s, 1H, ArOH); 13C NMR (50 MHz, DMSO) δ 115.73 (q),
118.81 (t), 119.99 (t), 122.83 (q), 123.57 (t), 126.34 (t), 127.00
(q), 127.48 (t), 127.86 (t), 128.66 (t), 129.31 (t), 129.52 (t),
129.60 (t), 129.80 (t), 129.86 (t), 129.95 (t), 133.33 (t), 133.81
(t), 135.04 (q), 136.64 (t), 137.02 (q), 144.53 (t), 147.65 (q),
154.97 (q), 155.55 (q), 162.28 (q), 192.74 (q); MS m/ z 445 (M+).
Anal. Calcd for C27H19N5O2‚0.6HCl: C, 69.39; H, 4.23; N,
14.98. Found: C, 69.17; H, 4.27; N, 14.22.
3
3
line), 7.77 (d, 1H, J ) 16.4 Hz, Hâ), 7.92 (d, 1H, J ) 16 Hz,
PhCHdCH-quinoline), 7.93 (d, 1H, 3J ) 8.5 Hz, H3-quinoline),
7.97-7.99 (m, 1H, H5-quinoline), 7.98 (d, 1H, 4J ) 2.7 Hz, H4′
3
or H6′), 8.03 (d, 1H, J ) 8.5 Hz, H8-quinoline), 8.07 (d, 1H,
4J ) 2.7 Hz, H4′ or H6′), 8.14 (s, 1H, H2), 8.43 (d, 1H, 3J ) 8.5
Hz, H4-quinoline); 13C NMR (100 MHz, 328 K, DMSO) δ 108.63
(q), 118.28 (q), 119.63 (t), 126.06 (t), 126.26 (t), 126.84 (q),
127.16 (t), 127.44 (t), 127.58 (t), 128.38 (t), 128.77 (t), 128.82
(q), 129.08 (t), 129.23 (t), 130.03 (t), 134.29 (t), 135.00 (q),
135.78 (t), 136.50 (t), 136.65 (q), 137.22 (t), 143.09 (t), 146.24
(q), 154.80 (q), 160.21 (q), 169.29 (q), 189.80 (q); MS m/ z 499
(M+ for 79Br). Anal. Calcd for C27H18NO4: C, 64.81; H, 3.63;
N, 2.80; Br, 15.97. Found: C, 64.55; H, 3.60; N, 2.93; Br, 15.49.
3′-Ca r b oxy-2′-h yd r oxy-5′-m et h yl-3-[2-(2-q u in olin yl)-
eth en yl]ch a lcon e (53): recrystallization from DMF; yield
69%; mp 163.2-163.7 °C; 1H NMR (400 MHz, 335 K, DMSO)
δ 2.67 (s, 3H, ArCH3), 7.72 (t, 1H, 3J ) 7.7 Hz, H5), 7.82-8.02
(m, 8H, H6-quinoline, H3-quinoline, HR, Hâ, 2H-olefin, H4,
H6), 8.06-8.09 (m, 1H, H7-quinoline), 8.06-8.09 (m, 1H, H7-
quinoline), 8.15-8.31 (m, 4H, H4′, H6′, H5-quinoline, H2), 8.83
(d, 1H, 3J ) 8.6 Hz, H4-quinoline); 13C NMR (50 MHz, DMSO)
δ 19.37 (p), 119.35 (t), 124.21 (t), 124.56 (t), 126.00 (t), 126.22
(q), 126.77 (q), 127.37 (t), 127.51 (t), 127.58 (q), 128.02 (t),
129.21 (t), 129.42 (t), 129.69 (t), 131.76 (t), 134.55 (t), 134.96
(q), 135.79 (t), 137.83 (t), 140.37 (t), 142.29 (t), 15;3.39 (q),
153.48 (q), 158.17 (q), 158.18 (q), 170.89 (q), 190.76 (q); MS
m/ z 435 (M+). Anal. Calcd for C28H21NO4‚0.8HCl: C, 72.38;
H, 4.73; N, 3.01. Found: C, 72.78; H, 4.94; N, 3.57.
3′-Ca r boxy-2′-h yd r oxy-3-[2-(2-qu in olin yl)eth en yl]ch a l-
con e (49): column chromatography using ethyl acetate/
petroleum ether (40-60)/acetic acid (10:10:1); recrystallization
from DMF; yield 33%; mp 237.2-240.2 °C; 1H NMR (400 MHz,
3
3
300 K, DMSO) δ 7.07 (t, 1H, J ) 7.7 Hz, H5′), 7.52 (t, 1H, J
) 7.7 Hz, H5), 7.57-7.61 (m, 1H, H6-quinoline), 7.63 (d, 1H,
3J ) 16.4 Hz, HR), 7.70 (d, 1H, 3J ) 15.9 Hz, PhCHdCH-
quinoline), 7.75-7.81 (m, 3H, H4, H6, H7-quinoline), 7.81 (d,
1H, 3J ) 15.9 Hz, PhCHdCH-quinoline), 7.90 (d, 1H, 3J ) 16.2
Hz, Hâ), 7.91 (d, 1H, 3J ) 8.6 Hz, H3-quinoline), 7.96 (dd, 1H,
3J ) 7.7 Hz, 4J ) 1.8 Hz, H4′/6′), 7.97 (d, 1H, 3J ) 8.2 Hz,
H5-quinoline), 8.01 (d, 1H, 3J ) 8.3 Hz, H8-quinoline), 8.04
(dd, 1H, 3J ) 7.7 Hz, 4J ) 1.8 Hz, H4′/6′), 8.20 (s, 1H, H2),
3
8.40 (d, 1H, J ) 8.6 Hz, H4-quinoline); 13C NMR (100 MHz,
300 K, DMSO) δ 115.38 (q), 118.72 (t, C5′), 119.94 (t, C3-
quinoline), 126.20 (t, C-olefin), 126.36 (t, C6-quinoline), 126.89
(q), 127.04 (q), 127.23 (t, C2), 127.82 (t, C5-quinoline), 128.28
(t, C8-quinoline), 129.05 (t, C4/6), 129.24 (t, C-olefin), 129.39
(t, C4/6), 129.50 (t, C5), 130.02 (t), C7-quinoline), 133.74 (t,
C-olefin), 134.65 (t, C4′/6′), 135.14 (q), 135.60 (t, C4′/6′), 136.88
(q), 136.92 (t, C4-quinoline), 142.99 (t, C-olefin), 147.19 (q),
5′-ter t-Bu tyl-3′-ca r boxy-2′-h yd r oxy-3-[2-(2-qu in olin yl)-
eth en yl)]ch a lcon e (54): column chromatography using ethyl
acetate/petroleum ether (40-60)/acetic acid (10:10:1); recrys-
tallization from methanol; 1H NMR (400 MHz, 335 K, DMSO)
δ 1.29 (s, 9H, C(CH3)3), 7.50 (t, 1H, J ) 7.5 Hz, H5), 7.53-
7.60 (m, 1H, H6-quinoline), 7.55 (d, 1H, J ) 16.4 Hz, HR), 7.62
(d, 1H, J ) 16.0 Hz, H-olefin), 7.66-7.68 (d, 1H, H3-quinoline),
7.71 (d, 1H, J ) 2.9 Hz, H4′ ïF Η6′), 7.73-7.79 (m, 2H, H7-
quinoline, H4 or H6), 7.86-7.95 (m, 3H, H4 or H6, H5-
quinoline, Hâ), 8.01 (br s, 1H, H2), 8.01-8.03 (m, 1H, H8-
quinoline), 8.05 (d, 1H, J ) 2.9 Hz, H4′ or H6′), 8.08 (d, 1H, J
) 16.0 Hz, H-olefin), 8.34 (d, 1H, J ) 8.4 Hz, H4-quinoline),
11.55 (s, 1H, ArOH); 13C NMR (50 MHz, DMSO) δ 31.08 (p),
33.37 (q), 119.75 (t), 120.24 (q), 121.59 (t), 125.57 (q), 126.05
(t), 126.84 (q), 127.08 (t), 127.59 (t), 127.98 (t), 128.29 (t),
128.39 (t), 128.45 (t), 128.67 (t), 129.30 (t), 129.48 (t), 129.65
(t), 131.59 (t), 133.32 (t), 135.64 (q), 136.33 (t), 136.73 (q),
139.53 (t), 147.40 (q), 155.28 (q), 163.19 (q), 171.05 (q), 190.50
(q); MS m/ z 477 (M+). Anal. (C31H27NO4‚0.9HCl) C, H, N.
5′-Ch lor o-3′-cya n o-2′-h yd r oxy-3-[2-(2-qu in olin yl)eth e-
n yl]ch a lcon e (55): recrystallization from DMF; yield 29%; mp
231.6-233.3 °C; 1H NMR (400 MHz, DMSO) δ 7.54-7.59 (m,
155.29 (q), 160.76 (q), 171.09 (q), 191.38 (q). Anal. (C27H19
NO4) C, H, N.
3′-Car boxy-5′-flu or o-2′-h ydr oxy-3-[2-(2-qu in olin yl)eth e-
n yl]ch a lcon e (50): recrystallization from DMF; yield 50%; mp
275.7-277.1 °C; 1H NMR (400 MHz, 335 K, DMSO) δ 7.53 (t,
-
3
3
1H, J ) 7.7 Hz, H5), 7.60 (d, 1H, J ) 16.5 Hz, HR), 7.58-
7.62 (m, 1H, H6-quinoline), 7.71 (d, 1H, 3J ) 15.7 Hz, H-olefin),
7.76-7.91 (m, 5H, H-olefin, H4, H6, H7-quinoline), 7.80 (d,
3
1H, J ) 16.5 Hz, Hâ), 7.89-7.93 (m, 2H, H4′, H6′), 7.97 (d,
3
3
1H, J ) 8.1 Hz, H5-quinoline), 8.03 (d, 1H, J ) 8.3 Hz, H8-
quinoline), 8.16 (s, 1H, H2), 8.42 (d, 1H, 3J ) 8.5 Hz,
H4-quinoline); 13C NMR (100 MHz, 335 K, DMSO) δ 116.68
3
2
(q, J CF ) 8.5 Hz), 119.63 (t, C3-quinoline), 119.81 (t, J CF
)
2
24.5 Hz, C4′/6′), 121.13 (t, J CF ) 24.4 Hz, C4′/6′), 125.81 (t),
126.18 (t), 126.83 (q), 127.11 (t), 127.54 (t), 127.64 (t), 128.22
(q), 128.62 (t), 128.75 (t), 129.12 (t), 129.22 (t), 129.90 (t),
134.00 (t), 134.93 (q), 136.69 (q), 136.99 (t), 143.33 (t), 146.48
1
(q), 153.40 (q, J CF ) 239.2 Hz), 154 86 (q), 156.89 (q), 169.52
(q), 190.01 (q); MS m/ z 439 (M+). Anal. (C27H18FNO4‚0.3H2O)
C, H, N, F.
3′-Car boxy-5′-ch lor o-2′-h ydr oxy-3-[2-(2-qu in olin yl)eth e-
n yl)]ch a lcon e (51): recrystallization from DMF; yield 48%;
mp 278.5-280.9 °C; 1H NMR (400 MHz, 335 K, DMSO) δ 7.52
(t, 1H, 3J ) 7.7 Hz, H5), 7.59 (d, 1H, 3J ) 16.2 Hz, HR), 7.59-
7.63 (m, 1H, H6-quinoline), 7.70 (d, 1H, 3J ) 15.9 Hz,
PhCHdCH-quinoline), 7.76 (d, 1H, 3J ) 15.9 Hz, PhCHdCH-
3
2H, H5, H6-quinoline), 7.66 (d, 1H, J ) 16.3 Hz, HR), 7.75-
7.78 (m, 1H, H7-quinoline), 7.85-8.02 (m, 7H, H3-quinoline,
H5-quinoline, H8-quinoline, Hâ, H-olefin, H4, H6), 8.20 (d, 1H,
3J ) 15.5 Hz, H-olefin), 8.23 (d, 1H, 4J ) 2.0 Hz, H4′/H6′),
8.37-8.39 (m, 2H, H2, H4-quinoline), 8.78 (d, 1H, 4J ) 2.0
Hz, H4′/6′); 13C NMR (50 MHz, DMSO) δ 102.88 (q), 114.37
(q), 119.79 (t), 120.88 (t), 122.06 (q), 122.80 (q), 126.13 (t),
126.89 (q), 127.52 (t), 127.43 (t), 129.33 (t), 9.73 (t), 130.01 (t),
130.18 (t), 133.05 (t), 134.53 (q), 135.09 (t), 136.45 (t), 136.88
(q), 138.66 (t), 146.75 (t), 147.42 (q), 155.18 (q), 162.44 (q),
192.35 (q). Anal. (C27H17ClN2O2‚0.3H2O) C, H, N, Cl.
3
quinoline), 7.76 (d, 1H, J ) 8.0 Hz, H4 or H6), 7.79-7.83 (m,
3
1H, H7-quinoline), 7.81 (d, 1H, J ) 8.3 Hz, H4 or H6), 7.89
(d, 1H, 4J ) 2.8 Hz, H4′ or H6′), 7.94 (d, 1H, 3J ) 16.7 Hz,
Hâ), 7.95 (d, 1H, 4J ) 2.8 Hz, H4′ or H6′), 7.96 (d, 1H, 3J )
8.6 Hz, H3-quinoline), 7.99 (d, 1H, 3J ) 7.5 Hz, H5-quinoline),
3
8.04 (d, 1H, J ) 8.3 Hz, H8-quinoline), 8.14 (s, 1H, H2), 8.46
3
(d, 1H, J ) 8.6 Hz, H4-quinoline); 13C NMR (100 MHz, 335
5′-Ch lor o-2′-h yd r oxy-3-[-2-(2-qu in olin yl)eth en yl)]-3′-(5-
tetr a zolyl)ch a lcon e (56): column chromatography using
dichloromethane/methanol (10:1); yield 10%; mp >300 °C; 1H
NMR (400 MHz, room temperature DMSO) δ 7.51-7.58 (m,
K, DMSO) δ 117.63 (q), 119.62 (t, C3-quinoline), 121.72 (q),
125.99 (t, C-olefin), 126.38 (t, C6-quinoline), 126.85 (q), 127.13
(t, C8-quinoline), 127.20 (t, C2), 127.63 (t, C5-quinoline), 128.03
(t, CR), 128.36 (q), 128.88 (t, C4 or C6), 129.15 (t, C4 or C6),
3
2H, H5, H6-quinoline), 7.63 (d, 1H, J ) 16.4 Hz, Ha˚), 7.74-