Month 2018
Design, Synthesis, and Antimycobacterial Activities of Diethylene Glycol
Tethered Moxifloxacin–Isatin Hybrids
1
1
-Cyclopropyl-6-fluoro-7-((4aR,7aR)-1-(2-(2-(3-
yield: 15%. H NMR (400 MHz, DMSO-d ) δ 0.89–1.59
(
2
8
6
(
hydroxyimino)-5-methyl-2-oxoindolin-1-yl)ethoxy)ethyl)
hexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl)-8-methoxy-4-
oxo-1,4-dihydroquinoline-3-carboxylic acid (5e).
yellow solid, yield: 23%. H NMR (400 MHz, DMSO-d )
m, 8H), 2.14–2.32 (m, 2H), 2.76–2.79 (m, 1H),
.99–3.01 (m, 1H), 3.12–3.27 (m, 3H), 3.50–3.84 (m,
H), 3.87 (t, 2H), 4.11–4.15 (m, 4H), 4.21 (t, 2H), 7.20
t, 1H, Ar–H), 7.45–7.50 (m, 2H, Ar–H), 7.65 (d, 1H,
Ar–H), 8.66 (1H, s, C2-H). ESI-MS m/z: 666 [M + H] .
Elemental Anal. Calcd (%) for C H F N O : C, 61.35;
Light
1
6
(
δ 0.94–1.56 (m, 8H), 2.12–2.35 (m, 5H), 2.74–2.76 (m,
+
1
8
7
(
1
H), 2.99–3.00 (m, 1H), 3.15–3.30 (m, 3H), 3.48–3.80 (m,
H), 3.88 (t, 2H), 4.11–4.12 (m, 1H), 4.20 (t, 2H),
.04–7.07 (m, 1H, Ar–H), 7.33 (s, 1H, Ar–H), 7.39–7.41
m, 1H, Ar–H), 7.94 (s, 1H, Ar–H), 8.62 (1H, s, C2-H),
3.48 (1H, brs, NOH). ESI-MS m/z: 648 [M + H] .
34 37 2 5 7
H, 5.60; N, 10.52; found: C, 61.07; H, 5.33; N, 10.27.
1
-Cyclopropyl-7-((4aR,7aR)-1-(2-(2-(3-(ethoxyimino)-2-
oxoindolin-1-yl)ethoxy)ethyl)hexahydro-1H-pyrrolo[3,4-b]
pyridin-6(2H)-yl)-6-fluoro-8-methoxy-4-oxo-1,4-
+
Elemental Anal. Calcd (%) for C H FN O : C, 63.05; H,
.91; N, 10.81; found: C, 62.83; H, 5.69; N, 10.57.
dihydroquinoline-3-carboxylic acid (5j).
Yellow solid,
34
38
5 7
1
yield: 16%. H NMR (400 MHz, DMSO-d ) δ 0.96–1.56
5
6
1
-Cyclopropyl-6-fluoro-7-((4aR,7aR)-1-(2-(2-(5-fluoro-3-
(m, 11H), 2.15–2.31 (m, 2H), 2.71–2.76 (m, 1H),
(
hydroxyimino)-2-oxoindolin-1-yl)ethoxy)ethyl)hexahydro-1H-
2.98–3.00 (m, 1H), 3.14–3.26 (m, 3H), 3.56–3.82 (m,
pyrrolo[3,4-b]pyridin-6(2H)-yl)-8-methoxy-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (5f). Light yellow solid,
yield: 15%. H NMR (400 MHz, DMSO-d ) δ 0.98–1.58
(
2
8
7
7
8
4
H), 3.87 (t, 2H), 4.11–4.12 (m, 1H), 4.20 (t, 2H),
.40–4.44 (2H, m, NOCH CH ), 7.12–7.16 (m, 2H,
2
3
1
6
Ar–H), 7.50 (d, 1H, Ar–H), 7.61–7.65 (m, 2H, Ar–H),
m, 8H), 2.11–2.36 (m, 2H), 2.74–2.77 (m, 1H),
+
8
.64 (1H, s, C2-H). ESI-MS m/z: 662 [M + H] .
.99–3.01 (m, 1H), 3.14–3.29 (m, 3H), 3.51–3.81 (m,
H), 3.87 (t, 2H), 4.11–4.12 (m, 1H), 4.21 (t, 2H),
.19–7.22 (m, 1H, Ar–H), 7.47–7.53 (m, 2H, Ar–H),
Elemental Anal. Calcd (%) for C H FN O : C, 63.53;
35
40
5 7
H, 6.09; N, 10.58; found: C, 63.25; H, 5.81; N, 10.29.
1
-Cyclopropyl-7-((4aR,7aR)-1-(2-(2-(3-(ethoxyimino)-5-
.65 (d, 1H, Ar–H), 8.66 (1H, s, C2-H), 13.44 (1H, brs,
methyl-2-oxoindolin-1-yl)ethoxy)ethyl)hexahydro-1H-
pyrrolo[3,4-b]pyridin-6(2H)-yl)-6-fluoro-8-methoxy-4-oxo-1,4-
+
NOH). ESI-MS m/z: 652 [M + H] . Elemental Anal.
Calcd (%) for C H F N O : C, 60.82; H, 5.41; N,
1
dihydroquinoline-3-carboxylic acid (5k).
solid, yield: 23%. H NMR (400 MHz, DMSO-d ) δ
Light yellow
3
3 35 2 5 7
1
0.75; found: C, 60.61; H, 5.19; N, 10.53.
6
0
.98–1.58 (m, 11H), 2.12–2.35 (m, 5H), 2.75–2.77 (m,
1
-Cyclopropyl-6-fluoro-8-methoxy-7-((4aR,7aR)-1-(2-(2-(3-
(
methoxyimino)-2-oxoindolin-1-yl)ethoxy)ethyl)hexahydro-1H-
1H), 2.99–3.00 (m, 1H), 3.12–3.30 (m, 3H), 3.48–3.84
(m, 8H), 3.88 (t, 2H), 4.11–4.12 (m, 1H), 4.20 (t, 2H),
pyrrolo[3,4-b]pyridin-6(2H)-yl)-4-oxo-1,4-dihydroquinoline-3-
carboxylic acid (5g). Yellow solid, yield: 33%. H NMR
(
(
3
1
4
.41–4.44 (2H, m, NOCH CH ), 7.03–7.05 (m, 1H,
2 3
400 MHz, DMSO-d ) δ 0.96–1.58 (m, 8H), 2.14–2.34
6
Ar–H), 7.35 (s, 1H, Ar–H), 7.34–7.37 (m, 1H, Ar–H),
.92 (s, 1H, Ar–H), 8.63 (1H, s, C2-H). ESI-MS m/z: 676
m, 2H), 2.75–2.77 (m, 1H), 2.99–3.00 (m, 1H),
.18–3.30 (m, 3H), 3.54–3.80 (m, 8H), 3.86 (t, 2H),
.11–4.16 (m, 4H), 4.20 (t, 2H), 7.12–7.16 (m, 2H,
7
+
[M + H] . Elemental Anal. Calcd (%) for C H FN O :
36 42 5 7
4
C, 63.99; H, 6.26; N, 10.36; found: C, 63.75; H, 5.99; N,
Ar–H), 7.48 (d, 1H, Ar–H), 7.63–7.65 (m, 2H, Ar–H),
8
1
0.09.
+
.64 (1H, s, C2-H). ESI-MS m/z: 648 [M + H] .
1-Cyclopropyl-7-((4aR,7aR)-1-(2-(2-(3-(ethoxyimino)-5-
Elemental Anal. Calcd (%) for C H FN O : C,
fluoro-2-oxoindolin-1-yl)ethoxy)ethyl)hexahydro-1H-
pyrrolo[3,4-b]pyridin-6(2H)-yl)-6-fluoro-8-methoxy-4-oxo-1,4-
3
4
38
5 7
63.05; H, 5.91; N, 10.81; found: C, 62.80; H, 5.63;
dihydroquinoline-3-carboxylic acid (5l). Light yellow solid,
N, 10.58.
1
yield: 19%. H NMR (400 MHz, DMSO-d ) δ 0.92–1.62
1
-Cyclopropyl-6-fluoro-8-methoxy-7-((4aR,7aR)-1-(2-(2-(3-
6
(
m, 11H), 2.14–2.36 (m, 2H), 2.77–2.79 (m, 1H),
2.99–3.01 (m, 1H), 3.13–3.28 (m, 3H), 3.50–3.82 (m,
H), 3.88 (t, 2H), 4.11–4.15 (m, 1H), 4.21 (t, 2H),
4.42–4.46 (2H, m, NOCH CH ), 7.19 (t, 1H, Ar–H),
(methoxyimino)-5-methyl-2-oxoindolin-1-yl)ethoxy)ethyl)
hexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl)-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (5h).
solid, yield: 23%. H NMR (400 MHz, DMSO-d ) δ
Light yellow
8
1
6
2
3
0
1
.96–1.58 (m, 8H), 2.12–2.36 (m, 5H), 2.74–2.76 (m,
H), 2.97–3.00 (m, 1H), 3.15–3.33 (m, 3H), 3.42–3.81
7.43–7.51 (m, 2H, Ar–H), 7.66 (d, 1H, Ar–H), 8.65 (1H,
s, C2-H). ESI-MS m/z: 680 [M + H] . Elemental Anal.
+
(m, 8H), 3.88 (t, 2H), 4.11–4.17 (m, 4H), 4.20 (t, 2H),
Calcd (%) for C H F N O : C, 61.85; H, 5.78; N,
35 39 2 5 7
7
1
.03–7.06 (m, 1H, Ar–H), 7.35 (s, 1H, Ar–H), 7.40 (d,
10.30; found: C, 61.57; H, 5.49; N, 10.05.
H, Ar–H), 7.91 (s, 1H, Ar–H), 8.60 (1H, s, C2-H).
+
ESI-MS m/z: 662 [M + H] . Elemental Anal. Calcd (%)
for C H FN O : C, 63.53; H, 6.09; N, 10.58; found: C,
REFERENCES AND NOTES
35
40
5 7
6
3.31; H, 5.82; N, 10.29.
[
1] Zhang, S.; Xu, Z.; Gao, C.; Ren, Q. C.; Le, C.; Lv, Z. S.; Feng,
L. S. Eur J Med Chem 2017, 138, 501.
2] Guidelines for the Management of Drug-Resistant Tuberculo-
1
-Cyclopropyl-6-fluoro-7-((4aR,7aR)-1-(2-(2-(5-fluoro-3-
(methoxyimino)-2-oxoindolin-1-yl)ethoxy)ethyl)hexahydro-1H-
[
pyrrolo[3,4-b]pyridin-6(2H)-yl)-8-methoxy-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (5i). Light yellow solid,
sis WHO/TB/96-210 (Rev.1); World Health Organization: Geneva,
1997.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet