Med Chem Res (2012) 21:2280–2291
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Ethyl 2-(1-(2-(5-methoxy-2-methyl-1H-indol-3-
yl)acetyl)piperidine-2-carboxamido)-3-
mercaptopropanoate, 14
2-Methoxy-4-methylphenyl
2-(6-methoxynaphthalen-2-
yl)propanoate, 18 White solid, purified by flash chroma-
tography (petroleum ether/ethyl acetate 4/1), mp 84–85°C,
yield 48%. 1H NMR (CDCl3) d 1.68 (d, 3H, CH3CH;
J = 8.0 Hz), d 2.30 (s, 3H, phenyl-CH3), d 3.65 (s, 3H,
phenyl-OCH3), d 3.91 (s, 3H, naphthyl-OCH3), d 4.12 (q,
After the reaction of compound F with L-cysteine ethyl ester
according to the general method, compound 14 was isolated
by flash chromatography (petroleum ether/ethyl acetate 1/1)
as the main reaction product. Yellow solid, mp 54–57°C,
yield 49%. IR (KBr). 1624, 1670, 1739, 2556 cm-1. 1H NMR
(CDCl3) d 1.30 (t, 3H, CH3CH2), d 1.40–1.70 (m, 7H, C-3
piper. C-4 piper., C-5 piper., SH), d 2.35 (s, 3H, indolyl-CH3),
d 2.80–3.30 (m, 6H, CH2CO C-6 piper., CH2SH), d 3.80 (s,
3H, CH3O), d 4.10–4.15 (m, 3H, CH3CH2O) d 4.70–4.90 (m,
2H, C-2 piper., CHCO), d 6.60 (s, 1H arom., C-4 indolyl), d
6.80–7.10 (m, 2H arom., C-6 indolyl, C-7 indolyl), d 7.90 (m,
1H, NHCO). Anal. (C23H31N3O5S), C, H, N.
1H, CH3CH), d 6.66–7.75 (m, 9H arom.). Anal.
(C22H22O4, 90.8 H2O), C, H, N.
3-(Pyridin-3-yl)propyl 2-(6-methoxynaphthalen-2-yl)pro-
panoate, 19 White solid, purified by flash chromatogra-
phy (petroleum ether/ethyl acetate 1/4), mp 55–56°C, yield
52%. 1H NMR (CDCl3) d 1.52 (d, 3H, CH3CH;
J = 8.0 Hz), d 1.82–1.85 (m, 2H, CH2CH2CH2), d 2.45 (t,
2H, pyridyl-CH2), d 3.80 (q, 1H, CH3CH), d 4.01 (s, 3H,
CH3O), d 4.05 (m, 2H, CH2O), d 7.05–7.35 (m, 8H arom.,
C10H6, C-4 pyridyl, C-5 pyridyl), d 8.30 (s, 1H arom., C-2
pyridyl), d 8.40 (d, 1H arom. C-6 pyridyl; J = 9.0 Hz).
Anal. (C22H25NO3), C, H, N.
Preparation of esters and amide of NSAIDs According to
the described general methods, the following derivatives of
NSAIDs were synthesized. Their IR spectra had a peak at
N-(2-Mercaptoethyl)-2-(3-benzoylphenyl)-2-propanamide,
20 Colourless oil, prepared, according to the general
method, from S-ketoprofen and cysteamine, and purified by
flash chromatography (petroleum ether/ethyl acetate 2/1),
yield 40%. 1H NMR (CDCl3) d 1.15 (t, 1H, SH), d 1.55 (d,
3H, CH3CH; J = 8.0 Hz), d 2.65 (m, 2H, CH2SH), d 3.65
(m, 2H, CH2CH2SH), d 3.8 (q, 1H CHCH3), d 7.30–7.70
(m, 9H arom.). Anal. (C18H19N2S), C, H, N.
1740–1760 cm-1
.
2-Methoxy-4-methylphenyl 2-(4-isobutylphenyl)propano-
ate, 15 White solid, purified by flash chromatography
(petroleum ether/ethyl acetate 5/1), mp 27–29°C, yield
51%. 1H NMR (CDCl3) d 0.92 (d, 6H, CH(CH3)2;
J = 8.0 Hz) d 1.61 (d, 3H, CH3CHCO; J = 8.0 Hz), d
1.88 (m, 1H, CH(CH3)2), d 2.32 (s, 3H, phenyl-CH3), d
2.48 (d, 2H, CH2CH(CH3)2; J = 8.0 Hz), d 3.69 (s, 3H,
CH3O), d 3.98 (q, 1H, CH3CHCO), d 6.67–6.83 (m, 3H
arom., C-3 phenyl, C-5 phenyl, C-6 phenyl), d 7.14 (d, 2H
arom.; J = 12.0 Hz), d 7.34 (d, 2H arom.; J = 12.0 Hz).
Anal. (C21H26O3), C, H, N.
Effect on acute inflammation For the in vivo experiments,
male Fischer-344 rats (200–280 g) or Balb-C mice
(20–30 g) were used. Animals were kept and treated
according to the European Communities Council Directive
of 24 November 1986 (86/609/EEC). They were housed in
controlled rooms, humidity 50–60%, temperature 23°C,
with a 12 h light/dark cycle, and free access to standard
laboratory chow and tap water.
3-(Pyridin-3-yl)propyl
2-(4-isobutylphenyl)propanoate,
16 Yellow oil, purified by flash chromatography (petro-
leum ether/ethyl acetate 3/1), yield 60%. 1H NMR (CDCl3) d
0.87 (d, 6H, CH(CH3)2), d 1.50 (d, 3H, CH3CHCO;
FCA Acute inflammation was induced by the id injection
of FCA (0.05 ml/paw) into the right hind paw of mice, the
left paw serving as control. The test compounds, suspended
in water with few drops of Tween 80, were given ip
(0.15–0.30 mmol/kg body weight) 5 min before the FCA
injection. Three hours later, the hind paws were excised
and weighted separately. The produced oedema was esti-
mated as paw weight increase compared to the control
animals that received only the liquid vehicle (Hadjipetrou-
Kourounakis et al., 1992).
J = 8.0 Hz),
d
1.77–1.96 (m, 3H, CH(CH3)2,
CH2CH2CH2), d 2.43–2.56 (m, 4H, CH2CH(CH3)2, pyridyl-
CH2), d 3.71 (q, 1H, CH3CHCO), d 4.01–4.14 (m, 2H,
CH2O), d 7.09–7.25 (m, 5H arom., C6H4, C-5 pyridyl), d 7.34
(d, 1H arom., C-4 pyridyl), d 8.34–8.45 (m, 2H arom. C-2
pyridyl, C-6 pyridyl). Anal. (C21H27NO2), C, H, N.
3-(Pyridin-3-yl)propyl
2-(3-benzoylphenyl)propanoate,
17 Yellow oil, purified by flash chromatography (petro-
leum ether/ethyl acetate 3/7), yield 60%. 1H NMR (CDCl3)
d 1.54 (d, 3H, CH3CH), d 1.90 (m, 2H, CH2CH2CH2), d
2.56 (t, 2H, pyridyl-CH2), d 3.80(q, 1H, CH3CH), d 4.09 (t,
2H, CH2O), d 7.16–7.78 (m, 11H arom., C6H5, C6H4, C-4
pyridyl, C-5 pyridyl), d 8.35 (s, 1H arom., C-2 pyridyl), d
8.42 (d, 1H arom. C-6 pyridyl; J = 9.0 Hz). Anal.
(C24H23NO3), C, H, N.
Carrageenan paw oedema An aqueous solution of carra-
geenan was prepared (1% w/v) and 0.1 ml of this was
injected into the right hind paw of male rats, the left paw
serving as control. The tested compounds (dissolved or
suspended in water with a few drops of Tween 80) were
given ip (0.3 mmol/kg of body weight) 5 min before the
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