Arch. Pharm. Chem. Life Sci. 2005, 338, 378−384
Anti-inflammatory/analgesic Floctafenine Derivatives
383
Spacing allyl 2-{[8-(trifluoromethyl)quinolin-4-yl]amino}benzoate
5Ϫ7
Table 3. Molecular formula, yields, and melting points of the
synthesized compounds.
A mixture of 1 (4.06 g, 0.01 mol) and the corresponding ketone
(0.01 mol) in sodium ethoxide solution (0.46 g, 0.02 mol) was re-
fluxed for 4 h. The reaction mixture was acidified with 10% hydro-
chloric acid and cooled. The precipitate formed was filtered and
crystallized from ethanol (Table 3). IR: 5: 3400 (NH), 1680 (CO),
1620 (CO). 1H-NMR (DMSO): 5: 2.53 (s, 3H, CH3), 4.14 (d, 2H,
O-CH2), 6.81 (d, 2H, CHϭCH), 7.48Ϫ8.91, (m, 9H, aromatic),
11.15 (s, 1H, NH) exchanged by D2O. 1H-NMR (DMSO): 6:
0.82Ϫ1.9 (m, 8H, cyclohexyl), 4.42 (d, 2H, O-CH2), 7.02Ϫ8.72 (m,
10H, -CHϭ and aromatic), 13.6 (s, 1H, NH) exchanged by D2O.
Mϩ M/Z: 7: 491.2 (1%). 1H-NMR (DMSO):7: 2.51 (d, 3H, CH3),
4.26 (d, 2H, O-CH2), 7.22Ϫ8.72 (m, 15H, aromatic and olefinic
protons CHϭCH), 10.6 (s, 1H, NH) exchanged by D2O.
Compound
Mol. formula
(Mol. weight)
Yield
[%]
M.P.
[°C]
2
3
C19H13F3N2O3
(374.31)
95
71
72
90
71
70
79
44
36
80
60
66
76
150
226
145
165
175
130
216
261
245
165
140
162
120
C29H22F3N5O3
(545.51)
4
C28H20F3N5O3
(531.00)
5
C22H17F3N2O3
(414.37)
Alkyl 2-{[8-(trifluoromethyl)quinolin-4-yl]amino}benzoate 9Ϫ11
6
C25H21F3N2O3
(454.44)
A mixture of 8a (3.32 g, 0.01 mol), thionyl chloride (15 mL) and
one drop dimethylformamide was refluxed for 2 h. The excess
thionyl chloride was distilled under reduced pressure using dry ben-
zene. The appropriate alcohol (0.01 mol) was added and refluxed in
dichloromethan and one drop of triethylamine for 2 h. The precipi-
tate formed was filtered off and crystallized from ethanol/ether
(Table 3). Mϩ M/Z: 9: 388.19 (37%). 1H-NMR (DMSO): 9: 0.6 (t,
3H, CH3), 0.78 (m, 2H, CH2- CH3), 1.33 (m, 2H, CH2-CH2-CH3),
4.10 (t, 2H, -O-CH2), 6.69Ϫ8.95 (m, 9H, aromatic), 11.19 (s, 1H,
NH) exchanged by D2O. 1HNMR (DMSO):10: 2.77Ϫ2.88 [d of d,
6H, 2(CH3)], 4.6 (m, 1H, -CH), 6.5 (d, 2H, -O-CH2), 7.54Ϫ8.36
(m, 9H, aromatic), 11.30 (s, 1H, NH) exchanged by D2O. 1H-NMR
(DMSO):11: 3.72 [d, 6H, 2(CH3)], 6.25 (m, 1H, CH-O), 7.62Ϫ8.33
(m, 9H, aromatic), 11.22 (s, 1H, NH) exchanged by D2O.
7
C28H21F3N2O3
(490.47)
9
C21H19F3N2O2
(388.38)
10
11
12
13
14
15
C21H19F3N2O2
(388.38)
C20H17F3N2O2
(374.35)
C17H13F3N4O
(346.31)
C24H16F4N4O
(452.40)
2-{[8-Ttrifluoromethyl)quinolin-4-yl]amino}benzohydrazide 12
A mixture of 1 (8.12 g, 0.02 mol) and hydrazine hydrate (1.35 g
,0.03 mol) in absolute ethanol (50 mL) and glacial acetic acid (one
drop) was refluxed for 12 h. The solvent was distilled under reduced
pressure and the residue formed was crystallized from aqueous etha-
nol (Table 3). 1H-NMR (DMSO):12: 4.43 (s, 2H, NH2) exchanged
by D2O, 7.18Ϫ8.69 (m, 9H, aromatic), 8.93(s, 1H, OϭC-NH) ex-
changed by D2O, 10.82 (s, 1H, -NH) exchanged by D2O.
C25H19F3N4O2
(464.43)
C25H19F3N4O3
(480.43)
2-{[8-(Trifluoromethyl)quinolin-4-yl]amino}substituted methylene
benzohydrazide 13Ϫ15
(DMSO): 2: 4.08 (d, 2H, -CH2), 6.16 (t, 1H, CHO) exchanged by
D2O, 7.25Ϫ8.72 (m, 9H, aromatic), 9.96 (s, 1H, NH) exchanged
by D2O.
A mixture of 12 (3.46 g, 0.01 mol) and the corresponding aldehyde
(0.01 mol) was refluxed in absolute ethanol (20 mL) and one drop
of glacial acetic acid for 4 h. The reaction was then poured on ice/
water and the precipitate formed was filtered off and crystallized
from aqueous ethanol (Table 3). IR: 13: 3400, 3300 (NH and
OϭC-NH), 1680 (CO). 1H-NMR (DMSO): 13: 6.95Ϫ8.66 (m, 13H,
aromatic), 9.88 (s, 1H, NϭCH-), 10.31(s, 1H, NH-CϭO) exchanged
2-[(1-Methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino]-
ethyl 2-{8-(trifluoromethyl)quinolin-4-yl]amino}benzoate (3) and
2-[(5-Oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)imino]ethyl 2-{[8-
(trifluoromethyl)quinolin-4-yl]amino}benzoate 4
1
by D2O, 11.9 (s, 1H, NH-) exchanged by D2O. H-NMR (DMSO):
14: 4.23 (s, 3H, O-CH3), 6.98Ϫ8.67 (m, 13H, aromatic), 9.88 (s, 1H,
NϭCH-), 10.34 (s, 1H, NH-CϭO) exchanged by D2O, 11.92 (s, 1H,
NH-) exchanged by D2O. IR: 15: 3300Ϫ3500 (NH, OH), 1680 (CO).
1H-NMR (DMSO):15: 3.85 (s, 3H, O-CH3), 6.92Ϫ8.57 (m, 12H,
aromatic), 9.78 (s, 1H, NϭCH-), 10.00 (s, 2H, OH, NH-CϭO) ex-
changed by D2O, 11.91 (s, 1H, NH-) exchanged by D2O.
A mixture of 2 (3.74 g, 0.01 mol) and the appropriate amine (0.01
mol) were kept under reflux in absolute ethanol in the presence of
one drop glacial acetic acid for 5 h. At the end of the reaction time,
the precipitate formed was filtered and crystallized from aqueous
ethanol (Table 3). IR: 3: 3400 (NH), 1660 (CO). 1H-NMR (DMSO):
3: 1.21 (s, 3H, CH3 -N), 3.95 (d, 2H, -OCH2), 7.08Ϫ8.68 (m, 16H,
aromatic, azomethane, CH- of pyrazole ring), 10.18 (s, 1H, NH)
exchanged by D2O. IR: 4: 3300(NH), 1680(CO). 1H-NMR
(DMSO): 4: 5.00 (d, 2H, O-CH2), 7.00Ϫ8.60 (m, 16H, aromatic,
azomethane, CH of pyrazole ring), 10.00 (s, 2H, 2(NH)) exchanged
by D2O.
Pharmacology
Carragenan- induced rat’s paw edema
Groups of adult male albino rats (150Ϫ200 g) of six animals each
were given the tested compounds orally at a dose level of 5g/kg one
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