Synthesis of novel pyridazinyl benzimidazole, benzothiazole and benzoxazole of expected anti-inflammatory activity

Article abstract of DOI:10.3184/030823409X466050

In this study, a novel series of 6-oxopyridazinyl benzazoles and 3, 6-dioxopyridazinyl benzazoles were prepared from the starting compounds, 2-hydrazinobenzimidazole, 2-hydrazinobenzothiazole and 2-hydrazinobenzoxazole by reaction with butyric acid deriva

Full text of DOI:10.3184/030823409X466050

448
RESEARCH
PAPER
JULY, 448-451
JOURNAL OF CHEMICAL RESEARCH 2009
Synthesis of novel pyridazinyl benzimidazole, benzothiazole and
benzoxazole of expected anti-inflammatory activity
Hanan M. Refaat, Omneya M. Khalil* and Suzan M. Abuel-Maaty
Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
In this study, a novel series of 6-oxopyridazinyl
from the starting compounds, 2-hydrazinobenzimidazole,
benzazoles and 3, 6-dioxopyridazinyl
benzazoles were prepared
by
2-hydrazinobenzothiazole and 2-hydrazinobenzoxazole
reaction with butyric acid derivatives and cyclic anhydrides respectively. The structures ofthe new compounds were
confirmed by elemental analysis as well as 'H NMR, IR and MS data. Some ofthe newly prepared compounds were
subjected to evaluation for their anti-inflammatory
activity using carrageenan induced paw edema at dose 100 mg
kg-' using indomethacin as a reference standard and were found to be bioactive.
Keywords: 6-oxopyridazinyl
benzazoles, 3, 6-dioxopyridazinyl
benzazoles, anti-inflammatory
activity
Commercially
available
nonsteroidal
anti-inflammatory
Experimental
drugs (NSAIDs) are widely used for reducing inflammatory
pain. NSAIDs act through the inhibition of a cyclooxygenase
Melting points were obtained on
a Griffin apparatus and are
uncorrected. Microanalyses for C, Hand N were carried out at the
Microanalytical Centre, Cairo University. IR spectra were recorded
on a Shimadzu 435 spectrometer, using KBr discs. 'H NMR spectra
were performed on a Joel NMR FXQ-200 MHz spectrometer, using
TMS as the internal standard.
(COX) enzyme.
one constitutive
This enzyme
(COX-I)
exists in two isoforms,
in many
which is produced
tissues such as the kidney and the gastrointestinal
and an inducible form (COX-2), which is expressed during
tract,
Mass spectra were recorded on
a GCMP-QPIOOO EX Mass
inflammation
at
a
site of injury.1-4 Prostaglandins
made by
spectrometer. Progress of the reactions were monitored by TLC using
precoated aluminum sheet silica gel MERCK 60F 254 and were
visualised by a UV lamp.
COX-l enzyme are important
for gastric cytoprotection,
whereas prostaglandins made by COX -2 cause inflammation. 5-7
Therefore, the development of new compounds which
selectively inhibit COX-2 has emerged as a growing research
area for generation of new anti-inflammatory drugs lacking
and renal side effects of currently used
General procedure for the synthesis of compounds 3-5 and 7-12:
To a stirred solution of (la, Ib or Ie) (0.01 mol) in glacial acetic acid
(20 mL) and acetic anhydride (I mL), the respective acid (0.01 mol)
(Ievulinic acid (2a), 4-(5-salicylamido)-4-oxobutyric acid (2b) and
4-biphenyl-4-oxobutyric acid (2e) or the respective acid anhydride
(0.01 mol) (succinic anhydride (6a), N-trifluoroacetylaspartic
anhydride (6b), 2-phenylsuccinic anhydride (6e), maleic anhydride
(6d), I, 2-cyclohexane dicarboxylic anhydride (6e) and 3, 4-pyridine
dicarboxylic anhydride (6f) were added and the mixture was refluxed
for 8 h. The solvent was evaporated under reduced pressure to half its
volume, cooled and poured onto water. The precipitate thus formed
was filtered, dried and recrystallised from ethanol.
the gastrointestinal
NSAIDs.8-11
In this respect, many benzoxazole12-14 and benzothiazole15-17
derivatives have been synthesised and claimed to have
significant analgesic and anti- inflammatory activity. In addition,
benzimidazole derivatives have also been reported as
potent analgesic and anti-inflammatory agents.18-21 Meantime,
many pyridazinone derivatives have been reported to function
as novel potent analgesic and anti-inflammatory agents
2-(3-Methyl-6-oxo-1, 4, 5, 6-tetrahydropyridazin-1-yl)benzimidazole
(3a): Yield: 51.0%; m.p.l96-199°C; IR: 3200(NH), 2900(CH aliph.),
1710 (C = 0); 'H NMR (CDClrdd: 1.25 (s, 3H, CH3), 2.66 (t, 2H,
J= 8 Hz, C-CH2), 3.36 (t, 2H,J= 8 Hz, CO-CH2), 7.20-7.29 (m, 3H,
and some have been shown to selectively inhibit COX-2
function.22-25
benzimidazole-Cs. 6. ,H), 8.18 (d, IH, J
CcH), 10.54 (brs, 1H, NH, Dp exchangeable); MS: m/z 228 (M+,
8.0%). Anal. Calcd for C12 0: C, 63.15; H, 5.26; N, 24.56.
= 7.8 Hz, benzimidazole-
The above mentioned findings prompted us to continue
our investigation25 of pyridazinone derivatives in an attempt
H12
N4
to generate new lead compounds for future development
anti-inflammatory agents. The aim of the present work is to
incorporate both molecules,
as
Found: C, 63.39; H, 5.25; N, 24.57%.
2-(3-Methyl-6-oxo-1, 4, 5, 6-tetrahydropyridazin-1-yl) benzothiazole
(3b): Yield: 40.0%; m.p. <300°C; IR: 2900(CH aliph.), 1690 (C = 0);
pyridazinone
and benzazole
of enhanced
'H NMR (DMSO-d6): 1.96 (s, 3H, CH3), 2.48 (t, 2H, J
=
7.6 Hz,
into the same molecule, with an anticipation
drug activity.
C-CH2), 3.41 (t, 2H, J
= 7.6 Hz, CO-CH2), 7.06 (t, 1H, J = 7.8 Hz,
benzothiazole-CoH),
7.34(d, IH,J= 7.8 Hz, benzothiazole-C,H),
benzothiazole-CcH),
7.25 (t, IH, J = 7.8 Hz, benzothiazole-Cd..!),
7.68 (d, 1H, J= 7.8 Hz,
MS: m/z 245 (M+, 42.74%). Anal. Calcd for
The starting materials,
2-hydrazinobenzothiazole
2-hydrazinobenzimidazole
(1 b) and 2-hydrazinobenzoxazole
(la),
(lc) were prepared using literature methods.26 Also, N-
trifluoro-acety laspartic anhydride (6b ) was prepared as
reported by reacting aspartic acid with trifluoroacetic anhydride
in trifluoroacetic acid.27 The synthesis of compounds 3-5
and 7-12 were accomplished by refluxing the requisite
2-hydrazinobenzazole (la-c) with either butyric acid
derivatives (2a-c) or cyclic anhydrides (6a-f) in acetic acid
containing acetic anhydride. The reaction took place with the
least sterically hindered carbonyl group upon the reaction
C12HllN30S: C, 58.77; H, 4.48; N, 17.14. Found: C, 58.71; H, 4.48;
N,17.IO%.
2-(3-(5-Salicylamido)-6- oxo -1, 4, 5, 6- tetrahydropyridazin-1-yl)
benzimidazole (4 a): Yield: 48.0%; m.p. < 300°C; IR: 3200-3100
(NH, OH), 2900(CH aliph.), 1710, 1665 (2C = 0); 'H NMR (DMSO-
d
6): 2.55-2.59 (m, 2H, C- CH2), 3.23-3.25 (m, 2H, CO- CH2),
7.01-7.06 (d, 2H,
J
=
7.9 Hz, benzimidazole-Cs.oH),
7.28 (d, 1H, J
7.18 (d,
= 7.8 Hz,
1H, J 7.8 Hz, benzimidazole-Cd..!),
=
benzimidazole-CcH),
7.68 (d, IH,
J
=
8.0 Hz, salicylamido-
CcH), 7.94 (d, 1H, J
=
8.0 Hz, salicylamido-Cr!:D, 8.20(s, 1H,
salicylamido-CoH), 12.05 (s, 1H, NH, DP exchangeable), 13.37(s,
IH, OH, Dp exchangeable); MS: m/z 349 (M+, 6.15%). Anal. Calcd
for C,sH,sNs03: C, 61.89; H, 4.29; N, 20.05. Found: C, 61.71; H,
4.31; N, 20.03%.
2-(3-(5-Salicylamido)-6- oxo -1, 4, 5, 6- tetrahydropyridazin-1-yl)
benzoxazole (4 b): Yield: 41.0%; m.p. 178-180°C; IR: 3300-3100
(NH, OH), 2950(CH aliph.), 1700, 1670 (2C = 0); 'H NMR (DMSO-
of N-trifluoroacetylaspartic
succinic anhydride. On the other hand, upon reaction of
the hydrazino derivatives with 3, 4-pyridinedicarboxylic
anhydride, the more electrophilic carbonyl group para to the
pyridine -N was thought to be attacked by the hydrazino group
and therefore the regioisomers (12a and 12b) were the sole
products.
anhydride
(6b) and 2-phenyl
d
6): 2.43 (t, 1H, J
CH.!.!a), 2.94 (t, 1H, J
CO -= CH.!.!a), 6.97 (t, 2H,
7.28-7.58 (m, 2H, benzoxazole -C4• ,H), 7.88 (d, 1H, J
=
8 Hz, C-CH.lie), 2.53 (t, 1H, J
8 Hz, CO --CH.lie), 3.24(t, 1H, J
8.8 Hz, -benzoxazole -Cs o.li),
8.2 Hz,
=
8 Hz, C-
=
=
8 Hz,
J
=
* Correspondent. E-mail: omneyafawzy@yahoo.com
=

JOURNAL OF CHEMICAL RESEARCH 2009 449
2a
(X,N)-N-\
~
X
NY
CH3
3a,b
2b
~N}-~~O
~x
N",
~-: CONH2
4a,b
OH
1a-c
2c
1b X =8
1c x= 0
1a X = NH
3a
3b X = 8
4b X=O
4a XX == NNHH
2a = Levulinic acid.
2b = 4-(5-8alicylamido)-4-oxobutyric
2c = 4-Biphenyl-4-oxobutyric acid.
acid.
Scheme
1
salicylamido-Cdi),
H), 8.15 (s, lH, salicylamido-CoH),
8.02 (d, lH,
J
=
8.2 Hz, salicylamido-Cr
8.68 (brs, 2H, NH2, 020
Op exchangeable). Anal. Calcd for CllH9NP2S: C, 53.44; H, 3.64;
N, 17.00. Found: C, 53.43; H, 3.65; N, 17.01%.
exchangeable), 12.16 (s, IH, NH, Op exchangeable), 13.36 (s, lH,
OH, Op exchangeable). Anal. Calcd for C'8H'4N404: C, 61.71; H,
4.00; N, 16.00. Found: C, 61.69; H, 4.02; N, 16.17%.
2-(3, 6-Dioxo-perhydropyridazin-l-yl) benzoxazole(7c): Yield: 25.0%;
m.p. 178-1800C; IR: 3200 (NH), 2900 (CH aliph.), 1700, 1680 (2C = 0);
'H NMR (OMSO-~): 2.79-2.80(m, 2H, NH-CO Cfu) 2.89-2.90
(m, 2H, N-CO-CliI), 7.12-7.15(m, 2H, benzoxazole -C~, ~H), 7.16-
7.26(m, 2H, benzoxazole -C4"H). Anal. Calcd for CllH9NP3: C,
57.14; H, 3.89; N, 18.18. Found: C, 57.21; H, 3.90; N, 18.22%.
2-(3, 6-Dioxo-5-trifluoroCJ£etylaminpoerhydropyridazin-l-yl) benzimid-
azole (Sa): Yield: 70.0%; m.p. 192-194°C; IR: 3300-3200 (NH),
1700, 1680, 1620 (3C = 0); 'H NMR (OMSO-~): 2.84 (m, 2H, CH2),
3.46 (m, lH, CH), 3.79 (brs, lH, NH, Op exchangeable), 7.13-
7.46(m, 4H, benzimidazole-H), 12.53, 12.86 (2 s, each lH, 2NH, 020
exchangeable). Anal. Calcd for C13HIOF3NS03:C, 45.74; H, 2.93; N,
20.52. Found: C, 45.75; H, 2.94; N, 20.51%.
2-(3-(4-Biphenyl)-6-oxo-l,
4, 5, 6-tetrahydropyridazin-l-yl)benzo-
thiazole (5): Yield: 40.0%; m.p. 220-222°C; IR: 2900 (CH aliph.),
1680 (C = 0); MS: m/z 283 (M+, 1.26). Anal. Calcd for C23H17N30S:
C, 72.06; H, 4.43; N, 10.96. Found: C, 72.15; H, 4.42; N, 10.91%.
2-(3,6-Dioxo-perhydropyridazin-l-yl)
73.0%; m.p. 194-195°C; IR: 3300 (NH), 2950 (CH aliph.) 1700,
1680 (2C 0); 'H NMR (OMSO-d6): 2.41-2.44(m, 2H, NH-CO-
CHI), 2.80-2.83 (m, 2H, N-CO-CHI)' 7.36(t, lH, 7.8 Hz,
benzimidazo1e-C -H), 7.46(t, IH, J = 7.8 Hz, benzimidazo1e-Cs-H),
7.79(d, lH,J= 7.8 Hz, benzimidazo1e-C,H), 7.95(d, lH,J= 7.8 Hz,
benzimidazo1e-Cc H), 11.02, 11.22(2 s, each lH, 2NH, 020
benzimidazole (7a): Yield:
=
J
=
6
2-(3, 6-Dioxo-5-trifiuoroacetylamino perhydropyridazin-l-yl) benzo-
thiazole (Sb): Yield: 45.0%; m.p. 204-206°C; IR: 3300-3200 (NH),
exchangeable ).Anal. Calcd forC" HION402:C, 57.39; H,4.34; N,24.34.
Found: C, 57.41; H, 4.33; N, 24.35%.
1700, 1680, 1620 (3C
= 0); 'H NMR (OMSO-d6): 1.96 (m, 2H,
2-(3, 6-Dioxo- perhydropyridazin-l-yl) benzothiazole (7b): Yield:
65.0%; m.p. 201-203 °C; IR: 3250 (NH), 2900 (CH aliph.) 1700, 1670
CH2), 3.36 (m, lH, CH), 4.07 (brs, lH, NH, Op exchangeable),
7.12(t, lH,J = 7.6 Hz, benzothiazo1e-CoH), 7.32 (t, lH, J = 7.6 Hz,
benzothiazo1e-Cs-H), 7.47 (d, IH, J = 7.6 Hz, benzothiazole-CrH),
(2C
= 0); 'H NMR (OMSO-~): 2.44-2.49(m, 2H, NH-CO- CHIl,
2.66-2.71 (m, 2H, N-CO-Cfu), 7.12-7.33(m, 2H, benzothiazole-
Cs,oH), 8.09-8.12(m, 2H, benzothiazole-C4, ,H), 12.47(s, lH, NH,
7.76 (d, lH,
J = 7.6 Hz, benzothiazo1e-Cc H), 10.29 (s, lH, NH,
Op exchangeable); MS: m/z 358 (M+, 6.79%). Anal. Calcd for

450 JOURNAL OF CHEMICAL RESEARCH 2009
o
6a
6b
(XX N
I
N~N)
:::,..
H
7a-c
0
~N
~H
~1~~ NHCOCF3
-
8 a-e
0
6e
(X
N
(X
N
~O H
'"""
I
~N
I r NHNH2
:::,.. X N
~ """
,
X
H
o
9 a,
b
1a -C
o
6d
6e
6f
(Xlt)
10 a,
b
0
o
(XINN~NN~
:::,..
H H
o
11
12a,b
1a X=NH
7a X=NH
1b X=S
7b X=S
1e
7e XX == 00
X=NH
X=NH
X=S
X=S
8e
10a XX==ONH
12b X = 0
8a
9a
8b
9b
10b X = S
12a X= NH
6a = Succinic anhydride
6b = Trifluoroacetylaspartic anhydride
6e = 2-Phenyl succinic anhydride
6d = Maleic anhydride
6e
= I, 2-Cyc1ohexane dicarboxylic anhydride
6f = 3, 4-Pyridine dicarboxylic anhydride
Scheme 2
2-(3, 6-Dioxo-5-phenylperhydropyridazin-l-yl)
benzothiazole (9b):
C13H9F3N403S: C, 43.57; H, 2.51; N, 15.64. Found: C, 43.58; H,
2.50; N, 15.66.
2-(3, 6-Dioxo-5-trifluoroacetylamino perhydropyridazin-l-yl) benz-
Yield: 58.0%; m.p.l96-198°C;
(CH aliph.), 1710, 1690(2C
IR: 3200-3100 (NH), 2970
0); 'H NMR (DMSO-~): 2.18, 2.32
=
oxazole (Sc): Yield: 55.0%; m.p. 185-187°C; IR: 3300-3200 (NH),
(2 m, each 1H, CH2), 3.94(m, 1H, CH), 7.20-7.36(m, 5H, ArH), 7.37
(t, 1H, J 7.5 Hz, benzothiazole-Co!.:D, 7.49(t, 1H, J 7.5 Hz,
benzothiazole-Cs-H), 7.84(d, IH, J = 7.5 Hz, benzothiazole-C,!.!),
8.06(d, IH,J = 7.5 Hz, benzothiazole-Cd.!), 11.30(s, 1H, NH, Dp
exchangeable). Anal. Ca1cd for C17H13N302S:C, 63.15; H, 4.02; N,
13.00. Found: C, 63.19; H, 4.04; N, 13.02%.
2-(3, 6-Dioxo-l, 2, 3, 6- tetrahydropyridazin-l-yl) benzimidazole
(lOa): Yield: 48.0%; m.p. 270-272 °C; IR: 3200 (NH), 1720, 1700
(2C = 0); MS: m/z 228 (M+, 12.42%). Anal. Ca1cd for CllH8N402: C,
57.89; H, 3.50; N, 24.56. Found: C, 57.91; H, 3.51; N, 24.54%.
2-(3, 6-Dioxo-l, 2, 3, 6- tetrahydropyridazin-l-yl) benzothiazole
(lOb): Yield: 56.0%; m.p. 160-163°C; IR: 3200 (NH), 1720, 1690
(2C = 0); 'H NMR (DMSO-d6): 7.25(d, IH,J= 9.6 Hz,pyridazinone
H), 7.33 (d, 1H, J= 9.6 Hz, pyridazinone H), 7.44 (t, 1H, J= 7.8 Hz,
1720, 1660, 1620 (3C
2H, CH2), 3.34 (m, 1H, CH), 7.22-7.29(m, 2H, benzoxazole -Cs
o!.:D, 7.32 (d, 1H, J 7.8 Hz, benzoxazole -CcH), 7.52 (d, 1H;
= 7.8 Hz, benzoxazole -C,!.:D, 13.82(s, 1H,NH, Dp exchangeable).
=
0); 'H NMR (DMSO-d6): 2.49-2.51 (m,
=
=
=
J
Anal. Ca1cd for C13H9F3N404:C, 45.61; H, 2.63; N, 16.37. Found: C,
45.60; H, 2.64; N, 16.36%.
2-(3, 6-Dioxo-5-phenylperhydropyridazin-l-yl) benzimidazole (9a):
Yield: 43.0%; m.p. 170-172°C; IR: 3250-3100 (NH), 2900(CH
aliph.), 1720, 1700 (2C
J= 17.1,5.1 CH!!e), 2.92 (dd, IH,J= 17.1, 10.2 CH!:!a),3.91(dd, 1H,
10.2,5.1, CH), 7.23-7.35(m, 5H, ArH), 7.39(t, IR, 7.5 Hz,
benzimidazole-Co!.:D, 7.48(t, IH, 7.5 Hz, benzimidazole-Cs-
!.:D, 7.83 (d, 1H, J 7.5 Hz, benzimidazole-Cd.!), 8.03(d, 1H,
= 7.5 Hz, benzimidazole-Cc!.:D, 12.31(s, 1H,NH, Dp exchangeable).
= 0); 'H NMR (DMSO-~): 2.49 (dd, 1H,
J
=
J =
J
=
=
J
benzothiazole-CoH),
7.76 (d, IH,J= 7.8 Hz, benzothiazole-Cd.!),
benzothiazole-CcH), 10.80 (s, IH, NH, DP exchangeable); MS:
7.51 (t, IH, J = 7.8 Hz, benzothiazole-Cs-!.!),
7.92 (d, IH,J= 7.8 Hz,
Anal. Calcd for C17H,4N402: C, 66.66; H, 4.57; N, 18.30. Found: C,
66.59; H, 4.56; N, 18.32%.

JOURNAL OF CHEMICAL RESEARCH 2009
451
m/z 245 (M+, 20.01 %). Anal. Calcd for CllH7N302S: C, 53.87; H,
2.85; N, 17.14. Found: C, 53.85; H, 2.84; N, 17.11%.
exert a significant contribution to the activities when they are present
together in the same molecule.
2-(3, 6-Dioxo-4, 5-tetramethylene perhydropyridazin-l-yl) benzimid-
azole (11): Yield: 38.0%; m.p. 225-227°C; IR: 3200, 3100 (NH),
The authors wish to thank Assoc. Prof. Dr. Dalal Mostafa,
2900(CH aliph.), 1700, 1680 (2C
= 0); 'H NMR (OMSO-d6): 1.38-
Department
University
screemng.
of Pharmacology,
for help in performing
Faculty of Pharmacy, Cairo
the anti-inflammatory
1.64(m, 4H, CHr{Qhh- CH2, 1.65-1.92(m, 4H, Qh-{CH2h- Qh),
2.66-2.68 (m, lH, pyrlciazinyl-Cd.!), 3.07-3.09(m, rH, pyridazinYl-
Cd.!), 6.95-7.28(m, 4H, benzimidazole-J.!), 11.20, 12.50 (2 s, each
lH, 2NH, Op exchangeable); MS: m/z 284 (M+, 21.51%). Anal.
Calcd for C,sH'6N402: C, 63.38; H, 5.63; N, 19.71. Found: C, 63.31;
H, 5.63; N, 19.73%.
Received 2 March 2009; accepted 25 May 2009
Paper 09/0470 doi: 10.3184/030823409X466050
Published online: 15 July 2009
2-(1, 4-Dioxo-l, 2, 3, 4-tetrahydropyrido [3, 4-dJ pyridazin-l-yl)
benzimidazole (12a): Yield: 35.7%; m.p. 278-280°C; IR: 3200 (NH),
1700,1680 (2C = 0); 'H NMR (OMSO-d6): 7.08-8.57(m, 7H, ArH),
12.48(s, 2H, 2NH, Op exchangeable); MS: m/z 279 (M+, 0.14%).
Anal. Calcd for C'4H9Ns02: C, 60.21; H, 3.22; N, 25.08. Found: C,
60.29; H, 3.23; N, 25.12%.
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W. Xie, J.G. Chipman, D.L. Robertson, R.L. Erikson and D.L. Simmons,
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D.A. Kujubu, B.S. Fletcher, B.C. Varnum, R.W. Lim and H.R. Herschman,
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4
T. H1a and K. Neilson, Proc. Nat!. Acad. Sci. USA, 1992,89,7384.
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1700, 1680 (2C
= 0); 'H NMR (OMSO-~): 7.27-7.29(m, 2H,
benzoxazole -Cs. oJ.!), 7.85-7.93(m, 2H, benzoxazole -C4. ,Ii) ,
8.50-8.54(2 overlapped d, 2H, pyrido-Cs. oJ.!), 9.10-9.14(m, lH,
pyrido-CrJ.!), 11.55-11.68(brs, lH, NH, Op exchangeable). Anal.
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H, 2.83; N, 20.08%.
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9
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The positive control group was given 10 mg kg" indomethacin one
hour before carrageenan injection.
The test compounds were suspended in 0.5% carboxymethyl-
cellulose (CMC) and given to the rats orally at a dose of 10 mg kg"
one hour prior to carrageenan injection. In all groups, both hind limbs
were dissected 4 h after carrageenan injection and weighed and the
difference in weight was calculated. The effect of the test compounds
were compared to control and standard by ordinary one-way ANOVA
(Table 1).
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It is interesting that most of the compounds of the present series
exhibit good activity relative to the standard, ranging from 37.1 to
58.2% oedema reduction (Table 1).
Compound 11, in which benzimidazole is linked to pyridazinone,
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It is apparent that compound 4a, with
displayed higher inhibition of paw oedema (44.7%) than its
derivative 4b, with benzoxazole moiety (41.0%), whereas,
a benzimidazole ring,
a
a
19 P. Vicini, M. Incerti, L. Amoretti,
V Ballabeni, M. Togno1ini and
compounds 3b, lOb and 12a were found to be nearly equipotent.
Thus, one could say that benzimidazole and pyridazinone groups
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1
Anti-inflammatory
activity of the tested compounds
M. Inayathullah,
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Group
Increase in paw
weight (Mean ± SEM)
% inhibition
of oedema
Control
3b
4b
10b
11
12a
4a
0.65±0.05
0.41±0.06"
0.39±0.07"
0.39±0.03"
0.27±0.03"
0.40±0.03"
0.36±0.03"
0.32±0.03"
37.1
41.0
39.8
58.2
39.4
44.7
50.5
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111,544.
Indomethacin
"Significantly different from control group at P<0.05 (One way
ANOVA followed by Tukey-Kramer multiple comparison test).