Beruflich Dokumente
Kultur Dokumente
ISSN- 0975-1491
ResearchArticle
SCREENINGOFINVITROANTIINFLAMMATORYACTIVITYOFSOMENEWLYSYNTHESIZED
FLUORINATEDBENZOTHIAZOLOIMIDAZOLECOMPOUNDS
B.S.SATHE*,V.A.JAGTAP,S.D.DESHMUKHANDB.V.JAIN
*Head,DepartmentofPharmaceuticalAnalysis,Smt.S.S.PatilCollegeofPharmacy,Chopda425107Email:drbss1978@rediffmail.com
Received:24March2011,RevisedandAccepted:22April2011
ABSTRACT
4Fluoro3chloroanillinetreatedwithPotassiumthiocyanateinpresenceofGlacialaceticacidandbrominewasconvertedinto2amino6fluoro7
chlorobenzothiazole, resulting into 2amino benzothiazole. The synthesized compound in presence of 2phenyl4benzylidine5oxazolinone
refluxed in pyridine to obtained 2(2Phenyl4benzylidenyl5oxoimidazolin1yl amino)6fluoro7substituted(1,3)benzothiazoles. The above
saidcompoundwastreatedwithortho,metaandparanitroanillines,ortho,meta,parachloroanillines,morpholino,Piperazine,diphenylaminein
thepresenceofDMFtoobtaindifferentderivatives.Somecompoundsshowedpromisingantimicrobialactivity.
Keywords:Flourine,Benzothiazole,Oxazalinone,Imidazoline,AntiInflammatory
INTRODUCTION
Fluorobenzothiazoles and Imidazoles exhibit the broad range of
antibacterial1, antifungal2, anthelmintic3, antiinflammatory4 and
antitubercular5 activity. In the recent years, the chemistry of
oxazolones6 has received much attention due to their use as
intermediates for synthesis of some heterocyclic systems. In the
present study we made an attempt to link78 fluorobenzothiazoles
with imidazoles for generating various derivatives, screened for
antiinflammatory activity. Benzylidine derivatives were found to
possess MAO Inhibitory activity, therefore in the present work we
have treated oxazolones benzothiazole ring to get potent anti
inflammatory9,10,11compounds.
C6H5
NH2
KSCN; Br2/HAC
NH3
N
S
Cl
NH2
O
O
H1C
Cl
C6H5
2 Oxazolone
C6H5
N
S
F
R
C6H5
CH
F
Cl
C6H5
4 (a-i)
CH
C6H5
MAERIALSANDMETHODS
Purity of compounds was checked by TLC. Melting points were
determinedbyopencapillariesmethodanduncorrected.IRspectra
(NaCl)arerecorded on FTIR(Schimadzu8300)spectrophotometer
using nujol mull technique. 1HNMR spectra are recorded on a
spectrophotometer(BrukerAMX)at500MHz,usingTMSasinternal
reference.
Generalprocedure
2amino6fluoro7chloro(1,3)benzothiazole(1)
To the glacial acetic acid (20ml) which is cooled below room
temperature, 8gm (0.08mol) of potassium thiocyanate and 1.45g
(0.01mol)offluorochloroanilinewasadded.Themixturewasplaced
infreezingmixtureoficeandsalt,mechanicallystirredwhile1.6ml
ofbrominein6mlofglacialaceticacidwasadded,fromadropping
funnelatsucharatethatthetemperatureneverrosebeyondroom
temperature. After all the bromine was added (105min), the
solution was stirred for 2 hours below room temperature and at
Satheetal.
IntJPharmPharmSci,Vol3,Suppl3,2011,220222
Table1:Analyticaldataofthesynthesizedcompounds(4ai)
Comp
No
M.P.
C
Yield
%
M.F.
ElementalAnalysis
%
C
Found
68.00
Calc.
67.50
117
80
C27H17N4O2SF
H
3.56
3.54
N
12.00
11.66
128
79
C27H18N4OSF
Found
Calc.
70.01
69.67
3.90
3.87
12.13
12.04
117
74
C35H23N4OSF
116
66
C29H18N5O3SF
Found
Calc.
Found
Calc.
74.90
74.20
65.09
65.04
4.15
4.06
3.56
3.36
10.09
9.89
13.89
13.08
126
68
C29H18N5O3SF
Found
Calc.
66.00
65.04
3.89
3.36
14.02
13.08
122
70
C29H18N5O3SF
Found
Calc.
66.09
65.04
3.45
3.36
12.80
13.08
111
72
C29H19N4OSF
Found
Calc.
71.09
71.02
3.90
3.87
12.56
11.42
85
77
C29H18N4OSFCl
Found
Calc.
67.77
66.28
3.89
3.42
10.89
10.66
115
70
C29H18N4OSFCl
Found
Calc.
67.05
66.28
3.67
3.42
11.09
10.66
4a
O
4b
NH
4c
N(C6H5)2
4d
NH
NO2
4e
NH
4f
NH
NO2
NO2
4g
NH
4h
NH
4i
NH
Cl
Cl
Table2:IRspectraldataofthesynthesizedcompounds(4ai)
Comp.
code
NH
cm1
4a
4b
4c
4d
4e
4f
4g
4h
4i
3353
3200
3200
3300
3350
3400
3351
3350
3349
Imidazolinering
carbonyl
cm1
1640
1640
1630
1640
1639
1630
1641
1643
1637
C=Nstretching
cm1
C=Cstretching
cm1
NO2
cm1
CF
cm1
CCl
cm1
1612
1673
1600
1600
1613
1640
1610
1600
1653
1485
1460
1490
1490
1487
1400
1460
1462
1493
802
799
890
1167
1161
1163
1167
1163
1167
1164
1169
1160
714
714
Invitroantiinflammatoryactivity:9,10,11
The synthesized compounds were screened for antiinflammatory
activity using inhibition of albumin denaturation technique which
was studied according to Mizushima and Kobayashi with slight
modification.Thestandarddrugandtestcompoundsweredissolved
inminimumquantityofdimethylformamide(DMF)anddilutedwith
phosphatebuffer(0.2M,pH7.4).
Final concentration of DMFinall solution was lessthan 2.5%. Test
solution (1ml) containing different concentrations of drug was
221
Satheetal.
IntJPharmPharmSci,Vol3,Suppl3,2011,220222
The percentage inhibition of denaturation was calculated by using
followingformula.
%ofInhibition=100X{Vt/Vc1}
Where,Vt=Meanabsorbanceoftestsample.
Vc=Meanabsorbanceofcontrol
Table3:Screeningofinvitroantiinflammatoryactivity
Compounds
Absorbancevalue
(Mean+SE)
Control
4a
4b
4c
4d
4e
4f
4g
4h
4i
IBUPROFEN
0.098+0.009
0.159+0.004
0.118+0.004
0.147+0.003.
0.138+0.002
0.170+0.002
0.164+0.002
0.121+0.001
0.176+0.004
0.170+0.003
0.190+0.002
Inhibitionof
denaturation(in
%)
62.92
20.40
50.00
40.80
73.80
68.02
23.46
79.93
73.80
93.87
CONCLUSION
All the newly synthesized fluorinated benzothiazole imidazole
compoundshavegivenappreciableyieldwithsatisfactoryelemental
analysis.ItisinferredfromtheTable3thatsynthesizedcompounds
(4ai), have shown significant antiinflammatory activity. However,
animalstudyandotherstudiesarenecessaryforitsactivityandalso
there is a need to elucidate its mechanism/s of anti inflammatory
action.
REFERENCES
1.
2.
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