Synthesis and biological activities of some new C-Aminomethylation of 5H-5-Aryl-6,7,8,9-tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one and 6H-6-Aryl-2,3,7,8,9,10-hexahydrothiazino[2,3-b]quinazolin-4(3H)-one

Article abstract of DOI:10.14233/ajchem.2016.19939

The synthesis of 5H-5-aryl-6,7,8,9-tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one and 6H-6-aryl-2,3,7,8,9,10-hexahydrothiazino[2,3-b]quinazolin-4(3H)-one, reaction between 4-aryl-3,4,5,6,7,8-hexahydroquinazolin-2-thione and methyl chloroacetate and ethyl β-bromo propionate. The Mannich reaction on 5H-5-aryl-6,7,8,9-tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one and 6H-6-aryl-2,3,7,8,9,10-hexahydrothiazino[2,3-b]quinazolin-4(3H)-one in ethanol, aqueous formaldehyde and different secondary amines yielded a single product C-Mannich base in each case. The obtained C-Mannich bases (compounds VIII and X) have been characterized on the basis of analytical spectral data. These C-Mannich bases have been screened for their antibacterial, antifungal, anti-inflammatory and analgesic activities.

Full text of DOI:10.14233/ajchem.2016.19939

Asian Journal of Chemistry; Vol. 28, No. 10 (2016), 2231-2235
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19939
Synthesis and Biological Activities of Some New C-Aminomethylation of
5H-5-Aryl-6,7,8,9-tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one and
6H-6-Aryl-2,3,7,8,9,10-hexahydrothiazino[2,3-b]quinazolin-4(3H)-one
*
DAMERAKONDA KUMARASWAMY and V. MALLAREDDY
Department of Pharmaceutical Chemistry, Vaagdevi College of Pharmacy, Hanamkonda, Warangal-506 001, India
*Corresponding author: E-mail: dks.july12@gmail.com
Received: 29 February 2016;
Accepted: 20 May 2016;
Published online: 30 June 2016;
AJC-17973
The synthesis of 5H-5-aryl-6,7,8,9-tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one and 6H-6-aryl-2,3,7,8,9,10-hexahydrothiazino[2,3-
b]quinazolin-4(3H)-one, reaction between 4-aryl-3,4,5,6,7,8-hexahydroquinazolin-2-thione and methyl chloroacetate and ethyl β-bromo
propionate. The Mannich reaction on 5H-5-aryl-6,7,8,9-tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one and 6H-6-aryl-2,3,7,8,9,10-
hexahydrothiazino[2,3-b]quinazolin-4(3H)-one in ethanol, aqueous formaldehyde and different secondary amines yielded a single product
C-Mannich base in each case. The obtained C-Mannich bases (compounds VIII and X) have been characterized on the basis of analytical
spectral data. These C-Mannich bases have been screened for their antibacterial, antifungal, anti-inflammatory and analgesic activities.
Keywords: Quinazoline, Thiazino, Thiazolo, C-Mannich base.
cyclohexanone in the presence of absolute alcohol and sodium
hydroxide to form 2-arylidene cyclohexanone [6,7,9,10].
After 2-arylidene cyclohexanone reacted with thiourea in
the presence of alcoholic KOH to form 4-aryl-3,4,5,6,7,8-
hexahydroquinazolin-2-thione. After the 4-aryl-3,4,5,6,7,8-
hexahydroquinazolin-2-thione reacted with methyl chloro-
acetate to form 5H-5-aryl-6,7,8,9-tetrahydrothiazolo[2,3-
b]quinazolin-3(2H)-one. Each of the thiazolo compounds will
be subjected to the Mannich condensation in ethanol by using
different acyclic or cyclic secondary amines and aqueous
formaldehyde [10] with a normal expectation of obtaining
C-Mannich bases (VIII), respectively. Physical data of
compounds showed in Table-1.
General procedure for synthesis of new C-Mannich
bases (X): Different aromatic aldehydes reacted with cyclo-
hexanone in the presence of absolute alcohol and sodium
hydroxide to form 2-arylidene cyclohexanone [11]. Then 2-
arylidene cyclohexanone reacted with thiourea in the presence
of alcoholic KOH to form 4-aryl-3,4,5,6,7,8-hexahydro-
quinazolin-2-thione. After that the 4-aryl-3,4,5,6,7,8-
hexahydroquinazolin-2-thione reacted with ethyl β-bromo
propionate to form 6H-6-aryl-2,3,7,8,9,10-hexahydrothiazino-
[2,3-b]quinazolin-4(3H)-one. Each of the thiazino compounds
will be subjected to the Mannich condensation in ethanol by
using different acyclic or cyclic secondary amines and aqueous
formaldehyde [12] with an expectation of obtaining C-Mannich
INTRODUCTION
Various 4(3H)-quinazolines and their derivatives are known
for their varied biological and pharmacological importance
[1]. The C-substituted amino alkyl moieties have been found
to be associated with CNS, analgesic and anti-inflammatory
activities. Therefore, in continuation of our investigations on
quinazolines and the Mannich bases [2-4]. The required
C-Mannich bases (VIII) and (X) have been prepared from its
different aromatic aldehydes [5], methyl chloroacetate, ethyl
β-bromo propionate and condensed with various secondary
amines in the presence of ethanol and aqueous formaldehyde
(Scheme-I). Purification of the products yielded a single com-
pound (TLC) in each case. These compounds have been charac-
terized by the analytical, IR and NMR spectral data (Table-1).
EXPERIMENTAL
Melting points were recorded in open capillaries using
Toshniwal melting point apparatus and are uncorrected. IR
spectra (νmax, cm-1) were recorded on Perkin-Elmer infracord-
283 spectrophotometer in nujal mull and NMR spectra on
varian EM-360 (90 MHz) spectrophotometer using TMS as
internal standard [6-8]. The C-Mannich bases (VIII) and (X)
were prepared by known procedures.
General procedure for synthesis of new C-Mannich
bases (VIII): Different aromatic aldehydes reacted with

2232 Kumaraswamy et al.
Asian J. Chem.
Ar
Ar
O
H
N
H
NH
Cl-CH2-COOCH3
S
N
H
N
H
S
IV
VII
Br-CH2-CH2-COOC2H5
R1
R2
C2H5OH
HN
HCHO &
Ar
O
H
N
Ar
O
H
N
R1
N
H
S
IX
CH2
N
S
N
H
R2
R1
HCHO &
C2H5OH
HN
VIII
R2
Ar
H
O
R1
R2
N
CH2
N
N
H
S
X
Scheme-I
bases (X), respectively. Physical data of compounds showed
in Table-1.
3010 (C-H stretch aromatic), 2850 (-OCH3 stretch), 1658 (C=O
stretch), 1496 (C=C stretch), 1470 (-N-CH2 stretch).1H NMR
spectra (CDCl3, δ ppm): 1.6 (t, 4H, 2CH2),1.9 (d, 4H, 2CH2),
2.5 (s, 6H, 2(CH3)2), 2.7 (s, 2H, CH2), 3.1 (s, 2H, CH2), 3.5 (s,
1H, CH), 3.8 (s, 3H, OCH3) 5.5 (s, 1H, CH), 5.7 (s, 1H, CH),
6.8 (d, 2H, Ar-H), 7.3 (d, 2H, Ar-H), 8.2(s, 1H, NH).
Antibacterial and antifungal screening: The antibac-
terial activity [13] of the test compounds (VIII and X) were
assayed against the following bacteria: Staphylococcus aureus
and Bacillus subtilis (Gram-positive); Klebsella pneumonia
and Escherchia coli (Gram-negative), employing filter-paper
strip method, Ciprofloxacin used as standard drug, the MIC
results are represented in Table-2.
Spectral data (IR and 1H NMR) of test compounds of VIII
and X (Scheme-I)
5-(4-Chloro phenyl)-2-(morpholinomethyl)-6,7,8,9,10,10a-
hexahydro-2H-thiazolo[2,3-b]quinazolin-3(5H)-one (VIII
G): IR (KBr, νmax, cm-1): 3220 (NH stretch), 3010 (C-H stretch
aromatic), 1658 (C=O stretch), 1496 (C=C stretch), 1470 (-
N-CH2 stretch), 682.15 (-Cl stretch). 1H NMR spectra (CDCl3,
δ ppm): 1.7 (t, 4H, 2CH2),1.9 (d, 4H, 2CH2), 2.6 (d, 4H, 2CH2),
3.1 (s, 2H, CH2), 3.5 (d, 4H, 2CH2), 3.8 (s,1H, CH), 5.5 (s,
1H, CH), 5.8 (s, 1H, CH), 7.3 (d, 4H, Ar-H), 8.8 (s, 1H, NH).
6-(4-Methoxy phenyl)-3-(dimethyl amino methyl)-2,3,
7,8,9,10,11,11a-octahydro-[1,3]-thiazino[2,3-b]quinazolin-
4(6H)-one (X I): IR (KBr, νmax, cm-1): 3220 (NH stretch),
The antifungal activity [14] was evaluated against two
fungi: Fusarium oxysporum and Dreschlera haloids, the test
compounds (VIII and X) screened for antifungal activity using

Vol. 28, No. 10 (2016)
Synthesis and Biological Activities of Some New C-Aminomethylation of 4(3H)-quinazolines 2233
TABLE-1
PHYSICAL DATA OF C-AMINOMETHYLATION OF 5H-5-ARYL-6,7,8,9-TETRAHYDROTHIAZOLO[2,3-b]QUINAZOLIN-3(2H)-ONE
AND 6H-6-ARYL-2,3,7,8,9,10-HEXAHYDROTHIAZINO[2,3-b]QUINAZOLIN-4(3H)-ONE
Substituent in VIII and X -NR1R2 in VIII and X at
Compound
m.f.
m.w.
m.p. (°C)
Yield (%)
at 4th position
2nd and 3rdposition
Dimethyl amino
Diethyl amino
4-Morpholino
1-Piperidino
VIII A
VIII B
VIII C
VIII D
VIII E
VIII F
VIII G
VIII H
VIII I
VIII J
VIII M
VIII N
VIII Q
VIII R
X A
X B
X C
X D
X E
X F
X G
X H
X I
Ar = C6H5
Ar = C6H5
Ar = C6H5
Ar = C6H5
C19H23N3OS
C21H27N3OS
C21H25N3O2S
C22H27N3OS
C19H22N3OSCl
C21H26N3OSCl
C21H24N3O2SCl
C22H26N3OSCl
C20H25N3O2S
C22H29N3O2S
C21H25N3OS
C23H29N3OS
C19H23N3O2S
C21H27N3O2S
C20H25N3OS
C22H29N3OS
C22H27N3O2S
C23H29N3OS
C20H24N3OSCl
C22H28N3OSCl
C22H26N3O2SCl
C23H28N3OSCl
C21H27N3O2S
C23H31N3O2S
C22H27N3OS
C24H31N3OS
C20H25N3O2S
C22H29N3O2S
341
369
383
381
375
403
417
415
371
399
367
395
357
385
355
383
397
395
389
417
431
429
385
413
381
409
371
399
236-238
242-244
249-251
246-248
234-236
240-242
246-248
244-246
233-235
239-241
230-232
240-242
228-230
241-243
224-226
232-234
238-240
236-238
244-246
246-248
249-251
247-249
235-237
240-242
233-246
238-240
232-234
234-236
72
75
70
62
74
72
68
56
72
76
74
72
72
76
74
78
72
65
72
76
62
58
75
70
72
70
74
70
Ar = C6H4-Cl(p)
Ar = C6H4-Cl(p)
Ar = C6H4-Cl(p)
Ar = C6H4-Cl(p)
Ar = C6H4-OCH3(o)
Ar = C6H4-OCH3(o)
Ar = C6H5-CH=CH
Ar = C6H5-CH=CH
Ar = C6H4-OH(o)
Ar = C6H4-OH(o)
Ar = C6H5
Dimethyl amino
Diethyl amino
4-Morpholino
1-Piperidino
Dimethyl amino
Diethyl amino
Dimethyl amino
Diethyl amino
Dimethyl amino
Diethyl amino
Dimethyl amino
Diethyl amino
4-Morpholino
1-Piperidino
Ar = C6H5
Ar = C6H5
Ar = C6H5
Ar = C6H4-Cl(p)
Ar = C6H4-Cl(p)
Ar = C6H4-Cl(p)
Ar = C6H4-Cl(p)
Ar = C6H4-OCH3(o)
Ar = C6H4-OCH3(o)
Ar = C6H5-CH=CH
Ar = C6H5-CH=CH
Ar = C6H4-OH(o)
Ar = C6H4-OH(o)
Dimethyl amino
Diethyl amino
4-Morpholino
1-Piperidino
Dimethyl amino
Diethyl amino
Dimethyl amino
Diethyl amino
Dimethyl amino
Diethyl amino
X J
X M
X N
X Q
X R
TABLE-2
Sabouraud dextrose of czapexs dox agar medium, flucanozole
used as standard drug, the MIC results are represented in
Table-3.
ANTIBACTERIAL ACTIVITIES OF C-AMINOMETHYLATION
OF 5H-5-ARYL-6,7,8,9-TETRAHYDROTHIAZOLO[2,3-b]
QUINAZOLIN-3(2H)-ONE AND 6H-6-ARYL-2,3,7,8,9,10-
HEXAHYDROTHIAZINO[2,3-b]QUINAZOLIN-4(3H)-ONE
Analgesic and anti-inflammatory testing: The analgesic
and anti-inflammatory [15] activities of the Mannich bases
(VIII and X) were determined by standard methods using
albino mice and albino rats, respectively as experimental
animals. Aspirin and diclofenac sodium were employed as
standard drugs. The screening of anti-inflammatory of test
compounds by carrageenan induced rat paw edema method is
used; diclofenac sodium was used as standard. The screening
of analgesic activity of test compounds by Eddy’s hot plate
method, Haffneris tail clip and Writhing methods were used,
aspirin was used as standard drug. The results are represented
in Tables 4 and 5.
Antibaterial activity MIC(µg/mL)
B. subtilis S. aureus
Compound
E. coli
6.25
50
100
200
100
50
50
100
25
100
100
100
200
200
50
100
200
50
100
50
100
100
25
K. pneumonia
6.25
100
200
400
100
100
50
Ciproflaxocin
VIII A
VIII B
VIII C
VIII D
VIII E
VIII F
VIII G
VIII H
VIII I
VIII J
VIII M
VIII N
VIII Q
VIII R
X A
3.12
6.25
50
50
50
6.25
25
50
50
50
50
50
50
50
3.12
12.5
50
100
50
12.5
100
25
100
50
50
50
100
100
50
12.5
50
100
100
12.5
50
25
100
50
100
100
50
100
50
200
400
100
200
200
400
400
100
50
RESULTS AND DISCUSSION
50
All the test compounds of present investigation were found
to be nontoxic as experimental animals were found to be safe.
Among the twenty eight compounds tested, exhibit a mild to
moderate antibacterial activity. Among this series, the test
compounds VIII A (Ar = C6H5, -NR1R2 = dimethyl amino)
and VIII E (Ar = C6H4 –Cl (p), -NR1R2 = dimethyl amino) and
X A (Ar = C6H5,-NR1R2 = dimethyl amino), X E (Ar = C6H4 –
Cl (p), -NR1R2 = dimethyl amino) exhibited most potent
antibacterial towards B. subtilis and S. aureus with MIC values
6.25 and 12.5 µg/mL, respectively. The compounds VIII F
(Ar = C6H4 –Cl (p) -NR1R2 = diethyl amino) VIII G (Ar =
6.25
100
100
50
6.25
25
50
50
50
50
50
50
50
50
X B
X C
X D
X E
X F
X G
X H
X I
X J
X M
X N
X Q
X R
50
200
50
100
200
200
400
100
400
400
200
100
200
100
200
200
100
50
100

2234 Kumaraswamy et al.
Asian J. Chem.
C6H4 –Cl (p), -NR1R2 = morpholino) VIII H (Ar = C6H4 –Cl
(p), -NR1R2 = piperidino) and X F (Ar = C6H4–Cl(p), -NR1R2
= diethylamino) XG (Ar = C6H4 –Cl (p), -NR1R2 = morpholino)
X H (Ar = C6H4 –Cl (p), -NR1R2 = piperidino) showed moderate
antibacterial activity towards B. subtilis, S. aureus and E. coli
with MIC values 25 µg/mL, respectively. Remaining all the
test compounds showed lower antibacterial activity than the
standard drug, ciprofloxacin show in Table-2.
The same test compounds were also found to exhibit a mild
to moderate fungicidal activity. These compounds effectively
inhibit the spore germination of both the fungi Dreschlera halodis
and Fusarium oxysporum.Among all the compounds tested, the
test compounds VIII E (Ar = C6H4 –Cl (p), -NR1R2 = dimethyl
amino) and VIII F (Ar = C6H4 –Cl (p) -NR1R2 = diethyl amino)
and X E (Ar = C6H4 –Cl (p), -NR1R2 = dimethyl amino) exhibited
most potent antifungal towards D. halodis, F. oxysporum and D.
halodis with MIC values 12.5 µg/mL, respectively. The
compounds VIIIG (Ar = C6H4 –Cl (p), -NR1R2 = morpholino)
VIII H (Ar = C6H4 –Cl (p), -NR1R2 = piperidino) and X F (Ar =
C6H4 –Cl (p) -NR1R2 = diethyl amino) X G (Ar = C6H4 –Cl (p),
-NR1R2 = morpholino) X H (Ar = C6H4 –Cl (p), -NR1R2 =
piperidino) showed moderate antifungal activity towards D.
halodis, F. oxysporum, D. halodis, F. oxysporum and D. halodis
with MIC values 25 µg/mL, respectively. Remaining all the test
compounds showed lower antifungal activity than the standard
drug (flucanozole) show in Table-3.
The test compounds showed mild to moderate anti-
inflammatory activity in the range of 36.19 to 79.67 % inhi-
bition of Carrageenan induced rat paw edema, show in Table-4.
Comparatively more activity with 79.67 and 75.23 % of
inhibition was observed for compounds VIIIA (Ar =C6H5,
-NR1R2 = dimethylamino) and XA (Ar = C6H5, -NR1R2 =
dimethylamino) at 4th h among all the test compounds.
Moderate activity was observed for compounds VIIIC (Ar =
C6H5, -NR1R2 = morpholino), VIIIE (Ar = C6H5-Cl (p),-NR1R2
= dimethylamino) and VIII I (Ar = C6H5-OCH3 (o), -NR1R2 =
dimethylamino) X M (Ar = C6H5- CH=CH, -NR1R2 = dimethyl
amino), X N (Ar = C6H5- CH=CH, -NR1R2 = diethyl amino)
with percentage inhibition of 71.61, 70.96, 68.25, 67.61and
66.66, respectively. Compound X Q (Ar = C6H4-OH (o),
-NR1R2 = dimethylmino) showed lowest inhibition with 36.19
% among all the test compounds.
TABLE-4
ANTI-INFLAMMATORY ACTIVITIES OF C-AMINOMETHYLA-
TION OF 5H-5-ARYL-6,7,8,9-TETRAHYDROTHIAZOLO[2,3-b]
QUINAZOLIN-3(2H)-ONE AND 6H-6-ARYL-2,3,7,8,9,10-
HEXAHYDROTHIAZINO[2,3-b] QUINAZOLIN-4(3H)-ONE
Time (h, percentage inhibition
of the paw volume)
Compound
1
NA
2
NA
3
NA
4
NA
Carraggenan
Diclofenac sodium
VIII A
VIII B
VIII C
VIII D
VIII E
VIII F
VIII G
VIII H
VIII I
VIII J
VIII M
VIII N
VIII Q
VIII R
X A
32.84***
11.49
3.44
54.00***
26.33***
22.41***
28.46***
25.62***
19.57***
27.40***
25.97***
24.91***
19.86**
17.77**
14.98*
22.64***
27.17***
13.58*
28.57***
21.95*
22.64**
27.87***
19.16*
18.46*
23.69**
26.13*
18.81
66.34***
47.68***
39.73***
40.39***
41.05***
48.67***
39.73***
43.04***
35.76***
41.34***
33.97***
34.61***
37.50***
33.33***
35.57***
48.39***
43.91***
43.58***
47.11***
45.19***
47.43***
42.94***
41.02***
44.55***
57.05***
49.03***
48.07***
35.25***
44.23***
80.31***
79.67***
63.22***
71.61***
55.48***
70.96***
49.67***
57.09***
60.64***
68.25***
58.73***
46.98***
57.77***
38.09***
36.50***
75.23***
61.26***
60.23***
54.92***
57.61***
58.09***
44.76***
54.76***
56.98***
60.15***
67.61***
66.66***
36.19***
60.58***
TABLE-3
20.68*
7.27
6.51
17.24
8.42
4.98
8.75
0.36
2.91
ANTIFUNGAL ACTIVITIES OF C-AMINOMETHYLATION
OF 5H-5-ARYL-6,7,8,9-TETRAHYDROTHIAZOLO[2,3-b]
QUINAZOLIN-3(2H)-ONE AND 6H-6-ARYL-2,3,7,8,9,10-
HEXAHYDROTHIAZINO[2,3-b]QUINAZOLIN-4(3H)-ONE
Antifungal activity MIC(µg/mL)
Compound
Dreschlera haloids
Fusarium oxysporum
Fluconazole
VIII A
VIII B
VIII C
VIII D
VIII E
VIII F
VIII G
VIII H
VIII I
VIII J
VIII M
VIII N
VIII Q
VIII R
X A
3.12
50
6.25
100
200
400
100
100
12.5
200
25
100
200
200
400
400
100
200
50
100
200
100
12.5
50
7.29
18.97*
4.01
5.47
5.83
9.12
7.29
3.64
6.56
13.13
14.59
7.29
7.66
8.02
5.47
13.13
10.94
X B
X C
X D
X E
X F
X G
X H
X I
X J
X M
X N
X Q
25
100
100
100
100
200
200
50
100
200
50
19.51
14.63
X B
X C
X D
X E
23.69*
28.91**
26.13**
200
50
100
50
100
12.5
25
X R
***p < 0.0 01; **p < 0.01; *p < 0.05
X F
X G
X H
X I
X J
X M
X N
X Q
X R
100
25
100
200
50
100
50
100
25
All the test compounds showed mild to moderate analgesic
activities compared with the standard drug, aspirin. Percentage
protection of analgesic activity in the range of 36-66, show in
Table-5. Comparatively superior analgesic activity exhibit
compounds VIII H (Ar = C6H5-Cl (p), -NR1R2 = piperidino)
and X H (Ar = C6H5-Cl (p), -NR1R2 = piperidino) with 66
400
100
400
400
200
100
200

Vol. 28, No. 10 (2016)
Synthesis and Biological Activities of Some New C-Aminomethylation of 4(3H)-quinazolines 2235
TABLE-5
Conclusion
ANALGESIC ACTIVITIES OF C-AMINOMETHYLATION OF 5H-
5-ARYL-6,7,8,9-TETRAHYDROTHIAZOLO[2,3-b] QUINAZOLIN-
3(2H)-ONE AND 6H-6-ARYL-2,3,7,8,9,10-HEXAHYDROTHIA-
ZINO[2,3-b] QUINAZOLIN-4(3H)-ONE
In the present investigations, the new C-Mannich bases
of quinazolinone derivatives were synthesized by using
appropriate synthetic procedures. Scheme-I showed the
reaction of C-aminomethylation of 5H-5-aryl-6,7,8,9-
tetrahydrothiazolo[2,3-b]quinazolin-3(2H)-one (VIII) and 6H-
6-aryl-2,3,7,8,9,10-hexahydrothiazino[2,3-b] quinazolin-
4(3H)-one (X). All the new derivatives were characterized by
physical and spectral data. It was noted that the most of the
derivatives were show mild to moderate antibacterial, anti-
fungal, anti-inflammatiory and analgesic activities.
Analgesic activity (% protection)
Test
Tail clip
method
Hotplate
method
Writhing
method
compound
Aspirin
VIII A
VIII B
VIII C
VIII D
VIII E
VIII F
VIII G
VIII H
VIII I
VIII J
VIII M
VIII N
VIII Q
VIII R
X A
X B
X C
X D
X E
X F
X G
X H
X I
68
40
44
42
32
50
48
62
64
34
40
42
40
40
45
40
48
40
42
56
50
58
66
40
44
32
40
48
45
64
42
40
42
34
52
46
60
62
37
42
44
43
43
41
46
44
48
44
52
52
60
62
42
40
30
44
46
40
68
44
42
44
36
50
48
58
64
40
44
40
40
36
43
42
40
42
46
54
54
56
60
44
40
48
48
40
46
ACKNOWLEDGEMENTS
The authors are grateful toVaagdevi College of pharmacy
for providing the facilities.
REFERENCES
1. I. Huseyin, Z. Istvan, A. Vildan and E. Ercin, Turk. J. Chem., 36, 583
(2012).
2. N.B. Patel and J.C. Patel, Arabian J. Chem., 4, 403 (2011).
3. A.R.E. Ossman and S.E. Barakat, Arzneimittelforschung, 44, 915 (1994).
4. A. Mallareddy, R. Rajareddy and V. Mallareddy, Indian J. Pharm. Sci.,
53, 229 (1991).
5. B.V. Kumar, H.G.S. Rathore and V.M. Reddy, Indian J. Chem., 21B,
1126 (1982).
6. B.V. Kumar and V.M. Reddy, Indian Drugs, 23, 98 (1985).
7. R. Lakhan and O.P. Singh, Arch. Pharm., 318, 228 (1985).
8. B.V. Kumar, A.B. Rao and V.M. Reddy, J. Indian Chem. Soc., 62, 257
(1985).
9. B.V. Kumar, A.B. Rao and V.M. Reddy, Indian J. Chem., 24B, 889,
(1985).
10. B.V. Kumar, A.B. Rao and V.M. Reddy, Indian Drugs, 22, 373 (1985).
11. V. Madhusudhan Rao, Ph.D. Thesis, Kakatiya University, Warangal, India
(1986).
X J
X M
X N
X Q
12. A.K. Chakravarthy, S. Tatikonda and M.R. Vanga, Heterocycl. Commun.,
12, 389 (2006).
X R
13. Microbiological Assays and Tests, I.P., II, p. 100 (1996).
14. Microbiological Assays, B.P., p. 11, 796, (1953).
15. H.G. Vogel, Drug Discovery and Evaluation: Pharmacological Assays,
Springer, p. 1013, 1014, 1031,1103 (2008).
and 64 % protection, compared with standard drug, aspirin.
Compounds VIII G (Ar = C6H5-Cl (p), -NR1R2 = morpholino)
and X H (Ar = C6H5-Cl (p), -NR1R2 = piperidino) exhibit
moderate analgesic activity with 62 and 60 % protection against
standard aspirin. Remaining all the test compounds showed
lower analgesic activity than the aspirin.