Synthesis and biological screening of some fluorinated dibenzofuran containing 3-chlorochromones and benzothiazepines

Article abstract of DOI:10.1002/jhet.139

(Chemical Equation Presented) Variously substituted chalcones were synthesized from 4-difluoromethoxy-dibenzofuran-1-carboxaldehyde. These chalcones were converted into corresponding 3-chlorochromones and dihydro-benzothiazepines. Synthesized compounds we

Full text of DOI:10.1002/jhet.139

732
Synthesis and Biological Screening of Some Fluorinated
Dibenzofuran Containing 3-Chlorochromones
and Benzothiazepines
Vol 46
Pratibha Randhavane and Bhausaheb Karale*
Department of Chemistry, Radhabai Kale Mahila Mahavidyalaya, Ahmednagar 414001, India
*E-mail: bkkarale@yahoo.com
Received July 3, 2008
DOI 10.1002/jhet.139
Published online 14 July 2009 in Wiley InterScience (www.interscience.wiley.com).
Variously substituted chalcones were synthesized from 4-difluoromethoxy-dibenzofuran-1-carboxalde-
hyde. These chalcones were converted into corresponding 3-chlorochromones and dihydro-benzothiaze-
pines. Synthesized compounds were tested for their antifungal, antibacterial, antiviral and antioxidant
activities.
J. Heterocyclic Chem., 46, 732 (2009).
INTRODUCTION
Halogeno substituted chromones with heterocyclic
substituent at 2-position are reported to have broncho-
dilatory [15], coronary spasmolytic [16], and antimicro-
bial properties [17,18].
In recent days, active research has been initiated on
halogen containing heterocycles, particularly fluorine
containing heterocycles. Incorporation of fluorine can
alter the course of reaction as well as biological activ-
ities. Introduction of fluorine atom into an organic mole-
cule largely enhances the pharmacological properties as
compared with nonfluorinated analogues [1]. Despite the
fact that fluorine has greater size than hydrogen, several
studies have demonstrated that fluorine is a reasonable
hydrogen mimic and exerts only a minor steric demand
at receptor sites [2].
1,4-Benzothiazepine derivatives are of considerable
interest because of their biological activities as inhibi-
tors of HIV-1 integrase [10], anti-tumor, antibiotics,
enzyme inhibitors, muscle relaxant, anticonvulsant, seda-
tives, and hypnotics [19]. Some dihydrobenzothiazepines
have excellent fungicidal activities [20]. Benzothiaze-
pines are also associated with chemotherapeutic applica-
tion such as antihypertension [21] and antibacterial
activities [11,22]. Benzothiazepines have been reported
as potent neuroleptic agents [23].
Fluorine containing organic compounds are associated
with antimicrobial [3], antibacterial [4], and anticancer
[5] activities. They also act as selective inhibitors of
biosynthesis of aminergic neurotransmitters [6].
Biological activities associated with these molecules
and importance of fluorine, prompted us to synthesize
some fluorine containing chalcones, 3-chlorochromones
and 1,4-benzothiazepines, and screen them for biological
activities.
Dibenzofurans are associated with biological activities
like antifungal [7], antibacterial [8], anti-inflammatory,
and antiallergic [9].
Chalcones are versatile synthones and can be cyclized
to give chromones [10], chlorochromones, and benzothia-
zepines [11]. Chalcones can be converted into 3-chloro-
chromones by using DMSOþCuCl2 system [11,12].
Chalcones possess a broad spectrum of biological
activities including antibacterial, anthelmintic, amoebici-
dal, antiulcer, antiviral, insecticidal, antiprotozoal, anti-
cancer, cytotoxic, immunosuppressive, etc. [13,14].
RESULT AND DISCUSSION
In this work, 2-hydroxy acetophenones 2 were treated
with 4-difluoro-methoxy-dibenzofuran-1-carboxaldehyde
1 in presence of 40% KOH to afford corresponding 3-(4-
(difluoromethoxy)dibenzofuran-1-yl)-1-(2-hydroxyphenyl)
prop-2-en-1-one 3. Compound 3 on treatment with copper
C
V
2009 HeteroCorporation

July 2009
Synthesis and Biological Screening of Some Fluorinated Dibenzofuran
Containing 3-Chlorochromones and Benzothiazepines
733
Table 1
Antioxidant activity. The antioxidant activity of
some of the synthesized compounds was determined by
DPPH method using Trolox as a reference standard.
Amongst, the compounds screened for antioxidant activ-
ity none of the compounds showed promising activity as
shown in Table 1.
Antioxidant activity results with test concentration 125 lg/mL.
Compd.
R1
R2
R3
% AO activity
3a
3f
4a
4e
5a
5b
H
H
H
Cl
H
H
H
Cl
H
H
H
H
H
H
ꢀ2.96
5.65
H
Cl
H
ꢀ2.71
ꢀ23.26
4.58
Antimicrobial activity. The antimicrobial activity of
some compounds was assessed against 24 hr culture of
some selected bacteria and fungi. The bacteria used were
Escherichia coli and Staphylococcus aureus; the fungi
used were Candida albicans and Aspergillus fumigatus.
The antimicrobial activity was performed by agar
well diffusion method at 100 and 1000 lg/mL conc. in
DMSO. Nutrient agar and potato dextrose agar were
used to culture the bacteria and fungi, respectively.
Amphotericin B and Vancomycin were used as stand-
ards for comparison of antifungal and antibacterial activ-
ities respectively. The activity is reported by measuring
the diameter of the zone of inhibition. All the screened
compounds were found inactive as shown in Table 2.
Antiviral activity. The antiviral activity of some of
the compounds was determined against Herpes Simplex
virus-2 by CPE inhibition assay. Vero cells (African
green monkey kidney cell line-ATCC # CCL-81) were
cultivated as monolayers in 5% carbon dioxide at 37ꢁC,
in Dulbecco’s modified Eagle medium (MEM) with 5%
fetal bovine serum (FBS).
Br
1.62
chloride in DMSO gave 3-chlorochromone 4 and with 2-
aminothiophenol in alcohol gave benzothiazepine 5.
The structures of compounds 3, 4, and 5 are confirmed
by spectral analysis (IR, 1H-NMR, and MS). The IR spec-
trum of compound 3a shows a strong absorption band
(cmꢀ1) at 3305 for AOH and 1633 for a, b-unsaturated
carbonyl groups. The IR spectrum of compound 4a shows
no absorption band for AOH, whereas the band at 1650 is
for carbonyl group of chromone. The IR spectrum of
compound 5a shows the absorption band at 3397 for
AOH, whereas the band for carbonyl group is absent.
1
The H-NMR spectra of 3a shows a doublet at 8.40 d
for one proton (J ¼ 15 Hz) for transcoupled protons of
1
a, b-unsaturated carbonyl group. In H-NMR spectrum
of 4a, the presence of triplet for one proton at 6.80 d (J
¼ 72.94 Hz) indicates coupling of proton of AOCHF2
1
group with two fluorine atoms. The H-NMR spectrum
The diluted extracts (100 lg/mL) were transferred to
the aspirated Vero cell monolayers. Cultures were incu-
bated at 37ꢁC for 60 minutes. 100 lL of virus (100
TCID50) was added to each well. The tray was trans-
ferred to an environmental chamber (37ꢁC).
of 5a shows three doublet of doublets at 3.21, 3.47, and
5.97 d, which are the characteristic peaks of dihydroben-
zothiazepine moiety.
The structures of all compounds are also confirmed
by mass spectral analysis. The mass spectra shows Mþ
peaks at corresponding masses of respective molecules.
Cultures were inspected periodically for virus-induced
cytopathic effect (viral CPE). Absence of CPE indicated
Table 2
Antimicrobial activity results.
Antifungal test models
Antibacterial test models
Conc.
(lg/ml)
C. albicans
ATCC 14503
A. fumigatus
ATCC 16424
S. aureus
209P
E. coli
ATCC 25922
Compd.
R1
H
R2
H
R3
H
Remark
3a
100
1000
100
1000
100
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
inactive
inactive
inactive
inactive
inactive
inactive
inactive
inactive
inactive
inactive
inactive
inactive
–
3f
H
H
Cl
H
H
Cl
H
H
H
H
H
H
–
–
–
–
–
–
4a
4e
5a
5b
–
–
–
–
–
–
1000
100
Cl
H
–
–
–
1000
100
–
–
–
–
–
–
1000
100
–
–
–
–
–
–
Br
1000
–
22
–
24
–
18
Amphotericin B (20 lg/ml)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

734
P. Randhavane and B. Karale
Vol 46
Table 3
1-(3,5-Dichloro-2-hydroxyphenyl)-3-(4-(difluoromethoxy)di-
benzofuran-1-yl) prop-2-en-1-one (3e). IR (KBr): 3320, 1642,
Antiviral activity results with test concentration 50 lg/mL.
1
1125, 1076 cmꢀ1; H-NMR (DMSO): d 6.77–7.87 (m, 6H, ar-
omatic, olefinic, and AOCHF2), 7.98–8.42 (m, 3H, aromatic)
8.48–8.50 (m, 2H, aromatic, and b to carbonyl), 12.83 (s, 1H,
AOH); Mass: Mþ 449 with isotopic peaks.
Compd.
R1
R2
R3
% CPE inhibition
3a
3f
4a
4e
5a
5b
Scoring
H
H
H
Cl
H
H
H
Cl
H
H
H
H
H
H
–
–
1-(4-Chloro-2-hydroxyphenyl)-3-(4-(difluoromethoxy)diben-
H
Cl
H
–
–
zofuran-1-yl)prop-2-en-1-one (3f). IR (KBr): 3305, 1635,
1
1599 and 1496, 1125, 1063 cmꢀ1; H-NMR (DMSO): d 6.73–
–
–
7.92 (m, 8H, aromatic, olefinic, and AOCHF2), 8.21–8.42 (m,
4H, aromatic, and b to carbonyl), 12.97 (s, 1H, AOH); Mass:
Mþ 414 with isotopic peaks.
3-Chloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-4H-
chromon-4-one (4a–f). Compound 3 (0.001 mole) was dis-
solved in 15 mL DMSO. To this reaction mixture excess of
CuCl2 (2 gm) was added. The reaction mixture was heated
under mild reflux for 3 hr and left overnight. Then 100 mL ice
Br
ꢀ0–25%
þþ26–50%
þþþ51–75%
þþþþ76–100%
complete inactivation of the virus. Partial inhibition was
considered to be a negative result. All the screened com-
pounds were found inactive as shown in Table 3.
Table 4
EXPERIMENTAL
Physical and analytical data of synthesized compounds.
All the recorded melting points were determined in open
capillary tubes and are uncorrected. IR spectra were recorded
on Perkin-Elmer FTIR spectrophotometer in KBr disc. 1H-
NMR spectra were recorded on Varian 300 MHz spectrometer
and Bruker Avance II 400 MHz spectrometer in DMSO or
CDCl3 as a solvent and TMS as an internal standard. Peak val-
ues are shown in d ppm. Mass spectra were recorded on a Q-T
micromass 5630 mass spectrometer.
3-(4-(Difluoromethoxy)dibenzofuran-1-yl)-1-(2-hydroxy-
phenyl)prop-2-en-1-one (3a–f). Equimolar amount of com-
pound 1 (0.02 mol) and 2 (0.02 mol) were dissolved in 25 mL
of alcohol in conical flask. To this reaction mixture 40% KOH
(10 mL) was added. The reaction mixture was stirred at room
temperature for 48 hr. The contents were then poured into
crushed ice and neutralized with acetic acid. The yellow solid
thus obtained was filtered and crystallized from alcohol to
afford compounds 3. The compounds synthesized by above
procedure are listed in Table 4.
Elemental
analysis
Calcd. (Found)
mp
Compound R1 R2 R3 (ꢁC)
Yield
(%)
C
H
3a
3b
3c
3d
3e
3f
H
H
H
H
Cl
H
H
H
H
H
Cl
H
H
H
H
H
Cl
H
H
H
H
H
H
Cl
H
H
H
H
H
Cl
H
H
H
H
H
Cl
H
157
66
67
65
67
61
68
49
52
51
55
50
55
51
53
51
55
50
51
69.47
3.71
(69.45) (3.73)
57.54 2.85
(57.53) (2.86)
66.34 3.29
(66.33) (3.31)
63.70 3.16
(63.68) (3.16)
58.82 2.69
(58.79) (2.71)
63.70 3.16
(63.68) (3.19)
64.02 2.69
(64.00) (2.71)
53.74 2.05
(53.73) (2.08)
61.34 2.34
(61.32) (2.32)
59.08 2.25
(59.05) (2.27)
54.86 1.88
(54.85) (1.90)
54.86 1.88
(54.85) (1.90)
68.98 3.93
(68.96) (3.94)
59.37 3.20
(59.35) (3.21)
66.53 3.59
(66.51) (3.60)
64.43 3.48
(64.40) (3.50)
60.44 3.08
(60.43) (3.10)
64.43 3.48
(64.40) (3.50)
Br 188
F
Cl
Cl
H
182
201
191
174
184
4a
4b
4c
4d
4e
4f
H
3-(4-(Difluoromethoxy)dibenzofuran-1-yl)-1-(2-hydroxyphenyl)-
prop-2-en-1-one (3a). IR (KBr): 3305, 1633, 1589 and 1501,
Br 200
1115 cmꢀ1 1H-NMR (DMSO): d 6.75–8.22 (m, 12H, aro-
;
matic, olefinic, and AOCHF2), 8.40 (d, 1H, J ¼ 15.00 Hz, b
F
Cl
Cl
H
193
216
205
215
205
to carbonyl), 12.61 (s, 1H, AOH); Mass: Mþ 380.
1-(5-Bromo-2-hydroxyphenyl)-3-(4-(difluoromethoxy)dibenzo-
furan-1-yl)prop-2-en-1-one (3b). IR (KBr): 3308, 1635, 1598
and 1515, 1125 cmꢀ1 1H-NMR (DMSO): d 6.81–8.31 (m,
;
11H, aromatic, olefinic, and AOCHF2), 8.43 (d, 1H, J ¼ 15.10
Hz, b to carbonyl), 12.72 (s, 1H, AOH); Mass: Mþ 459.
3-(4-(Difluoromethoxy)dibenzofuran-1-yl)-1-(5-fluoro-2-
hydroxyphenyl)prop-2-en-1-one (3c). IR (KBr): 3313, 1638,
5a
5b
5c
5d
5e
5f
H
1
1610 and 1519, 1177, 1130 cmꢀ1; H-NMR (DMSO): d 6.87–
Br 217
7.91 (m, 7H, aromatic, olefinic, and AOCHF2 ), 8.13–8.20 (m,
3H, aromatic), 8.40–8.44 (m, 1H, aromatic) 8.55 (d, 1H, J ¼
15.30 Hz, b to carbonyl), 12.87 (s, 1H, AOH); Mass: Mþ 398.
1-(5-Chloro-2-hydroxyphenyl)-3-(4-(difluoromethoxy)dibenzo-
furan-1-yl)prop-2-en-1-one (3d). IR (KBr): 3311, 1636, 1601
F
193
185
213
215
Cl
Cl
H
and 1510, 1125, 1066 cmꢀ1 1H-NMR (DMSO): d 6.72–7.75
;
(m, 7H, aromatic, olefinic, and AOCHF2), 7.98–8.42 (m, 4H,
aromatic) 8.48 (d, 1H, J ¼ 15.17 Hz, b to carbonyl), 12.77 (s,
1H, AOH); Mass: Mþ 414 with isotopic peaks.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
Synthesis and Biological Screening of Some Fluorinated Dibenzofuran
Containing 3-Chlorochromones and Benzothiazepines
735
Scheme 1
cold water was added in it. The solid thus obtained was fil-
tered and washed with dil. HCl and again with water. The
product was crystallized from acetic acid to afford compounds
4. The compounds synthesized by above procedure are listed
in Table 4.
perature and poured into crushed ice. The solid thus obtained
was separated by filtration and crystallized with alcohol to
afford compounds 5. The compounds synthesized by above
procedure are listed in Table 4.
2-(2-(4-(Difluoromethoxy)dibenzofuran-1-yl)-2,3-dihydro-
benzo[b][1,4]thiazepin-4-yl)phenol. (5a). IR (KBr): 3397,
3-Chloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-4H-
chromon-4-one (4a). IR (KBr): 1650, 1128, 1072 cmꢀ1; H-
1
1598 and 1499, 1123 cmꢀ1 1H-NMR (CDCl3): d 3.21 (dd,
;
NMR (CDCl3): d 6.80 (t, 1H, J ¼ 72.94 Hz, AOCHF2), 7.15–
8.13 (m, 10H, aromatic); Mass: Mþ 491 with isotopic peaks.
6-Bromo-3-chloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-
1H,) 3.47 (dd, 1H), 5.97 (dd, 1H), 6.81 (t, 1H, J ¼ 72.97Hz,
AOCHF2), 6.99–7.90 (m, 14H, aromatic), 15.77 (s, 1H,
AOH); Mass: Mþ 487.
4-Bromo-2-(2-(4-(difluoromethoxy)dibenzofuran-1-yl)-2,3-
dihydrobenzo[b][1,4] thiazepin-4-yl)phenol (5b). IR (KBr):
3395, 1595 and 1518, 1116 cmꢀ1 1H-NMR (CDCl3): d 3.23
;
(dd, 1H), 3.49 (dd, 1H), 5.95 (dd, 1H), 6.84 (t, 1H, J ¼
72.95Hz, AOCHF2), 7.02–7.85 (m, 13H, aromatic), 15.79(s,
1H, AOH); Mass: Mþ 566.
2-(2-(4-(Difluoromethoxy)dibenzofuran-1-yl)-2,3-dihydro-
benzo[b][1,4]thiazepin-4-yl)-4-fluorophenol (5c). IR (KBr):
;
3398, 1170, 1145 cmꢀ1 1H-NMR (CDCl3): d 3.24 (dd, 1H),
4H-chromon-4-one (4b). IR (KBr): 1647, 1135, 1065 cmꢀ1
;
1H-NMR (CDCl3): d 6.83 (t, 1H, J ¼ 72.95 Hz, AOCHF2)
7.25–7.77 (m, 8H, aromatic), 8.22 (d, 1H, aromatic ); Mass:
Mþ 491 with isotopic peaks.
3-Chloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-6-fluoro-
4H-chromon-4-one (4c). IR (KBr): 1658, 1169, 1132, 1078
cmꢀ1
;
1H-NMR (CDCl3): d 6.87 (t, 1H, J ¼ 72.95 Hz,
AOCHF2) 7.35–7.92 (m, 8H, aromatic), 8.32 (m, 1H, aro-
matic); Mass: Mþ 430 with isotopic peaks.
3,6-Dichloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-4H-
3.50 (dd, 1H), 5.95 (dd, 1H), 6.85 (t, 1H, J ¼ 72.96Hz,
AOCHF2), 7.32–8.20 (m, 13H, aromatic), 15.82 (s, 1H,
AOH); Mass: Mþ 505.
chromon-4-one (4d). IR (KBr): 1652, 1135, 1075 cmꢀ1 1H-
;
NMR (CDCl3): d 6.85 (t, 1H, J ¼ 72.94 Hz, AOCHF2), 7.25–
7.74 (m, 8H, aromatic), 8.22(d, 1H, aromatic); Mass: Mþ 447
with isotopic peaks.
4-Chloro-2-(2-(4-(difluoromethoxy)dibenzofuran-1-yl)-2,3-
dihydrobenzo[b][1,4] thiazepin-4-yl)phenol. (5d). IR (KBr):
1
3,6,8-Trichloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-
4H-chromon-4-one (4e). IR (KBr): 1662, 1134, 1107, 1072,
3390, 1590 and 1489, 1131, 1070 cmꢀ1; H-NMR (CDCl3): d
3.23 (dd, 1H), 3.58 (dd, 1H), 6.00 (dd, 1H), 6.82 (t, 1H, J ¼
72.95 Hz, AOCHF2), 7.15–7.98 (m, 13H, aromatic), 15.77(s,
1H, AOH); Mass: Mþ 521 with isotopic peaks.
2,4-Dichloro-2-(2-(4-(difluoromethoxy)dibenzofuran-1-yl)-2,3-
dihydrobenzo[b] [1,4]thiazepin-4-yl)phenol (5e). IR (KBr):
3409, 1125, 1072 cmꢀ1 1H-NMR (CDCl3): d 3.29(dd, 1H),
;
3.47 (dd, 1H), 6.00 (dd, 1H), 6.85 (t, 1H, J ¼ 72.96 Hz,
AOCHF2), 7.11–7.95 (m, 10H, aromatic),8.02 (d, 1H, aro-
matic), 8.23 (d, 1H, aromatic), 15.74 (s, 1H, AOH); Mass: Mþ
556 with isotopic peaks.
1
1052, 1015 cmꢀ1; H-NMR (CDCl3): d 6.97 (t, 1H, J ¼ 72.96
Hz, AOCHF2) 7.26–7.70 (m, 6H, aromatic), 7.81 (d, 1H, J ¼
2.48 Hz, aromatic), 8.26 (d, 1H, J ¼ 2.48 Hz, aromatic);
Mass: Mþ 481 with isotopic peaks.
3,7-Dichloro-2-(4-(difluoromethoxy)dibenzofuran-1-yl)-4H-
chromon-4-one (4f). IR (KBr): 1655, 1125, 1080 cmꢀ1
;
1H-
NMR (CDCl3): d 6.88 (t, 1H, J ¼ 72.93Hz, AOCHF2), 7.23–
7.80 (m, 9H, aromatic), Mass: Mþ 447 with isotopic peaks.
2-(2-(4-(Difluoromethoxy)dibenzofuran-1-yl)-2,3-dihydro-
benzo[b][1,4]thiazepin-4-yl)phenol (5a–f). Compound
3
3-Chloro-2-(2-(4-(difluoromethoxy)dibenzofuran-1-yl)-2,3-
dihydrobenzo[b][1,4] thiazepin-4-yl)phenol. (5f). IR (KBr):
(0.001 mol) and 2-aminothiophenol (0.001 mol) were dissolved
in 15 mL ethanol in 100 mL RBF. The reaction mixture was
heated under reflux for 4 hr. Then 5 mL glacial acetic acid
was added and heating was continued for further 4 hr. After
completion of reaction, the contents were cooled to room tem-
3395, 1592 and 1501, 1131 cmꢀ1 1H-NMR (CDCl3): d 3.25
;
(dd, 1H), 3.49 (dd, 1H), 5.99 (dd, 1H), 6.82 (t, 1H, J ¼
72.95Hz, AOCHF2), 7.21–8.06 (m, 13H, aromatic), 15.80 (s,
1H, AOH); Mass: Mþ 521 with isotopic peaks.
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

736
P. Randhavane and B. Karale
Vol 46
[13] Chen, M.; Christensen, S. B.; Blom, J.; Lemmich, E. Nadel-
mann, L.; Fich, K.; Theander, T.G.; Kharazmi, A. Antimicrob Agents
1993, 37, 2550.
Acknowledgments. Authors are highly thankful to Dr. Saji
George, Nicholas Piramal Research Centre, Mumbai for provid-
ing the biological activities. Authors are also thankful to the Prin-
cipal Dr. T. N. Gholap for providing the necessary facilities.
[14] Chen, M.; Theander, T. G.; Christensen, S. B.; Kharazmi,
A. Antimicrob Agents Chemother 1994, 38, 1470.
[15] Wiley, P. F. J Am Chem Soc 1952, 74, 4329.
REFERENCES AND NOTES
[16] (a) Jongerbreur, G. Arch Int Pharmacodyn 1952, 90, 384;
(b) Schmtz, J.; Hirt, R.; Eichenberger, F. E.; Lavener, H. Helv Chim
Acta 1953, 36, 620. (c) Wander, A. G. Brit. Pat., 27, 728, 768. (d)
Koo, J. J Org Chem 1961, 26, 1635.
[1] Chu, D. T. W.; Fernandes, P. B.; Claiborne, A. K.; Pihuliac,
E.; Maleczka, C. W.; Pernet, A. G. J Med Chem 1985, 28, 1558.
[2] Park, K. B.; Kitteringham, N. R.; O’Neill, P. M. Annu Rev
Pharmacol Toxicol 2001, 41, 443.
[17] Pawar, S. B.; Shelke, S. N.; Sonawane, S. M.; Gill, C. H.;
Karale, B. K. Orient J Chem 2007, 23, 215.
[3] Shelke, S. N.; Dalvi, N. R.; Kale, S. B.; More, M. S.; Gill,
C. H.; Karale, B. K. Indian J Chem 2007, 46B, 1174.
[4] Patel, V. M.; Desai, K. R. Indian J Chem 2005, 44B, 1084.
[5] Hammam, A. E. G.; El-Salam, O. I. A.; Mohammed, A.
M.; Hafez, N. A. Indian J Chem 2005, 44B, 1887.
[6] Kollonitsh, J.; Patchet, A. A.; Marburg, S.; Maycock, A. L.;
Perkins, L. M.; Doldouras, G. A.; Duggan, D. E.; Aster, S. D. Nature
1978, 274, 906.
[18] Halnor, V. B.; Joshi, N. S.; Karale, B. K.; Gill, C. H. Het
Comm 2005, 11, 16.
[19] (a) Neamati, N.; Turpin, J. A.; Orr, A.; Rice, W. G.; Pom-
mier, Y.; Garafalo, A.; Brizzi, A.; Campiani, G.; Fiorini, I.; Nacci, V.
J Med Chem 1999, 42, 3334. (b) Garafelo, A.; Balconi, G.; Botta, M.;
Corelli, F.; D’ Incalci, M.; Fabrizi, G.; Lamba, D.; Nacci, V. Eur J
Med Chem 1993, 28, 213. (c) Grunewald, G. L.; Dahanukar, V. H.;
Ching, P.; Criscione, K. R. J Med Chem 1996, 39, 3539. (d) Tosh-
iyuki, H.; Takiharo, I.; Hisao, J.P. 7272107. Chem Abstr 1972, 77,
140187f.
[7] Qu, J.; Xie, C.; Guo, H.; Yu, W.; Lou, H. Phytochemistry
2007, 68, 1767.
[8] Purohit, N. V.; Sanghavi, T. Indian J Hetercycl Chem 2005,
14, 235.
[9] Balasubramanian, G.; Gharat, L. A.; Lakdawala, A. D.;
Anupindi, R. R. PCT Int Appl W.O. 2004037805 A1 254, 6 May
(2004). Chem Abstr 140, 391192 (2004).
[20] Singh, K. P.; Srivastava, V.; Singh and Siddiqui, J. Indian J
Chem 2005, 44B, 2178.
[21] Inoue, H.; Konda, M.; Hashiyama, T.; Oskuka, H.; Watanbe,
A.; Okamura, K.; Takida, M.; Date, T.; Narita, T.; Murata, S.; Odwara,
A.; Sasaki, H.; Nagao, T. Chem Pharm Bull 1997, 45, 1008.
[10] Joshi, N. S.; Shaikh, A. A.; Deshpande, A. P.; Karale, B.
K.; Bhirud, S. B.; Gill, C. H. Indian J Chem 2005, 44B, 422.
[11] Karale, B. K.; Chavan, V. P.; Mane, A. S.; Hangarge,
R. V.; Gill, C. H.; Shingare, M. S. Korean J Med Chem 2000,
10, 84.
[22] Agarkar, S. V.; Gurav, V. M. Indian J Heterocycl Chem
2004, 13, 273.
[12] Sahasrabuddhe, A. S.; Ghiya, B. J. Indian J Chem 1990,
29B, 61.
[23] Bajaj, K.; Srivastava, V. K.; Kumar, A. Indian J Chem
2003, 42B, 1149.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet