Synthesis of substituted N-[4(5-Methyl/phenyl-1,3,4-oxadiazol-2- Yl)-3,6-dihydropyridin-1(2H)-yl]benzamide/benzene sulfonamides as anti-inflammatory and anti-cancer agents

Article abstract of DOI:10.1002/jhet.62

Fourteen novel substituted N-[4(5-methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6- dihydropyridin-1(2H)-yl] benzamide/benzene sulfonamides (11a-n) were synthesized in fair to good yields via sodium borohy-dride reduction of the corresponding substituted N-(benzoylimino)-4-(5-methyl/5-phenyl-1,3,4-oxadia- zol-2yl) pyridinium ylide (10a-n) in absolute ethanol.

Full text of DOI:10.1002/jhet.62

March 2009
Synthesis of Substituted N-[4(5-Methyl/phenyl-1,3,4-oxadiazol-2-
yl)-3,6-dihydropyridin-1(2H)-yl]benzamide/benzene Sulfonamides
as Anti-Inflammatory and Anti-Cancer Agents
309
Madhavi Gangapuram and Kinfe K. Redda*
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University,
Tallahassee, Florida 32307
*E-mail: kinfe.redda@famu.edu
Received September 19, 2008
DOI 10.1002/jhet.62
Published online 23 March 2009 in Wiley InterScience (www.interscience.wiley.com).
Fourteen novel substituted N-[4(5-methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-1(2H)-yl]
benzamide/benzene sulfonamides (11a–n) were synthesized in fair to good yields via sodium borohy-
dride reduction of the corresponding substituted N-(benzoylimino)-4-(5-methyl/5-phenyl-1,3,4-oxadia-
zol-2yl) pyridinium ylide (10a–n) in absolute ethanol.
J. Heterocyclic Chem., 46, 309 (2009).
reduction of N-ylides constitute some of the most impor-
tant methods for preparing tetrahydropyridines. From our
previous research, Redda and coworkers reported the syn-
thesis and anti-inflammatory activity profiles of a few
1,2,3,6-terahydropyrines [32]. The results showed the
pharmacological activites of the derivatives of THP
depended on the nature of the substituents on the THP
ring system (Fig. 1). This investigation is a continuation
of synthesis of 1,2,3,6-tetrahydropyridine designed to
modify the tetrahydropyridine ring and phenyl moieties by
introducing groups with various electronic properties.
Incorporation of the 1,3,4-oxadiazole moiety might
enhance biological activity of the tetrahydropyridine deriv-
atives. Hence, it was thought worthwhile to synthesize
1,3,4-oxadizol-2-yl tetrahydropyridines and study their
anti-inflammatory and anti-cancer activities.
INTRODUCTION
Non steroidal anti-inflammatory drugs (NSAIDs) are
of huge therapeutic benefit in the treatment of rheumatoid
arthritis and anti-inflammatory, analgesic, and antipyretic
activities and are widely used to treat acute and chronic
inflammatory disorders [1,2]. NSAIDs are not only useful
in the treatment of inflammatory diseases but they can
also reduce the risk of Alzheimer’s disease [3,4].
Although NSAIDs are the most widely used drugs, their
long-term clinical employment is associated with signifi-
cant side effects and the steady use determines the onset
of gastrointestinal lesions, bleeding, and nephrotoxicity
[5,6]. Therefore, the discovery of new safer anti-inflam-
matory drugs represents a challenging goal for such a
research area. Functionalized tetrahydropyridine (THP)
ring systems are widely found in biologically active natu-
ral products and pharmaceuticals [7–12]. The anti-inflam-
matory activities of compounds consisting of reduced pyr-
idine systems have been investigated [13–18]. The chem-
istry of substituted 1,3,4-oxadiazoles and their derivatives
received considerable attention during the last decade as
potential antimicrobial, antifungal, anti-inflammatory, an-
algesic, CNS-stimulating, anticonvulsive, anti-cancer, diu-
retic, and antihypertensive agents [19–30]. The electro-
philic cyclization of iminium ions (Mannich cyclization)
to generate unsaturated azacyclic systems [31] and the
synthesis of tetrahydropyridine derivatives by partial
In the current investigation, we have synthesized
many analogs maintaining the 1,3,4-oxadiazole-2-yl-
1,2,3,6-tetrahydropyridine ring and having modifications
on the oxadiazole, phenyl ring, and interchanging the
sulfonyl/carbonyl groups at position X to compare their
biological activities. We expect that these structural
modifications would affect the compounds electron
density, lipophilicity, and the compounds steric
configurations.
Chemistry. The starting compound was 4-(5-methyl/
phenyl-1,3,4-oxadiazol-2-yl)pyridine (3) obtained by the
C
V
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310
M. Gangapuram and K. K. Redda
Vol 46
were performed on silica gel (200–425 mesh). All reactions
and purification procedures were monitored by TLC on What-
man AL SIL g/UV, 250 lm layer flexible plates, with visual-
ization under UV light.
Figure 1. General structure of the target compounds. R ¼ ACH3,
C6H5; R1 ¼ C6H5, 4-OCH3AC6H4, 4-FAC6H4, 4-BrAC6H4, 4-tert-
butyl-C6H4, X ¼ CO, SO2.
General procedure-1
Synthesis of 4-(5-methyl-1,3,4-oxadiazol-2-yl)pyridine (3). To
a solution of isonicotinic acid hydrazide 25 g (182.3 mmol) in
triethyl orthoacetate (135 mL) was added and refluxed for 24
h. The excess triethyl orthoacetate was distilled under reduced
pressure, and the residue was washed with cold ethanol. The
residue was recrystallized from ethanol and obtained as brown
crystals, yield 24 g (81.7%); Mp 148–150ꢀC; 1H NMR
(CDCl3): d 2.66 (s, 3H, ACH3); 7.88 (dd, J ¼ 1.8, 1.5 Hz, 2H,
C3, C5AH); 8.81 (dd, J ¼ 1.8, 1.5 Hz; 2 H, C2, C6AH).
Synthesis of 4-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridine (3). To
a solution of isonicotinic acid hydrazide 20 g (145.6 mmol) in
triethyl orthobenzoate (135 mL) was added and refluxed for 24
h. The excess triethyl orthobenzoate was distilled under
reduced pressure, and the residue was washed with cold etha-
nol. The residue was recrystallized from ethanol and obtained
as light yellow color solid, yield 29.17 g (89.8%); Mp 160–
0
reaction of isonicotinic acid hydrazide and triethyl
orthoacetate/triethylorthobenzoate, which was heated
under reflux for 24 h [33] as outlined in Scheme 1. Sub-
stituted N-[4(5-methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6-
dihydropyridin-1(2H)-yl]benzamide/benzenesulfonamides
(11a–n) were prepared via partial reduction of N-ylides
with a mild reducing agent, as outlined in Scheme 2.
The ylides were prepared by coupling N-aminopyridi-
num salt (8) with appropriate acyl chlorides or sulfonyl
chlorides. O-mesitylene sulfonyl hydroxylamine
(MSH) (7) was used to prepare the N-amino salt as an
aminating agent [34]. Reaction of N-aminopyridinium
derivatives with substituted acylating agents like acyl
chlorides and sulfonyl chlorides, followed by treatment
with a base afforded N-ylides (10) as stable crystalline
solids. Sodium borohyride reduction of (10a–n) in
absolute ethanol furnished the target compounds sub-
161ꢀC. 1H NMR (CDCl3):
d 7.51–7.61 (m. 3H, C3 ,
0
0
0
0
C4 C5 AH); 7.98 (d, J ¼ 5.1 Hz, 2H, C2 , C6 AH); 8.12 (dd, J
¼ 1.8, 1.5 Hz; 2 H, C3, C5AH), 8.84 (d, J ¼ 6.9 Hz, 2H, C2,
C6AH).
General procedure-2
Synthesis of 1-(benzoylimino)-4-(5-methyl-1,3,4-oxadiazol-2yl)
pyridinium ylide (10a). To an ice cooled solution of 4-(5-
methyl-1,3,4-oxadiazol-2yl)pyridine (4.35 g, 26.99 mmol) in
15 mL of dry methylene chloride was added dropwise O-mesi-
tylenesulfonylhydroxylamine (5.81 g, 26.99 mmol) in 10 mL
of dry methylene chloride over 5 min with stirring. The reac-
tion stirred at 0ꢀC for 3 h at which time 60 mL of ether was
added and the suspension filtered. The precipitate was recrys-
tallized from ethyl acetate-methanol (5:1 v/v) to give 1-amino-
4-(5-methyl-1,3,4,-oxadiazol-2-yl)pyridinium mesitylene sulfo-
nate (7) in 57.5% yield. The N-aminopyridinium salt (2.0 g,
5.096 mmol) in 30 mL of anhydrous tetrahydrofuran (THF)
containing triethylamine at 70ꢀC was stirred for 5 min before
benzoyl chloride (1.43 g, 10.19 mmol) was added. The mixture
was allowed to proceed for 12 h at which time 70 mL of satu-
rated sodium bicarbonate (NaHCO3) was used to arrest the
reaction. The product 1-[(benzoylimino)-4-(5-methyl-1,3,4-oxa-
diazol-2yl)]pyridinium ylide (10a) was extracted with (2 ꢁ
100 mL) of chloroform and dried over anhydrous sodium sul-
fate. The solvent was removed in vacuo to give crude product,
which was purified by column chromatography (2.5 ꢁ 22 cm)
on silica gel (200–425 mesh) using ethyl acetate: methanol
(9:1 v/v) as eluent. The resultant product (10a) was off-white
solid obtained in 34.4% yield, Mp 273–275ꢀC; IR (KBr): m
1593 (C¼¼O)/cm; 1H NMR (CDCl3): d 2.71 (s, 3H, ACH3 of
stituted
N-[4(5-methyl/phenyl-1,3,4-oxadiazol-2-yl)-
3,6-dihydropyridin-1(2H)-yl] benzamide/benzene sulfo-
namides (11a–n).
RESULTS AND DISCUSSION
The results of synthesis of the pyridinium ylides
(10a–n) and corresponding tetrahydropyridines (11a–n)
are summarized in Table 1 and Table 2. The tetrahydro-
pyridines are thermally stable and soluble in chloroform,
dichloromethane, and other polar solvents. Analytical
data of these compounds 10a–n and 11a–n are presented
in Tables 3 and 4. The pharmacological evaluations of
the compounds for anti-inflammatory and anti cancer
activities are underway.
EXPERIMENTAL
The structures of the products described were confirmed by
IR, 1H NMR, and elemental analysis data. 1H NMR spectra
were determined on a Varian Gemini HX 300 MHz spectrome-
ter using CDCl3 as solvent unless otherwise specified. Chemi-
cal shifts (d) are reported in parts per million (ppm) downfield
from TMS as an internal standard. Infrared spectra were run
with KBr pellets on a Perkin–Elmer 1430 FT spectrometer.
Elemental analyses were performed by Galbraith Laboratories
(Knoxville, TN). Melting points were determined on a Mel-
Temp 3.0 melting point apparatus and were uncorrected.
Chemicals and solvents were purchased from Sigma-Aldrich
Chemical Company (Milwaukee, WI), Fisher Scientific Com-
pany (Suwannee, GA). Separations on column chromatography
0
0
0
oxadiazol ring), 7.43 (m, 3H, C3 , C4 and C5 AH), 8.18 (m,
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2009
Synthesis of Substituted N-[4(5-Methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-
1(2H)-yl] benzamide/benzene Sulfonamides as Anti-Inflammatory and Anti-Cancer Agents
311
Scheme 2. Reaction conditions: (i) DMF, Et3N, 0ꢀC, 45 min; (ii) 70% HC1O4, p-dioxane, 0ꢀC, 45 min; (iii) 4-substituted pyridine, CH2C12, 0ꢀC,
3 h; (iv) 4-substituted acyl/sulfonyl chloride, dry THF, 70ꢀC; (v) NaBH4, abs. EtOH, 7 h, X ¼ CO, SO2. R1 ¼ C6H5, 4-OCH3AC6H4, 4-FAC6H4,
4-BrAC6H4, 4-tert-C4H9AC6H4.
0
0
4H, C3, C5 and C2 , C6 AH), 9.18 (d, J ¼ 7.2 Hz, 2H, C2,
10e was obtained following general procedure 2 as yellow
crystalline solid obtained in 24.6% yield, Mp 246–248ꢀC; IR
(KBr): m 1604 (C¼¼O)/cm; 1H NMR (CDCl3): d 1.35 (s 9H,
tert-butyl group), 2.70 (s, 3H, ACH3 of oxadiazol ring), 7.44
C6AH).
Synthesis of 1-[(4-methoxy benzoyl)imino]-4-(5-methyl-
1,3,4-oxadiazol-2-yl) pyridinium ylide (10b). The compound
10b was obtained following general procedure 2 as yellow
crystalline solid obtained in 50.6% yield, Mp 253–254ꢀC; IR
(KBr) m 1605 (C¼¼O)/cm ; 1H NMR (CDCl3): d 2.70 (s, 3H,
ACH3 of oxadiazol ring), 3.86 (s, 3H, AOCH3 group), 6.94
0
0
0
(d, 2H, J ¼ 8.4 Hz, C3 , C5 AH), 8.09 (d, 2H, J ¼ 8.1 Hz, C2 ,
0
C6 AH), 8.18 (d, 2H, J ¼ 6.9 Hz, C3, C5AH), 9.18 (d, 2H, J
¼ 7.2 Hz, C2, C6AH).
Synthesis of 4-(5-methyl-1,3,4-oxadiazol-2-yl)-1-[(phenyl-
sulfonyl)amino]pyridinium ylide (10f). The compound 10f
was obtained following general procedure 2 as brown crystal-
line solid obtained in 47.8% yield, Mp 268–269ꢀC; IR (KBr):
m 1332, 1205 (SO2)/cm; 1H NMR (CDCl3): d 2.69 (s, 3H,
0
0
(d, J ¼ 9.0 Hz, 2H, C3 ,C5 AH), 8.16 (dd, J ¼ 7.2, 8.7 Hz,
0
0
4H, C3,C5, and C2 ,C6 AH), 9.18 (d, J ¼ 7.5 Hz, 2H, C2,
C6AH).
Synthesis of 1-[(4-fluorobenzoyl)imino]-4-(5-methyl-1,3,4-
oxadiazol-2-yl) pyridinium ylide (10c). The compound 10c
was obtained following general procedure 2 as white solid
obtained in 51.3% yield, Mp 283–284ꢀC; IR (KBr): m 1604
(C¼¼O)/cm; 1H NMR (CDCl3): d 2.71 (s, 3H, ACH3 of oxa-
0
0
ACH3 of oxadiazol ring), 7.37–7.45 (m, 3H, C3 , C4 and
0
C5 AH), 8.16 (ddd, 4H, J ¼ 7.2, 1.7, and 2.3 Hz, C3, C5 and
0
0
C2 , C6 AH), 9.16 (d, 2H, J ¼ 7.2 Hz, C2, C6AH).
Synthesis of 1-{[(4-methoxyphenyl)sulfonyl]imino}-4-(5-
methyl-1,3,4-oxadiazol-2-yl) pyridinium ylide (10g). The com-
pound 10g was obtained following general procedure 2 as
brown crystalline solid obtained in 56.2% yield, Mp 218–
0
0
diazol ring), 7.09 (t, 2H, J ¼ 9.0 Hz, C3 , C5 AH), 8.16 (d,
0
0
2H, J ¼ 6.0 Hz, C2 , C6 AH), 8.21 (d, 2H, J ¼ 7.2 Hz, C3,
C5AH), 9.16 (d, 2H, J ¼ 6.6 Hz, C2, C6AH).
1
Synthesis of 1-[(4-bromobenzoyl)imino]-4-(5-methyl-
1,3,4-oxadiazol-2-yl) pyridinium ylide (10d). The com-
pound 10d was obtained following general procedure 2 as
yellow color solid obtained in 61.9% yield, Mp 290–
291ꢀC; IR (KBr): m 1601 (C¼¼O)/cm; 1H NMR (CDCl3): d
2.69 (s, 3H, ACH3 of oxadiazol ring), 7.53 (d, 2H J ¼ 8.4
220ꢀC; IR (KBr): m 1280, 1137 (SO2)/cm; H NMR (CDCl3):
d 2.66 (s, 3H, ACH3 of oxadiazol ring), 3.81 (s, 3H, AOCH3
0
0
group), 6.87 (d, 2H, J ¼ 8.8 Hz, C3 , C5 AH), 7.74(dd, 2H, J
0
0
¼ 1.9, 5.0 Hz, C2 , C6 AH), 8.06 (d, 2H, J ¼ 7.1 Hz, C3,
C5AH), 8.63 (d, 2H, J ¼ 7.1 Hz, C2, C6AH).
Synthesis of 1-(benzoylimino)-4-(5-phenyl-1,3,4-oxadiazol-
2yl) pyridinium ylide (10h). The compound 10h was obtained
following general procedure 2 as white crystalline solid
obtained in 39.6% yield, Mp 262–263ꢀC; IR (KBr): m 1548
(C¼¼O)/cm; 1H NMR (CDCl3): d 7.38–7.62 (complex multip-
let, 6H, phenyl protons), 8.16 (ddd, 4H, J ¼ 4.2, 1.5, 1.5 Hz,
0
0
0
0
Hz, C3 , C5 AH), 8.03 (d, 2H, J ¼ 8.4 Hz, C2 , C6 AH),
8.20 (d, 2H, J ¼ 7.2 Hz, C3, C5AH), 9.15 (d, 2H, J ¼ 7.2
Hz, C2, C6AH).
Synthesis of 1-[(4-tert-butylbenzoyl)imino]-4-(5-methyl-
1,3,4-oxadiazol-2-yl) pyridinium ylide (10e). The compound
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312
M. Gangapuram and K. K. Redda
Vol 46
Table 1
Pyridinium ylides synthetic data (10a–n).
Compound
R
R1
X
M.W.
Mp (ꢀC)
Yield (%)
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
10l
10m
10n
CH3
CH3
C6H5
4-OCH3AC6H4
4-FAC6H4
4-BrAC6H4
4-tert-C4H9AC6H4
C6H5
4-OCH3AC6H4
C6H5
4-OCH3AC6H4
4-FAC6H4
CO
CO
CO
CO
CO
SO2
SO2
CO
CO
CO
CO
SO2
SO2
SO2
280.28
319.32
307.28
375.4
273–275
253–254
283–284
290–291
246–248
268–269
218–220
262–263
277–278
296–297
271–272
211–213
259–261
242–244
34.4
50.6
51.3
61.9
24.6
47.8
56.2
39.6
48.5
50.5
82.5
43.6
37.5
74.2
CH3
CH3
CH3
CH3
340.9
316.34
346.36
342.35
372.38
360.34
398.46
378.4
CH3
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-tert-C4H9AC6H4
C6H5
4-OCH3AC6H4
4-tert-C4H9AC6H4
408.43
434.51
0
0
00
00
00
0
0
0
C2 , C6 and C2 , C6 AH), 8.29 (d, 2H, J ¼ 7.2 Hz, C3,
C5 AH), 7.55–7.63 (m, 3H, C3 , C4 , C5 AH), 8.19 (ddd, 4H, J
0
0
00
00
C5AH), 9.21 (d, 2H, J ¼ 7.2 Hz, C2, C6AH).
¼ 5.4, 3.3, 2.4 Hz, C2 , C6 and C2 , C6 AH), 8.34 (d, 2H, J ¼
6.6 Hz, C3, C5AH), 9.21 (d, 2H, J ¼ 6.9 Hz, C2, C6AH).
Synthesis of 1-[(4-tert-butylbenzoyl)imino]-4-(5-phenyl-
1,3,4-oxadiazol-2-yl) pyridinium ylide (10k). The compound
10k was obtained following general procedure 2 as yellow
shiny crystals obtained in 82.5% yield, Mp 271–272ꢀC; IR
Synthesis of 1-[(4-methoxybenzoylimino)]-4-(5-phenyl-
1,3,4-oxadiazol-2yl) pyridinium ylide (10i). The compound 10i
was obtained following general procedure 2 as yellow solid
obtained in 48.5% yield, Mp 277–278ꢀC; IR (KBr): m 1593
1
(C¼¼O)/cm; H NMR (CDCl3): d 3.84 (s, 3H, OCH3), 6.92 (d,
1
00
00
0
0
2H, J ¼ 8.7 Hz C3 , C5 AH), 7.54–7.65 (m, 3H, C3 , C4 ,
(KBr): m 1585 (C¼¼O)/cm; H NMR (CDCl3): d 1.33 (s, 9H, t-
0
0
0
00
00
00
C5 AH), 8.15(dd, 4H, J ¼ 1.2, 8.7 Hz, C2 , C6 and C2 ,
butyl group), 7.43 (d, 2H, J ¼ 8.4 Hz, C3 , C5 AH), 7.53–7.64
00
0
0
0
0
C6 AH), 8.28 (d, 2H, J ¼ 7.2 Hz, C3, C5AH), 9.21 (d, 2H, J
(m, 3H, C3 , C4 , C5 AH), 8.09 (d, 2H, J ¼ 8.4 Hz, C2 ,
0 00 00
¼ 7.2 Hz, C2, C6AH).
C6 AH), 8.15 (dd, 2H, J ¼ 1.2, 6.6 Hz, C2 , C6 AH), 8.28 (d,
2H, J ¼ 7.2 Hz, C3, C5AH), 9.20 (d, 2H, J ¼ 7.2 Hz, C2,
C6AH).
Synthesis of 1-[(4-fluorobenzoylimino)]-4-(5-phenyl-1,3,4-
oxadiazol-2yl) pyridinium ylide (10j). The compound 10j was
obtained following general procedure
2
as yellow solid
Synthesis of 4-(5-Phenyl-1,3,4-oxadiazol-2-yl)-1-[(phenyl)-
sulfonyl]imino] pyridinium Ylide (10l). The compound 10l
was obtained following general procedure 2 as yellow crystals
obtained in 50.5% yield, Mp 296–297ꢀC; IR (KBr): m 1557
1
00
(C¼¼O)/cm; H NMR (CDCl3): d 7.38 (d, 2H, J ¼ 8.7 Hz C3 ,
Table 2
Tetrahydropyridines synthetic data (11a–n).
Compound
R
R1
X
M.W.
Mp (ꢀC)
Yield (%)
11a
11b
11c
11d
11e
11f
11g
11h
11i
11j
11k
11l
11m
11n
CH3
CH3
C6H5
4-OCH3AC6H4
4-FAC6H4
4-BrAC6H4
4-tert-C4H9AC6H4
C6H5
4-OCH3AC6H4
C6H5
4-OCH3AC6H4
4-FAC6H4
CO
CO
CO
CO
CO
SO2
SO2
CO
CO
CO
CO
SO2
SO2
SO2
284.31
314.34
302.30
363.21
340.42
320.37
350.39
366.21
376.41
364.37
402.49
382.44
412.46
438.54
208–210
238–240
215–217
215–217
211–213
208–210
150–152
203–204
217–218
213–215
209–211
162–163
135–136
163–164
61.0
54.3
68.7
33.8
65.4
48.2
54.4
30.4
44.8
51.4
32.5
33.6
42.5
48.5
CH3
CH3
CH3
CH3
CH3
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-tert-C4H9AC6H4
C6H5
4-OCH3AC6H4
4-tert-C4H9AC6H4
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DOI 10.1002/jhet

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Synthesis of Substituted N-[4(5-Methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-
1(2H)-yl] benzamide/benzene Sulfonamides as Anti-Inflammatory and Anti-Cancer Agents
313
Table 3
Elemental analysis of pyridinium ylides (10a–z).
Analysis % Cacld/Found
Compound
R
R1
X
Molecular formula
C15H12N4O2
M.W.
C
H
N
10a
CH3
C6H5
CO
280.28
64.28
64.11
60.18
60.43
58.63
58.69
47.99
48.27
66.07
66.03
54.16
53.97
52.02
51.53
67.02
67.31
67.73
67.57
66.66
67.04
72.34
72.39
60.31
60.71
62.06
61.93
63.58
63.32
4.32
4.30
4.73
4.57
3.77
3.79
3.44
3.11
5.98
6.06
3.82
3.76
4.07
4.27
3.94
4.19
4.33
4.61
3.64
3.47
5.57
5.38
3.73
3.53
3.47
3.25
5.10
5.14
19.99
19.83
17.55
17.40
18.23
18.04
14.92
14.61
16.22
15.99
17.71
17.56
16.18
16.30
15.63
15.78
15.05
14.66
15.55
15.60
14.06
13.82
14.81
14.44
16.08
16.01
12.89
12.42
10b
10c
10d
10e
10f
CH3
CH3
4-OCH3AC6H4
4-FAC6H4
CO
CO
CO
CO
SO2
SO2
CO
CO
CO
CO
SO2
SO2
SO2
C16H14N4O3 0.5 H2O
C15H11FN4O2 0.9 H2O
C15H11BrN4O2 0.9 H2O
C19H20N4O2 0.25 H2O
C14H12N4O3S
319.32
307.28
375.4
CH3
4-BrAC6H4
CH3
4-tert-C4H9AC6H4
C6H5
340.9
CH3
316.34
346.36
342.35
372.38
360.34
398.46
378.4
10g
10h
10i
CH3
4-OCH3AC6H4
C6H5
C15H14N4O4S
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C20H14N4O2
4-OCH3AC6H4
4-FAC6H4
C21H16N4O3
10j
C20H13FN4O2
10k
10l
4-tert-C4H9AC6H4
C6H5
C24H22N4O2
C19H14N4O3S
10m
10n
4-OCH3AC6H4
4-tert-C4H9AC6H4
C20H16N4O4S
408.43
434.51
C23H22N4O3S
obtained in 43.6% yield, Mp 211–213ꢀC; IR (KBr): m 1282,
1150 (SO2)/cm; H NMR (CDCl3): d 7.37–7.64 (complex mul-
General procedure-3
1
N-[4[(5-Methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-1(2H)-
yl] benzamide (11a). A solution of 1-(Benzoylimino)-4-(5-
methyl-1,3,4-oxadiazol-2yl) pyridinium ylide 10a (0.25 g, 0.79
mmol) in dichloromethane: ethanol (1:1 v/v, 40 mL) was
added dropwise to a stirred suspension of sodium borohydride
(0.12 g, 3.16 mmol) in 10 mL of absolute ethanol over a pe-
riod or 30 min. The resulting solution was stirred for 4 h at
0ꢀC and then overnight for a total of 24 h. The excess sodium
borohyride was treated with 50 mL distilled water. It was then
extracted with dichloromethane (200 mL) and dried over anhy-
drous sodium sulfate. The dichloromethane filtrate was evapo-
rated in vacuo and the product chromatographed on a column
of silica gel using ethyl acetate: methanol (9:1 v/v) as an elu-
ent. The solid obtained was further crystallized from dichlor-
methane: ethylacetate (3:2 v/v) and furnished 11a as a white
flakes (61.0% yield), Mp 208–210ꢀC; IR (KBr): m 3213 (NH),
1638 (C¼¼O)/cm; 1H NMR (CDCl3): d 2.54 (s, 3H, ACH3 of
oxadiazol ring), 2.86 (m, 2H, C3AH), 3.34 (t, J ¼ 5.7 Hz, 2H,
C2AH), 3.84 (m, 2H, C6AH), 6.65 (m, 1H, C5AH olefinic pro-
0
tiplet, 6H, phenyl protons), 7.80 (d, 2H, J ¼ 6.9 Hz, C2 ,
0
00
00
C6 AH), 8.12 (d, 2H, J ¼ 6.9 Hz, C2 , C6 AH), 8.20 (d, 2H, J
¼ 6.3 Hz, C3, C5AH), 8.67 (d, 2H, J ¼ 6.6 Hz, C2, C6AH).
Synthesis of 1-{[(4-methoxyphenyl)sulfonyl]imino}-4-(5-
phenyl-1,3,4-oxadiazol-2-yl)-pyridinium Ylide (10m). The
compound 10m was obtained following general procedure 2 as
yellow solid obtained in 37.5% yield, Mp 259–261ꢀC; IR
(KBr): m 1280, 1134 (SO2)/cm; 1H NMR (CDCl3): d 3.81 (s,
00
00
AOCH3), 6.88 (d, 2H, J ¼ 8.7 Hz, C3 , C5 AH), 7.54–7.65
0
0
0
0
(m, 3H, C3 , C4 , C5 AH), 7.76 (d, 2H, J ¼ 8.7 Hz, C2 ,
0
00
00
C6 AH), 8.12 (d, 2H, J ¼ 6.9 Hz, C2 , C6 AH), 8.19 (d, 2H, J
¼ 6.6 Hz, C3, C5AH), 8.70 (d, 2H, J ¼ 6.3 Hz, C2, C6AH).
Synthesis of 1-{[(4-tert-butylphenyl)sulfonyl]imino}-4-(5-
phenyl-1,3,4-oxadiazol-2-yl) pyridinium ylide (10n). The com-
pound 10n was obtained following general procedure 2 as yel-
low solid obtained in 74.2% yield, Mp 242–244ꢀC; IR (KBr):
m 1296, 1136 (SO2)/cm; 1H NMR (CDCl3): d 1.28 (s, 9H, t-
00
00
butyl group), 7.41 (d, 2H, J ¼ 8.4 Hz, C3 , C5 AH), 7.52–7.64
0
0
0
0
0
0
(m, 3H, C3 , C4 , C5 AH), 7.74 (d, 2H, J ¼ 8.4 Hz, C2 ,
ton), 7.17 (brs, 1H, ANH D2O exchange), 7.48 (m, 3H, C3 ,C4
0
00
00
0
0
0
C6 AH), 8.11 (dd, 2H, J ¼ 1.5, 6.9 Hz, C2 , C6 AH), 8.19 (d,
2H, J ¼ 6.6 Hz, C3, C5AH), 8.70 (d, 2H, J ¼ 6.3 Hz, C2,
C6AH).
and C5 AH), 7.74 (d, J ¼ 7.5 Hz, 2H, C2 ,C6 AH).
4-Methoxy-N-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzamide (11b). The compound 11b was
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

314
M. Gangapuram and K. K. Redda
Vol 46
Table 4
Elemental analysis of tetrahydropyridines (11a–z).
Analysis % Cacld/Found
Compound
R
R1
X
Molecular formula
C15H16N4O2
M.W.
C
H
N
11a
11b
11c
11d
11e
11f
CH3
C6H5
CO
284.31
63.37
63.34
61.13
61.11
59.60
59.45
49.60
49.51
67.04
67.4
5.67
5.73
5.77
5.83
5.00
5.05
4.16
4.38
7.11
7.15
5.03
5.11
5.18
5.30
4.95
5.04
5.59
5.40
4.70
4.75
6.51
6.56
4.74
4.78
4.89
4.96
5.98
5.91
19.71
19.62
17.82
17.65
18.53
18.37
15.43
15.15
16.46
16.26
17.49
17.65
15.99
15.79
15.30
15.01
15.55
14.59
15.38
15.18
13.92
13.79
14.65
14.34
13.58
13.47
12.78
12.45
CH3
CH3
4-OCH3AC6H4
4-FAC6H4
CO
CO
CO
CO
SO2
SO2
CO
CO
CO
CO
SO2
SO2
SO2
C16H18N4O3
C15H15FN4O2
C15H15BrN4O2
C19H24N4O2
314.34
302.30
363.21
340.42
320.37
350.39
342.35
376.41
364.37
402.49
382.44
412.46
438.54
CH3
4-BrAC6H4
CH3
4-tert-C4H9AC6H4
C6H5
CH3
C14H16N4O3S
C15H18N4O4S
C20H18N4O21.1H2O
C21H20N4O3
52.49
52.74
51.42
51.70
65.60
65.58
67.01
66.81
65.93
65.92
71.62
71.78
59.67
59.38
58.24
58.26
62.99
62.89
11g
11h
11i
CH3
4-OCH3AC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-OCH3AC6H4
4-FAC6H4
11j
C20H17FN4O2
C24H26N4O2
11k
11l
4-tert-C4H9AC6H4
C6H5
C19H18N4O3S
C20H20N4O4S
C23H26N4O3S
11m
11n
4-OCH3AC6H4
4-tert-C4H9AC6H4
obtained following general procedure 3 as off-white solid
54.3% yield, Mp 238–240ꢀC; IR (KBr): m 3183 (NH), 1625
(C¼O)/cm; 1H NMR (CDCl3): d 2.54 (s, 3H, CH3), 2.85 (m,
2H, C3AH), 3.32 (t, 2H, J ¼ 6.0 Hz, C2AH), 3.82 (brs, 2H,
C6AH), 3.84 (s, AOCH3 group), 6.64 (m, C5AH, olefinic),
(brs, 2H, C6AH), 6.64 (m, 1H, C5AH, olefinic proton), 7.72 (t,
0
0
2H, J ¼ 8.6 Hz, C3 , C5 AH), 7.13 (brs, NH proton, D2O
0
0
exchange), 7.75 (d, 2H, J ¼ 8.4 Hz, C2 , C6 AH).
4-tert-Butyl--N-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzamide (11e). The compound 11e was
obtained following general procedure 3 as off-white solid
65.4% yield, Mp 211–213ꢀC; IR (KBr): m 3274 (NH), 1643
0
0
6.92 (d, 2H, J ¼ 8.7 Hz, C3 ,C5 AH), 7.14 (brs, ANH, D2O
0
0
exchange), 7.72 (d, 2H, J ¼ 8.4 Hz, C2 , C6 AH).
1
4-Fluoro-N-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzamide (11c). The compound 11c was
obtained following general procedure 3 as white granules
68.7% yield, Mp 215–217ꢀC; IR (KBr): m 3190 (NH), 1636
(C¼¼O)/cm; H NMR (CDCl3): d 1.31 (s 9H, tert-butyl group),
2.52 (s, 3H, ACH3 of oxadiazol ring), 2.84 (m, 2H, C3AH),
3.30 (t, 2H, J ¼ 5.4 Hz, C2AH), 3.81 (brs, 2H, C6AH), 6.62
(m, 1H, C5AH, olefinic proton), 7.14 (brs, 1H, ANH proton,
1
0
0
(C¼¼O)/cm; H NMR (CDCl3): d 2.52 (s, 3H, CH3 of oxadia-
D2O exchange), 7.43 (d, 2H, J ¼ 8.3 Hz, C3 , C5 ,AH), 7.66
0 0
zol ring), 2.84 (m, 2H, C3AH), 3.30 (t, 2H, J ¼ 6.2 Hz,
C2AH), 3.81 (brs, 2H, C6AH), 6.62 (m, 1H, C5AH, olefinic
(d, 2H, J ¼ 8.1 Hz, C2 , C6 AH).
N-[4-(5-Methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-1
(2H)-yl]-benzene sulfonamide (11f). The compound 11f was
obtained following general procedure 3 as white solid 48.2%
yield, Mp 208–210ꢀC; IR (KBr): m 3069 (NH), and 1332,
1164 (SO2)/cm; 1H NMR (CDCl3): d 2.53 (s, 3H, ACH3 of
oxadiazol ring), 2.85 (m, 2H, C3AH), 3.31 (t, 2H, J ¼ 5.8
Hz, C2AH), 3.82 (brs, 2H, C6AH), 6.63 (m, 1H, C5AH,
olefinic proton), 7.16 (brs, ANH, D2O exchange), 7.40–7.54
0
0
proton), 7.71 (t, 2H, J ¼ 8.6 Hz, C3 , C5 AH), 7.15 (brs, 1H,
0
NH proton, D2O exchange), 7.75 (d, 2H, J ¼ 8.4 Hz, C2 ,
0
C6 AH).
4-Bromo-N-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro
pyridin-1(2H)-yl]-benzamide (11d). The compound 11d was
obtained following general procedure 3 as yellow solid 33.8%
yield, Mp 216–217ꢀC; IR (KBr): m 3185 (NH), 1635 (C¼¼O)/
1
0
0
0
0
(m 3H, C3 , C4 , C5 AH), 7.73 (d, 2H, J ¼ 7.3 Hz, C2 ,
cm; H NMR (CDCl3): d 2.53 (s, 3H, CH3 of oxadiazol ring),
0
C6 AH).
2.85 (m, 2H, C3AH), 3.31 (t, 2H, J ¼ 6.2 Hz, C2AH), 3.81
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2009
Synthesis of Substituted N-[4(5-Methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-
1(2H)-yl] benzamide/benzene Sulfonamides as Anti-Inflammatory and Anti-Cancer Agents
315
4-Methoxy-N-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzene sulfonamide (11g). The compound
11g was obtained following general procedure 3 as white gran-
ules 54.4% yield, Mp 150–152ꢀC; IR (KBr): m 3078 (NH), and
4-Methoxy-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzene-sulfonamide (11m). The compound
11m was obtained following general procedure 3 as white
solid 42.5% yield, Mp 135–136ꢀC; IR (KBr): m 3089 (NH),
1330, 1154 (SO2)/cm; 1H NMR (CDCl3): d 2.67 (m, 2H,
C3AH), 2.81 (t, 2H, J ¼ 5.4 Hz, C2AH), 3.51 (d, 2H, J ¼ 3.0
Hz, C6AH), 3.87 (s, 3H, AOCH3), 5.45 (s, 1H, ANH, D2O
exchange), 6.63 (m, 1H, C5AH, olefinic proton), 6.98 (d, 2H,
1
1331, 1163 (SO2)/cm; H NMR (CDCl3): d 2.50 (s, 3H, ACH3
of oxadiazol ring), 2.49 (m, 2H, C3AH), 2.77 (t, 2H, J ¼ 5.4
Hz, C2AH), 3.45 (d, 2H, J ¼ 3 Hz, C6AH), 3.86 (s, 3H,
AOCH3), 5.47 (s, 1H, ANH, D2O exchange), 6.46 (m, 1H,
0
0
0
0
00
00
C5AH olefinic proton), 6.96 (d, 2H, J ¼ 9.0 Hz, C3 , C5 AH),
J ¼ 9.0 Hz, C3 , C5 AH), 7.45–7.54 (m, 3H, C3 , C4 ,
0
0
0
0
0
7.86 (dd, 2H, J ¼ 3.0, 6.9 Hz, C2 ,C6 AH).
C5 AH), 7.88 (d, 2H, J ¼ 9.0 Hz, C2 , C6 AH), 8.02 (dd, 2H, J
00 00
N-[4-(5-Phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-1
(2H)-yl]benzamide (11h). The compound 11h was obtained
following general procedure 3 as white granules 30.4% yield,
¼ 1.2, 6.6 Hz, C2 , C6 AH).
4-tert-butyl-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]benzene sulfonamide (11n). The compound
11n was obtained following general procedure 3 as white solid
48.5% yield, Mp 163–134ꢀC; IR (KBr): m 3088 (NH), 1335,
1152 (SO2)/cm; 1H NMR (CDCl3): d 1.33 (s, 9H, t-butyl
group), 2.67 (m, 2H, C3AH), 2.81 (t, 2H, J ¼ 5.4 Hz, C2AH),
3.52 (d, 2H, J ¼ 2.4 Hz, C6AH), 5.55 (brs, 1H, ANH, D2O
exchange), 6.64 (m, 1H, C5AH, olefinic proton), 6.98 (d, 2H,
1
Mp 203–204ꢀC; IR (KBr): m 3189 (NH), 1635 (C¼¼O)/cm; H
NMR (CDCl3): d 2.93 (m, 2H, C3AH), 3.36 (t, 2H, J ¼ Hz,
C2AH), 3.88 (brs, 2H, C6AH), 6.79 (m, 1H, C5AH, olefinic
proton), 7.21 (brs, 1H, ANH, D2O exchange), 7.40–7.53 (com-
0
0
0
00
00
00
plex m, 6H, C3 , C4 , C5 and C3 , C4 , C5 AH), 7.74 (d, 2H, J
0
0
00
¼ 7.2 Hz, C2 , C6 AH), 8.05 (dd, 2H, J ¼ 1.2, 6.0 Hz C2 ,
00
00
00
0
0
0
C6 AH,).
J ¼ 9.0 Hz, C3 , C5 AH), 7.45–7.54 (m, 3H, C3 , C4 , C5 AH),
0
0
4-Methoxy-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzamide
7.88 (d, 2H, J ¼ 9.0 Hz, C2 , C6 AH), 8.02 (dd, 2H, J ¼ 1.2,
00 00
(11i). The
compound
11i
6.6 Hz, C2 , C6 AH).
was obtained following general procedure 3 as white solid
44.8% yield, Mp 217–218ꢀC; IR (KBr): m 3221 (NH), 1638
(C¼¼O)/cm; 1H NMR (CDCl3): d 2.91 (m, 2H, C3AH), 3.34
(t, 2H, J ¼ 5.7 Hz, C2AH), 3.83 (s, 3H, AOCH3), 3.86 (brs,
2H, C6AH), 6.78 (m, 1H, C5AH, olefinic proton), 6.90 (d,
Acknowledgment. The authors are grateful to the National
Institute of Health, the National Institute of General Medical
Sciences, MBRS Program (GM 08111), Research Center at
Minority Institutions Grant (RCMI) RR 03020, and Pharmaceu-
tical Research Center NIH/NCRR Grant 1 C06 RR12512-01.
00
00
2H, J ¼ 8.7 Hz, C3 , C5 AH), 7.15 (brs, 1H, ANH, D2O
0
0
0
exchange), 7.45–7.54 (m, 3H, C3 , C4 , C5 AH), 7.71 (d, 2H,
00
00
0
J ¼ 7.8 Hz, C2 , C6 AH), 8.05 (dd, 2H, J ¼ 1.5, 6.0 Hz, C2 ,
0
C6 AH).
REFERENCE AND NOTES
4-Fluoro-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydro-
pyridin-1(2H)-yl]-benzamide (11j). The compound 11j was
obtained following general procedure 3 as white solid 51.4%
yield, Mp 213–215ꢀC; IR (KBr): m 3185 (NH), 1637 (C¼¼O)/
[1] Vane, J. R.; Botting, R. M. Int J Tissue React 1998, 20, 3.
[2] Carty, T. J.; Marfat, A. Curr Opinion Anti-Inflamm Immu-
nomodul Invest Drugs 1999, 1, 89.
[3] Andersen, K.; Launer, L. J.; Ott, A.; Hoes, A. W.; Breteler,
M. M. B.; Hofman, A. Neurology 1995, 45, 1441.
[4] Breitner, J. C. S. Annu Rev Med 1996, 47, 401.
[5] Sveigard, H. H.; Dalgaard, L. Pharm Res 2000, 17, 70.
[6] Ma, Y.; Loesewetter, D. O.; Kagpda, E. M.; Huang, B. X.;
Eckelman, W. C. J Chromatogr B 2002, 766, 319.
[7] Yeung, J. M.; Corleto, L. A.; Knaus, E. E. J Med Chem
1982, 25, 191.
1
cm; H NMR (CDCl3): d 2.92 (m, 2H, C3AH), 3.34 (t, 2H, J
¼ 5.8 Hz, C2AH), 3.86 (brs, 2H, C6AH), 6.78 (m, 1H, C5AH,
00
00
olefinic proton), 7.10 (t, 2H, J ¼ 8.7 Hz, C3 , C5 AH), 7.25
0
0
(brs, 1H, ANH, D2O exchange), 7.45–7.55 (m, 3H, C3 , C4 ,
0
0
0
C5 AH), 7.71 (d, 2H, J ¼ 7.8 Hz, C2 , C6 AH), 8.05 (dd, 2H, J
00
00
¼ 0.9, 6.3 Hz, C2 , C6 AH).
4-tert-Butyl-N-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-3,6-dihyd-
ropyridin-1(2H)-yl]benzamide (11k). The compound 11k was
obtained following general procedure 3 as white solid 32.5%
yield, Mp 209–211ꢀC; IR (KBr): m 3211 (NH), 1638 (C¼¼O)/
[8] Tiffany, L. W.; Redda, K. K. Med Chem Res 2003, 12,
69.
[9] Redda, K. K.; Corleto, L. A.; Knaus, E. E. J Med Chem
1979, 22, 1079.
1
cm; H NMR (CDCl3): d 1.31 (s, 9H, t-butyl group), 2.94 (m,
[10] Redda, K. K.; Kode, R. N.; Heiman, A. S.; Onayemi, F. Y.;
Clark, J. B. Chem Pharm Bull 1991, 39, 786.
2H, C3AH), 3.40 (t, 2H, J ¼ 5.7 Hz, C2AH), 3.92 (d, 2H, J ¼
2.4 Hz, C6AH), 6.78 (m, 1H, C5AH, olefinic proton), 7.39
(brs, 1H, ANH, D2O exchange), 7.43–7.53 (m, 5H, phenyl
[11] Kode, R. N.; Redda, K. K.; Onayemi, F. Y.; Melles, H.;
Choi, J. J Heterocycl Chem 1995, 32, 307.
00
00
protons), 7.69 (d, 2H, J ¼ 8.1 Hz, C3 , C5 AH), 8.05 (d, 2H, J
[12] Pelle, C. J.; Okoro, C. O.; Wison, T. L.; Onubogu, U. C.;
Yoon, K. J.; Redda, K. K. Synth Commun 1995, 26, 2703.
[13] Okoro, C. O.; Yoon, K. J.; Wilson, T. L.; Onubogu, U.;
Redda, K. K. Med Chem Res 1999, 9, 133.
00
00
¼ 8.1 Hz, C2 , C6 AH).
N-[4-(5-Phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-1
(2H)-yl]-benzene sulfonamide (11l). The compound 11l was
obtained following general procedure 3 as white granules
33.6% yield, Mp 162–163ꢀC; IR (KBr): m 3106 (NH), 13323,
1168 (SO2)/cm; 1H NMR (CDCl3): d 2.65 (m, 2H, C3AH),
2.81 (t, 2H, J ¼ 5.7 Hz, C2AH), 3.03 (brs, 2H, C6AH), 5.72
(brs, 1H, ANH, D2O exchange), 6.62 (m, 1H, C5AH, olefinic
[14] Choi, J.; Wilson, T. L.; Ly, A. M.; Okoro, C. O.; Onubogu,
U. C.; Redda, K. K. Med Chem Res 1995, 5, 281.
[15] Redda, K. K.; Rao, K. N.; Heiman, A. S.; Melles, H.
J Pharm Sci 1992, 81, 463.
[16] Holla, B. S.; Gonsalves, R.; Shenoy, S. Eur J Med Chem
2000, 35, 267.
0
0
0
00
proton), 7.44A7.64 (complex m, 6H, C3 , C4 , C5 and C3 ,
00
00
0
0
C4 , C5 AH), 7.96 (dd, 2H, J ¼ 1.2 and 7.2 Hz, C2 , C6 AH),
[17] Cesur, N.; Birteksox, S.; Otuk, G. Acta Pharm Turcia 2002,
44, 23.
00
00
8.01 (dd, 2H, J ¼ 1.5, 6.0 Hz, C2 , C6 AH).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

316
M. Gangapuram and K. K. Redda
Vol 46
[18] Laddi, U. V.; Desai, S. R.; Bennur, R. S.; Bennur, S. C. In-
[27] Yoon, K.; Wilson, T. L.; Ly, A. M.; Okoro, C. O.; Onu-
bogo, U. C.; Redda, K. K. Drugs Exp Clin Res 2000, 26, 73.
[28] Okoro, C. O.; Wilson, T. L.; Choi, J. O.; Redda, K. K. Med
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