Sulfonylureas as dual acting agents - Synthesis and biological activity

Article abstract of DOI:10.1002/jccs.200700111

2-Amino-5-aryl/alkyl-1,3,4-thiadiazoles 3a-e were used as intermediates in the synthesis of some 1,3-substituted urea derivatives 5a-o to evaluate their antidiabetic activity as well as antibacterial activity. The obtained compounds exhibited marginal activity against the animal models and the selected microorganisms.

Full text of DOI:10.1002/jccs.200700111

Journal of the Chinese Chemical Society, 2007, 54, 771-777
771
Sulfonylureas as Dual Acting Agents - Synthesis and Biological Activity
Ameya A. Chavan and Nandini R. Pai*
Department of Organic Chemistry, D.G. Ruparel College, Senapati Bapat Marg,
Mahim, Mumbai-400 016, India
2-Amino-5-aryl/alkyl-1,3,4-thiadiazoles 3a-e were used as intermediates in the synthesis of some
1,3-substituted urea derivatives 5a-o to evaluate their antidiabetic activity as well as antibacterial activity.
The obtained compounds exhibited marginal activity against the animal models and the selected microor-
ganisms.
Keywords: Sulfonylureas; Antidiabetic; Antibacterial; 1,3,4-Thiadiazoles.
INTRODUCTION
Non insulin-dependent diabetes mellitus (NIDDM) is
apeutic agent for the treatment of pneumococcal and other
bacterial infections. It is also used for broncho-pneumonia
and upper respiratory infections, even though currently it
has been largely supplanted by sulfadiazine and sulfamer-
azine due to its high toxicity.18
characterized by a high level of blood glucose, abnor-
malities of insulin secretion and by insulin resistance of the
peripheral tissues.1 Insulin plays a key role in the path-
ogenesis of type II diabetes and is often associated with a
variety of other disorders like obesity, dyslipidaemia (hy-
pertrigly-ceridaemia) and low levels of high-density lipo-
protein (HDL) cholesterol and hypertension.2,3 This con-
stellation of disturbances is summarized under the name
metabolic syndrome and is associated with a high risk for
development of late diabetic complications, e.g. coronary
artery disease4 and nephropathy.5
It was planned to suitably incorporate the sulfonyl-
urea moiety into the 1,3,4-thiadiazole ring system and to
explore the possibilities of some altered biological action;
hence, the following sulfonylurea derivatives were synthe-
sized and screened for antidiabetic and antibacterial activ-
ity.
RESULTS AND DISCUSSION
The sulfonylurea compounds are reasonable blood
glucose lowering agents, although all of these are not nec-
essarily effective in every patient. The side-effects in most
persons have proven negligible and usually disappear when
the dose is lowered or discontinued. No real toxicity has
been shown after several decades of therapeutic use in mil-
lions of persons.6 Sulfonylureas are the most widely used
antidiabetic agents. These agents act on pancreatic b-cells
stimulating insulin secretion.7
Iskander et al.19 have carried out structure-activity re-
lationships of a series of glibenclamide analogues. Choo et
al.20 have carried out structure activity relationship meth-
ods based on antitumor diarylsulfonylureas. Abd El-Salam
et al.18 have synthesized some substituted pyridylsulfanil-
amide derivatives and evaluated their antibacterial activity.
In view of the above work, we thought there was a need to
develop new chemical entities (NCEs) of sulfonylureas
that may possess some of the required biological activities.
The synthesis involves reaction of aromatic/aliphatic
acids 1a-e with thiosemicarbazide 2, using sulfuric acid for
dehydrative cyclization to produce 2-amino-5-aryl/alkyl-
1,3,4-thiadiazoles 3a-e. These 2-amino-5-aryl/alkyl-1,3,4-
thiadiazoles 3a-e on further treatment with sulfonylure-
thanes 4a-c yield the desired substituted sulfonylureas
5a-o. The structures of the intermediates 3a-e and 4a-c, as
1,3,4-Thiadiazole, is a versatile pharmacophore which
exhibits a wide variety of biological activities. A few of
them which are worthy of mention are diuretic,8,9 CNS de-
pressants,10,11 hypoglycemic,12,13 anti-inflammatory,14 and
anti-microbial activities.15-17
Sulphanilamide’s effectiveness extends to acute chronic
Gram negative and Gram positive infections. For example,
sulfapyridine (N¢-2-pyridylsulfanilamide) is a chemother-
* Corresponding author. E-mail: nandini_pai@hotmail.com

772 J. Chin. Chem. Soc., Vol. 54, No. 3, 2007
Chavan and Pai
well as the final products 5a-o, were confirmed on the basis
but water was allowed ad libitum. At the end of 18 hrs.
blood samples were taken from all the animals for glucose
of both analytical and spectroscopic data.
Antidiabetic activity
Table 1. Different substituents R and R’ for compounds 5a-o
Wistar rats of either sex weighing between 200-250 g
were used. The animals were kept at 23 ± 1 °C with a 12 h
light/dark cycle (light at 7 a.m. to 7 p.m.). Acclimatisation
was done for 7 days after the arrival of the animals. The ani-
mals were housed under controlled conditions with stan-
dard diet and water ad libitum.
Compounds
R
R’
5a
5b
Diabetes was induced by injecting the alloxan through
the tail vein of the rats. The blood glucose levels of all the
animals were monitored for 4 days. Determination of blood
glucose levels was accomplished by using a glucometer
(ACCU-CHEK Active - Roche). On the 5th day, the ani-
mals showing blood glucose levels above 250 mg/dL were
segregated and were divided into 3 groups. viz., (i) vehicle
treated group (ii) drug treated group comprised of 5 sub-
groups for 5 test compounds and (iii) standard treated group.
Each group as well as sub-group was comprised of 6 ani-
mals.
5c
5d
5e
5f
The animals in all the groups were fasted for 18 hrs.
5g
Scheme
5h
5i
5j
5k
5l
5m
5n
5o

Sulfonylureas as Antidiabetic Agents
J. Chin. Chem. Soc., Vol. 54, No. 3, 2007 773
determination. This was regarded as ‘zero’ day reading.
The standard as well as the test drugs were suspended in 5%
gum acacia and administered by oral route at a dose of 200
mg/kg. The concentration of the compound was adjusted
such that 0.25 mL per 100 g body weight administered
orally gave the desired dose on a body weight basis. The
treatment was continued for a period of 8 days. Blood sam-
ples were withdrawn on the 2nd day, 4th day, 6th day, 8th day
and glucose levels were determined.
All the newly synthesized compounds showed anti-
bacterial activity against S. aureus, S. epidermis and E.
coli, the data of which is presented in Table 3.
Thus a series of sulfonylureas having a heterocyclic
nucleus and an aromatic ring in 1,3-positions of urea moi-
ety have been synthesized which display antidiabetic as
well as antibacterial activity.
The estimated levels of blood glucose were analysed
statistically, the summary of which is presented in Table 2.
All the compounds showed reduction in blood glucose
level.
EXPERIMENTAL
Melting points were determined in open capillaries
1
on a Thomas Hoover apparatus and are uncorrected. H
NMR spectra were recorded on a Bruker AM 400 (400
MHz) instrument using tetramethylsilane (TMS) as an in-
ternal standard and DMSO as a solvent. Chemical shifts are
given in parts per million (ppm). Splitting patterns are des-
ignated as follows: s- singlet, d- doublet, t- triplet, q- quar-
tet and m- multiplet. Mass spectra (MS) were recorded on
Shimadzu GC-MS. Elemental analysis (C, H, N) was per-
formed on a Perkin Elmer 240 analyzer, and all compounds
are within ± 0.4% of theory unless otherwise specified. All
products were purified by recrystallisation. The reactions
were followed up and the purity of products was carried out
on pre-coated TLC plates (Silica gel 60 F254 , Merck), visu-
alizing the spots in ultraviolet light. The biological activity
experiments were carried out at Bombay Veterinary Col-
lege (antidiabetic activity) and also at the Chemo Test Lab-
oratory (antimicrobial activity).
Antibacterial activity
The cup plate method21 using Hi-Media agar medium
was employed to study the antibacterial activity of 5a-o
against E. coli (ATCC9637), S. aureus (ATCC6538P), S.
typhi (NCTC786) and S. epidermis (ATCC12228). Prepa-
ration of nutrient broth, subculture, base layer medium,
agar medium and peptone water was done as per the stan-
dard procedure. Each test compound (5 mg) was dissolved
in 50 mL of 1N NaOH (100 mg/mL), which was used as
sample solution. Sample size for all the compounds was
fixed as 0.1 mL.
The cups were made by scooping out agar medium
with a sterilized cork borer in a petri dish, which was previ-
ously inoculated with the microorganisms. The solution of
each test compound (0.1 mL) was added to the cups, and
petri dishes were subsequently incubated at 37° for 48 h.
Sulfadiazine was used as reference drug and 1N NaOH as a
control. Zone of inhibition produced by each compound
was measured in mm, as shown in Table 3.
2-Amino-(5-aryl/alkyl)-1,3,4-thiadiazoles 3a-e
To a 3 neck round bottom flask (r.b.f.) fitted with a re-
flux condenser was added carboxylic acid 1 (0.01 mol),
Table 2. Antidiabetic activity of the tested compounds
Mean blood glucose concentration [mg/dL] after drug administration in alloxan induced Wistar rats at
Treatment Group
0 day
2nd day
4th day
6th day
8th day
Control (vehicle)
Compound-5a
273.0
274.8
270.0
275.8
267.8
282.0
272.8
270.4
267.8
267.8
267.6
269.8*
260.4*
264.2Nsp
264.2Nsp
271.4**
257.4**
252.4***
255.6***
248.4***
251.0***
255.0***
242.6**
254.0**
256.0***
254.4**
253.4**
259.4***
242.2***
256.4**
257.6***
259.8**
255.0**
263.8**
242.6***
Compound-5d
Compound-5g
Compound-5j
Compound-5m
Standard (Gliclazide)
All the values of the drug treated groups are significant Vs vehicle treated rats; Nsp = Nonsignificant; * p < 0.05, ** p < 0.01,
*** p < 0.001.

774 J. Chin. Chem. Soc., Vol. 54, No. 3, 2007
Chavan and Pai
Table 3. Antibacterial activity of the tested compounds
Concentration in
mg/mL
S. aureus
(ZOI in mm)
S. epidermis
(ZOI in mm)
E. coli
(ZOI in mm)
Compound
5a
5b
5c
5d
5e
5f
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
9.82
10.64
9.84
9.08
9.62
9.94
9.66
9.40
9.32
9.22
9.20
9.10
9.30
9.46
10.12
10.76
9.88
9.92
4.20
3.86
4.12
3.88
3.82
4.16
4.02
4.00
4.18
3.80
3.86
2.18
2.94
3.98
4.00
10.14
10.52
10.12
10.04
10.66
9.86
5g
5h
5i
9.78
10.00
9.88
5j
5k
5l
10.12
10.02
10.14
9.48
5m
5n
5o
St.
10.14
10.80
St. = Reference standard; Sulphadiazine was used as a standard antibacterial agent.
The test was done using the Cup plate method.
ZOI = Zone of inhibition.
thiosemicarbazide 2 (0.012 mol) and conc. H2SO4 (15 mL)
slowly under cooling. The resultant reaction mixture was
refluxed on a water bath for 3 h, then poured into crushed
ice and neutralized with ammonia solution cautiously. A
yellow coloured solid separates out. It was filtered off,
washed with saturated sodium bicarbonate solution and
water, dried and recrystallized from ethanol.22
3d. Yield (48%), mp. 110-2 °C; IR: n 3345 (NH2),
1
1027 (N-N), 725 (C-S-C) cm-1; H NMR (DMSO-d6): d
2.37 (s, 3H, Ar-CH3), 4.1 (s, 2H, NH2, D2O-exchange, dis-
appear); MS: 115. Anal. Calcd. for C3H5N3S: C, 31.30; H,
4.35; N, 36.52; S, 27.83. Found: C, 31.27; H, 4.39; N,
36.58; S, 27.78%.
3e. Yield (48%), mp. 116-8 °C; IR: n 3348 (NH2),
1029 (N-N), 727 (C-S-C) cm-1; 1H NMR (DMSO-d6): d 4.1
(s, 2H, NH2, D2O-exchange, disappear), 4.67 (s, 2H, -CH2-
Cl); MS: 149.5. Anal. Calcd. for C3H4ClN3S: C, 24.08; H,
2.67; N, 28.09; S, 21.40. Found: C, 24.12; H, 2.62; N,
28.03; S, 21.45%.
3a. Yield (53%), mp. 112-4 °C; IR: n 3350 (NH2),
1565 (C=C of aromatic ring), 1030 (N-N), 730 (C-S-C)
1
cm-1; H NMR (DMSO-d6): d 4.1 (s, 2H, NH2, D2O-ex-
change, disappear), 7.24-7.5 (m, 5H, Ar); MS: 177. Anal.
Calcd. for C8H7N3S: C, 54.24; H, 3.95; N, 23.73; S, 18.08.
Found: C, 54.29; H, 3.89; N, 23.77; S, 18.05%.
3b. Yield (51%), mp. 117-9 °C; IR: n 3354 (NH2),
1554 (C=C of aromatic ring), 1036 (N-N), 727 (C-S-C)
cm-1; 1H NMR (DMSO-d6): d 2.37 (s, 3H, Ar-CH3) 4.1 (s,
2H, NH2, D2O-exchange, disappear), 7.14-7.38 (m, 4H,
Ar); MS: 191. Anal. Calcd. for C9H9N3S: C, 56.54; H, 4.71;
N, 21.99; S, 16.75. Found: C, 56.51; H, 4.66; N, 22.05; S,
16.78%.
Sulfonylurethanes 4a-c
To a 4 neck r.b.f fitted with a reflux condenser was
added a mixture of 4-methyl benzenesulfonylchloride (0.01
mol) and 20% aqueous ammonia solution. The reaction
mixture was heated at 75-80 °C for 3 h. After completion of
the reaction, the reaction mixture was maintained for 1 h. at
15 °C. The solid that separated was filtered, washed with
water till neutral and dried to obtain 4-methyl benzenesul-
fonamide.
3c. Yield (45%), mp. 120-2 °C; IR: n 3365 (NH2),
1559 (C=C of aromatic ring), 1039 (N-N), 724 (C-S-C)
1
cm-1; H NMR (DMSO-d6): d 4.1 (s, 2H, NH2, D2O-ex-
A mixture of 4-methyl benzenesulfonamide (0.01
mol), ethyl methyl ketone (40 mL) and potassium carbon-
ate was taken in a 4 necked r.b.f and heated to 80 °C for 30
mins. Methyl chloroformate was added dropwise by means
change, disappear), 7.34-7.43 (m, 4H, Ar); MS: 211.5.
Anal. Calcd. for C8H6ClN3S: C, 45.39; H, 2.84; N, 19.86; S,
15.13. Found: C, 45.44; H, 2.79; N, 19.90; S, 15.15%.

Sulfonylureas as Antidiabetic Agents
J. Chin. Chem. Soc., Vol. 54, No. 3, 2007 775
of a dropping funnel at 45 °C in 1 h. The mixture was then
heated for 8 h at 50 °C. After the completion of reaction
(monitored by TLC), the reaction mixture was poured on
ice water and extracted with ethyl acetate (to remove or-
ganic impurities). The pH of the aqueous layer was ad-
justed to 2 to 3 by hydrochloric acid and again extracted
with ethyl acetate. The organic layer was dried over anhy-
drous sodium sulfate and later concentrated to dryness. The
solid thus obtained was recrystallized from ethanol.23
4a. Yield (70%), mp. 146-8 °C; IR: n 1635 (CO-NH),
1363 (asym. SO2), 1170 (sym. SO2) cm-1; 1H NMR (DMSO-
d6): d 2.33 (s, 3H, Ar-CH3), 3.65 (s, 3H, -O-CH3), 7.32-7.79
(m, 4H, Ar), 7.9 (s, 1H, NH, D2O-exchange, disappear);
MS: 229. Anal. Calcd. for C9H11NO4S: C, 47.16; H, 4.80;
N, 6.11; S, 13.97. Found: C, 47.19; H, 4.76; N, 6.16; S,
13.94%.
5b. Yield (63%), mp. 251-3 °C; IR: n 3330 (NH),
1721 (CO), 1645 (CO-NH), 1356 (asym. SO2), 1184 (sym.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.32 (t, 3H, -CH2-CH3),
3.84 (s, 3H, N-CH3), 4.33 (q, 2H, -O-CH2), 6.1 (s, 2H, NH,
D2O-exchange, disappear), 7.24-7.50 (m, 5H, Ar), 7.52 (s,
1H, -CH=N); MS: 436. Anal. Calcd. for C16H16N6O5S2: C,
44.03; H, 3.67; N, 19.26; S, 14.68. Found: C, 44.11; H,
3.60; N, 19.33; S, 14.60%.
5c. Yield (68%), mp. 264-6 °C; IR: n 3345 (NH),
1716 (CO), 1640 (CO-NH), 1359 (asym. SO2), 1162 (sym.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.33 (t, 3H, -CH2-CH3),
4.35 (q, 2H, -O-CH2), 6.1 (s, 2H, NH, D2O-exchange, dis-
appear), 7.26-7.52 (m, 5H, Ar), 7.42-8.27 (m, 4H, -SO2-
Ar); MS: 432. Anal. Calcd. for C18H16N4O5S2: C, 50.00; H,
3.70; N, 12.96; S, 14.81. Found: C, 50.09; H, 3.64; N,
12.87; S, 14.85%.
4b. Yield (65%), mp. 164-6 °C; IR: n 1644 (CO-NH),
1372 (asym. SO2), 1165 (sym. SO2) cm-1; 1H NMR (DMSO-
d6): d 1.32 (t, 3H, -CH2-CH3), 3.65 (s, 3H, -O-CH3), 3.82 (s,
3H, N-CH3), 4.27 (q, 2H, -O-CH2), 7.52 (s, 1H, -CH=N),
7.9 (s, 1H, NH, D2O-exchange, disappear); MS: 291. Anal.
Calcd. for C9H13N3O6S: C, 37.11; H, 4.47; N, 14.43; S,
11.00. Found: C, 37.17; H, 4.42; N, 14.39; S, 11.06%.
4c. Yield (68%), mp. 172-4 °C; IR: n 1652 (CO-NH),
1357 (asym. SO2), 1175 (sym. SO2) cm-1; 1H NMR (DMSO-
d6): d 1.32 (t, 3H, -CH2-CH3), 3.65 (s, 3H, -O-CH3), 4.27
(q, 2H, -O-CH2), 7.4-8.25 (m, 4H, Ar), 7.9 (s, 1H, NH,
D2O-exchange, disappear); MS: 287. Anal. Calcd. for
C11H13NO6S: C, 45.99; H, 4.53; N, 4.88; S, 11.15. Found:
C, 45.96; H, 4.57; N, 4.83; S, 11.12%.
5d. Yield (67%), mp. 273-5 °C; IR: n 3335 (NH),
1650 (CO-NH), 1360 (asym. SO2), 1165 (sym. SO2) cm-1;
1H NMR (DMSO-d6): d 2.35 (s, 6H, Ar-CH3), 6.1 (s, 2H,
NH, D2O-exchange, disappear), 7.14-7.38 (m, 4H, Ar),
7.36-7.83 (m, 4H, -SO2-Ar); MS: 388. Anal. Calcd. for
C17H16N4O3S2: C, 52.58; H, 4.12; N, 14.43; S, 16.49.
Found: C, 52.64; H, 4.15; N, 14.36; S, 16.43%.
5e. Yield (59%), mp. 247-9 °C; IR: n 3325 (NH),
1725 (CO), 1635 (CO-NH), 1358 (asym. SO2), 1185 (sym.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.34 (t, 3H, -CH2-CH3),
2.37 (s, 3H, Ar-CH3), 3.84 (s, 3H, N-CH3), 4.31 (q, 2H,
-O-CH2), 6.1 (s, 2H, NH, D2O-exchange, disappear), 7.14-
7.38 (m, 4H, Ar), 7.54 (s, 1H, -CH=N); MS: 450. Anal.
Calcd. for C17H18N6O5S2: C, 45.33; H, 4.00; N, 18.66; S,
14.22. Found: C, 45.40; H, 3.92; N, 18.61; S, 14.27%.
5f. Yield (61%), mp. 271-3 °C; IR: n 3338 (NH), 1715
(CO), 1642 (CO-NH), 1362 (asym. SO2), 1167 (sym. SO2)
cm-1; 1H NMR (DMSO-d6): d 1.31 (t, 3H, -CH2-CH3), 2.39
(s, 3H, Ar-CH3), 4.29 (q, 2H, -O-CH2), 6.1 (s, 2H, NH, D2O-
exchange, disappear), 7.14-7.38 (m, 4H, Ar), 7.44-8.29 (m,
4H, -SO2-Ar); MS: 446. Anal. Calcd. for C19H18N4O5S2: C,
51.12; H, 4.03; N, 12.55; S, 14.35. Found: C, 51.06; H,
4.07; N, 12.61; S, 14.26%.
1-(5-Aryl/alkyl-1,3,4-thiadiazol-2-yl)-3-(substituted
sulfonyl)urea 5a-o (General Procedure)
A mixture of sulfonylurethanes 4a-c (0.01 mol) and
amines 3a-e (0.01 mol) in toluene (50 mL) was placed into
a 3 neck round bottom flask fitted with a reflux condenser
and a mechanical stirrer. The reaction mixture was refluxed
and stirred for 4 h, cooled to room temperature, and the re-
sulting solid was filtered off, dried and recrystallized from
methanol to obtain the desired product 5a-o.
5g. Yield (65%), mp. 266-8 °C; IR: n 3340 (NH),
1643 (CO-NH), 1356 (asym. SO2), 1168 (sym. SO2) cm-1;
1H NMR (DMSO-d6): d 2.37 (s, 3H, Ar-CH3), 6.1 (s, 2H,
NH, D2O-exchange, disappear), 7.35-7.44 (m, 4H, Ar),
7.36-7.83 (m, 4H, -SO2-Ar); MS: 408.5. Anal. Calcd. for
C16H13ClN4O3S2: C, 47.00; H, 3.18; N, 13.71; S, 15.67.
Found: C, 47.08; H, 3.11; N, 13.65; S, 15.73%.
5a. Yield (70%), mp. 276-8 °C; IR: n 3320 (NH),
1640 (CO-NH), 1354 (asym. SO2), 1170 (sym. SO2) cm-1;
1H NMR (DMSO-d6): d 2.37 (s, 3H, Ar-CH3), 6.1 (s, 2H,
NH, D2O-exchange, disappear), 7.26-7.52 (m, 5H, Ar),
7.38-7.85 (m, 4H, -SO2-Ar); MS: 374. Anal. Calcd. for
C16H14N4O3S2: C, 51.33; H, 3.74; N, 14.97; S, 17.11.
Found: C, 51.27; H, 3.69; N, 14.84; S, 17.13%.
5h. Yield (55%), mp. 281-3 °C; IR: n 3342 (NH),

776 J. Chin. Chem. Soc., Vol. 54, No. 3, 2007
Chavan and Pai
1723 (CO), 1638 (CO-NH), 1356 (asym. SO2), 1180 (sym.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.32 (t, 3H, -CH2-CH3),
3.84 (s, 3H, N-CH3), 4.33 (q, 2H, -O-CH2), 6.1 (s, 2H, NH,
D2O-exchange, disappear), 7.35-7.44 (m, 4H, Ar), 7.54 (s,
1H, -CH=N); MS: 470.5. Anal. Calcd. for C16H15ClN6O5S2:
C, 40.81; H, 3.19; N, 17.85; S, 13.60. Found: C, 40.76; H,
3.25; N, 17.79; S, 13.64%.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.34 (t, 3H, -CH2-CH3),
3.82 (s, 3H, N-CH3), 4.31 (q, 2H, -O-CH2), 4.68 (s, 2H,
-CH2-Cl), 6.1 (s, 2H, NH, D2O-exchange, disappear), 7.5 (s,
1H, -CH=N); MS: 408.5. Anal. Calcd. for C11H13ClN6O5S2:
C, 32.31; H, 3.18; N, 20.56; S, 15.67. Found: C, 32.25; H,
3.23; N, 20.59; S, 15.70%.
5o. Yield (64%), mp. 263-5 °C; IR: n 3335 (NH),
1718 (CO), 1639 (CO-NH), 1361 (asym. SO2), 1182 (sym.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.30 (t, 3H, -CH2-CH3),
4.27 (q, 2H, -O-CH2), 4.66 (s, 2H, -CH2-Cl), 6.1 (s, 2H,
NH, D2O-exchange, disappear), 7.42-8.27 (m, 4H, -SO2-
Ar); MS: 404.5. Anal. Calcd. for C13H13ClN4O5S2: C,
38.57; H, 3.21; N, 13.84; S, 15.82. Found: C, 38.51; H,
3.24; N, 13.89; S, 15.87%.
5i. Yield (59%), mp. 284-6 °C; IR: n 3346 (NH), 1717
(CO), 1643 (CO-NH), 1366 (asym. SO2), 1170 (sym. SO2)
cm-1; 1H NMR (DMSO-d6): d 1.32 (t, 3H, -CH2-CH3), 4.31
(q, 2H, -O-CH2), 6.1 (s, 2H, NH, D2O-exchange, disap-
pear), 7.35-7.44 (m, 4H, Ar), 7.4-8.25 (m, 4H, -SO2-Ar);
MS: 466.5. Anal. Calcd. for C18H15ClN4O5S2: C, 46.30; H,
3.21; N, 12.00; S, 13.72. Found: C, 46.37; H, 3.18; N,
12.05; S, 13.65%.
5j. Yield (68%), mp. 274-6 °C; IR: n 3325 (NH), 1648
1
(CO-NH), 1362 (asym. SO2), 1178 (sym. SO2) cm-1; H
ACKNOWLEDGEMENT
NMR (DMSO-d6): d 2.39 (s, 6H, Ar-CH3), 6.1 (s, 2H, NH,
D2O-exchange, disappear), 7.36-7.83 (m, 4H, -SO2-Ar);
MS: 312. Anal. Calcd. for C11H12N4O3S2: C, 42.31; H,
3.85; N, 17.95; S, 20.51. Found: C, 42.34; H, 3.80; N,
17.99; S, 20.45%.
The authors are thankful to Dr. (Mrs.) R. S. Nehate,
Bombay Veterinary College, for the antidiabetic screening
of the compounds; Mr. Atul Pusalkar and Ms. Borna Basu,
Chemo Test Laboratory for antimicrobial screening of the
compounds. The authors are also grateful to the U.G.C. for
financial assistance.
5k. Yield (57%), mp. 270-2 °C; IR: n 3329 (NH),
1721 (CO), 1652 (CO-NH), 1359 (asym. SO2), 1174 (sym.
SO2) cm-1; 1H NMR (DMSO-d6): d 1.34 (t, 3H, -CH2-CH3),
2.37 (s, 3H, Ar-CH3), 3.82 (s, 3H, N-CH3), 4.33 (q, 2H,
-O-CH2), 6.1 (s, 2H, NH, D2O-exchange, disappear), 7.53
(s, 1H, -CH=N); MS: 374. Anal. Calcd. for C11H14N6O5S2:
C, 35.29; H, 3.74; N, 22.46; S, 17.11. Found: C, 35.33; H,
3.79; N, 22.42; S, 17.13%.
Received August 1, 2006.
REFERENCES
5l. Yield (62%), mp. 265-7 °C; IR: n 3334 (NH), 1724
(CO), 1657 (CO-NH), 1368 (asym. SO2), 1182 (sym. SO2)
cm-1; 1H NMR (DMSO-d6): d 1.32 (t, 3H, -CH2-CH3), 2.35
(s, 3H, Ar-CH3), 4.29 (q, 2H, -O-CH2), 6.1 (s, 2H, NH,
D2O-exchange, disappear), 7.44-8.29 (m, 4H, -SO2-Ar);
MS: 370. Anal. Calcd. for C13H14N4O5S2: C, 42.16; H,
3.78; N, 15.13; S, 17.30. Found: C, 42.22; H, 3.71; N,
15.06; S, 17.34%.
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