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European	Journal	of	Chemistry	4	(4)	(2013)	396‐401	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2013	EURJCHEM	

DOI:10.5155/eurjchem.4.4.396‐401.878	

	
	

	

	

European	Journal	of	Chemistry	
Journal	homepage:	www.eurjchem.com	

	 	 	

Synthesis,	characterization	and	in	vitro	biological	evaluation	of	some	new	
diarylsulfonylurea‐chalcone	hybrids	as	potential	5‐lipoxygenase	inhibitors	

Bharat	Kumar	Bugata	a,*,	Satya	Venkata	Gopala	Krishna	Kaladhar	Dowluru	a,	Vasudeva	Rao	Avupati	b,	
Venkateswara	Rao	Gavalapu	b,	Divakara	Laxman	Somayajulu	Nori	c	and	Sreenu	Barla	a	

a	Department	of	Biochemistry	and	Bioinformatics,	Gitam	University,	Rushikonda,	Visakhapatnam‐530045,	Andhra	Pradesh,	India	
b	Pharmaceutical	Chemistry	Division,	Andhra	University	College	of	Pharmaceutical	Sciences,	Andhra	University,	Visakhapatnam‐530003,	Andhra	Pradesh,	India	
c	Department	of	Chemistry,	Gitam	University,	Rushikonda,	Visakhapatnam‐530045,	Andhra	Pradesh,	India	

*Corresponding	author	at:	Department	of	Biochemistry	and	Bioinformatics,	Gitam	University,	Rushikonda,	Visakhapatnam‐530045,	Andhra	Pradesh,	India.	
Tel.:	+91.0891.2792928;	fax:	+91.0891.2790399.	E‐mail	address:	bharat8891@gmail.com		(B.K.	Bugata).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	15	July	2013	
Received	in	revised	form:	04	August	2013	
Accepted:	06	August	2013	
Online:	31	December	2013	

KEYWORDS	

	 A	series	of	some	new	diarylsulfonylurea‐chalcone	hybrids	(4a‐4y)	have	been	synthesized	via
Claisen‐Schmidt	 condensation	 reaction	 by	 treating	 1‐(3‐acetylphenyl)‐3‐tosylurea	 with
various	aromatic/heteroaromatic	aldehydes	in	the	presence	of	alkali	and	characterized	by	FT‐
IR,	 1H	 NMR,	 13C	 NMR	 and	 LC	mass	 spectral	 analysis.	 All	 the	 synthesized	 compounds	 were
evaluated	 for	 their	 in	 vitro	 5‐Lipoxygenase	 inhibitory	 activity	 using	 potato	 5‐lipoxygenase
enzyme.	Among	 the	 tested	 compounds	4r	 and	4o	 exhibited	 significant	 inhibitory	activity	 at
IC50	 values	 7.88±0.14	 and	 11.77±0.21	 µg/mL,	 respectively.	 This	 level	 of	 activity	was	 found
comparable	 to	 that	 of	 the	 reference	 drug	 Abietic	 acid	 (LI01020)	 with	 IC50	 value	 4.34±0.37
µg/mL	and	it	could	be	a	remarkable	starting	point	to	develop	new	lead	molecules.	

Chalcone	
5‐Lipoxygenase	
Diarylsulfonylurea	
Abietic	acid	(LI01020)	
Claisen‐Schmidt	condensation		
Diarylsulfonylurea‐chalcone	hybrid	

	
1.	Introduction	
	

Lipoxygenases	 are	 a	 class	 of	 non‐heme,	 iron‐containing	
enzymes	 that	 catalyze	 the	 incorporation	 of	molecular	 oxygen	
into	 1,4,‐cis,cis‐pentadiene‐containing	 fatty	 acids	 (e.g.	 linoleic	
and	arachidonic	acids)	to	form	hydroperoxide	products	[1].	The	
human	 isozymes,	5‐,	12‐	and	15‐Lipoxygenases	are	associated	
with	 different	 disease	 states,	 which	 suggests	 that	 selective	
inhibition	may	be	 important	 in	 targeting	 them	for	 therapeutic	
purposes.	5‐Lipoxygenase	(5‐LO),	which	was	first	discovered	in	
1976,	plays	an	essential	role	in	the	biosynthesis	of	leukotrienes	
(LTs)	that	exert	a	large	number	of	different	biological	activities	
mediated	 by	 specific	 G‐protein	 coupled	 receptors.	 LTB4	 is	 a	
typical	 proinflammatory	 mediator	 that	 recruits	 and	 activates	
leukocytes,	whereas	cysteinyl‐leukotrienes	C4,	D4	and	E4	cause	
vascular	permeability	and	smooth	muscle	contraction.	 In	view	
of	these	properties,	development	of	drugs	with	5‐LO	inhibitory	
activity	has	been	hypothesized	to	possess	therapeutic	potential	
for	 treatment	 of	 asthma,	 allergic	 disorders	 and	 other	
inflammatory	diseases	 [2].	Based	on	 the	mechanism	of	action,	
the	 lipoxygenase	 inhibitors	 have	 been	 classified	 into	 four	
distinct	classes:		
(i) Iron	chelating	inhibitors,		
(ii) Competitive	reversible	inhibitors,		
(iii) Inhibitors	of	the	5‐LO	activating	protein	(FLAP)	and		
(iv) Anti‐oxidative	 [3].	 Intensive	 discovery	 efforts	 in	 the	

development	of	clinically	useful	drugs	from	the	inhibitors	
of	5	LO	enzyme	have	led	to	one	marketed	drug;	Zileuton	
(A‐64066)	 and	 others,	 namely	 MK‐3000,	 MK‐886,	 MK‐
0591,	ZM	211965,	AKBA,	BW	A4C,	LDP‐977,	Bay‐X‐1005,	
and	 Abt‐761,	 which	 are	 evaluated	 at	 different	 stages	 of	
drug	development	[2,3].	

Diarylsulfonylureas	 are	 the	 structural	 analogs	 of	 urea	
(NH2CONH2)	with	aromatic	sulfonyl	group	in	the	position	3	and	
an	 aromatic	 or	 heteroaromatic	 ring	 at	 the	 position	 1.	
Diarylsulfonylureas	 became	 widely	 available	 since	 1955	 as	
popular	antidiabetic	drugs	in	clinical	practice	for	the	treatment	
of	 type	 2	 diabetes,	 by	 virtue	 of	 their	 insulin	 secretagogue	
properties.	 The	 synthesis	 of	 compounds	 containing	
diarylsulfonylurea	 moiety	 has	 been	 a	 subject	 of	 extensive	
research	 in	 the	 recent	 past	 because	 of	 their	 enormous	
biological	 activities	 such	 as	 hypoglycemics	 [4],	 Vibrio	 fischeri	
quorum	sensing	regulators	[5],	CXCR2	receptor	antagonists	[6],	
antimalarials	 [7],	 antibacterials	 [8],	 human	 thromboxane	 A2	
receptor	 isoforms	 TPα	 and	 TPβ	 antagonists	 [9],	 reversible	
inhibitors	 of	 human	 steroid	 sulfatase	 [10],	 KATP‐channel	
openers	[11],	ANG	II	(AT1)	receptor	antagonists	[12],	oncolytics	
[13],	 acyl‐CoA	 inhibitors	 [14],	 vasodilators	 [15],	 aldehyde	
dehydrogenase	inhibitors	[16],	cancer	chemotherapeutics	[17],	
diuretic	 [18],	 β3	 adrenergic	 receptor	 agonists	 [19],	 non	
competitive	 inhibitors	 of	 acetohydroxyacid	 synthase	 from	
Mycobacterium	 tuberculosis	 [20],	 and	 as	 peroxisome	
proliferator	activated	receptor	gamma	(PPARγ)	agonists	[21].		

Similarly,	 chalcones	 (α,β‐unsatured	 ketones)	 have	 also	
been	 gained	 huge	 significance	 as	 these	 compounds	 exhibit	
several	biological	activities,	such	as	antimicrobial	[22],	antiviral	
[23],	 antioxidant	 [24],	 radical	 inhibitor	 [25],	 antitumor	 [26],	
carbonic	 anhydrase	 inhibitor	 [27],	 xanthine	 oxidase	 inhibitor	
[28],	antibacterial	[29],	plant	growth	regulator	[30],	free	radical	
scavenger	 [31],	 anti‐inflammatory	 [32]	 and	 analgesic	 [33].	
These	activities	are	largely	attributed	due	to	the	α,β‐unsatured	
ketone	moiety	[34].	Consequently	a	number	of	strategies	have	
been	originated	to	synthesize	them	[35‐37].	

	



Bugata	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	396‐401	 397	
 

	

CH3

O

HNC

O

HNS

O

O

H3C

CH3

O

Methyl chloroformate

20% KOH

Temp: 0 oC CH3

O

HNC

O

H3CO

NH2S
O

O
H3CToluene

Reflux: 3 h
Toluene sulphonamide

KOH
Ethanol

O

HNC

O

HNS

O

O

R

2

Aromatic/
Heteroaromatic

Aldehydes

NH2

1

H3C

ClCOOCH3

3

4a-4y

R CHO

 
	

Scheme	1
	
	
Based	 on	 the	 above	 observations,	 an	 attempt	 has	 been	

made	 in	 the	 present	 study	 to	 combine	 these	 two	 bioactive	
pharmacophores	 in	 a	 single	 molecular	 platform	 through	
molecular	 hybridization	 strategies.	 Hence,	 it	 was	 considered	
worthwhile	 to	 synthesize	 and	 characterize	 some	 novel	
diarylsulfonylurea‐chalcone	 hybrids	 (4a‐4y)	 in	 the	 present	
study	 [38].	To	 the	best	 of	 our	 knowledge	 there	 is,	 to	 date,	 no	
report	 that	 diarylsulfonylurea‐chalcone	 hybrid	 derivatives	
have	any	inhibitory	activity	against	5‐LO.	
	
2.	Experimental	 	
	
2.1.	Instrumentation	

	
Melting	points	were	 taken	 in	open	capillary	 tubes	and	are	

therefore	 uncorrected.	 Purity	 of	 the	 compounds	was	 checked	
on	silica	gel	G	TLC	plates	of	2	mm	thickness	using	n‐hexane	and	
ethyl	 acetate	 as	 solvent	 system.	The	 visualization	 of	 spot	was	
carried	 out	 in	 an	 iodine	 chamber.	 The	 FT‐IR	 spectra	 were	
recorded	 on	Perkin‐Elmer	 spectrometer.	 The	 1H	NMR	 spectra	
were	scanned	on	a	Bruker	400	MHz.	spectrometer	in	DMSO‐d6	
using	 TMS	 as	 internal	 standard	 and	 chemical	 shifts	 are	
expressed	in	δ	ppm.	The	ESI	mass	spectra	were	recorded	on	an	
Agilent	6100	QQQ	spectrometer	(positive	ion	mode).	

	
2.2.	General	procedure	for	the	synthesis	of	
diarylsulfonylurea‐chalcone	hybrids	(4a‐4y)	
	

The	 reaction	 sequence	 employed	 in	 the	 synthesis	 of	
diarylsulfonylurea‐chalcone	 hybrids	 (4a‐4y)	 is	 shown	 in	 the	
Scheme	1.	The	key	intermediates	 in	 the	present	study	(2)	and	

(3)	 were	 synthesized	 from	 (1)	 as	 reported	 earlier	 [33,34].	
Subsequent	 Claisen‐Schmidt	 condensation	 [39]	 of	 the	
intermediate	 1‐(3‐acetylphenyl)‐3‐tosylurea	 (3)	 with	
appropriate	 aromatic/heteroaromatic	 aldehydes	 in	 ethanolic	
KOH	 solution	 (100%)	 to	 give	 the	 corresponding	
diarylsulfonylurea‐chalcone	 hybrids	 (4a‐4y)	 in	 good	 yield.	 All	
the	 structures	 of	 the	 compounds	 were	 appropriately	
established	by	spectroscopic	data	and	analytical	methods.	

(E)‐1‐[3‐(3‐(phenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	 (4a):	
Colour:	Yellow.	Yield:	97%.	M.p.:	151.3	oC.	FT‐IR	(KBr,	vmax,	cm‐

1):	 3317,	 3314	 (N‐H),	 3011	 (C‐H),	 1656	 (C=O),	 1621	 (C=C),	
1555	(CONH),	1549	(N‐H	bend),	1300	(SO2,	asym.),	1329	(C‐N),	
1120	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	
3H,	CH3),	7.41‐7.59	(m,	9H,	Ar‐H),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.65	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.96	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	8.07	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	10.33	(s,	1H,	NH),	
11.73	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 421	 [M+H]+.	 Anal.	 calcd.	 for	
C23H20N2O4S:	C,	65.42;	H,	4.33;	N,	6.35.	Found:	C,	65.70;	H,	4.79;	
N,	6.66%.	

(E)‐1‐[3‐(3‐(tolyl)	 acryloyl)	 phenyl]‐3‐tosylurea	 (4b):	
Colour:	Yellow.	Yield:	89%.	M.p.:	233.8	oC.	FT‐IR	(KBr,	vmax,	cm‐

1):	 3428,	 3317	 (N‐H),	 3073	 (C‐H),	 1645	 (C=O),	 1616	 (C=C),	
3073	(C‐H),	1575	(CONH),	1337	(C‐N),	1542	(N‐H	bend),	1337	
(C‐N)	1298	(SO2,	asym.),	1182	(SO2,	sym.).	 1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):	2.30	(s,	3H,	CH3),	2.34	(s,	3H,	CH3),	7.17‐7.38	
(m,	8H,	Ar‐H),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.62	(d,	J	=	15.2	Hz,	
1H,	HC=CH	(H‐α)),	7.91	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	8.07	
(d,	 J	 =	8.1	Hz,	2H,	Ar‐H),	10.33	(s,	1H,	NH),	11.73	 (s,	1H,	NH).	
ESI‐MS	 (m/z):	 435	 [M+H]+.	 Anal.	 calcd.	 for	 C24H22N2O4S:	 C,	
66.34;	H,	5.10;	N,	6.45.	Found:	C,	66.32;	H,	5.13;	N,	6.55%.	



398	 Bugata	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	396‐401	
	

(E)‐1‐[3‐(3‐(4‐N,N‐dimethylaminophenyl)	 acryloyl)	 phenyl]‐
3‐tosylurea	(4c):	Colour:	Yellow.	Yield:	88%.	M.p.:	150.5	oC.	FT‐
IR	(KBr,	vmax,	cm‐1):	3460	(N‐H),	3341	(C=O),	3038	(C‐H),	1651	
(C=C),	1591	(CONH),	1531	(N‐H	bend),	1353	(C‐N),	1310	(SO2,	
asym.),	1156	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	2.38	(s,	6H,	CH3),	7.36‐7.77	(m,	8H,	Ar‐H),	7.43	
(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.69	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	
7.84	(d,	 J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	8.01	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	10.89	(s,	1H,	NH),	12.02	(s,	1H,	NH).	ESI‐MS	(m/z):	464	
[M+H]+.	Anal.	calcd.	for	C25H25N3O4S:	C,	64.78;	H,	5.44;	N,	9.06.	
Found:	C,	64.71;	H,	5.25;	N,	9.11%.	

(E)‐1‐[3‐(3‐(2,4‐dimethoxyphenyl)	 acryloyl)	 phenyl]‐3‐
tosylurea	(4d):	Colour:	Yellow.	Yield:	84%.	M.p.:	163.3	oC.	FT‐IR	
(KBr,	 vmax,	 cm‐1):	 3225	 (N‐H),	 2888	 (C‐H),	 1716	 (C=O),	 1655	
(C=C),	1593	(CONH),	1528	(N‐H	bend),	1356	(C‐N),	1312	(SO2,	
asym.),	1153	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	3.85	(s,	6H,	OCH3),	7.41	(d,	J	=	8.1	Hz,	2H,	Ar‐
H),	 7.66‐7.98	 (m,	 7H,	 Ar‐H),	 7.69	 (d,	 J	 =	 15.2	 Hz,	 1H,	 HC=CH	
(H‐α)),	 7.85	 (d,	 J	 =	8.1	Hz,	2H,	Ar‐H),	7.98	 (d,	 J	 =	15.2	Hz,	1H,	
HC=CH	 (H‐β)),	 9.01	 (s,	 1H,	 NH),	 10.98	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	 481	 [M+H]+.	 Anal.	 calcd.	 for	 C25H24N2O6S:	 C,	 62.49;	 H,	
5.03;	N,	5.83.	Found:	C,	62.23;	H,	5.16;	N,	5.78%.	

(E)‐1‐[3‐(3‐(3,4,5‐trimethoxyphenyl)	 acryloyl)	 phenyl]‐3‐
tosylurea	(4e):	Colour:	Yellow.	Yield:	88%.	M.p.:	198.6	oC.	FT‐IR	
(KBr,	 vmax,	 cm‐1):	 3355,	 3305	 (N‐H),	 2976	 (C‐H),	 1595	 (C=O),	
1516	(C=C),	1471	(CONH),	1441	(N‐H	bend),	1307	(C‐N),	1280	
(SO2,	asym.),	1135	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	
ppm):	2.30	(s,	3H,	CH3),	3.71	(s,	3H,	OCH3),	3.85	(s,	6H,	OCH3),	
7.25	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.43‐7.77	(m,	6H,	Ar‐H),	7.69	(d,	J	
=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.85	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.98	
(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	8.92	(s,	1H,	NH),	10.41	(s,	1H,	
NH).	ESI‐MS	(m/z):	511	[M+H]+.	Anal.	calcd.	for	C26H26N2O7S:	C,	
61.16;	H,	5.13;	N,	5.49.	Found:	C,	61.22;	H,	5.21;	N,	5.51%.	

(E)‐1‐[3‐(3‐(2‐hydroxyphenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4f):	Colour:	Yellow.	Yield:	86%.	M.p.:	258.9	oC.	FT‐IR	(KBr,	vmax,	
cm‐1):	3225	(N‐H),	1716	 (C=O),	1655	(C=C),	1592	(C‐H),	1528	
(N‐H	bend),	1449	(CONH),	1341	(C‐N),	1300	(SO2,	asym.),	1153	
(SO2,	sym.).	 1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	3H,	
CH3),	7.37‐7.93	(m,	8H,	Ar‐H),	7.47	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.70	
(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.81	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.88	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	10.12	(s,	1H,	OH),	10.64	
(s,	1H,	NH);	11.98	(s,	1H,	NH).	ESI‐MS	(m/z):437	[M+H]+.	Anal.	
calcd.	 for	 C23H20N2O5S:	 C,	 63.29;	 H,	 4.62;	 N,	 6.42.	 Found:	 C,	
63.33;	H,	4.71;	N,	6.55%.	

(E)‐1‐[3‐(3‐(3‐hydroxyphenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4g):	 Colour:	 Yellow.	 Yield:	 82%.	 M.p.:	 185.2	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3226	 (N‐H),	 1716	 (C=O),	 1655	 (C=C),	 1592	 (C‐H),	
1528	(N‐H	bend),	1449	(CONH),	1341	(C‐N),	1300	(SO2,	asym.),	
1153	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	
3H,	CH3),	7.22‐7.63	(m,	8H,	Ar‐H),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.45	(s,	1H,	OH),	7.69	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.81	(d,	
J	 =	 15.4	Hz,	 1H,	HC=CH	 (H‐β)),	 7.83	 (d,	 J	 =	 8.1	Hz,	 2H,	 Ar‐H),	
10.87	(s,	1H,	NH),	12.12	(s,	1H,	NH).	ESI‐MS	(m/z):	437	[M+H]+.	
Anal.	calcd.	for	C23H20N2O5S:	C,	63.29;	H,	4.62;	N,	6.42.	Found:	C,	
63.31;	H,	4.77;	N,	6.51%.	

(E)‐1‐[3‐(3‐(4‐hydroxyphenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4h):	 Colour:	 Yellow.	 Yield:	 89%.	 M.p.:	 185.7	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3415,	 3350	 (N‐H)	 3057	 (C‐H),	 1616	 (C=O),	 1583	
(C=C),	1555	(CONH),	1517	(N‐H	bend),	1337	(C‐N)	1304	(SO2,	
asym.),	1174	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.43	(d,	J	=	8.1	Hz,	3H,	Ar‐H),	7.66	(d,	J	=	15.2	
Hz,	1H,	HC=CH	(H‐α)),	7.67‐8.12	(m,	7H,	Ar‐H),	7.86	(d,	J	=	15.2	
Hz,	1H,	HC=CH	(H‐β)),	7.87	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	9.43	(s,	1H,	
OH),	 9.45	 (s,	 1H,	 NH),	 11.93	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 437	
[M+H]+.	Anal.	calcd.	for	C23H20N2O5S:	C,	63.29;	H,	4.62;	N,	6.42.	
Found:	C,	63.32;	H,	4.72;	N,	6.55%.	

(E)‐1‐[3‐(3‐(3‐ethoxy‐4‐hydroxyphenyl)	 acryloyl)	 phenyl]‐3‐
tosylurea	(4i):	Colour:	Yellow.	Yield:	89%.	M.p.:	174.3	oC.	FT‐IR	
(KBr,	 vmax,	 cm‐1):	 3381,	 3346	 (N‐H),	 3092	 (C‐H),	 1713	 (C=O),	
1664	(C=C),	1595	(CONH),	1536	(N‐H	bend),	1423	(C‐N),	1299	
(SO2,	asym.),	1090	(SO2,	sym.).		1H	NMR	(400	MHz,	DMSO‐d6,	δ,	

ppm):	 2.30	 (s,	 3H,	 CH3),	 6.54	 (s,	 2H,	 CH2),	 6.82	 (s,	 3H,	 CH3),	
6.97‐7.34	(m,	7H,	Ar‐H),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.69	(d,	J	
=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.82	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.94	
(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	8.78	(s,	1H,	OH),	10.45	(s,	1H,	
NH),	11.66	(s,	1H,	NH).	ESI‐MS	(m/z):	481	[M+H]+.	Anal.	calcd.	
for	C25H24N2O6S:	C,	62.49;	H,	5.03;	N,	5.83.	Found:	C,	62.58;	H,	
5.12;	N,	5.89%.	

(E)‐1‐[3‐(3‐(3‐methoxy‐4‐hydroxyphenyl)	 acryloyl)	 phenyl]‐
3‐tosylurea	(4j):	Colour:	Yellow.	Yield:	93%.	M.p.:	178.6	oC.	FT‐
IR	(KBr,	vmax,	cm‐1):	3367,	3304	(N‐H),	3058	(C‐H),	1726	(C=O),	
1659	(C=C),	1592	(CONH),	1532	(N‐H	bend),	1345	(C‐N),	1313	
(SO2,	asym.),	1157	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	
ppm):	 2.30	 (s,	 3H,	 CH3),	 3.96	 (s,	 3H,	OCH3),	 6.85‐7.45	 (m,	 7H,	
Ar‐H),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.87	(d,	J	=	8.1	Hz,	2H,	Ar‐
H),	7.68	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.96	(d,	J	=	15.2	Hz,	
1H,	HC=CH	(H‐β)),	8.43	(s,	1H,	OH),	9.28	(s,	1H,	NH),	10.87	(s,	
1H,	 NH).	 ESI‐MS	 (m/z):	 467	 [M+H]+.	 Anal.	 calcd.	 for	
C24H22N2O6S:	C,	61.79;	H,	4.75;	N,	6.00.	Found:	C,	61.65;	H,	4.66;	
N,	6.11%.	

(E)‐1‐[3‐(3‐(2‐nitrophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4k):	 Colour:	 Yellow.	 Yield:	 86%.	 M.p.:	 231.8	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3471,	 3242	 (N‐H),	 3092	 (C‐H),	 1708	 (C=O),	 1650	
(C=C),	1586	(CONH),	1528	(N‐H	bend),	1349	(C‐N),	1304	(SO2,	
asym.),	1158	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	6.95‐7.18	(m,	8H,	Ar‐H),	7.41	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	7.69	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.87	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.95	(d,	 J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.22	(s,	1H,	
NH),	10.55	(s,	1H,	NH).	ESI‐MS	(m/z):	466	[M+H]+.	Anal.	calcd.	
for	C23H19N3O6S:	C,	59.35;	H,	4.11;	N,	9.03.	Found:	C,	59.32;	H,	
4.16;	N,	9.21%.	

(E)‐1‐[3‐(3‐(3‐nitrophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4l):	Colour:	Yellow.	Yield:	89%.	M.p.:	172.2	oC.	FT‐IR	(KBr,	vmax,	
cm‐1):	3413,	3263	(N‐H),	3063	(C‐H),	1689	(C=O),	1625	(C=C),	
1585	(CONH),	1521	(N‐H	bend),	1342	(C‐N),	1315	(SO2,	asym.),	
1161	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	
3H,	CH3),	6.95‐7.41	(m,	8H,	Ar‐H),	7.43	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.67	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.78	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	7.91	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	10.97	(s,	1H,	NH),	
11.94	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 466	 [M+H]+.	 Anal.	 calcd.	 for	
C23H19N3O6S:	C,	59.35;	H,	4.11;	N,	9.03.	Found:	C,	59.32;	H,	4.23;	
N,	9.21%.	

(E)‐1‐[3‐(3‐(5‐hydroxy‐2‐nitrophenyl)	 acryloyl)	 phenyl]‐3‐
tosylurea	(4m):	Colour:	Yellow.	Yield:	85%.	M.p.:	166.2	oC.	FT‐
IR	(KBr,	vmax,	cm‐1):	3383,	3290	(N‐H),	3068	(C‐H),	1649	(C=O),	
1614	(C=C),	1581	(CONH)	1547	(N‐H	bend),	1346	(C‐N),	1306	
(SO2,	asym.),	1156	(SO2,	sym.).			1H	NMR	(400	MHz,	DMSO‐d6,	δ,	
ppm):	2.30	(s,	3H,	CH3),	6.86‐7.23	(m,	7H,	Ar‐H),	7.42	(d,	J	=	8.1	
Hz,	2H,	Ar‐H),	7.70	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.83	(d,	J	=	
8.1	Hz,	2H,	Ar‐H),	7.88	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	8.42	
(s,	1H,	OH),	10.41	(s,	1H,	NH),	11.72	(s,	1H,	NH).	ESI‐MS	(m/z):	
482	 [M+H]+.	Anal.	 calcd.	 for	C23H19N3O7S:	 C,	 57.37;	H,	 3.98;	N,	
8.73.	Found:	C,	57.44;	H,	3.78;	N,	8.24%.	

(E)‐1‐[3‐(3‐(3‐fluorophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4n):	 Colour:	 Yellow.	 Yield:	 84%.	M.p.:	 183.5	 oC.	 	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3241	 (N‐H),	 3029	 (C‐H),	 1704	 (C=O),	 1647	 (C=C),	
1591	(CONH),	1522	(N‐H	bend),	1344	(C‐N),	1294	(SO2,	asym.),	
1160	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	
3H,	CH3),	7.18‐7.97	(m,	8H,	Ar‐H),	7.41	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.66	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.88	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	8.03	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	10.03	(s,	1H,	NH),	
11.16	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 439	 [M+H]+.	 Anal.	 calcd.	 for	
C23H19FN2O4S:	 C,	 63.00;	 H,	 4.37;	 N,	 6.39.	 Found:	 C,	 63.12;	 H,	
4.44;	N,	6.43%.	

(E)‐1‐[3‐(3‐(4‐fluorophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4o):	 Colour:	 Yellow.	 Yield:	 87%.	 M.p.:	 150.3	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3383,	 3289	 (N‐H),	 3068	 (C‐H),	 1649	 (C=O),	 1615	
(C=C),	1581	(CONH),	1512	(N‐H	bend),	1346	(C‐N),	1306	(SO2,	
asym.),	1156	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.05‐7.68	(m,	8H,	Ar‐H),	7.69	(d,	 J	=	15.2	Hz,	
1H,	HC=CH	(H‐α)),	7.79	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.42	(d,	J	=	8.1	
Hz,	2H,	Ar‐H),	7.99	 (d,	 J	 =	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.94	 (s,	



Bugata	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	396‐401	 399	
 

1H,	 NH),	 11.01	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 439	 [M+H]+.	 Anal.	
calcd.	 for	 C23H19FN2O4S:	 C,	 63.00;	 H,	 4.37;	 N,	 6.39.	 Found:	 C,	
63.12;	H,	4.24;	N,	6.32%.	

(E)‐1‐[3‐(3‐(2‐chlorophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4p):	 Colour:	 Yellow.	 Yield:	 88%.	 M.p.:	 244.5	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3225	 (N‐H),	 3071	 (C‐H),	 1716	 (C=O),	 1695	 (C=C),	
1684	(CONH),	1558	(N‐H	bend),	1340	(C‐N),	1300	(SO2,	asym.),	
1153	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	
3H,	CH3),	6.66‐7.15	(m,	8H,	Ar‐H),	7.41	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.66	(d,	 J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.83	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	8.05	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	10.89	(s,	1H,	NH),	
12.13	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 455	 [M+H]+.	 Anal.	 calcd.	 for	
C23H19ClN2O4S:	 C,	 60.72;	 H,	 4.21;	 N,	 6.16.	 Found:	 C,	 60.65;	 H,	
4.32;	N,	6.14%.	

(E)‐1‐[3‐(3‐(4‐chlorophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4q):	 Colour:	 Yellow.	 Yield:	 92%.	 M.p.:	 227.5	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3450,	 3340	 (N‐H),	 3049	 (C‐H),	 1650	 (C=O),	 1626	
(C=C),	1588	(CONH),	1566	(N‐H	bend),	1341	(C‐N),	1270	(SO2,	
asym.),	1133	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.38	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.45‐7.63	(m,	8H,	
Ar‐H),	7.67	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.88	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.90	(d,	 J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.73	(s,	1H,	
NH),	11.21	(s,	1H,	NH).	ESI‐MS	(m/z):	455	[M+H]+.		Anal.	calcd.	
for	C23H19ClN2O4S	:	C,	60.72;	H,	4.21;	N,	6.16.	Found:	C,	60.65;	H,	
4.37;	N,	6.15%.	

(E)‐1‐[3‐(3‐(2,4‐dichlorophenyl)	 acryloyl)	 phenyl]‐3‐
tosylurea	(4r):	Colour:	Yellow.	Yield:	85%.	M.p.:	220.5	oC.	FT‐IR	
(KBr,	 vmax,	 cm‐1):	 3454,	 3345	 (N‐H),	 3069	 (C‐H),	 1708	 (C=O),	
1633	(C=C),	1617	(CONH),	1584	(N‐H	bend),	1359	(C‐N)	1270	
(SO2,	asym.),	1135	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	
ppm):	2.30	(s,	3H,	CH3),	6.66‐7.35	(m,	7H,	Ar‐H),	7.44	(d,	J	=	8.1	
Hz,	2H,	Ar‐H),	7.66	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.74	(d,	J	=	
8.1	Hz,	2H,	Ar‐H),	7.88	(d,	 J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	9.68	
(s,	1H,	NH),	10.91	(s,	1H,	NH).	ESI‐MS	(m/z):	490[M+H]+.	Anal.	
calcd.	 for	 C23H18Cl2N2O4S:	 C,	 56.45;	H,	 3.71;	N,	 5.72.	 Found:	 C,	
56.53;	H,	3.82;	N,	5.86%.	

(E)‐1‐[3‐(3‐(3‐bromophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4s):	 Colour:	 Yellow.	 Yield:	 84%.	 M.p.:	 214.2	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3445,	 3349	 (N‐H),	 3068	 (C‐H),	 1642	 (C=O),	 1596	
(C=C),	1511	(CONH),	1447	(N‐H	bend),	1334	(C‐N),	1306	(SO2,	
asym.),	1168	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.35‐7.68	(m,	8H,	Ar‐H),	7.41	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	7.69	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.78	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.98	(d,	 J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	9.12	(s,	1H,	
NH),	 8.99	 (s,	 1H,	NH).	 ESI‐MS	 (m/z):	 500	 [M+H]+.	 Anal.	 calcd.	
for	C23H19BrN2O4S:	C,	55.32;	H,	3.83;	N,	5.61.	Found:	C,	55.28;	H,	
3.82;	N,	5.55%.	

(E)‐1‐[3‐(3‐(4‐bromophenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4t):	Colour:	Yellow.	Yield:	81%.	M.p.:	244.2	oC.	FT‐IR	(KBr,	vmax,	
cm‐1):	3439,	3349	(N‐H),	3019	(C‐H),	1639	(C=O),	1579	(C=C),	
1513	(CONH),	1442	(N‐H	bend),	1329	(C‐N),	1312	(SO2,	asym.),	
1177	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.30	(s,	
3H,	CH3),	7.33‐7.61	(m,	8H,	Ar‐H),	7.44	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	
7.67	(d,	 J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.72	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	7.98	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	9.11	(s,	1H,	NH),	
8.99	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 500	 [M+H]+.	 Anal.	 calcd.	 for	
C23H19BrN2O4S:	 C,	 55.32;	 H,	 3.83;	 N,	 5.61.	 Found:	 C,	 55.22;	 H,	
3.81;	N,	5.52%.	

(E)‐1‐[3‐(3‐(4‐allyloxyphenyl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4u):	 Colour:	 Yellow.	 Yield:	 85%.	 M.p.:	 162.2	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3328,	 3227	 (N‐H),	 3058	 (C‐H),	 1632	 (C=O),	 1588	
(C=C),	1502	(CONH),	1458	(N‐H	bend),	1326	(C‐N),	1281	(SO2,	
asym.),	1127	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	4.49	(s,	2H,	CH2),5.33	(s,	2H,	CH2),	5.51	(s,	1H,	
CH),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.67‐7.91	(m,	8H,	Ar‐H),	7.83	
(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.87	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	
8.04	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	8.98	(s,	1H,	NH),	9.96	(s,	
1H,	 NH).	 ESI‐MS	 (m/z):	 477	 [M+H]+.	 Anal.	 calcd.	 for	
C26H24N2O5S:	C,	65.53;	H,	5.08;	N,	5.88.	Found:	C,	65.34;	H,	5.90;	
N,	5.75%.	

(E)‐1‐[3‐(3‐(Phenylethene‐yl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4v):	 Colour:	 Yellow.	 Yield:	 94%.	 M.p.:	 178.3	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3443,	 3297	 (N‐H),	 3060	 (C‐H),	 1630	 (C=O),	 1573	
(C=C),	1509	(CONH),	1447	(N‐H	bend),	1354	(C‐N),	1301	(SO2,	
asym.),	1141	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.33‐7.12	(m,	11H,	Ar‐H),	7.42	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.68	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.78	(d,	J	=	8.1	
Hz,	2H,	Ar‐H),	7.92	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	10.97	(s,	
1H,	 NH),	 11.99	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 447	 [M+H]+.	 Anal.	
calcd.	 for	 C25H22N2O4S:	 C,	 67.25;	 H,	 4.97;	 N,	 6.27.	 Found:	 C,	
67.18;	H,	4.12;	N,	6.23%.	

(E)‐1‐[3‐(3‐(pyridine‐3‐yl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4w):	 Colour:	 Yellow.	 Yield:	 86%.	 M.p.:	 231.8	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3423,	 3218	 (N‐H),	 3016	 (C‐H),	 1686	 (C=O),	 1650	
(C=C),	1593	(CONH),	1520	(N‐H	bend),	1352	(C‐N),	1303	(SO2,	
asym.),	1146	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	6.97‐7.54	(m,	8H,	Ar‐H),	7.41	(d,	J	=	8.1	Hz,	2H,	
Ar‐H),	7.68	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐α)),	7.88	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.93	(d,	J	=	15.4	Hz,	1H,	HC=CH	(H‐β)),	10.45	(s,	1H,	
NH),	11.99	(s,	1H,	NH).	ESI‐MS	(m/z):	422	[M+H]+.	Anal.	calcd.	
for	C22H19N3O4S:	C,	62.69;	H,	4.54;	N,	9.97.	Found:	C,	62.69;	H,	
4.62;	N,	9.78%.	

(E)‐1‐[3‐(3‐(pyridine‐4‐yl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4x):	 Colour:	 Yellow.	 Yield:	 89%.	 M.p.:	 188.0	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3388,	 3277	 (N‐H),	 2887	 (C‐H),	 1649	 (C=O),	 1620	
(C=C),	1586	(CONH),	1498	(N‐H	bend),	1346	(C‐N),	1296	(SO2,	
asym.),	1156	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.42	(d,	J	=	8.1	Hz,	2H,	Ar‐H),	7.53‐7.81	(m,	8H,	
Ar‐H),	7.66	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.79	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.89	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	10.42	(s,	1H,	
NH),	11.64	(s,	1H,	NH).	ESI‐MS	(m/z):	422	[M+H]+.	Anal.	calcd.	
for	C22H19N3O4S:	C,	62.69;	H,	4.54;	N,	9.97.	Found:	C,	62.71;	H,	
4.66;	N,	9.88%.	

(E)‐1‐[3‐(3‐(Anthracen‐9‐yl)	 acryloyl)	 phenyl]‐3‐tosylurea	
(4y):	 Colour:	 Yellow.	 Yield:	 93%.	 M.p.:	 174.4	 oC.	 FT‐IR	 (KBr,	
vmax,	 cm‐1):	 3298,	3242	 (N‐H),	2887	 (C‐H),	1694m(C=O),	 1600	
(C=C),	1537	(CONH),	1452	(N‐H	bend),	1343	(C‐N),	1319	(SO2,	
asym.),	1157	(SO2,	sym.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.30	(s,	3H,	CH3),	7.31‐7.54	(m,	13H,	Ar‐H),	7.42	(d,	J	=	8.1	Hz,	
2H,	Ar‐H),	7.73	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.81	(d,	J	=	8.1	
Hz,	2H,	Ar‐H),	8.11	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	10.78	(s,	
1H,	 NH),	 12.11	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 521	 [M+H]+.	 Anal.	
calcd.	 for	 C31H24N2O4S:	 C,	 71.52;	 H,	 4.65;	 N,	 5.38.	 Found:	 C,	
71.48;	H,	4.53;	N,	5.25%.	

	
2.3.	Pharmacological	activity	
	

The	 5‐LO	 inhibitory	 potential	 of	 the	 synthesized	
compounds	 (4a‐4y)	was	determined	by	 5‐LO	 inhibition	 assay	
(UV‐Kinetic	method)	as	described	by	Sircar	et	al.	 [40].	For	the	
evaluation	of	5‐LO	inhibitory	activity,	the	enzymatic	activity	of	
5‐LO	was	measured	spectrophotometrically	using	potato	5‐LO	
[41]	and	an	incubation	mixture	containing	80	mM	linoleic	acid	
and	50	mM	sodium	phosphate	buffer	 (pH	=	6.3).	The	 reaction	
was	 initiated	 by	 the	 addition	 of	 an	 enzyme	 buffer	 mix	 to	
substrate	 (Linoleic	 acid)	 and	 the	 enzyme	 activity	 was	
monitored	as	an	increase	in	rate	of	absorbance	at	234	nm	on	a	
UV/visible	 spectrophotometer	 (Varion	 Cary‐50	 UV‐Visible	
spectrophotometer)	 for	 120	 sec.	 Each	 experiment	 was	
conducted	 by	 incubating	 along	 with	 control	 at	 various	
concentrations	of	 the	 test	 substances	with	 enzyme	buffer	mix	
for	 2	 min	 before	 addition	 of	 the	 substrate.	 The	 percentage	
inhibition	 was	 calculated	 by	 comparing	 slope	 or	 increase	 in	
absorbance	 of	 test	 substance	 with	 that	 of	 control	 enzyme	
activity.	The	assay	was	performed	in	triplicate	and	mean	values	
were	 used	 for	 the	 calculation.	 The	 IC50	 values	 were	 obtained	
using	 fenny	 probed	 analysis	 software.	 The	 result	 for	 the	 test	
compound	was	compared	with	the	positive	control	abietic	acid	
(LI01020)	[42].	The	results	of	5‐LO	inhibitory	activity	are	given	
in	Table	1.	

	



400	 Bugata	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	396‐401	
	
	
Table	1.	Physical	characterization	and	5‐LO	inhibitory	activity	data	of	diarylsulfonylurea‐chalcone	hybrids	4a‐4y	produced	via	Scheme	1.	

Compound	 R	 Yield	a	(%)	 Molecular	weight	(g)	 Molecular	formula	 M.p.	(oC)	 IC50	(µg/mL)	
(mean±SEM) c

4a	 C6H5	 97	 420 C23H20N2O4S 151.3	 38.66±0.25
4b	 4‐MeC6H4	 89	 434	 C24H22N2O4S	 233.8	 25.24±0.45	
4c	 4‐NMe2C6H4	 88	 463	 C25H25N3O4S	 150.5	 35.11±0.23	
4d	 2,4‐diOMeC6H3	 84	 480	 C25H24N2O6S	 163.3	 23.11±0.32	
4e	 3,4,	5‐triOMeC6H2	 88	 510	 C26H26N2O7S	 198.6	 22.18±0.11	
4f	 2‐OHC6H4	 86	 436 C23H20N2O5S 258.9	 35.13±0.45
4g	 3‐OHC6H4	 82	 436 C23H20N2O5S 185.2	 46.22±0.12
4h	 4‐OHC6H4	 89	 436 C23H20N2O5S 185.7	 39.24±0.34
4i	 3‐OEt,4‐OHC6H3	 89	 480 C25H24N2O6S 174.3	 26.31±0.52
4j	 3‐OMe,4‐OHC6H3	 93	 466 C24H22N2O6S 178.6	 22.18±0.17
4k	 2‐NO2C6H4	 86	 465 C23H19N3O6S 231.8	 24.28±0.13
4l	 3‐NO2C6H4	 89	 465 C23H19N3O6S 172.2	 33.66±0.61
4m	 5‐OH,2‐NO2C6H3	 85	 481	 C23H19N3O7S	 166.2	 44.18±0.53	
4n	 3‐FC6H4	 84	 438	 C23H19FN2O4S	 183.5	 18.12±0.42	
4o	 4‐FC6H4	 87	 438 C23H19FN2O4S 150.3	 11.77±0.21
4p	 2‐ClC6H4	 88	 454	 C23H19ClN2O4S	 244.5	 24.81±0.51	
4q	 4‐ClC6H4	 92	 454 C23H19ClN2O4S 227.5	 15.32±0.16
4r	 2,4‐diClC6H3	 85	 489 C23H18Cl2N2O4S 220.5	 7.88±0.14
4s	 3‐BrC6H4	 84	 499 C23H19BrN2O4S 214.2	 29.41±0.27
4t	 4‐BrC6H4	 81	 499 C23H19BrN2O4S 244.2	 18.12±0.32
4u	 4‐Allyl‐OC6H4	 85	 476 C26H24N2O5S 162.2	 29.13±0.23
4v	 Phenylethene‐yl	 94	 446 C25H22N2O4S 178.3	 44.38±0.13
4w	 Pyridin‐3‐yl	 86	 421	 C22H19N3O4S	 231.8	 41.22±0.49	
4x	 Pyridin‐4‐yl	 89	 421 C22H19N3O4S 188.0	 33.31±0.22
4y	 Anthracen‐9‐yl	 93	 520	 C31H24N2O4S	 174.4	 14.91±0.77	
Standard	b	 ‐	 ‐	 ‐	 ‐	 ‐	 4.34±0.37	
a	Crystallization	solvent	is	ethanol.	
b	Abietic	acid	(LI01020).	
c	SEM	=	Standard	error	of	the	mean.	
	
	
3.	Results	and	discussion		
	
3.1.	Synthesis	
	

The	 reaction	 sequence	 employed	 in	 the	 synthesis	 of	
diarylsulfonylurea‐chalcone	 hybrids	 (4a‐4y)	 is	 shown	 in	 the	
Scheme	1	and	their	physical	properties	are	depicted	in	Table	1.	
The	key	 intermediate	 in	 the	present	study	1‐(3‐acetylphenyl)‐
3‐tosylurea	 (3)	 was	 synthesized	 by	 reaction	 of	 3‐
aminoacetophenone	(1)	with	methylchloroformate	under	basic	
conditions	 at	 0	 °C	 temperature	 to	 give	methyl‐3‐acetylphenyl	
carbamate	 (2)	 followed	 by	 the	 reaction	 with	 toluene	
sulphonamide	 and	 on	 the	 other	 hand	 subsequent	 Claisen‐
Schmidt	condensation	of	the	intermediate	(3)	with	appropriate	
aromatic/heteroaromatic	aldehydes	 in	ethanolic	KOH	solution	
to	give	 the	corresponding	diarylsulfonylurea‐chalcone	hybrids	
(4a‐4y)	 in	 good	 yield	 (Scheme	 1).	 All	 the	 structures	 of	 the	
compounds	 were	 appropriately	 established	 by	 spectroscopic	
data	and	analytical	methods.	
	
3.2.	5‐Lipoxygenase	inhibitory	activity	
	

The	 investigation	 of	 in	 vitro	 5‐LO	 inhibitory	 activity	
screening	data	 (Table	1)	 revealed	 that	 the	compounds	4r	 and	
4o	 demonstrated	 comparatively	 the	 most	 potent	 inhibitory	
activity,	with	 IC50	 values	 of	 7.88±0.14	 µg/mL	 and	 11.77±0.21	
µg/mL,	 respectively.	 It	 is	 interesting	 to	 note	 that	 the	
compounds	 4y,	 4q,	 4t	 and	 4n	 also	 showed	 appreciable	
inhibitory	 activity	with	 IC50	 values	 of	 14.91±0.77,	 15.32±0.16,	
18.12±0.32	 and	 18.12±0.42	 µg/mL,	 respectively.	 The	 other	
compounds	 such	 as	4b,	4d,	4i‐4l,	4p,	4s,	4u	 and	4x	 showed	
moderate	level	of	activity	at	concentrations	(IC50)	ranging	from	
22.18±0.11	to	33.31±0.22	µg/mL.	The	compounds	4a,	4c,	4f‐h,	
4m,	4v	and	4w	exhibited	comparatively	 less	activity	with	 IC50	
values	 ranging	 from	 35.11±0.23	 to	 46.22±0.12	 µg/mL	 in	
comparison	 with	 the	 standard	 drug	 (Abietic	 acid	 (LI01020),	
IC50:	4.34±0.37	µg/mL).		

A	close	look	at	the	SAR	(Structure‐Activity	Relationship)	of	
these	 compounds	 clearly	 exhibited	 the	 inherent	 phenomenon	
of	 5‐LO	 inhibitory	 activity	 associated	 with	 the	 basic	 skeleton	
consisting	 of	 diarylsulfonylurea	 and	 α,β‐unsaturated	 ketone	
moieties	 as	 seen	 in	 case	 of	 the	 unsubstituted	 compound	 4a	

with	IC50	value	of	38.66±0.25	µg/mL,	which	in	some	cases	was	
enhanced	by	the	influence	of	some	substituents	and	decreased	
by	 some	 other	 substituents.	 For	 example,	 the	 compounds	 4r	
(2,4‐diCl,	 IC50:	 7.88±0.14	 µg/mL)	 >	 4o	 (4‐F,	 IC50:	 11.77±0.21	
µg/mL)	 >	 4q	 (4‐Cl,	 IC50:	 15.32±0.16	 µg/mL)	 >	 4n	 (3‐F,	 IC50:	
18.12±0.42	 µg/mL)	 >	4t	 (4‐Br,	 IC50:	 18.12±0.32	 µg/mL)	 >	4p	
(2‐Cl,	 IC50:	 24.81±0.51	 µg/mL)	 >	 4s	 (3‐NH2,	 IC50:	 29.41±0.27	
µg/mL)	having	halogen	substituents	either	at	ortho	or	meta	or	
para	positions	significantly	enhanced	 the	activity.	A	 reduction	
in	the	activity	was	observed	when	the	substituted	phenyl	ring	B	
was	 replaced	 by	 a	 cinnamyl	 moiety,	 as	 seen	 in	 the	 case	 of	
compound	4v	(IC50	value	44.38±0.13	µg/mL).	The	presence	of	a	
3‐pyridyl	 ring	 in	 compound	 4w	 in	 the	 place	 of	 substituted	
phenyl	 ring	 B	 of	 α,β‐	 unsaturated	 carbonyl	 system	 enhanced	
the	activity	 compared	 to	 the	one	possessing	 cinnamyl	moiety,	
but	less	than	that	of	the	one	having	substituted	phenyl	ring.	It	is	
also	 interesting	 to	 see	 the	 presence	 of	 4‐pyridyl	 ring	 in	 the	
place	of	substituted	phenyl	ring	B	contributed	to	an	increase	in	
activity	 compared	 to	 the	 one	 possessing	 3‐pyridyl	 ring,	
respectively	as	seen	in	the	case	of	compounds	4x	and	4w	with	
IC50	values	33.31±0.22	and	41.22±0.49	µg/mL,	 respectively.	 It	
was	observed	that	the	replacement	of	substituted	phenyl	ring	B	
with	allyloxy	group	at	para	position	enhanced	5‐LO	 inhibitory	
activity	 (4u,	 IC50:	 29.13±0.23	 µg/mL).	 The	 presence	 of	 a	 9‐
anthracenyl	ring	 in	compound	4y	 (IC50:	14.91±0.77	µg/mL)	 in	
the	 place	 of	 substituted	 phenyl	 ring	 B	 of	 α,β‐	 unsaturated	
carbonyl	 system	 significantly	 increased	 the	 activity	 compared	
to	the	one	possessing	3‐pyridyl	and	4‐pyridyl	ring	systems.		

However,	 it	 was	 noticed	 that	 various	 aromatic/hetero‐
aromatic	 rings	 substituted	 at	 position	 3	 of	 α,β‐unsaturated	
carbonyl	system	followed	its	activity	order	as	anthreacen‐9‐yl	>	
pyridin‐4‐yl	 >	 phenyl	 >	 pyridin‐3‐yl	 moieties,	 respectively.	 It	
was	 also	noted	 that	 the	 compounds	 substituted	with	 electron	
releasing	groups	was	found	to	be	biologically	relevant	and	the	
activity	order	was	(4e	(3,4,5‐tri‐OCH3,	IC50:	22.18±0.11	µg/mL)	
>	4d	 (2,4‐di‐OCH3,	 IC50:	23.11±0.32±0.23	µg/mL)	>	4b	 (4‐CH3,	
IC50:	 25.24±0.45	 µg/mL)	 >	 4c	 (4‐N(CH3)2,	 IC50:	 35.11±0.23	
µg/mL)),	 respectively.	 It	 is	 important	 that	 less	 activity	 was	
observed	when	the	hydroxyl	groups	are	substituted	at	different	
positions	on	the	phenyl	ring	as	seen	in	the	case	of	compounds	
4f‐4h	and	 the	order	of	activity	was	4f	 (2‐OH,	 IC50:	35.13±0.45	
µg/mL)	>	4h	(4‐OH,	IC50:	39.24±0.34	µg/mL)	>	4g	(3‐OH,	IC50:	



Bugata	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	396‐401	 401	
 

44.18±0.53	 µg/mL)	 respectively.	 The	 compounds	 4j	 (IC50:	
22.18±0.17	µg/mL)	 having	methoxyl	 group	 at	 substitution	 on	
the	 phenyl	 ring	 B	 at	 position	 3,	 4i	 (IC50:	 26.31±0.52	 µg/mL)	
having	 ethoxy	 group	 at	 substitution	 on	 the	 phenyl	 ring	 B	 at	
position	3	and	4m	(IC50:	44.18±0.53	µg/mL)	having	nitro	group	
at	substitution	on	the	phenyl	ring	B	at	position	2	along	with	the	
hydroxyl	group	substitution	at	positions	4	(in	case	of	4j	and	4i)	
and	5	(in	case	of	4m),	respectively	showed	enhanced	level	of	5‐
LO	 inhibitory	 activity	 when	 compared	 with	 that	 of	 the	
compounds	 (4f‐4h)	 possessing	 only	 hydroxyl	 group	
substitution.	 It	 is	 notable	 that	 enhanced	 level	 of	 activity	 was	
observed	when	the	nitro	group	introduced	on	the	phenyl	ring	B	
of	α,β‐unsaturated	carbonyl	system	at	2	and	3	positions	as	seen	
in	the	case	of	compounds	4k	and	4l	with	IC50	values	24.28±0.13	
and	33.66±0.6	µg/mL,	respectively.	
	
4.	Conclusion	
	

In	 summary,	we	synthesized	and	 characterized	a	 series	of	
diarylsulfonylurea‐chalcone	hybrids	(4a‐4y).	For	the	first	time,	
this	 class	 of	 compounds	 were	 screened	 for	 5‐LO	 inhibitory	
activity	 and	 the	 results	 revealed	 the	 positive	 contribution	 of	
halogen	 substituents	 on	 the	 phenyl	 ring	 B	 of	 α,β‐unsaturated	
ketone	 towards	 the	 observed	 5‐LO	 inhibitory	 activity.	 The	
observed	 activity	 may	 also	 be	 due	 to	 diarylsulfonylurea	 and	
α,β‐unsaturated	 ketone	 moieties	 forming	 part	 of	 the	 basic	
structure	of	these	molecules.	The	results	indicated	that	further	
development	 of	 such	 compounds	 might	 be	 of	 biological	
interest.	
	
Acknowledgements	
	

One	 of	 the	 authors	 (Bharat	 Kumar)	 is	 thankful	 to	 Gitam	
University,	Visakhapatnam,	for	providing	necessary	facilities	to	
carry	out	research	work.		
	
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