Synthesis of Some New Substituted Quinazolin-4-3H-Ones as
potent anticonvulsant agents
Neha Garg#, Trilok Chandra, S. Lata, K.K Saxena and Ashok Kumar*
Medicinal Chemistry Division Department of Pharmacology Medical College,
Meerut-250004 (U.P.) India
Abstract:
All the synthesized compounds (1-32) were screened for their anticonvulsant activity at a
dose of 30 mg/kg.Some of the compounds were found to exhibit good anticonvulsant
activity. All the synthesized compounds have been characterized by elemental (C,H,N)
and spectral (IR,1H-NMR) analysis.The Compound 31 was found to be most potent
compound of this series showed 90% protection against MES.
Keywords:
Benzylidenoquinazolinones,thiazolyquinazolnones,thiazolidinylthiazolylquinazolidinones,anticonvulsant activity, acute toxicity studies.
Introduction:
Quinazolinone nucleus have been gaining prominence due to the fact that it’s derivative
have
been
found
to
possess
wide
spectrum
of
activities
like
anticonvulsantactivity[1,2,3,4],anti-infammotaryactivity[5],have patented quinazolinone[6]
,derivatives
as
potent
anticonvulsantactivity.
Moreover
thiadiazole[7],
,thiazolidinones[8,9], are other important pharmacodynamic heterocyclic nuclei, which
incorporated in different heterocyclic templates have been reported to possess potent
anticonvulsant activity.In the light of the above observation was throught worthwhile to
*For Correspondence : Ashok Kumar, Professer Medicinal Chemistry Division, Department of Pharmacology,
L.L.R.M. Medical College, Meerut (U.P.) -250004 , India.Tel:+91-09917053074 ,Fax:+91(0121)760888,
Email.-rajputak@gmail.com
#
Part of the thesis work
synthesized some new derivatives of quinazilinone by incorporate both thiazolyl and
thaiazolydinoyl moieties at second position of quinazolinone nucleus with the hope to
posses better anticonvulsant activity.
Chemistry:
Bromination of
3-substitutedphenyl -6,8-dibromo-2-methylquinazolin-4(3H)-ones i.e
compounds 3-4 yielded 3-substitutedphenyl -2 bromomethyl-6,8-dibromoquinazolin4(3H)-ones i.e compounds 5-6.These brominated products on treatment with 99%
hydrazine
hydrate
afforded
dibromoquinazolin-4(3H)-ones
chloroacetylchloride
gave
7-8.
3-substitutedphenyl-2–hydrazinomethyl-6,8Compounds
7-8
on
reaction
with
3-substitutedphenyl-2–chloroacetylhydrazinomethyl-6,8-
dibromoquinazolin-4(3H)-ones 9-10. further compounds 9-10 were converted in to
thiazol congeners i.e. 3-substitutedphenyl-2–(2'-aminothiazol-4'-yl)hydrazinomethyl -6,8dibromoquinazolin-4(3H)-ones 11-12 by the reaction of thiourea.further compounds 1112 reacted with different aromatic aldehydes to give 3-substitutedphenyl-2–(2'benzylidenylimino-thiazol-4'-yl)hydrazinomethyl-6,8-dibromoquinazolin-4(3H)-ones 1322.substituted benzylidene congeners 13-22 were cyclized on reacting with thioglycolic
acid and anhydrous ZnCl2 to yield 3-substitutedphenyl-2–[2'- (2''-phenylthizolidine-4''on-3''-yl]hydrazinomethyl-6,8-dibromoquinazolin-4(3H)-ones-23-32.
Meterials and Methods:
The melting points of compounds were determined in open capillaries and are
uncorrected. Homogeneity of the synthesized compounds was routinely checked by thin
layer chromatography on Silica Gel-G plates. The eluent was a mixture of different polar
and nonpolar solvent in different proportion and spots were located by iodine. The IR
spectra were recorded on Bruker IFS-66 V FTIR( max in cm–1). The 1H NMR spectra
were recorded by Brucker DRX-400 FTNMR instrument using CDCl3 and DMSO-d6 as
solvent and tetramethyl silane (TMS) as internal reference standard.All Chemical shift()
values were recorded in ppm..Elemental analysis (C,H,N)of these newly synthesized
compounds were performed on a Carlo Erba-1108 elemental analyzer.
Synthesis of 3, 5-dibromoanthralic acid (1):
It was prepared according to the method of wheeler and oates[10].Bromine (0.8mol) in
acetic acid (20ml) was added dropwise to the solution of anthranilic acid (0.4 mol) in
absolute ethanol (60ml).The solid product thus crystallized out washed with hot water
and dried .It was recrytalilized from methanol.compound 1: m.p 219C(Reported m.p
218C).
Synthesis of 2-methhylbenzoxazinone-6,8-dibromo(2):
It was prepared according to the method of Bogert and Seil
[11]
.A mixture of 3,5-
dibromoanthralic acid (0.01 mol) and acetic anhydride (0.02 mol) were refluxed for 2-3
hours with constant stirring. The excess of acetic anhydride was distilled off on cooling a
solid separated out which was filtered, washed with petroleum ether (60-80 ºC) and dried
in vacuum compound 2: m.p 182C (Reported m.p 184C).
Synthesis of 3-(p-hydroxyphenyl)-6,8-dibromo-2-methylquinazolin-4(3H)-one(3):
A mixture of compound 2 (0.2 mol) and substituted aniline (0.2 mol) was heated on a free
flame for 10-20 minutes in conical flask.After the disappearance of water droplets in
conical flask, it was kept at room temperature.On cooling a jelly like mass obtained
which was dissolved in methanol,refluxed and poured into water .The solid thus obtained
was filtered, dried and finally recrystallized with ethanol. compound 3: m.p 202C; yield
62%;molecular formula C15H10N2O2Br2. IR (KBr) max in Cm-1 610 (C-Br),1635 (C=N),
1550 (C C of aromatic ring),1720(C=O of quinazolin ring),1734 (OH): 1H-NMR
(CDCl3) in ppm 2.30 (s, 3H, CH3),7.25-7.90(m,6H,Ar-H),9.30(s,1H,,OH exchangable).
The compound 4 have been prepared by employing the aforementioned method and their
physical and analytical data are shown in Table-I
Synthesis
of
3-(p-hydroxyphenyl)-2-bromomethyl-6,8-dibromoquinazolin-4(3H)-
one(5):
Bromine (0.4 mol) in acetic acid (20ml) was added dropwise to the solution of compound
3 (0.2 mol) in acetic acid (50ml).The reaction mixture was poured onto crushed ice then
left overnight at room temperature The precipitate thus obtained was filtered ,washed
with water ,dried and recrystallized with ethanol Compound 5: m.p 214C; yield
70%;molecular formula C15H9N2O2Br3. IR (KBr) max in Cm-1 608 (C-Br), 1550 (C C
of aromatic ring),
1632 (C=N), 1715 ( C=O of quinazolin ring), 3425
(OH):1HNMR(CDCl3)inppm2.75(s,2H,CH2),7.207.85(m,6H,ArH),9.86(s,1H,,OHexch
angable). The compound 6 have been prepared by employing the aforementioned method
and their physical and analytical data are shown in Table-I
Synthesis of 3-(p-hydroxyphenyl)2–hydrazinomethyl-6,8-dibromoquinazolin-4(3H)one(7):
A mixture of compound 5 (0.1 mol) and hydrazine hydrate (99%) (0.2 mol) in methanol
was refluxed for 10 hours The excess of solvent was distilled off and the reaction mixture
was poured onto ice. The solid thus obtained was filtered, washed with water,dried and
recrystallized from methanol compound 7.m.p.222ºC;yield64%; molecular formula
C15H12N4O2Br2. IR (KBr) max in Cm-1 610 (C-Br),1270(N-N),1300 (C-N), 1550 (C C
of aromatic ring),1720(C=O of quinazolin ring) ,1620(C=N), 3425(OH) ,3300(NH,NH2) :
1
H-
NMR
(CDCl3)
in
ppm
2.64(s,2H,CH2),7.22-7.82(m,6H,Ar-
H),9.85(s,1H,,OHexchangable). The compound 8 have been prepared by employing the
aforementioned method and their physical and analytical data are shown in Table-I
Synthesis
of
3-(p-hydroxyphenyl)-2-chloroacetyhydrazinomethyl-6,8–dibromo-
quinazolin-4 (3H)-one (9) :
To the solution of compound 7 (0.01 mol)
in dry benzene (60) chloroacetylchloride
(0.02 mol) was added gradually with stirring under cool condition. The reaction mixture
was further stirred for another 2 hours at room temperature and then refluxed for 4 hours
.Benzene was removed by distillation ,to yield the product ,which was fjnally
recrystallized from methanol to afford compound 9.m.p.242 ºC ; yield 70%; molecular
formula C17H12N4O3Br2Cl. IR (KBr) max in Cm-1 610(C-Br), 760(C-Cl), 1270(N-N),
1320 (C-N), 1550 (C C of aromatic ring), 1715 ( C=O of quinazolin ring), 1618 (C=N),
3480 (OH) ,3320(N-H), 2956(C-H aliphatic) :,3055 (C-H aromatic) ,3480 (OH)
1
H-
NMR(CDCl3)in ppm 2.60 (s, 2H, CH2 ),(s,2H,-CHCl2) , 7.25-7.80(m,6H,ArH),9.85(s,1H,,OH exchangable). The compound 10 have been prepared by employing the
aforementioned method and their physical and analytical data are shown in Table-I
Synthesis
of
3-(p-hydroxyphenyl)-2–(2'-aminothiazol-4'-yl)hydrazinomethyl-6,8-
dibromoquinoazolin-4(3H)-one(11):
A mixture of compound 9, (0.02 mol) thiourea (0.02 mol) and acetone (60 ml) was
refluxed for 12 hours. The completion of the reaction was monitored by TLC it was then
concerted and cooled, where upon the solid separated out was filtered and then
recrystallized from methanol.The solid thus obtained was washed with 2% saturated
sodium carbonate solution and water to librate the base completely dried and
recrystallized from ethanol to give compound 11: m.p.250 ºC; yield 68%; molecular
formula C18H14N6O2SBr2. IR (KBr) max in Cm-1 612(C-Br), 690(C-S-C), 1270(N-N),
1220 (C-N), 1580 (C C of aromatic ring), 1715 ( C=O of quinazolin ring), 1616 (C=N),
3485 (OH) ,3390(N-H).1H-NMR(CDCl3)in ppm 2.55 (s, 2H, CH2 NH), 6.40(s,2H,NH2
exchangable
with
D2O),
7.25-7.84(m,7H,Ar-H),7.89
(brs,2H,NH.NH2),10.00(s,1H,,OH exchangable). The compound 12 have been prepared
by employing the aforementioned method and their physical and analytical data are
shown in Table-I
Synthesis of 3-(p-hydroxyphenyl)-2–(2'-benzylidenylimino-thiazol-4'-yl) hydrazinomethyl-6,8-dibromoquinoazolin-4(3H)-one(13):
To the solution of compound 11 (0.01 mole) in methanol (80ml), benzaldehyde (0.01)
with few drops of glacial acetic acid was added and then reaction mixture refluxed for 10
hours ,completion of the reaction was monitored by TLC. After distillation of excess of
solvent the reaction mixture was cooled ,diluted with cold water and filtered. The solid
thus collected was recrystalized from ethanol to furnish compound 13 :m.p.260 ºC ; yield
58%; molecular formula C25H18N6O2SBr2. . IR (KBr) max in Cm-1 608 (C-Br), 690(C-SC), 1270(N-N), 1219 (C-N), 1575 (C C of aromatic ring), 1717 ( C=O of quinazolin
ring), 1620 (C=N), ,3382(N-H) 3485 (OH).1H-NMR(CDCl3)in ppm 2.56 (s, 2H, CH2NH),7.05-7.90(m,12H,Ar-H),7.85
(brs,2H,NH.NH
exchangable
with
D2O),4.624(s,1H,=CH-Ar),10.04(s,1H,,OH exchangable). The compounds 14-22 have
been prepared by employing the aforementioned method and their physical and analytical
data are shown in Table-I
Synthesis of 3-(p-hydroxyphenyl)-2-[2'-(2''-phenylthizolidine-4''on-3''yl] hydrazinomethyl-6,8-dibromoquinoazolin-4(3H)-one(23):
A mixture of compound 13 (0.01), thioglycolic acid (0.01) and anhydrous ZnCl2 (2
gm)in absolute ethanol was refluxed for 10 hours.The progress and completion of
reaction was checked by TLC. After refluxing , excess of solvent was distilled off and
residue was poured in cold water , filtered, dried and finally the product was recrystalized
from benzene to furnish compound 23 :m.p.268 ºC ; yield 60%; molecular formula
C27H20N6O3S2Br2.. . IR (KBr) max in Cm-1 610 (C-Br), 682(C-S-C), 1217 (C-N), 1574
(C C of aromatic ring), 1740 ( C=O of quinazolin ring), 1622 (C=N), ,3370(N-H) 3515
(OH).1H-NMR(CDCl3)in ppm 2.45 (s, 2H, -CH2NH), 4.05(s,2H,-CH2 of thiazolidinone
ring7
),707-7.10(m,12H,Ar-H),7.94
(brs,2H,NH.NH
exchangable
with
D2O),4.60(s,1H,=CH-Ar),10.08(s,1H,,OH exchangable). The compounds 24-32 have
been prepared by employing the aforementioned method and their physical and analytical
data are shown in Table-I
Biological Methods:
The pharmacological activities of compounds were evaluated by the following standard
procedures. All the newly synthesized compounds were evaluated for anticonvulsant
activity and acute toxicity. Anticonvulsant activity was determined by supramaximal
eletroshock seizures pattern test (SMES). Albino rats of either sex weighing between 90150 gm were divided into 10 groups of 10 animals in each group. Only mice were used
for performing acute toxicity studies. The effect of unknown compounds were compared
with the standard drug and propylene glycol treated group served as control. The
statistical evaluation of observations was done by using appropriate statistical tests. All
the compounds were screened for their anticonvulsant activity and approximate lethal
dose (ALD50)
Anticonvulsant activity1.
Supramaximal electroshock seizure pattern test (SMES): This activity was
performed by following the method of Toman et al[12] in albino rats. Rats of
either sex weighing 90-150 gm were divided into groups of ten animal
each.The test drugs and phenytoin sodium reference drug were administrated
intraperitoneally in rats. After one hours they were subjected to a shock of 150
M.A for 0.2 seconds and the presence or absence of extensor response was
noted. Animals in which extensor response was abolished were taken as
protected rats.
2.
Approximate lethal dose (ALD50): The LD50 was determined in mice
weighing 25-30 gm of either sex by the method of smith[13]. The text
compounds were administed orally in one group and the same volume of
propylene glycol in another group of animals consisting six mice in graded
doses. During the study the animals were allowed to take food and water
adlibidum. After 24 hours of drug administration percent mortality in each
group was observed. From the data obtained ALD50 was calculated.
Result and Discussion:
Newly synthesized compounds were tested in vivo in order to evaluate their
anticonvulsant activity at a dose of 30mg/kg i.p. The anticonvulsant effects of
all the
compounds of this series reported in Table II.The characteristic feature of this series is
the presence of a five membered thiazole ring at second position of 2-Methyl-6,8-
dibromo-3-substitutedphenyl quinazolin -4 (3H)-onyl moieties which were further
substituted with alkyl benzylidenyl groups at the second position of five membered
thiadiazole ring .It was observed that compounds haveing 2-Methyl-6,8-dibromo-3-(4chiorophenyl) quinazolin-4(3H)-onyl moiety showed more degree of protection in
comparison to 2-methyl-6,8-dibromo-3-phenylquinazolin-4(3H) onyl moieties. All the
compounds 13-22 exhibiting promising anticonvulsant activity .It was observed that
compounds having phenyl group (compounds13 and18) as subsituent showed least
activity (50 and 60% respectively).while compounds (16 and 21 )substituted with 3mehoxy-4-hydroxy phenyl ring exhibited the maximum percent protection (70 and 80 %)
respectively against seizures induced by MES. Compounds substituted with 4mehoxyphenyl group (15and20) exhibited 60 and 70% inhibition of seizures respectively.
Compounds having 4-hydroxyphenyl and 4-N,N-dimethylamino phenyl also elicited
remarkable anticonvulsant activity of 60%( compounds 14 and 17) and 70% (compounds
19 and 22 )respectively. Further the next step of the series was characterized by the
presence of thiazolidinone (-thiolactum ring )in addition to thiadiazole ring .All
compounds showed potent anticonvulsant activity compounds 26 and 31 substituted with
3-methoxy-4-hydroxyphenyl group have shown most potent activity of 80 and 90%
respectively. However compound 26 showed equipotent activity while compound 31
have shown more potent activity than standard drug phenytoin sodium cycloaddition of
thioglycolic acid
on schiffs bases (13-22)forms their corresponding thiazolidinone
derivatives (23-32) (Table-II).which in general increases the anticonvulsant activity
except in compounds 25 and 30 which showed the same degree of protection i.e. 70%
against MES test.compounds 23 and 28 having phenyl ring at second position of
thiazolidinone ring showed 60 and 70% protection respectively. Where as compounds 25
and 30 having 4-mehoxyphenyl group exhibited 70% protection each compound with 4hydroxyphenyl group i.e. compounds 24 and 29 have also shown remarkable percentage
protection of 70 and 80 % respectively.Eighty percent protection was also exhibited by
the compounds substituted with 4-N,N-dimethylaminophenyl group against seizures
induced by MES. There fore considering the compounds of this step it may be concluded
that compounds 21 and 31 have shown most potent response. These compounds were
also tested at three graded doses i.e. 7.5,15 and 30 mg/kg i.p. Interestingly at all the three
doses compound 21 exhibited activity equipotent to standard drug phenytoin sodium
Moreover compound 31 was found to exhibit more
potent activity than phenytoin
sodium at all the three dose levels.
1. The compounds having 2-methyl-3-(4-chorophenyl)-6,8-dibromoquinazolin4(3H) onyl moiety showed more protection than the compounds having 2-methyl3-phenyl-6,8-dibromoquinazolin-4(3H)onyl moiety.
2. Thiazolidinones showed more potent anticonvulsant activity in comparison to
their corresponding thiazoles.
3. Substitution with 3-methoxy-4-hydroxyphenyl group was found to be more
benificial for the anticonvulsant activity.
Ackowledgement:
We are thankful to SAIF Punjab University Chandigarh for elemental and spectral
analysis.
Refererences:
1. Kumar A et al ,2006,Thiazolidinoyl and azetidinyl quinazolinones as
potential anticonvulsant agents.,Oriental.J.Chem.,22:219-230.
2. Guan et al ,2007.,Synthesis of some quinazolin -2-(1H)-one and 1,2,4triazolo
[4,3-a]
quinazolin
derivatives
as
potent
anticonvulsants.J.Pharm.Pharmaceut. Sci 10(3):254-262.
3. Zappala.M et al 2003.,1-Aryl-6,7-methylenedioxy-3H-quinazolin -4-ones as
anticonvulsant agents.,Bioorg and Medic.Chem.Laters 13: 4427-4430.
4. El-Helby AG.and Wahab M.H.A.,2003,Design and synthesis of some new
derivatives of 3H-quinazolin-4-one with promising anticonvulsant activity
.,Acta Pharm.,53:127-138.
5. Alagarsamy V et al 2006.Pharmacological evaluation of 2-substituted
(1,3,4) thiadiazolo quinazolines.Indian J of Pharmaceu .Sci.,68:108-111.
6. Bajaj K.et al.,2003,Newer substituted benzoxaepinyl quinazolinones as
potent antipsycotropic and anticonvulsant agents.,Arzeim-forsch/Drug
research.,53: 480-485.
7. Mohan RR et al ,1985,Synthesis of some newer Quinazolinyl ,Oxadiazoles,
Tiosemicarbazides,Thiadiazoles as pharmacologically active agents ,Indian
J of Chem,24B:78-82.
8. Archana et al ,2002, Synthesis of newer thiadiazolyl and thiazolidinonyl
quinazolin-4(3H)-ones as potent as anticonvulsant agents.,Eur.J Med
Chem..,37:873-882.
9. Archana et al ,2003, Synthesis of newer indolyl thiadiazoles and their
thiazodinones and formazanes as potential anticonvulsant agents.,Indian J
Pharmaceu.sci.,65:358-362.
10. Wheeler A.S and oats W M ,1910.The bromination of anthranilic acid.
J.Am.Chem.Soc,32:,770-773.
11. Bogert M T and Seli H A,1907.Resarches on quinazolines on dialkyl -4quinazolones and the products obtained by alkylating -2-alkyl-4quinazolones(2-alkyl-4-hydroxy quinazolones). J.Am.Chem.Soc,29 :517536.
12. Toman J.E.P,et al.,1946,J .Neuro Physo 9: 231-240.
13. SmithQ.E,1960, Phamacological screening tests progress in medicinal
chemistry, Butterworths London .,1:
Table-II Anticonvulsant activity of compounds (1-32 )
Com
p.
R
R'
P.G.a
Phenytoin
sodiumb
Dose
(mg/kg
i.p.)
2 ml
30
Anticonvulsant activity (SMES)
No. of animals
% seizure
exhibiting convulsions
protection
10
0
2
80***
ALD50
(Mg/kg
i.p.)
1.
2.
3.
4.
5
6
7
8
9
10.
11.
12.
13.
14.
-4-OH
-2-Cl
-4-OH
-2-Cl
- 4-OH
-2-Cl
- 4-OH
-2-Cl
-4-OH
-2-Cl
-4-OH
-4-OH
-H
-4-OH
30
30
30
30
30
30
30
30
30
30
30
30
9
8
8
8
8
7
7
6
6
5
5
4
10
20
20
20
20
30
30
40**
40**
50**
50**
60**
> 1000
>1000
>1000
>1000
>1000
>1000
>1000
> 1000
> 1000
> 1000
> 1000
> 1000
15.
16.
-4-OH
-4-OH
30
30
3
3
70**
70**
17.
18.
19
20
21
-4-OH
-2-Cl
-2-Cl
-2-Cl
-2-Cl
-4-OCH3
3-OCH3,
- 4-OH
-4N (CH3)2
-H
-4-OH
-4-OCH3
3-OCH3,
- 4-OH
22
23
24
25
26
2-Cl
-4-OH
-4-OH
-4-OH
-4-OH
30
30
30
30
7.5
15
30
30
30
30
30
30
4
4
3
3
9
6
2
3
4
2
3
2
60**
60**
70**
70**
10
40**
80***
70**
60**
80***
70**
80***
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
27
28
29
30
31
-4-OH
-2-Cl
-2-Cl
-2-Cl
-2-Cl
32
-2-Cl
30
30
30
30
7.5
15
30
30
3
3
2
3
8
5
1
2
70**
70**
80***
70**
20
50**
90***
80***
-4N (CH3)2
-H
- 4-OH
-4-OCH3
3-OCH3,
4-OH
-4N (CH3)2
-H
-4-OH
-4-OCH3
3-OCH3,
4-OH
-4N(CH3)2
* P < 0.05
** P< 0.01
*** P < 0.001
a. P.G.- Propylene glycol standard for control
b. Phenytoin sodium = reference standard for anticonvulsant activity.
c. Supramaximal electroshock seizure pattern test
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
> 1000
> 2000
> 1000
COVERING LATTER
From,
Dr. Ashok Kumar
Prof -cum-druggist of Pharmacology
L.L.R.M. Medical College, Meerut- (U.P.)250004
(India)
To,
The Executive Editor,
Pakistan Journal of Scientific and Industrial Research,
Scientific Information centre,
PCSIR Laboratories Campus,
Shahrah-e-Dr.Salimuzzaman Siddiqui,
Karachi-75280,Pakistan.
Dear Sir,
I am herewith sending online my research paper entitled, "Synthesis
of Some New Substituted quinizolin-4-3H-Ones as potent anticonvulsant
agents" for publication in your esteemed journal. I shall be kind enough if
you can acknowledge the receipt of the paper via E-mail.
Thanking you.
Yours Sincerely,
(Ashok Kumar)
Auther’s Names1. Neha Garg
Department of Pharmacology
L.L.R.M Medical College, Meerut-250004 (U.P.) India
e-mail- nehagarg198@gmail.com
2. Trilok Chandra
Department of Pharmacology
L.L.R.M Medical College, Meerut-250004 (U.P.) India
e-mail- trilokchandra08@yahoo.com
3. S.Lata
Professor and head
Department of Pharmacology
L.L.R.M Medical College, Meerut-250004 (U.P.) India
e-mail - dr.sumanlata@yahoo.com
4. K.K Saxena
Professor
Department of Pharmacology
L.L.R.M Medical College, Meerut-250004 (U.P.) India
e-mail - sexenadrkk@gmail.com
5. Ashok Kumar
Professor
Department of Pharmacology
L.L.R.M Medical College, Meerut-250004 (U.P.) India
e-mail - rajputak@gmail.com
Reviewers Names1. SM Sondhi [Ph.D]
Professor
Department of Chemistry
IIT Roorkee Uttranchal
2. SM Verma [Ph.D]
Professor
Department of Chemistry
IIT BHU
3. Anamik Shah [Ph.D]
Professor
Department of Chemistry
Saurastra University
4. Mala Nath [Ph.D]
Professor
Department of Chemistry
IIT Roorkee Uttranchal