J Pharm Chem Biol Sci , September-November 2015; 3(3):329-345
Journal of Pharmaceutical, Chemical and Biological
Sciences ISSN: 2348-7658
Impact Factor (GIF): 0.615 Impact Factor (SJIF): 2.092
September-November 2015; 3(3): 329-345
A Review on Various Biological Activities of 1,3,4- Thiadiazole Derivatives
Lincy Joseph1, Mathew George1, Prabha Mathews1*
1Department of Pharmaceutical Chemistry, Pushpagiri College of Pharmacy, Thiruvalla- 689107, Kerala, India 2Department of Pharmacology, Pushpagiri College of Pharmacy, Thiruvalla- 689107, Kerala, India *Corresponding Author: Prabha Mathews, Department of Pharmaceutical Chemistry, Pushpagiri College of Pharmacy, Thiruvalla- 689107, Kerala, India Received:23 August 2015 Revised:01 September 2015 Accepted:06 September 2015
INTRODUCTION
The biological activity of compounds mainly
depends on their molecular structure.
Heterocyclic moieties can be found in a large
number of compounds which display large
number of biological activity. Thiadiazole is a
versatile moiety that exhibits a wide variety of
activity due to the presence of N=C-S moiety in
the ring. They have become an important class
of heterocycles of great interest of researches
because of their broad types of biological
activity. Many drugs containing 1,3,4-
thiadiazole nucleus like acetazolamide(1),
butazolamide(2),
Review Article
ABSTRACT
Large number of studies has been repoted on1,3,4- thiadiazole and their derivatives because of their
wide range of biological activities. They are found to have antibacterial, anti inflammatory, anticancer,
anti diabetic, anti convulsant, anti tubercular activities. Many drugs containing thiadiazole derivatives
are available in market such as acetazolamide, methazolamide, sulphamethazole, cefazoline. The
synthesis of novel thiadiazole derivatives and investigation of their chemical and biological activities
have gained more importance. Modification of the thiadiazole ring has proven highly effective with
improved potency and lesser toxicity. This review article highlights the recently synthesized
thiadiazole possessing important biological activities.
Keyword: 1,3,4- Thiadiazole; antimicrobial activity; anti inflammatory activity; anti diabetic activity; anti
cancer activity; anti- tubercular activity; anti convulsant activity; antioxidant activity
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sulfamethazole(3) are available in market. In
addition other analogues have found to be used
as dye, pesticides, lubricants and conducting
polymers [1]. N N
SAcHNSO2NH2
(1)
N N
S SO2NH2
NH
OCH3
(2)
N
S
N
CH3
NHS
OO
NH2 (3)
In the present review, emphasis on the
biological activities of substituted 1,3,4-
thiadiazole and structurally related thiadiazoles.
CHEMISTRY
Thiadiazole is an important five membered
heterocyclic ring containing two nitrogen atoms
and a sulphur atom as hetero atoms with the
general formula of C2H2N2S. They occur in four
isomeric forms namely 1, 2, 3-thiadiazole,
1,2,4 thiadiazole, 1,2,5- thiadiazole, 1,3,4-
thiadiazole. Among them 1, 3, 4 thiadiazole ring
exhibits more versatile activities.
NS
N
1,2,3-thiadiazole
NS
N
1,2,4-thiadiazole
NS
N
1,2,5- thiadiazole
S
N N
1,3,4-thiadiazole
The ring system is less aromatic than benzene,
thiophene, and pyridine. The aromatic
character is measured by π electron
delocalization which decreases in the order 1, 2,
5 thiadiazole>thiophene>thiazole>1, 3, 4-
thiadiazole2. The electron withdrawing nature
of the nitrogen atoms ensures that electrophilic
attack at carbon is very rare and nucleophilic
substitution reactions are common.
Electrophilic attack at the sulphur atom has
been observed. 1, 3, 4 – thiadiazoles are weak
base due to the inductive effects of extra
hetero atoms and are readily alkylated and
acylated at N3 [1]. The ring is relatively stable in
aqueous acid solutions but the ring gets cleaved
in aqueous basic solutions. 1, 3, 4-thiadiazole
core skeletons are subjected to various
substitution reactions with alkyl halides, acid
chlorides, and sulfonyl chlorides to afford
various drug like 2-amino-substituted 1, 3, 4-
thiadiazole derivatives [3]. When substituents
are introduced into 2’ or 5’ position of this ring,
the ring is highly reactive and forms different
derivatives of thiadiazole easily.
The reactivity of ring nitrogen atom arises from
electrophilic reactions depending on tautomeric
equilibrium of thione-thiol or amine-imine. In
thione or imine form deprotonation of ring N-H
can take place and ring nitrogen atom becomes
vulnerable to alkylation or acylation or
transformation to 1,3,4 –thiadiazolium salt. The
reactions are conducted with electrophiles such
as alkyl halides, trimethylsilylmethyl trifluoro
methanesulfonate, formaldehyde [4] etc.
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Tautomerism exhibited by thiadiazole is as follows:
X = -SH, -NH2
X' = -S, -NH
Few examples for electrophilic substitution on
ring nitrogen is as follows [4]:
1. Alkylation by methyl halides (always iodides
and bromides) were frequently reported to
produce 3-methyl- 1, 3, 4- thiadiazoles in
aprotic solvents such as DMF in the presence of
K2CO3
2. When amino thiadiazole is treated with
bromo ethanol solution hydroxyl alkyl
thiadiazoles are formed.
S
N N
R NH2 BrCH2CH2OH
Reflux, 3h
S
N N
R1 NH HBr
CH2CH2OH
3. When treated with formaldehyde in the
presence of ethanol and acetic acid forms
hydroxyl methyl derivatives.
S
N NH
RS SCH2O, EtOH
Acetic acid
S
N N
RS S
CH2OH
BIOLOGICAL ACTIVITIES OF 1, 3, 4-
THIADIAZOLE DERIVATIVES
Remarkable progress has been made in the
development of thiadiazole derivatives in the
recent years and the most recent studies have
revealed that of thiadiazole derivatives has a
wide spectrum of pharmacological properties
like anticancer, antitubercular, antimicrobial,
antidiabetic, antioxidant, anti-inflammatory,
anticonvulsant, diuretic activities. Following are
some of the examples of biological activities of
thiadiazole derivatives.
S
N N
R1 R
2
+ CH3I
S
N N+
R1 R
2
CH3
+
S
N+
N
R1 R
2
CH3
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Antimicrobial activity
Mahendrasinh M Raj [5] et al synthesized
thiadiazole derivatives by the reaction
between benzoic acid 2-hydroxy benzoic acid
with thiosemicarbazide using conc. H2SO4 as
oxidising agent. The synthesized compounds
were characterized by IR. H1NMR and
nitrogen estimation and screened for their
antibacterial and antifungal activities by
paper disc diffusion technique. All the
synthesized compounds showed moderate
activity against bacteria and fungi.
O OH
R
+S
NHNH2
NH2
conc. H2SO4
Ethanol
N
S
N
NH2
R
Carboxylic acid R= H, OH
THiosemicarbazide5
- phenyl
-1, 3, 4
- thiadiazole
Arun Kumar [6] et al synthesized thiadiazole
from thiosemicarbazide. Thiosemicarbazide
derivative on cyclisation with different
aromatic carboxylic acids in the presence of
POCl3 formed 1, 3, 4 thiadiazole derivatives
which were characterized by elemental
analysis, IR, H1NMR and Mass spectral data’s
and screened for their antimicrobial activities
and showed significant antimicrobial
activities.
N
SCl
NH2
CS2, C2H5OH
NH2NH2, H2O
N
SCl
NH
S
NH
NH2
RCOOH
POCl3
N
SCl
NH
S
N
N R
Guanghui Zong [7] et al synthesized a series
of novel glycosyl thiadiazole derivatives were
designed and synthesized by condensation of
sugar aldehydes and substituted
thiosemicarbazide followed by oxidative
cyclization by treating with manganese
dioxide. Compounds exhibited excellent
fungicidal activities.
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O
OH
OHOH
OH
OH
O
OR
OHC
O
O
CH3
CH3
O
OR1
CH
O
O
CH3
CH3
NNHNH
NH
S
R2 CHCl3
MnO2O
OR1
O
O
CH3
CH3
S
NN
NH
R2
S
NHR
2
NHNH2
CH2Cl2
Sobhi M Gomha [8] et al synthesized some
novel compounds, namely, 3-(2-methyl-1H-
indol-3-yl)-6-aryl-[1, 2, 4] triazolo [3,4-b][1,
3,4] thiadiazoles via bromination of 2-
methyl-3-[4-(arylideamino)-5-mercapto-4H-
[1,2,4triazol-3-yl]-1H indoles. New
thiadiazoles, triazoles and oxadiazoles with
indole moieties were prepared by the
cyclization of corresponding
thiosemicarbazides with microwave
irradiation using different reaction conditions.
The structure of the synthesized compounds
was confirmed by elemental analysis and
spectral analysis. The antibacterial activity of
the newly synthesized compounds against
Staphylococcus aureus, Bacillus subtilis,
(gram-positive) E.coli(gram-negative) and
antifungal activity against Candida albicans
were studied under the same condition using
trimethoprim as reference in Muller-Hinton
agar medium by disc agar diffusion method.
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NH
CH3
NN
NSH
N RBr2/ AcOH
NH
CH3
NN
NSH
N R
Br
NH
CH3
NN
N
N
S R
Anti inflammatory activities
Mohammad Asif [9] et al syntheszed 2,4-
diphenyl-5-imino-1,3,4-thiadiazole derivatives
by cyclization of α-chlorobenzal
phenylhydrazone derivatives using potassium
thiocyanate. Α-chlorobenzal phenylhydrazone
derivatives were synthesized by chlorination
of hydrazonyl derivatives using PCl5 which in
turn was synthesized from benzoyl chloride
and phenyl hydrazine in pyridine. The
thiadiazole derivatives synthesized were
characterized by IR, H1NMR and elemental
analysis and screened for in vivo anti-
inflammatory activity by carageenan induced
paw oedema and a few of them showed
promising activity when compared to
standard drug diclofenac sodium.
R1
R2
O
Cl
+
NHNH2
R3
R4
CH3OH
Pyridine
R1
R2
O
NH NH
R4
R3
Benzoyl chloride derivative
Phenyl hydrazine derivative
Hydrazonoyl derivatives
R1
R2
Cl
N NH
R4
R3
Chlorobenzal phenyl hydrazone derivatives
CH3OH
PCl5
R1
R2
S
N
N
NH
R3
R4
2,4- diphenyl 5
-imino
-
2- 1,3,4
-thiadiazoline dreivatives
Shiv K Gupta [10] et al synthesized
disubstituted thiadiazole derivatives by
reaction between salicylic acid and
thiosemicarbazide in presence of conc. H2SO4.
In vivo anti-inflammatory activity was
evaluated and compared with standard drug
ibuprofen and all compounds showed
moderate anti inflammatory activity.
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O
OH
OH
+ NH2
NH NH2
S OH
NH NH
S
NH2
H2SO4
N
S
N
NH2
OH
carboxylic acid derivativethiosemicarbazide
thiadiazole derivative
Alok pandey [11] et al synthesized Schiff
bases of 2-amino-5-aryl-1,3,4-thiadiazole
derivatives with different aromatic aldehyde.
1, 3, 4 – thiadiazole derivatives were
prepared by the reaction of
thiosemicarbazide, sodium acetate and
aromatic aldehyde. All the compounds were
evaluated for their analgesic activity against
swiss albino mice, anti inflammatory activity
against wister albino rats, and antibacterial
activity against Staphylococcus and E. coli
bacteria and tubercular activity against
Mycobacterium tuberculosis. All the
synthesized compounds exhibited analgesic,
anti-inflammatory, antibacterial and anti-
tubercular activities act various minimum
inhibitory concentration levels.
CHO
R CH3COONa
R
NNH
S
NH2
CH3COONaBr2/CH3COOH
R
N
S
N
NH2
R
N
S
N
N
CH3
ArCHO
C2H5OH
NH2NHCSNH2
Abhay Kumar Verma [12] et al synthesized N-
phenyl thiosemicarbazide from aromatic
amine by refluxing with CS2 and hydrazine
hydrate in ethanol and from phenyl
isothiocyanate by reacting with hydrazine
hydrate in ethanol. The synthesized
thiosemicarbazides where condensed with
aromatic carboxylic acid in presence of conc.
H2SO4 to form thiadiazole analogues. The
compounds were screened for anti
inflammatory activity by carageenan induced
rat paw edema method and the compounds
exhibited significant to moderate anti
inflammatory activity.
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NH2 NSC
anilinephenyl isothiocyanate
NH2
-NH2
C2H5OH
CS2, C2H5OH
NH3, NH2
-NH2
NH NH
NH2
S
DMF
ConcH2SO4
8-12 minutes
O
OH
R
NH S
NN
R
phenyl thiosemicarbazide
Microwave
Anti cancer activity
Arun Naskar [13] et al synthesized 2-amino-5-
aryl -1,3,4- thiadiazoles by oxidative
cyclization of thiosemicarbazones using FeCl3
catalyst and from this Schiff bases were
prepared by condensation with aldehyde and
synthesized compounds were characterized
by IR, NMR, and CHN analysis. Anticancer
activity was evaluated using Ehrlich’s Ascites
carcinoma cells and all the compounds
exhibited significant anticancer activity
compared to control.
CHO
R1
+ NH2
NH NH2
S
-H2O
R1
NNH
S
NH2
Fe3+
Cyclization
N N
SNH2
R1
Ethanol, 6h reflux
CHO
R2
N N
S
N
R1
R2
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Suddasatwa Banerjee [14] et al synthesized
thiadiazole derivatives with new amino group
by refluxing furan-2-carboxylic acid with
thiosemicarbazide in presence of conc.H2SO4
and then different Schiff bases were prepared
by reacting with various substituted
aldehydes in presence of few drops of glacial
acetic acid. The structures of the synthesized
compounds were confirmed by spectral
data’s. Screening for in vitro anticancer
activity was carried out using MTT (3-[4,5-
dimethylthiazol-2-yl]-2,5-diphenyl terazolium
bromide) assay on HT-29 colorectal cancer
cell line. The compounds had shown
significant activity at very less concentration.
O
O
OH+ NH2NHCSNH2
Conc. H2SO4, Reflux
C2H5OH
O
N
S
N
NH2
O
R
Ethanol, G.A.A
O
N
S
N
NR
Doaa E. Abdel Rahman [15] et al synthesized
substituted imidazo [2,1-b]-1, 3, 4 –
thiadiazoles , substituted 1, 3, 4-
thiadiazolo[3,2-a] pyrimidines and substituted
thioureas. Structures elucidated by IR, NMR
and Mass spectroscopy. All the compounds
were evaluated for their cytotoxic activity
against tumor cell line A549(non-small cell
lung cancer cell line) using Sulfo-Rodamine B
(SRB) standard method. Most of the tested
compounds exhibited potent cytotoxicity.
Docking studies were performed to explore
the possible binding modes of these
compounds with the binding site of fibroblast
stromelysin-1 enzyme, which is involved in
several pathological conditions including
cancer.
Synthesis of substituted imidazo [2,1-b]-1, 3, 4 – thiadiazoles
Br
N
S
N
NH2
i) phenacyl bromide,dioxane, reflux 5h
saturated sodium acetatesolution
Br
N
S
N
N
R
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Synthesis of substituted 1, 3, 4-thiadiazolo[3,2-a] pyrimidines
Br
N
S
N
NH2
malononitrile, triethyl amine
ethanol, refluxBr
N
S
N
N
NH2
NH
Synthesis of thiourea substituted thiadiazole derivative
Br
N
S
N
NH2
RNCS
Ethanol, reflux
Br
N
S
N
NH
NH
RS
Antidiabetic activity
Prasanna A Datar [16] et al designed
thiadiazole compounds as antidiabetic agent
using docking studies. The designed
thiadiazole derivatives are synthesized by
cyclization between aromatic acid and
thiosemicarbazide using conc. H2SO4 and
condensing the product with aldehyde in
presence by microwave irradiation. The
compounds were subjected to antidiabetic
activity by in vitro α amylase inhibitory
method and in vivo method in alloxan
induced diabetes rat model. Molecular
docking revealed that synthesized derivatives
and target proteins were actively involved in
binding and had significant correlation with
biological activity.
ArCOOH + NH2NHCSNH2
H2SO4
-CO2
S
N N
NH2
Ar-
RCHO
Microwave
S
N N
NAr-
R
S. R Pattan [17] et al synthesized thiadiazole
derivatives by cyclization between aromatic
acid and thiosemicarbazide using conc. H2SO4
and Schiff bases of thiadiazole were
synthesized by reacting with various aromatic
substituted adehydes. Structures of the
compounds were established based on
spectral data. All the compounds were
evaluated for antidiabetic activity by alloxan
induced tail tipping method and most of the
compounds showed promising activities.
ArCOOH + NH2NHCSNH2
H2SO4
-CO2
S
N N
NH2
Ar-
RCHO
Microwave
S
N N
NAr-
R
M Sai Harika [18] et al synthesized 5-phenyl-
1,3,4- thiadiazol 2 amine by reacting benzoic
acid with thiosemicarbazide, which on
reaction with different aromatic aldehydes
afforded 5-phenyl-N-[(E)-
phenylmethylidene]-1,3,4-thiadiazol-2-amine
derivatives. The compounds on treatment
with thioglycolic acid in presence of ZnCl2
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gave 2-phenyl-3-(5-phenyl-1,3,4-thiadiazol-2-
yl)-1,3- thiazolidin-4-one. The structures of
the compounds were confirmed by spectral
datas. The synthesized compounds were
evaluated for their antidiabetic activity by
alloxan induced rat model using the
parameters like serum glucose, serum
triglycerides, SGOT, SGPT, and body weight
ArCOOH + NH2NHCSNH2
H2SO4
-CO2
S
N N
NH2
Ar-
RCHO
Microwave
S
N N
NAr-
R
SHCH2COOHZnCl2
S
N N
N
S
O
Ar-
Ar-
Anti oxidant activity
Sandeep K Chitale [19] et al synthesized
thiadiazole from aromatic acid and
thiosemicarbazide, and Schiff bases were
prepared by reacting with different aldehydes
and isatin using glacial acetic acid as catalyst.
Elemental analysis, IR, H1 NMR and mass
spectral data elucidated structure of newly
synthesized compounds and tested for in
vitro antioxidant activity by testing nitric
oxide and hydrogen peroxide scavenging
activity. Some of these novel derivatives
showed moderate to potent antioxidant
activity.
ArCOOH + NH2NHCSNH2
Conc. H2SO4
Ethanol
S
N N
NH2
Ar-
RCHO, G.A.A
MicrowaveSN
N
Ar-
N
R
Brijendra Kumar Soni [20] et al synthesized
thiadiazole derivative and evaluated for in
vitro antioxidant activity by hydrogen
peroxide and nitric oxide scavenging activity
and lipid peroxidation inhibitory activity.
Some of the compounds showed potent
antioxidant activity.
ArCOOH + NH2NHCSNH2
Conc. H2SO4
Ethanol
S
N N
NH2
Ar-
RCHO, G.A.A
MicrowaveSN
N
Ar-
N
R
Anticonvulsant activity
Masi Hasmin. H [21] et al designed and
synthesized a series of Carboxamide moiety
with substituted 1,3,4-thiadiazoles. These
title compounds were prepared by
condensation of benzoxazine with 2,5-
disubstituted-1,3,4- thiadiazole . Structure
elucidations of the synthesized compounds
were done by spectral analysis. The
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anticonvulsant activity of the title compounds
were evaluated by using PTZ model
(60mg/kg) and carbamazepine taking as a
reference standard (100 mg/kg). All
synthesized compounds showed no sedation
side effect as compared to reference
standard (carbamazepine). Their study
indicated that bromo substituted compounds
have significant protection against
pentylenetetrazole induced convulsions
which can be regarded as strong candidates
for future anti- convulsant research.
O OH
R1
+NH2
NH NH2
S
POCl3
30min,Reflux
S
N N
NH2R
1
Mohammad Shahar Yar [21] et al synthesized
a series of five membered heterocyclic
compounds by the reaction between isoniazid
and various substituted isothiocyanates and
was tested for their anticonvulsant activity by
determining their ability to provide
protection against convulsions induced by
electro convulsometer comparing with
standard drug phenytoin sodium. Among the
synthesized compounds, 2-(4-chlorophenyl)
amino-5-(4-pyridyl)-1,3,4-thiadiazole and 2-
(4-chlorophenyl)amino-5-(4-pyridyl)-1, 3, 4-
oxadiazole were found promising compounds
of the series.
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N
NH
NH2
O
NCS
R
N
NH
NH
O
S
NH
R
Conc, H2SO4
S
N N
NH
RN
A Rahman [22] et al synthesized various
substituted amine derivatives, piperidine,
aniline, and 2-amino-oxazole derivatives of
thiadiazole and characterized by spectral
data. The anticonvulsant activity of the drug
was screened using MES (Maximium
Electrshock Seizure) model using standard
drugs phenytoin and carbamazepine. Most of
these compounds showed promising
anticonvulsant activity.
Synthesis of intermediate:
N N
S SHNH2
NH2NH2 N N
S NHNH2
NH2
CH3 CH3
O O
N N
SNH2 N
N
CH3
CH3
O
Cl
Cl
N N
SNH
NN
CH3
CH3
O
Cl
From this intermediate various amine
substituted derivatives like piperidine, aniline,
2-amino –oxazole derivatives are synthesized
by reacting with corresponding amine.
Structures of thus synthesized compounds are
as follows:
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N N
SNH
NN
CH3
ON
CH3
CH3
30 amine substituted thiadiazole derivative
NN
S
NH
NN
CH3
CH3
O
NH
aniline substituted thiadiazole derivative
NN
S
NH
NN
CH3
CH3
ONH
O
N
benzoxazole substituted thiadiazole derivative
N N
SNH
NN
CH3
CH3
ON
piperidine substituted thiadiazole derivative
Anti tubercular activity
Karigar Asif A [23] et al synthesized a series of
thiadiazole derivatives using equimolar
mixture of aromatic aldehydes thioglycolic
acid and thiosemicarbazide in H2SO4. The
structures of all the synthesized compounds
were confirmed by FTIR.
NMR and Mass spectral data and their
antitubercular activity studied against
Mycobacterium tuberculosis using microplate
alamar blue assay (MABA). All the synthesized
compounds showed good anti tubercular
activity.
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CONCLUSION
Thiadiazole are important class f heterocyclic
compounds. Among the different isomers of
thiadiazole 1,3,4- thiadiazole is most studied
compound because of its various
pharmacological activities such as anticancer,
antitubercular, antimicrobial, antidiabetic,
antiinflammatory, anticonvulsant, antioxidant
activities. This review gives an overview of the
wide spectrum of pharmacological activities
exhibited by thiadiazole derivatives. The
importance of thiadiazole moiety can be
magnified by carrying out further studies on its
possible substitution and thus to synthesize
better agents that can have strong future
commitments.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no
competing interests.
REFERENCES
1. Storr RC, Gilchrist TL. Science of synthesis
Houben-Weyl Methods of molecular
transformations: Hetarenes and Related
Ring systems, five membered Herarenes
with three or more heteroatoms. Germany:
Thieme; 2003.
2. Mehta D, Taya P, Neethu. A review on
various biological activities of thiadiazole.
Int J Pharmacy Pharm Sci 2015; 7(4): 39-47.
3. Yang SJ, Lee SH, Kwak HJ, Gong YD.
Regioselective synthesis of 20 amino
substituted 1, 3, 4-oxadiazole and 1, 3, 4 –
thiadiazole derivatives via Reagent-based
cyclization of thiosemicarbazide
intermediate. J Organic Chem 2013; 78:
438-444.
4. Hu Y, Li YC, Wang XM, Yang YH, Zhu HL. 1, 3,
4- Thiadiazoles, Synthesis Reactions and
Applications in Medical, Agricultural and
Material Chemistry. Chem Rev 2014; 1-40.
RCHO + HSCH2COOH
H2SO4
OH
R S
OH
O
-H2O
NH2NHCSNH2
NH
R S
OH
O
NH
SH NH2
-H2OS
N
R
NH NH2
S
O
SN
R
N NH2
SH
OH
-H2O
S N N
SNH2
R
Joseph et al 344
J Pharm Chem Biol Sci , September-November 2015; 3(3):329-345
5. Raj MM, Patel HV, Raj LM, Patel NK.
Synthesis and biological evaluation of some
new 1, 3, 4- thiadiazole derivatives for their
antimicrobial activities. Int J Pharm Chem
Biol Sci 2013; 3(3):814-820.
6. Kumar A, Amir M, Ali I, Khan SA. Synthesis
of Pharmaceutically important 1, 3, 4-
thiadiazole and imidazolinone derivatives as
antimicrobials. Indian J Chem 2009; 4813:
1288-1293.
7. Zong G, Zhao H, Jiang R, Zhang J, Liang X,
Baoju Li, Shi Y, Wang D. Design synthesis
and bioactivity of novel glycosyl thiadiazole
derivatives. Molecules 2014; 19: 7832-7849.
8. Gomha SM. Synthesis under microwave
irradiation of [1,2,4] triazolo [3,4-b][1,3,4]
thiadiazoles and other diazoles bearing
indole moieties and their antimicrobial
evaluation. Molecules 2011; 16: 8244-8256.
9. Asif M, Asthana C. 2,4Disubstituted -5-
imino-1,3,4-thiadiazole derivatives:
synthesis and characterization and
evaluation of anti-inflammatory activities.
Int J Chem Tech Res 2009; 1(4): 1200-1205.
10. Guptha SK, Sharma PK. Synthesis and anti-
inflammatory activity of disubstituted 1,3,4-
thiadiazole. Int J Drug Formulation Res
2011; 2(2): 344-350.
11. Panday A, Dewangan D, Verma S, Mishra A,
Dubey RD. Synthesis of Schiff base of
2.amino-5-aryl-1,3,4-thiadiazole and its
analgesic, antiinflammatory, antibacterial
and antitubercular activity. Int J Chem Tech
Res 2011; 3(1): 178-184.
12. Verma AK, Martin A. Synthesis charact-
erization and antiinflammatory activity of
analogues of 1, 3, 4 – thiadiazole. Int J of
Pharm Arch 2014; 3(9): 1-5.
13. Naskar A, Singha T, Guria T, Singh J, Kumar
AB, Maity TK. Synthesis, characterization
and evaluation of anticancer activity of
some new schiff bases of 1, 3, 4-thiadiazole
derivatives. Int J Pharmacy Pharm Sci 2015;
7(3): 397-402.
14. Banerjee S, Swaroop TVSS, Ferdy IC, Singh
A, lakshmi SM, Dr. Mohan, Dr. Saravunan J.
Indo Am J Pharm Res 2014; 2(2): 1074-
1082.
15. Rahman DEA, Moham KO. Synthesis of
novel 1,3,4- thiadiazole analogues with
expected anticancer activity. Der Pharma
Chemica 2014; 6(1): 323-335.
16. Datar PA, Deokule TA. Design and synthesis
of thiadiazole derivatives as antidiabetic
agents. Med Chem 2014; 4(4): 390-399.
17. Pattan SR, Kittur BS, Sastry BS, Jadav SG,
Thakum DK, Madamwar SA, Shinde HV.
Synthesis and evaluation of some novel 1,
3, 4 – thiadiazole for anti diabetic activity.
Indian J Chem 2011; 50(B): 615-618.
18. Harika MS, Nagasudha B, Raghavendra HG.
Synergistic activity of thiadiazole and
thiadiazolidinone derivatives against alloxan
induced diabetes in rats. Scholars Academ J
Pharm 2014; 3(3): 301-305.
19. Chitale SK, Ramesh B, Bhalgat CM, Jaishree
V, Puttaraj C, Bharathi DR. Synthesis and
antioxidant screening of some novel 1, 3, 4-
thiadiazole derivatives. Research J Pharm
Technol 2011; 4(10): 1540-1544.
20. Soni BK, Singh T, Bhalgat CM, Kamlesh B,
Kumar SM, Pavani M. In vitro antioxidant
studies of some 1, 3, 4 – thiadiazole
derivatives. Int J Res Pharm Biomed Sci
2011; 2: 1590-1592.
21. Masi HH, Gajjor AK, Savjani JK, Masi Inayal.
Synthesis and anticonvulsant activity of
novel 2,5-disubstituted 1, 3, 4- thiadiazole
derivatives. Int J Pharmtech Res 2011; 3(4):
2017-2024.
22. Shahar Yar M, Akhter MW. Synthesis and
anticonvulsant activity of substituted
oxadiazole and thiadiazole derivatives. Acta
Poloniae Pharmaceutica Drug Res 2009;
66(4): 393-397.
23. Rahman A, Shakya AK, Wahab S, Ansari NH.
Synthesis of some new thiadiazole
derivatives and their anticonvulsant
Joseph et al 345
J Pharm Chem Biol Sci , September-November 2015; 3(3):329-345
activity. Bulgarian Chem Commun 2014;
46(4): 750-756.
24. Karigar AA, Himaja M, Male SV, Prathap KJ,
Sikarwar MS. One pot synthesis and
antitubercular activity of 2-amino -5-aryl -
5H thiazolo [4,3-b]-1, 3, 4- thiadiazoles. Int
Res J Pharm 2011; 2(1): 153-158.
Cite this article as: Lincy Joseph, Mathew George, Prabha Mathews. A Review on Various Biological Activities
of 1,3,4- Thiadiazole Derivatives . J Pharm Chem Biol Sci 2015; 3(3):329-345