Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
Research Article Medicinal Chemistry
ISSN
International Journal of Pharma and Bio Sciences 0975-6299
ONE POT SYNTHESIS OF 3-(SUBSTITUTED PHENOXYMETHYL)-6-
PHENYL/SUBSTITUTED PHENOXYMETHYL-1,2,4-TRIAZOLO[3,4-B][1,3,4]
THIADIAZOLE DERIVATIVES AS ANTIMICROBIAL AGENTS
RAJESH D. HUNASHAL1* AND D. SATYANARAYANA2
1
Department of Pharmacology, Karnataka Institute of Medical Sciences, Vidhyanagar, Hubli-580 021, Karnataka, India
2
Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences, Paneer, Deralakatte, Mangalore-574 160,
Karnataka. India
ABSTRACT
The reaction of thiocarbohydrazide with substituted phenoxy acetic acid to obtained 3-
substituted-4-amino-5-mercapto-1,2,4-triazoles (1) by condensing compound 1 with aromatic
carboxylic acid and substituted phenoxy acetic acids resulted the title compound
triazolothiadiazoles 2a-j. The purity of the newly synthesized compounds was confirmed by
TLC. Structures of all the newly synthesized compounds were confirmed by spectral data. All
the newly synthesized compounds were screened for their in-vitro antimicrobial activity.
Among the series the compounds 2e, 2f and 2b, 2c, 2f, 2d, 2i were exhibited equipotent
antibacterial and antifungal activity at MIC of 1 µg/mL when compared with standard drugs
respectively. From the results the compounds 2c, 2f, 2j were showed comparable
antitubercular activity against M. tuberculosis H37Rv at MIC of 0.50 µg/mL, when compared
with standard drug Rifampin and INH which showed MIC of 0.25 µg/mL.
KEYWORDS: 1,2,4-triazoles, triazolothiadiazoles, antimicrobial activity, antibacterial activity, antifungal
activity, antitubercular activity
RAJESH D. HUNASHAL
Department of Pharmacology, Karnataka Institute of Medical Sciences,
Vidhyanagar, Hubli-580 021, Karnataka, India
*Corresponding author
This article can be downloaded from www.ijpbs.net
P - 183
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
INTRODUCTION
Microbial infections are the major threat in the world; these infections are treated with different
antimicrobial agents. Resistance to antimicrobial agents by microorganism was recognized from
the beginning1. The spread of this phenomenon is abetted by short generation time and genetic
versatility of microorganisms, as well as by poor antibiotics prescribing and utilization practices.
The antibiotics prescribed have the different adverse effects, such as; sulphonamides,
fluroquinolones and β–lactam antibiotics are allergic to some individuals, cephalosporin and
polyene antibiotics share common nephrotoxicity2, aminoglycoside antibiotics exert ototoxic,
antitubercular drugs cause progressive liver damage and antiviral drugs causes hematologic
toxicity particularly in human immunodeficiency viruses (HIV) infection produced3. The azole
antifungal agents in clinical use contain either two or three nitrogens in the azole ring and are
thereby classified as imidazoles (e.g., ketoconazole, miconazole, clotrimazole) or triazoles (e.g.,
voriconazole, genaconazole, terconazole, itraconazole, fluconazole)respectively. With the
exception of ketoconazole, use of the imidazoles is limited to the treatment of superficial
mycoses, whereas the triazoles have a broad range of applications in the treatment of both
superficial and systemic fungal infections. Diseases which very recently seemed on their way of
extinction, such as fungal and tuberculosis are once again becoming serious public health
problems because of societal changes and resistance emergence by pathogens4. These
developments and the associated increase in microbial infections intensified the search for new,
safer and more efficacious agents to combat serious microbial infections. Therefore there is a
need to develop novel molecules as antimicrobial, antitubercular and antifungal agents.
The efficiency of triazole derivatives as chemotherapeutic agent is well established and
their chemistry has been comprehensively studied. Literature survey revealed that various
compounds of 1,2,4-triazoles bearing aryl groups or heterocyclic residues5 and condensed
heterocyclic derivatives of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole rings which possess excellent
biological activities, viz. Antibacterial6,7 antifungal8, antitubercular9,10, cytotoxic11, anticancer12,13,
anti-inflammatory14-16, analgesic17, anticonvulsant18 and anthelmintic19 activities. In view of
these facts and in continuation of our research program on synthesis and biological importance of
various heterocyclic compounds20-23, now we are reporting the synthesis and antimicrobial activity
of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives as shown in scheme 1.
Experimental section
All research chemicals were purchased from Acros organics, Sigma-Aldrich, Lancaster Co. and
used as such for the reactions. Reactions were monitored by thin layer chromatography (TLC) on
pre-coated silica gel plates from E. Merck and Co. Melting points of synthesized compounds
were determined in Thermonik melting point apparatus and uncorrected and IR spectra were
recorded on Thermo Nicolet IR200 FT-IR spectrometer. The 1H NMR and 13C NMR were
recorded on Bruker AVANCE II 400. Chemical shifts are reported in δ ppm units with respect to
TMS. The mass spectra were recorded using GCMS-QP 2010. A novel series of substituted
triazolothiadiazoles 2a-j were synthesized as shown in scheme 1 by the reaction between
thiocarbohydrazide and substituted phenoxy acetic acid, which on fusion to form 3-(substituted
phenoxymethyl)-4-amino-5-mercapto-1,2,4-triazole (1). General method for synthesis of 3-
(substituted phenoxymethyl)-6-phenyl/substituted phenoxy methyl-1,2,4-triazolo[3,4-b][1,3,4]
thiadiazole (2a-j) Equimolar proportions of N′-4-amino-5-(substituted phenoxymethyl)-2H-1,2,4-
triazole-3(4H)-thione (1) and aromatic carboxylic acid or substituted phenoxy acetic acid was
This article can be downloaded from www.ijpbs.net
P - 184
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
added to 10 ml of dry phosphorous oxy chloride and the solution was refluxed on water bath for 6
hr. Excess of phosphorous oxychloride was removed under vacuum. The thick mass obtained
was treated with water and left overnight. Solid thus obtained was filtered washed with 2%
sodium carbonate solution, then with cold water, dried and recrystallized from ethanol.
3-phenoxymethyl-6-phenyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (2a)
IR (KBr, cm-1): 3048.1 (Ar C-H), 2914.2 (OCH2), 2747.1 (CH2), 1587.8 (C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.4-6.7 (m, 10H, Ar-H), 5.1 (s, 2H, OCH2).
13
C-NMR (400 MHz, DMSO-d6, δ ppm): 175.0 (thiadiazole-C2), 162.8 (triazole-C3), 147.9
(triazolothiadiazole-C5), Ar C [160.2 (C1), 129.3 (C3 and C5), 115.1 (C2), 114.0 (C4 and C6)], Ar
C (thiadiazole) [134.6 (C1), 129.3 (C3 and C5), 128.2 (C4), 127.6 (C2 and C6)], 65.8 (OCH2).
MS (ESI) (M+1) : m/z 309.2; calcd.308.3.
3,6-bis(phenoxymethyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (2b)
IR (KBr, cm-1): 3050.1 (Ar C-H), 2910.3 (OCH2), 2745.5 (CH2), 1587.8 (C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.4-6.7 (m, 10H, Ar-H), 5.2 (s, 4H, (OCH2)2).
13
C-NMR (400 MHz, DMSO-d6, δ ppm): 172.4 (thiadiazole-C2), 161.9 (triazole-C3), 147.2
(triazolothiadiazole-C5), Ar C [153.2 (C1), 129.9 (C3 and C4), 125.2 (C5), 117.0 (C2 and C6)], Ar
C (thiadiazole) [158.6 (C1), 129.3 (C3 and C5), 122.1 (C4), 112.2 (C2 and C6)], 65.5 (OCH2)2.
MS (ESI) : m/z 338.2; calcd.338.2.
6-[(2,4-dichlorophenoxy)methyl]-3-phenoxymethyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (2c)
IR (KBr, cm-1): 3056.2 (Ar C-H), 2911.6 (OCH2), 2744.3 (CH2), 1617.5 (C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.1-6.6 (m, 8H, Ar-H), 5.1 (s, 4H, (OCH2)2).
13
C-NMR (400 MHz, DMSO-d6, δ ppm): 163.2 (thiadiazole-C2), 162.2 (triazole-C3), 147.3
(triazolothiadiazole-C5), Ar C [152.4 (C1), 130.7 (C3), 129.3 (C2 and C4), 128.3 (C5), 116.8 (C6)],
Ar C (thiadiazole) [156.5 (C1), 130.4 (C3 and C5), 122.6 (C4), 113.8 (C2 and C6)], 66.2 (OCH2)2.
MS (ESI) (M+1) : m/z 408.3; calcd.407.2.
3-[(4-chlorophenoxy)methyl]-6-phenyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (2d)
IR (KBr, cm-1): 3050.2 (Ar C-H), 2915.6 (OCH2), 2745.6 (CH2), 1650.2 (C=N), 765.2 (C-Cl).
1
H NMR (DMSO-d6, δppm): 7.4-6.7 (m, 9H, Ar-H), 5.2 (s, 2H, OCH2).
MS (ESI) (M+1): m/z 342.7; calcd: 343.8.
3-[(4-chlorophenoxy)methyl]-6-phenoxymethyl-1,2,4-triazolo [3,4-b][1,3,4]thiadiazole (2e)
IR (KBr, cm-1): 3045.1 (Ar C-H), 2912.6 (OCH2), 2747.5 (CH2), 1665.8 (C=N), 766.7 (C-Cl).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.4-6.7(m, 9H, Ar-H), 5.2 (s, 4H, (OCH2)2).
MS (ESI) (M+1) : m/z 373.2; calcd.372.2.
6-[(2,4-dichlorophenoxy)methyl]-3-[(4-chlorophenoxy)methyl]-1,2,4-triazolo[3,4-
b][1,3,4]thiadiazole (2f)
IR (KBr, cm-1): 3050.5 (Ar C-H), 2918.8 (OCH2), 2740.2 (CH2), 1660.7 (C=N), 775.2 (C-Cl).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.1-6.6 (m, 7H, Ar-H), 5.1 (s, 4H, (OCH2)2).
13
C-NMR (400 MHz, DMSO-d6, δ ppm): 163.2 (thiadiazole-C2), 162.7 (triazole-C3), 148.0
(triazolothiadiazole-C5), Ar C [152.7 (C1), 131.1 (C3), 130.3 (C2 and C4), 128.1 (C5), 116.4 (C6)],
Ar C (thiadiazole) [153.7 (C1), 130.4 (C3), 123.7 (C4), 127.9 (C2), 127.7 (C5), 116.8 (C6)], 66.7
(OCH2)2.
MS (ESI) (M+2) : m/z 443.7; calcd.441.7.
3-[(4-nitrophenoxy)methyl]-6-phenyl-1,2,4-triazolo[3,4-b] [1,3,4] thiadiazole (2g)
IR (KBr, cm-1): 3068.8 (Ar C-H), 2922.1 (OCH2), 2746.3 (CH2), 1617.5 (C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 8.1-7.1 (m, 9H, Ar-H), 5.2 (s, 2H, OCH2).
MS (ESI) : m/z 453.3; calcd.453.3.
This article can be downloaded from www.ijpbs.net
P - 185
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
3-[(4-nitrophenoxy)methyl]-6-phenoxymethyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (2h)
IR (KBr, cm-1): 3052.1 (Ar C-H), 2915.3 (OCH2), 1583.3 (C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.4-6.7 (m, 8H, Ar-H), 5.2 (s, 4H, (OCH2)2).
MS (ESI): m/z 482.9; calcd.483.2.
3-[(2,4-dichlorophenoxy)methyl]-6-phenyl-1,2,4-triazolo[3,4-b] [1,3,4]thiadiazole (2i)
IR (KBr, cm-1): 3070.2 (Ar C-H), 2917.3 (OCH2), 2747.1 (CH2), 1617.2(C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.4-6.6 (m, 10H, Ar-H), 5.2 (s, 2H, OCH2).
13
C-NMR (400 MHz, DMSO-d6, δ ppm): 173.5 (thiadiazole-C2), 161.2 (triazole-C3), 147.3
(triazolothiadiazole-C5), Ar C [153.6 (C1), 131.1 (C3), 129.3 (C2 and C4), 129.1 (C5), 116.7 (C2)],
Ar C (thiadiazole) [133.2 (C1), 130.1 (C3 and C5), 128.6 (C4), 127.2 (C2 and C6)], 66.2 (OCH2).
MS (ESI) (M+2) : m/z 379.2; calcd.377.2.
3-[(2,4-dichlorophenoxy)methyl]-6-phenoxymethyl-1,2,4-triazolo [3,4-b][1,3,4] thiadiazole (2j)
IR (KBr, cm-1): 3050.1 (Ar C-H), 2910.3 (OCH2), 1587.8 (C=N).
1
H NMR (400 MHz, DMSO-d6, δ ppm): 7.4-6.7 (m, 8H, Ar-H), 5.2 (s, 4H, (OCH2)2).
13
C-NMR (400 MHz, DMSO-d6, δ ppm): 163.2 (thiadiazole-C2), 162.2 (triazole-C3), 147.3
(triazolothiadiazole-C5), Ar C [152.4 (C1), 130.7 (C3), 129.3 (C2 and C4), 128.3 (C5), 116.8 (C6)],
Ar C (thiadiazole) [156.5 (C1), 130.4 (C3 and C5), 122.6 (C4), 113.8 (C2 and C6)], 66.2 (OCH2)2.
In-vitro antimicrobial activity
Antibacterial and antifungal activity of the synthesized compounds were performed by agar
dilution method24 using standard bacterial and fungal strains, such as; Streptococcus aureus
(ATCC 9144), Bacillus subtilis (ATCC 6633), Psedomonas aeruginosa (ATCC 25668),
Escherichia coli (ATCC 25922), Candida albicans (ATCC 2091), Aspergillus niger (ATCC
6275) and Aspergillus fumigatus (ATCC 13073) respectively. Antitubercular activities of the
synthesized compounds were performed by broth dilution assay25 by incubated the test
compounds at 37oC for 21 days using middle brook 7H9 broth media against M. tuberculosis
H37Rv strain.
RESULTS AND DISCUSSION
The IR spectrum of compound 1 showed characteristic absorption bands at 3457.4 cm-1 was
assigned to NH2 and the other at 1282.1/2580 cm-1 was attributed to C=S/SH. These were
disappeared by the formation of triazolothiadiazoles 2a-j. Similarly the 1H NMR characteristic
signal singlet showed at δ 13.2/7.8 due to SH/NH proton derived from tautomeric equilibrium of
compound 1 and δ 2.1 due to NH2 protons. Which were absent in the 1H NMR spectra of
triazolothiadiazoles. It suggest that Cyclocondensation of the SH and NH2 functions of 1 with
aromatic carboxylic acid and substituted phenoxy acetic acids resulted triazolothiadiazoles ring.
The structure of compounds was further conformed by evidence for the formation of
triazolothiadiazoles ring which was obtained by recording mass spectral data. The
characterization data of all compounds is tabulated in Table 1.
In-vitro antimicrobial activity
Antibacterial and antifungal screening data revealed that all the compounds showed moderate to
good antibacterial and antifungal activity respectively. Antibacterial and antifungal results are given
in Table 2. Compounds showed antibacterial and antifungal activity at MIC values of 1-64 µg/mL
respectively. Compounds 2e (R=4-Cl, R1=C6H5OCH2), 2f (R=4-Cl, R1=2,4-ClC6H3OCH2)
inductively electron withdrawing substituents on phenoxy methyl rings were exhibited equipotent
This article can be downloaded from www.ijpbs.net
P - 186
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
antibacterial activity against S. aureus, B. substilis at MIC of 1 µg/mL whereas these compounds
showed comparable activity against gram negative bacteria P. aeruginosa, E.coli at MIC of 2
µg/mL. Compounds 2c (R=H, R1=2,4-ClC6H3OCH2), 2d (R=4-Cl, R1=C6H5) showed comparable
antibacterial activity against gram positive bacteria S. aureus, B. substilis at MIC of 2 µg/mL.
Compounds 2j (R=4-Cl, R1= C6H5OCH2), 2d (R=4-Cl, R1=C6H5) showed comparable antibacterial
activity against E.coli at MIC of 2 µg/mL. Rest of the compounds showed weak activity against
both gram positive (S. aureus, B. substilis) and gram negative (P. aeruginosa, E. coli) bacteria,
when compared with standard drug Ceftriaxone which showed MIC of 1µg/mL. The compound 2f
(R=4-Cl, R1=2,4-ClC6H3OCH2) having electron withdrawing moiety on phenoxy methyl rings were
found to be equipotent antifungal activity against A. niger and A. fumigatus at MIC of 1 µg/mL.
Compounds 2d (R=4-Cl, R1=C6H5), 2i (R=2,4-Cl, R1=C6H5) showed equipotent antifungal activity
against A. niger at MIC of 1 µg/mL. Whereas compounds 2b (R=H, R1=C6H5OCH2), 2c (R=H,
R1=2,4-ClC6H3OCH2), 2f (R=4-Cl, R1=2,4-ClC6H3OCH2) were exhibited equipotent antifungal
activity against A. fumigatus and compounds 2b (R=H, R1=C6H5OCH2), 2c (R=H, R1=2,4-
ClC6H3OCH2), 2f (R=4-Cl, R1=2,4-ClC6H3OCH2) were showed equipotent antifungal activity
against A. fumigatus at MIC of 1 µg/mL respectively. The compounds 2e (R=4-Cl, R1=C6H5OCH2),
2j (R=4-Cl, R1= C6H5OCH2) showed equipotent antifungal activity against A. niger and A.
fumigatus at MIC of 2 µg/mL. Out of ten synthesized compounds, compound 2f (R=4-Cl, R1=2,4-
ClC6H3OCH2) showed comparable antifungal activity against C. albican. In contrary, all
compounds have shown less antifungal activity against C. Albicans when compared with standard
drug Fluconazole which showed at MIC of 1 µg/mL. In general these compounds are found to
possess more antifungal activity than antibacterial activity. Hence, it reveals that the compounds
having electron withdrawing substituents on phenoxy methyl rings were found to be more active.
The compounds showed antitubercular activity at MIC values of 0.25-2 µg/mL. From the results the
compounds 2c (R=H, R1=2,4-ClC6H3OCH2), 2f (R=4-Cl, R1=2,4-ClC6H3OCH2), 2j (R=4-Cl, R1=
C6H5OCH2) having chloro groups on phenoxymethyl rings were showed comparable antitubercular
activity against M. tuberculosis H37Rv at MIC of 0.50 µg/mL, when compared with standard drug
Rifampin and INH which showed MIC of 0.25 µg/mL. Rest of the compounds in the series showed
moderate antitubercular activity. The results are shown in Table 2.
This article can be downloaded from www.ijpbs.net
P - 187
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
S R O
H2N NH2 O
N N + OH
H H
R = H, 2,4- Cl
R N N R N NH
O O
N SH N S
NH2 NH2
1
R1-COOH
R N N
O
N S
N
2a-j R1
Scheme 1
This article can be downloaded from www.ijpbs.net
P - 188
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
Table 1
Characterization data of 2a-j
The C, H, N analysis was found to be ± 0.4 %.
* Recrystallization solvent ethanol.
#
Stationary Phase: Silica gel G, Mobile phase: Chloroform: Benzene (1:1), Iodine vapors as visualizing
agent.
This article can be downloaded from www.ijpbs.net
P - 189
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
Table 2
In-vitro antimicrobial activity of 2a-j
a
The screening organism. Gram-positive bacteria: Streptococcus aureus (ATCC 9144, Sa),
Bacillus subtilis (ATCC 6633, Bs).
b
The screening organisms. Gram-nagative bacteria: Psedomonas aeruginosa (ATCC
25668, Pa), Escherichia coli (ATCC 2091, Ec).
c
The screening fungal organisms: Candida albicans (ATCC 2091,Ca), Aspergillus niger
(ATCC 6275, An), Aspergillus fumigatus (ATCC 13073, Af).
d
The screening organisms: Mycobacterium tuberculosis H37Rv (Mt); ND: Not determined.
CONCLUSION
In conclusion the synthesized title compounds resulted in good yields. The SAR study of the title
compounds reveals better activity. Indicating the triazolothiadiazole ring scaffold influences the
pharmacological activity. From the activity data, the compounds having electron withdrawing group
such as halogens are found to be more activity as compared to others. It is observed that the
chloro at ortho and para position on phenoxymethyl rings increases the activity. However, the
difference in activity profile with structural modifications provides further scope to explore these
compounds for better bioactivity. Thus substituted triazolothiadiazole moieties appear to be
another interesting source of antifungal and anti-tubercular agents. Further studies are required to
This article can be downloaded from www.ijpbs.net
P - 190
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
know the mechanism of action of these compounds.The authors have declared no conflict of
interest.
ACKNOWLEDGEMENT
The authors are thankful to Dr. Vasantha Kamath, Director, and Dr. U. S. Hangaraga, Principal,
Karnataka Institute of Medical Sciences, Hubli, India for providing necessary facilities to carry out
this research work. We are grateful to director, SAIF, Punjab University, Chandigarh, India for
providing the spectral data.
REFERENCES
1. M. Rama Prabha1 and K. Vasantha. Phytochemical and antibacterial activity of alotropis
procera (ait.) R. Br. Flowers. Int J Pharma Bio Sci,1:P-1-6, (2012)
2. J. G. Hardman and L. E. Limbird. Goodman and Gilman’s The Pharmacological basis of
therapeutics, 10th Edn, McGraw-Hill publisher: 1143-1165, (2001)
3. K. D. Thripathi. Essesntials of Medical Pharmacology, 4th Edn, Japyee Brothers Medical
Publishers (P) Ltd.: 627-698, (2003)
4. L. A. Mitscher. Foye’s Principles of medicinal Chemistry, 5th eds, Lippincott Williams and
Wilkins, A Wolters Kluwer Company: 819-820, (2002)
5. Olcay B., Bahittin K., Murat K. Synthesis and anticancer evaluation of some new
unsymmetrical 3,5-diaryl-4H-1,2,4-triazole derivatives. Turk J Chem, 30: 29- 40, (2006)
6. Francis G., Cedric L., Fabrice P., Damien C., Patrice L., Marc Le, B. Design, synthesis, and
evaluation of 1-(N-benzylamino)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal
agents. Bioorg Med Chem Lett, 18:1820-1824, (2008)
7. Ilango K., Valentina P. Synthesis and biological activities of novel 1,2,4-triazolo-[3,4-b]-1,3,4-
thiadiazoles. Der Pharma Chemica, 2(2): 16-22, (2010)
8. Desai N. C., Shukla H. K., Thaker K. A. Synthesis of some new 5-[2-{(1,2,3-benzotriazol)-1-
yl-methyl}-1'-(4'-substituted aryl-3'-chloro-2'-oxoazetidine)]-amino-1,3,4-thiadiazoles:
Antifungal and antibacterial agents. J Indian Chem Soc, 61:239-241(1984).
9. Iraj C., Charalabou Z., Panagiotis G., Athina S., Jasmina G. Sulfonamide-1,2,4-triazole
derivatives as antifungal and antibacterial agents: Synthesis, biological evaluation,
lipophilicity and conformational studies. Bioorg Med Chem, 16:1150-1161, (2008)
10. Kucukguzel I., Esra T., Guniz Kucukguzel S., Rollas S., De Clercq E. Synthesis of some
novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-
dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and anti-tuberculosis
agents. Eur J Med Chem, 43:381-392, (2008).
11. Ilango K., Valentina P. Facile synthesis and cytotoxic activity of 3,6-disubstituted 1,2,4-
triazolo-[3,4-b]-1,3,4-thiadiazoles. Eur J Med Chem, 1 (1): 50-53, (2010)
12. Mahendra R. S., Kiran K. M., Hanimi R. G., Tatikonda S., Chakravarthy A. K., Dolly P.
Synthesis of new S-derivatives of clubbed triazolyl thiazole as anti-mycobacterium
tuberculosis agents. Bioorg Med Chem, 15: 3997- 4008, (2007)
13. Upadhayaya R. S., Sinha N., Jain S., Kishore N., Chandra R., Arora S. Optically active
antifungal azoles: synthesis and antifungal activity of (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-{2-
This article can be downloaded from www.ijpbs.net
P - 191
Int J Pharm Bio Sci 2012 Oct; 3(4): (P) 183 - 192
[4-aryl-piperazin-1-yl]-ethyl}-tetrazol-2-yl/1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol. Bioorg Med
Chem, 12: 2225-2228, (2004)
14. Navidpour L., Shafaroodi H., Abdi K., Amini M., Ghahremani M. H., A. Dehpour R., Shafiee
A. Design, synthesis, and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4H-1,2,4-
triazoles as selective COX-2 inhibitors. Bioorg Med Chem, 14:2507-2517, (2006)
15. El Shehry M.F., Abu-Hashem A.A., El-Telbani E.M. Synthesis of 3-[(2,4-
dichlorophenoxy)methyl]-1,2,4-triazolo(thiadiazoles and thiadiazines) as anti-inflammatory
and molluscicidal agents. Eur J Med Chem, 45:1906–1911, (2010)
16. Metwally K. A., Yaseen S. H., Lashine E. M., El-Fayomi H. M., El-sadek M. E. Non-
carboxylic analogues of arylpropionic acids: Synthesis, anti-inflammatory activity and
ulcerogenic potential. Eur J Med Chem, 42: 152-160, (2007)
17. Srivastava V., Sen S., Shekar R. New Bridgehead nitrogen heterocycles of furan as potent
antimicrobial agents. Indian J Chem, 33: 344, (1994)
18. Almarirad A., Mehrdad T., Kebriaeezadeh A., Mehrabi N., Dalvandia A., Shafieea, A.
Synthesis and anticonvulsant activity of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-
1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg Med Chem Lett, 14: 6057-6059, (2004)
19. Imitiaz Hussain M., Kumar V. Synthesis of 3- [2-benzotiazolyl methyl-1,2,4 triazolo [3,4b]
[1,3,4] thiadiazole-6-yl-subsituted as possible anthelmintics. Indian J Chem, 31B: 673-676,
(1992)
20. Ronad P. M., Satyanarayana D., Hunashal R. D., Maddi V. S. Synthesis of novel Substituted
7-(benzylidenamino)-4-methyl-2H-chromen-2-one derivatives as anti-inflammatory and
analgesic agents. Arch Pharm Chem Life Sci, 341: 696-700 (2008)
21. Hunashal R. D., Satyanarayana D., Maddi V. S. Synthesis and Antimicrobial activity of 2-[4-
(substituted benzylidenamino)-5-(substituted phenoxymethyl)-4H-1,2,4-triazol-3-yl thio]
acetic acid derivatives. E J Chem, 9: 1206-1212, (2012)
22. Ronad P. M., Hunashal R. D., Satyanarayana D., Maddi V. S. Synthesis and evaluation of
antiinflammatory and analgesic activities of a novel series of substituted N-(4-methyl-2oxo-
2H-chromen-7-yl) benzamides. Arzneim Forsch, 58: 641-646, (2008)
23. Hunashal R. D., Ronad P. M., Satyanarayana D., Maddi V. S., Kamadod M. A., Synthesis
and biological activities of N’-[4-(substituted benzylidenamino)-3-(2′,4′-
dichlorophenoxymethyl)-1,2,4-triazol-5yl)] isonicotinyl hydrazides. Int J Drug Design Drug
Disc, 1:107-114, (2010)
24. Murry P.R., Baron E.J., Pfaller M.A., Tenover F.C., Yolken R.H. Comparison of disc diffusion
and E test methods with agar dilution for antimicrobial susceptibility testing. Am Soc
Microbiol 20: 556-563, (1995)
25. Richard S., Lynn S. M., Avery C. G. Antimicrobial Susceptibility Testing Protocols, CRC
Press, Taylor and Francis Group publisher: 58-64, (2007)
This article can be downloaded from www.ijpbs.net
P - 192
