Indian Journal of Chemistry

Vol. 54B, April 2015, pp 556-564

Synthesis and biological screening of 1,2,4-triazole derivatives

Dinesh R Godhania*, Anand A Jogela, Anil M Sanghanib & Jignasu P Mehtaa
a
Department of Chemistry (DST-FIST & UGC NON-SAP Department) Mahatma Gandhi Campus,
Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar 364 002, India
b
Chemistry Department, Sir P. P. Institute of Science, Bhavnagar 364 002, India
E-mail: drgodhani@yahoo.com
Received 25 February 2014; accepted (revised) 26 December 2014

A series of 2-((arylamino)methyl)-5-(3-methoxyphenyl)-1-phenyl-1H-1,2,4-triazole-3-thione derivatives have been

synthesized and characterized by FT-IR, NMR, mass spectral and elemental analysis. Compounds (MM4a-m) have been
evaluated for their in vitro antibacterial activity against selected gram-positive and gram-negative bacteria and in vitro
antifungal activity against fungal pathogens by using broth dilution method. The compounds have been screened for
antitubercular activity against Mycobacterium tuberculosis H37Rv strain by using L J Slope method. Of all the compounds,
MM4d, MM4e, MM4j and MM4k show good antibacterial activity and MM4a, MM4d, MM4e and MM4j compounds have
been found to possess good antitubercular activity.
Keywords: Scaffold of 1,2,4-triazole, antibacterial activity, antifungal activity, antitubercular activity

1,2,4-Triazole and its derivatives represent one of the synthesized 5-mercapto-3-(3’-pyridyl)-4H-1,2,4-triazole

most biologically active class of heterocyclic com-
pounds. 1,2,4-Triazole derivatives are known to exhibit
antimicrobial1-4, antitubercular5-9 and anticancer
properties10-12. It also possesses various biological
activities such as, anti-inflammatory13, anticonvulsant14,
analgesic15, antiviral16, etc.
The 1,2,4-triazole focus has been included into a
wide range of therapeutically significant agents. Some
other drugs including this heterocycle are Ribavirin
(antiviral)17, Rizatriptan (antimigraine)18, Estazolam and
Alprazolam (anxiolytic)19-21, Letrozole and Anastrozole
(breast cancer)22,23. There are number of drugs, which are
containing 1,2,4-triazole nucleus, such as Itraconazole,
Fluconazole and Posaconazole, that have been used
for the treatment of fungal infection disease24-27.
Rufinamide (anticonvulsant)28, the analogous structure of
triazole containing drugs.
It has been noticed continuously over the years that
interesting biological activities were associated with
1,2,4-triazole derivatives.
Several methods for synthesis of 1,2,4-triazole are
available in literature, which involve conventional one
pot, multicomponents, microwave assisted, under
solvent free condition, regioselective and signification
method. Joshi et al. have synthesized 1,2,4 triazoles
by rapid and efficient microwave-assisted method29.
Synthesis of 4-amino-3-mercapto-5-substituted-1,2,4-
triazoles has been carried out by many workers and
few are summarized here. Kshirsagar et al. have
and have evaluated their anticonvulsant and anti-
infective activity30. The moiety of 1,2,4-triazole has
been found to possess antifungal and anti-HIV
activities31. This group of researchers have mentioned
that new thione substituted 1,2,4_triazole ring systems
possess good biological activities such as antiproli-
ferative, antimicrobial, antifungal and anticancer
properties. In addition, mercapto-1,2,4-triazoles have
been found to be of great utility to prepare other
heterocyclic compounds32. Mir et al. have synthesized
a new series of α-[5-(2-furyl)-1,2,4-triazol-3-ylthio]
acetohydrazide and related compounds and evaluated
their antitubercular activity33. The aim of present
study is to synthesize new bioactive agents containing
1,2,4-triazoles. The alteration of parent moieties may
lead to compounds that have more efficiency in
biological activity. Newly synthesized structures were
modifications of the 1,2,4-triazoles, which lead to
develop sent of new antimicrobial agents34.
Results and Discussion
Synthetic approach
The chemistry of 1,2,4-triazole heterocyclic
derivative has been of significant interest because of
their synthetic and extensive biological implication in
the field of medicinal chemistry. In many cases, 1,2,4-
tri-azole ring system and their derivatives have been
reported to exhibit enormous biological activities. In
 GODHANI et al.: 1,2,4-TRIAZOLE DERIVATIVES 557

this approach, synthesis is simply modification of
Mannich base reaction. The reaction scheme for the
synthesis of title compounds is depicted in Figure 1.
Mannich reaction is a three-component condensation
reaction involving active hydrogen containing
compound, formaldehyde and a primary or secondary
amine38. The presence of amine group of aromatic
substrates by Mannich reaction is of significant
importance for the synthesis and adaptation of biolo-
gically active compounds39.
Chemistry
A series of compound 5-(3-methoxyphenyl)-1-phenyl-
2-((m-tolylamino)methyl)-1H-1, 2, 4-triazole-3(2H)-
thione (MM4a) was characterized and identified by
their FT-IR, 1H NMR, 13C NMR, mass spectra and
elemental analyses. IR spectrum of this compound
MM4a showed absorption frequency bands which
appeared at 3061, 1040, 1597 and 1118 cm-1 which is
due to the presence of C–H, C–O, C=N, C=S groups
respectively. The 1H NMR spectrum of MM4a showed a
singlet at δ 4.105 corresponding to Ar-NH proton. A
doublet at δ 4.171 was due to N-CH2-N proton. A
singlet was observed at δ 3.705 was due to presence
of Ar-OCH3. The 13C NMR spectrum of MM4a suggests
the presence of triazole ring structure. A range of aro-
matic and triazole ring carbons given at δ 111.60-139.58
(C–H, C–N and –C–C triazole and benzene ring, 15C),

Figure 1 — Reaction scheme of 2-((arylamino)methyl)-5-(3-methoxyphenyl)-1-phenyl-1H-1,2,4-triazole-3(2H)-thione MM4a-m.

558 INDIAN J. CHEM., SEC B, APRIL 2015

187.2 (–C=S, triazole ring, 1C), 161.68 (–C–OCH3, MM4a, MM4b, MM4c, MM4d, MM4e, MM4f, MM4g,
attached to methoxy, 1C), 161.49 (–C=N, triazole ring, MM4i, MM4j, MM4k and MM4m were found to
1C), 58.11 (Ar–OCH3, 1C), 75.17 (N–CH2, attached to show moderate activity against E. coli bacteria (MIC=
triazole ring, 1C), 147.22 (C–NH, 1C), 163.04 (–C–CH3 125-250 µg/mL for each). Similarly, compounds MM4f,
benzene ring, 1C), 21.21 (Ar–CH3, benzene ring, 1C) MM4j and MM4m were found to be more active with
were more prominent. MS: m/z (relative abundance; %), MIC= 62.5-100 µg/mL, while compounds MM4a,
M+• 403 a.m.u. suggest the molecular formula MM4b, MM4c, MM4d, MM4e, MM4g, MM4h,
C23H22N4OS. MM4i, MM4k and MM4l showed moderate activity
against P. aeruginosa for each compound. Compounds
Antimicrobial activity
MM4c, MM4d, MM4e, MM4f, MM4g, MM4h, MM4i
The newly synthesized compounds (MM4a-m) were
and MM4j were moderately active against S. aureus.
screened for their antimicrobial activity against
Compounds MM4j, MM4k and MM4m showed good
gram-positive bacteria S. aureus (MTCC-96),
activity, while com-pounds MM4a, MM4b, MM4c,
S.pyogenes (MTCC-442), gram-negative E. coli
MM4d, MM4e, MM4f, MM4g, MM4h and MM4m
(MTCC-443), P. aeruginosa (MTCC-1688) and
showed moderate active against S. pyogenus with MIC
fungal pathogens C. albicans (MTCC 227), A. niger
= 125-250 µg/mL. Compounds MM4j, MM4l and
(MTCC 282) and A. clavatus (MTCC 1323)
MM4m were more effective against all bacterial strains
Antimicrobial assay studied. Results of antifungal activity were suggestive
The compound MM4l (MIC= 62.5-100 µg/mL for that the synthesized compounds were ineffective
each) was found to be more active, while compounds against fungal pathogens. Where compounds MM4b,
Table I — Antimicrobial and Antitubercular activity result of compounds MM4a-m
Minimal Inhibition Concentrations (Bacteria) Relative
Minimal Inhibition Concentrations
in µg/mL ± SD percentage
(fungi) in µg/mL ± SD
Gram-negative Gram-positive inhibition
Compd Ar A. clavatus
E. coli P. aeruginosa S. aureus S. pyogenus C. albicans A. niger
MTCC MTCC MTCC MTCC MTCC MTCC MTCC M. tuberculosis
1323 H37Rv strain
443 1688 96 442 227 282
MM4a 3-CH3-C6H4 250±3.313** 250±3.455** 500±3.554 250±3.842** 1000±5.214 500±5.364 500±5.416 90±1.321***
*** ** ** **
MM4b 4-NO2-C6H4 125±2.143 200±3.537 500±2.567 250±3.185 250±5.385 1000±4.654 1000±4.471 65±2.854
MM4c 4-F-C6H4 200±4.248** 250±4.594** 250±3.623** 250±4.116** 500±5.263 1000±5.337 1000±4.384 32±1.321
MM4d 3-Cl-C6H4 250±3.899** 125±3.357*** 250±4.228*** 125±3.462*** 1000±4.261 1000±4.231 1000±2.433 88±2.487**
2,5-CH3-
MM4e 125±3.254*** 200±4.649** 200±3.778** 200±4.273** 250±4.749** 1000±4.221 1000±3.489 90±1.321***
C6H3
MM4f 4-Cl-C6H4 200±2.295** 100±4.558*** 200±4.468** 200±4.151** 1000±5.337 1000±5.314 1000±5.569 65±2.559
** ***
MM4g 2-Cl-C6H4 250±3.147 250±3.561 200±2.343** 200±2.549** 1000±5.493 1000±5.148 1000±5.488 68±3.657
MM4h 2-NO2-C6H4 500±2.625 200±2.324** 250±4.621** 250±3.235** 1000±5.785 1000±4.449 250±5.473** 73±2.547
MM4i 3-NO2-C6H4 250±3.854*** 200±2.137** 500±3.527 500±4.383 500±4.389 1000±5.234 1000±4.448 72±1.651
MM4j 4-CH3-C6H4 250±2.765** 100±2.748*** 125±3.576*** 100±3.467*** 1000±5.358 500±5.329 1000±4.524 89±1.037***
MM4k 2-CH3-C6H4 250±3.473** 125±3.441*** 250±1.459** 100±2.885*** 500±4.852 1000±5.334 1000±2.462 85±2.043**
2,4-CH3-
MM4l 100±2.672*** 250±3.984** 500±4.534 100±2.163*** 500±3.187 1000±2.431 1000±4.678 86±2.123**
C6H3
4-OCH3-
MM4m 250±4.789** 100±3.456*** 500±3.215 200±3.834** 250±3.258** 1000±3.327 1000±4.417 84±2.423**
C6H4
Ampicillin 100 ± 1.543 --- 250± 1.531 100 ± 1.370 --- --- --- ---
Chloramphenicol 50 ± 2.136 50 ± 2.264 50 ± 1.825 50 ± 1.377 --- --- --- ---
Gentamycin 0.05 ± 0.07 1 ± 0.215 0.18 0.5 ± 0.117 --- --- --- ---
Ciprofloxin 25 ± 1.325 25 ± 1.363 50 ± 1.237 10 ± 1.213 --- --- --- ---
Norfloxacin 10 ± 1.124 10 ± 1.234 10 ± 2.115 10 ± 1.462 --- --- --- ---
Nystatin --- --- --- --- --- 100 ± 1.347 100 ± 1.432 ---
Greseofulvin --- --- --- --- --- --- 100 ± 2.476 ---
99 ± 2.734
Isoniazide --- --- --- --- --- --- --- ( 0.2 µg/mL
MIC)
 GODHANI et al.: 1,2,4-TRIAZOLE DERIVATIVES
MM4e and MM4m were moderate active against C.
albicans with MIC= 250 µg/mL. The observed
activity may be due to presence of chloro, methoxy
and nitro groups in these compounds40. These results
clearly demonstrated final compounds MM4a-m exhibit
significant antibacterial activity, whereas results of
biological screening showed ineffectiveness against
different fungal pathogen. On the basis of MIC values, it
is our observation that presence of 4-F, 3-Cl, 2,5, -
CH3, 4-Cl, 2-Cl, 4-CH3, 2-CH3, 2,4-CH3, 3-CH3
groups at the position of triazole ring led to a significant
variation in the antimicrobial activity41. The data are
summarized in Table I.
Antitubercular activity
The newly synthesized compounds (MM4a-m) were
screened for their antitubercular activity against M.
tuberculosis (H37Rv strain). Cultures were collected
from Institute of Microbial Technology, Chandigarh.
The activity of compounds was determined standard
protocol by using L J Slope method.
Antitubercular assay
The results of the antitubercular activity are sum-
arized in Table I. The investigation of antitubercular
activity data revealed that compounds MM4a, MM4d,
MM4e, MM4j and MM4m displayed good activity
against M. tuberculosis (H37Rv strain) at 250 µg/mL
concentration of each compound compared to standard
drug isonaizide, which showed 99% inhibition at
0.2 µg/mL concentration.
Material and Equipments
Melting points are determined on a Gallenkamp
melting point apparatus and are uncorrected. Completion
of reaction and purity of synthesized compounds were
checked on thin layer chromatography (TLC), TLC
was performed throughout the reaction on Merck
silica gel GF254 aluminum sheets using mixture of
benzene: ethyl acetate (8:2 V/V) as mobile phase and
visualized under ultraviolet (UV) light or iodine vapour.
All compounds were purified by combi flash chromato-
graphy using ethyl acetate: hexane as eluent. Elemental
analysis (% C, H, N) was carried out by a Perkin-Elmer
2400 CHN analyzer. FT-IR spectra of compounds were
recorded on Thermo-Nicolet FT-IR-200 spectrophoto-
meter in KBr disc (cm-1). 1H NMR (200 MHz) and
13
C NMR (50 MHz) spectra were recorded on Bruker
DRX spectrometer using CDCl3 as a solvent and TMS
as an internal standard. Chemical shifts were reported
in parts per million (δ). Mass spectra of synthesized
559
compounds (MM4a-m) were carried out by using the
Shimadzu GC-MS (Shimadzu 2010 plus) direct probe
method. Compounds (MM4a-m) were synthesized by
using Random synthesizer Syrris IKA-RCA with safety
control.
Experimental Procedure
Procedure for synthesis with elemental and chara-
cterization data of 3-methoxy benzoyl chloride,
compound 1
Synthesis of intermediate step was carried out using
standard methods available in the literature. A brief
notation is given here. A mixture of 5.0 g 3-methoxy
benzoic acid and 7.5 mL thionyl chloride in 250 mL
RBF (round bottom flask) was refluxed about 8 hr.
After completion of the reaction, excess thionyl chloride
was distilled and the solution allowed to stand at room
temperature to get a solid product of 3-methoxy benzoyl
chloride 1. The characterization data are summarized
here.
IR (KBr): 3059 (Ar– C–H stretching), 1038 (Ar–O–C
stretching), 1466 (Ar–CH3 bending), 758 cm-1 (C–Cl
stretching); 1H NMR (CDCl3, 200 MHz): δ 7.204-7.940
(m, 4H, Ar–H), 3.706 (s, 3H, methoxy, Ar–OCH3);
13
C NMR (CDCl3, 50 MHz): δ 115.3-160.4 (benzene
ring, C–H, 6C), 167 (benzene ring, _C=O 1C), 55.6
(Ar–OCH3, 1C); Yield: 67 %, m.p.101-104°C; MS:
m/z (relative abundance, %), M+• 171 a.m.u. Anal. Calcd
for C8H7ClO2: C, 56.32; H, 4.14; N, 0.00. Found: C,
56.32; H, 4.13; N, 0.00%.
Procedure for synthesis with elemental and charac-
terization data of 3-methoxybenzoyl isothiocyanate,
compound 2
A solution of 3-methoxy benzoyl chloride 1
(0.01mol) in dry acetone (50 mL), ammonium
thiocyanate (0.01 mol) was added with constant
stirring at RT. Reaction mixture was stirred for an
hour, and after completion of the reaction, the formed
precipitate of ammonium chloride was filtered, the
filtrate contained 3-methoxy benzoyl isothiocyanate
2.
IR (KBr): 3058 (Ar–C–H stretching), 1037 (Ar–O–C
stretching), 1465 (Ar–CH3 bending), 2116 (–N=C stre-
tching of isothiocynate), 1119 cm-1 (–C=S stretching);
1
H NMR (CDCl3, 200 MHz): δ 7.206-7.945 (m, 4H,
Ar–H), 3.708 (s, 3H, methoxy, Ar–OCH3); 13C NMR
(CDCl3, 50 MHz): δ 115.6-160.3 (benzene ring, C–H
and C=O, 7C), 146.8 (attached to benzene ring,
C=N=S, 1C), 55.7 (Ar–OCH3, 1C); Yield: 72%, m.p.
560 INDIAN J. CHEM., SEC B, APRIL 2015

170-74°C; MS: m/z (relative abundance; %), M+• 194
a.m.u. Anal. Calcd for C9H7NO2S: C, 55.94; H, 4.65;
N, 7.25. Found: C, 55.93; H, 4.64; N, 7.23%.
Procedure for synthesis with elemental and charac-
terization data of 5-(3-methoxyphenyl)-1-phenyl-
1H-1,2,4-triazole-3(2H)-thione, Compound 3
The phenyl hydrazine (0.01 mol) was added to
compound 2, and the reaction mixture was refluxed
for 5 hr, solid product was filtered, washed with water
and cold acetone was added to get compound 3.
IR (KBr): 3056 (Ar–C–H stretching), 1041 (Ar–O–C
stretching), 1468 (Ar–CH3 bending), 1665 (–C=N stre-
tching ), 1117 cm-1 (–C=S stretching); 1H NMR (CDCl3,
200 MHz): δ 7.208-7.940 (m, 9H, Ar–H), 3.705 (s, 3H,
methoxy, Ar–OCH3), 4.105 (s, 1H, N–NH); 13C NMR
(CDCl3, 50 MHz): δ 111.61-129.26 (C–H and C–C,
triazole and benzene ring, 11C), 163.07 (–C=S, triazole
ring, 1C), 161.68 (–C–OCH3, attached to methoxy, 1C),
139.55 (–C=N, triazole ring, 1C), 58.13 (Ar–OCH3, 1C);
Yield: 69 %, m.p. 196-98°C; MS: m/z (relative abun-
dance; %), M+• 282 a.m.u. Anal. Calcd for
C15H13N3OS: C, 66.58; H, 4.62; N, 14.83. Found: C,
66.55; H, 4.60; N, 14.81%.
Procedure for synthesis with elemental and charac-
terization data of 5-(3-methoxyphenyl)-1-phenyl-2-
((m-tolylamino)methyl)-1H -1, 2, 4-triazole-3(2H)-
thione; (MM4a) (Ref 35-37)
A mixture of compound 3 (0.01 mol) formaldehyde
(0.01 mol) and derivative of aniline (0.01 mol) in 1,4-
Table II — Physico-chemical data of the prepared compounds MM4a-m
dioxane (50 mL) was stirred for 22 hr. After completion
of the reaction, it was neutralized with Liq. ammonia
and extracted with ethyl acetate to get 1,2,4-triazole
derivatives, which was crystallized from 1,4-dioxane.
The final step of the synthesis involved Mannich
based reaction involving replacement of hydrogen by
substituting various aryl groups. This approach leads
synthesis of a new series of 1,2,4-triazole derivatives.
Other compounds MM4b-m of this series were prepared
by using a similar method and their physico-chemical
data are summarized in (Table II).
IR (KBr): 2986 and 3061 (Ar–C–H stretching),
3410 (Ar–O–H stretching), 1040 (Ar–O–C stretching),
1473 (Ar–CH2 bending), 756 and 856 (C–H out of
plane), 1597 (–C=N stretching), 1118 cm-1 (–C=S
stretching); 1H NMR (CDCl3, 200 MHz): δ 7.208-
7.940 (m, 13H, Ar–H), 3.705 (s, 3H, methoxy, Ar–
OCH3), 4.105 (s, 1H, Ar–NH, secondary amine),
4.171 (d, 2H, –CH2), 3.440-3.442 (m, 3H, Ar–CH3
benzene ring); 13C NMR (CDCl3, 50 MHz): δ 111.60-
139.58 (C–H, C–N and –C–C, triazole and benzene
ring, 15C), 187.2 (–C=S, triazole ring, 1C), 161.68 (–
C–OCH3, attached to methoxy, 1C), 161.49 (–C=N,
triazole ring, 1C), 58.11 (Ar–OCH3, 1C), 75.17 (N–CH2,
attached to triazole ring, 1C), 147.22 (C–NH, 1C), 163.04
(–C–CH3 benzene ring, 1C), 21.21 (Ar–CH3, benzene ring,
1C); MS: m/z (relative abundance; %), M+• 403 a.m.u.
Anal. Calcd for C23H22N4OS: C, 68.63; H, 5.51; N,
13.92. Found: C, 68.62; H, 5.49; N, 13.92%.
Elemental and characterization data of 5-(3-
methoxyphenyl)-2 - (((4-nitrophenyl)amino)methyl)-

Compd Ar Mol. Formula Yield m.p. (°C) / (%) Found (Calcd )%

(%) Crystallization solvent C H N
Calcd Found Calcd Found Calcd Found

MM4a 3-CH3-C6H4 C23H22N4OS 62 234-38 / Methanol (68.63) 68.62 (5.51) 5.49 (13.92) 13.92
MM4b 4-NO 2 -C H
6 4 C H N O
22 19 5 3 S 68 235-38 / Methanol (60.96) 60.95 (4.42) 4.42 (16.16) 16.14
MM4c 4-F-C6H4 C22H19FN4OS 64 212-14 / B:E (65.01) 65.01 (4.71) 4.70 (13.78) 13.76
MM4d 3-Cl-C6H4 C22H19ClN4OS 71 229-32 / Methanol (62.48) 62.47 (4.53) 4.52 (13.25) 13.23
MM4e 2,5-CH3-C6H3 C24H24N4OS 67 219-24 / B:E (69.20) 69.19 (5.81) 5.79 (13.45) 13.44
MM4f 4-Cl-C6H4 C22H19ClN4OS 72 230-33 / B:E (62.48) 62.46 (4.53) 4.51 (13.25) 13.23
MM4g 2-Cl-C6H4 C22H19ClN4OS 74 230-34 / Methanol (62.48) 62.46 (4.53) 4.50 (13.25) 13.24
MM4h 2-NO2-C6H4 C22H19N5O3S 69 236-38 / E:H (60.96) 60.94 (4.42) 4.40 (16.16) 16.15
MM4i 3-NO2-C6H4 C22H19N5O3S 74 234-38 / Methanol (60.96) 60.95 (4.42) 4.40 (16.16) 16.14
MM4j 4-CH3-C6H4 C23H22N4OS 59 232-35 / Methanol (68.63) 68.62 (5.51) 5.50 (13.92) 13.91
MM4k 2-CH3-C6H4 C23H22N4OS 62 235-37 / Methanol (68.63) 68.60 (5.51) 5.48 (13.92) 13.90
MM4l 2,4-CH3-C6H3 C24H24N4OS 57 238-40 / E:H (69.20) 69.17 (5.81) 5.80 (13.45) 13.43
MM4m 4-OCH3-C6H4 C23H22N4O2S 59 228-34 / B:E (66.01) 66.00 (5.30) 5.28 (13.39) 13.38
B:E = Benzene : Ethyl acetate, E: H = Ethyl acetate: Hexane
 GODHANI et al.: 1,2,4-TRIAZOLE DERIVATIVES
1-phenyl-1H -1,2,4-triazole-3(2H)-thione, MM4b:
IR (KBr): 2987 and 3093 (Ar–C–H stretching), 1035
(Ar–O–C stretching), 1469 (Ar–CH3 bending), 758 and
854 (C–H out of plane), 1659 (–C=N stretching), 1118 (–
C=S stretching), 1617 (–NH in plane bending), 1256
cm-1 (N–O stretching); 1H NMR (CDCl3, 200 MHz):
δ 6.543-7.853 (m, 13H, Ar–H), 3.623 (s, 3H, methoxy,
Ar–OCH3), 3.569 (s, 1H, Ar–NH, secondary amine),
3.765 (d, 2H, –CH2); 13C NMR (CDCl3, 50 MHz):
δ 117.62-144.35 (C–H, C–N and –C–C triazole and ben-
zene ring, 15C), 187.26 (–C=S, 1C), 55.59 (–C–OCH3,
attached to methoxy, 1C), 161.38 (–C=N, triazole ring,
1C), 57.63 (Ar–OCH3, 1C), 76.18 (N–CH2, attached
to triazole ring, 1C), 160.84 (–C–NH, 1C), 136.47
(Ar–NO2, benzene ring, 1C); MS: m/z (relative abun-
dance; %), M+• 434 a.m.u. Anal. Calcd for
C22H19N5O3S: C, 60.96; H, 4.42; N, 16.16. Found: C,
60.95; H, 4.42; N, 16.14%.
Elemental and characterization data of 2-(((4-
fluorophenyl)amino)methyl)-5-(3-methoxyphenyl)-
1-phenyl-1H -1,2,4-triazole-3(2H)-thione, MM4c:
IR (KBr): 2985 and 3058 (Ar–C–H stretching), 1039
(Ar–O–C stretching), 1398 (Ar–CH3 bending), 755
and 789 (C–H out of plane), 1598 (–C=N stretching),
1120 (–C=S stretching), 1398 cm-1 (C–F stretching);
1
H NMR (CDCl3, 200 MHz): δ 7.224-8.449 (m, 13H,
Ar–H), 3.567 (s, 3H, methoxy, Ar–OCH3), 3.428 (s,
1H, Ar–NH, secondary amine), 3.785 (d, 2H, –CH2);
13
C NMR (CDCl3, 50 MHz): δ 111.23-141.64 (C–H,
C–N and –C–C triazole and benzene ring, 15C),
187.23(–C=S, 1C), 160.13 (–C–OCH3, attached to
methoxy, 1C), 161.87 (–C=N, triazole ring, 1C), 55.78
(Ar–OCH3, 1C), 75.35 (N–CH2, attached to triazole
ring, 1C), 143.47 (–C–NH, 1C), 148.65 (C–F benzene
ring, 1C); MS: m/z (relative abundance; %), M+• 407
a.m.u. Anal Calcd for C22H19FN4OS: C, 65.01; H,
4.71; N, 13.78. Found: C, 65.01; H, 4.70; N, 13.76%.
Elemental and characterization data of 2-(((3-
chlorophenyl)amino)methyl)-5-(3-methoxyphenyl)-
1-phenyl-1H-1,2,4-triazole-3(2H)-thione, MM4d: IR
(KBr): 2923 (Ar–C–H stretching), 3318 (Ar–O–H
stretching), 1040 (Ar–O–C stretching), 1463 (Ar–CH3
bending), 756 and 856 (C–H out of plane), 1659
(–C=N stretching), 1118 cm-1 (–C=S stretching);
1
H NMR (CDCl3, 200 MHz): δ 7.878-8.751 (m, 13H,
Ar–H), 3.724 (s, 3H, methoxy, Ar–OCH3), 3.733 (s,
1H, Ar–NH, secondary amine), 3.887 (d, 2H, –CH2);
13
C NMR (CDCl3, 50 MHz): δ 110.86-140.43 (C–H,
C–N and –C–C triazole and benzene ring, 15C),
187.27 (–C=S, 1C), 160.54 (–C–OCH3, attached to
561
methoxy, 1C), 162.62 (–C=N, triazole ring, 1C),
55.72 (Ar–OCH3, 1C), 75.39 (N–CH2, attached to
triazole ring, 1C), 148.83 (C–NH, 1C), 135.16 (C–Cl,
benzene ring, 1C); MS: m/z (relative abundance; %),
M+• 423 a.m.u. Anal. Calcd for C22H19ClN4OS: C,
62.48; H, 4.53; N, 13.25. Found: C, 62.47; H, 4.52; N,
13.23%.
Elemental and characterization data of 2-(((2,5-
dimethylphenyl)amino)methyl)-5-(3-methoxyphen-
yl)-1-phenyl-1H -1,2,4-triazole-3(2H)-thione, MM4e:
IR (KBr): 2985 and 3060 (Ar–C–H stretching), 3378
(Ar–O–H stretching), 1035 (Ar–O–C stretching), 1472
(Ar–CH3 bending), 755 and 856 (C–H out of plane),
1698 (–C=N stretching), 1117 cm-1 (–C=S stretching);
1
H NMR (CDCl3, 200 MHz): δ 6.945-8.738 (m, 12H,
Ar–H), 3.749 (s, 3H, methoxy, Ar–OCH3), 3.765 (s,
1H, Ar–NH, secondary amine), 3.432 (d, 2H, –CH2),
3.587 (s, 6H, Ar–CH3, benzene ring); 13C NMR (CDCl3,
50 MHz) δ 110.62-139.31 (C–H, –C–N and –C–C
triazole and benzene ring, 16C), 162.13 (C–H, 1C),
187.51 (–C=S, 1C), 55.87 (Ar–OCH3, methoxy, 1C),
161.28 (–C=N, triazole ring, 1C), 74.86 (N–CH2,
attached to triazole ring, 1C), 161.67 (C–NH, 1C),
18.43 and 25.72 (Ar–CH3, 2C); MS: m/z (relative
abundance; %), M+• 417 a.m.u. Anal. Calcd for
C24H24N4OS: C, 69.20; H, 5.81; N, 13.45. Found: C,
69.19; H, 5.79; N, 13.43%.
Elemental and characterization data of 2-(((4-
chlorophenyl)amino)methyl)-5-(3-methoxyphenyl)-
1-phenyl-1H -1,2,4-triazole-3(2H)-thione, MM4f:
IR (KBr): 2986 and 3059 (Ar–C–H stretching), 3407
(Ar–O–H stretching), 1041 (Ar–O–C stretching), 1474
(Ar–CH3 bending), 756 (C-Cl stretching), 1597 (–
C=N stretching), 1117 cm-1 (–C=S stretching); 1H
NMR (CDCl3, 200 MHz): δ 7.437-8.321 (m, 13H,
Ar–H), 3.438 (s, 3H, Ar–OCH3), 3.634 (s, 1H, Ar–NH,
secondary amine), 3.823 (d, 2H, –CH2); 13C NMR
(CDCl3, 50 MHz): δ 111.83-139.21 (C–H, C–N and –C–
C triazole and benzene ring, 15C), 186.43 (–C=S,
triazole ring, 1C), 160.78 (–C–OCH3, attached to
methoxy, 1C), 161.29 (–C=N, triazole ring, 1C),
55.82 (Ar–OCH3, 1C), 75.36 (N–CH2, attached to
triazole ring, 1C), 147.39 (–C–NH, 1C), 126.37 (C–Cl,
benzene ring, 1C); MS: m/z (relative abundance; %),
M+• 421 a.m.u. Anal. Calcd for C22H19ClN4OS: C,
62.48; H, 4.53; N, 13.25. Found: C, 62.46; H, 4.51; N,
13.24%.
Elemental and characterization data of 2-(((2-
chlorophenyl)amino)methyl)-5-(3-methoxyphenyl)-
1-phenyl-1H -1,2,4-triazole-3(2H)-thione, MM4g:
IR (KBr): 3058 (Ar–C–H stretching), 3413 (Ar–O–H
562 INDIAN J. CHEM., SEC B, APRIL 2015
stretching), 1043 (Ar–O–C stretching), 1484 (Ar–CH3
bending), 758 (C-Cl stretching), 1663 (–C=N stretching),
1119 cm-1 (–C=S stretching); 1H NMR (CDCl3, 200
MHz): δ 7.473-7.895 (m, 13H, Ar–H), 3.463 (s, 3H,
Ar–OCH3), 3.526 (s, 1H, Ar–NH, secondary amine),
3.742 (d, 2H, –CH2); 13C NMR (CDCl3, 50 MHz):
δ 119.92-139.28 (C–H, C–N and –C–C triazole and
benzene ring, 15C), 187.38 (–C=S, triazole ring, 1C),
160.28 (–C–OCH3, attached to methoxy, 1C), 157.44
(–C=N, triazole ring, 1C), 55.73 (Ar–OCH3, 1C),
75.59 (N–CH2, attached to triazole ring, 1C), 145.26
(–C–NH, 1C), 127.57 (C–Cl, benzene ring, 1C); MS:
m/z (relative abundance; %), M+• 423 a.m.u. Anal. Calcd
for C22H19ClN4OS: C, 62.48; H, 4.53; N, 13.25.
Found: C, 66.46; H, 4.50; N, 13.24%.
Elemental and characterization data of 5-(3-meth-
oxyphenyl)-2-(((2-nitrophenyl)amino)methyl)-1-
phenyl-1H-1,2,4-triazole-3(2H)-thione, MM4h: IR
(KBr): 2984 and 3063 (Ar–C–H stretching), 3404
(Ar–O–H stretching), 1040 (Ar–O–C stretching),
1473 (Ar–CH3 bending), 755 and 856 (C–H out of
plane), 1598 (–C=N stretching), 1123 cm-1 (–C=S
stretching), 1243 (N–O stretching); 1H NMR (CDCl3,
200 MHz): δ 6.498-7.863 (m, 13H, Ar–H), 3.626 (s, 3H,
methoxy, Ar–OCH3), 3.564 (s, 1H, Ar–NH, secondary
amine), 3.773 (d, 2H, –CH2); 13C NMR (CDCl3, 50
MHz): δ 112.25-144.43 (C–H, C–N and –C–C triazole
and ben-zene ring, 15C), 187.14 (–C=S, 1C), 157.63 (–
C–OCH3, attached to methoxy, 1C), 160.74 (–C=N,
triazole ring, 1C), 58.29 (Ar–OCH3, 1C), 76.23 (N–CH2,
attached to triazole ring, 1C), 160.54 (–C–NH, 1C),
137.92 (C–NO2, benzene ring, 1C); MS: m/z (relative
abundance; %), M+• 433 a.m.u. Anal. Calcd for
C22H19N5O3S: C, 60.96; H, 4.42; N, 16.16. Found: C,
60.94; H, 4.40; N, 16.15%.
Elemental and characterization data of 5-(3-meth-
oxyphenyl)-2-(((3 - nitrophenyl)amino)methyl)-1-
phenyl-1H-1,2,4-triazole-3(2H)-thione, MM4i: IR
(KBr): 2983 and 3087 (Ar–C–H stretching), 3401
(Ar–O–H stretching), 1041 (Ar–O–C stretching), 1473
(Ar–CH3 bending), 755 and 856 (C–H out of plane),
1601 (–C=N stretching), 1118 (–C=S stretching),
1243 cm-1 (N–O stretching); 1H NMR (CDCl3, 200
MHz): δ 6.545-7.859 (m, 13H, Ar–H), 3.626 (s, 3H,
methoxy, Ar–OCH3), 3.571 (s, 1H, Ar–NH, secondary
amine), 3.764 (d, 2H, –CH2); 13C NMR (CDCl3, 50
MHz): δ 111.13-145.42 (C–H, C–N and –C–C
triazole and benzene ring, 15C), 187.35 (–C=S, 1C),
158.47 (–C–OCH3, attached to methoxy, 1C), 160.88 (–
C=N, triazole ring, 1C), 58.82 (Ar–OCH3, 1C), 76.34
(N–CH2, attached to triazole ring, 1C), 160.41 (–C–
NH, 1C), 137.43 (C–NO2, benzene ring, 1C); MS: m/z
(relative abun-dance; %), M+• 433 a.m.u. Anal. Calcd
for C22H19N5O3S: C, 60.96; H, 4.42; N, 16.16. Found:
C, 60.95; H, 4.40; N, 16.14%.
Elemental and characterization data of 5-(3-meth-
oxyphenyl)-1-phenyl-2-((p - tolylamino)methyl)-1H
1,2,4-triazole-3(2H)-thione, MM4j: IR (KBr): 2984
and 3062 (Ar–C–H, stretching), 3325 (Ar–O–H, stret-
ching), 1041 (Ar–O–C stretching), 1474 (Ar–CH2 ben-
ding), 756 and 856 (C–H out of plane), 1660 (–C=N
stretching), 1119 (–C=S stretching), 1599 cm-1 (Ar–
NH in plane bending); 1H NMR (CDCl3, 200 MHz):
δ 7.206-7.944 (m, 13H, Ar–H), 3.709 (s, 3H, methoxy,
Ar–OCH3), 4.110 (s, 1H, Ar–NH, secondary amine),
4.173 (d, 2H, –CH2), 3.442-3.444 (m, 3H, Ar–CH3 ben-
zene ring); 13C NMR (CDCl3, 50 MHz): δ 111.63-141.52
(C–H, C–N and –C–C triazole and benzene ring, 15C),
187.6 (–C=S, triazole ring, 1C), 161.71 (–C–OCH3,
attached to methoxy, 1C), 161.32 (–C=N, triazole
ring, 1C), 58.13 (Ar–OCH3, 1C), 75.11 (N–CH2, attached
to triazole ring, 1C), 147.24 (C–NH, 1C), 163.08 (–C–CH3
benzene ring, 1C), 21.23 (Ar–CH3, benzene ring, 1C);
MS: m/z (relative abundance; %), M+• 401 a.m.u. Anal.
Calcd for C23H22N4OS: C, 68.63; H, 5.51; N, 13.92.
Found: C, 68.62; H, 5.50; N, 13.91%.
Elemental and characterization data of 5-(3-meth-
oxyphenyl)-1-phenyl-2-((o - tolylamino)methyl)-1H
1,2,4-triazole-3(2H)-thione, MM4k: IR (KBr): 2925
and 3060 (Ar–C–H, stretching), 3315 (Ar–O–H, stret-
ching), 1042 (Ar–O–C stretching), 1473 (Ar–CH2
bending), 754 and 856 (C–H out of plane), 1600
(–C=N stretching), 1190 (–C=S stretching), 1561 cm-1
(Ar–NH in plane bending); 1H NMR (CDCl3, 200 MHz):
δ 7.212-7.952 (m, 13H, Ar–H), 3.712 (s, 3H, methoxy,
Ar–OCH3), 4.125 (s, 1H, Ar–NH, secondary amine),
4.177 (d, 2H, –CH2), 3.441-3.443 (m, 3H, Ar–CH3
benzene ring); 13C NMR (CDCl3, 50 MHz): δ 113.53-
140.59 (C–H, C–N and –C–C triazole and benzene
ring, 15C), 187.2 (–C=S, triazole ring, 1C), 160.23 (–
C–OCH3, attached to methoxy, 1C), 157.82 (–C=N,
triazole ring, 1C), 58.56 (Ar–OCH3, 1C), 75.32 (N–CH2,
attached to triazole ring, 1C), 148.33 (C–NH, 1C), 164.28
(Ar–C, 1C), 21.26 (Ar–CH3, 1C); MS: m/z (relative
abundance; %), M+• 401 a.m.u. Anal. Calcd for
C23H22N4OS: C, 68.63; H, 5.51; N, 13.92. Found: C,
68.60; H, 5.48; N, 13.90%.
Elemental and characterization data of 2-(((2,4-
dimethylphenyl)amino)methyl)-5-(3-methoxyphen-
yl)-1-phenyl-1H-1,2,4-triazole-3(2H)-thione, MM4l:
IR (KBr): 2986 and 3059 (Ar–C–H stretching), 3387
(Ar–O–H stretching), 1040 (Ar–O–C stretching), 1473
 GODHANI et al.: 1,2,4-TRIAZOLE DERIVATIVES
(Ar–CH3 bending), 756 and 856 (C–H out of plane),
1665 (–C=N stretching), 1118 cm-1 (–C=S stretching);
1
H NMR (CDCl3, 200 MHz): δ 7.741-8.505 (m, 12H,
Ar–H), 3.630 (s, 3H, methoxy, Ar–OCH3), 3.703 (s,
1H, Ar–NH, secondary amine), 3.570 (d, 2H, –CH2),
3.426 (s, 6H, Ar–CH3, benzene ring); 13C NMR (CDCl3,
50 MHz): δ 112.56-139.20 (C–H, C–N and –C–C
triazole and benzene ring, 16C), 187.10 (–C=S, 1C)
161.42 (Ar–C, 1C), 161.79 (–C=N, triazole ring, 1C),
55.68 (Ar–OCH3, 1C), 76.13 (N–CH2, attached to triazole
ring, 1C), 160.03 (C–NH, 1C), 19.08 and 25.13 (Ar–CH3,
2C); MS: m/z (relative abundance; %), M+• 415 a.m.u.
Anal. Calcd for C24H24N4OS: C, 69.20; H, 5.81; N,
13.45. Found: C, 69.17; H, 5.80; N, 13.43%.
Elemental and characterization data of 5-(4-meth-
oxyphenyl)-2-(((3 - methoxyphenyl)amino)methyl)-
1-phenyl-1H-1,2,4-triazole-3(2H)-thione, MM4m: IR
(KBr): 2984 and 3041 (Ar–C–H stretching), 3386
(Ar–O–H stretching), 1039 (Ar–O–C stretching), 1468
(Ar–CH3 bending), 756 and 854 (C–H out of plane), 1665
(–C=N stretching), 1119 (–C=S stretching), 1624 cm-1
(–NH in plane bending); 1H NMR (CDCl3, 200 MHz):
δ 7.495-8.728 (m, 13H, Ar–H), 3.531 (s, 3H, methoxy,
Ar–OCH3), 3.672 (s, 1H, Ar–NH, secondary amine),
3.486 (d, 2H, –CH2), 3.943 (s, 3H, Ar–OCH3, benzene
ring); 13C NMR (CDCl3, 50 MHz): δ 112.23-141.83
(C–H, C–N and –C–C, triazole and benzene ring, 16C),
186.24 (–C=S, 1C), 154.36 (Ar–C, 1C), 160.53 (–C=N,
triazole ring, 1C), 55.26 and 55.88 (Ar–OCH3, 2C),
76.28 (N–CH2, attached to triazole ring 1C), 164.15
(C–NH, 1C), 134.83 (Ar–C, 1C); MS: m/z (relative
abundance; %), M+• 419 a.m.u. Anal. Calcd for
C23H22N4O2S: C, 66.01; H, 5.30; N, 13.39. Found: C,
66.00; H, 5.28; N, 13.38%.
Statistical Analysis
Standard deviation value is expressed in terms of
±SD. Based on calculated value by using one-way
ANOVA method followed by independent two-sample t
test; it has been observed that differences below 0.001
levels are considered as statistically significant. Com-
pounds were screened for their antibacterial, antifungal
and antitubercular activities in six sets (n) against
bacteria and fungi used in the here protocol.
Conclusion
In present study, successful synthesis of 1,2,4-
triazoles (MM4a-m)have been reported. The compounds
were screened against gram-positive, gram-negative
bacterial strain and fungal pathogens. It is evident
from the results that 1,2,4-triazoles, when substituted
563
by electronegative groups like chloro, flouro, methoxy
present on aromatic ring enhanced the antimicrobial
activity. The newly synthesized 1,2,4-triazoles were
also screened for antitubercular activity and the
results suggest that our compounds possessed good
biological activities. The compound MM4d, MM4e,
MM4j and MM4k exhibited moderate to good
antimicrobial and antitubercular activities, which
depends on the electronegative nature of the
substituent groups.
Acknowledgement
Authors are appreciative to Head, Department of
Chemistry, Maharaja Krishnakumarsinhji Bhavnagar
University, Bhavnagar for providing research as well
as instrumental facilities. Authors are also thankful to
Microcare Laboratory, Surat for antimicrobial and
antitubercular activities and also thank CSMCRI
Bhavnagar for providing spectral analysis facility.
One of the co-authors (Anand A. Jogel) is thankful to
University Grants Commission, New Delhi for
providing RGNFS to carry out his Ph.D. programme.
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