Some 6-substituted 3-aryl-7-oxothiazolo[4,5-d]pyrimidin-2(3H)-thione derivatives and their antimicrobial activities

Article abstract of DOI:10.1080/10426500701323333

In this study, 3-aryl-6-substituted thiazolopyrimidin-2(3H)-thione derivatives 4 and 6 have been synthesized by reacting thiazolopyrimidines 2 with -bromoacetophenone 3 and 2-chloro-N-(2-thiazolyl)acetamides 5. The structure elucidation of the obtained co

Full text of DOI:10.1080/10426500701323333

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Some 6-Substituted 3-
Aryl-7-oxothiazolo[4,5-
d]pyrimidin-2(3H)-thione
Derivatives and Their
Antimicrobial Activities
Seref Demirayak a , Faten Dali Ali a , Baland Sirvan
Osman a & Yagmur Tunali b
a Faculty of Pharmacy, Department of
Pharmaceutical Chemistry , Anadolu University ,
Eskisehir, Türkiye
b Faculty of Pharmacy, Department of
Pharmaceutical Microbiology , Anadolu University ,
Eskisehir, Türkiye
Published online: 15 Jun 2007.
To cite this article: Seref Demirayak , Faten Dali Ali , Baland Sirvan Osman & Yagmur
Tunali (2007) Some 6-Substituted 3-Aryl-7-oxothiazolo[4,5-d]pyrimidin-2(3H)-thione
Derivatives and Their Antimicrobial Activities, Phosphorus, Sulfur, and Silicon and the
Related Elements, 182:8, 1793-1803, DOI: 10.1080/10426500701323333
To link to this article: http://dx.doi.org/10.1080/10426500701323333
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Phosphorus, Sulfur, and Silicon, 182:1793–1803, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701323333
Some 6-Substituted
3-Aryl-7-oxothiazolo[4,5-d]pyrimidin-2(3H)-thione
Derivatives and Their Antimicrobial Activities
Seref Demirayak
Faten Dali Ali
Baland Sirvan Osman
Anadolu University, Faculty of Pharmacy, Department of
Pharmaceutical Chemistry, Eskisehir, Tu¨rkiye
Yagmur Tunali
Anadolu University, Faculty of Pharmacy, Department of
Pharmaceutical Microbiology, Eskisehir, Tu¨rkiye
In this study, 3-aryl-6-substituted thiazolopyrimidin-2(3H)-thione derivatives
4 and 6 have been synthesized by reacting thiazolopyrimidines 2 with ω-
bromoacetophenone 3 and 2-chloro-N-(2-thiazolyl)acetamides 5. The structure elu-
cidation of the obtained compounds was performed by IR, 1 H-NMR, MASS spec-
troscopy, and elemental analyses. The antibacterial and antifungal activities of the
compounds were investigated, and it was reported that the compounds showed re-
markable antimicrobial activities.
Keywords 7-Oxothiazolo[4,5-d]pyrimidin-2(3H)-thione; antimicrobial activity; thiazole
INTRODUCTION
Substituted thiazol-2(3H)-thione derivatives can be regarded as ana-
logues of rhodanines and/or dithiocarbamates, whose their antimicro-
bial activities are well known. It was reported that the antimicrobial
activities of rhodanine and dithiocarbamates might be due to the in situ
formation of isothiocyanates.1,2 Although, it was thought that thiazol-
2(3H)-thiones could not be converted into isothiocyanates contrary to
rhodanine or dithiocarbamates, they have well known antimicrobial
and anticancer activities.3,4 On the other hand, thiazolopyrimidines
Received December 12, 2006; accepted February 10, 2007.
Address correspondence to Seref Demirayak, Department of Pharmaceutical Chem-
istry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Turkey. E-mail:
sdemiray@anadolu.edu.tr
1793

1794
S. Demirayak et al.
that have been reported to possess antimicrobial, anticancer, and an-
tiviral activities can be considered as analogues of purine bases in
nucleotides.5−19
In
evaluation
of
these
findings,
3-aryl-6-substituted
thiazolopyrimidin-2(3H)-thiones derivatives 4 and 6 were synthe-
sized and their antimicrobial and anifungal activities were tested.
RESULTS AND DISCUSSION
Chemistry
The synthesis of intermediates and target compounds were performed
by the reactions illustrated in Scheme 1 and 2.
Compounds 1, namely, 3-aryl-4-amino-5-carboxamidothiazole-
2(3H)-thiones, were synthesized in excellent yields following the
methods described by Gewald.3,5,20 It involved the reaction of cyanoac-
etamide with sulphur and the appropriate arylisothiocyanates in the
presence of triethylamine as a basic catalyst. The aminothiazoles
1 were used for the preparation of the starting compounds 2, i.e.,
3-aryl-7-oxothiazolo[4,5-d]pyrimidin-2(3H)-thiones.20 To achieve this
SCHEME 1

Oxothiazolo-Thione Derivatives
1795
SCHEME 2
cyclization, the aminothiazoles 1 were heated in a mixture of triethyl
orthoformate and acetic anhydride. The target compounds 4 and 6 were
prepared by reacting the thiazolopyrimidines 2 and the appropriate 2-
bromoacetophenone 3 or 2-chloro-N-(substituted 2-thiazolyl)acetamide
derivatives 5 in acetone in the presence of potassium carbonate.
The thiazolylacetamide derivatives 5 were obtained by reacting the
suitable 2-aminothiazole or 2-aminobenzothiazole derivatives with
chloroacetyl chloride in the presence of triethylamine in THF in a
common procedure.21
Spectroscopic methods confirm the structure of the new compounds.
IR spectra of 4 and 6 exhibited characteristic carbonyl bands due to
7-oxothiazolo[4,5-d] pyrimidin-2(3H)-thione s and benzoyl or thiazoly-
lacetamide residues, respectively. In the NMR spectra, methylene and
thiazolopyrimidine-4-H protons common for all compounds resonated
at expected regions.
Antimicrobial Activity
Compounds 4a–l and 6a–f were evaluated for antibacterial and
antifungal activity against representative bacteria Gram-negative
rods Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris,
Salmonella thyphimurium, Klebsiella pneumoniae, and Gram-positive
cocci Staphylococcus aureus and Enterococcus faecalis and fungi Can-
dida albicans and Candida globrata as shown in Table I. The antibac-
terial agent, chloramphenicol, and the antifungal agent, ketoconazole,
were used as controls.

1796
S. Demirayak et al.
TABLE I Antibacterial and Antifungal Activities of the Compounds
MIC (µg/mL) of Bacterial and Fungal Strains
Comp.
E.C.
P.A.
P.V.
S.T.
K.P.
E.F.
S.A.
C.A.
C.G.
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
6a
6b
6c
6d
6e
6f
1.25
1.25
1.25
1.25
2.5
1.25
1.25
1.25
1.25
1.25
1.25
2.5
1.25
1.25
1.25
2.5
2.5
25
5
5
5
5
5
5
5
5
2.5
5
5
5
5
5
5
5
5
10
5
10
5
10
5
10
10
5
1.25
2.5
1.25
2.5
1.25
1.25
2.5
1.25
2.5
2.5
2.5
10
2.5
1.25
2.5
1.25
2.5
1.25
1.25
1.25
1.25
1.25
2.5
1.25
2.5
2.5
2.5
1.25
2.5
1.25
6.25
1.25
2.5
1.25
1.25
1.25
1.25
2.5
1.25
1.25
2.5
2.5
1.25
2.5
5
5
10
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
10
5
10
5
5
10
5
—
5
2.5
2.5
2.5
5
2.5
2.5
5
5
5
2.5
2.5
5
5
5
2.5
2.5
5
5
1.25
—
10
10
10
5
1.25
1.25
2.5
1.25
2.5
5
10
10
10
5
1.25
1.25
0.62
1.25
—
2.5
2.5
1.25
—
5
5
—
5
—
2.5
A
B
1.25
—
1.25
—
—
E.C. = Escherichia coli; P.A. = Pseudomonas aeruginosa; P.V. = Proteus vulgaris;
S.T. = Salmonella thyphimurium; K.P. = Klebsiella pneumoniae; E.F. = Enterococcus
faecalis; S.A. = Staphylococcus aureus; C.A. = Candida albicans; C.G. = Candida
globrata; A = Chloramphenicole; B = Ketoconazole.
The results of the tests showed that all of the bacteria were sensi-
tive to the control antibacterial chloramphenicole. With the exception
of Pseudomonas aeruginosa and Proteus vulgaris, quite low MIC values
(1.25 µg/mL) were observed for all studied compounds against the bacte-
ria. It was noteworthy that the MIC values obtained for the compounds
under investigation against the bacteria mentioned above were either
equal or quite close to that of chloramphenicole. However, the MIC val-
ues for P. aeruginosa, and P. vulgaris against chloramphenicole were
larger than that of others (i.e., 5 µg/mL). The values obtained for the
new compounds were either equal or quite close to these values as well.
Taking into account the antifungal activity, the most sensitive fungi
to the control antifungal ketoconazole was C. albicans (MIC 2.5 µg/mL).
It was found that the MIC values obtained for the compounds were
consistent and were 5 µg/mL or 10 µg/mL.
By considering the obtained results, it may be concluded that the
new products have noticeable antibacterial and/or antifungal activities.

Oxothiazolo-Thione Derivatives
1797
However, no significant difference in activity was observed for different
substituents, on the new compounds.
EXPERIMENTAL
Chemistry
Melting points were determined by using an Electrothermal 9100 dig-
ital melting point apparatus and were uncorrected. Spectroscopic data
were recorded on the following instruments: FTIR: Schimadzu 8400
1
FTIR spectrophotometer, H-NMR: Bruker DPX 400 NMR spectrome-
ter in DMSO-d6 and AGILENT 1100 MSD MS spectrometer. Analyses
for C, H, N were within 0.4% of the theoretical values.
ω-Bromoasetophenone
2-aminothiazole
derivatives,22
2-bromocyclohexanone,23
and
derivatives,21
2-aminobenzothiazole,24
cyanoacetamide25 were prepared according to literature methods. 2-
Chloro-N-(substituted 2-thiazolyl)acetamide derivatives were obtained
by reacting the appropriate 2-aminothiazole or 2-aminobenzothiazole
derivatives with chloroacetyl chloride in the presence of triethylamine
in THF in a common procedure.21 3-Aryl-4-amino-5-carboxamido-
thiazole-2(3H)-thione derivatives were obtained by reacting the
appropriate aryl isothiocyanate derivatives with cyanoacetamide
in the presence of triethylamine in ethanol.3,5,20 Some character-
istics of the synthesized compounds were given in Table II and
III.
TABLE II Some Characteristics of the Compounds 4
Comp.
-R
-Rꢀ
M.p.(◦C)
Yield(%)
Mol. Formula/Anal. C,H,N,S)
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
H
H
H
OCH3
OCH3
OCH3
OCH3
Cl
H
204–205
225–226
268–269
241–243
229–230
198–199
211–213
232–233
225–226
216–219
221–223
202–204
63
67
61
69
72
62
75
70
73
64
78
76
C19H13N3O2S2
C20H15N3O2S2
C20H15N3O3S2
C19H12ClN3O2S2
C20H15N3O3S2
C21H17N3O3S2
C21H17N3O4S2
C20H14ClN3O3S2
C19H12ClN3O2S2
C20H14ClN3O2S2
C20H14ClN3O3S2
C19H11Cl2N3O2S2
CH3
OCH3
Cl
H
CH3
OCH3
Cl
H
4j
4k
4l
Cl
Cl
Cl
CH3
OCH3
Cl

1798
S. Demirayak et al.
TABLE III Some Characteristics of the Compounds 6
Comp.
R
Rꢀ
M.p.(◦C) Yield(%) Mol. Formula/Anal. C,H,N,S)
6a
6b
6c
6d
6e
6f
H
CH3
CH3
CH2-CH2
C6H5
H
H
CH3
211–212
200–202
267–268
54
57
60
55
71
68
C16H11N5O2S3 . 1/ H O
2
2
C17H13N5O2S3 . 1/ H O
2
2
C18H15N5O2S3 . 1/ H O
2
2
CH2-CH2- 225–226
H
CH=CH-
C20H17N5O2S3 . 1/ H O
2
2
263–264
298–299
C22H15N5O2S3 . 1/ H O
2
2
CH=CH
C20H13N5O2S3 . 1/ H O
2
2
General Method for the Preparation of
3-Aryl-7-oxo-thiazolo[4,5-d] pyrimidin-2(3H)-thione
Derivatives
A mixture of 3-aryl-4-amino-5-carboksamido-2,3-dihydrothiazol-2-
thione (0.01 mol ) triethyl orthoformate (15 mL) and acetic anhydride
(15 mL) was refluxed for 12 h. The solution obtained was concen-
trated under vacuum. The residue was triturated with ethanol, fil-
tered, and recrystallized from ethanol. The obtained products were
used in the following step. The following two compounds have been
prepared for the first time: 3-(4-methoxyphenyl)-7-oxothiazolo[4,5-
d]pyrimidin-2(3H)-thione (m.p. 222–223◦C) and 3-(4-chlorophenyl)-7-
oxothiazolo[4,5-d] pyrimidin-2(3H)-thione (m.p. 242–243◦C).
General Method for the Preparation of 3-Substituted 6-(2-aryl-
2-oxo-1-ethyl)-7-oxothiazolo[4,5-d]pyrimidin-2(3H)-thione,
4a–t, and 3-Phenyl-6-[N-(substituted thiazole-2-yl)-2-
acetamido]-7-oxothiazolo[4,5-d]pyrimidine-2(3H)-thione, 6a–f,
Derivatives
A mixture of an appropriate 2 (5 mmol), an appropriate 3 or 5
(5 mmol), and potassium carbonate (0.83 g, 6 mmol) in acetone (100 mL)
was refluxed. In the case of compounds 4, the reflux time was two h
and in the case of the compounds 6, the reflux time was twelve h. The
solvent was evaporated at low temperature. The residue was washed
with water and then ethanol. The raw product was recrystallized from
ethanol.
4a IR (KBr, cm−1) : 1687 (C=O), 1587–1433 (C=N, C=C), 1228 (C=S).
1H NMR (400 MHz) (DMSO-d6) δppm : 5.69 (2H, s, COCH2), 7.49–7.52
(2H, m, 3-phenyl C2,6-H), 7.57–7.65 (5H, m, Ar-H), 7.74–7.76 (1H, m,
benzoyl C4-H), 8.1 (2H, d, J = 8.5 Hz, 3-phenyl C2,6-H), 8.46 (1H, s,
thiazolopyrimidine C5-H). MS(ES) m/z : 381 (M+2, 4%), 379 (M+, 8%),
378 (M-1, 25%), 364 (100%).

Oxothiazolo-Thione Derivatives
1799
4b IR (KBr, cm−1) : 1689 (C=O), 1606–1427 (C=N, C=C), 1230 (C=S).
1H NMR (400 MHz) (DMSO-d6) δppm : 2.09 (3H, s, Ar-CH3), 5.65 (2H,
s, COCH2), 7.43 (2H, d, J = 8.08 Hz, benzoyl C3,5-H), 7.49–7.71 (2H, m,
3-phenyl C2,6-H), 7.57–7.64 (3H, m, 3-phenyl C3,4,5-H), 7.99 (2H, d, J =
8.21Hz, benzoyl C2,6-H), 8.45 ( 1H, s, thiazolopyrimidine C5-H).
4c IR (KBr, cm−1) : 1676 (C=O), 1596–1417 (C=N, C=C), 1236 (C=S).
1H NMR (90 MHz) (DMSO-d6) δppm : 3.88 (3H, s, OCH3), 5.62 (2H, s,
COCH2), 7.07 (2H, d, J = 8.9 Hz, 3-phenyl C3,5-H), 7.44–7.64 (5H, m,
benzoyl Ar-H), 8.02 (2H, d, J = 8.9 Hz, 3-phenyl C2,6-H), 8.44 (1H, s,
thiazolopyrimidine C5-H).
4d IR (KBr, cm−1) : 1676 (C=O), 1589–1429 (C=N ve C=C), 1230
(C=S). 1H NMR (400 MHz) (DMSO-d6) δppm : 5.68 (2H, s, -CH2-CO-),
7.50 (2H, d, J = 7.09 Hz, 3-phenyl C2,6-H), 7.57–7.64 (3H, m, 3-phenyl
C3,4,5-H), 7.70 (2H, d, J = 8.49 Hz, benzoyl C3,5-H), 8.11 (2H, d, J =
8.53 Hz, benzoyl C2,6-H), 8.44 (1H, s, thiazolopyrimidine C5-H).
4e IR (KBr, cm−1) : 1685 (C=O), 1600–1409 (C=N, C=C), 1234 (C=S),
1170–1029 (C O). 1H NMR (400 MHz) (DMSO-d6) δppm : 3.86 (3H, s,
-OCH3), 5.69 (2H, s, COCH2-), 7.13 (2H, d, J = 8.96 Hz, 3-aryl C3,5-H),
7.40 (2H, d, J = 8.92 Hz, 3-Aryl C2,6-H), 7.61–7.65 (2H, m, benzoyl C3,5
-
H), 7.74–7.78 (1H, m, benzoyl C4-H), 8.1 (2H, d, J = 8.38 Hz, benzoyl
C2,6-H), 8.46 (1H, s, thiazolopyrimidine C5-H).
4f IR (KBr, cm−1) : 1685 (C=O), 1606–1427 (C=N, C=C), 1232 (C=S),
1170–1022 (C O). 1H NMR (400 MHz) (DMSO-d6) δppm : 2.42 (3H, s,
Ar-CH3), 3.85 (3H, s, Ar-OCH3), 5.64 (2H, s, -COCH2-), 7.14 (2H, d, J =
8.92 Hz, 3-aryl C3,5-H), 7.40 (2H, d, J = 9.14 Hz, 3-aryl C2,6-H), 7.43
(2H, d, J = 9.09 Hz, benzoyl C3,5-H), 8.10 (2H, d, J = 8.13 Hz, benzoyl
C2,6-H), 8.45 (1H, s, thiazolopyrimidine C5-H).
4g IR (KBr, cm−1) : 1674 (C=O), 1600–1421 (C=N, C=C), 1224 (C=S),
1182–1020 (C O). 1H NMR (90 MHz) (DMSO-d6) δppm : 3.84 (3H, s,
Ar-OCH3), 3.88 (3H, s, Ar-OCH3), 5.66 (2H, s, -COCH2-), 7.07 (2H, d,
J = 8.86 Hz, 3-phenyl C3,5-H), 7.42 (2H, d, J = 8.09 Hz, benzoyl C3,5
-
H), 8.02 (2H, d, J = 8.9 Hz, 3-phenyl C2,6-H), 8.11 (2H, d, J = 8.13 Hz,
benzoyl C2,6-H), 8.45 (1H, s, thiazolopyrimidine C5-H). MS(ES) m/z :
442 (M+3, 7%), 441 (M+2, 32%), 440 (M+1, 5%), 439 (M+, 10%), 438
(M-1, 35%), 255 (100%).
4h IR (KBr, cm−1): 1689 (C=O), 1600–1433 (C=N, C=C), 1236 (C=S),
1170–1093 (C O). 1H NMR (90 MHz) (DMSO-d6) δppm : 3.86 (3H, s,
Ar-OCH3), 5.65 (2H, s, -COCH2-), 7.11 (2H, d, J = 8.66 Hz, 3-phenyl
C
3,5-H), 7.72 (2H, d, J = 8.37 Hz, benzoyl C3,5-H), 8.08 (2H, d, J = 8.60
Hz, 3-phenyl C2,6-H), 8.12 (2H, d, J = 8.43 Hz, Benzoyl C2,6-H), 8.42
(1H, s, thiazolopyrimidine C5-H).
4i IR (KBr, cm−1) : 1693 (C=O), 1595–1429 (C=N, C=C), 1230 (C=S).
1H NMR (400 MHz) (DMSO-d6) δppm : 5.69 (2H, s, -COCH2-), 7.58

1800
S. Demirayak et al.
(2H, d, J = 8.66 Hz, 3-aryl C2,6-H), 7.6–7.65 (2H, m, benzoyl C3,5-H),
7.69 (2H, d, J = 8.7 Hz, 3-aryl C3,5-H), 7.74-7.78 (1H, m, benzoyl C4-H),
8.10 (2H, d, J = 8.39 Hz, benzoyl C2,6-H), 8.47 (1H, s, thiazolopyrimidine
C5-H).
4j IR (KBr, cm−1) : 1689 (C=O), 1606–1429 (C=N, C=C), 1228 (C=S).
1H NMR (90 MHz) (DMSO-d6) δppm : 2.44 (3H, s, Ar-CH3), 5.66 (2H,
s, -COCH2-), 7.42 (2H, d, J = 8.92 Hz, benzoyl C3,5-H), 7.55 (2H, d,
J = 8.71 Hz, 3-aryl C2,6-H), 7.71 (2H, d, J = 8.66 Hz, 3-aryl C3,5-H), 8.04
(2H, d, J = 8.89 Hz, benzoyl C2,6-H), 8.46 (1H, s, thiazolopyrimidine C5-
H). MS(ES) m/z : 432 (M+4, 3%), 430 (M+3, 5%), 429 (M+2, 10%), 428
(M+1, 45%), 427 (M+, 25%), 426 (M-1, 100%).
4k IR (KBr, cm−1) : 1685 (C=O), 1602–1429 (C=N, C=C), 1228(C=S),
1
1170–1085 (C-O). H NMR (90 MHz) (DMSO-d6) δppm : 3.88 (3H, s,
Ar-CH3), 5.63 (2H, s, -COCH2-), 7.13 (2H, d, J = 8.92 Hz, benzoyl C3,5
-
H), 7.57 (2H, d, J = 8.71 Hz, 3-aryl C2,6-H), 7.69 (2H, d, J = 8.66 Hz,
3-aryl C3,5-H), 8.07 (2H, d, J = 8.89 Hz, benzoylC2,6-H), 8.46 (1H, s,
thiazolopyrimidine C5-H).
4l IR (KBr, cm−1) : 1695 (C=O), 1630–1427 (C=N, C=C), 1230 (C=S).
1H NMR (400 MHz) (DMSO-d6) δppm : 5.68 (2H, s, -CH2-CO-), 7.57
(2H, d, J = 8.46 Hz, 3-aryl C2,6-H), 7.70 (2H, d, J = 8.72 Hz, 3-aryl
C
3,5-H), 7.71 (2H, d, J = 8.81 Hz, benzoyl C3,5-H), 8.04 (2H, d, J = 8.37
Hz, benzoyl C2,6-H), 8.46 (1H, s, thiazolopyrimidine C5-H).
6a IR (KBr, cm−1) : 3178 (N H), 1685 (C=O), 1558–1429 (C=N,
C=C), 1234 (C=S), 1168–1091–1022 (C-O). 1H NMR (90 MHz) (DMSO-
d6) δppm : 5.00 (2H, s, COCH2), 7.06–7.7 (7H, m, Ar-H and thiazole
C4,5-H), 8.48 (1H, s, thiazolopyrimidine C5-H), 12.5 (1H, bs, NH).
6b IR (KBr, cm−1) : 3272 (N H), 1677 (C=O), 1587–1429 (C=N,
1
C=C), 1239 (C=S), 1170–1021 (C O). H-NMR(400 MHz)(CDCl3)
δ
(ppm) : 2.78 (3H, s, thiazole-4-CH3), 4.99 (2H, s, COCH2), 7.49–7.57
(2H, m, 3-phenyl C2,6-H), 7.63–7.73 (3H, m, 3-phenyl C3,4,5-H), 7.91
(1H, s, thiazole C5-H), 8.57 (1H, s, thiazolopyrimidine C5-H), 10.68 (1H,
bs, NH).
6c IR (KBr, cm−1) : 3201 (N H), 1664 (C=O), 1557–1419 (C=N, C=C),
1
1238 (C=S), 1089–1024 (C O). H NMR (400 MHz) (CDCl3) δppm :
2.14 (3H, s, 4-CH3), 2.23 (3H, s, 5-CH3), 4.95 (2H, s, COCH3), 7.46–7.48
(2H, m, 3-phenyl C2,6-H), 7.55–7.64 (3H, m, 3-phenyl C3,4,5-H), 8.48
(1H, s, thiazolopyrimidine C5-H), 12.25 (1H, bs, NH). MS(ES) m/z : 432
(M+3, 5%), 431 (M+2, 10%), 430 (M+1, 15%), 429 (M, 20%), 428 (M-1,
100%).
6d IR (KBr, cm−1) : 3218 (N H), 1683 (C=O), 1558–1431 (C=N,
C=C), 1236 (C=S). 1H NMR (400 MHz) (CDCl3) δppm : 1.7–1.85 (4H,
m, tetrahydrobenzothiazole C5,6-H), 2.5-2.65 (4H, m, tetrahydroben-
zothiazole C4,7-H), 4.96 (2H, s, COCH2), 7.45–7.48 ((2H, m, 3-phenyl

Oxothiazolo-Thione Derivatives
1801
C2,6-H), 7.56–7.63 (3H, m, 3-phenyl C3,4,5-H), 8.48 (1H, s, thiazolopy-
rimidine C5-H), 12.4 (1H, bs, NH). MS(ES) m/z : 457 (M+2, 5%), 456
(M+1, 12%), 455 (M, 25%), 454 (M-1, 100%).
6e IR (KBr, cm−1) : 3253 (N H), 1550–1431 (C=N, C=C), 1238
1
(C=S), 1072–1027 (C O). H NMR (400 MHz) (CDCl3) δppm : 5.02
(2H, s, COCH2), 7.31–7.35 (2H, m, 3-phenyl C2,6-H), 7.39–7.48 (3H, m,
3-phenyl C3,4,5-H), 7.53–7.63 (3H, m, thiazole-4-phenyl C3,4,5-H), 7.68
(1H, s, thiazole-C5-H), 7.87–7.91 (2H, m, thiazole-4-phenyl C2,6-H), 8.5
(1H, s, thiazolopyrimidine C5-H), 12.84 (1H, bs, NH). MS(ES) m/z : 479
(M+2, 5%), 478 (M+1, 15%), 477 (M, 20%), 476 (M-1, 100%).
6f IR (KBr, cm−1) : 3182 (N H), 1681 (C=O), 1602–1429 (C=N, C=C),
1
1232 (C=S), 1022 (C O). H NMR (400 MHz) (CDCl3) δppm : 5.07
(2H, s, COCH2), 7.34–7.36 (1H, m, benzothiazole C6-H), ), 7.42–7.51
(3H, m, 3-Phenyl C2,6-H and benzothiazole C5-H), 7.55-7.65 (3H, m, 3-
phenyl C3,4,5-H), 7.78–7.8 (1H, m, benzothiazole C7-H), 7.98-8.02 (1H,
m, benzothiazole C4-H), 8.52 (1H, s, thiazolopyrimidine C5-H), 12.43
(1H, bs, NH).
Antimicrobial Activity
The study was designed to compare MICs obtained by the NCCLS refer-
ence M27-A2 broth microdilution method.26,27 Two MIC readings were
performed with each chemical agent. For both the antibacterial and
antifungal assays, the compounds were dissolved in DMSO. Further
dilutions of the compounds and standard drugs in a test medium were
prepared at the required quantities of 10, 5, 2.5, 1.25, 0.62, 0.31, 0.15,
0.075, and 0.040 µg/ml concentrations with Mueller-Hinton Broth and
Sabouroud Dextrose Broth.
In order to ensure that the solvent per se had no effect on bacteria or
yeast growth, a control test was also performed containing inoculated
broth supplemented with only DMSO at the same dilutions used in our
experiments; the solvent was found inactive in culture medium.
All the compounds were tested for their in vitro growth inhibitory
activity against human pothogenic as Gram-negative rods Escherichia
coli (ATCC 35218), Pseudomonas aeruginosa (ATCC 27853), Pro-
teus vulgaris (NRLL B-123), Salmonella thyphimurium (NRRL B-
4420), Klebsiella pneumoniae (ATCC 700603) and as Gram-positive
cocci Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis
(ATCC 29212) and fungi Candida albicans (obtained from Faculty of
Medicine Osmangazi University, Eskisehir, Turkiye) and Candida glo-
brata (ATCC 36583). Chloramphenicol and ketokanozole were used as
control drugs. The observed data regarding antibacterial and antifungal
activity of the compounds and the control drugs are given in Table I.

1802
S. Demirayak et al.
For the control antibiotic, chloramphenicol, lowest MIC values were
obtained against E. coli,. S. thyphimurium, K. pneumoniae, E. faecalis,
and S. aureus, i.e., 1.25 µg/mL and for the control antifungal, ketocona-
zole, the lowest MIC value was obtained against C. albicans, i.e. 1.25
µg/mL. The lowest MIC value for the compounds under investigation
was obtained for 6f against E. faecalis, i.e., 0.62 µg/mL.
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