Quinazoline derivatives with antitubercular activity

Article abstract of DOI:10.1016/S0014-827X(00)00100-2

4-Quinazolinol was prepared by the reaction of anthranilic acid and formamide. The hydroxy group was converted into the thiol function by treatment with phosphorus(V)sulfide, and the subsequent alkylation of the thiol group was carried out with alkylhalid

Full text of DOI:10.1016/S0014-827X(00)00100-2

www.elsevier.nl/locate/farmac
Il Farmaco 55 (2000) 725–729
Quinazoline derivatives with antitubercular activity
a,
b
a
b
c
&
Jirˇ´ı Kunesˇ *, Jaroslav Bazˇant , Milan Pour , Karel Waisser , Milan Slosa´rek ,
Jirˇ´ı Janota c
a Laboratory of Structure and Interactions of Biologically Acti6e Molecules, Department of Inorganic and Organic Chemistry,
Faculty of Pharmacy, Charles Uni6ersity, 500 05 Hradec Kra´lo6e´, Czech Republic
b Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles Uni6ersity, 500 05 Hradec Kra´lo6e´, Czech Republic
c Institute of Public Health, CZ 100 42 Prague, Czech Republic
Received 26 April 2000; accepted 12 September 2000
Abstract
4-Quinazolinol was prepared by the reaction of anthranilic acid and formamide. The hydroxy group was converted into the
thiol function by treatment with phosphorus(V)sulfide, and the subsequent alkylation of the thiol group was carried out with
1
alkylhalides under the conditions of phase-transfer catalysis. The structure of the substances was confirmed by H, 13C NMR, IR,
and MS. Most of the synthesized compounds exhibited antimycobacterial activity against the strains of Mycobacterium
tuberculosis, Mycobacerium a6ium, Mycobacterium fortuitum, Mycobacterium kansasii and Mycobacterium intracellulare. 4-(S-
Butylthio)quinazoline (3c) was even more active than isoniazide against atypical strains of mycobacteria. © 2000 Elsevier Science
S.A. All rights reserved.
Keywords: Quinazoline; Alkylthioquinazoline; Antimycobacterial activity
1. Introduction
2. Chemistry
In the course of the research into potential antituber-
cular agents, an important relationship was found be-
tween the structure and antitubercular effect, as the
alkylthio group bound to an electron-deficient carbon
atom was identified as a possible pharmacophore of
antitubercular activity [1]. This hypothesis was con-
firmed for a number of compounds containing this
structural moiety, such as 2-alkylthiobenzothiazoles [2–
4], 1-aryl-5-alkylthio-1.2.3.4-tetrazoles [5,6], substituted
4-alkylthiopyridine-4-carbothioamides and 4-carboni-
triles, and substituted 2-alkylthiopyridine-4-carbo-
thioamides and 4-carbonitriles [7]. The aim of this work
was to verify the validity of the above hypothesis for
the derivatives of quinazoline. It was thus necessary to
prepare a set of derivatives of 4-alkylthioquinazoline,
and to assess their activity against various strains of
mycobacteria.
The precursor of the target compounds, 4-quinazoli-
nol (1) was prepared by the condensation of formamide
with anthranilic acid [8] (Scheme 1).
In the following step, the hydroxy group in position
4 of the quinazoline skeleton was converted into the
thiomoiety by the treatment of 1 with phospho-
* Corresponding author. Fax: +420-49-521 0002.
E-mail address: kunes@faf.cuni.cz (J. Kunesˇ).
Scheme 1. TBAB: tetrabutylammonium bromide.
0014-827X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0014-827X(00)00100-2

726
J. Kunesˇ et al. / Il Farmaco 55 (2000) 725–729
rus(V)sulfide in anhydrous pyridine, which yielded com-
pound 2.
solved in aqueous KOH. Acidification of the solution
with acetic acid afforded the product crystals, which
were filtered off and dried. Yield 93%, m.p. 300–2°C;
literature: m.p. 311–312°C [9].
To prepare 4-alkylthioquinazolines, two alkylation
methods were chosen: alkylation under the conditions
of classical nucleophilic substitution, and under the
conditions of phase-transfer catalysis. Comparison of
both methods showed that better results were obtained
with the use of phase-transfer catalysts. The target
compounds (3a–j) were thus obtained by the reaction
of 4-quinazolinethiole and the appropriate alkylhalide
in a two-phase medium with tetrabutylammonium bro-
mide as a catalyst.
3.2.3. 4-Alkylthioquinazolines (3a–j)
The appropriate alkylhalide (1.1 mol. eq.), 1 M KOH
(15 ml), and tetrabutylammonium bromide (200 mg)
were added to a suspension of 4-quinazolinethiol (1 g, 6
mmol) in cyclohexane (15 ml), and the mixture was
heated at reflux for 12–40 h. The crude product was
purified by column chromatography (silica gel Merck,
mobile phase petrolether–ethylacetate 9:1). The data of
the prepared 4-alkylthioquinazolines (3a–j) are summa-
rized in Table 1.
The structures of the prepared compounds were
1
confirmed by spectral methods (IR, H, 13C NMR and
MS).
3.2.3.1. 4-Ethylthioquinazoline (3a). IR (KBr) 1258(m),
1323(s), 1333(s), 1487(s), 1544(s), 1564(s), 1911(w),
2489(w), 2932(m), 2977(m). LRMS: 190 (M+), 162
(ꢀC2H5), 129 (ꢀSꢀC2H5), 75 (C6H4).
3. Experimental
3.1. Chemistry
1H NMR (300 MHz, CDCl3) l 8.91s (H2), 7.96d 1H
J=8.24 (H5), 7.86d 1H J=8.24 (H8), 7.77–7.69m 1H
(H7), 7.50–7.41m 1H (H6), 3.29q 2H J=14.69, 7.42
(CH2), 1.38t 3H J=7.42 Hz (CH3).
The melting points of the substances were determined
on a Koffler apparatus and are uncorrected. IR spectra
were obtained on a Nicolet Impact 400 spectrometer in
KBr pellets or in chloroform. The H and 13C NMR
1
13C NMR l 171.3, 153.4, 147.7, 133.3, 128.6, 127.0,
123.8, 123.7, 23.8, 14.1.
spectra were recorded for CDCl3 solutions at ambient
temperature on a Varian Mercury–Vx BB 300 spec-
trometer operating at 300 MHz. Chemical shifts were
recorded as l values in parts per million (ppm), and
were indirectly referenced to tetramethylsilane via the
3.2.3.2. 4-Propylthioquinazoline (3b). IR (KBr) 1259(m),
1323(s), 1333(s), 1486(s), 1544(s), 1564(s), 1911(w),
2487(w), 2935(m), 2969(m). LRMS: 205 (M+), 162
(ꢀC3H7), 129 (ꢀSꢀC3H7), 75 (C6H4).
solvent signal (7.26 for H and 77.0 for 13C). Multiplic-
1
ities are given together with the coupling constants (in
Hz). Mass spectra of all substances were measured on a
MAGNUM FINNIGAN MAT spectrometer with low
resolution.
The reactions and the purity of all compounds was
checked by TLC (Silufol UV254/366, Kavalier, Votice,
Czech Republic) in petrolether–ethylacetate (8:2) using
UV detection and iodine vapours.
1H NMR (300 MHz, CDCl3) l 8.96s (H2), 8.07ddd
1H J=8.24, 1.37, 0.55 (H5), 7.92d 1H J=8.24 (H8),
7.85–7.77m 1H (H7), 7.58–7.50m 1H (H6), 3.34t 2H
J=7.42 (CH2), 1.88–1.74m 2H (CH2), 1.08t 3H J=
7.42 Hz (CH3).
13C NMR l 171.7, 153.5, 147.8, 133.5, 128.7, 127.1,
124.0, 123.9, 31.4, 22.4, 13.5.
3.2.3.3. 4-Butylthioquinazoline (3c). IR (CHCl3)
1259(m), 1323(s), 1333(s), 1487(s), 1543(s), 1565(s),
2934(m), 2963(m). LRMS: 218 (M+), 162 (ꢀC4H9),
129 (ꢀSꢀC4H9), 75 (C6H4).
3.2. General procedure for the synthesis of the com-
pounds
3.2.1. 4-Quinazolinol (1)
1H NMR (300 MHz, CDCl3) l 8.92s (H2), 8.01d 1H
J=8.24 (H5), 7.88d 1H J=8.24 (H8), 7.80–7.71m 1H
(H7), 7.53–7.44m 1H (H6), 3.31t 2H J=7.42 (CH2),
1.79–1.66m 2H (CH2), 1.55–1.37 2H (CH2), 0.92t 3H
J=7.42 Hz (CH3).
A mixture of formamide (7.5 g, 170 mmol) and
anthranilic acid (13.7 g, 100 mmol) was stirred at
120–125°C for 4 h. The crude product was then filtered
off, and recrystallized from ethanol. Yield 47%, m.p.
214–7°C; literature: m.p. 215.5–216.5°C [8].
13C NMR l 171.5, 153.4, 147.7, 133.3, 128.6, 127.0,
123.9, 123.7, 30.9, 23.1, 22.0, 13.6.
3.2.2. 4-Quinazolinthiol (2)
Phosphorus(V)sulfide (28.65 g, 128 mmol) was added
to a solution of 4-quinazolinol (18.5 g, 126.7 mmol) in
anhydrous pyridine (200 ml), and the mixture was
heated at reflux for 20 h. The reaction mixture was then
poured onto ice, and the resultant precipitate was dis-
3.2.3.4. 4-Hexylthioquinazoline (3d). IR (CHCl3)
1258(m), 1323(s), 1333(s), 1487(s), 1543(s), 1565(s),
1911(w), 2486(w), 2931(m), 2960(m). LRMS: 247 (M+),
162 (ꢀC6H13), 129 (ꢀSꢀC6H13), 75 (C6H4).

J. Kunesˇ et al. / Il Farmaco 55 (2000) 725–729
727
3.2.3.7. 4-Phenethylthioquinazoline (3g). IR (CHCl3)
1259(m), 1322(s), 1333(s), 1487(s), 1544(s), 1565(s),
2984(m). LRMS: 266 (M+), 162 (ꢀC8H9), 129
(ꢀSꢀC8H9), 75 (C6H4).
1H NMR (300 MHz, CDCl3) l 8.94s (H2), 8.03d 1H
J=8.24 (H5), 7.89d 1H J=8.24 (H8), 7.77dt 1H J=
8.24, 1.37 (H7), 7.55dt 1H J=8.24, 1.37 (H6), 3.32t 2H
J=7.42 (CH2), 1.83–1.68m 2H (CH2), 1.53–1.38m 2H
(CH2), 1.37–1.19m 2H (CH2), 0.86t 3H J=7.42 Hz
(CH3).
1H NMR (300 MHz, CDCl3) l 9.02s (H2), 8.07ddd
1H J=8.24, 0.82, 0.55 (H5), 7.97d 1H J=8.24 (H8),
7.88–7.81m 1H (H7), 7.60–7.53m 1H (H6), 7.39–
7.18m 5H (H2%, H3%, H4%, H5%, H6%), 3.63t 2H J=7.42
(CH2), 3.11t 2H J=7.42 Hz (CH2).
13C NMR l 171.6, 153.4, 147.8, 133.4, 128.6, 127.0,
123.9, 123.8, 31.3, 29.4, 28.8, 28.6, 22.4, 13.9.
13C NMR l 171.3, 153.5, 147.8, 140.0, 133.6, 128.7,
128.6, 128.4, 127.2, 126.5, 124.0, 123.9, 35.3, 30.8.
3.2.3.5. 4-Cetylthioquinazoline (3e). IR (KBr) 1279(m),
1323(s), 1333(s), 1487(s), 1543(s), 1565(s), 2927(m),
2956(m). LRMS: 386 (M+), 162 (ꢀC16H33), 129
(ꢀSꢀC16H33), 75 (C6H4).
3.2.3.8. 4-Allylthioquinazoline (3h). IR (CHCl3)
1259(m), 1323(s), 1333(s), 1486(s), 1545(s), 1564(s),
1910(w), 2487(w), 2932(m), 2984(m). LRMS: 202 (M+),
162 (ꢀC3H5), 129 (ꢀSꢀC3H5), 75 (C6H4).
1H NMR (300 MHz, CDCl3) l 8.97s (H2), 8.09ddd
1H J=8.24, 1.38, 0.55 (H5), 7.96d 1H J=8.24 (H8),
7.83dt 1H J=8.24, 1.38 (H7), 7.57dt 1H J=8.24, 1.38
(H6), 3.37t 2H J=7.41 (CH2), 1.88–1.72m 2H (CH2),
1.56–1.20m 26H (CH2), 0.87t 3H J=7.41 Hz (CH3).
13C NMR l 172.0, 153.4, 147.6, 133.6, 128.6, 127.2,
124.0, 123.9, 34.0, 32.8, 31.9, 29.7, 29.6, 29.6, 29.5, 29.4,
29.3, 29.2, 29.0, 28.9, 28.8, 28.2, 22.7, 14.1.
1H NMR (300 MHz, CDCl3) l 8.99s (H2), 8.08ddd
1H J=8.52, 1.38, 0.55 (H5), 7.96d 1H J=8.52 (H8),
7.84dt 1H J=8.52, 1.38 (H7), 7.58dt 1H J=8.52, 1.38
(H6), 6.12–5.95m 1H (CH), 5.40ddd 1H J=17.03,
2.74, 1.37 (CH2), 5.19ddd 1H J=10.17, 2.20, 1.1
(CH2), 4.06dd 2H J=6.87, 1.1 Hz (CH2).
13C NMR l 170.8, 153.4, 147.9, 133.7, 132.7, 128.7,
127.3, 123.9, 123.8, 118.6, 32.2.
3.2.3.6. 4-Benzylthioquinazoline (3f). IR (KBr) 1259(m),
1322(s), 1333(s), 1495(s), 1545(s), 1565(s), 1910(w),
2933(m), 2983(m). LRMS: 252 (M+), 162 (ꢀC7H7),
129 (ꢀSꢀC7H7), 75 (C6H4).
3.2.3.9. 4-Isopropylthioquinazoline (3i). IR (CHCl3)
1258(m), 1323(s), 1333(s), 1487(s), 1542(s), 1565(s),
2466(w), 2935(m), 2969(m). LRMS: 204 (M+), 162
(ꢀC3H7), 129 (ꢀSꢀC3H7), 75 (C6H4).
1H NMR (300 MHz, CDCl3) l 9.02s (H2), 8.05ddd
1H J=8.24, 1.37, 0.55 (H5), 7.96d 1H J=8.24 (H8),
7.83dt 1H J=8.24, 1.37 (H7), 7.55dt 1H J=8.24, 1.37
Hz (H6), 7.42–7.22m 5H (H2%, H3%, H4%, H5%, H6%).
13C NMR l 172.8, 153.4, 147.9, 136.8, 133.7, 129.1,
128.6, 128.4, 127.4, 127.3, 123.7, 123.6, 33.7.
1H NMR (300 MHz, CDCl3) l 8.91s (H2), 7.97–
7.92m 1H (H5), 7.85d 1H J=8.52 (H8), 7.75–7.68m
1H (H7), 7.48–7.40m 1H (H6), 4.32–4.17m 1H (CH),
1.43d 6H J=7.14 Hz (CH3).
Table 1
Characteristics of the compounds
Comp.
R
M.p. (°C)
M.p. (°C)
33–34 [10]
Yield (%)
Molecular formula
10H10N2S
MW
3a
3b
3c
3d
3e
3f
3g
3h
3i
C2H5
C3H7
C4H9
C6H13
32–34
33–35
oil
75
75
80
74
70
80
78
80
83
64
C
190.27
204.29
218.32
246.37
386.64
252.33
264.36
201.27
204.29
218.32
C11H12N2S
C12H14N2S
C14H18N2S
C24H38N2S
C15H12N2S
C16H14N2S
C11H9N2S
C11H12N2S
C12H14N2S
oil
C16H33
31–33
89–91
oil
oil
oil
CH2C6H5
CH2CH2C6H5
CH2CH=CH2
CH(CH3)2
CH2CH(CH3)2
103–4 [11]
oil a [12]
3j
oil
a B.p. 150°C [7,8].

728
J. Kunesˇ et al. / Il Farmaco 55 (2000) 725–729
Table 2
Antimycobacterial activity (MIC, mmol/l) of 4-alkylthioquinazolines (INH=isoniazide)
Mycobacterium
INH
Comp.
a
b
c
d
e
f
g
h
i
j
M. tubercululosis CNCTC TBC 1/47
M. kansasii CNCTC My 235/80
M. fortuitum CNCTC My 187/73
M. a6ium CNCTC My 66/72
M. a6ium D 5/93
M. a6ium CNCTC My 80/72
M. intracellulare D 39/93
M. intracellulare D 38/92
4
500
60
250
62
125
250
62
125
125
125
125
500
250
250
63
63
63
63
32
32
32
32
32
125
500
63
63
63
125
125
125
500
63
125
63
125
63
63
63
250
250
250
250
250
125
250
125
32
63
125
63
125
125
125
63
125
250
125
125
\1000
\1000
\1000
\1000
\1000
\1000
\1000
125
63
32
63
63
32
32
63
125
250
125
125
500
63
\1000
500
63
63
\1000
250
63
13C NMR l 171.5, 153.4, 147.8, 133.3, 128.6, 126.9,
123.7, 123.7, 34.9, 22.7.
quinazoline skeleton, out of which seven had not been
described in the literature as yet. The structures of the
1
substances were corroborated by IR, MS, H and 13C
3.2.3.10. 4-Isobutylthioquinazoline (3j). IR (CHCl3)
1258(m), 1321(s), 1333(s), 1486(s), 1543(s), 1565(s),
1911(w), 2483(w), 2929(m), 2964(m). LRMS: 218 (M+),
162 (ꢀC4H9), 129 (ꢀSꢀC4H9), 75 (C6H4).
NMR spectra. The IR spectra of the quinazoline
derivatives showed characteristic CꢀHarom vibrations in
the range of 3079–3045 cm−1, CꢀHalif in the range of
2977–2855 cm−1, and the bands of CꢀC and CꢀN
bonds of aromatic cycles in the range of 1565–1486
cm−1. A molecular fragment at m/z 129 corresponding
to the quinazoline skeleton, and molecular fragments
indicative of the individual alkyl and alkylthio groups
were evident in the mass spectra. The structures of the
1H NMR (300 MHz, CDCl3) l 8.95s (H2), 8.10d 1H
J=8.24 (H5), 7.93d 1H J=8.24 (H8), 7.81dt 1H J=
8.24, 1.37 (H7), 7.55dt 1H J=8.24, 1.37 (H6), 3.29d
2H J=6.60 (CH2), 2.13–1.97m 1H (CH), 1.08d 6H
J=6.60 Hz (CH3).
13C NMR l 171.8, 153.4, 147.8, 133.5, 128.7, 127.2,
124.0, 123.9, 37.8, 28.3, 22.0.
1
compounds were also confirmed by NMR. In the H
NMR spectra, the signal of H2 appeared as a singlet in
the range of 9.02–8.90 ppm, H5 and H8 were observed
mostly as doublets in the range of 8.10–7.96 and
7.96–7.89 ppm, and H7 and H6 mostly as triplets in the
range of 7.88–7.69 ppm and 7.60–7.41 ppm. The spec-
tra also contained the signals of the substituents at-
tached to sulphur in position 4.
The compounds were subjected to antitubercular ac-
tivity assays, and the results are summarized in Table 2.
As a result of this evaluation, a few conclusions could
be made.
3.3. Microbiology
To evaluate the antimycobacterial activity of the
substances in vitro, the following strains were used:
Mycobacterium tuberculosis CNCTC TBC 1/47, My-
cobacterium kansasii CNCTC My 235/80, Mycobac-
terium fortuitum CNCTC My 187/73, Mycobacterium
a6ium CNCTC My 66/72, Mycobacterium a6ium D
5/93, Mycobacterium a6ium CNCTC My 80/72, My-
cobacterium intracellulare D 39/93 and Mycobacterium
intracellulare D 38/92.
In case of derivatives with an unbranched alkyl in the
molecule, the activity depends on the length of this
chain, with a maximum for a four-carbon residue.
Further lengthening of the chain leads to a decrease of
activity and cetylderivative was very poorly active.
Branching of the chain leads to antitubercular com-
pounds as well: branching on the a-carbon as opposed
to branching on the b-carbon increases the activity.
When an unsaturated alkyl is bound to sulphur in
position 4, the antitubercular activity decreases. Impor-
tant antitubercular activity was found in the case of
compounds with the benzylthio and 2-phenylethylthio
groups in position 4; the latter was the second most
active substance of the series. The most active deriva-
tive of the set was 4-butylthioquinazoline. Its activity,
especially against atypical strains of mycobacteria, was
The antimycobacterial activities of the compounds
&
against these strains were determined in the Sula
semisynthetic medium (SEVAC, Prague). The com-
pounds were added to the medium in dimethylsulfoxide
solutions. The following concentrations were used:
1000, 500, 250, 125, 62 and 31 mmol/l. Minimum
inhibitory concentrations (MICs) were determined after
incubation at 37°C for 14 days. MIC was the lowest
concentration of a substance, at which the inhibition of
the growth of mycobacteria occurred.
4. Results and discussion
In the course of this work, we prepared ten com-
pounds with different substituents at position 4 of the

J. Kunesˇ et al. / Il Farmaco 55 (2000) 725–729
729
&
[3] K. Waisser, J. Kunesˇ, M. Macha´cˇek, E. Sido´ova´, Z. Odlerova´,
Vztahy mezi chemickou strukturou la´tek a jejich protituberku-
much higher as compared to the activity of the clini-
cally used antitubercular isoniazide.
&
lo´zn´ı aktivitou: 6-acylamido-2-alkylthiobenzothiazoly, Cesk.
Farm. 36 (1987) 137. Chem. Abstr. 107 (1987) 74109s.
[4] M. Macha´cˇek, J. Kunesˇ, E. Sido´ova´, Z. Odlerova´, K. Waisser,
This study thus represents a further confirmation of
the hypothesis of the alkylthio group bound to an
electron-deficient carbon atom being a pharmacophore
of antitubercular activity, as the results fall well in line
with it.
&
Vztahy mezi chemickou strukturou la´tek a jejich antimykobakte-
ria´ln´ı aktivitou vu˚cˇi atypicky´m kmenu˚m. II. 6-acylamido-2-
alkylthiobenzothiazoly, kvantitativn´ı vztahy ke spektru u´cˇinku˚,
&
Cesk. Farm. 38 (1989) 9. Chem. Abstr. 111 (1989) 4058h.
&
[5] K. Waisser, J. Kunesˇ, A. Hraba´lek, M. Macha´cˇek, Z. Odlerova´,
New group of potential antituberculotics: 5-alkylthio-1-aryltetra-
zoles, Collect. Czech. Chem. Commun. 61 (1996) 791.
Acknowledgements
&
[6] J. Kunesˇ, A. Hraba´lek, M. Pour, M. Pilarˇ, K. Waisser, Z.
Odlerova´, 5-alkylthio-1-aryltetrazoly — potencialno protitu-
berkuleznye reparaty, Zh. Org. Khim. 34 (1998) 786. Chem.
Abstr. 130 (1999) 223214b.
This study was supported by the Ministry of Educa-
tion of the Czech Republic, (Project CEZ J 13/98:
111600001, and Project Nos. VS97124 and LB98233).
[7] V. Klimesˇova´, M. Svoboda, K. Waisser, M. Pour, J. Kaustova´,
New pyridine derivatives as potential antimicrobial agents, Far-
maco 54 (1999) 666.
[8] M.M. Endicott, E. Witk, M. Mercury, M.L. Sherrill, Quinazo-
line derivatives, J. Am. Chem. Soc. 68 (1946) 1299.
[9] N.J. Leonard, D. Curtin, Preparation of 4-mercapto- and 4-
aminoquinazolines, J. Org. Chem. 11 (1946) 349.
References
&
[1] K. Waisser, V. Klimesˇova´, Z. Odlerova´, Antituberculotics. LXX.
[10] D.J. Fry, J.D. Kendall, A.J. Morgan, The reactivity of the
alkylthio group in nitrogen ring compounds. Part IV. Quar-
ternary Salts of 4-Substituted Quinazolines, J. Chem. Soc. (1960)
5062.
[11] J. Tulecki, J. Kalinowska-Torz, Substances protecting against
radioactivity X: 4-thioquinazolines, Ann Pharm. 6 (1967) 69.
[12] A.S. Narang, A.N. Kaushal, B.K. Bahl, K.S. Narang, Thiope-
gan derivatives XLIV. Syntheses of 3-substituted-4,11-thiopega-
nium 2,9,11-triene perchlorates, Indian J. Appl. Chem 33 (1970)
228. Chem. Abstr. 74 (1970) 141683q.
The alkylthiogroup bound to the electron-deficient atom of
carbon as the pharmacophore of antituberculotic activity, Folia
Pharm. Univ. Carol. 18 (1995) 31. Chem. Abstr. 123 (1995)
107578e.
&
[2] K. Waisser, J. Kunesˇ, M. Macha´cˇek, E. Sido´ova´, Z. Odlerova´,
Vztahy mezi chemickou strukturou a protituberkulo´zn´ı ktivitou
ve skupineˇ 2-alkylthio-6-(bicyklo[2.2.1]-hept-5-en-2,3-dikarbox-
imido)benzothiazolu, Cesk. Farm. 35 (1986) 58. Chem. Abstr.
&
105 (1986) 3362s.
.