Synthesis of Novel Tetrazole Containing Quinoline and 2,3,4,9-Tetrahydro-1H-β-Carboline Derivatives

Article abstract of DOI:10.1002/jhet.2546

This presentation describes the successful synthesis of novel tetrazole-based quinoline and tetrahydro-1H-β-carboline derivatives via one-pot multicomponent reactions in moderate to good yields. These reactions have presumably proceeded through Ugi-azide or Ugi-azide/Pictet–Spengler processes, respectively.

Full text of DOI:10.1002/jhet.2546

Month 2015
Synthesis of Novel Tetrazole Containing Quinoline and 2,3,4,9-
Tetrahydro-1H-β-Carboline Derivatives
Mehdi Ghandi,* Shahnaz Rahimi, and Nahid Zarezadeh
School of Chemistry, College of Science, University of Tehran, Tehran, P.O. Box 14155 6455, Iran
*
E-mail: Ghandi@khayam.ut.ac.ir
Received September 9, 2014
DOI 10.1002/jhet.2546
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
This presentation describes the successful synthesis of novel tetrazole-based quinoline and tetrahydro-1H-
β-carboline derivatives via one-pot multicomponent reactions in moderate to good yields. These reactions
have presumably proceeded through Ugi-azide or Ugi-azide/Pictet–Spengler processes, respectively.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
activities such as anti-inflammatory [8], antimalarial [9],
anticancer [10], analgesic [11], and antifungal [12]. In
addition, quinoline-containing compounds have been
extensively used in medicinal chemistry because of the
presence of this core structure in a number of commercial
drugs including quinine [13], chloroquine [14], mefloquine
[15], and amodiaquine [16].
The known properties of privileged tetrazole heterocy-
cles [17] present in many important biological compounds
and drugs such as losartan and valsartan, the two widely
used angiotensin receptor blockers [18] and in clinical
phase drug BMS-317180 as a potent orally available
ligand of the growth hormone secretagogue [19] along
with the documented above-mentioned properties of
quinoline-containing compounds and our own interest in
IMCRs [20] prompted us to undertake a study on the
synthesis of novel 1,5-DS-1H-T based quinoline and
tetrahydro-1H-β-carboline derivatives via one-pot multi-
component reactions.
Multi-component reactions (MCRs) are processes in
which at least three different simple substrates react in
one-pot to give the target materials [1]. These reactions,
which have gained significant attention during the past
years, do not occur through a single-step procedure, but
rather via several sequential steps involving cascades or
domino reactions [2]. Simplicity, greater efficiency, and
atom economy with generation of molecular complexity
and diversity in one-pot transformations are some advan-
tages of these reactions [3]. These reactions are highlighted
as diversity-oriented syntheses and can be extended to
combinatorial strategies [4].
Theisocyanide-basedmulticomponentreactions(IMCRs)
5] have emerged as efficient and powerful tools for the
[
synthesis of highly complex natural and diverse drug-like
compounds. The most popular IMCR is probably the Ugi
reaction, in which a carboxylic acid, a primary amine, an
aldehyde, and an isocyanide react in a one-pot manner to
afford an N-substituted acyl aminoamide containing four
independently varying groups in one reaction [6]. The
Ugi-azide reaction, a variant of the Ugi multicomponent
process,inwhichthecarboxylicacidisreplacedbyhydrazoic
RESULTS AND DISCUSSION
In this work, we describe the one-pot synthesis of
tetrazole-based quinolines, which have the 1,5-DS-1H-T
ring system based on the Ugi-azide method. For this,
2-chloroquinoline-3-carbaldehydes 3a–b were initially
synthesized using the previously reported procedure
starting from amines 1a–b (Scheme 1) [21]. Reaction of
acid or trimethylsilyl azide (TMSN ) has been utilized for
3
preparation of novel biologically promising 1,5-disubsti-
tuted-1H-tetrazole (1,5-DS-1H-T) [7].
Quinoline-containing compounds have been extensively
used in medicinal chemistry because of various biological
©
2015 HeteroCorporation

M. Ghandi, S. Rahimi, and N. Zarezadeh
Vol 000
Scheme 1. Synthesis of aldehydes 3a–b.
À1
1
13
a combination of aldehydes 1a–b, various amines 4a–f,
spectrophotometer, in cm . H and C NMR spectra
were recorded on a B400 Bruker Avance III 400-MHz
isocyanides 5a–b, and TMSN using the Ugi standard con-
3
1
13
ditions in MeOH afforded DS-1H-T 6a–k in moderate to
spectrometer at 400 ( H) and 100MHz ( C) using CDCl
3
excellent yields (Scheme 2, Table 1). The structure of
as solvent and with the residual solvent signal as internal
6
a–k was confirmed from analytical data.
reference (CDCl , 7.24 and 77.0ppm). Mass spectra of
3
In the next step, we decided to use the Pictet–Spengler
the products were obtained with an HP (Agilent technolo-
gies) 5937 Mass Selective Detector. Elemental analyses
were carried out by a CHN-Rapid Heraeus elemental ana-
lyzer (Wellesley, MA).
reaction [22] method for the construction of tetrahydro-β-
carboline (THBC), which is abundantly found in the plant
and animal kingdom, and many exhibit potent biological
activities [23]. Therefore, the described Ugi-azide proce-
dure was carried out with aldehydes 1a–b, isocyanides
Representative procedure for the synthesis of 6a–k. To a
stirring solution of 2-chloroquinoline-3-carbaldehyde
(1.0 mmol) in MeOH (5 mL) was added amine
(1.0 mmol), and the mixture was stirred for 10min.
Isocyanide (1.0 mmol) and TMIS (0.115 g, 1.0 mmol)
were then added and the mixture stirred for 24h at room
temperature. After completion as indicated by TLC, the
solid product was filtered and washed with MeOH and
EtOH. Recrystallization of the solid from EtOH finally
afforded the products 6a–k.
5
a–b, TMSN , and tryptamine followed by addition of
3
formaldehyde and trifluoroacetic acid (Table 2). To our de-
light, the novel quinoline-based 2-tetrazolylmethyl-2,3,4,9-
tetrahydro-1H-β-carbolines 7a–d were obtained within
5min in moderate to good yields (Table 2). As was ex-
pected, the cyclization of the presumably generated 7a–d
Fig. 1) under the Pictet–Spengler condition has proceeded
1
(
successfully to the corresponding tetrazole-based 2,3,4,9-
tetrahydro-1H-β-carboline scaffolds.
N-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
In conclusion, one-pot, four and five component reac-
tions respectively for the synthesis of quinoline-1,5-DS-
hyl)aniline (6a). White solid Yield: 79%; mp 229–231°C;
À1
1
IR (KBr) 3292 (NH), 1599, 1389, 1293cm ; H NMR
(500 MHz, DMSO): δ 1.21–2.02 (10H, m, 5CH2 of
cyclohexyl), 4.29–4.49 (1H, m, CH of cyclohexyl), 5.33
(1H, d, J 8.2 Hz, CHNH), 6.31 (1H, d, J 8.2 Hz,
CHNH), 6.72 (2H, d, J 7.8 Hz, Ar), 6.78 (1H, t, J
7.4 Hz, Ar), 7.17 (2H, t, J 7.7 Hz, Ar), 7.51 (1H, t,
J 7.5 Hz, Ar), 7.72 (1H, t, J 8.1 Hz, Ar), 7.77 (1H, d, J
8.7 Hz, Ar), 8.00 (1H, d, J 8.4 Hz, Ar), 8.51 (1H, s, Ar);
1H-T or quinoline-2,3,4,9-tetrahydro-1H-β-carboline-1,5-
DS-1H-T derivatives were described. Overall, a number
of the desired products were obtained in moderate to good
yields based on the Ugi-azide or Ugi-azide/Pictet–Spengler
processes. These new structures broaden the quinoline and
tetrahydro-1H-β-carboline scaffolds, and many of them
may represent interesting pharmacophores.
13
C NMR (125MHz, DMSO): δ 24.7 (CH ), 25.1(CH ),
2
2
2
5.2 (CH ), 32.9 (CH ), 33.1 (CH ) 49.6 (CHNH), 58.6
2 2 2
EXPERIMENTAL
(CH of cyclohexyl), 113.8 (2C), 119.6, 127.3, 127.5,
28.1, 128.2, 129.2, 129.6 (2C), 131.1, 138.3, 144.9,
1
+
All commercially available chemicals and reagents were
purchased from Merck Chemical Company and used with-
out further purification. Melting points were determined
with an Electrothermal model 9100 apparatus and are un-
corrected. IR spectra were recorded on a Shimadzu 4300
147.4, 148.6, 153.6 (C―Ar); ms: m/z (%) 418 (77, M
35
+ 37
[ Cl]), 420 (26, M [ Cl]), 336 (6), 267 (100), 244 (7),
231 (59), 216 (14). Anal. Calcd for C H ClN O: C,
22
17
2
65.94; H, 5.53; N, 20.06%. Found: C, 65.86; H, 5.75; N,
19.96%.
Scheme 2. Synthesis of tetrazole-based quinolones 6a–k.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Tetrazole Containing Quinoline and -1H-β-Carboline Derivatives
Table 1
Synthesis of tetrazole-based quinolones 6a–k.
a
Entry
1
Quinolines
Isocyanide
Amine
Product
Yield (%)
79
4
4
a
a
5
5
a
3
3
a
a
6a
2
65
b
6
6
b
c
3
4
72
74
4
4
a
a
3
3
a
a
5c
5d
6
6
d
e
5
6
85
70
4
4
a
a
3
3
a
a
5
5
e
f
6
6
f
7
8
76
68
4
4
a
3
3
b
a
5
5
d
b
g
b
6h
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Ghandi, S. Rahimi, and N. Zarezadeh
Vol 000
Table 1
(
Continued)
a
Entry
9
Quinolines
Isocyanide
Amine
Product
Yield (%)
78
76
4
4
4
b
b
b
3
3
3
a
a
b
5c
6i
1
1
0
5
5
d
d
6
6
j
1
76z
k
a
Isolated yields.
N-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
hyl)-4-methylaniline (6b).
(125 MHz, DMSO): δ 21.3 (Me), 24.4 (CH ), 24.6
2
White solid; Yield: 65%; mp
51–253°C; IR (KBr) 3299 (NH), 1617, 1387,
(2CH ), 32.4 (CH ), 32.7 (CH ), 48.8 (CHNH), 57.4 (CH
2
2
2
2
1
of cyclohexyl), 110.6, 114.1, 118.9, 126.8, 127.5, 127.8,
128.2, 129.0, 130.2, 131.1, 137.6, 138.3, 146.0, 146.5,
À1
1
293 cm ; H NMR (500MHz, DMSO): δ 1.20–2.05
+
35
(
10H, m, 5CH of cyclohexyl), 2.11 (3H, s, Me), 4.58–
149.1, 153.7 (C―Ar); ms: m/z (%) 432 (76, M [ Cl]),
2
+
37
4
.66 (1H, m, CH of cyclohexyl), 6.43 (1H, d, J 8.6 Hz,
434 (25, M [ Cl]), 281 (100), 245 (79), 216 (12), 152
CHNH), 6.71 (2H, d, J 8.3Hz, Ar), 6.86 (1H, d, J 8.6 Hz,
CHNH), 6.92 (2H, d, J 8.2Hz, Ar), 7.65 (1H, t, J 7.4 Hz,
Ar), 7.82 (1H, t, J 7.4Hz, Ar), 7.99 (1H, d, J 8.4Hz, Ar),
(17), 128 (19). Anal. Calcd for C H ClN : C, 66.58; H,
5.82; N, 19.41%. Found: C, 66.60; H, 5.66; N, 19.53%.
24
25
6
N-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
1
3
8
.04 (1H, d, J 8.0 Hz, Ar), 8.54 (1H, s, Ar); C NMR
hyl)-3,4-dimethylaniline (6d).
White solid; Yield: 74%;
(
(
125 MHz, DMSO): δ 20.0 (Me), 24.4 (CH ), 24.6
mp 243–245°C; IR (KBr) 3305 (NH), 1616, 1388,
1312 cm ; H NMR (500MHz, DMSO): δ 1.20–2.01
2
À1
1
2CH ), 32.4 (CH ), 32.6 (CH ), 49.1 (CHNH), 57.4 (CH
2
2
2
of cyclohexyl), 113.7 (2C), 126.6, 126.8, 127.5, 127.7,
(10H, m, 5CH of cyclohexyl), 2.02 and 2.07 (6H, 2s,
2
1
1
4
28.1, 129.6 (2C), 130.1, 131.1, 137.7, 143.6, 146.5,
2Me ), 4.59–4.67 (1H, m, CH of cyclohexyl), 6.44 (1H,
2
+
35
49.1, 153.7 (C―Ar); ms: m/z (%) 432 (100, M [ Cl]),
d, J 8.7 Hz, CHNH), 6.53 (1H, d, J 7.8 Hz, Ar), 6.66
(1H, s, Ar), 6.82 (1H, d, J 8.4 Hz, Ar), 6.85 (1H, d, J
8.3 Hz, CHNH), 7.64 (1H, t, J 7.5 Hz, Ar), 7.82 (1H, t,
J 7.6 Hz, Ar), 7.99 (1H, d, J 8.4 Hz, Ar), 8.04 (1H, d, J
+
37
34 (33, M [ Cl]), 281 (100), 245 (43), 216 (7), 152
(8), 128 (11). Anal. Calcd for C H ClN : C, 66.58; H,
24 25 6
5
.82; N, 19.41%. Found: C, 66.60; H, 5.66; N, 19.53%.
13
N-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
8.1 Hz, Ar), 8.56 (1H, s, Ar); C NMR (125MHz,
hyl)-3-methylaniline (6c).
White solid; Yield: 72%; mp
DMSO): δ 18.4 (Me), 19.7 (Me), 24.5 (CH ), 24.7
2
2
34–236°C; IR (KBr) 3294 (NH), 1601, 1389, 1305,
(2CH ), 32.5 (CH ), 32.7 (CH ), 49.0 (CHNH), 57.3
2
2
2
À1
1
cm ; H NMR (500MHz, DMSO): δ 1.18–2.02 (10H,
m, 5CH of cyclohexyl), 2.16 (3H, s, Me), 4.58–4.66
(CH of cyclohexyl), 110.9, 115.2, 125.6, 126.8, 127.5,
127.7, 128.1, 130.1, 130.3, 131.1, 136.7, 137.7, 143.9,
2
+
(
(
1H, m, CH of cyclohexyl), 6.46 (1H, br s, CHNH), 6.49
1H, s, Ar), 6.58 (1H, d, J 7.9Hz, Ar), 6.65 (1H, s, Ar),
146.5, 149.2, 153.8 (C―Ar); ms: m/z (%) 446 (74, M
35
+
37
[ Cl]), 448 (24, M [ Cl]), 295 (100), 259 (65), 244
6
.97–7.02 (2H, m, CHNH, Ar), 7.65 (1H, t, J 7.5 Hz,
Ar), 7.83 (1H, t, J 7.6Hz, Ar), 8.00 (1H, d, J 8.4Hz, Ar),
.06 (1H, d, J 8.1 Hz, Ar), 8.55 (1H, s, Ar); C NMR
(16), 216 (10), 203 (7). Anal. Calcd for C H ClN : C,
67.18; H, 6.09; N, 18.80%. Found: C, 67.02; H, 6.25;
N, 18.86%.
25
27
6
1
3
8
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Tetrazole Containing Quinoline and -1H-β-Carboline Derivatives
Table 2
Synthesis of quinoline-based tetrazoles 7a–d.
Aldehyde
Isocyanide
Product
Yield (%)
68
4
4
4
4
a
b
a
b
3
3
a
a
7
a
7
0
7
7
b
7
7
2
9
3
3
b
b
c
7d
N-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
126.8, 127.6, 127.8, 128.1, 130.3, 131.1, 137.8, 139.9,
hyl)-4-methoxyaniline (6e). White solid; Yield: 85%; mp
146.5, 149.2, 152.2, 153.8 (C―Ar); ms: m/z (%) 448
(60, M [ Cl]), 450 (20, M [ Cl]), 344 (5), 296 (100),
+
35
+ 37
2
20–223°C; IR (KBr) 3293 (NH), 1597, 1399,
À1
1
1
339 cm ; H NMR (500MHz, DMSO): δ 1.18–2.06
281 (39), 261 (8), 229 (7). Anal. Calcd for C H ClN O:
24
25
6
(
4
10H, m, 5CH of cyclohexyl), 3.60 (3H, s, OMe), 4.60–
.68 (1H, m, CH of cyclohexyl), 6.40 (1H, d, J 8.8 Hz,
C, 64.21; H, 5.61; N, 18.72%. Found: C, 64.27; H, 5.73;
N, 18.64%.
2
CHNH), 6.67–6.80 (5H, m, CHNH, Ar), 7.66 (1H, t, J
4-chloro-N-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
hyl)aniline (6f). White solid; Yield: 70%; mp 227–230°C; IR
(KBr) 3331 (NH), 1596, 1404, 1291 cm ; H NMR
(500MHz, DMSO): δ 1.20–2.00 (10H, m, 5CH2 of
cyclohexyl), 4.60–4.68 (1H, m, CH of cyclohexyl), 6.50 (1H, d,
J 8.2Hz, CHNH), 6.81 (2H, d, J 8.7Hz, Ar), 7.15 (2H, d, J
7
.4Hz, Ar), 7.83 (1H, t, J 7.3Hz, Ar), 7.99 (1H, d, J
.4Hz, Ar), 8.05 (1H, d, J 8.0Hz, Ar), 8.58 (1H, s, Ar);
À1
1
8
13
C NMR (125 MHz, DMSO): δ 24.5 (CH ), 24.7
2
(
(
2CH ), 32.5 (CH ), 32.7 (CH ), 49.7 (CHNH), 55.1
OMe), 57.4 (CH of cyclohexyl), 114.7 (2C), 115.0 (2C),
2 2 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Ghandi, S. Rahimi, and N. Zarezadeh
Vol 000
Figure 1. Proposed mechanism for the formation of tetrazole-based 2,3,4,9-tetrahydro-1H-β-carboline 7a–d.
8
.7 Hz, Ar), 7.26 (1H, d, J 8.2 Hz, CHNH), 7.65 (1H, t, J 7.4Hz,
(1H, t, J 7.6Hz, Ar), 8.00 (2H, t, J 7.3 Hz, Ar), 8.55 (1H, s,
Ar); C NMR (125MHz, DMSO): δ 20.0 (Me), 28.8 (CMe2),
13
Ar), 7.83 (1H, t, J 7.4 Hz, Ar), 7.99 (1H, d, J 8.4Hz, Ar), 8.06
13
(1H, d, J 7.9 Hz, Ar), 8.49 (1H, s, Ar); C NMR (125MHz,
29.3 (CMe ), 30.4 (CMe ), 31.2 (CMe ), 50.1 (CHNH), 52.7
2
3
3
DMSO): δ 24.4 (CH ), 24.6 (2CH ), 32.4 (CH ), 32.7 (CH ),
(CCH C), 66.2 (CMe ), 113.2 (2C), 126.5, 126.8, 127.6, 127.8,
2
2
2
2
2
2
4
8.8 (CHNH), 57.3 (CH of cyclohexyl), 114.9 (2C), 121.4,
128.1, 129.8 (2C), 130.5, 131.1, 137.9, 143.0, 146.5, 149.1,
+
35
+
126.8, 127.5, 127.8, 128.2, 128.9 (2C), 129.6, 131.2, 137.5,
153.6 (C―Ar); ms: m/z (%) 462 (61, M [ Cl]), 464 (20, M
+
37
1
44.9, 146.6, 149.1, 153.4 (C―Ar); ms: m/z (%) 452 (39, M
[ Cl]), 350 (100), 292 (12), 281 (91), 257 (7), 245 (41). Anal.
3
5
+ 37
[ Cl]), 454 (26, M [ Cl]), 344 (11), 326 (5), 314 (5), 301
100), 265 (30). Anal. Calcd for C H Cl N : C, 60.93; H,
Calcd for C H ClN : C, 67.44; H, 6.75; N, 18.15%. Found:
26
31
6
(
C, 67.48; H, 6.53; N, 18.27%.
23
22
2 6
4.89; N, 18.54%. Found: C, 61.05; H, 4.73; N, 18.62%.
N-((2-chloroquinolin-3-yl)(1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
N-((2-chloro-6-methylquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-
yl)methyl)-3-methylaniline (6i). White solid; Yield: 78%; mp 187–
189°C; IR (KBr) 3316 (NH), 1593, 1395, 1334cm ; H NMR
À1 1
yl)methyl)-3,4-dimethylaniline (6g). White solid; Yield: 76%,
mp 198–200°C; IR (KBr) 3301 (NH), 1590, 1342,
(500MHz, DMSO): δ 0.77 (9H, s, CMe ), 1.84 and 1.87 (6H,
3
À1
1
1
261cm ; H NMR (500MHz, DMSO): δ 1.21–2.01
2s, CMe ), 2.02 (1H, d, J 14.9Hz, CCHC), 2.15 (3H, s, Me),
2
(
2
10H, m, 5CH of cyclohexyl), 2.02 and 2.07 (6H, 2s,
2.24 (1H, d, J 14.9Hz, CCHC), 6.43–6.51 (3H, m, CHNH, Ar),
6.57 (1H, s, Ar), 6.99 (1H, t, J 7.7 Hz, Ar), 7.12 (1H, d, J
9.1 Hz, CHNH), 7.65 (1H, t, J 7.5Hz, Ar), 7.83 (1H, t, J 7.6 Hz,
Ar), 7.96 (1H, d, J 8.5Hz, Ar), 8.04 (1H, d, J 8.1 Hz, Ar), 8.54
2
Me ), 2.45 (3H, s, Me), 4.60–4.67 (1H, m, CH of
2
cyclohexyl), 6.41 (1H, d, J 8.8 Hz, CHNH), 6.51 (1H, d, J
7
6
7
.8Hz, Ar), 6.64 (1H, s, Ar), 6.80 (1H, d, J 9.1Hz, Ar),
.84 (1H, d, J 8.2Hz, CHNH), 7.64 (1H, d, J 8.5Hz, Ar),
.78 (1H, s, Ar), 7.87 (1H, d, J 8.5 Hz, Ar), 8.42 (1H, s,
13
(1H, s, Ar); C NMR (125MHz, DMSO): δ 21.3 (Me), 28.7
(CMe ), 29.4 (CMe ), 30.5 (CMe ), 31.2 (CMe ), 49.9 (CHNH),
2
2
3
3
13
Ar); C NMR (125MHz, DMSO): δ 18.4 (Me), 19.7 (Me),
1.0 (Me), 24.5 (CH ), 24.7 (2CH ), 32.5 (CH ), 32.7
52.8 (CCH C), 66.3 (CMe ), 109.9, 113.6, 118.9, 126.8, 127.6,
2 2
2
127.8, 128.2, 129.2, 130.6, 131.1, 137.9, 138.5, 145.4, 146.5,
2
2
2
+
35
(CH ), 48.9 (CHNH), 57.4 (CH of cyclohexyl), 110.9,
149.1, 153.6 (C―Ar); ms: m/z (%) 462 (25, M [ Cl]), 464 (8,
2
+
37
1
15.2, 125.5, 126.7, 126.8, 127.2, 130.0, 130.1, 133.2,
M [ Cl]), 448 (11), 350 (75), 296 (27), 281 (100), 257 (7).
1
36.7, 137.0, 137.5, 144.0, 145.1, 148.2, 153.8 (C―Ar);
Anal. Calcd for C H ClN : C, 67.44; H, 6.75; N, 18.15%.
Found: C, 67.48; H, 6.53; N, 18.27%.
26
31
6
+
35
+ 37
ms: m/z (%) 460 (45, M [ Cl]), 462 (15, M [ Cl]), 364
7), 309 (100), 295 (11), 273 (71), 258 (19). Anal. Calcd for
C H ClN : C, 67.74; H, 6.34; N, 18.23%. Found: C,
(
N-((2-chloroquinolin-3-yl)(1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methyl)-3,4-dimethylaniline (6j). White solid; Yield: 76%; mp
26
29
6
À1
1
67.66; H, 6.12; N, 18.21%.
197–199°C; IR (KBr) 3311 (NH), 1614, 1397, 1312cm ; H
N-((2-chloroquinolin-3-yl)(1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-
NMR (500MHz, DMSO): δ 0.77 (9H, s, CMe ), 1.84 and 1.88
3
5
-yl)methyl)-4-methylaniline (6h). White solid; Yield: 68%, mp
(6H, 2s, CMe ), 2.00–2.06 (7H, m, 2Me , CCHC), 2.15 (1H, d,
2
2
À1
1
196–198°C; IR (KBr) 3309 (NH), 1615, 1392, 1327 cm ; H
J 14.9 Hz, CCHC), 6.43 (2H, d, J 9.2Hz, CHNH, Ar), 6.57 (1H,
s, Ar), 6.84 (1H, d, J 8.1 Hz, Ar), 7.02 (1H, d, J 9.4 Hz, CHNH),
7.64 (1H, t, J 7.5 Hz, Ar), 7.82 (1H, t, J 7.6 Hz, Ar), 8.00 (2H, t,
NMR (500MHz, DMSO): δ 0.77 (9H, s, CMe ), 1.85 and 1.88
3
(6H, 2s, CMe ), 2.02 (1H, d, J 14.9Hz, CCHC), 2.09 (3H, s,
2
13
Me), 2.26 (1H, d, J 14.9Hz, CCHC), 6.43 (1H, d, J 9.4Hz,
J 9.3Hz, Ar), 8.55 (1H, s, Ar); C NMR (125MHz, DMSO): δ
CHNH), 6.65 (2H, d, J 8.2 Hz, Ar), 6.92 (2H, d, J 8.2 Hz, Ar),
18.3 (Me), 19.8 (Me), 28.7 (CMe ), 29.4 (CMe ), 30.5 (CMe ),
2
2
3
7.11 (1H, d, J 9.4 Hz, CHNH), 7.64 (1H, t, J 7.6 Hz, Ar), 7.82
31.2 (CMe ), 49.9 (CHNH), 52.7 (CCH C), 66.2 (CMe ), 110.1,
3
2
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Tetrazole Containing Quinoline and -1H-β-Carboline Derivatives
114.6, 125.5, 126.8, 127.6, 127.8, 128.1, 130.3, 130.7, 131.1,
(CH CH N), 57.2 (CH of cyclohexyl), 57.7 (CH), 106.3,
2 2
1
36.9, 137.9, 143.4, 146.5, 149.1, 153.6 (C―Ar); ms: m/z (%)
110.9, 117.4, 118.4, 120.5, 126.5, 126.8, 127.4, 127.7,
128.6, 128.8, 131.4, 131.9, 135.8, 139.7, 146.5, 149.1,
+
35
+ 37
476 (56, M [ Cl]), 478 (19, M [ Cl]), 364 (100), 320 (14),
+
35
306 (18), 295 (97), 259 (45). Anal. Calcd for C H ClN : C,
152.4 (C―Ar); ms: m/z (%) 497 (1, M [ Cl]), 499
27
33
6
+
37
67.98; H, 6.97; N, 17.62%. Found: C, 68.16; H, 7.11; N, 17.54%.
(0.33, M [ Cl]), 292 (22), 215 (35), 171 (100), 143
(74), 115 (20). Anal. Calcd for C28 : C, 67.53; H,
N-((2-chloro-6-methylquinolin-3-yl)(1-(2,4,4-trimethylpentan-2-yl)-
H-tetrazol-5-yl)methyl)-4-methylaniline (6k).
H28ClN
7
1
White solid;
5.67; N, 19.69%. Found: C, 67.59; H, 5.75; N, 19.81%.
Yield: 78%; mp 222–225°C; IR (KBr) 3296 (NH), 1596,
2-((2-chloroquinolin-3-yl)(1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-
À1
1
1387, 1339cm ; H NMR (500 MHz, DMSO): δ 0.77 (9H,
5-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3–23]indole (7b).
White
s, CMe ), 1.84 and 1.88 (6H, 2s, CMe ), 2.02 (1H, d, J
solid; Yield: 70%; mp 205–207°C; IR (KBr) 3278 (NH), 1619,
1399, 1325cm ; H NMR (500MHz, DMSO): δ 0.50 (9H, s,
3
2
À1 1
1
4.9 Hz, CCHC), 2.09 (3H, s, Me), 2.26 (1H, d, J 14.9 Hz,
CCHC), 2.45 (3H, s, Me), 6.41 (1H, d, J 9.4 Hz, CHNH),
.64 (2H, d, J 8.1Hz, Ar), 6.91 (2H, d, J 8.0 Hz, Ar), 7.09
1H, d, J 9.4 Hz, CHNH), 7.64 (1H, d, J 7.8 Hz, Ar), 7.75
CMe ), 1.77–2.01 (8H, m, CMe , CCH C), 2.63 (2H, br s,
3
2
2
6
CH CH N), 3.05 (1H, br s, CH CHN), 3.24 (1H, br s,
2 2 2
CH CHN), 4.00 (2H, AB-q, J 13.9Hz, CH N), 6.42 (1H, s,
2 2
(
13
(
1H, s, Ar), 7.87 (1H, d, J 8.5Hz, Ar), 8.43 (1H, s, Ar);
NMR (125MHz, DMSO): δ 20.0 (Me), 21.0 (Me), 28.8
CMe ), 29.3 (CMe ), 30.5 (CMe ), 31.2 (CMe ), 50.0
C
CH), 6.89–6.97 (2H, m, Ar), 7.22 (1H, d, J 6.7Hz, Ar), 7.30
(1H, d, J 6.4Hz, Ar), 7.67 (1H, br s, Ar), 7.85 (1H, br s, Ar),
7.99 (1H, d, J 7.4 Hz, Ar), 8.16 (1H, d, J 7.1 Hz, Ar), 8.65 (1H,
(
2
2
3
3
13
(
CHNH), 52.7 (CCH C), 66.2 (CMe ), 113.0 (2C), 126.5,
s, Ar), 10.66 (1H, s, NH); C NMR (125 MHz, DMSO): δ
2
2
1
26.8, 127.3, 127.6, 129.8 (2C), 130.4, 133.1, 137.3, 137.6,
21.9 (CH CH N), 29.1 (CMe ), 30.0 (CMe ), 31.0 (CMe ),
46.4 (CH N), 47.0 (CH CH N), 52.5 (CCH C), 58.8 (CH),
2 2 2 2
2
2
2
3
3
+
1
43.1, 145.1, 148.2, 153.6 (C―Ar); ms: m/z (%) 476 (30, M
3
5
+ 37
[
Cl]), 478 (10, M [ Cl]), 462 (19), 364 (70), 350 (44),
65.6 (CMe ), 106.3, 110.8, 117.3, 118.3, 120.4, 126.3, 126.5,
2
2
95 (100), 281 (60). Anal. Calcd for C H ClN : C, 67.98;
126.9, 127.5, 127.9, 128.7, 131.7, 132.0, 135.8, 140.9, 146.4,
27
33
6
+
35
H, 6.97; N, 17.62%. Found: C, 68.16; H, 7.11; N, 17.54%.
Representative procedure for the synthesis of 7a–d. To a
stirring solution of 2-chloroquinoline-3-carbaldehyde
149.9, 152.7 (C―Ar); ms: m/z (%) 527 (1, M [ Cl]), 529
+
37
(0.33, M [ Cl]), 345 (5), 245 (8), 187 (49), 171 (100), 143
(83). Anal. Calcd for C30 : C, 68.23; H, 6.49; N,
H
34ClN
7
(
(
(
1.0 mmol) in MeOH (5 mL) was added tryptamine
0.160 g, 1.0mmol), isocyanide (1.0 mmol), and TMIS
0.115 g, 1.0mmol) and the mixture stirred for 6h at
18.57%. Found: C, 68.15; H, 6.61; N, 18.53%.
2-((2-chloro-6-methylquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
hyl)-2,3,4,9-tetrahydro-1H-pyrido[3–23]indole (7c).
White solid;
room temperature. Formaldehyde solution (0.122 cc,
7.0% in MeOH, 1.5 mmol) and TFA (0.228 g, 2.0 mmol)
Yield: 72%; mp 196–198°C; IR (KBr) 3296 (NH), 1592, 1339,
1307cm ; H NMR (500 MHz, DMSO): δ 1.15–1.97 (10H,
À1
1
3
were then added and the mixture stirred for 15 min. After
completion as indicated by TLC, the solvent was
evaporated under reduced pressure. The crude was then
dissolved in DCM (20 mL) and washed with saturated
NaHCO3 (10 mL) and brine (10mL) solutions,
respectively. The organic layer was dried over anhydrous
Na SO . After evaporation of the solvent under reduced
m, 5CH of cyclohexyl), 2.47 (3H, s, Me), 2.74 (2H, br s,
2
CH CH N), 2.92–3.05 (2H, m, CH CH N), 3.80 (2H, AB-q, J
2
2
2
2
14.3Hz, CH N), 4.81 (1H, br s, CH of cyclohexyl), 6.10 (1H,
2
s, CH), 6.93 (1H, t, J 7.3Hz, Ar), 7.00 (1H, t, J 7.3Hz, Ar),
7.25 (1H, d, J 7.8 Hz, Ar), 7.36 (1H, d, J 7.5 Hz, Ar), 7.67 (1H,
d, J 8.5Hz, Ar), 7.86 (1H, d, J 8.5Hz, Ar), 7.95 (1H, s, Ar),
13
8.74 (1H, s, Ar), 10.66 (1H, s, NH); C NMR (125 MHz,
2
4
pressure, the crude product was purified by column
chromatography on silica gel using a mixture of Hex-
AcOEt (3:1 V/V) as eluent to afford compounds 7a–d.
DMSO): δ 21.1 (Me), 21.5 (CH CH N), 24.4 (CH ), 24.6
2
2
2
(CH ), 24.7 (CH ), 32.7 (CH ), 32.9 (CH ), 47.4 (CH N), 47.9
2
2
2
2
2
(CH CH N), 57.2 (CH of cyclohexyl), 57.6 (CH), 106.4, 110.9,
2
2
2
-((2-chloroquinolin-3-yl)(1-cyclohexyl-1H-tetrazol-5-yl)met
117.4, 118.4, 120.5, 126.5, 126.8, 127.2, 127.3, 128.7, 131.9,
hyl)-2,3,4,9-tetrahydro-1H-pyrido[3–23]indole (7a).
White
solid; Yield: 68%; mp 209–211°C; IR (KBr) 3280 (NH),
133.6, 135.8, 137.5, 138.9, 145.1, 148.2, 152.5 (C―Ar); ms:
m/z (%) 511 (1, M [ Cl]), 513 (0.33, M [ Cl]), 295 (8), 259
(8), 217 (9), 190 (17), 171 (100). Anal. Calcd for C29H30ClN :
7
+
35
+ 37
À1
1
1
619, 1392, 1330cm ; H NMR (500MHz, DMSO): δ
1
.15–1.97 (10H, m, 5CH of cyclohexyl), 2.74 (2H, br s,
C, 68.02; H, 5.91; N, 19.15%. Found: C, 67.93; H, 6.07; N,
19.27%.
2
CH CH N), 2.97–3.05 (2H, m, CH CH N), 3.81 (2H,
2
2
2
2
AB-q, J 13.9Hz, CH N), 4.83 (1H, br s, CH of
cyclohexyl), 6.13 (1H, s, CH), 6.90–7.02 (2H, m, Ar),
2-((2-chloro-6-methylquinolin-3-yl)(1-(2,4,4-trimethylpentan-2-
yl)-1H-tetrazol-5-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]in
dole (7d). White solid; Yield: 79%; mp 231–234°C; IR
2
7
7
.25 (1H, d, J 7.7 Hz, Ar), 7.36 (1H, d, J 7.5 Hz, Ar),
.67 (1H, t, J 7.2 Hz, Ar), 7.84 (1H, t, J 7.3 Hz, Ar), 7.98
À1
1
(KBr) 3296 (NH), 1630, 1375, 1340cm ; H NMR
(
(
1H, d, J 8.2Hz, Ar), 8.21 (1H, d, J 7.4Hz, Ar), 8.88
1H, s, Ar), 10.66 (1H, s, NH); C NMR (125MHz,
(500MHz, DMSO): δ 0.50 (9H, s, CMe ), 1.77 and 1.85
3
1
3
(6H, 2s, CMe ), 1.92 (2H, AB-q, J 15.1Hz, CCH C), 2.46
2
2
DMSO): δ 21.4 (CH CH N), 24.4 (CH ), 24.5 (CH ),
(3H, s, Me), 2.60–2.63 (2H, m, CH CH N), 3.00–3.04 (1H,
2 2
2
2
2
2
2
4.7 (CH ), 32.8 (CH ), 32.9 (CH ), 47.4 (CH N), 47.9
m, CH CH N), 3.22–3.26 (1H, m, CH CH N), 3.99 (2H,
2 2 2 2
2
2
2
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Ghandi, S. Rahimi, and N. Zarezadeh
Vol 000
AB-q, J 14.2Hz, CH N), 6.40 (1H, s, CH), 6.89 (1H, t, J
[10] Alqasoumi, S. I.; Al-Taweel, A. M.; Alafeefy, A. M.;
Noaman, E.; Ghorab, A. M. Eur J Med Chem 2010, 45, 738.
2
7
7
8
8
.1 Hz, Ar), 6.97 (1H, t, J 7.2 Hz, Ar), 7.22 (1H, d, J
.7 Hz, Ar), 7.30 (1H, d, J 7.4Hz, Ar), 7.67 (1H, d, J
.4 Hz, Ar), 7.88 (1H, d, J 7.7Hz, Ar), 7.89 (1H, s, Ar),
[
11] (a) Milyutin, A. V.; Amirova, L. R.; Kolla, V. E.;
Nazmetdinov, F. Ya.; Drovosekova, L. P.; Andreichikov, Yu. S. Pharm
Chem 1998, 32, 422; (b) Nekrasov, D. D.; Chizh, V. G.;
J
13
AndreichikovYu, S.; Tul’bovich, G. A.; Aleksandrova, G. A. Pharm
Chem J 1997, 31, 140.
[12] Musiol, R.; Serda, M.; Hensel-Bielowka, S.; Polanski, J.
Curr Med Chem 2010, 17, 1960.
.53 (1H, s, Ar), 10.65 (1H, s, NH); C NMR (125MHz,
DMSO): δ 21.0 (Me), 21.9 (CH CH N), 29.1 (CMe ), 30.0
2
2
2
(
CMe ), 31.0 (CMe ), 46.5 (CH N), 47.0 (CH CH N), 52.5
3 3 2 2 2
[13] (a) Gelb, M. H. Curr Opin Chem Biol 2007, 11, 440;
(
CCH C), 58.8 (CH), 65.5 (CMe ), 106.3, 110.9, 117.3,
2
2
(b) Wiesner, J.; Ortmann, R.; Jomaa, H.; Schlitzer, M. Angew Chem Int
118.3, 120.4, 126.2, 126.5, 126.7, 127.2, 127.3, 132.0,
Ed 2003, 42, 5274.
1
33.8, 135.8, 137.7, 140.2, 145.1, 149.0, 152.7 (C―Ar);
[14] Sharma, N.; Mohanakrishnan, D.; Sharma, U. K.; Richa, R. K.;
Arun Sinha, A. K.; Sahal, D. Eur J Med Chem 2014, 79, 350.
+
35
+ 37
ms: m/z (%) 541 (1, M [ Cl]), 543 (0.33, M [ Cl]), 359
5), 259 (8), 230 (9), 217 (11), 171 (100). Anal. Calcd for
C H ClN : C, 68.68; H, 6.69; N, 18.09%. Found: C,
[15] Gonçalves, R. S. B.; Kaiser, C. R.; Lourenço, M. C. S.;
(
de Souza, M. V. N.; Wardell, J. L.; Wardell, S. M. S. E.; da Silva, A. D.
Eur J Med Chem 2010, 45, 6095.
31
36
7
68.76; H, 6.53; N, 17.81%.
[16] Ongarora, D. S. B.; Gut, J.; Rosenthal, P. J.;
Masimirembwa, C. M.; Chibale, K. Bioorg Med Chem Lett 2012, 22, 5046.
[17] (a)
Cárdenas-Galindo,
L.
E.;
Islas-Jácome,
A.;
Alvarez-Rodríguez, N. V.; El Kaim, L.; Gámez-Montaño, R. Synthesis
2014, 46, 49; (b) Roh, J.; Vávrová, K.; Hrabálek, A. Eur J Org Chem
2012, 6101; (c) Rajasekaran, A.; Thampi, P. P. Eur J Med Chem 2004,
Acknowledgments. The authors wish to thank the Research
Council of the University of Tehran for financial supports.
39, 273.
[18] (a) García, G.; Rodríguez-Puyol, M.; Alajarín, R.; Serrano, I.;
Sánchez-Alonso, P.; Griera, M.; Vaquero, J.; Rodríguez-Puyol, D.;
Alvarez-Builla, J.; Díez-Marques, M. J Med Chem 2009, 52, 7220;
REFERENCES AND NOTES
(
b) Massingham, P. C. R. Eur J Med Chem 1997, 32, 687.
19] Cano, P. A.; Islas-Jácome, A.; González-Marrero, J.;
Yépez-Mulia, L.; Calzada, F.; Gámez-Montaño, R. Bioorg Med Chem
014, 22, 1370.
20] (a) Ghandi, M.; Tabatabaei Ghomi, A.; Kubicki, M. J Org
[
[
1] (a) Liang, B.; Kalidindi, S.; Porco, J. A., Jr.; Stephenson, C. R.
J Org Lett 2010, 12, 572; (b) Ganem, B. Acc Chem Res 2009, 42, 463;
c) Cui, S. L.; Lin, X. F.; Wang, Y. G. Org Lett 2006, 8, 4517.
2] Kriis, K.; Ausmees, K.; Pehk, T.; Lopp, M.; Kanger, T. Org
Lett 2010, 12, 2230.
2
(
[
[
Chem 2013, 78, 2611; (b) Ghandi, M.; Tabatabaei Ghomi, A.;
Kubicki, M. Tetrahedron 2013, 69, 3054; (c) Ghandi, M.; Zarezadeh, N.;
Taheri, A. Tetrahedron Lett 2012, 53, 3353; (d) Ghandi, M.;
Zarezadeh, N.; Taheri, A. Tetrahedron Lett 2011, 52, 1228; (e) Ghandi, M.;
Zarezadeh, N.; Taheri, A. Tetrahedron 2010, 66, 8231.
[21] (a) Wang, G.-B.; Wang, L.-F.; Li, C.-Z.; Sun, J.; Zhou, G.-M.;
Yang, D.-C. Res Chem Intermed 2012, 38, 77; (b) Baruah, B.; Bhuyan, P.
J Tetrahedron 2009, 65,7099.
[
3] (a) Dömling, A. Chem Rev 2006, 106, 17; (b) Banfi, L.;
Riva, R. Org React 2005, 65, 1; (c) Ramón, D. J.; Yus, M. Angew Chem
2
005, 117, 1628.
[
4] (a) Schramm (née Dediu), O. G.; Müller, T. J. J. Synlett 2006,
1
4
3
841; (b) Schreiber, S. L.; Burke, M. D. Angew Chem Int Ed 2004, 43,
6; (c) Burke, M. D.; Berger, E. M.; Schreiber, S. L. Science 2003,
02, 613.
5] (a) Hulme, C.; Gore, V. Curr Med Chem 2003, 10, 51;
b) Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.;
Mathen, J. S.; Balagopal, L. Acc Chem Res 2003, 36, 899; (c) Ugi, I.;
Verner, B.; Dömling, A. Molecules 2003, 8, 53; (d) Zhu, J. Eur J Org
Chem 2003, 2003, 1133.
6] (a) Faggi, C.; García-Valverde, M.; Marcaccini, S.; Menchi, G.
Org Lett 2010, 12, 788; (b) Trifilenkov, A. S.; Ilyin, A. P.; Kysil, V. M.;
[22] (a) Stöckigt, J.; Antonchick, A. P.; Wu, F.; Waldmann, H.
[
Angew Chem Int Ed 2011, 50, 8538; (b) Pictet, A.; Spengler, T. Ber Dtsch
Chem Ges 1911, 44, 2030.
(
[23] (a) Chen, Z.; Cao, R.; Shi, B.; Yi, W.; Yu, L.; Song, H.;
Ren, Z. Chem Pharm Bull 2010, 58, 901; (b) Cao, R.; Guan, X.;
Shi, B.; Chen, Z.; Ren, Z. Eur J Med Chem 2010, 45, 2503; (c) Chen, Z.;
Cao, R.; Shi, B.; Yi, W.; Yu, L.; Song, H. Bioorg Med Chem Lett 2010,
20, 3876; (d) Li, S.; Yang, B.; Zhang, Q.; Zhang, J.; Wang, J.; Wu, W.
Nat Prod Commun 2010, 5, 1591; (e) Rook, Y.; Schmidtke, K.;
Gaube, F.; Schepmann, D.; Wünch, B.; Heilmann, J.; Lhemann, J.;
Winckler, T. J Med Chem 2010, 53, 3611; (f) Tonin, L. T. D.;
Panice, M. R.; Nakamura, C. V.; Rocha, K. J. P.; dos Santos, A. O.;
Ueda-Nakamura, T.; da Costa, W. F.; Sarragiotto, M. H. Biomed
Pharmacother 2010, 64, 386; (g) Winkler, J. D.; Londregan, A. T.;
Hamann, M. T. Org Lett 2006, 8, 2591; (h) Shilabin, A. G.; Kasanah, N.;
Tekwani, B. L.; Hamann, M. T. J Nat Prod 2008, 71,1218; (i) Kawasaki, T.;
Higuchi, K. Nat Prod Rep 2005, 22, 761; (j) Boursereau, Y.; Coldham, I.
Bioorg Med Chem Lett 2004, 14, 5841; (k) Schlecker, W.; Huth, A.;
Ottow, E.; Mulzer, J. Synthesis 1995, 1225; (l) Molina, P.; Fresneda, P. M.;
Zafra, G. S.; Almendros, P. Tetrahedron Lett 1994, 35, 8851;
(m) Molina, P.; Fresneda, P. M. J Chem Soc Perkin Trans 1 1988,
1819; (n) Allen, J. R.; Holmstedt, B. R. Phytochemistry 1979, 19,
1573.
[
Sandulenkoa, Y. B.; Ivachtchenko, A. V. Tetrahedron Lett 2007,
4
8, 2563.
[
7] (a) Cano, P. A.; Islas-Jácome, A.; González-Marrero, J.;
Yépez-Mulia, L.; Calzada, F.; Gámez-Montaño, R. Bioorg Med
Chem 2014, 22, 1370; (b) Safa, K. D.; Shokri, T.; Abbasi, H.;
Teimuri-Mofrad, R. J Heterocyclic Chem 2014, 51, 80; (c) Gunawan, S.;
Hulme, C. Org Biomol Chem 2013, 11, 6036; (d) Ramezanpour, S.;
Balalaie, S.; Rominger, F.; Alavijeh, N. S.; Bijanzadeh, H. R. Tetrahedron
013, 69, 10718; (e) Lin, X. F.; Li, Y.; Li, S. Y.; Xiao, Z. K.; Lu, J. M.
Tetrahedron 2012, 68, 5806; (f) El Kaim, L.; Grimaud, L. Tetrahedron,
009, 65, 2153.
8] Chen, Y. L.; Chen, I. L.; Lu, C. M.; Tzeng, C. C.; Tsaob, L. T.;
Wang, J. P. J Med Chem 2004, 12, 387.
9] Joshi, A. A.; Viswanathan, C. L. Anti-Infect Agents Med
Chem 2006, 5, 105.
2
2
[
[
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet