Discovery of novel methanone derivatives acting as antimycobacterial agents

Article abstract of DOI:10.3109/14756366.2011.559945

A series of pyrazoline derivatives were synthesized and in vitro activity against Mycobacterium tuberculosis H37Rv was carried out. Among the synthesized compounds, compounds (4d) and (4f) 4-aminophenyl-3-(3,4-dimethoxyphenyl)-6,7- dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone and 4-aminophenyl-6,7-dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c] pyrazol-2-ylmethanone were found to be the most active agent against M. tuberculosis H37Rv with a minimum inhibitory concentration of 10μg/mL.

Full text of DOI:10.3109/14756366.2011.559945

Journal of Enzyme Inhibition and Medicinal Chemistry, 2011; 26(6): 890–894
© 2011 Informa UK, Ltd.
ISSN 1475-6366 print/ISSN 1475-6374 online
DOI: 10.3109/14756366.2011.559945
SHORT COMMUNICATION
Discovery of novel methanone derivatives acting as
antimycobacterial agents
Mohamed Ashraf Ali1, Sylvaine Bastian2,3, Rusli Ismail1, Tan Soo Choon1, Sadath Ali4,
Alexandra Aubry2,3, Suresh Pandian4, Pankaj Saraswat4, Abhimanyu Singh4, and Ramakant Gaur4
1Pharmacogenetic and Novel erapeutics Research, Institute for Research in Molecular Medicine, Universiti of Sains
Malaysia, Pennag, Malaysia, 2UPMC Université Paris 06, ER5, laboratoire de Bactériologie-Hygiène, Paris, France,
AP-HP, Hôpital Pitié-Salpêtrière, laboratoire de Bactériologie-Hygiène, Paris, France, Centre National de Référence des
Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France, 3Centre National de Référence
des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France, and 4New Drug Discovery
Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar, Rajasthan, India
Abstract
A series of pyrazoline derivatives were synthesized and in vitro activity against Mycobacterium tuberculosis H37Rv was
carried out. Among the synthesized compounds, compounds (4d) and (4f) 4-aminophenyl-3-(3,4-dimethoxyphenyl)-
6,7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone and 4-aminophenyl-6,7-dimethoxy-3-phenyl-
2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone were found to be the most active agent against M. tuberculosis
H37Rv with a minimum inhibitory concentration of 10μg/mL.
Keywords: Mycobacterial agents, pyrazoline, indanone, Mycobacterium tuberculosis
Introduction
problem and the need of new potent drugs that are highly
Mycobacterium tuberculosis (MTB) is a genus of one of
the major health issues worldwide, that is, tuberculosis
(TB)1. According to WHO statistical reports, about 1.3
million people died from TB in 2008 and a new person
is infected every second in the world1. Until 50 years ago,
there were no medicines available for the treatment of
TB. Streptomycin was the first antibiotic used in TB, and
nowadays the standard TB treatment includes rifampi-
cin, isoniazid, ethambutol, and pyrazinamide2. ese are
responsible for the development of multidrug-resistant
TB (MDR-TB, i.e. resistant to both isoniazid and rifam-
picin) and more recently of extremely drug-resistant TB
(XDR-TB, i.e. MDR-TB also resistant to fluoroquinolones
and to one of the following second-line anti-TB injectable
drugs: kanamycin, capreomycin, or amikacin), which are
effective in eradicating the disease deep.
is need lead us to focus our research in the devel-
opment of novel drugs for TB. Literature survey of novel
chemotherapeutic agents reveals that the substituted
pyrazoline derivatives are proved to be active against
many mycobacterial species3–15. In the present work, we
have synthesized novel heterocyclic molecules and tested
the compounds against the tubercle bacterium. Two of the
compounds showed a moderate activity against MTB.
Results and discussion
Chemistry
Pyrazoline derivatives 4a–4u described in this study
are shown in Table 1 and a reaction sequence for the
preparation is outlined in Scheme 1. In the initial step,
5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone
nearly untreatable, especially in HIV-infected patients3–5
A medication for TB still remains as an unresolved
.
Address for Correspondence: Mohamed Ashraf Ali, Pharmacogenetic and Novel erapeutics Research, Institute for Research
in Molecular Medicine, Universiti of Sains Malaysia, Pennag-11800, Malaysia. Tel: 91-9911128001. Fax: 91-11-26059666. E-mail:
asraf80med@rediffmail.com
(Received 03 November 2010; revised 07 January 2011; accepted 28 January 2011)
890

Methanone derivatives as antimycobacterial agents 891
Table 1. Physicochemical characteristics and antimycobacterial activity of compounds 4a–4u.
O
N
R1
N
O
O
H3C
H3C
R
4a-u
Compound
R
R1
Yield (%)
84
Melting point (°C)
MIC-MTBa (μg/mL)
>10.0
>10.0
>10.0
10.0
4a
4b
4c
4d
4e
4f
4g
4h
4i
Pyridyl-
4-Aminophenyl
4-Aminophenyl
4-Aminophenyl
4-Aminophenyl
4-Aminophenyl
4-Aminophenyl
4-Aminophenyl
144
162
143
141
128
103
176
145
164
184
198
168
144
162
153
151
128
153
166
165
174
2-Chlorophenyl-
4-Fluorophenyl-
3,4-Dimethoxyphenyl-
4-Methoxyphenyl-
Phenyl-
60
67
72
80
>10.0
10.0
62
4-Cyanophenyl-
Pyridyl-
71
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
>10.0
3,4-Dimethoxyphenyl-
3,4-Dimethoxyphenyl-
3,4-Dimethoxyphenyl-
3,4-Dimethoxyphenyl-
3,4-Dimethoxyphenyl-
3,4-Dimethoxyphenyl-
3,4-Dimethoxyphenyl-
4-Methoxyphenyl-
66
2-Chlorophenyl-
4-Fluorophenyl-
3,4-Dimethoxyphenyl-
4-Methoxyphenyl-
Phenyl-
67
4j
4k
4l
72
80
80
4m
4n
4o
4p
4q
4r
4s
4t
74
4-Cyanophenyl-
Pyridyl-
68
89
2-Chlorophenyl-
4-Fluorophenyl-
3,4-Dimethoxyphenyl-
4-Methoxyphenyl-
Phenyl-
4-Methoxyphenyl-
74
4-Methoxyphenyl-
64
4-Methoxyphenyl-
78
4-Methoxyphenyl-
92
4-Methoxyphenyl-
67
4u
4-Cyanophenyl-
4-Methoxyphenyl-
70
aMycobacterium tuberculosis H37Rv.
O
O
O
O
N
R1
b
O
N
H3C
a
O
H3C
H3C
R-CHO
2a-g
H3C
O
+
R
H3C
R
H3C
O
O
3a-g
1
4a-u
Scheme 1. Protocol for synthesis. (a) Reagents: NaOH/EtOH and (b) R1CONHNH2.
analoguesweresynthesizedbycondensing5,6-dimethoxy-
1-indanone with appropriate aldehyde in dilute methan-
olic sodium hydroxide solution at room temperature. e
product 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-
indanone was then treated with appropriate acid hydraz-
ide in the presence of glacial acetic acid to get methanone
derivatives in 62–84% yield after recrystallization with
ethanol. e purity of the compounds was checked by
thin-layer chromatography (TLC) and elemental analy-
ses. Both analytical and spectral data (1H NMR, IR) of all
the synthesized compounds were in full agreement with
the proposed structures. e elemental analysis results
were within 0.4% of the theoretical values.
with minimum inhibitory concentration of <10 μg/ mL
against MTB. Compounds with electron-donating
groups substituted on the phenyl ring were shown
to have higher activity potentials. Among the 21
newly synthesized compounds, compounds (4d)
and (4f), 4-aminophenyl-3-(3,4-dimethoxyphenyl)-
6,7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]
pyrazol-2-ylmethanone
and
4-aminophenyl-6,7-
dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c]
pyrazol-2-ylmethanone, were found to have highest
activity against MTB H37Rv. e minimum inhibitory
concentration of this compound (4d) and (4f) were
found to be 10 μg/mL. However, the compounds substi-
tuted with electron-withdrawing groups such as 4-cy-
anophenyl, 2-chlorophenyl, 4-flurophenyl, and pyridyl
produced low inhibitory activity against MTB. On the
other hand, the compounds like 4-methoxyphenyl
Antimycobacterial activity
Among the 12 compounds synthesized, most of the
compounds were found below-to-moderate active
© 2011 Informa UK, Ltd.

892 M.A. Ali et al.
also showed low antitubercular activity. Out of all the
substitutions of the phenyl ring, the results indicate
that the amino with 3,4-dimethoxyphenyl substitution
and amino with phenyl substitution cause remarkable
improvement in antimycobacterial activity.
e present investigation describes the synthesis of
pyrazoline analogues and evaluation of antimycobacte-
rial activity. e heterocycles synthesized in the present
work display low-to-moderate activity against MTB. e
synthesis and screening for biological activity of further
series of compounds and molecular docking simula-
tion for possible action on InhA are currently under
investigation.
(KBr) cm−1: 3320 (NH2), 3042 (CH), 1590 (C=N), 1680
(C=O), 1320 (C-N). H NMR (DMSO-d6) ppm: 2.48 (2H,
m, CH2), 3.09 (1H, m, CH), 3.82 (6H, s, OCH3), 5.16 (1H,
d, CH), 5.4 (2H, s, CO=NH2), 6.6–7.5 (6H, m, aromatic),
6.6–7.5 (4H, m, pyridine). EI-MS (m/z): 415 (M+1); Cal/
Ana: [C (69.55) 69.54, H (5.35) 5.37, N (13.52) 13.54].
1
4-Aminophenyl-3-(2-chlorophenyl)-6,7-dimethoxy-2,3,3a,
4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone (4b) IR:
(KBr) cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672
(C=O), 1320 (C-N), 786 (C-Cl). 1H NMR (DMSO-d6) ppm:
2.38 (2H, m, CH2), 3.81 (6H, s, OCH3), 3.08 (1H, m, CH),
5.16 (1H, d, CH), 5.4 (2H, s, CO=NH2), 6.6–7.75 (10H, m,
aromatic), EI-MS (m/z): 448 (M+1); Cal/Ana: [C (67.04)
67.08, H (4.95) 4.93, N (9.38) 9.37].
Experimental
e entire chemicals were supplied by E. Merck (India)
and S.D. Fine Chemicals (India). Melting points were
determined by open tube capillary method and are
uncorrected. Purity of the compounds was checked
on TLC plates (silica gel G) in the solvent system
toluene–ethyl formate–formic acid (5:4:1) and ben-
zene–methanol (8:2), the spots were located under
iodine vapours or UV light. IR spectra were obtained
on a Perkin-Elmer 1720 FT-IR spectrometer (KBr pel-
4-Aminophenyl-3-(4-fluorophenyl)-6,7-dimethoxy-2,3,3a,
4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone (4c) IR:
(KBr) cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672
(C=O), 1320 (C-N), 776 (C-F). 1H NMR (DMSO-d6) ppm:
2.36 (2H, m, CH2), 3.82 (6H, s, OCH3), 3.09 (1H, m, CH),
5.16 (1H, d, CH), 5.4 (2H, s, CO=NH2), 6.6–7.65 (10H, m,
aromatic), EI-MS (m/z): 432 (M−1); Cal/Ana: [C (69.59)
69.57, H (5.14) 5.12, N (9.74) 9.72].
1
lets). H NMR spectra were recorded or a Bruker AC
300 MHz spectrometer using TMS as internal standard
in DMSO/CDCl3. Mass spectra were recorded on a
Bruker Esquire LCMS using ESI and elemental analy-
ses were performed on a Carlo Erba 1106 elemental
analyzer. Column chromatography was performed on
silica gel (230–400 mesh) using petroleum ether–ethyl
acetate as eluent.
4-Aminophenyl-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-
2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone
(4d) IR: (KBr) cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N),
1
1672 (C=O), 1320 (C-N). H NMR (DMSO-d6) ppm: 2.36
(2H, m, CH2), 3.82 (12H, s, OCH3), 3.09 (1H, m, CH),
5.16 (1H, d, CH), 5.4 (2H, s, CO=NH2), 6.6–7.65 (9H, m,
aromatic), EI-MS (m/z): 474 (M+1); Cal/Ana: [C (68.48)
68.47, H (5.75) 5.72, N (8.87) 8.85].
General procedure
Synthesis of 2-[(E)-1-(substituted phenyl)methylidene]-5,
4-Aminophenyl-6,7-dimethoxy-3-(4-methoxyphenyl)-2,3,3a,
4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone(4e) IR:
(KBr) cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672
6-dimethoxy-1-indanone (3a–3g)10,11
5,6-Dimethoxy-1-indanone (1.92 g, 0.01 mol), appropri-
ate aldehyde (1.02 g, 0.01 mol), dissolved in ethanol and
sodium hydroxide (30%, 5 mL) with 10 mL of petroleum
ether, was stirred under room temperature for 4 h. e
resulting solution allowed to stand overnight and then
poured into cold water and neutralize with HCl. e solid
separate was filtered, dried and purified by ethanol.
1
(C=O), 1320 (C-N). H NMR (DMSO-d6) ppm: 2.36 (2H,
m, CH2), 3.82 (9H, s, OCH3), 3.09 (1H, m, CH), 5.16 (1H,
d, CH), 6.4 (2H, s, CO=NH2), 6.6–7.65 (10H, m, aromatic),
EI-MS (m/z): 444 (M+1); Cal/Ana: [C (70.41) 70.42, H
(5.68) 5.67, N (9.47) 9.48].
4-Aminophenyl-6,7-dimethoxy-3-phenyl-2,3,3a,4-tetra-
hydroindeno[1,2-c]pyrazol-2-ylmethanone (4f) IR: (KBr)
cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672 (C=O),
1320 (C-N). 1H NMR (DMSO-d6) ppm: 2.36 (2H, m, CH2),
3.82 (6H, s, OCH3), 3.09 (1H, m, CH), 5.16 (1H, d, CH),
6.4 (2H, s, CO=NH2), 6.6–7.65 (11H, m, aromatic), EI-MS
(m/z): 415 (M+2); Cal/Ana: [C (72.62) 72.64, H (5.61) 5.62,
N (10.16) 10.18].
General procedure
Synthesis of pyrazol-2-ylmethanone
To
a 2-[(E)-1-(substituted phenyl)methylidene]-5,6-
dimethoxy-1-indanone (3a–3o) (0.001 mol) in 15 mL
of glacial acetic acid, 0.002 mol of appropriate aromatic
acid hydrazide was added and the reaction mixture
was refluxed for 15 h and cooled. Excess of solvent was
removed under reduced pressure and the reaction mix-
ture was cooled poured on to crushed ice (20 g). e
product obtained was filtered, washed with water, and
recrystallized from methanol.
4 - [ 2 - ( 4 - A m i n o b e n z o y l ) - 6 , 7 - d i m e t h o x y - 2 , 3 , 3 a ,
4-tetrahydroindeno[1,2-c]pyrazol-3-yl]benzonitrile(4g) IR:
(KBr) cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672
1
(C=O), 1320 (C-N). H NMR (DMSO-d6) ppm: 2.36 (2H,
4-Aminophenyl-6,7-dimethoxy-3-(4-pyridyl)-2,3,3a,
4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone (4a) IR:
m, CH2), 3.82 (6H, s, OCH3), 3.09 (1H, m, CH), 5.16 (1H,
d, CH), 6.4 (2H, s, CO=NH2), 6.6–7.65 (10H, m, aromatic),
Journal of Enzyme Inhibition and Medicinal Chemistry

Methanone derivatives as antimycobacterial agents 893
EI-MS (m/z): 439 (M+1); Cal/Ana: [C (71.22) 71.20, H
(5.06) 5.07, N (12.78) 12.80].
cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672 (C=O),
1320 (C-N). 1H NMR (DMSO-d6) ppm: 2.36 (2H, m, CH2),
3.82 (12H, s, OCH3), 3.09 (1H, m, CH), 5.16-(1H, d, CH),
6.6-7.55 (9H, m, aromatic), EI-MS (m/z): 484 (M+1);
Cal/Ana: [C (69.55) 69.54, H (5.21) 5.22, N (8.69) 8.67].
3,4-Dimethoxyphenyl-6,7-dimethoxy-3-(4-pyridyl)-2,3,3a,
4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone (4h) IR:
(KBr) cm−1: 3040 (CH), 1592 (C=N), 1672 (C=O), 1320
(C-N), 788 (C-Cl). 1H NMR (DMSO-d6) ppm: 2.36 (2H, m,
CH2), 3.82 (12H, s, OCH3), 3.09 (1H, m, CH), 5.16-(1H, d,
CH), 6.6–7.25 (5H, m, aromatic), 7.6–8.35 (4H, m, pyri-
dine), EI-MS (m/z): 460 (M+1); Cal/Ana: [C (67.96) 67.98,
H (5.48) 5.46, N (9.14) 9.16].
6,7-Dimethoxy-3-(4-pyridyl)-2,3,3a,4-tetrahydroindeno[1,2-c]
pyrazol-2-yl-3-methoxyphenylmethanone (4o) IR: (KBr)
cm−1: 3040 (CH), 1592 (C=N), 1672 (C=O), 1320 (C-N), 788
(C-Cl). 1H NMR (DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82
(9H, s, OCH3), 3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.25
(6H, m, aromatic), 7.6–8.45 (4H, m, pyridine), EI-MS
(m/z): 430 (M+1); Cal/Ana: [C (69.92) 69.94, H (5.40) 5.42,
N (9.78) 9.76].
3-(2- Chlorophenyl)-6,7- dimethoxy-2,3,3a,4-tetra-
h y d r o i n d e n o [ 1 , 2 - c ] p y ra z o l - 2 - y l - 3 , 4 - d i m e t h ox y -
phenylmethanone (4i) IR: (KBr) cm−1: 3040 (CH), 1592
(C=N), 1672 (C=O), 1320 (C-N), 788 (C-Cl). 1H NMR
(DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82 (12H, s, OCH3),
3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.55 (9H, m,
aromatic), EI-MS (m/z): 493 (M+1); Cal/Ana: [C (65.79)
65.80, H (5.11) 5.13, N (5.68) 5.66].
3 - ( 2 - C h l o r o p h e n y l ) - 6 , 7 - d i m e t h o x y - 2 , 3 , 3 a ,
4-tetrahydroindeno[1,2- c]pyrazol-2-yl-3-methoxy-
phenylmethanone (4p) IR: (KBr) cm−1: 3040 (CH), 1592
(C=N), 1672 (C=O), 1320 (C-N), 788 (C-Cl). 1H NMR
(DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82 (9H, s, OCH3),
3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.55 (10H, m,
aromatic), EI-MS (m/z): 463 (M+1); Cal/Ana: [C (67.46)
67.48, H (5.01) 5.03, N (6.05) 6.06].
3,4-Dimethoxyphenyl-3-(4-fluorophenyl)-6,7-dimethoxy-2,
3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone
(4j) IR: (KBr) cm−1: 3040 (CH), 1592 (C=N), 1672
(C=O), 1320 (C-N), 770 (C-F). 1H NMR (DMSO-d6)
ppm: 2.36 (2H, m, CH2), 3.82 (12H, s, OCH3), 3.09 (1H,
m, CH), 5.16-(1H, d, CH), 6.6–7.55 (9H, m, aromatic),
EI-MS (m/z): 477 (M+1); Cal/Ana: [C (68.06) 68.08, H
(5.29) 5.27, N (5.88) 5.86].
3 - ( 4 - F l u o r o p h e n y l ) - 6 , 7 - d i m e t h o x y - 2 , 3 , 3 a ,
4-tetrahydroindeno[1,2- c]pyrazol-2-yl-3-methoxy-
phenylmethanone (4q) IR: (KBr) cm−1: 3040 (CH), 1592
(C=N), 1672 (C=O), 1320 (C-N), 770 (C-F). 1H NMR
(DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82 (9H, s, OCH3),
3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.55 (10H, m,
aromatic), EI-MS (m/z): 447 (M+1); Cal/Ana: [C (69.94)
69.02, H (5.19) 5.17, N (6.27) 6.26].
3,4-Dimethoxyphenyl-3-(3,4- dimethoxyphenyl)-6,
7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-
ylmethanone (4k) IR: (KBr) cm−1: 3322 (NH2), 3040 (CH),
1592 (C=N), 1672 (C=O), 1320 (C-N). 1H NMR (DMSO-d6)
ppm: 2.36 (2H, m, CH2), 3.82 (18H, s, OCH3), 3.09 (1H, m,
CH), 5.16-(1H, d, CH), 6.6–7.55 (8H, m, aromatic), EI-MS
(m/z): 519 (M+1); Cal/Ana: [C (67.17) 67.18, H (5.83) 5.84,
N (5.40) 5.41].
3 - ( 3 , 4 - D i m e t h ox y p h e ny l ) - 6 , 7 - d i m e t h ox y- 2 , 3 , 3 a ,
4-tetrahydroindeno[1,2- c]pyrazol-2-yl-3-methoxy-
phenylmethanone (4r) IR: (KBr) cm−1: 3322 (NH2), 3040
(CH), 1592 (C=N), 1672 (C=O), 1320 (C-N). 1H NMR
(DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82 (15, s, OCH3),
3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.55 (9H, m,
aromatic), EI-MS (m/z): 489 (M+1); Cal/Ana: [C (68.84)
68.86, H (5.78) 5.80, N (5.73) 5.75].
6 , 7 - D i m e t h o x y - 3 - ( 4 - m e t h o x y p h e n y l ) - 2 , 3 , 3 a ,
4-tetrahydroindeno[1,2-c]pyrazol-2-yl-3,4-dimethoxy-
phenylmethanone (4l) IR: (KBr) cm−1: 3322 (NH2), 3040
(CH), 1592 (C=N), 1672 (C=O), 1320 (C-N). 1H NMR
(DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82 (15H, s, OCH3),
3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.55 (9H, m,
aromatic), EI-MS (m/z): 489 (M+1); Cal/Ana: [C (68.84)
68.82, H (5.78) 5.76, N (5.73) 5.71].
6 , 7 - D i m e t h o x y - 3 - ( 4 - m e t h o x y p h e n y l ) - 2 , 3 , 3 a ,
4-tetrahydroindeno[1,2- c]pyrazol-2-yl-3-methoxy-
phenylmethanone (4s) IR: (KBr) cm−1: 3322 (NH2), 3040
(CH), 1592 (C=N), 1672 (C=O), 1320 (C-N). 1H NMR
(DMSO-d6) ppm: 2.36 (2H, m, CH2), 3.82 (12H, s, OCH3),
3.09 (1H, m, CH), 5.16-(1H, d, CH), 6.6–7.55 (10H, m,
aromatic), EI-MS (m/z): 459 (M+1); Cal/Ana: [C (70.73)
70.75, H (5.72) 5.74, N (6.11) 6.13].
3,4-Dimethoxyphenyl-6,7-dimethoxy-3-phenyl-2,3,3a,
4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone (4m) IR:
(KBr) cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672
(C=O), 1320 (C-N). 1H NMR (DMSO-d6) ppm: 2.36 (2H, m,
CH2), 3.82 (12H, s, OCH3), 3.09 (1H, m, CH), 5.16-(1H, d,
CH), 6.6–7.55 (10H, m, aromatic), EI-MS (m/z): 459 (M+1);
Cal/Ana: [C (70.73) 70.72, H (5.72) 5.73, N (6.11) 6.13].
6,7-Dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c]
pyrazol-2-yl-3-methoxyphenyl methanone (4t) IR: (KBr)
cm−1: 3322 (NH2), 3040 (CH), 1592 (C=N), 1672 (C=O),
1320 (C-N). 1H NMR (DMSO-d6) ppm: 2.36 (2H, m, CH2),
3.82 (9H, s, OCH3), 3.09 (1H, m, CH), 5.16-(1H, d, CH),
6.6–7.55 (11H, m, aromatic), EI-MS (m/z): 429 (M+1);
Cal/Ana: [C (72.88) 72.86, H (5.65) 5.63, N (6.54) 6.53].
4-[2-(3,4-Dimethoxybenzoyl)-6,7-dimethoxy-2,3,3a,4-tetra-
hydroindeno[1,2-c]pyrazol-3-yl]benzonitrile (4n) IR: (KBr)
© 2011 Informa UK, Ltd.

894 M.A. Ali et al.
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Acknowledgements
e authors wish to express their thanks to Pharma-
cogenetic and Novel erapeutic Research, Institute
for Research in Molecular Medicine, Universiti of Sains
Malaysia, Pennag, Malaysia and Alwar Pharmacy College,
Alwar, Rajasthan, India, UPMC Université Paris 06, EA
1541, laboratoire de Bactériologie-Hygiène, F-75005,
Paris, France and AP-HP, Hôpital Pitié-Salpêtrière, labo-
ratoire de Bactériologie-Hygiène, F-75013, Paris, France,
Centre National de Référence des Mycobactéries et de
la Résistance des Mycobactéries aux Antituberculeux,
F-75013 Paris, France for providing research facilities.
Declaration of interest
e authors report no conflicts of interest. e authors
alone are responsible for the content and writing of the
paper.
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