CHAPTER 9 STUDIES ON INDAZOLES
SECTION – I
STUDIES ON CYCLOHEXENONE
DERIVATIVES
182
9.1
INTRODUCTION
Cyclohexenones are derivatives of cyclohexane with carbonyl group
at 1- position duoble bond at position-2(I). There are different types of
cyclohexenone derivatives but the groups attached to carbon atom exerted
the greatest difference in structure and properties.
(I)
9.2
LITERATURE REVIEW
9.2.1 SYNTHETIC ASPECT
1-8
Preparation of cyclohexenone derivatives is described in literature
are
discussed below.
(1)
9
Page Philip C. and co-workers ave been prepared ethyl substituted
cyclohexenone derivative (II).
Methyl vinyl
ketone
(II)
183
(2)
A review of the earlier literature by Gerald et al
10
describes
representative synthetic procedure of cyclohexenone derivative (III).
(III)
(3)
Eman H. A. et al.
11
have been prepared cyclohexenone derivative (IV)
from chalcone.
R
X
X
EAA
K2CO3/Acetone
R
COOEt
(IV)
9.2.2 THERAPEUTIC IMPORT ANCE
184
Cyclohexenones
have
various
medicinal
applications
such
as
anthelmintic, hypoglycemic, nematocidal, antibacterial, antifungal, antiviral,
12
analgesic etc. Antiarhythmic activity
been
investigated.
Cyclohexenone
of some cyclohexenone derivatives have
possess
cardiovascular,
osteoporosis,
menpausal symptoms, estrogen dependent and cancers activities, which was
13
reported by Jacobsen Poul et al. .
14
De Mesmaeker et al.
prepared cyclohexenone carbonyl benzo
thiophene (I) as herbicides.
(O2)nS
CF3
(I)
15
Eddington, et al.
synthesised and evaluted anticonvulsant activity of
cyclohexene derivatve (II) and their corresponding 5-methyl cyclohex-2-enone
(III).
C6H4Br
(II)
185
C6H4Cl
EtOOC
(III)
Cyclohexenone and its derivatives have been prepared and reported as
broad
16
17
spectrum of physiological properties viz. antibiotic , bactericidal ,
18
herbicidal, antimicrobial , anticonvulsant. Alekseeva L.M. and co-workers have
synthesised cyclohexenone derivatives which are useful in neurotropic
activity. Toshiyuki et al. have prepared some novel cyclohexenones and screened
for allergy inhibitor, antithrombitic platelet aggregation inhibitors and
fibrinogen antagonist activity.
19
Collis David J. et al.
have documented cyclohexenone derivatives
which possess estrogenic activity . V. K. Ahluwalia et al.
20
have reported
some new cyclohexenone as anti HIV-I, gastric secretion inhibitors and
21
pesticidal activity . Nagarajan and shenoy
have prepared substituted
cyclohexenones which shown to possess marked antiinflammatory activity .
Nagao et al.
22
have reported antiarhythmics activity of cyclohexenones.
Inverse agonist for GABA activity of some 23
derivatives have been
investigated.
24
Antimicrobial activity have been studied by Salamu and Atshikh.
Cyclohexenone possess neutropeptide-γ-receptor antagonist activity which
was
25
reported by Takehiro and co-workers. Broughton Howard
have
demonstrated cyclohexenone as GABA α 5 receptor ligands for enhancing
186
cognition properties. Cyclohexenone possess inhibitory activity against the
26
growth of lettuce seedling found by kimura and co-workers . Parekh and coworkers
27
Y u. et al.
synthesised new cyclohexenones as antimicrobial agents. Shklyaev
28
have prepared cyclohexenones as potent biological agents. Cragoe
et al. 29 have synthesize some cyclohexenone derivatives which was useful in
the treatment of brain injur.y
These valid observations prompted as to combine this nucleus into well
known pharmaceutical properties of 3,5-dibromo-4-methoxy acetophenone
nucleus so as to enhance the overall activities of resulting moiet,y which have
been described as under.
187
9.3
SECTION – I
9.3
EXPERIMENTAL
9.3.1 SYNTHESIS
AND BIOLOGICAL SCREENING OF ETHYL
4-(3,5- DIBROMO-2-HYDROXY-4-METHYLPHENYL)-2-OXO-6(SUBSTITUTED PHENYL)CYCLOHEX-3-ENE-1-CARBOXYLATES
(CYCLOHEXENONE DERIVATIVES)
Therapeutic
importance
of
cyclohexenones
aroused
considerable
interest to synthesis ethyl 4-(3,5-dibromo-2Hydroxy-4-methylphenyl)-6-aryl-2oxo cyclohex-3-ene-1- caboxylates by the cyclocondensation of (2E)-1-(3,5dibromo-2-hydroxy -4-methylphenyl)-3-aryl-prop-2-en-1-ones in the presence of
anhydrous K 2 CO 3 with ethyl aceto acetate biodynamic behavior
R
Ethyl aceto acetate
R K2CO3 in
dry acetone
Chalcone derivatives
Cyclohexenone derivatives
R= Aryl
Scheme 9.1: Synthesis of cyclohexenone derivatives
The structure elucidations of synthesized derivatives were carried out by IR, 1H
NMR and Mass Spectroscopy. Every compound was evaluated for in-vitro
biological assay for antibactieral and antifungal activity comared with standard
drugs.
9.3.2 GENERAL SYNTHESIS OF ETHYL 4-(3,5-DIBROMO-2-HYDROXY4-METHYLPHENYL)-2-OXO-6-SUSBTITUTEDPHENYLCYCLOHEX-3ENE-1-CARBOXYLATES
188
(A) Synthesis of chalcone derivatives (1e)
See Chapter 2, Experimental Section 2.3
B) Synthesis of Ethyl 4-(3,5-Dibromo-2-hydroxy-4-methylphenyl)-2- oxo-6-(4N,N-dimethylaminophenyl)cyclohex-3-ene-1-carboxylates
To a solution of (2E)-1-(3,5-dibromo-2Hydroxy--4-methyl phenyl)-3-(4- N,N
dimethylamino phenyl)-prop-2-en-1-one (4.39gm, 0.01 mol) in dry acetone,
anhydrous K 2 CO 3
(5.52gm, 0.04 mol) and ethyl acetoacetate (2.60gm, 0.02
mol) was mixed and stirred at 25°C. The insoluble is filtered and solvent from the
filtrate on evaporation gave a solid. It was purified from methanol. Yield 64%, m.p.
120°C, Similarly, other compounds were prepared. The spectral data viz 1H NMR, IR
and mass specta along with physical constant for 11c are given in characrization
report 9.4.
189
9.4
CHARACTERIZATION
DATA
AND
PHYSICAL
CONSTANT
Characterization data and physical constant of following derivatives were
prepared of cyclohexenone derivatives.
R
Cyclohexenone derivatives
Sr.
R=
No.
Molecular
Yield M. P.
%
°C
Formula
TLC
Mobile Phase
Hexane :Ethyl
acetate/ Rf value
Mass
ESI
mode
m/z=
[M+]
11a
C6 H5 -
C 22 H 20 Br 2 O 4
58
115
5:5/ 0.55
509
11b
3-Br-C 6 H 4 -
C 22 H 19 Br 3 O 4
63
300
6:4/ 0.45
-----
11c
2-Cl-C 6 H 4 -
C 22 H 19 Br 2 ClO 4
71
80
5:5/ 0.54
----
11d
4-Cl-C 6 H 4 -
C 22 H 19 Br 2 ClO 4
69
100
5:5/ 0.6
543
11e
N,N-di-CH 3 -C 6 H 4 -
C 24 H 25 Br 2 NO 4
64
120
5:5/ 0.58
551
11f
4-OCH 3 -C 6 H 4 -
C 23 H 22 Br 2 O 5
59
125
5:5/ 0.57
539
C 24 H 24 Br 2 O 6
57
222
6:4/ 0.58
----
11g 3,4-di-OCH 3 -C 6 H 3 11h
2-NO 2 -C 6 H 4 -
C 22 H 19 Br 2 NO 6
58
168
6:4/ 0.47
554
11i
3-NO 2 -C 6 H 4 -
C 22 H 19 Br 2 NO 6
61
135
5:5/ 0.51
-----
11j
3-OC 6 H 5 -C 6 H 4
C 28 H 24 Br 2 O 5
68
139
5:5/ 0.49
601
190
9.4.1
Sr.
No.
1
H NMR (CDCl3) of cyclohexenone derivatives.
-CH3,
-CH3
-CH2,
-CH2
C-H, C-H, Ar-H
C-H of
-OH
-N(CH3)2
cyclohexene
A/ B/ C A/ B/ C
11a 1.24/3/t, 4.24/2/q
2.52/3/s
A/ B/ C
2.52,
2.86/2/dd
11b
1.25/3/t, 4.16/2/q
2.55/3/s
2.54,
2.80/2/dd
11c
1.23/3/t, 4.20/2/q
2.57/3/s
2.50,
2.89/2/dd
11d
1.25/3/t, 4.27/2/q
2.52/3/s
2.54,
2.81/2/dd
11e
1.25/3/t, 4.24/2/q
2.54/3/s
2.55,
2.84/2/dd
11f
1.24/3/t, 4.24/2/q
2.52/3/s
2.59,
2.86/2/dd
11g
1.25/3/t, 4.25/2/q
2.52/3/s
2.54,
2.86/2/dd
11h
1.24/3/t, 4.24/2/q
2.52/3/s
2.50,
2.84/2/dd
11i
1.24/3/t, 4.27/2/q
2.52/3/s
2.53,
2.76/2/dd
11j
1.04/3/t, 4.24/2/q
2.82/3/s
2.59,
2.76/2/dd
A/ B/ C
3.61/1/d,
4.38/1/s,
6.12/1/s,
3.63/1/d,
4.34/1/s,
6.15/1/s,
3.60/1/d,
4.34/1/s,
6.17/1/s,
3.61/1/d,
4.38/1/s,
6.12/1/s,
3.63/1/d,
4.34/1/s,
6.15/1/s,
3.65/1/d,
4.35/1/s,
6.17/1/s,
3.68/1/d,
3.91/1/s,
6.4/1/s,
3.63/1/d,
3.91/1/s,
6.14/1/s,
3.65/1/d,
3.91/1/s,
6.15/1/s,
3.68/1/d,
3.91/1/s,
6.19/1/s,
A/ B/ C
7.057.43/6/m
A/ B/ C A/ B/ C
12.30/1/s -------
7.037.45/5/m
12.35/1/s -------
7.067.43/5/m
12.37/1/s -------
7.347.39/5/m
12.42/1/s -------
6.567.41/5/m
13.01/1/s
7.347.43/5/m
12.35/1/s -(OCH3)
3.60/3/s
7.367.43/5/m
12.4/1/s
7.147.84/6/m
12.37/1/s -------
7.127.18/5/m
12.42/1/s -------
7.1512.4/1/s
7.34/10/m
3.02/6/s
(-OCH3)2
3.74/3/m
3.78/3/m
-------
A= Chemical Shift, , ppm ; B = No. of Protons; C = Multiplicity
Multiplicity abbreviations: dd- doubledublet, d – doublet, m – multiplet, s - singlet
191
1HNMR of compound 11c
192
1
HNMR of compound 11d
193
1
HNMR of compound 11e
194
9.4.2
IR (KBr)cm-1 of cyclohexenone derivatives.
Sr. - OHstr. -C-H str -CH str -C=Ostr C= C
No.
C-OC
C-Br
C-Cl
11a
3450
3050
2827
1741
1666
1263
650
-----
11b
3470
3042
2820
1740
1670
1253
660
-----
11c
3440
3040
2835
1745
1670
1260
650
580
11d
3465
3040
2935
1745
1650
1275
560
565
11e
3448
3062
2927
1741
1666
1263
648
-----
11f
3482
3050
2935
1745
1640
1270
650
-----
11g
3490
3050
2865
1739
1670
1281
672
-----
11h
3500
3050
2870
1760
1672
1239
680
N=O/
1580
11i
3495
3050
2895
1755
1680
1281
672
N=O/
1570
11j
3480
3050
2880
1760
1675
1280
680
-----
195
IR specrum of compound 11e
Mass specrum of compound 11e
196
9.5
BIOLOGICAL SCREENING
The biological screening was carried out as per chapter 2.5.
The activity study reveals that m o s t o f compounds were effective against
employed strains when compared with standard drugs.
It was found that the synthesized cyclohexenone derivatives shows excellent active
against various bacteria and antifungal pathogen viz. compounds 11c against
Streptococcus pneumoniase, 11e against Vibrio cholerae, 11a, b, e, f and i against
Bacillus subtillis; 11c, f and i, against Clostridium tetani in comparison with
Amipicilin. Compounds 11b and g against Salmonella typhi, compound 11e against
Escherichia coli ; 11a, e and f compared to nystatin against Candida albicans, 11b
and 11g against A.fumigatus
9.6
CONCLUSION
The emerging synthetic route allows the built up complex heterocyclic ring
using a simple reaction of the compounds studied. Most of the compounds are active
against various bacteria and fungis. This study trigger the invention in the research
of antimicrobial medicine.
197
SECTION II
CHAPTER - STUDIES ON INDAZOLES
198
9.7
INTRODUCTION
Heterocyclic compounds bearing a 1,2-diazole ring system i.e.
pyrazole ring system, attached to benzene ring system are known as benzo
pyrazoles or indazoles
(I). Buchner first described Indazole in 1869.
(I)
The compounds of medicinal interest in this group so far have been
non- steroidal antiinflammatory agents or analgesics.
9.8
LITERATURE REVIEW
9.8.1 SYNTHETIC ASPECT
30-35
Various method
for the preparation of indazoles have been described in
the literature among the popular are
1.
36,37
Indazoles can be synthesized by condensing
hydrazine hydrate with
cyclohexenone derivatives.
2.
Reaction of substituted azo sulfides with potassium-t-butoxide in
38
DMSO lead to the corresponding 1-H indazole derivatives .
199
t-BuOK
R
R
DMSO
3.
Cyclocondensation of activated acetylene with hydrazine afforded
39
indazole derivatives .
R
R
NO2
NO2
4.
Cyclization of 2,6-dialkoxy or hydroxyl acetophenone hydrazones
in presence of PPA can be use for the preparation of Indazoles.
5.
40
41
Synthesis of some indazole derivatives by heating benzylidene aniline
derivatives in DMF was reported by Okhim L-Y
u et al.
R
R1
O2 N
R
R1
O2 N
R DMF
R
N3
6.
42
Indazole ring system
can also be designed by the diazotization of
200
substituted anilines eg o-toludine.
HNO2
R
R
(CH3)4N+OAc -
R
7.
43
Carbon Stephan and co-workers have described that the condensation
of 2-acyl aryl mesylates with hydrazines affords corresponding indazole
derivatives.
9.8.2 THERAPEUTIC IMPORT ANCE
Indazole derivatives are biologically interesting class of compounds.
They
are
Antitumor
associated
44,45
,
various
46
Antiallergic ,
48
pharmacological
Antipsychotics,
properties
such
as,
47
Antiinflammatory ,
49
50
51
Antipyretic, Antineoplastic , Antiviral , Antihypertensive , Cytotoxic ,
52
53
54
edative , Herbicidal , Enzyme inhibitors , Fungicidal, Pesticidal
55
As reported earlier, indazoles are non-steroidal antiinflammatory
56
agents or analgesics, the prototype is benzydamine (I) , a fairly potent
nonsteroidal antiinflammatory agent with significant antipyretic and analgesic
201
57
58
properties.The other examples are bendazac (II) and tetrydamine (III) .
O-CH2-CH2-CH2-N(CH3)2
H2CC6H5
(I)
O-CH2-COOH
C6H5
(II)
NH-CH3
(III)
59
More over Y am aguchi Masahisa et al.
prepared some
202
indazole derivatives as novel anti asthametic agents and bronchodialations.
Ooe Taknori et al.
60
reported some indazoles as hematinics, immuno
stimulants and antitumor agents. Some indazole derivatives
61
showed activity
for enhancing macrophage phagocytosis, improving immunity and antitumor
activity.
62
Lavielle Gilbert et al.
documented the [(pyrrolidinyl) methyl]-
indazoles(IV) as 5-HT, like agonists and remedy for the treatment of migrains
and schizoprenia.
R
(IV)
63
Mewshaw Richard Eric et al.
have synthesized 4-amino ethoxy
64
indazoles useful as dopamine D2 agonists. Allan David and co-workers have
synthesized some indazole derivatives (V) and postulated them as fibrinogen
antagonist.
R
COOH
R'
(V)
Jain A.C. et al. have described the synthesis, separation of tautomers
203
and
biological
activities
of
4,6-diaryl-3-oxo-2,3a,4,5-tetrahydro-2H-
indazoles (VI).
OMe
MeO
(VI)
Thomas Lee and co-workers
65
demonstrated the preparation and
formulation of 6-(imidazolinyl amino) indazoles (VII) as
β-2 adreno-
receptor agonists.
(VII)
S everal co -workers hav e pat ent e d indazol e deri vati ve s usefu l as
hypolipidemic or hypocholersterolemic
67
Richard Charles et al.
66
and cardiovascular , agents Effland
constructed 3-(pyridyl amino) indazoles and reported
their use as antidepressants and anxiolytics.
A wide variety of pharmacological properties have been encountered
with indazole systems. Keeping the above in mind some novel indazole
derivative have been synthesised which have been described as unde.r
204
9.9
EXPERIMENTAL
9.9.1 SYNTHESIS AND BIOLOGICAL SCREENING OF 6-(3,5-DIBROMO2- HYDROXY-4-METHYL PHENYL)-4-(ARYL)-2,3A,4,5 TETRAHYDRO-3HINDAZOL 3-ONE (INDAZOLE DERIVATIVES)
The synthesis of indazole has attracted the attention of chemists because of
their potential pharmcodynamic properties. Looking to the interesting properties of
indazoles, it appeared interest to synthesise a series of 6-(3,5-dibromo-4-methyl
phenyl)-4-aryl-2,3a,4,5-tetrahydro-2H-indazol-3-ones for obtaining biologically
potent agents, which were prepared by reacting ethyl 4-(3,5-dibromo-4methylphenyl)-6-aryl-2-oxocyclochex-3-ene- 1-carboxylates in glacial acetic
acid.with hydrazine. H2O.
R
R
NH2NH2.H2O
CH3COOH
Indazole derivatives
Cyclohexenone derivatives
R= Aryl
Scheme 9.2 Synthesis of Indazole derivatives
The structure elucidation of synthesized derivatives were carried out by IR, 1H NMR
and Mass Spectroscopy. Every compound was evaluated for in-vitro biological
assay for antibactieral and antifungal activity compared with standard drugs.
9.9.2
GENERAL
SYNTHESIS
OF
6-(3,5-DIBROMO-2-HYDROXY-4-
METHYLPHENYL)--4-ARYL-2,3A,4,5-TETRAHYDRO-2H-INDAZOL-3ONES
(A) Synthesis chalcone derivatives (1e)
205
See Chapter 2, Experimental Section 2.3
(B) Synthesis of of cyclohexenone derivatives (11e).
See Chapter 9, Experimental Section (B)
(C)
Synthesis
of
6-(3,5-Dibromo-2-hydroxy-4-methylphenyl)-4--(4-N,N-
dimethylaminopheyl)l-2,3a,4,5-tetrahydro-3H-indazol-3-ones
A
mixture
of
ethyl
4-(3,5-dibromo-2hydroxy-4-methylphenyl)-6-(4-N,N-
dimethylaminophenyl)-2-oxocyclohex-3-ene-1-carboxylate(5.51
gm,
0.01mol);
hydrazine hydrate (0.5gm 0.01 mol), acetic acid (2 ml) and ethanol (20 ml), was
boiled at 80°C for 4 hours on water bath. The residue obtained after cooling was
filtered and isolated and purified from methanol. M. P. 154°C, Yield 65 %. Similarly,
other compounds were prepared. The spectral data viz 1H NMR, IR and mass specta
along with physical constant for 12e are given in characrization report 9.10.
206
CHARACTERIZATION DATA AND PHYSICAL
CONSTANT
9.10
9.10.1 Characterization data and physical constant of following derivatives were
prepared of indazole derivatives.
R
Indazole derivatives
Sr.
R=
No.
Molecular
Formula
Yield M. P.
TLC
%
°C Mobile Phase
Hexane :Ethyl
acetate/ Rf value
Mass
ESI
mode
m/z=
[M+]
12a
C6 H5 -
C 20 H 16 Br 2 N 2 O 2
72
220
5:5/ 0.55
477
12b
3-Br-C 6 H 4 -
C 20 H 15 Br 3 N 2 O 2
60
190
6:4/ 0.45
556
12c
2-Cl-C 6 H 4 -
C 20 H 15 Br 2 ClN 2 O2 68
160
5:5/ 0.54
511
12d
4-Cl-C 6 H 4 -
C 20 H 15 Br 2 ClN 2 O2 70
198
5:5/ 0.6
511
12e N,N-di-CH 3 - C 6 H 4 - C 22 H 21 Br 2 N 3 O 2
65
154
5:5/ 0.58
520
12f
C 21 H 18 Br 2 N 2 O 3
75
140
5:5/ 0.57
507
12g 3,4-di-OCH 3 C 6 H 3 - C 22 H 20 Br 2 N 2 O 4
60
170
6:4/ 0.58
537
12h
2-NO 2 -C 6 H 4 -
C 20 H 15 Br 2 N 3 O 4
58
182
6:4/ 0.47
522
12i
3-NO 2 -C 6 H 4 -
C 20 H 15 Br 2 N 3 O 4
60
198
5:5/ 0.51
522
12j
3-OC 6 H 5 -C 6 H 4
C 26 H 20 Br 2 N 2 O 3
70
167
5:5/ 0.49
569
4-OCH 3 -C 6 H 4 -
207
9.10.2 1H NMR (CDCl3) of indazole derivatives.
Sr.
No.
-CH3,
-CH2
A/ B/ C A/ B/ C
C-H, C-H,
C-H
Ar-H
-CONH -N(CH3)2
A/ B/ C
A/ B/ C
A/ B/ C
A/ B/ C
12a
2.55/1/s 2.22,
2.85/1/m,
2.75/2/m 4.02/1/dd,
6.21/1/m,
7.127.47/6/m
9.39/1/s
-------
12b
2.56/1/s 2.40,
2.86/1/m,
2.76/2/m 4.09/1/dd,
6.20/1/m,
7.167.48/5/m
9.39/1/s
-------
12c
2.55/1/s 2.38,
2.85/1/m,
2.77/2/m 4.02/1/dd,
6.21/1/m,
7.067.47/5/m
9.39/1/s
-------
12d
2.54/1/s 2.37,
2.86/1/m,
2.75/2/m 4.03/1/dd,
6.26/1/m,
7.307.49/5/m
9.39/1/s
-------
12e
2.55/1/s 2.62,
2.88/1/m,
2.99/2/m 4.03/1/dd,
6.22/1/m,
7.017.52/5/m
9.39/1/s
12f
2.54/1/s 2.62,
2.85/1/m,
2.99/2/m 4.03/1/dd,
6.22/1/m,
7.107.52/5/m
9.39/1/s -(OCH3)
3.60/3/s
12g
2.54/1/s 2.62,
2.87/1/m,
2.99/2/m 4.04/1/dd,
6.24/1/m,
7.227.52/6/m
9.39/1/s
(-OCH3)2
3.74/3/m
3.77/3/m
12h
2.55/1/s 2.62,
2.85/1/m,
2.99/2/m 4.02/1/dd,
6.20/1/m,
7.418.01/5/m
9.39/1/s
-------
12i
2.56/1/s 2.62,
2.86/1/m,
2.99/2/m 4.02/1/dd,
6.21/1/m,
7.528.15/5/m
9.39/1/s
-------
12j
2.54/1/s 2.62,
2.88/1/m,
2.99/2/m 4.04/1/dd,
6.24/1/m,
6.917.52/10/m
9.39/1/s
-------
2.90/6/s
A= Chemical Shift, , ppm ; B = No. of Protons; C = Multiplicity
Multiplicity abbreviations: dd- doubledublet, d – doublet, m – multiplet, s - singlet
208
1
HNMR of compound 12b
209
1
HNMR of compound 12c
210
1
HNMR of compound 12d
211
9.10.3 IR (KBr)cm-1 of indazole derivatives.
Sr.
No.
- OHstr.
-CH str
C=N
-C=O
C-Br
C-Cl
12a
3480
2925
1642
1660
630
-----
12b
3490
2950
1632
1670
630
-----
12c
3480
2925
1642
1660
630
580
12d
3510
2950
1630
1673
670
558
12e
3400
2925
1652
1662
670
-----
12f
3485
2875
1540
1660
630
-----
12g
3485
2898
1525
1660
680
-----
12h
3502
2890
1590
1608
672
N=O/
1530
12i
3495
2890
1595
1670
630
N=O/
1520
12j
3508
2790
1570
1663
670
-----
212
IR spectrum of compound 12e
Mass spectrum of compound 12e
213
9.11
BIOLOGICAL SCREENING
The biological screening was carried out as per chapter 2.5.
The activity study reveals that m o s t o f compounds were effective against
employed strains when compared with standard drugs.
For Streptococcus pneumoniase
compound, 12b, c and
, compound 12c, g, f, h; Vibrio cholerae,
h ; Bacillus subtilis compound, 12f, g, h and j ;
Clostridium tetani, compound 8a, c, d, f, h g; Salmonella typhi, compound 12c and h
and Candida albicans, compound 8d and j were found active in comparison with
standard drugs.
9.12 CONCLUSION
The synthesis of indazole derivatives inspires us to develop two heterocycles
which are having therapeutic importance using simple reagents. Most of the
compounds are active against various bacteria and fungis.
214