Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
40 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
CHAPTER-4 Synthesis and biological activities of Isoxazoles and
Pyrazoles
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
41 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.1 Introduction
Aryl ketones and aromatic aldehydes were condensed in presence of base resulted
Chalcones.
Isoxazole is an azole with an oxygen atom next to nitrogen. Isoxazole rings are found in
natural products like ibotonic acid .Isoxazoles are the basic for a number of drugs like cox-2
inhibitor, nitric oxide donor–furaxan etc. A highly appreciable number of five membered
heterocycles containing nitrogen atom and oxygen atoms obtained by laboratory synthesis.
Which are having potential therapeutic and pharmaco therapeutic activities. Some of useful
synthetic analogues with improved therapeutic activity can be obtained from single lead
compound by structural modifications. A lot of modifications have been done during the last few
years on Isoxazole nucleous.
Chalcone derivatives have different activities1-9. Therefore new compounds are
synthesized.
Synthesis of heterocyclic molecules inventive advance methods are available, this subject
is ever innovative area for the world of chemistry. Pyrazoles and isoxazoles nucleus blocks have
used widely for pharma world. Their derivatives are brilliantly used with high pharmacology
properties. Like Hypoglycemic, Analgesic, Antiinflammatory, Anti-bacterial, Anti-HIV and
Anti-cancer activity10, with other hand use in schizophrenia, Hypertension and alzheimer
disease11. They are also used in Insecticides12 and Pesticides. Pyrazoles are used in recently Anti-
parasites activity13 and kinase inhibitor.
Pyrazoles and isoxazoles are well known five member heterocyclic compounds and
several procedures for its synthesis have been extensively studied.
NH
N
O
N
1,3-oxazole 1H-imidazole
Fig-3.1
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
42 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Henry Feuer and Sheldon Markofsky14,15 using the Michael-type addition between
sodium 1-alkane nitronates and a-nitro olefins, which were generated insitu from 2-nitroalkyl
acetates leads largely to the formation of 3,5-dialkyI isoxazoles. The latter also are obtained by
the demethylolation of 2-alkyl-2,4-dinitro 1-alkanols and by the rearrangement of secondary 8-
dinitroalkanes in weakly basic media. The Michael-type addition between 2-alkane nitronates
and α-nitro olefins can really proceeds in reasonably good yields16-20. In contrast, 1-alkane
nitronates give the desired Michael adducts, secondary α-dinitro alkanes, only in poor yields, No
explanations have been given to account for the poor yields in this reaction. however, reports in
the literature in which attempts to prepare phenyl-substituted α -dinitro alkenes gave rise largely
to isoxazoles and isoxaoline N-oxides21-23 For example, Heim obtained in the mbase-catalyzed
reaction between phenyl nitro methane and benzaldehyde, in addition to 1,2,3-triphenyl- l,3-
dinitropropane and nitrostilbene, 3,4,5- triphenylisoxazole. Heim and other workers22,24-26 were
able to show that phenyl-substituted α-dinitro compounds were unstable in the presence of base
and eliminated nitrous acid to form isoxazoline N-oxides and isoxazoles
R
H
NO2-
R1
H
NO2-
H+
RH
NO2-
H
O2-N
R1
N OR
R1
+HNO2
+
Fig-3.2
Tweedie S. R. et al.27 have synthesized hetraryl amines couples with aryl halides
catalysed by palladium & base.
N
O
NH2
+
Br
CN
N
O
NH
Br
pd2(dba)3 ligand
micro wave 2 hrs
Fig-3.3
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
43 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yavari I. et al28 were synthesized isoxazole derivatives in the presence of
triphenylphosphine by the reaction of acetylenes and alkyl 2-nitroethanoates.
PPh3 +COOMe
COOMe
+ EtONO2
Oreflux
N O
COOMe
MeOOC COOEt
Fig-3.4
3.2 Biological activity:-
Oxazolidine-2-one, benzo[d]isoxazole are made in Cushman M. et al.29.
O
O
OCH3MeOOC
N
O
OCH3
Fig-3.5
New isoxazole and pyrazole series found by D. Thomas 30. Some compounds are having
effective properties which is made from glutarate.
N X
OR
R1 COOH
R=pyridine derivatives
R1=aryl & heteroaryl derivatives
Fig-3.6
Liljefors T. et al.31 have synthesized a series of Aryl piperidyl isoxazololes and evaluated
for GABAA antagonists. 2 & 4-substituted compounds having good activities.
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
44 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
O N
NHOH
Ph
O N
NHOH
OPh
O N
S
NH
OH
Ph
Fig-3.7
The strength of binding on receptors of indazole derivatives and isoxazole derivatives
have described by Barceló32.
Amgad G. Habeeb et al.33 also reported a isoxazolines belonging various
substitutes at 3rd position of the aromatic ring, which made for analysis as analgesic inhibitory,
anti-inflammatory agents.
When isoxazolines have not Carbon-3 Me substituent, shown potency analgesic and AI
activities.
N
O
R2
R3
R1
Me
R1= H, Me
R2,R
3= H, F,SMe,SO2Me
Fig-3.8
Chih Y. Ho et al.34 have repoted a series of pyrazol-phenylamines dervatives have
developed to keep potency against the angiogenesis task, the receptor tyrosine enzyme obtained
moving factor and to develop the broad tumor cell antiproliferative activity of these derivatives.
These work finds in (JNJ-10198409).
Giovannoni M. P. et al.35 have synthesized a number of arylpiperazinyl
alkylpyridazinones and checked for painkiller activity. They were observed that they checked
compounds at the appropriate dose, shown high pain remover activity, in specific compounds,
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
45 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
substitute molecules leading in which was able to reduce huge abdominal methods by more than
half in test. In the investigation of the compound’s action it seen analgesic effect.
NH
N
NH
F
H3CO
H3CO
N
N O
NHO
(H2C)3
N
N
Cl
Fig-3.9
Christian Peifer et al.36 have reported the discovery of isoxazoleas a potent biphasic
inhibitors. In the designed of isoxazoles, some molecules have 76 enzymes and tested of their
cellular effects shown 18 (CKP138) to be a high dual inhibitors of CK1δ and p38α. And In 2006,
Johnson & Johnson Pharmaceutical Research & Development37, has been reported the synthesis
of a series of Amino dihydrobenzopyrano isoxazole derivatives using substituted
salicylaldehydes and ethyl 4-bromocrotonate. Among the synthesized isoxazoles, few have
proven that most potency blockers with potent serotonin (5-HT) reuptake inhibiting activity.
Serotonin is one of the important monoamine for human body and the deficit of 5-HT mainly
lead to the depression.
O N
N
F
N
N
O N
O
R2
R1
R1,R
2 = H,Me.NHAr
Fig-3.10
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
46 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Carr J. B. et. al.38 have been synthesized a series of highly substituted isoxazoles and
screened for helminthic activity checked by dose range of 17 to 499 mg/kg to the mouse
roundworm, Nlppostrongjlus Erazikensis. They were found that the newly synthesized isoxazole
derivatives have potent anthelmintic activity.
O N
R1
R2
R2=H,Br,Cl
R1=Cl,Br,OH,CH3SO3,CH3CONH2
Fig-3.11
Biological evaluate of potency HAD-C3 and HAD-C8 isoxazoles and pyrazoles based di
azide suitable for bind profile by photo labeling experiment in cell is shown. In isoxazoles and
pyrazoles based compounds showed less nanomolar activity against HAD-C3 and HAD-C8. The
pyrazoles base the active HAD-C8 inhibitor reports in the literatures with IC-50 of 18 nm.
In studies suggestions the unlike the isoxazoles base ligand the pyrazole base ligand
having flexible to the another binding site as HAD-C8. Some molecules shown the different
activities at minimum concentration, indicates they are cells holey and the azides or diazides
group doesn’t obstruct with the neuro-protection property, cellular cyto-toxicity, or influence cell
permeability39.
Anti oxidant antimicrobial activities of P.Manoj kumar et.al.40-43 synthesized some new
series of 1-isonicotinyl 3,5 dimethyl-4-arylazo isoxazoles which shows Antioxidant Antibacterial
and Antimicrobial activities against staphy lococcus aurous and antibacterial against albican. The
antioxidant activity is compared with standard drug ascorbic acid.
Y X
ZN N
O
NHCOCH3
O
X=C/O Y=N/O Z=C/N
Fig-3.12
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
47 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Immunological activities of Stanislaw ryng and Michael zimeki synthesized some new
derivatives of isoxazoles including isoxazole triazoline derivatives which shown immune
modulator activity. The compounds were tested for their ability to affect the proliferative
response of moule sphlenocytes to conconavalin (A) and secondary humoral immune response of
sphlenocytes to sheep red blood cells measured as the number of antibody forming cells and
Cyclosporine A served as a reference compound.
NHO
N
S
N
NH
R
R= aromatic &aliphatic
NN
NO
COOEt
COOEt
nociceptive activity
Fig-3.13
K.Karthikeyan, T.veenuseelan et.al.44-46 was developed a systematic procedure for the
synthesis of pyrazolyl isoxazole and they performed the activity of anti nociceptive action by
using various animal tissues. The lead molecule was synthesized by using 1, 3 dipolar cyclo
addition of pyrazole derived nitric oxide with various dipolarophiles suchmas N-substituted
maleimide, diethyl acetylene dicarboxylate and phenyl acetylene. The given structure of
synthesized pyrazolyl isoxazoles shows maximum anti nociceptive activity.
Five member N2 contained heterocyclic compound possess wide spectrum of activity47.
Isoxazole48-50 and Pyrazole51-52 have proven record of biological activities, which contains two
nitrogen atoms. In view of the pharmacological profiles of these two chemical moieties as
described above, we considered it interesting to synthesized two chemically different but
pharmacologically compatible molecules with the aim of obtaining some novel heterocyclic
systems with potentially improved biological properties. In the present investigation a new series
of novel 3-[bis-3,5(methyltrifluoro)phenyl]-5-phenylisoxazole / 3-[bis-
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
48 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3,5(methyltrifluoro)phenyl]-5-(4-chlorophenyl)-1H-pyrazole [TV-116 TO 145] were synthesize
and evaluate for vitro microbial activity.
3.3 Current work
With the biodynamic activities of chalcones and as a fine synthon for different
fluorinated compounds, the awareness has been paying attention on the creation of new
chalcones. With a observation to obtained compounds having good biological activity, two new
synthesized 3-[bis-3,5(methyltrifluoro)phenyl]-5-phenylisoxazole and 3-[bis-
3,5(methyltrifluoro)phenyl]-5-(4-chlorophenyl)-1H-pyrazole by the Cyclization of different (E)-
1-[bis-3,5(methyltrifluoro)phenyl]-3-phenylprop-2-en-1-one by hydroxyl amine/sodium acetate
and hydrazine hydride.
We have synthesised two new series of 3-[bis-3,5(methyltrifluoro)phenyl]-5-
phenylisoxazole and 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-chlorophenyl)-1H-pyrazole (TV -
116 to 145) The structures of all the synthesized compounds were elucidated by FT-IR, mass
spectra, 1H NMR and elemental analyses. The newly synthesized compounds were subjected to
antimicrobial activity
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
49 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Series:- 2 Isoxazole
3.4 Reaction Scheme
Methanol
O
RCF3
CF3
R= TV 116 to 130
CF3
CF3
N O
R
NH2OH.HCl/CH3COONa
Fig-3.14
Table 3.1 Physical Data Table of Series-2
Code R1 M.F. M.W.
M.P.
ºC
Yield
%
Rf1 Rf2
TV-116 4-Cl C17H8ClF6NO 391 165 76 0.40 0.69
TV-117 4-F C17H8F7NO 375 145 71 0.48 0.60
TV-118 4-Br C17H8BrF6NO 436 164 80 0.45 0.68
TV-119 4-CH3 C18H11F6NO 371 154 77 0.50 0.65
TV-120 4-OCH3 C18H11F6NO2 387 157 58 0.49 0.69
TV-121 3-Cl C17H8ClF6NO 491 157 60 0.59 0.61
TV-122 4-F C17H8F7NO 374 159 76 0.40 0.68
TV-123 3-Br C17H8BrF6NO 436 167 73 0.48 0.62
TV-124 3-OCH3 C18H11F6NO2 387 171 81 0.45 0.68
TV-125 3,4-DiOCH3 C19H13F6NO3 417 167 70 0.50 0.69
TV-126 2-Cl C17H7Cl2F6NO 391 168 57 0.49 0.60
TV-127 2-F C17H8ClF6NO 375 149 63 0.45 0.68
TV-128 2-Br C17H8F7NO 436 159 62 0.43 0.65
TV-129 2-OCH3 C18H11F6NO2 387 182 61 0.47 0.76
TV-130 H C17H9F6NO 344 169 72 0.49 0.68
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
50 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Table-3.1
TLC Solvent system Rf1: Hexane: Ethyl acetate – 7:3;
Rf2: Chloroform: Methanol - 9:1.
3.5 Plausible Reaction Mechanism
HR1
OF3C
F3C
OHNH2
R1
F3C
F3C
O
O :NH2
R1
F3C
F3C
O
O :NH2
H
F3C
F3CN O
OH H
R1
F3C
F3CN O
H
R1H
-H2O
F3C
F3CN O
R1
F3C
F3CN O
R1
Fig-3.15
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
51 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.6 Experimental
3.6.1 Materials and Methods
Open capillary tubes are used for melting points. TLC has been checked for formation of
compounds regularly and spots were seen by iodine. FT-IR-8400 instrument is using for IR
spectra. Shimadzu GC-MS-QP-2010 model used for Mass spectra. Brucker Ac 400 MHz
spectrometer was used for 1H NMR.
3.6.2 General procedure for the synthesis of 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-
substitutedphenyl)isoxazole (TV- 116 to 130)
A mixture of (E)-1-[bis-3,5(methyltrifluoro)phenyl]-3-(4-substitutedphenyl)propenone (0.021
Mole), hydroxylamine hydrochloride (0.021 Mole) and Sodium acetate in ethyl alcohol (25 ML)
was refluxed for 6.5 hrs. The solvent was distilled out under vacuum and added into chilled
water. The solid was filtered, washed and crystallized. TLC was used for completion of the
reaction.
3.6.2.1 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-chlorophenyl)isoxazole (TV-116)
CF3
F3C Cl
N O
Yield: 77%; mp 203ºC; Analytical Calculation for C17H8ClF6NO : Carbon, 51.13; Hydrogen,
2.06; Chlorine, 9.05; Fluorine, 29.10; Nitrogen, 3.58; Oxygen, 4.08; Found: Carbon, 52.02;
Hydrogen, 2.02; Chlorine, 9.01; Fluorine, 29.04; Nitrogen, 3.49; Oxygen, 4.01; IR (cm-1): 3049
(C-H stretching of aromatic ring), 1703 (C=O stretching ), 1681, 1585 and 1531 (C=C stretching
of aromatic ring), 1240 (N-O stretching ), 1084 (C-H in plane deformation of aromatic ring),
1012 (C-F stretching), 829 (C-H out of plane bending of 1,4-disubutituion); MS: m/z 391; 1H
NMR (DMSO-d6) δ ppm: 5.27-5.28 (s, 1H ,Ha), 7.06-7.08 (d, 1H, Hb), 7.10-7.14 (m, 1H, Hc),
7.27-7.29 (d, 2H, Hdd’,), 7.46-7.48 (m, 2H, Hee’,), 7.82-7.83 (m, 1H, Hf).
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
52 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.6.2.2 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-fluorophenyl)isoxazole (TV-117).
Yield: 58%; mp 201ºC; Analytical Calculation for C17H8F7NO: Carbon, 54.41; Hydrogen, 2.15;
Fluorine, 35.44; Nitrogen, 3.73; Oxygen, 4.26; Found: Carbon, 54.31; Hydrogen, 2.06; Fluorine,
30.37; Nitrogen, 3.63; Oxygen, 4.15%; MS: m/z 375.
3.6.2.3 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-bromophenyl)isoxazole (TV-118).
Yield: 67%; mp 189ºC; Analytical Calculation for C17H8BrF6NO: Carbon, 46.82; Hydrogen,
1.85; Bromine, 18.32; Fluorine, 26.14; Nitrogen, 3.21; Oxygen, 3.67; Found: Carbon, 46.71;
Hydrogen, 1.67; Bromine, 18.21; Fluorine, 26.05; Nitrogen, 3.11; Oxygen, 3.54%; MS: m/z 436.
3.6.2.4 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-methylphenyl)isoxazole (TV-119).
CF3
F3C F
N O
CF3
F3C Br
N O
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
53 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 68%; mp 186ºC; Analytical Calculation for C17H9F7O: Carbon, 58.23; Hydrogen, 2.99;
Fluorine, 30.70; Nitrogen, 3.77; Oxygen, 4.31; Found: Carbon, 58.03; Hydrogen, 2.75; Fluorine,
30.40; Nitrogen, 3.57; Oxygen, 4.11%; MS: m/z 371.
3.6.2.5 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-methoxyphenyl)isoxazole (TV-120)
Yield: 74%; mp 221ºC; Analytical Calculation for C17H9BrF6O: Carbon, 55.82; Hydrogen, 2.86;
Fluorine, 29.43; Nitrogen, 3.62; Oxygen, 8.26; Found: Carbon, 55.52; Hydrogen, 2.76; Fluorine,
29.13; Nitrogen, 3.22; Oxygen, 8.06%; MS: m/z 387.
3.6.2.6 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-chlorophenyl)isoxazole (TV-121).
CF3
F3C CH3
N O
CF3
F3C OCH3
N O
CF3
F3C
N O
Cl
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
54 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 56%; mp 204ºC; Analytical Calculation for C19H14F6O3: Carbon, 52.13; Hydrogen, 2.06;
Chlorine, 9.05; Fluorine, 29.10; Nitrogen, 3.58; Oxygen, 4.08; Found: Carbon, 52.02; Hydrogen,
2.02; Chlorine, 9.01; Fluorine, 29.04; Nitrogen, 3.49; Oxygen, 4.01%; MS: m/z 391.
3.6.2.7 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-fluorophenyl)isoxazole (TV-122).
Yield: 76%; mp 224ºC; Analytical Calculation for C17H8Cl2F6O: Carbon, 54.41; Hydrogen, 2.15;
Fluorine, 35.44; Nitrogen, 3.73; Oxygen, 4.26; Found: Carbon, 54.21; Hydrogen, 2.01; Fluorine,
35.11; Nitrogen, 3.53; Oxygen, 4.11%; MS: m/z 375.
3.6.2.8 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-bromophenyl)isoxazole (TV-123).
Yield: 71%; mp 212ºC; Analytical Calculation for C18H12F6O2: Carbon, 46.82; Hydrogen, 1.85;
Bromine, 18.32; Fluorine, 26.14; Nitrogen, 3.21; Oxygen, 3.67; Found: Carbon, 46.62;
Hydrogen, 1.65; Bromine, 18.02; Fluorine, 16.14; Nitrogen, 3.11; Oxygen, 3.27%; MS: m/z 436.
3.6.2.9 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3- methoxyphenyl)isoxazole (TV-124)
CF3
F3C
N O
F
CF3
F3C
N O
Br
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
55 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 80%; mp 195ºC; Analytical Calculation for C17H9ClF6O: Carbon, 55.82; Hydrogen, 2.86;
Fluorine, 29.43; Nitrogen, 3.62; Oxygen, 8.26; Found: Carbon, 55.76; Hydrogen, 2.72; Fluorine,
29.32; Nitrogen, 3.54; Oxygen, 8.12% MS: m/z 387.
3.6.2.10 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3,4-dimethoxyphenyl)isoxazole (TV-125)
Yield: 77%; mp 182ºC; Analytical Calculation for C17H9BrF6O: Carbon, 54.69; Hydrogen, 3.14;
Fluorine, 27.32; Nitrogen, 3.36; Oxygen, 11.50; Found: Carbon, 54.52; Hydrogen, 3.07;
Fluorine, 27.23; Nitrogen, 3.24; Oxygen, 11.43%; MS: m/z 417.
3.6.2.11 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-chlorophenyl)isoxazole (TV-126)
CF3
F3C
N O
OCH3
CF3
F3C
N O
OCH3
OCH3
CF3
F3C
N O
Cl
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
56 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 58%; mp 242ºC; Analytical Calculation for C17H9ClF6O: Carbon, 52.13; Hydrogen, 2.06;
Chlorine, 9.05; Fluorine, 29.10; Nitrogen, 3.58; Oxygen, 4.08; Found: Carbon, 52.08; Hydrogen,
2.04; Chlorine, 9.01; Fluorine, 29.01; Nitrogen, 3.43; Oxygen, 4.01% MS: m/z 391.
3.6.2.12 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-fluorophenyl)isoxazole (TV-127)
Yield: 60%; mp 212ºC; Analytical Calculation for C17H9F7O: Carbon, 54.41; Hydrogen, 2.15;
Fluorine, 35.44; Nitrogen, 3.73; Oxygen, 4.26; Found: Carbon, 54.31; Hydrogen, 2.06; Fluorine,
35.37; Nitrogen, 3.63; Oxygen, 4.15% MS: m/z 375.
3.6.2.13 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-bromophenyl)isoxazole (TV-128)
Yield: 62%; mp 224ºC; Analytical Calculation for C19H14F6O: Carbon, 46.82; Hydrogen, 1.85;
Bromine, 18.32; Fluorine, 26.14; Nitrogen, 3.21; Oxygen, 3.67; Found: Carbon, 46.71;
Hydrogen, 1.67; Bromine, 18.21; Fluorine, 26.05; Nitrogen, 3.11; Oxygen, 3.54%; MS: m/z 436.
3.6.2.14 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-methoxyphenyl)isoxazole (TV-129).
CF3
F3C
N O
F
CF3
F3C
N O
Br
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
57 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 66%; mp 209ºC; Analytical Calculation for C18H12F6O2: Carbon, 55.82; Hydrogen, 2.86;
Fluorine, 29.43; Nitrogen, 3.62; Oxygen, 8.26; Found: Carbon, 55.76; Hydrogen, 2.73; Fluorine,
29.39; Nitrogen, 3.57; Oxygen, 8.22%; MS: m/z 387.
3.6.2.15 3-[bis-3,5(methyltrifluoro)phenyl]-5-phenylisoxazole (TV-130)
Yield: 76%; mp 200ºC; Analytical Calculation for C17H10F6O: Carbon, 59.31; Hydrogen, 2.93;
Fluorine, 33.11; Oxygen, 4.65; Found: Carbon, 59.31; Hydrogen, 2.93; Fluorine, 33.11; Oxygen,
4.65%; MS: m/z 344.
CF3
F3C
N O
H3CO
CF3
F3C
N O
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
58 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Series:- 3 Pyrazole
3.7 Reaction Scheme
O
CF3
CF3
R
CF3
CF3
N NH
R
Methanol
R = TV 130 to 145
NH2NH2.H20
sodium acetate
Fig-3.16
Table 3.2 Physical Data Table of Series-3
Code R1 M.F. MW MP
Yield % R f1 Rf2
TV-131 4-Cl C17H9ClF6N2 390 165 76 0.40 0.69
TV-132 4-F C17H9F7N2 374 145 71 0.48 0.60
TV-133 4-Br C17H9BrF6N2 435 164 80 0.45 0.68
TV-134 4-CH3 C18H12F6N2 370 154 77 0.50 0.65
TV-135 4-OCH3 C18H12F6N2 386 157 58 0.49 0.69
TV-136 3-Cl C17H9ClF6N2 490 157 60 0.59 0.61
TV-137 4-F C17H9F7N2 374 159 76 0.40 0.68
TV-138 3-Br C17H9BrF6N2 435 167 73 0.48 0.62
TV-139 3-OCH3 C18H12F6N2 386 171 81 0.45 0.68
TV-140 3,4-DiOCH3
C19H14F6N2 416 167 70 0.50 0.69
TV-141 2-Cl C17H8ClF6N2 390 168 57 0.49 0.60
TV-142 2-F C17H9ClF6N2 374 149 63 0.45 0.68
TV-143 2-Br C17H9F7N2 435 159 62 0.43 0.65
TV-144 2-OCH3 C18H12F6N2 386 182 61 0.47 0.76
TV-145 H C17H10F6N2 343 169 72 0.49 0.68
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
59 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Table-3.2
TLC Solvent system Rf1: Hexane: Ethyl acetate – 8:2;
Rf2: Chloroform: Methanol - 7:3.
3.8 Plausible Reaction Mechanism
Fig-3.17
NH2NH2
R1
F3C
F3C
O
HN :NH2
R1
F3C
F3C
O
HN :NH2HR1
OF3C
F3C
H
H
F3C
F3CN NH
H
R1F3C
F3CN NH
OH H
R1F3C
F3CN NH
R1
-H2O
F3C
F3CN O
R1
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
60 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.9 Experimental
3.9.1 Materials and Methods
Melting points were determined in open capillary tubes and are uncorrected. Formation
of the compounds was routinely checked by TLC on silica gel-G plates of 0.5 mm thickness and
spots were located by iodine. IR spectra were recorded Shimadzu FT-IR-8400 instrument using
potassium bromide pellet method. Mass spectra were recorded on Shimadzu GC-MS-QP-2010
model using direct injection probe technique. 1H NMR was determined in DMSO-d6 solution on
a bruker Ac 400 MHz spectrometer. Elemental analysis of the all the synthesized compounds
was carried out on elemental vario EL III carlo erba 1108 model and the results are in
agreements with the structures assigned.
3.9.2 General procedure for the synthesis of 3-[bis-3,5(methyltrifluoro)phenyl]-5-
(substitutedphenyl)-1H-pyrazole (TV- 131 to 145)
A mixture of (E)-1-[bis-3,5(methyltrifluoro)phenyl]-3-(4-substitutedphenyl)prop-2-en-1-one
(0.02 mol), hydrazine hydrate (0.02 mol) and sodium acetate in ethanol (30 ml) was refluxed for
4 hr. The mixture was concentrated by distilling out the solvent under reduced pressure and
poured into ice water. The precipitate obtained was filtered, washed and recrystallized. The
completion of the reaction was monitored by TLC.
3.9.2.1 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-chlorophenyl)-1H-pyrazole (TV-131)
CF3
F3C Cl
N NH
Yield: 77%; mp 203ºC; Analytical Calculation for C17H9ClF6N2 : Carbon, 52.26; Hydrogen,
2.32; Chlorine, 9.07; Fluorine, 29.18; Nitrogen, 7.17; Found: Carbon, 52.16; Hydrogen, 2.14;
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
61 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Chlorine, 8.94; Fluorine, 29.02; Nitrogen, 7.01%; IR (cm-1): 3363/3271 (Carbon-H stretch of
aromatic ring), 1703 (Carbon=O stretch), 1662, 1597 and 1523 (Carbon=Carbon stretch of
aromatic ring), 1070 (C-H in plane deformation of aromatic ring), 1014 (C-F stretching), 833 (C-
H out of plane bending of 1,4-disubutituion), 1012 (C-F stretching); MS: m/z 390; 1H NMR
(DMSO-d6) δ ppm: 7.09-7.11 (s, 1H ,Ha), 7.27-7.29 (d, 2H, Hbb’), 7.44-7.46 (d, 2H, Hcc’), 7.61-
7.65 (m,1H, Hdd’,), 7.88 (s, 1H, He), 12.50 (s, 1H, Hf).
3.9.2.2 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-fluorophenyl)-1H-pyrazole (TV-132)
Yield: 58%; mp 201ºC; Analytical Calculation for C17H9F7N2: Carbon, 54.56; Hydrogen, 2.42;
Fluorine, 35.53; Nitrogen, 7.49; Found: Carbon, 54.46; Hydrogen, 2.12; Fluorine, 35.23;
Nitrogen, 7.33%; MS: m/z 374.
3.9.2.3 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-bromophenyl)-1H-pyrazole (TV-133)
Yield: 67%; mp 189ºC; Analytical Calculation for C17H9BrF6N2: Chlorine, 46.92; Hydrogen,
2.08; Bromine, 18.36; Fluorine, 26.19; Nitrogen, 6.44; Found: Carbon, 46.52; Hydrogen, 2.01;
Bromine, 18.21; Fluorine, 26.01; Nitrogen, 6.44%; MS: m/z 435.
CF3
F3C
N NH
F
CF3
F3C Br
N NH
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
62 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.9.2.4 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-methylphenyl)-1H-pyrazole (TV-134).
Yield: 68%; mp 186ºC; Analytical Calculation for C17H10F6N2: Carbon, 58.38; Hydrogen, 3.27;
Fluorine, 30.78; Nitrogen, 7.57; Found: Carbon, 58.10; Hydrogen, 3.16; Fluorine, 30.58;
Nitrogen, 7.23 %; MS: m/z 370.
3.9.2.5 3-[bis-3,5(methyltrifluoro)phenyl]-5-(4-methoxyphenyl)-1H-pyrazole (TV-135).
Yield: 74%; mp 221ºC; Analytical Calculation for C18H13F6ON2: Carbon, 55.97; Hydrogen, 3.13;
Fluorine, 29.51; Nitrogen, 7.25; Oxygen, 4.14; Found: Carbon, 55.77; Hydrogen, 3.03; Fluorine,
29.21; Nitrogen, 7.25; Oxygen, 4.04%; MS: m/z 386.
3.9.2.6 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-chlorophenyl)-1H-pyrazole (TV-136).
CF3
F3C CH3
N NH
CF3
F3C OCH3
N NH
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
63 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 56%; mp 204ºC; Analytical Calculation for C17H9ClF6N2: Carbon, 52.26; Hydrogen, 2.32;
Chlorine, 9.07; Fluorine, 29.18; Nitrogen, 7.17; Found: Carbon, 52.06; Hydrogen, 2.04;
Chlorine, 8.74; Fluorine, 29.12; Nitrogen, 7.10%%; MS: m/z 390.
3.9.2.7 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-fluorophenyl)-1H-pyrazole (TV-137)
Yield: 76%; mp 224ºC; Analytical Calculation for C17H9F7N2: Carbon, 54.56; Hydrogen, 2.42;
Fluorine, 35.53; Nitrogen, 7.49; Found: Chlorine, 54.36; Hydrogen, 2.14; Fluorine, 35.13;
Nitrogen, 7.33%; MS: m/z 374.
3.9.2.8 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-bromophenyl)-1H-pyrazole (TV-138).
CF3
F3C
N NH
Cl
CF3
F3C
N NH
F
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
64 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 71%; mp 212ºC; Analytical Calculation for C17H9BrF6N2: Carbon, 46.92; Hydrogen, 2.08;
Bromine, 18.36; Fluorine, 26.19; Nitrogen, 6.44; Found: Carbon, 46.82; Hydrogen, 2.01;
Bromine, 18.30; Fluorine, 26.10; Nitrogen, 6.40%; MS: m/z 435.
3.9.2.9 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3-methoxyphenyl)-1H-pyrazole (TV-139)
Yield: 80%; mp 195ºC; Analytical Calculation for C18H13F6ON2: Carbon, 55.97; Hydrogen, 3.13;
Fluorine, 29.51; Nitrogen, 7.25; Oxygen, 4.14; Found: Carbon, 55.47; Hydrogen, 3.12; Fluorine,
29.34; Nitrogen, 7.15; Oxygen, 4.04%; MS: m/z 386.
3.9.2.10 3-[bis-3,5(methyltrifluoro)phenyl]-5-(3,4 dimethoxyphenyl)-1H-pyrazole (TV-140).
CF3
F3C
N NH
Br
CF3
F3C
N NH
OCH3
CF3
F3C
N NH
OCH3
OCH3
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
65 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 77%; mp 182ºC; Analytical Calculation for C19H14F6N2O2: Carbon, 54.81; Hydrogen,
3.39; Fluorine, 27.38; Nitrogen, 6.73; Oxygen, 7.69; Found: Carbon, 54.51; Hydrogen, 3.29;
Fluorine, 27.18; Nitrogen, 6.43; Oxygen, 7.49%; MS: m/z 416.
3.9.2.11 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-chlorophenyl)-1H-pyrazole (TV-141).
Yield: 58%; mp 242ºC; Analytical Calculation for C17H9ClF6N2 : Carbon, 52.26; Hydrogen,
2.32; Chlorine, 9.07; Fluorine, 29.18; Nitrogen, 7.17; Found: Carbon, 52.06; Hydrogen, 2.02;
Chlorine, 8.82; Fluorine, 28.85; Nitrogen, 6.95%, MS: m/z 379.
3.9.2.12 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-fluorophenyl)-1H-pyrazole (TV-142)
Yield: 60%; mp 212ºC; Analytical Calculation for C17H9F7N2: Carbon, 54.56; Hydrogen, 2.42;
Fluorine, 35.53; Nitrogen, 7.49; Found: Carbon, 54.37; Hydrogen, 2.27; Fluorine, 35.18;
Nitrogen, 7.16%; MS: m/z 374.
3.9.2.13 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-bromophenyl)-1H-pyrazole (TV-143)
CF3
F3C
N NH
Cl
CF3
F3C
N NH
F
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
66 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Yield: 62%; mp 224ºC; Analytical Calculation for C17H9BrF6N2: Carbon, 46.92; Hydrogen, 2.08;
Bromine, 18.36; Fluorine, 26.19; Nitrogen, 6.44; Found: Carbon, 46.72; Hydrogen, 1.95;
Bromine, 18.16; Fluorine, 16.19; Nitrogen, 6.14%; MS: m/z 435.
3.9.2.14 3-[bis-3,5(methyltrifluoro)phenyl]-5-(2-methoxyphenyl)-1H-pyrazole (TV-144).
Yield: 66%; mp 209ºC; Analytical Calculation for C18H13F6ON2: Carbon, 55.97; Hydrogen, 3.13;
Fluorine, 29.51; Nitrogen, 7.25; Oxygen, 4.14; Found: Carbon, 55.97; Hydrogen, 3.13; Fluorine,
29.51; Nitrogen, 7.25; Oxygen, 4.14%; MS: m/z 386.
CF3
F3C
N NH
Br
CF3
F3C
N NH
H3CO
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
67 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.9.2.15 3-[bis-3,5(methyltrifluoro)phenyl]-5-(phenyl)-1H-pyrazole (TV-145).
Yield: 76%; mp 200ºC; Analytical Calculation for C17H10F6N2: Carbon, 57.31; Hydrogen, 2.83;
Fluorine, 32.00; Nitrogen, 7.86; Found: Carbon, 57.21; Hydrogen, 2.53; Fluorine, 31.34;
Nitrogen, 7.66%; MS: m/z 356.
3.10 Spectral discussion
3.10.1 Mass spectral study
Shimadzu GC-MS-QP-2010 model was using for mass spectra. Proper fragmentation
came in spectral studies. Molecular weight peaks came of respective compounds. It has given
below.
CF3
F3C
N NH
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
68 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Mass fragmentation pattern for TV-116
CF3
F3C Cl
N O
m/z=392
CF3
F3C
N O
F3C Cl
N OF3C
N O
Cl
N O
CF3
F3C
N O
CF3
N O
Cl
N O
N O
m/z=357m/z=324
m/z=289
m/z=256
m/z=281m/z=213
m/z=69
m/z=180
Fig-3.18
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
69 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Mass fragmentation pattern for TV-131
CF3
F3C Cl
N NH
m/z=391
CF3
F3C
N NH
F3C Cl
N NHF3C
N NH
Cl
N NH
CF3
F3C
N NH
CF3
N NH
Cl
N NH
N NH
m/z=356m/z=323
m/z=288
m/z=255
m/z=280m/z=212
m/z=68
m/z=179
Fig-3.19
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
70 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.10.2 IR spectral study
Shimadzu FT-IR-8400 model records IR spectra using KBr pellet method. Various
functional groups here in molecule were identified by characteristic frequency obtained for them.
For Chalcones TV-116 to 145, assenting bands for secondary amine were observed at 3450-3200
cm-1 correspondingly. -N-H stretching bands at 3250-3390 cm-1 observed. Aromatic ring
skeleton (C=C starching) groups were observed at1600-1400 cm-1. C-N stretching aromatic of
isoxazole ring were observed at 1180-1200 cm-1 and 1300-1360 cm-1. C-Cl stretching were
observed at 700-850 cm-1. Another characteristic C-F (stretching vibration) was observed at
1000-1100 cm-1, which suggested formation of desired products TV - 116 to 145.
3.10.3 1H NMR spectral study
In 1H NMR DMSO-d6 used as a solvent with Brucker 400 MHz spectrometer & TMS
used as a standard. Synthesis compounds structures were proven by all protons and their
chemical shifts.
1H NMR spectra confirmed the structures of Chalcones TV - 116 to 145 on the basis of
following signals: Aromatic fluoro-ring protons observed at 7.4-7.8 δ ppm and aromatic other
ring protons observed around 7.0-7.2 δ ppm. A singlet for the (C-H) proton of five member ring
at 5.0-6.0 δ ppm, and singlets for N-H of pyrazole at 8.80-12.60 δ ppm and correspondingly.
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
71 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Mass spectrum of TV – 116
Fig-3.20
IR spectrum of TV – 116
Fig-3.21
CF3
F3C Cl
N O
CF3
F3C Cl
N O
M.W.- 391
Chapter:-4
Synthesis, Characterization and Biological Evaluation of some Chalcones and their
1H NMR spectrum of TV – 116
Expanded 1NMR spectrum of TV
Synthesis and biological activities of Isoxazole &Pyrazole
Characterization and Biological Evaluation of some Chalcones and their Derivatives
Fig-3.22
NMR spectrum of TV – 116
Fig-3.23
Synthesis and biological activities of Isoxazole &Pyrazole
72 Characterization and Biological Evaluation of some Chalcones and their
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
73 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Mass spectrum of TV – 131
Fig-3.24
IR spectrum of TV – 131
Fig-3.25
CF3
F3C Cl
N NH
CF3
F3C Cl
N NH
M.W.- 391
Chapter:-4
Synthesis, Characterization and Biological Evaluation of some Chalcones and their
1H NMR spectrum of TV – 131
Expanded 1NMR spectrum of TV
Synthesis and biological activities of Isoxazole &Pyrazole
Characterization and Biological Evaluation of some Chalcones and their Derivatives
Fig-3.26
1NMR spectrum of TV – 131
Fig-3.27
Synthesis and biological activities of Isoxazole &Pyrazole
74 Characterization and Biological Evaluation of some Chalcones and their
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
75 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.11 Biological evaluation
3.11.1 Antimicrobial evaluation
Antibacterial and antifungal activity was tested for all compounds. Staphyl-ococcus
(Aureus) Mtcc-96, Strept-ococcus (Pyogenes) Mtcc-443 as gram positive, e-coli mtcc (442),
pseudomonas (aeruginosa) mtcc (441) as gram negative, candida (albicans) mtcc (227),
aspergillus (niger) mtcc (282), aspergillus (clavatus) mtcc (1323) was taken with different drugs.
microbial type culture collection (mtcc) strains was used. Compounds growth at lowest
concentration was prevented. For MIC broth dilution method is more appropriate.
1. For both primary and secondary screening serial dilutions were prepared.
2. In absence of antibiotic in control tube is subculture immediately.
3. Drug concentration is check by control of MIC.
4. MIC records the lowest concentration growth of organism.
5. Amount of growth is tested.
Used methods for 1st and 2nd screening: -
In stock solution synthesis drugs concentration was 2000 (µg mL-1)
First screening: - In 1st screening (250 µg mL-1), (500 µg mL-1), (1000 µg mL-1) concentration
was taken of all compounds. Only Active drug will go in 2nd screening.
Second screening: - In second screening concentration of all drugs were taken even less then
first screening.
Reading Result: -As MIC 99.2% inhibited zone was taken showing highest dilution.
Results are given below.
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
76 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.12 Table-1:- Screening Result of antimicrobial activity for TV-116 to 130.
Code Concentration of minimum inhibition µg mL-1
Gram Positive Gram Negative Fungal species
S.a. S. p. E.c. P.a. C. a. A. n. A.c. TV-116 15 15 84 16 14 19 18 TV-117 16 16 21 17 19 18 13 TV -118 17 18 18 15 15 15 14 TV -119 15 19 19 18 17 17 19 TV -120 18 18 18 17 13 21 15 TV -121 13 17 15 14 14 18 17 TV -122 16 16 17 21 16 15 16 TV -123 21 16 16 16 19 16 20 TV -124 18 20 18 14 21 20 15 TV -125 16 18 20 19 16 15 18 TV -126 14 20 19 16 20 16 17 TV -127 17 14 14 15 13 20 21 TV -128 15 17 16 18 16 14 17 TV -129 16 21 15 17 15 14 16 TV -130 21 15 16 21 18 15 15 Gentamycin 21 18 13 19 - - - Ampicillin 20 15 14 16 - - - Chloramphenicol 19 17 20 12 - - - Iprofloxacin 21 20 18 15 - - - Norfloxacin 10 12 10 10 - - - Nystatin - - - - 13 18 16 Gresiofulvin - - - - 22 17 19
Table-3.3
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
77 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
Antimicrobial Screening Results for TV-131 to145
Code
Concentration of minimum inhibition µg mL -1
Gram Positive Gram Negative Fungal species
S.a. S. p. E.c. P.a. C. a. A. n. A.c.
TV -131 19 14 16 19 84 18 19
TV -132 16 13 18 16 21 15 18
TV -133 15 21 15 15 18 17 15
TV -134 15 19 22 15 19 16 17
TV -135 18 18 18 18 18 17 21
TV -136 16 14 16 16 15 16 18
TV -137 21 21 15 21 17 19 15
TV -138 15 16 20 15 16 17 16
TV -139 18 18 16 18 18 15 20
TV -140 17 19 18 17 20 20 15
TV -141 14 19 16 14 19 17 16
TV -142 14 14 17 14 14 13 20
TV -143 21 16 15 21 16 14 14
TV -144 16 22 14 16 15 19 14
TV -145 18 16 17 18 16 15 15
Gentamycin 21 18 13 19 - - -
Ampicillin 20 15 14 16 - - -
Chloramphenicol 19 17 20 12 - - -
Iprofloxacin 21 20 18 15 - - -
Norfloxacin 10 12 10 10 - - -
Nystatin - - - - 13 18 16
Gresiofulvin - - - - 22 17 19
Table-3.4
Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
78 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
3.12 References
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Chapter:-4 Synthesis and biological activities of Isoxazole &Pyrazole
80 Synthesis, Characterization and Biological Evaluation of some Chalcones and their
Derivatives
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