The present invention relates to an antifungal agent. In particular, the present invention relates to an antifungal agent used for the treatment against fungal pathogens easily developing resistance to commonly used antifungal agents. Further, the present invention relates to a process for producing such derivatives and acid addition salts thereof and to a pharmaceutical composition comprising a derivative and a pharmaceutically acceptable salt thereof. In particular, the present invention relates to the overcoming challenge of treatment and prevention of invasive fungal infections is underscored by their high incidence in immune compromised hosts, as well as by their formidable morbidity and mortality. Furthermore, the present invention relates to intermediates in the synthesis of chromen-2-one compounds used as an antifungal agent, and a method for its preparation targeting . Candida spp. that is currently the third-to-fourth leading cause of bloodstream infections. More particularly, the present invention relates to a derivative containing a Schiff bases for treatment of various antimicrobial infections
BACKGROUND OF THE INVENTION
The importance of Schiff base complexes for bioinorganic chemistry, biomedical applications, supramolecular chemistry, catalysis and material science, separation and encapsulation processes, and formation of compounds with unusual properties and structures has been well recognized and reviewed. They also serve as a back bone for the synthesis of various heterocyclic compounds. Schiff bases have been utilized as synthons in the preparation of a number of industrial and biologically active compounds like formazans, 4-thiazolidinines, benzoxazines, and so forth, via ring closure,
Schiff base (also known as imine or azomethine) is an analogue of a ketone or aldehyde in which the carbonyl group has been replaced by an imine or azomethine group. A Schiff base compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group. The antifungal Schiff bases or the like are used for example in the treatment of bloodstream infections. However, it was recently discovered synthetic Schiff bases as a type of antifungal agents. Even in these type agents, however, there is an urgent need for the development of more effective anti-fungal agent, in terms of their action against fungal pathogens easily developing resistance to commonly used antifungal agents. Several Schiff bases have been reported for their significant biological activities like antitumor, antiviral, anti-inflammatory agents, insecticidal, antibacterial, antituberculosis, antimicrobial, anticonvulsant activity etc. Schiff bases also exhibit antimalarial, antiproliferative, and antipyretic activities
Krishna Murthy et al, Indian J. Chem. 10 (1972), 34-40 have tested 4-methyl-7-(3-phenylisoxazol-5-yl-methoxy)-coumarin for fungicidal and bacteriostatic action with little or

no success, US Patent US5073563 describes similar substructure -methoxycoumarin type of compounds which possess monoaminooxidase (MAO)-inhibiting activity. Another prior art US20090312406 reported related scaffolds for antiviral compounds but didn't reach the exact structure of the present invention. The present invention provides an antifungal agent more effective than conventional anti-fungal agents and intermediates.
SUMMARY OF THE INVENTION
The present inventors have conducted extensive investigations. The result is the following
inventions:
I. A compound represented by the general formula:

^^
wherein R are different from each other and denote individually as hydrogren , methyl , halogen , N02 or methoxy , wherein R represents a hydrogen atom or a lower alkyl group;The aromatic ring or a condensed ring which may have one or more hetero-atoms and may have one or more substituents; or an aromatic ring or a condensed ring thereof wherein a part or whole of an aromatic ring or a condensed ring thereof which may have one or more heteroatoms, and may have one or more substituents are saturated.
The substituent R is hydrogen atom, a halogen atom, a lower alkyl group, a halogenated lower alkyl group, lower alkoxyl group, a halogenated lower alkoxy group, a hydroxyl group, a thiol group, nitro group, cyano group, lower alkanoyl group, a phenyl group which may have one or more substituents , phenoxy group which may have one or more substituent groups, bromophenyl, chloro phenyl, dichloro phenyl at different positions in the aromatic ring, or a salt thereof.
The term "alkyl" refers to a straight or branched monovalent hydrocarbon containing, unless otherwise stated, 1-20 carbon atoms (e.g., C 1-C 10). Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl. The term "alkylene"

refers to a straight or branched bivalent hydrocarbon, containing 1-20 carbon atoms (e.g., C 1-C10).
Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy. The term "acyloxy" refers to an —O— C(O)—R radical in which R can be H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl.
The term "aryl" refers to a monovalent 6-carbon monocyclic, 10-carbon bicyclic, 14-carbon tricyclic aromatic ring system. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl. The term "arylene" refers to a bivalent 6-carbon monocyclic, 10-carbon bicyclic, 14-carbon tricyclic aromatic ring system. The term "aryloxyl" refers to an —O-aryl. The term "arylamino" refers to an —N(R)-aryl in which R can be H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl. The term "heteroaryl" refers to a monvalent aromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system having one or more heteroatoms (such as O, N, S, or Se). Examples of heteroaryl groups include pyridyl, furyl, imidazolyl, benzimidazolyl, pyrimidinyl, thienyl, quinolinyl, indolyl, and thiazolyl. The term "heteroarylene" refers to a bivalent aromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system having one or more heteroatoms (such as O, N, S, or Se).
The coumarin compounds described herein include the compounds themselves, as well as their salts, their solvates, and their prodrugs, if applicable. A salt, for example, can be formed between an anion and a positively charged group (e.g., amino) on a coumarin compound. Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate. Likewise, a salt can also be formed between a cation and a negatively charged group (e.g., carboxylate) on a coumarin compound. Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and an ammonium cation such as tetramethylammonium ion. The coumarin compounds also include those salts containing quaternary nitrogen atoms. Examples of prodrugs include esters and other pharmaceutically acceptable derivatives, which, upon administration to a subject, are capable of providing active coumarin compounds.
A process for producing chromen-2-one which comprises reacting 2-Bromo-l-phenylethanone with 7- Hydroxy- 4-methylcoumarin

A process for producing intermediate 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one by reacting 2-Bromo-l-phenylethanone with 7- Hydroxy- 4-methylcoumarin and their salts thereof
A process for producing 7-(2-((substituted phenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2one by intermediate 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one by reacting 2-Bromo-l-phenylethanone with 7- Hydroxy- 4-methylcoumarin
A process for producing 7-(2-((substituted phenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2one by intermediate 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one by reacting 2-Bromo-l-phenylethanone with 7- Hydroxy- 4-methylcoumarin by reaction with aniline and substituted aniline compounds
Further, this invention relates to a method for treating bacterial infections, more specifically for the treatment against Candida species.
The details of one or more embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will be apparent from the description and the claims.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING
Figure 1: (a) The binding orientation and interaction of SB-4 in the binding pocket; (b) comparison of binding mode and interaction of Terbinafine and SB-4 in the binding pocket of human squalene epoxidase (PDB ID: 6C6N).
Figure 2: (a) The binding orientation and interaction of SB-4 in the binding pocket; (b) comparison of binding mode and interaction of Clotrimazole and SB-4 in the binding pocket of 14-alpha-demethylase (PDB ID: 5TZ1).
Figure 3: Synthesis of Schiff bases as claimed in the claims.
DETAILED DESCRIPTION OF THE INVENTION
Shown below are exemplary compounds of this invention:

Formula

Structure

X
II



III



IV



tT■cy %
V

VI
VII


o
=f

VIII
IX

N —if x)—u o —i
o" ^ *
O (f \) N O P >


XI
XII
XIII
XIV
XV
XVI

The route shown in Scheme 1 exemplifies synthesis of the coumarin compounds of the present invention. Equimolar amounts of 2-bromo-l-phenylethanone 1 (O.Olmol), 7-hydroxy-4-methylcoumarin 2 (0.01 mol) and Anhydrous K2C03 (0.02 mol) in dry acetonitrile was refluxed for about 8 h. The mixture was filtered and solvent was removed under reduced pressure. The resulting solid was washed with aqueous sodium hydroxide solution (20%) and with excess of water. The crude product was purified by recrystallization from ethanol to afford compound 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one.
A mixture of compound 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one. (0.01 mol), substituted aniline (O.Olmol) and 1 ml of glacial acetic acid in methanol was refluxed on water bath for 12 h. The mixture was allowed to cool, and then the separated solid was washed with water filtered and recrystalhzed from methanol to generate the exemplary compounds as illustrated in figure 3.

A chromen-2-one compound thus synthesized can be further purified by flash column chromatography, high performance liquid chromatography, crystallization, or any other suitable methods.
The compounds mentioned herein may contain a non-aromatic double bond and one or more asymmetric centers. Thus, they can occur as racemates and racemic mixtures, single enantiomers, individual diastereomers, diastereomeric mixtures, and cis- or trans-isomeric forms. All such isomeric forms are contemplated.
The drugs are used against microbes are known as antimicrobials. A microorganism, or microbe, is a microscopic organism, which may exist in its single-celled form or in a colony of cells. An antimicrobial is an agent that kills microorganisms or stops their growth. The antimicrobial agents are classified as disinfectants ("nonselective antimicrobials"), which kill a wide range of microbes on non-living surfaces to prevent the spread of illness, antiseptics (which are applied to living tissue and help reduce infection during surgery), and antibiotics (which destroy microorganisms within the body). Antibacterial agents can be further subdivided into bactericidal agents, which kill bacteria, and bacteriostatic agents, which slow down or stall bacterial growth. In response, further advancements in antimicrobial technologies have resulted in solutions that can go beyond simply inhibiting microbial growth. Instead, certain types of porous media have been developed to kill microbes on contact.
Antimicrobial medicines can be grouped according to the microorganisms they act primarily against for example, antibacterials are used against bacteria and antifungal are used against fungi.
All the target compounds were docked into the binding pocket of the 5TZ1 target protein and docking pose analysis revealed the similar binding mode and interaction with amino acid residues. The molecular docking score values and interacting amino acid residues within 3A for all synthesized compounds are shown in Table 1 and the data is presented in Table 2.The docking score values for all the synthesized compounds ranges from -7.229 kcal/mol to -10.674kcal/mol. In order to understand the binding orientation and amino acid residues interaction, one of the top poses (Formula: IV). The binding pose revealed that the coumarin core of the compound juxtaposed into the amino acid residues comprised of Pro230, Phe233, His377, Ser378, and Met508. Most of the residues carry hydrophobic characteristic that justifies the coumarin group orientation and binding (Figure 2). The carbonyl group of coumarin core forms H-bond with backbone atoms of Ser-378 and n-n stacking has been observed with His-377 amino acid residues. The nature of amino acid residues within a binding radius of 3 A comprised of aliphatic, hydrophobic i.e. isoleucine (He 131, Ile304); leucine (Leul21, Leu376), and methionine (Met508); aromatic, hydrophobic i.e. phenylalanine (Phel26, Phe228, Phe233), tyrosine (Tyrll8, Tyrl32), proline (Pro230) and

histidine (His377); and the polar, uncharged i.e. threonine (Thr311) and serine (Ser378) amino acid residues. Among all the analyzed compounds, 2, 9 did not display any kind of interaction, however comparing the docking score with other docked compound, and they fall in mid-range of the docking score. Furthermore, all other compounds have established the H-bond with Ser378 and 71-71 stacking with Tyrl32, Phe228, and His377. Comparison of docked pose with clotrimazole binding mode shows similar binding orientation and interactions with binding amino acid residues (Figure lb). Comparing the binding amino acid residues, most of the residues belong to hydrophobic amino acid residues
Without further elaboration, it is believed that the above description has adequately enabled the present invention. The following examples are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. All of the publications cited herein are hereby incorporated by reference in their entirety.
Table 1: Comparison of binding affinity of target compounds, and standard drugs (Clotrimazole and Terbinafine) against 14-alpha-demethylase (PDB ID: 5TZ1).

Docking Score
Formula
II
III
IV
V
VI

Amino Acid Residues within 3 A of the binding site
Leul21, Phel26, Ilel31, Tyrl32, Phe228,
-9.47 Pro230, Phe233, Gly303, Ile304, Gly307,
Leu376, HIE377, Ser378, Met508
Tyrll8, Leul21, Thrl22, Phel26, Ilel31,
-9.83 Tyrl32, Phe228, Pro230, Phe233, Ile304,
Gly307, Gly308, Leu376, Ser378, Met508
Tyrll8, Leul21, Phel26, Ilel31, Tyrl32,
-7.91 Phe228, Phe233, Gly303, Ile304, Gly307,
Gly308, Leu376, Ser378, Met508
Tyrll8, Leul21, Phel26, Ilel31, Tyrl32,
-10.17 Phe228, Pro230, Phe233, Ile304, Thr311,
Leu376, HIE377, Ser378, Met508
Tyrll8, Leu 121, lie 131, Tyrl32, Phe228,
-10.39 Pro230, Phe233, Gly303, Ile304, Gly307,
Thr311, Leu376, Hie377, Ser378, Met508
Leul21, Tyrl32, Phe228, Pro230, Phe233,
-10.04 Gly307, Thr311, Leu376, HIE377,
Ser378, Met508, Val509

Amino Acid Residues involved in interactions
H-bond interaction with Ser378
pi-pi interaction with Phe228
H-bond interaction with Ser378, and pi-pi interaction with Hie377
H-bond interaction with Ser378
H-bond interaction with Ser378, pi-pi interaction with Phe228

Tyrl 18, Leu 121, Pro230, Phe233, HIE377, Ser378, Tyrl 18, Leu 121, Phe228, Pro230, Gly307, Gly308, Met508
Tyrl 18, Leu 121, Phe228, Pro230, Thr311,Leu376, Met508
VII
■10.05
VIII
IX
.09
X
■10.16
XI
-8.26
XII
-8.84
XIII
-9.97
XIV
-9.56
XV
■10.67
XVI
-7.22
Clotrimazole -8.090

lie 131, Tyrl32, Phe228,
Ile304, Gly307, Leu376,
Met508
Phel26, lie 131, Tyrl32,
Phe233, Gly303, Ile304,
Leu376, Hie377, Ser378,
Thrl22, Phel26, Tyrl32, Phe233, Gly307, Gly308, HIE377, Ser378, Ser507,
Leul21, Phel26, Tyrl32, Phe228, Pro230, Phe233, Gly307, HIP310, Thr311, Leu376, HIE377, Ser378, Met508, Val509
Tyrl 18, Leu 121, lie 131, Tyrl32, Phe228, Pro230, Phe233, Ile304, Gly307, Gly308, Leu376, Ser378, Ile379, Met508 Tyrll8, Leul21, Thrl22, Phel26, Ilel31, Tyrl32, Phe228, Pro230, Phe233, Gly303, Ile304, Gly307, Leu376, HIE377, Ser378, Met508
Tyrl 18, Leul21, Phel26, Tyrl32, Phe228, Pro230, Phe233, Gly307, Hip310, Thr311, Leu376, HIE377, Ser378, Met508, Val509
Tyrl 18, Leul21, Thrl22, Phel26, Tyrl32, Phe228, Pro230, Phe233, Gly307, Hip310, Thr311, Leu376, HIE377, Ser378, Met508, Val509
Tyrl 18, Leul21, Phel26, Ilel31, Tyrl32, Phe228, Pro230, Phe233, Gly307, Thr311, Leu376, HIE377, Ser378, Met508 Tyr64, Tyrl 18, Leul21, Thrl22, Phel26, Tyrl32, Phe228, Pro230, Thr311, Leu376, Hie377, Ser378, Phe380, Ser507, Met508, Val509
Tyrll8, Leul21, Thrl22, Phel26, Ilel31, Tyrl32, Phe228, Gly303, Gly307, His310,

H-bond interaction with Ser378
pi-pi interaction with Phe228
H-bond interaction with Hie377, Ser378, pi-pi interaction with HEM601
pi-pi interaction with Phe228
H-bond interaction with Hie377, Ser378
H-bond interaction with Ser378, pi-pi interaction with HEM601
H-bond interaction with Ser378, pi-pi interaction with Tyrl32
H-bond interaction with Ser378
pi-pi interaction with Hie377
71-71 interaction with Tyrll8andPhe228

Thr311, Leu376, Met508, Val509

Tyrll8, Leul21, Thrl22, Phel26, Ilel31,
Terbinafine -8.174 Tyrl32, Pro230, Phe233, Gly307, Thr311,
Leu376, His377, Ser378, Phe380, Met508

7i-cation interaction withTyrll8

Table-2 - Data for Exemplary compounds

Example IR (KBr) v (cm-1)

1H NMR (CDC13, 5 ppm)

II
III
IV
V
VI
VII
VIII
IX
X
XI

3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1152 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str.) 3061 (CH, Ar Str.), 2902 (CH, Ali Str.), 1152 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str. 3061 (CH, Ar Str.), 2900 (CH, Ali Str.), 1163 (C-O-C, Str.), 1615 (C=N Str), 1209 (C-N Str.). 3064 (CH, Ar Str.), 2901 (CH, Ali Str.), 1163 (C-O-C, Str.), 1615 (C=N Str), 1209 (C-N Str. 3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1162 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str. 3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1156 (C-O-C, Str.), 1615 (C=N Str), 1237 (C-N Str.
3063 (CH, Ar Str.), 2900 (CH, Ali
Str.), 1156 (C-O-C, Str.), 1594
(C=N Str), 1209 (C-N Str.)
2900 (CH, Ali Str.), 1112 (C-O-C,
Str.), 1594 (C=N Str), 1237 (C-N
Str.).
2900 (CH, Ali Str.), 1112 (C-O-C,
Str.), 1615 (C=N Str), 1208 (C-N
Str.).
2900 (CH, Ali Str.), 1156 (C-O-C,
Str.), 1594 (C=N Str), 1209 (C-N
Str.).
3064 (CH, Ar Str.), 2906 (CH, Ali

6.51-8.45 (14H, Ar.), 5.41 (2H, s, OCH ), 2.58 (3H, s, CH3).
6.62-7.98 (13H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3), 2.38 (3H, s, CH3).
6.61-8.08 (13H, Ar.), 5.47 (2H, s, OCH2), 2.57 (3H, s, CH3).
6.60-8.00 (13H, Ar.), 5.58 (2H, s, OCH ), 2.58 (3H, s, CH ).
6.67-8.11 (12H, Ar.), 5.41 (2H, s, OCH ), 2.58 (3H, s, CH ).
6.71-8.11 (13H, Ar.), 5.41 (2H, s, OCH ), 2.58 (3H, s, CH ).
. 6.60-8.02 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, QT).
6.63-8.10 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, CH3).
6.60-8.00 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, OCH3).
6.60-8.00 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, CH3).
6.59-8.00 (12H, Ar.), 5.41 (2H, s, OCH2),

6.60-8.12 (13H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3).
6.65-8.12 (13H, Ar.), 5.58 (2H, s, OCH2), 2.58 (3H, s, CH3).
Str.), 1156 (C-O-C, Str.), 1594 2.57 (3H, s, CH3) (C=N Str), 1228 (C-N Str.). 3062 (CH, Ar Str.), 2902 (CH, Ali XII Str.), 1156 (C-O-C, Str.), 1615 (C=N Str), 1208 (C-N Str.).
3063 (CH, Ar Str.), 2900 (CH, Ali XIII Str.), 1156 (C-O-C, Str.), 1594 (C=N Str), 1237 (C-N Str.).

6.64-8.12 (13H, Ar.), 5.58 (2H, s, OCH2), 2.58 (3H, s, CH3).
3060 (CH, Ar Str.), 2902 (CH, Ali
XIV Str.), 1152 (C-O-C, Str.), 1615
(C=N Str), 1237 (C-N Str.).
r 2.57 (3H, s, OCH3).
3060 (CH, Ar Str.), 2902 (CH, Ah 6 6i_8 02 (13H, Ar.), 5.41 (2H, s, OCH ),
XV Str.), 1152 (C-O-C, Str.), 1594
(C=N Str), 1228 (C-N Str.).
3064 (CH, Ar Str.), 2900 (CH, Ah 6.60.7.97 (13H, Ar.), 5.41 (2H, s, OCH ),
2.58 (3H, s, CH3), 2.38 (3H, s, CH3).
XVI Str.), 1156 (C-O-C, Str.), 1615
(C=N Str), 1228 (C-N Str.).
Antifungal Activity (In vitro data )
The antifungal testing was performed using the cup diffusion technique. The synthesized compounds, as 1 mg/ml solutions in dimethylformamide (DMF), were evaluated in vitro for activity against C. albicans by the cup diffusion technique.. Compounds showing inhibitory zones of at least 20 mm were considered active and were further evaluated for their minimal inhibitory concentration (MIC) using the two-fold serial dilution method . Clotrimazole and Terbinafine were used as standard antifungal agents. Dimethylformamide was used as a control. Sterile nutrient agar was inoculated with the test organisms (each 100 mL of the medium received 1 mL of 24 h broth culture), and then seeded agar was poured into sterile petri dishes. Cups (8 mm in diameter) were cut in the agar, and each cup received 0.1 mL of
o
the test compound solution. The plates were then incubated at 37 C for 24 h. The activity was estimated as zones of inhibition in mm diameter (Table 3 ) Clotrimazole and Terbinafine solutions (0.01%) were used as reference standards. DMF did not show any inhibition zones.
Minimum inhibitory concentration (MIC) measurement
Using the two-fold serial dilution method, the test organisms were grown in suitable broth for
o
48 h for fungi at 37 C. Two-fold serial dilutions of the test compounds solutions were prepared using the suitable broth to obtain concentrations between 1000 and 15.62 ug/ml. The tubes were then inoculated with the test organism (each 5 ml received 0.1 ml of the
o
above inoculum) and were incubated at 37 C for 48 hr. The tubes were then observed for the

presence or absence of microbial growth. The lowest concentration showing no growth was taken as the minimum inhibitory concentration. The MIC values of the prepared compounds are listed in Table 3.
Table 3- The Antifungal Activity of exemplary compounds 1-16.
Formula Zone of Inhibition MIC (ug/ml) Against C.
(in mm) Against C. Albicans Albicans

I 20 31.24
II 14 NC
III 20 31.24
IV 24 15.62
V 14 NC
VI 20 62.48
VII 18 NC
VIII 22 31.24
IX 18 NC
X 16 NC
XI 18 NC
XII 14 NC
XIII 16 NC
XIV 18 NC
XV 18 NC
XVI 18 NC
Clotrimazole 26 1.95
Terbinafine 26 2.60
The detailed description is further supported with given set of examples
Step I. Synthesis of 4-methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one, Reagents and conditions :(i) Anhydrous acetonitrile, Anhydrous K2C03, Reflux.
Procedure
Equimolar amounts of 2-bromo-l-phenylethanone (O.Olmol), 7-hydroxy-4-methylcoumarin (0.01 mol) and Anhydrous K2C03 (0.02 mol) in dry acetonitrile was refluxed for about 8 h. The mixture was filtered and solvent was removed under reduced pressure. The resulting solid was washed with aqueous sodium hydroxide solution (20%) and with excess of water. The crude product was purified by recrystallization from ethanol to afford compound 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one

The physical parameters were- Percentage yield : 55.00%,Melting range : 138-140oC, Rf value : 0.86 (Mobile phase : n-Hexane: Ethyl acetate (1:2), Molecular formula : C18H1404
IR (KBr) v (cm-1): 3032 (CH, Ar Str.), 2932 (CH, Ali Str.), 1085 (C-O-C, Str.), 1690 (C=0 Str). 1HNMR(CDC13, 5ppm): 6.70-8.01 (9H, Ar), 5.28 (2H, s, OCH2), 2.81(3H, s, CH3).
Step II. Synthesis of target compounds (Schiff bases) Synthesis of the target compounds. Reagents and conditions :(i) Methanol, Glacial Acetic acid, Reflux., Reagents and conditions :(i) Methanol, Glacial Acetic acid, Reflux.
General procedure- A mixture of compound 4-Methyl-7-(2-oxo-2-phenylethoxy)-2H-chromen-2-one (0.01 mol), substituted aniline (O.Olmol) and 1 ml of glacial acetic acid in methanol was refluxed on water bath for 12 h. The mixture was allowed to cool, and then the separated solid was washed with water filtered and recrystallized from methanol to afford the resultant compounds 1 to 16. The physical parameters were of the target compounds were following:
Example 1: 7-(2-((phenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 52.00%, Melting range : 168-170 o C, Rf value : 0.30, Mobile phase : n-Hexane: Ethyl acetate (3: l),Molecular formula : C24H19N03
IR (KBr) v (cm-1): 3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1152 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.51-8.45 (14H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3).
Example 2: 7-(2-((4-methylphenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 54.00%,Melting range : 70-71 oC, Rf value : 0.45,Mobile phase : n-Hexane: Ethyl acetate (3:1), Molecular formula : C25H21N03
IR (KBr) v (cm-1): 3061 (CH, Ar Str.), 2902 (CH, Ali Str.), 1152 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.62-7.98 (13H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3), 2.38 (3H, s, CH3).
Example 3: 7-(2-((4-chlorophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one (SB-3)
Percentage yield : 60.00%,Melting range : 140-142 oC ,Rf value : 0.43 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18 C1N03

IR (KBr) v (cm-1): 3061 (CH, Ar Str.), 2900 (CH, Ali Str.), 1163 (C-O-C, Str.), 1615 (C=N Str), 1209 (C-N Str.). 1HNMR (CDC13, 5 ppm): 6.61-8.08 (13H, Ar.), 5.47 (2H, s, OCH2),
2.57 (3H, s, CH3).
Example 4: 7-(2-((4-bromophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 62.00% ,Melting range : 150-152 oC ,Rf value : 0.35 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18 BrN03
IR (KBr) v (cm-1): 3064 (CH, Ar Str.), 2901 (CH, Ali Str.), 1163 (C-O-C, Str.), 1615 (C=N Str), 1209 (C-N Str.). 1HNMR (CDC13, 5 ppm): 6.60-8.00 (13H, Ar.), 5.58 (2H, s, OCH2),
2.58 (3H, s, CH3).
Example 5: 7-(2-((3, 4-dichlorophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 67.00% ,Melting range : 68-70 oC ,Rf value : 0.43, Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H17C12N03
IR (KBr) v (cm-1): 3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1162 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str.). 1HNMR(CDC13, 5 ppm): 6.67-8.11 (12H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3).
Example 6: 7-(2-((2-nitrophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 62.00% ,Melting range : 50-52 oC ,Rf value : 0.44 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18N205
IR (KBr) v (cm-1): 3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1156 (C-O-C, Str.), 1615 (C=N Str), 1237 (C-N Str.). 1HNMR(CDC13, 5 ppm): 6.71-8.11 (13H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3).
Example 7: 7-(2-((3-chlorophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 58.00% ,Melting range : 50-52 oC ,Rf value : 0.60, Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18C1N03
IR (KBr) v (cm-1): 3063 (CH, Ar Str.), 2900 (CH, Ali Str.), 1156 (C-O-C, Str.), 1594 (C=N Str), 1209 (C-N Str.). 1HNMR(CDC13, 5 ppm): 6.60-8.02 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, CH3).
Example8: 7-(2-((4-nitrophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one

Percentage yield : 53.00% ,Melting range : 148-150 oC ,Rf value : 0.75,Mobile phase : n-Hexane: ethyl acetate: (3:1) ,Molecular formula : C24H18N205
IR (KBr) v (cm-1): 3063 (CH, Ar Str.), 2900 (CH, Ali Str.), 1112 (C-O-C, Str.), 1594 (C=N Str), 1237 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.63-8.10 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, CH3).
Example 9: 7-(2-((4-methoxyphenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 50.00%, Melting range : 58-60 oC, Rf value : 0.63 , Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C25H21N04
IR (KBr) v (cm-1): 3062 (CH, Ar Str.), 2900 (CH, Ali Str.), 1112 (C-O-C, Str.), 1615 (C=N Str), 1208 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.60-8.00 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, OCH3).
Example 10: 7-(2-((2-chlorophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 54.00% ,Melting range : 150-152 oC ,Rf value : 0.49 ,Mobile phase : n-Hexane: Ethyl acetate (3: l)„Molecular formula : C24H18C1N03
IR (KBr) v (cm-1): 3062 (CH, Ar Str.), 2900 (CH, Ali Str.), 1156 (C-O-C, Str.), 1594 (C=N Str), 1209 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.60-8.00 (13H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, CH3).
Example 11: 7-(2-((2-chloro-4-nitrophenyl)imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 58.00%,Melting range : 90-92oC,Rf value : 0.82,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H17C1N205
IR (KBr) v (cm-1): 3064 (CH, Ar Str.), 2906 (CH, Ali Str.), 1156 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.59-8.00 (12H, Ar.), 5.41 (2H, s, OCH2), 2.57 (3H, s, CH3).
Example 12: 7-(2-((3-nitrophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 54.00%,Melting range : 112-114 oC ,Rf value : 0.58 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18N205

IR (KBr) v (cm-1): 3062 (CH, Ar Str.), 2902 (CH, Ali Str.), 1156 (C-O-C, Str.), 1615 (C=N Str), 1208 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.60-8.12 (13H, Ar.), 5.41 (2H, s, OCH2), 2.58 (3H, s, CH3).
Example 13: 7-(2-((2-bromophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 57.00% ,Melting range : 128-130 oC ,Rf value : 0.39 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18BrN03
IR (KBr) v (cm-1): 3063 (CH, Ar Str.), 2900 (CH, Ali Str.), 1156 (C-O-C, Str.), 1594 (C=N Str), 1237 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.65-8.12 (13H, Ar.), 5.58 (2H, s, OCH2), 2.58 (3H, s, CH3).
Example 14 7-(2-((4-fluorophenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 52.00% ,Melting range : 130-132 oC ,Rf value : 0.45 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C24H18FN03
IR (KBr) v (cm-1): 3060 (CH, Ar Str.), 2902 (CH, Ali Str.), 1152 (C-O-C, Str.), 1615 (C=N Str), 1237 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.64-8.12 (13H, Ar.), 5.58 (2H, s, OCH2), 2.58 (3H, s, CH3).
Example 15 7-(2-((2-methoxyphenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 53.00% ,Melting range : 60-62 oC ,Rf value : 0.34 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C25H21N04
IR (KBr) v (cm-1): 3060 (CH, Ar Str.), 2902 (CH, Ali Str.), 1152 (C-O-C, Str.), 1594 (C=N Str), 1228 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.61-8.02 (13H, Ar.), 5.41 (2H, s, OCH2),
2.57 (3H, s, OCH3).
Example 16 7-(2-((2-methylphenyl) imino)-2-phenylethoxy)-4-methyl-2H-chromen-2-one
Percentage yield : 55.00% ,Melting range : 64-65 oC ,Rf value : 0.68 ,Mobile phase : n-Hexane: Ethyl acetate (3:1) ,Molecular formula : C25H21N03
IR (KBr) v (cm-1): 3064 (CH, Ar Str.), 2900 (CH, Ali Str.), 1156 (C-O-C, Str.), 1615 (C=N Str), 1228 (C-N Str.). 1HNMR(CDC13, 5ppm): 6.60-7.97 (13H, Ar.), 5.41 (2H, s, OCH2),
2.58 (3H, s, CH3), 2.38 (3H, s, CH3).

Other Embodiments
All of the features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.
From the above description, one skilled in the art can easily ascertain the essential characteristics of the present invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, other embodiments are also within the scope of the following claims.

We claim:

1. An anti-fungal compound of general formula,
CH-,

^^

wherein R = hydrogren, methyl, halogen, N02 or methoxy;
wherein R represents a hydrogen atom or a lower alkyl group;
wherein R represents one or more hetero-atoms and may have one or more substituents.
2. The substituent R as claimed in clam 1, is hydrogen atom, results in formula I.

I
3. The substituent R as claimed in clam 1, is methyl atom,
wherein the methyl substituent is at position 4 results in formula II;


II
wherein the methyl substituent is at position 2 results in formula XV.

XVI
4. The substituent R as claimed in clam 1, is hetero atom, wherein the heteroatom is chloro; wherein the heteroatom is at position 4 results in formula III;

wherein the heteroatom is at position 3 results in formula VII;




N O
\ //
C

VII
wherein the heteroatom is at position 2 results in formula X;
^N
o ^ o

X
wherein the heteroatom chloro is a dichloro derivative at two different positions results in formula V;


/ ~\\ f

// \
c
V wherein the heteroatom is bromo at position 4 results in formula IV ;
o^o
Br
IV

wherein the heteroatom is bromo at position 2 results in formula XIII;

XIII
wherein the heteroatom is flouro at position 4 results in formula XIV.

XIV
5. The substituent R as claimed in clam 1, is other than hetero atom, wherein the other substituent is N02
wherein the N02 substituent is at position 2 results in formula VI;

VI
wherein the N02 substituent is at position 4 results in formula VIII;