The present disclosure relates generally to anti-microbial compounds. More specifically, the disclosure is directed to benzofuran and pyrazole substituted 1, 3, 4-oxadiazoles compounds of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof. The present disclosure also provides pharmaceutical compositions comprising the compounds and process of preparation of the compounds.
BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art. [0003] Antimicrobial agents are considered "miracle drugs" that are our prominent weapons to cure contagious diseases. Over decades of exploitation and overuse of the available drugs has lead to an uncontrolled rise in multidrug resistant pathogens. Multi-drug resistant pathogens' threat has increased at an alarming level around the world which has led to a global health crisis. To overcome the development of resistance and to combat it, it is crucial to synthesize a new class of antibacterial agents with novel mechanisms possessing promising biological and pharmacological activities.
[0004] In the development of novel drugs having wide range of pharmaceutical applications, 1, 3, 4-oxadiazoles are of keen interest. The 1,3,4-oxadiazoles nucleus is bioactive, a fruitful source and holds core stage in the area of drug discovery and many of them have been developed into clinically used drugs, e.g. Zibotentan, Tiodazosin, Raltegravir and Fenadiazole (shown below).

o=s=o
HN OCH3
H
N N
CHa
Zibotentan
(anti-cancer drug)
O
O Raltegravir
(HIV/AIDS)

NH2 Tiodazosin
a-1 adrenergic antagonist

Fenadiazole
Hhypnotic drug (Sleeping pills)

[0005] The literature is flooded with reports of a variety of biological activities of substituted-l,3,4-oxadiazoles including anticancer, antibacterial, antiviral, anti-tubercular, anti-HIV activity, anti-fungal agents, anti-inflammatory, analgesic, antitumor, antiepileptic activity, anticonvulsant, insecticidal and anti-allergic. They are also useful as dye pigments. Commercially available drugs in the market like Tiodazosin also contain oxadiazole nucleus which acts as anti-hypertensive agents.
[0006] There is a need in the art to develop novel compounds employing the core of 1, 3, 4-oxadiazole for effective anti-microbial activity.
OBJECTS OF THE INVENTION
[0007] An object of the present disclosure is to provide novel pharmaceutical
compounds with anti-microbial activity.
[0008] An object of the present disclosure is to provide pharmaceutical
compounds with anti-bacterial activity, low toxicity, which inhibit the activity of
/?- ketoacyl-acyl carrier protein synthase III enzyme and interfere with DNA
topoisomerase II.
[0009] Another object of the present disclosure is to provide a process of
preparation of these pharmaceutical compounds.

SUMMARY OF THE INVENTION
[0010] This summary is provided to introduce a selection of concepts in a
simplified form that are further described below in Detailed Description section.
This summary is not intended to identify key features or essential features of the
claimed subject matter, nor is it intended to be used as an aid in determining the
scope of the claimed subject matter.
[0011] Aspects of the present disclosure relate to compounds of l-(5-(5-
(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-aryl/heteroaryl-l,3,4-oxadiazol-
3(2H)-yl) ethanone, their salts or stereoisomers.
[0012] In an aspect, the present disclosure provides an anti-microbial
pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a
pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,

y
Formula I wherein Ri may be selected from (C6-Ci4)aryl, or (C5-Cio)heteroaryl, wherein Ri may be unsubstituted or substituted with one or more of halogen, amino, cyano, nitro, hydroxy, (Ci-Ce) alkyl, -COOH, -OR2, or -CH=CH-R2; and wherein R2 may be selected from (C1-C6) alkyl, phenyl, or -CFb-phenyl.
[0013] In an embodiment, the (C6-Ci4)aryl may be selected from phenyl,
naphthyl, or anthracenyl. hi an embodiment, the (C5-Cio)heteroaryl may be
selected from furanyl, thienyl, or pyrrolyl.
[0014] In an embodiment, the compound of Formula I may be selected from:

l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3 -yl) -2-(4-methoxyphenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(2-chl orophenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(2-fluorophenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethenone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(4-
(benzyloxy)phenyl)-l,3,4-oxadiazol-3(2H)yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-styryl-l,3,4-
oxadiazol-3(2H)-yl) ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(furan-2-yl)-l,3,4-
oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(thiophen-2-yl)-l,3,4-
oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(naphthalen-l-yl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
1 -(5-(5-(benzofuran-2-yl)-1 -phenyl- lH-pyrazol-3 -yl)-2-phenyl-1,3,4-
oxadiazol-3(2H)-yl) ethanone;
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a
pharmaceutically acceptable solvate thereof. [0015] In an aspect, the present disclosure provides a pharmaceutical composition comprising an anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable excipient. [0016] In another aspect, the present disclosure provides a process of preparing an anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein the process comprises the steps as shown in the general scheme I:
(a) reacting a carbohydrazide of Formula 1 with compounds of Formula 2 in the presence of a solvent to obtain a compound of Formula 3; and

(b) reacting a compound of Formula 3 with acetic anhydride to give a compound of Formula I.



N~NH2 * Y
Ph

N-N H

Scheme I [0017] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The following drawings form part of the present specification and are
included to further illustrate aspects of the present disclosure. The disclosure may
be better understood by reference to the drawings in combination with the detailed
description of the specific embodiments presented herein.
Figure 1 provides the binding mode analysis and interaction of compounds la, lb,
Ic and If, as per an embodiment of the present disclosure, in the active site of
DNA gyrase.
Figure 2 provides the binding mode analysis and interactions of compounds la,
lb, Ic and If, as per an embodiment of the present disclosure, in the active site of
/?- ketoacyl-acyl carrier protein synthase III enzyme.
.DETAILED DESCRIPTION OF THE INVENTION
[0019] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated

variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0020] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply. [0021] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0022] In some embodiments, numbers have been used for quantifying weights, percentages, ratios, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term "about." Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0023] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0024] As used in the description herein and throughout the claims that follow, the meaning of "a," "an," and "the" includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of "in" includes "in" and "on" unless the context clearly dictates otherwise. [0025] Unless the context requires otherwise, throughout the specification which follow, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense that is as "including, but not limited to."
[0026] Also, use of "(s)" as part of a term, includes reference to the term singly or in plurality, for example, the term pharmaceutically acceptable salt(s) indicates a single salt or more than one salt of the compound of Formula I. [0027] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. [0028] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention. [0029] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or

patentability. When any such inclusion or deletion occurs, the specification is
herein deemed to contain the group as modified.
[0030] The description that follows, and the embodiments described therein, is
provided by way of illustration of an example, or examples, of particular
embodiments of the principles and aspects of the present disclosure. These
examples are provided for the purposes of explanation, and not of limitation, of
those principles and of the disclosure.
[0031] It should also be appreciated that the present disclosure can be
implemented in numerous ways, including as a system, a method or a device. In
this specification, these implementations, or any other form that the invention may
take, may be referred to as processes. In general, the order of the steps of the
disclosed processes may be altered within the scope of the invention.
[0032] The headings and abstract of the invention provided herein are for
convenience only and do not interpret the scope or meaning of the embodiments.
[0033] The following discussion provides many example embodiments of the
inventive subject matter. Although each embodiment represents a single
combination of inventive elements, the inventive subject matter is considered to
include all possible combinations of the disclosed elements. Thus, if one
embodiment comprises elements A, B, and C, and a second embodiment
comprises elements B and D, then the inventive subject matter is also considered
to include other remaining combinations of A, B, C, or D, even if not explicitly
disclosed.
[0034] The term "or", as used herein, is generally employed in its sense
including "and/or" unless the content clearly dictates otherwise.
[0035] The term, "(Ci-C6)alkyl", as used herein, refers to the radical of saturated
aliphatic groups, including straight or branched-chain alkyl groups having six or
fewer carbon atoms in its backbone, for instance, C1-C6 for straight chain and C3-
C6 for branched chain. As used herein, (Ci-Ce)alkyl refers to an alkyl group
having from 1 to 6 carbon atoms. Representative examples of alkyl include, but
are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl,
sec-butyl, isobutyl, fert-butyl, isopentyl, 2-methylbutyl and 3-methylbutyl.

[0036] Furthermore, unless stated otherwise, the alkyl group can be unsubstituted or substituted with one or more substituents, for example, from one to four substituents, independently selected from the group consisting of halogen, hydroxy, cyano, nitro and amino. Examples of substituted alkyl include, but are not limited to hydroxymethyl, 2-chlorobutyl, trifluoromethyl and aminoethyl. [0037] The term "(C6-Ci4)aryl" or "aryl" as used herein refers to monocyclic or bicyclic or tricyclic hydrocarbon groups having 6 to 14 ring carbon atoms, wherein at least one carbocyclic ring is having a n electron system. Examples of (C6-C14) aryl ring systems include, but are not limited to, phenyl and naphthyl. [0038] The term, "(C5-Cio)heteroaryl", as used herein refers to a 5- to 10-membered, monocyclic or bicyclic, unsaturated ring system containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur. Representative examples of heteroaryls include, but are not limited to, furan, pyrrole, thiophene, imidazole, oxazole, thiazole, triazole, tetrazole, benzofuran, indole, benzoxazole, benzothiazole, isoxazole, triazine, purine, pyridine, pyrazine, quinoline, isoquinoline, phenazine, oxadiazole, pteridine, pyridazine, quinazoline, pyrimidine, isothiazole, benzopyrazine and tetrazole. [0039] The term, "halogen" as used herein refers to chlorine, fluorine, bromine or iodine atom.
[0040] The term, "therapeutically effective amount" as used herein refers to an amount of a compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof or a composition comprising a compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, effective in producing the desired therapeutic response in a particular subject suffering from a disease or disorder.
[0041] The term, "subject" as used herein refers to an animal, preferably a mammal, and most preferably a human. The term "mammal" used herein refers to warm-blooded vertebrate animals of the class 'mammalia' , including humans, characterized by a covering of hair on the skin and, in the female, milk-producing

mammary glands for nourishing the young, the term mammal includes animals such as cat, dog, rabbit, bear, fox, wolf, monkey, deer, mouse, pig and human. [0042] The terms, "treatment", "treat" and "therapy" and the like as used herein refer to alleviate, slow the progression, attenuation, prophylaxis or as such treat the existing diseases or condition (e.g., bacterial infection or fungal infection). Treatment also includes treating, preventing development of, or alleviating to some extent, one or more of the symptoms of the diseases or condition. [0043] Aspects of the present disclosure provide compounds with the 1, 3, 4-oxadiazole core substituted at the C2, C3 and C5 position to give anti-microbial activity. The C2, C3 and C5 positions are substituted with an aryl or heteroaryl group Ri, ethanone, and a pyrazole ring substituted with benzofuran and phenyl. [0044] In an embodiment, the present disclosure provides an anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,

N
Formula I wherein Ri may be selected from (C6-Ci4)aryl, or (C5-Cio)heteroaryl, wherein Ri may be unsubstituted or substituted with one or more of halogen, amino, cyano, nitro, hydroxy, (Ci-Ce) alkyl, -COOH, -OR2, or -CH=CH-R2; and
wherein R2 may be selected from (C1-C6) alkyl, phenyl, or -CFb-phenyl. [0045] In an embodiment, the (C6-Ci4)aryl may be selected from phenyl, naphthyl, or anthracenyl. In an embodiment, the (C5-Cio)heteroaryl may be selected from furanyl, thienyl, or pyrrolyl.

[0046] In an embodiment, Ri may be unsubstituted or substituted with CI, F, Br, I,
-OR2, or -CH=CH-R2.
[0047] In a preferred embodiment, R2 may be selected from methyl, ethyl, phenyl,
or -CFb-phenyl.
[0048] In an embodiment, the (C6-Ci4)aryl may be selected from phenyl, or
naphthyl; wherein the substituents may be selected from CI, F, Br, -OCH3, -O-
CH2-phenyl, -CH=CH-phenyl,
[0049] In an embodiment, the (C5-Cio)heteroaryl may be selected from furanyl, or
thienyl.
[0050] In an embodiment, the compound of Formula I may be selected from:
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3 -yl) -2-(4-methoxyphenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(2-chl orophenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(2-fluorophenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethenone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(4-
(benzyloxy)phenyl)-l,3,4-oxadiazol-3(2H)yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-styryl-l,3,4-
oxadiazol-3(2H)-yl) ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(furan-2-yl)-l,3,4-
oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(thiophen-2-yl)-l,3,4-
oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(naphthalen-l-yl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
1 -(5-(5-(benzofuran-2-yl)-1 -phenyl- lH-pyrazol-3 -yl)-2-phenyl-1,3,4-
oxadiazol-3(2H)-yl) ethanone;
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a
pharmaceutically acceptable solvate thereof.

[0051] In an embodiment, the compounds are effective anti-microbial agents. In a preferred embodiment, the compounds may be effective against gram positive and gram negative bacteria, including, but not limited to, Staphylococcus aureus, Escherichia coli, Proteus vulgaris, and Salmonella typhi.
[0052] Without being bound to theory, it is believed that the anti-microbial
activity of the compounds is due to the inhibition of the /?-ketoacyl-acyl carrier
protein synthase III enzyme and by interfering with DNA topoisomerase II of the
microbes. By affecting the DNA directly, the compounds of the present disclosure
avoid development of resistance and mutation in the microbes.
[0053] In an embodiment, the compound of Formula I can be converted into a
pharmaceutically acceptable salt. The pharmaceutical acceptable salts of the
compound of Formula I according to the disclosure are prepared in a manner
known to one skilled in the art. Pharmaceutically acceptable salts of the
compound of the present disclosure include but are not limited to, an acid salt of a
compound of the present disclosure containing an amine or other basic group can
be obtained by reacting the compound with a suitable organic or inorganic acid,
resulting in pharmaceutically acceptable anionic salt forms. Examples of anionic
salts include the acetate, benzenesulfonate, benzoate, bicarbonate, bitartrate,
bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride,
edetate, edisylate, estolate, esylate, fumarate, glyceptate, gluconate, glutamate,
glycollylarsanilate, hexylresorcinate, hydrobromide, hydrochloride,
hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylsulfate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate/diphosphate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate, tannate, tartrate, teoclate, tosylate, and triethiodide salts.
[0054] In yet another embodiment, the pharmaceutically acceptable salts of the compound of the present disclosure containing acidic functional group can be prepared by reacting with a suitable base. Such a pharmaceutically acceptable salt may be made with a base which affords a pharmaceutically acceptable cation, which includes alkali metal salts (especially sodium and potassium), alkaline earth

metal salts (especially calcium and magnesium), aluminum salts and ammonium
salts, as well as salts made from physiologically acceptable organic bases such as
trimethylamine, triethylamine, morpholine, pyridine, piperidine, picoline,
dicyclohexylamine, N,N'-dibenzylethylenediamine, 2-hydroxy ethyl amine, bis-(2-
hydroxyethyl)amine, tri-(2-hydroxyethyl)amine, procaine, dibenzylpiperidine,
dehydroabietylamine, N,N'-bisdehydroabietylamine, glucamine, N-
methylglucamine, collidine, quinine, quinoline, and basic amino acids such as lysine and arginine.
[0055] In an embodiment, the pharmaceutically acceptable solvates include, but are not limited to, monohydrates, dihydrates, sesquihydrates, tetrahydrates or combinations thereof.
[0056] In an embodiment, the present disclosure provides a pharmaceutical composition comprising an anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof and one or more of a pharmaceutically acceptable excipient(s).
[0057] In an embodiment, the excipient(s) may be selected from diluent, carrier, binder, disintegrant, glidant, lubricant, coating material, filler, solvent, surfactants, solubilizers, emulsifier, coloring agent, flavoring agent, or combinations thereof. However, a person of skill in the art would appreciate that any other excipient(s) may be employed without deviating from the spirit and scope of the invention. [0058] In an embodiment of the present disclosure, the pharmaceutical composition of compound of Formula I may be in the form of a tablet, a pill, a capsule, a solution, a gel, granules, a suspension, elixir, suppositories, a patch, cream, ointment, aerosol, spray or a powder.
[0059] In an embodiment, the composition may be administered orally, bucally, intraperitonially, parenterally, intravenously, intramuscularly, subcutaneously, topically, transdermally, rectally, intramuscularly, or their combinations. [0060] In the formation of the composition for various forms of administration a suitable excipient may be employed in the required quantity. For example, a tablet may be formed by using magnesium stearate, gum, talc, starch, sucrose, and

lactose; gelatin capsules or suppositories may be prepared by using waxes, oils, and fats; solutions, suspensions or elixirs may be prepared by using water, physiological sodium chloride solution, ethanol, glycerol, sugar solution, or a mixture of these solvents.
[0061] In an embodiment, the composition may comprise about 1% to about 90%, for example about 5% to about 70%, about 20% to about 50% by weight of the compound of Formula I. The amount of the compound of Formula I in the pharmaceutical compositions normally is from about 5 mg to 500 mg or may be lower than or higher than the lower and the upper limit respectively. The dose of the compound of Formula I, which is to be administered, can cover a wide range depending on the type of disease or disorder to be treated. The dose to be administered daily is to be selected to suit the desired effect, based on the subject, weight, past medical records or general health, weight, gender or age. [0062] In some embodiment, the composition may also be formed along with other pharmaceutically active component(s). In an embodiment, the combination of compound of present disclosure with other active component or treatment includes co-administration of a compound of Formula I with the other component or treatment as either a single combination dosage form or as multiple, separate dosage forms, administration of the compound of the present disclosure first, followed by the other component or treatment and administration of the other component or treatment first, followed by the compound of present disclosure. Further therapeutic agents are administered either simultaneously or sequentially. [0063] The pharmaceutical compositions containing the compound of Formula I according to the disclosure are prepared in a manner known to one skilled in the art.
[0064] In another embodiment, the present disclosure provides a pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof for use as an anti¬microbial agent.
[0065] In another embodiment, the present disclosure provides a medicament comprising a pharmaceutical compound of Formula I, a stereoisomer, a tautomer,

a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate
thereof.
[0066] In another embodiment, the present disclosure provides a process of
preparing an anti-microbial pharmaceutical compound of Formula I, a
stereoisomer, a tautomer, a pharmaceutically acceptable salt or a
pharmaceutically acceptable solvate thereof, wherein the process comprises the
steps as shown in the general scheme I.



NH2*
V

Scheme I where Ri is as defined previously. [0067] In another embodiment, the process comprises the steps of:
(a) reacting a carbohydrazide of Formula 1 with the compounds of Formula 2
in the presence of a solvent to obtain a compound of Formula 3; and
(b) reacting the compound of Formula 3 with acetic anhydride to give a
compound of Formula I.
[0068] In a preferred embodiment, the solvent may be ethanol.
[0069] In an embodiment, the reaction of compounds of Formula 1 with
compounds of Formula 2 may be catalyzed by a catalyst, preferably acetic acid.
[0070] The process gives high yields of the compounds. In some embodiments,
the yield may be achieved of up to 90%.
[0071] In another embodiment, the present disclosure provides a method of
treating anti-microbial infection in a subject by administering a therapeutically
effective amount of the compound or composition.

[0072] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art. EXAMPLES
[0073] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may vary. Examplel: Synthesis of compounds
[0074] The starting material 5-(Benzofuran-2-yl)-l-phenyl-lH-pyrazole-3-carbohydrazide (1) was synthesized according to scheme 2 which has been reported earlier (N.-J. Siddiqui, M. Idrees, N.T. Khati, M.G. Dhonde, Synthesis and antimicrobial activities of some new pyrazoles, oxadiazoles and isoxazole bearing benzofuran moiety, South African J. Chem. 66 (2013) 248-253).

fVu° (COW\ r1 o

Scheme 2 [0075] Nine compounds of Formula I, i.e., Formula Ia-i were synthesized using the Scheme 3 described below.



H T? H EtOH, AcOH f.
N^
o
2a-i

Scheme 3 [0076] Synthesis of l-(5-(5-(benzofuran-2-yl)-l-phenyl-li/-pyrazol-3 -yl) -2-(4-methoxyphenyl)-l,3,4-oxadiazol-3(2//)-yl)ethanone (la): 3.18 gms of carbohydrazide of Formula 1 was allowed to react with 1.21mL of 4-methoxybenzaldehyde (Formula 2a) in 25 mL of ethanol and 0.15mL of acetic acid and was refluxed for 2 hours to give iV'-(4-methoxy benzylidene)-5-(benzofuran-2-yl)-l-phenyl-l//-pyrazole-3-carbohydrazide (Formula 3a) in good yield. 2.18g, 0.005 mol of iV'-(4-methoxy benzylidene)-5-(benzofuran-2-yl)-l-phenyl-l//-pyrazole-3-carbohydrazide was taken in acetic anhydride (30mL). The reaction mixture was refluxed for 6h, allowed to cool and poured on crushed ice, reaction content was kept overnight, product obtained was filtered, washed, dried and re-crystallized from ethanol to get white crystalline solid, la.


Formula la
[0077] The structural identity of la was established on the basis of elemental analysis and spectral studies 'H-NMR, 13C-NMR, and IR and further supported by its Mass spectra. Characterization data-Appearance: White solid; Rf: 0.76; IR (KBr, -Umax in cm"1): 3065, 3018 (-C-H str., arom.), 2940 (C-H asym. str., aliph.), 2851 (C-H sym. str., aliph.), 1450 (C-H asym.def, aliph.), 1367 (C-H sym.def, aliph.), 1516, 1500 (C=C str., arom.), 1111,1032,1069 (C-H i.p.def, arom.), 845, 801 (C-H o.o.p.def, arom.), 1208, 1238 (C-O-C asym. str., ether), 1032, 1069 (C-O-C sym. str., ether), 1720 (C=0 str., -COCH3 group), 1595 (C=N str., pyrazole and oxadiazole), 1238,1288, 1310 (C-N str., pyrazole), 1004,1032 (N-N str., oxadiazole); ^-NMR (DMSO-de) 5 ppm:3.36 (s, 3H, -OCH3 attached to aromatic ring), 2.32 (s, 3H, CH3 attached to -COCH3 group), 6.46 (s, 1H, at C4 of pyrazole ring), 6.60 (s, 1H, at C2 of oxadiazole ring), 7.259-7.211 (m, 1H), 7.351-7.30 (m, 1H), 7.41 (s, 1H), 7.50-7.46 (m, 3H), 7.54-7.63 (m, 8H); 13C-NMR (DMSO-de) 5 ppm: 24 (s, IC, COCH3), 55 (s, 1C,0CH3), 74, 106, 107, 111, 121, 123, 125, 126, 127, 129, 135, 138, 139, 143, 144, 153, 154 (s,C9 of benzofuran moiety), 160 (s, IC, aromatic C-atom of benzene attached to -OCH3), 162 (s, C2-atom of oxadiazole), 171 (s, IC, Carbonyl C-atom of-COCH3 group);ESI-MS (m/z):479 [M+l]+, 501 [M+Na]+.
[0078] Similarly, compounds (Ib-Ii) were synthesized from (3b-3i) by following the same procedure followed for Formula la. All the final compounds (Ib-Ii) were purified and re-crystallized using ethanol.

[0079] Table No. 1 below represents provides the name, structure and physical properties of the compounds of Formula (Ib-Ii).
Table No. 1: Characterization of compounds of Formula I(b-i)

Structure Characterization data
/^%i. ^-0 N
(i ^V \ / N
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3 -yl) -2 -(2-chlorophenyl) -1,3,4-oxadiazol-3(2H)-yl)ethanone (lb) Appearance: White solid; Rf: 0.72; IR (KBr, umax in cm1): 3063, 3012 (C-H str., arom.), 2948 (C-H asym. str., aliph.), 2853 (C-H sym. str., aliph.), 1453 (C-H asym.def., aliph.), 1362 (C-H sym.def., aliph.), 1518,1501(C=C str., arom.), 1112, 1035,1063 (C-H i.p.def., arom.), 840,806 (C-H o.o.p.def, arom.), 1202,1232 (C-O-C asym. str., ether), 1035,1063 (C-O-C sym. str., ether), 1718 (C=0 str., -COCH3 group), 1590 (C=N str., pyrazole and oxadiazole), 1235,1284,1312 (C-N str., pyrazole), 1007,1035 (N-N str., oxadiazole); lH NMR 5 ppm (DMSO-d6):2.37 (s, 3H, CH3 attached to -COCH3 group), 6.5 (s, 1H, at C4 of pyrazole ring), 6.61 (s, 1H, at C2 of oxadiazole ring), 7.20-7.60 (m, 14H, Aromatic + benzofuran protons)
(l 1^^ \ /
^~N V V
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3 -yl) -2 -(2-fluorophenyl) -1,3,4-oxadiazol-3(2H)-yl)ethenone (Ic) Appearance:White solid;Rf: 0.73; IR (KBr, v max in cm-1): 3063, 3015 (C-H str., arom.), 2945 (C-H asym. str., aliph.), 2858 (C-H sym. str., aliph.), 1457(C-H asym.def, aliph.), 1369 (C-H sym.def, aliph.), 1518,1505 (C=C str., arom.), 1122, 1040,1060 (C-H i.p.def, arom.), 848, 808 (C-H o.o.p.def, arom.), 1209,1231 (C-O-C asym. str., ether), 1033, 1066 (C-O-C sym. str., ether), 1720 (C=0 str., -COCH3

group), 1591 (C=N str., pyrazole and oxadiazole), 1237,1286,1313 (C-N str., pyrazole), 1009,1040 (N-N str., oxadiazole); 1H NMR 5 ppm (DMSO-d6):2.36 (s, 3H, CH3 attached to -COCH3 group), 6.49 (s, 1H, at C4 of pyrazole ring), 6.67 (s, 1H, at C2 of oxadiazole ring), 7.11-7.67 (m, 14H, Aromatic + benzofuran protons).
Q
N\ / \ //
^-N v V
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(4-(benzyloxy)phenyl)-l,3,4-oxadiazol-3(2H)yl)ethanone (Id) Appearance: White solid; Rf: 0.71; IR (KBr, umax in cm-l);3061, 3015 (C-H str., arom.), 2938 (C-H asym. str., aliph.), 2856 (C-H sym. str., aliph.), 1448 (C-H asym.def, aliph.), 1372 (C-H sym.def, aliph.), 1517,1502 (C=C str., arom.), 1115, 1034,1066 (C-H i.p. def, arom.), 841,805 (C-H o.o.p.def, arom.), 1203,1232 (C-O-C asym. str., ether), 1034, 1066 (C-O-C sym. str., ether), 1724 (C=0 str., -COCH3 group), 1592 (C=N str., pyrazole and oxadiazole), 1233,1286,1313 (C-N str., pyrazole), 1006, 1034 (N-N str., oxadiazole); 1H-NMR (DMSO-d6) 5 ppm:5.22 (s, 2H, -0-CH2-C6H5), 2.32 (s, 3H, CH3 attached to -COCH3 group), 6.51 (s, 1H, at C4 of pyrazole ring), 6.60 (s, 1H, at C2 of oxadiazole ring), 7.08-7.70 (m, 19H, Aromatic + benzofuran protons)
Appearance:White solid;Rf: 0.73; IR (KBr, umax in cm-1) 3069, 3014 (C-H str., arom.), 2946 (C-H asym. str., aliph.), 2852 (C-H sym. str., aliph.), 1459 (C-H asym.def, aliph.), 1361 (C-H sym.def,

l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-styryl-l,3,4-oxadiazol-3(2H)-yl) ethanone (Ie)

l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(furan-2-yl)-l,3,4-oxadiazol-3(2H)-yl)ethanone (If)

aliph.), 1518, 1507 (C=C str., arom.), 1110, 1036, 1061 (C-H i.p. def., arom.), 848, 804 (C-H o.o.p.def, arom.), 1206,1232 (C-O-C asym. str., ether), 1036, 1061 (C-O-C sym. str., ether), 1720 (C=0 str., -COCH3 group), 1599 (C=N str., pyrazole and oxadiazole), 1240, 1281, 1314 (C-N str., pyrazole), 1002, 1036 (N-N str., oxadiazole); 1H-NMR (DMSO-d6) 8 ppm:5.22 (s, 2H, -0-CH2-C6H5), 2.32 (s, 3H, CH3 attached to -COCH3 group), 6.62 (s, 1H, Ph-CH=CH-), 6.25 (s, 1H, Ph-CH=CH-), 6.51 (s, 1H, at C4 of pyrazole ring), 6.60 (s, 1H, at C2 of oxadiazole ring), 7.08-7.70 (m, 15H, Aromatic + benzofuran ring).
Appearance:White solid; Rf: 0.70; IR(KBr, v max in cm-1) 3068,3012 (C-H str., arom.), 2944 (C-H asym. str., aliph.), 2862 (C-H sym. str., aliph.), 1457 (C-H asym.def, aliph.), 1364 (C-H sym.def, aliph.), 1519,1513 (C=C str., arom.), 1121, 1035,1062 (C-H i.p.def, arom.), 848,812 (C-H o.o.p.def, arom.), 1212,1232 (C-O-C asym. str., ether), 1035,1062 (C-O-C sym. str., ether), 1718 (C=0 str., -COCH3 group), 1596 (C=N str., pyrazole and oxadiazole), 1237, 1289, 1311 (C-N str., pyrazole), 1006,1033 (N-N str., oxadiazole). 1H NMR (DMSO-d6) 8 ppm: 2.12 (s, 3H, CH3 attached to -COCH3 group), 6.54 (s, 1H, at C4 of pyrazole ring), 6.66 (s, 1H, at C2 of oxadiazole ring), 7.09-

l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(thiophen-2-yl)-l,3,4-oxadiazol-3(2H)-yl)ethanone (Ig)
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3 -yl) -2 -(naphthalen-1 -yl) -1,3,4 -oxadiazol-3(2H)-yl)ethanone (Ih)

7.50 (m, 13H, furan + benzofuran protons) Appearance:White solid; Rf: 0.72;IR(KBr, umax in cm-1) 3069,3019 (C-H str., arom.), 2943 (C-H asym. str., aliph.), 2859 (C-H sym. str., aliph.), 1454 (C-H asym.def, aliph.), 1362 (C-H sym.def, aliph.), 1511,1503 (C=C str., arom.), 1119, 1028,1074 (C-H i.p.def, arom.), 844,809 (C-H o.o.p.def, arom.), 1201, 1232 (C-O-C asym. str., ether), 1028, 1074 (C-O-C sym. str., ether), 1723(C=0 str., -COCH3 group), 1593 (C=N str., pyrazole and oxadiazole), 1232, 1284,1312 (C-N str., pyrazole), 1005,1028 (N-N str., oxadiazole). 1H-NMR (DMSO-d6)5 ppm: 2.20 (s, 3H, CH3 attached to -COCH3 group), 6.64 (s, IH, at C4 of pyrazole ring), 6.65 (s, IH, at C2 of oxadiazole ring), 7.15-7.60 (m, 13H, thiophene + benzofuran protons). Appearance:White solid;Rf: 0.70; IR (KBr, v max in cm-1): 3066,3020 (C-H str., arom.), 2944 (C-H asym. str., aliph.), 2867 (C-H sym. str., aliph.), 1455 (C-H asym.def, aliph.), 1365 (C-H sym.def, aliph.), 1522,1510 (C=C str., arom.), 1116, 1039, 1066 (C-H i.p.def, arom.), 847,808 (C-H o.o.p.def, arom.), 1204,1229 (C-O-C asym. str., ether), 1031,1067 (C-O-C sym. str., ether), 1721 (C=0 str., -COCH3 group), 1594 (C=N str., pyrazole and oxadiazole), 1234, 1289,1312 (C-N str., pyrazole), 1005, 1036 (N-N str., oxadiazole). 1H-NMR (DMSO-d6) 8 ppm:

2.22 (s, 3H, CH3 attached to -C0CH3 group), 6.67 (s, 1H, at C4 of pyrazole ring), 6.57 (s, 1H, at C2 of oxadiazole ring), 7.19-7.77 (m, 17H, napthal + benzofuran protons)
fl ^"^ \ /
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-phenyl-l,3,4-oxadiazol-3(2H)-yl) ethanone (Ii) Appearance:White solid;IR Rf: 0.73; (KBr, umax in cm-1) 3061, 3018 (C-H str., arom.), 2946 (C-H asym. str., aliph.), 2863 (C-H sym. str., aliph.), 1459 (C-H asym.def, aliph.), 1369 (C-H sym.def, aliph.), 1513,1506 (C=C str., arom.), 1119,1036,1069 (C-H i.p. def, arom.), 841,808 (C-H o.o.p.def arom.), 1205, 1236 (C-O-C asym. str., ether), 1036, 1062 (C-O-C sym. str., ether), 1723 (C=0 str., -COCH3 group), 1596 (C=N str., pyrazole and oxadiazole), 1236, 1283, 1314 (C-N str., pyrazole), 1002,1036 (N-N str., oxadiazole). 1H-NMR (DMSO-d6) 5 ppm: 2.18 (s, 3H, CH3 attached to -COCH3 group), 6.61 (s, 1H, at C4 of pyrazole ring), 6.52 (s, 1H, at C2 of oxadiazole ring), 6.95-7.31 (m, 15H, Aromatic + benzofuran protons).
[0080] Table No. 2 provides the physical characteristics of the synthesized compounds la-Ii.
Table No. 2. Physical characteristics of the synthesized compounds la-Ii

Compound Mol. Formula MP
(°C) % Yield % Analys Found (Calcu is ated)

C H N
la C28H22N4O4 182 90 70.28 (70.44) 04.63 (4.60) 11.71 (11.75)

lb C27H19CIN4O3 180 90 67.20 (67.15) 3.98
(3.97) 11.65 (11.60)
Ic C27H19FN4O3 191 88 69.50 (69.52) 4.09 (4.11) 12.10 (12.01)
Id C34H26N4O4 190 85 73.65 (73.63) 4.78 (4.73) 10.15 (10.10)
Ie C29H22N4O3 194 86 73.38 (73.40) 4.63 (4.67) 11.76 (11.81)
If C25H18N4O4 170 90 68.56 (68.49) 4.12 (4.14) 12.75 (12.78)
Ig C25H18N4O3S 190 82 66.15 (66.07) 3.95 (3.99) 12.37 (12.33)
Ih C31H22N4O3 196 83 74.75 (74.69) 4.40 (4.45) 11.18 (11.24)
Ii C25H18N4O3S 220 82 66.12 (66.07) 3.95 (3.99) 12.37 (12.33)
Example 2: Anti-bacterial activity
[0081] 2.1 Zone of inhibition: Anti-bacterial investigation for the compounds Ia-Ii was performed using zone of inhibition test against S. aureus, P. vulgaris, E. coli and S. typhi. The synthesized compounds were tested at varying concentrations with DMSO solvent. All the compounds (Ia-Ii) were screened for their in-vitro antimicrobial activity using disc-diffusion method against panel of pathogenic microorganism including S. aureus as Gram positive bacterial strain, and E. coli, P. vulgaris, S. typhi as Gram negative bacterial strains. Calculated weight of each compound (Ia-Ii) was dissolved in dimethyl sulphoxide and diluted to get desired concentration of 31-1000ug/mL. lOmL of Mueller Hinton Agar was poured on Petri plates were allowed to solidify. In lOmL fresh nutrient broth Microorganism culture was inoculated to obtained suspension, by using distilled water was further diluted 10 times maintained at 37°C. Among that 0.1 mL of culture was spread over nutrient agar in plate. Sterile paper discs (6 mm) of Whatmann No.l were soaked with set solution allowed to dry at room temperature then applied on plates and incubated at 37°C for 24hr. Zone of inhibition was noted in mm in four directions and expressed as mean. [0082] Chloramphenicol was taken as a reference sample. Results are provided in Tables 3 and 4. Among the synthesized compounds (la, lb, Id and If) were found

to show best activity against S. aureus, E. coli and P. vulgaris with reference to the std. drug Chloramphenicol. All the compounds showed activity against Gram negative bacteria S. typhi.
Table No. 3 Anti-bacterial activity of the compounds [Zone of Inhibition
(mm)]

Compd. S. aureus (Gram +ve) P.vulgaris (Gram -ve)

Cone. (ugfaL) Cone. ((JgtoL)

1000 500 250 125 63.5 31 1000 500 250 125 63.5 31
la 23 21 20 19 16 15 28 23 22 18 16 14
lb 25 21 20 19 16 15 25 21 19 15 18 11
Ic 21 21 20 21 16 18 28 23 22 18 18 15
Id 26 23 22 19 18 17 26 24 21 20 19 16
Ie 23 22 19 17 16 15 25 22 20 14 16 12
If 27 25 17 19 20 16 28 23 20 20 18 14
Ig 24 16 18 17 15 13 24 25 19 16 17 12
Ih 22 23 20 18 17 14 23 21 19 18 16 14
Ii 22 21 19 21 19 14 22 21 19 18 16 15
DMSO
Chloramphenicol 24 22 20 19 17 15 28 24 20 17 16 13
Table No. 4 Anti-bacterial activity of the compounds [Zone of Inhibition
(mm)]

Compd. E. coli (Gram -ve) S. typhi{Gmm -ve)

Cone. ((JginL) Cone. ((JginL)

1000 500 250 125 63.5 31 1000 500 250 125 63.5 31
la 25 26 21 22 18 14 16 17 12 13 12 10
lb 26 22 21 19 19 17 18 16 12 14 08 09
Ic 27 25 22 19 17 16 19 17 13 12 11 10
Id 26 25 22 23 17 11 16 13 09 10 08 10
Ie 24 22 21 19 16 14 19 16 14 13 10 11
If 26 24 23 21 19 16 19 17 11 10 11 10
Ig 22 22 19 17 16 14 17 13 11 12 10 09
Ih 23 26 24 20 16 15 14 13 11 10 09 07
Ii 22 20 19 16 13 15 19 15 13 10 09 07
DMSO
Chloramphenicol 26 24 23 21 17 14 17 15 12 11 09 08
[0083] 2.2 Minimum Inhibitory Concentration: The minimum inhibitory concentration of the compounds Ia-Ii was determined for each of these bacteria. Nutrient broth was prepared, sterilized in autoclave, and cooled to room

temperature. The test bacteria were inoculated in the broth with different concentrations of synthesized compounds la-Ii in aseptic condition and allowed to grow for 24 hours at 37°C in incubator to determine the MIC. The growth of bacteria was determined with a turbidometer. The MIC values for synthesized compounds and standard drugs against gram-negative and gram-positive bacterial strains are depicted in Table No. 5.
Table No. 5: Minimum inhibitory concentrations of compounds

Compound Gram +ve Gram -ve

S. aureus P. vulgaris E. coli S. typhi

MIC((ug/mL)
la 10 06 05 10
lb 10 11 05 13
Ic 08 06 06 10
Id 10 07 04 10
Ie 12 10 08 13
If 10 09 06 10
Ig 13 10 09 13
Ih 12 10 08 15
Ii 13 09 11 17
DMSO 0 0 0 0
Chloramphenicol 08 07 05 11.
Example 3: Molecular docking studies
[0084] 3.1 X-ray crystal structure of DNA gyrase enzyme: Molecular docking studies were carried out to understand the binding mode analysis of synthesized compounds against X-ray crystal structure of DNA gyrase enzyme, PDB ID: 1AB4 (J.H.M. Cabral, A.P. Jackson, C. V Smith, N. Shikotra, A. Maxwell, R.C. Liddington, Crystal structure of the breakage-reunion domain of DNA gyrase, Nature. 388 (1997) 903) using AutoDock4.2. The structural pocket of Gyrase A dimer interface (helix 3 and helix 4) is in close proximity to the catalytic residue TYR122, (key catalytic residue involved in the DNA breakage-reunion reaction of DNA gyrase). All the designed compounds (la-Ii) were well accommodated in the active-site cavity of DNA gyrase with excellent estimated free binding energy between -9.41 to -7.33 Kcal/mole, compared to reference compound chloramphenicol (-6.64kcal/mole) (refer Figure 1 and Table No. 6 below). While

the standard drug chloramphenicol formed three hydrogen bonds (with Gln94, Arg91 and Tyr266 with a bond distance of 1.93, 2.00 and 1.83A respectively), it did not completely occupy the large active-site cavity of DNA gyrase due to its structural features.
Table No. 6: Molecular docking studies of compounds in DNA gyrase

Compound Binding free energy (AGcaic: Kcal/mol) Active site residues involved in the interaction
la -7.33 Arg91(1.905A), 7i-cation Lys42 (2.784A)
lb -8.63 Gln94 (2.861 A),
Ic -8.75 Gln94 (2.102A), Alall7 (1.798A)
Id -8.85 Arg91(1.866A)
Ie -7.68 Gln94 (1.646A), 7i-cation Lys42 (3.050A)
If -8.99 Gln94 (1.808A), Alall7 (1.85 lA)
Ig -7.53 Gln94 (3.804A)
Ih -9.41 Ser97 (2.675A)
Ii -7.94 Gln94 (2.933A)
Chloramphenicol -6.64 Arg91(1.743A), Gln94 (A), Gln267 (2.134A)
[0085] 3.2 /?- ketoacyl-acyl carrier protein synthase III enzyme: Molecular docking studies were carried out to understand the orientation and binding mode of synthesized compounds in the active site (PDB ID: 1MZS) of ft- ketoacyl-acyl carrier protein synthase III enzyme (R.A. Daines, I. Pendrak, K. Sham, G.S. Van Aller, A.K. Konstantinidis, J.T. Lonsdale, C.A. Janson, X. Qiu, M. Brandt, S.S. Khandekar, C. Silverman, M.S. Head, First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling, J. Med. Chem. 46 (2003) 5-8). All the synthesized compounds (Ia-Ii) completely occupied the catalytic triad (formed by residue Cysll2, Arg249, and Asn279, located at the bottom of a hydrophobic tunnel), and adenine-binding site (formed by residue Trp32 and Argl51), the adenine subunit of the acetyl-CoA substrate bound to a region on the surface of the protein adjacent to the tunnel, with good free binding energy from -8.55 to -9.98kcal/mole, compared to standard drug chloramphenicol (-7.77kcal/mole) (refer Figure 2 and Table No. 7). Compounds [lb (-9.88kcal/mole), (Ic, -9.4kca/mole) and If (-8.98kcal/mole)] benzofuran ring oxygen established a

hydrogen bond with Argg36. Compound If formed additional hydrogen bonding with G1209, while standard drug chloramphenicol formed hydrogen bond with Arg247 and Asn247 (potential residue in catalytic triad). Table No. 7: Molecular docking studies of compounds (Ia-Ii) in the active site
P~ ketoacyl-acyl carrier protein synthase III enzyme

Compound Binding free energy (AGcaic: Kcal/mol) Active site residues involved in the interaction
la -8.55 Thr37, Phe213, Asn247, Arg249
lb -9.88 Thr37 (2.844A)
Ic -9.54 Thr37 (2.582A)
Id -9.90 Arg249(2.174A), n-n interaction His244(3.324A)
Ie -9.34 Thr37, Phe213,Arg249
If -8.98 Thr37 (2.926A), Gly209 (2.905A)
Ig -8.83 Thr37, Phe213,Arg249
Ih -9.08 Arg249 (2.038A), 71-71 interaction Phe213(3.819A)
Ii -8.87 Arg249 (2.249A)
Chloramphenicol -7.17 Arg249 (1.619A), Asn247 (2.157A), Asn247 (2.035A)
[0086] The docking studies suggested that halogen substituted (compound lb and Ic), heterocyclic (Id) and with methoxy (la), were more potent than other compounds indicating that polar hydrophobicity plays a key role in determining the potency. The compounds were well accommodated in the active site of/?-ketoacyl-acyl carrier protein synthase III enzyme and DNA gyrase. [0087] Further, to validate the AutoDock procedure of the section 3.1 and 3.2, re-docking and RMSD values were also considered. All the compounds showed RMSD values <2 A, indicating good correlation within the best cluster result. Example 4: Drug likeness
[0088] Lipinski's rule of five is a prerequisite to ensure drug-like properties when using rational drug design. In order to screen the pharmacokinetic behavior, the in-silico ADME parameters of the designed compounds were calculated using the Swiss ADME software (http://www.swissadme.ch). All the synthesized compounds (Ia-Ii) showed ADME parameters in an acceptable range and

possessed significant drug-like characteristics based on Lipinski's rule of 5 (mol. wt. < 500 Da; log P o/w < 5; HBD < 5; HBA <10) as provided in Table No. 8. Table No. 8: Physicochemical properties for drug-likeness based on
Lipinski's rule of five

Compound Mol. Wt. No of HBA No of HBD Log Po/w Lipinski's violation
la 478.50 6 0 3.68 0
lb 482.92 5 0 4.12 0
Ic 466.46 6 0 4.37 0
Id 554.59 6 0 4.06 0
Ie 474.51 5 0 4.06 0
If 438.43 6 0 2.84 0
Ig 454.50 5 0 3.63 0
Ih 498.53 5 0 4.06 0
Ii 448.47 5 0 4.00 0
Where Mol. Wt.: Molecular weight, HBD: Hydrogen bond donor; HBA: Hydrogen bond acceptor; and Log P0/w: Octanol/water partition coefficient.
Example 5: In-silico toxicity assessment
[0089] In-silico toxicity risk was predicted using, open-source program OSIRIS Property Explorer and compared with standard chloramphenicol which was found to be toxic (mutagenic, tumorigenic and irritant), when compared to compounds Ia-Ii as provided in Table No. 9. All the compounds (Ia-Ii) were found to be non-toxic except reproductive effect, while the standard chloramphenicol was also found to have reproductive effect.
Table No. 9. In-silico toxicity risk prediction of designed compounds

Compou nd Mutage nic Tumori genie Irritant Reprod
uctive
effectiv
e Solubili
ty TPSA Drug-likene
ss Drug score
la None None None Yes -5.63 82.09 2.7 0.36
lb None None None Yes -6.34 72.86 5.46 0.30
Ic None None None Yes -5.92 72.80 3.74 0.35
Id None None None Yes -6.95 82.09 -3.12 0.11
Ie None None None Yes -6.26 72.86 3.92 0.29
If None None None Yes -5.29 86.0 4.77 0.44
Ig None None None Yes -5.62 101.1 6.29 0.39
Ih Yes Yes None Yes -7.21 72.86 4.79 0.11

Ii yes None None Yes -5.61 72.86 5.29 0.31
Ref Yes Yes Yes Yes -2.37 115.3 -4.61 0.06
[0090] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.
ADVANTAGES OF THE INVENTION
[0091] The present disclosure provides novel and effective anti-microbial
compounds.
[0092] The present disclosure provides compounds that have low toxicity, inhibit
the activity of ft- ketoacyl-acyl carrier protein synthase III enzyme and interfere
with DNA topoisomerase.
[0093] The present disclosure provides a process of synthesizing the compounds
that gives high yield.

We Claim:

1. An anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,

N
Formula I wherein Ri is selected from (C6-Ci4)aryl, or (C5-Cio)heteroaryl; wherein Ri is unsubstituted or substituted with one or more of halogen, amino, cyano, nitro, hydroxy, (Ci-Ce) alkyl, -COOH, -OR2, or -CH=CH-R2; and wherein R2 is selected from (C1-C5) alkyl, phenyl, or -CFb-phenyl.
2. The compound as claimed in claim 1, wherein the (C6-Ci4)aryl is selected from phenyl, naphthyl, or anthracenyl.
3. The compound as claimed in claim 1, wherein the (C5-Cio)heteroaryl is selected from furanyl, thienyl, or pyrrolyl.

4. The compound as claimed in claim 1, wherein the Ri is unsubstituted or substituted with CI, F, Br, I, -OR2, or -CH=CH-R2.
5. The compound as claimed in claim 1, wherein R2 is selected from methyl, phenyl, or -CFb-phenyl.
6. A compound of Formula I selected from:
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3 -yl) -2-(4-methoxyphenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(2-chl orophenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;

l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(2-fluorophenyl)-
l,3,4-oxadiazol-3(2H)-yl)ethenone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(4-
(benzyloxy)phenyl)-l,3,4-oxadiazol-3(2H)yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-styryl-l,3,4-
oxadiazol-3(2H)-yl) ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(furan-2-yl)-l,3,4-
oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(thiophen-2-yl)-l,3,4-
oxadiazol-3(2H)-yl)ethanone;
l-(5-(5-(benzofuran-2-yl)-l-phenyl-lH-pyrazol-3-yl)-2-(naphthalen-l-yl)-
l,3,4-oxadiazol-3(2H)-yl)ethanone;
1 -(5-(5-(benzofuran-2-yl)-1 -phenyl- lH-pyrazol-3 -yl)-2-phenyl-1,3,4-
oxadiazol-3(2H)-yl) ethanone; or a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.
7. A pharmaceutical composition comprising an anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof and one or more of a pharmaceutically acceptable excipient(s)

Formula I 8. A process of preparing an anti-microbial pharmaceutical compound of Formula I, a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a

pharmaceutically acceptable solvate thereof, wherein the process comprises the steps of:
(a) reacting a carbohydrazide of Formula 1 with the compound of Formula 2 in the presence of a solvent to obtain a compound of Formula 3; and
(b) reacting the compound of Formula 3 with acetic anhydride to give a compound of Formula I.