Small molecules for the treatment of mycobacterial diseases

Abstract

The present invention relates to tetracyclic quinolone compounds, its 5 pharmaceutically acceptable salts and pharmaceutical compositions. The invention further relates to a combination therapeutic product comprising one or more electron transport chains for treating mycobacterial infections such as tuberculosis by administering a therapeutically effective amount of a compound of the invention to a patient. The compounds of the invention are beneficial in the methods described 10 herein for treating mycobacterial diseases, particularly tuberculosis (TB), multi- drug resistant (MDR), extensively drug resistant (XDR), NTM infections etc.

Description

SMALL MOLECULES FOR THE TREATMENT OF MYCOBACTERIAL DISEASES FIELD OF THE INVENTION

[0001] The invention relates to compounds for treating mycobacterial infections such as tuberculosis (TB), multi-drug resistant (MDR), extensively drug resistant (XDR), NTM infections, etc.

[0002] The present invention more particularly relates to a tetracyclic quinolone compounds, its stereoisomer, and pharmaceutically acceptable salts, and the synthesis of such compounds.

[0003] The present invention also relates to pharmaceutical compositions of the tetracyclic quinolone compounds its stereoisomer and pharmaceutically acceptable salts. BACKGROUND OF THE INVENTION

[0004] Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. With an estimated 1.5 million death incidences in 2020 (including both HIV-positive and HIV-negative people) due to tuberculosis (TB), Mtb remains the leading cause of death due to a single infectious agent worldwide despite the availability of treatment methods and prevention. The synergy of the human immunodeficiency virus (HIV)-TB co-infection has aggravated this as a significant public health problem. Until 2019, the number of TB cases was indeed decreasing, although slowly. However, the onset of the COVID-19 pandemic in the world has led to an adverse setback in TB treatments and diagnosis, resulting in a rise in the number of TB cases again, especially drug-resistant forms of TB. Currently used TB treatment is riddled with the use of multiple drugs for at least six months. Such lengthy treatment has resulted in the rise of multidrug-resistant (MDR), and extremely drug-resistant (XDR) strains of Mtb. Emergence and increase in the incidence rate of MDR-TB and XDR-TB are a threat to the success achieved over the years in TB control. Therefore, novel therapeutic regimens must be discovered to address the scourge of drug-resistant TB. This necessitates the development ofnew therapeutic agents with novel mechanisms of action to prevent cross-resistance with the currently used anti-tubercular agents. The U.S. Food and Drug Administration has recently approved three new drugs. These drugs are Bedaquiline (BDQ), a diarylquinoline ATP synthase inhibitor; Delamanid, a nitro-dihydro- imidazooxazole; and Pretomanid, a nitroimidazooxazine derivative. Delamanid and Pretomanid inhibit mycolic acid biosynthesis. Pretomanid also inhibits respiration through the release of nitric oxide during hypoxia. However, these drugs are approved only for the treatment of MDR-TB. In the light of the emergence of drug resistance, developing new potential clinical candidates is critical in controlling the TB pandemic.

[0005] The emergence of Bedaquiline as an inhibitor of ATP synthase and the recent discovery of small molecules targeting the cytochrome bc1:aa3 in Mtb triggered interest in oxidative phosphorylation for the development of anti- tuberculosis drugs. The mycobacterial cytochrome bc1:aa3 consists of a menaquinone: cytochrome c reductase (bc1), and a cytochrome aa3-type oxidase. The clinical-stage drug candidate Q203 interferes with the function of the subunit b of the menaquinone: cytochrome c reductase. Despite the affinity of Q203 for the bc1:aa3 complex, the drug is only bacteriostatic and does not kill drug-tolerant persisters. This raises the possibility that the alternate terminal bd-type oxidase (cytochrome bd oxidase) can maintain membrane potential and menaquinol oxidation in the presence of Q203. Importantly, Mtb strains defective in biosynthesis of cytochrome bd oxidase are hypersensitive to the Q203 and Bedaquiline. These observations suggest a synergy between different inhibitors of oxidative phosphorylation.

[0006] New drugs are needed to combat multidrug-resistant tuberculosis. The electron transport chain (ETC) maintains the electrochemical potential across the cytoplasmic membrane and allows the production of ATP, the energy currency of any living cell. The electron transport chain of the tubercle bacilli contains two terminal oxidases, the cytochrome bc1:aa3, and the cytochrome bd oxidase. Our approach is to inhibit both the terminal oxidases to stop respiration, kill non- replicating drug-tolerant Mtb, and eradicate the infection in vivo at a fast rate.Exploiting this potent synthetic lethal interaction with new drugs promises to shorten tuberculosis treatment. SUMMARY OF THE INVENTION

[0007] The present invention provides a compound of general formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof,wherein, X1 and X2 are independently selected from -CR-, -CH2- and -O-, wherein both X1and X2are not simultaneously O; R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -CF3, - OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl; R1, which may be same or different at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, -CF3, -OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, - (CRaRb)r-C(O)ORc, -NRdRe, -C(O)Rf, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, - S(O)0-2Rc, and -S(O)2NRdRe; R2 is a group -A-B, wherein A is absent or a linker group of the formula -[CRgRh]- , -O-, -C(O)-, -C(O)O-, -OC(O)-, -CH(ORi)-, -N(Ri)-, N(Rj)-C(O)-, -N(Rj)-C(O)O- , -C(O)-N(Rj)-, -N(Rj)C(O)N(Ri)-, -S-, -SO-, -SO2-, -S(O)2N(Ri)-, or -N(Rj)SO2- B is independently selected from hydrogen, deuterium, halogen, cyano, nitro, -CF3, -OCF3, NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r- C(O)ORc, -(CRaRb)r-C(O)ORc, -C(O)Rf, NRdRe, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, - S(O)0-2Rc, and, -S(O)2NRdRe, C1-6alkyl, C2-6alkenyl, C2-6alkynyl,C3-6 cycloalkyl, C3-6 cycloalkenyl, heterocyclyl, and the substituents of alkyl, aryl, cycloalkyl, heterocyclyl or heteroaryl are independently selected from halo, cyano, nitro, hydroxy, carboxy, NRkRl, C1-2 alkoxy, C1-2 haloalkoxy, or C1-2 alkyl; wherein Ra and Rb, are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, and substituted or unsubstituted cycloalkyl; or Raand Rbtogether with the carbon atom to which they are attached, may form an unsubstituted or substituted 3 to 7 membered saturated carbocyclic ring; Rc, is selected from the group consisting of hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted haloalkyl, and substituted or unsubstituted alkyl; Rd and Re, are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl; or Rd and Re can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by oxo, halo, cyano, nitro, hydroxy, carboxy, -NRmRn, C1-4 alkoxy, C1-4 alkyl, C3-8 cycloalkyl, C3-8cycloalkyl-C1-3alkyl, C1-4alkanoyl, C1-4alkylsulphonyl, or -C(O)NRmRn, - NRmC(O)Rn, -NRmS(O)2Rnand -S(O)2NRmRn; wherein Rmand Rnare each independently selected from hydrogen, C1-4 alkyl or C3-6 cycloalkyl and C3-6cycloalkyl C1-2alkyl; Rfis substituted or unsubstituted alkyl or substituted or unsubstituted aryl; Rg and Rh, are each independently selected from hydrogen or C1-2 alkyl; Ri and Rj are each independently selected from hydrogen or C1-2 alkyl; Rkand Rlare independently selected from the group consisting of hydrogen or C1-2alkyl; 'r' is an integer ranging from 0 to 3; 'p' is an integer ranging from 0 to 4; and 'q' is an integer ranging from 0 to 4.

[0008] In a preferred embodiment, the compound of formula (I) is selected from the group consisting of, 3-bromo-6,12-dihydrobenzo[c]acridin-7(5H)-one;2-bromo-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-hydroxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-hydroxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-phenoxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-phenoxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-(4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(3,3-difluoropyrrolidin-1-yl)benzo[c]acridin-7(12H)-one; 3-(pyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-(3,3-difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(3,3-difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-morpholino-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(phenylamino)benzo[c]acridin-7(12H)-one; 3-(4-(trifluoromethoxy)phenyl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one; 6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-bromo-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 2-bromo-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-fluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one ; 2-fluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-hydroxy-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-phenoxy-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-(4-(trifluoromethoxy)phenoxy)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one; 3-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one; 3-(3,3-difluoroazetidin-1-yl)-6,12-dihydro-7H-chromeno[4,3-b]quinolin- 7-one; and 2-bromo-8,10-difluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one;or a pharmaceutically acceptable salt thereof.

[0009] In an embodiment of the present invention, the compound of general formula (I) is an anti-tuberculosis agent.

[0010] The present invention provides a process for preparing the compound of general formula (I), comprising: (i) C-C / C-N / C-O coupling of cyclic ketone of formula (2), wherein X1 and X2, are as defined above, with a boronic acid, boronic ester or an amine in the presence of a base and a catalyst to produce a substituted cyclic ketone of formula (4), wherein X1, X2, R2, and q are as defined above;(ii) intermolecular cyclization of substituted cyclic ketone of formula (4), with anthranilic acid of formula (5), wherein R1, p, and q are as defined above, to produce a compound of formula (I),wherein X1, X2, R1, R2, p and q are as defined above.

[0011] In an embodiment of the present invention, there is provided a process as disclosed herein, wherein step (i) is a C-O coupling (Chan-Lam Coupling) of cyclic ketone of formula (2a) with a boronic acid or ester of formula (3) in the presence of a base and a copper catalyst to produce a compound of formula (4);orwherein step (i) is a C-N coupling (Buchwald-Hartwig Coupling) of cyclic ketone of formula (2b) with an aliphatic or aromatic amine in the presence of a suitable base, a palladium catalyst, and a suitable ligand to produce compound of formula (4);or wherein step (i) is a C-C coupling (Suzuki Coupling) of cyclic ketone of formula (2c) with a boronic acid of formula (3) in the presence of a base and a palladium catalyst to produce a substituted cyclic ketone compound of formula (4)Wherein Y, X1, X2, R1, R2, p, and q are as defined above.

[0012] In an alternative embodiment the present invention provides a process for preparing the compound of general formula (I) as claimed in claim 1, comprising: (i) intermolecular cyclization of substituted cyclic ketone of formula (2), with anthranilic acid of formula (5), wherein R1,and p are as defined in claim 1, to produce a compound of formula (Ia); and(ii) substitution reaction of (Ia) to afford the compound of formula (I) wherein X1, X2, R1, R2, p and q are as defined above.

[0013] In an embodiment of the present invention, the Pd or Cu metal containing catalyst are selected from the group such as Pd2(dba)3, Pd(OAc)2, Pd(Ph3)4, Pd(dppf)Cl2, Cu(OAc)2 etc. and the base is selected from the group such as NEt3, DIPEA, pyridine, Cs2CO3, NaOtBu, Na2CO3, K2CO3etc.

[0014] The present invention also provides the intermediate of the process for preparing the compound of general formula (I), selected from the group consisting of: 6-(4-(trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen-1(2H)-one; 7-(4-(trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen-1(2H)-one; 7-(4-(trifluoromethoxy)phenoxy)chroman-4-one; 7-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 6-(3,3-difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 6-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 7-(4-(trifluoromethoxy)phenyl)chroman-4-one; 7-(3,3-difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 6-morpholino-3,4-dihydronaphthalen-1(2H)-one; 7-(3,3-difluoropyrrolidin-1-yl)chroman-4-one; 7-(3,3-difluoroazetidin-1-yl)chroman-4-one; and 7-(phenylamino)-3,4-dihydronaphthalen-1(2H)-one

[0015] The present invention also provides a pharmaceutical composition for treating mycobacterial infections comprising: the compound of general formula (I) and one or more pharmaceutically acceptable excipients selected from the group consisting of water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid, lower alkyl ethers of cellulose, salicylic acid, fatty acids, fatty acid amines, fatty acid monoglycerides,diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone or combinations thereof.

[0016] The present invention also provides a pharmaceutical composition comprising: the compound of general formula (I) with one or more antibacterial agents.

[0017] The present invention also provides a pharmaceutical composition, comprising: the compound of general formula (I) with one or more anti-tuberculosis agents selected from the group consisting of cytochrome bc inhibitor, NDH2inhibitor, ATP synthase inhibitor, and / or menaquinone biosynthesis inhibitor, electron transport chain dependent inhibitors such as clofazimine.

[0018] These and other features, aspects, and advantages of the present subject matter will be better understood with reference to the following description and appended claims. This summary is provided to introduce a selection of concepts in a simplified form. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. DETAILED DESCRIPTION OF THE INVENTION

[0019] The invention will now be described in detail with certain preferred and optional embodiments so that various aspects thereof may be more fully understood and appreciated. 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] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions,and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any or more of such steps or features. Definitions

[0021] For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are delineated here. These definitions should be read in light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

[0022] The term "at least one" is used to mean one or more and thus includes individual components as well as mixtures / combinations.

[0023] Throughout this specification, unless the context requires otherwise the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated element or step or group of element or steps but not the exclusion of any other element or step or group of element or steps.

[0024] The term “including” is used to mean “including but not limited to”. “including” and “including but not limited to” are used interchangeably.

[0025] For convenience, before further description of the present disclosure, certain terms employed in the specification and examples are delineated here. These definitions should be read in the light of the remainder of the disclosure and understood by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art; however, for convenience and completeness, particular terms and their meanings are set forth below.

[0026] The articles "a", "an" and "the" are used to refer to one or more than one (i.e., to at least one) of the grammatical object of the article.

[0027] The terms "comprise" and "comprising" are used in the inclusive, open sense, meaning that additional elements may be included. It is not intended to be construed as "consists of only".

[0028] Throughout this specification, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated element or step or group of elements or steps but not the exclusion of any other element or step or group of elements or steps.

[0029] Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. Definitions and Abbreviations

[0030] Unless otherwise stated, the following terms used in the specification have the meanings given below. For purposes of interpreting the specification, the following definitions will apply, and whenever appropriate, terms used in the singular will also include the plural and vice versa.

[0031] The terms "halogen" or "halo" means fluorine, chlorine, bromine, or iodine.

[0032] The term "alkyl" refers to an alkane-derived hydrocarbon radical that includes solely carbon and hydrogen atoms in the backbone, contains no unsaturation, has from one to six carbon atoms, and is attached to the remainder of the molecule by a single bond, for example, C1-6alkyl, representative groups include, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl and the like. Unless set forth or recited to the contrary, all alkyl groups described may be straight chain or branched.

[0033] The term "alkenyl" refers to a hydrocarbon radical containing from 2 to 10 carbon atoms and including at least one carbon-carbon double bond. Non- limiting Examples of alkenyl groups include, for example, C2-6 alkenyl, C2-4 alkenyl, ethenyl, 1-propenyl, 2-propenyl (allyl), and the like. Unless set forth orrecited to the contrary, all alkenyl groups described may be straight chain or branched.

[0034] The term "alkynyl" refers to a hydrocarbon radical containing 2 to 10 carbon atoms and including at least one carbon-carbon triple bond. Non-limiting examples of alkynyl groups include, for example, C2-6alkynyl, C2-4alkynyl, ethynyl, propynyl, butynyl, and the like. Unless set forth or recited to the contrary, all alkynyl groups described may be straight chain or branched.

[0035] The term "haloalkyl" refers to an alkyl group as defined above that is substituted by one or more halogen atoms as defined above. For example, C1-6haloalkyl or C1-4 haloalkyl. Suitably, the haloalkyl may be monohaloalkyl, dihaloalkyl, or polyhaloalkyl, including perhaloalkyl. A monohaloalkyl can have one iodine, bromine, chlorine, or fluorine atom. Dihaloalkyl and polyhaloalkyl groups can be substituted with two or more of the same halogen atoms or a combination of different halogen atoms. Suitably, a polyhaloalkyl is substituted with up to 12 halogen atoms.

[0036] The term "alkoxy" denotes an alkyl group attached via an oxygen linkage to the rest of the molecule. Representative examples of such groups are -OCH3 and -OC2H5. Unless set forth or recited to the contrary, all alkoxy groups described may be straight chain or branched. The term “haloalkoxy” refers to an alkoxy group as defined above that is substituted by one or more halogen atoms as defined above. For example, C1-6 haloalkoxy or C1-4 haloalkoxy. In an aspect of the present disclosure, the haloalkoxy used herein is selected as -OCF3.

[0037] The term "cycloalkyl" refers to a non-aromatic mono or multicyclic ring system having 3 to 12 carbon atoms, such as C3-10 cycloalkyl, C3-6 cycloalkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. Examples of multicyclic cycloalkyl groups include, but are not limited to, perhydronaphthyl, adamantyl, norbornyl groups, bridged cyclic groups, or spirobicyclic groups, e.g., spiro(4,4)non-2-yl and the like.

[0038] The term "aryl" refers to an aromatic radical having 6 to 14 carbon atoms, including monocyclic, bicyclic, and tricyclic aromatic systems, such as phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, and the like.

[0039] The term "heterocyclic ring" or "heterocyclyl ring" or "heterocyclyl", unless otherwise specified, refers to substituted or unsubstituted non-aromatic 3 to 15 membered ring which consists of carbon atoms with one or more heteroatom(s) independently selected from N, O or S. The heterocyclic ring may be a mono, bi, or tricyclic ring system, which may include fused, bridged, or spiro ring systems, and the nitrogen, carbon, oxygen, or sulphur atoms in the heterocyclic ring may be optionally oxidized to various oxidation states. In addition, the nitrogen atom may be optionally quaternized, the heterocyclic ring or heterocyclyl may optionally contain one or more olefinic bonds, and one or two carbon atoms / in the heterocyclic ring or heterocyclyl may be interrupted with -CF2-, -C(O)-, -S(O)-, - S(O)2, etc. In addition, heterocyclic ring may also be fused with aromatic ring.

[0040] The term "heteroaryl" unless otherwise specified, refers to a substituted or unsubstituted 5 to 14 membered aromatic heterocyclic ring with one or more heteroatom / s independently selected from N, O, or S. The heteroaryl may be a mono, bi, or tricyclic ring system. The heteroaryl ring may be attached by any atom of the heteroaryl ring that results in the creation of a stable structure.

[0041] The term "treating" or "treatment" of a state, disorder, infection, or condition includes: (a) preventing or delaying the appearance of clinical symptoms of the state, disorder, or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition; (b) inhibiting the state, disorder or condition, i.e., arresting or reducing the development of the disease or at least one clinical or subclinical symptom thereof; (c) lessening the disease, disorder or condition or at least one of its clinical or subclinical symptoms or (d) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.

[0042] As used herein, the term “effective amount” refers to the amount of each active agent required to confer the desired effect (e.g., Antibacterial) on the subject, either alone or in combination with one or more other active agents. An effective amount varies, as recognized by those skilled in the art, depending on the particular condition being treated, the severity of the condition, the individual patient parameters including age, size, physical condition, weight and gender, the nature of concurrent therapy (if any), the duration of the treatment, the specific route of administration and like factors within the knowledge and expertise of the health practitioner. These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation. It is generally preferred that a maximum dose of the individual components or combinations thereof be used, that is, the highest safe dose according to sound medical judgment. It will be understood by those of ordinary skill in the art, however, that a patient may insist upon a lower dose or tolerable dose for medical reasons, psychological reasons, or virtually any other reasons. A "therapeutically effective amount" means the amount of a compound that, when administered to a subject for treating a disease, disorder, or condition, is sufficient to cause the effect in the subject, which is the purpose of the administration. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity, and the age, weight, physical condition, and responsiveness of the subject to be treated. Pharmaceutically Acceptable Salts

[0043] The compounds of the invention may form salts with acid or base. The compounds of the invention may be sufficiently basic or acidic to form stable, nontoxic acid or base salts, administration of the compound as a pharmaceutically acceptable salt may be appropriate. Non-limiting Examples of pharmaceutically acceptable salts are inorganic, organic acid addition salts formed by the addition of acids, including hydrochloride salts. Non-limiting examples of pharmaceutically acceptable salts are inorganic, organic base addition salts formed by the addition of bases. The compounds of the invention may also form salts with amino acids. Pharmaceutically acceptable salts may be obtained using standard procedures wellknown in the art, for example, by reacting sufficiently basic compounds such as an amine with a suitable acid.

[0044] Screening of the compounds of invention for antibacterial activity, particularly against Mtb can be achieved by using various in-vitro mentioned herein below or methods known in the art. Pharmaceutical Compositions

[0045] The invention relates to pharmaceutical compositions containing the compounds of the formula (I), or pharmaceutically acceptable salts thereof disclosed herein. In particular, pharmaceutical compositions containing a therapeutically effective amount of at least one compound of formula (I) described herein and at least one pharmaceutically acceptable excipient (such as a carrier or diluent). Preferably, the contemplated pharmaceutical compositions include the compound(s) described herein in an amount sufficient to treat the bacterial infections described herein when administered to a subject. In another aspect, the invention relates to a method of treating diseases, disorders, or conditions associated with bacterial infections such as tuberculosis caused by Mtb. In this method, a subject in need of such treatment is administered a therapeutically effective amount of a compound of formula (I) as defined above or a pharmaceutically acceptable salt thereof as described herein.

[0046] It is to be understood that the invention encompasses the compounds of formula (I) as defined above or pharmaceutically acceptable salts thereof in the manufacture of a medicament for treating a disease or disorder mentioned herein. Standard experimental procedures are followed for the synthesis of respective compounds. Chemicals and solvents were generally used from common suppliers and were used further without purification. Silica gel 60 F254 analytical thin layer chromatography (TLC) plates were used from Merck and visualized under UV light and / or with potassium permanganate stain and / or with ninhydrin stain and / or Iodine. Chromatographic purifications were performed using the Biotage flash column chromatography system. Deuterated solvents to record NMR spectra were purchased from Sigma-Aldrich. All NMR spectra were recorded using a 500MHz NMR spectrometer. Chemical shifts (δ) and coupling constants (J) are given in ppm and Hz, respectively. Mass spectrometry analysis (m / z) and HPLC were performed utilising Agilent LCMS (1290 LC / MSD) single quad system.

[0047] The present invention provides a compound of general formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof,wherein, X1 and X2 are independently selected from -CR-, -CH2- and -O- , wherein both X1and X2are not simultaneously O; R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -CF3, - OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl; R1, which may be same or different at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, -CF3, -OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, - (CRaRb)r-C(O)ORc, , -NRdRe, -C(O)Rf, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, -S(O)0-2Rc, and -S(O)2NRdRe; R2 is a group -A-B, wherein, A is absent or a linker group of the formula -[CRgRh]- , -O-, -C(O)-, -C(O)O-, -OC(O)-, -CH(ORi)-, -N(Ri)-, N(Rj)-C(O)-, -N(Rj)-C(O)O- , -C(O)-N(Rj)-, -N(Rj)C(O)N(Ri)-, -S-, -SO-, -SO2-, -S(O)2N(Ri)-, or -N(Rj)SO2- B is independently selected from hydrogen, deuterium, halogen, cyano, nitro, CF3, OCF3, NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r- C(O)ORc, -(CRaRb)r-C(O)ORc, -C(O)Rf, NRdRe, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, -S(O)0-2Rc, and-S(O)2NRdRe, C1-6alkyl, C2-6alkenyl, C2-6alkynyl,C3-6 cycloalkyl, C3-6 cycloalkenyl, heterocyclyl, and the substituents of alkyl, aryl, cycloalkyl, heterocyclyl or heteroaryl are independently selected from halo, cyano, nitro, hydroxy, carboxy, NRkRl, C1-2 alkoxy, C1-2 haloalkoxy, or C1-2 alkyl; wherein Ra and Rb, are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, and substituted or unsubstituted cycloalkyl; or Raand Rbtogether with the carbon atom to which they are attached, may form an unsubstituted or substituted 3 to 7 membered saturated carbocyclic ring; Rc, is selected from the group consisting of hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted haloalkyl, and substituted or unsubstituted alkyl; Rd and Re, are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, or Rd and Re can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by oxo, halo, cyano, nitro, hydroxy, carboxy, NRmRn, C1-4 alkoxy, C1-4 alkyl, C3-8 cycloalkyl, C3-8cycloalkyl-C1-3alkyl, C1-4alkanoyl, C1-4alkylsulphonyl, or C(O)NRmRn, NRmC(O)Rn, NRmS(O)2Rnand S(O)2NRmRn; wherein Rmand Rnare each independently selected from hydrogen, C1-4 alkyl or C3-6 cycloalkyl and C3-6cycloalkyl C1-2alkyl; Rfis substituted or unsubstituted alkyl or substituted or unsubstituted aryl; Rg and Rh, are each independently selected from hydrogen or C1-2 alkyl; Ri and Rj are each independently selected from hydrogen or methyl; Rkand Rlare independently selected from the group consisting of hydrogen or C1-2alkyl; 'r' is an integer ranging from 0 to 3; 'p' is an integer ranging from 0 to 4; and 'q' is an integer ranging from 0 to 4.

[0048] In an embodiment of the present disclosure, there is provided a compound of general formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof,wherein, X1and X2are independently selected from -CR-, -CH2- and -O- , wherein both X1 and X2 are not simultaneously O; R is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl; R1, which may be same or different at each occurrence, is independently selected from the group consisting of halogens such as fluorine, chlorine, bromine, and iodine, cyano, nitro, -CF3, -OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, - C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, -(CRaRb)r-C(O)ORc, , -NRdRe, - C(O)Rf, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, -S(O)0-2Rc, and -S(O)2NRdRe; R2 is a group -A-B, wherein, A is absent or a linker group of the formula -[CRgRh]- , -O-, -C(O)-, -C(O)O-, -OC(O)-, -CH(ORi)-, -N(Ri)-, N(Rj)-C(O)-, -N(Rj)-C(O)O- , -C(O)-N(Rj)-, -N(Rj)C(O)N(Ri)-, -S-, -SO-, -SO2-, -S(O)2N(Ri)-, or -N(Rj)SO2- B is independently selected from hydrogen, halogen, cyano, nitro, CF3, OCF3, NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, -(CRaRb)r- C(O)ORc, -C(O)Rf, NRdRe, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, -S(O)0-2Rc, and-S(O)2NRdRe, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, C3-6cycloalkenyl, C2-6heterocyclyl, and the substituents of alkyl, aryl, cycloalkyl, heterocyclyl or heteroaryl are independently selected from halo, cyano, nitro, hydroxy, carboxy, NRkRl, C1-2 alkoxy, C1-2 haloalkoxy, or C1-2 alkyl; wherein Raand Rb, are independently selected from hydrogen, halogen, substituted or unsubstituted C1-4alkyl, and substituted or unsubstituted C1-4cycloalkyl; or Raand Rb together with the carbon atom to which they are attached, may form an unsubstituted or substituted 3 to 7 membered saturated carbocyclic ring; Rc, is selected from the group consisting of hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted haloalkyl, and substituted or unsubstituted alkyl; Rdand Re, are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, or Rd and Re can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by oxo, halo, cyano, nitro, hydroxy, carboxy, NRmRn, C1-4alkoxy, C1-4alkyl, C3-8cycloalkyl, C3-8 cycloalkyl-C1-3 alkyl, C1-4 alkanoyl, C1-4 alkylsulphonyl, or C(O)NRmRn, NRmC(O)Rn, NRmS(O)2Rn and S(O)2NRmRn; wherein Rm and Rn are each independently selected from hydrogen, C1-4alkyl or C3-6cycloalkyl and C3-6 cycloalkyl C1-2 alkyl; Rf is substituted or unsubstituted alkyl or substituted or unsubstituted aryl; Rgand Rh, are each independently selected from hydrogen or C1-2alkyl; Riand Rjare each independently selected from hydrogen or methyl; Rk and Rl are independently selected from the group consisting of hydrogen or C1-2alkyl; 'r' is an integer ranging from 0 to 3; 'p' is an integer ranging from 0 to 3; and 'q' is an integer ranging from 1 to 3.

[0049] In yet another embodiment of the present disclosure, there is provided a compound of general formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof,wherein, X1 and X2 are independently selected from -CR-, -CH2- and -O- , wherein both X1and X2are not simultaneously O; R is selected as hydrogen; R1, which may be same or different at each occurrence, is independently selected from the group consisting of halogens such as fluorine, chlorine, bromine, and iodine; R2 is a group -A-B, wherein, A is absent or a linker group of the formula -O-, or - N(Ri)-; B is independently selected from hydrogen, halogen, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -NRdRe, C3-6 cycloalkyl, C3-6 cycloalkenyl, C2-6 heterocyclyl, and the substituents of alkyl, aryl, cycloalkyl, heterocyclyl or heteroaryl are independently selected from halo, cyano, nitro, hydroxy, carboxy, NRkRl, C1-2 alkoxy, C1-2 haloalkoxy, or C1- 2 alkyl; Riand Rjare each independently selected from hydrogen or methyl; Rkand Rlare independently selected from the group consisting of hydrogen or C1-2 alkyl; or Rdand Recan be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by halo group 'p' is an integer ranging from 0 to 2; and 'q' is an integer ranging from 1 to 2.

[0050] In still another embodiment of the present disclosure, R is hydrogen; R1is hydrogen or fluorine; R2 is a group -A-B, wherein, A is absent or a linker group of the formula -O-, or - N(Ri)-; B is independently selected from hydrogen, fluorine, bromine, hydroxy, substituted or unsubstituted aryl, substituted or unsubstituted C2-4heterocyclyl, or NRdRe, and the substituents of alkyl, aryl, cycloalkyl, or heterocyclyl areindependently selected from halo, hydroxy, C1-2 alkoxy, C1-2 haloalkoxy, or C1-2alkyl, Rd and Re can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-6 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by halo group, 'p' is an integer ranging from 0 to 2; and 'q' is an integer ranging from 1 to 2. GENERAL METHODS OF PREPARATION

[0051] The compound of general formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof,wherein, X1and X2are independently selected from -CR-, -CH2- and -O- , wherein both X1 and X2 are not simultaneously O; R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -CF3, - OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl; R1, which may be same or different at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, -CF3, -OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, - (CRaRb)r-C(O)ORc, -NRdRe, -C(O)Rf, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, - S(O)0-2Rc, and -S(O)2NRdRe; R2 is a group -A-B, wherein A is absent or a linker group of the formula -[CRgRh]- , -O-, -C(O)-, -C(O)O-, -OC(O)-, -CH(ORi)-, -N(Ri)-, N(Rj)-C(O)-, -N(Rj)-C(O)O- , -C(O)-N(Rj)-, -N(Rj)C(O)N(Ri)-, -S-, -SO-, -SO2-, -S(O)2N(Ri)-, and, -N(Rj)SO2-B is independently selected from hydrogen, deuterium, halogen, cyano, nitro, -CF3, -OCF3, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, - (CRaRb)r-C(O)ORc, -C(O)Rf, NRdRe, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, - S(O)0-2Rc, and, -S(O)2NRdRe, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, heterocyclyl, and the substituents of alkyl, aryl, cycloalkyl, heterocyclyl or heteroaryl are independently selected from halo, cyano, nitro, hydroxy, carboxy, NRkRl, C1-2alkoxy, or C1-2alkyl; wherein Ra and Rb, are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, and substituted or unsubstituted cycloalkyl; or Ra and Rb together with the carbon atom to which they are attached, may form an unsubstituted or substituted 3 to 7 membered saturated carbocyclic ring; Rc, is selected from the group consisting of hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted haloalkyl, and substituted or unsubstituted alkyl; Rdand Re, are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl; or Rd and Re can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by oxo, halo, cyano, nitro, hydroxy, carboxy, -NRmRn, C1-4 alkoxy, C1-4 alkyl, C3-8 cycloalkyl, C3- 8 cycloalkyl-C1-3 alkyl, C1-4 alkanoyl, C1-4 alkylsulphonyl, or -C(O)NRmRn, - NRmC(O)Rn, -NRmS(O)2Rnand -S(O)2NRmRn; wherein Rmand Rnare each independently selected from hydrogen, C1-4alkyl or C3-6cycloalkyl and C3-6 cycloalkyl C1-2 alkyl; Rfis substituted or unsubstituted alkyl or substituted or unsubstituted aryl; Rgand Rh, are each independently selected from hydrogen or C1-2alkyl; Ri and Rj are each independently selected from hydrogen or C1-2 alkyl; Rk and Rl are independently selected from the group consisting of hydrogen or C1-2alkyl;'r' is an integer ranging from 0 to 3; 'p' is an integer ranging from 0 to 4; and 'q' is an integer ranging from 0 to 4, is prepared by the following general process comprising: i) C-C / C-N / C-O coupling of cyclic ketone of formula (2), wherein X1 and X2, are as defined above, with a boronic acid or ester or an amine in the presence of a base and a catalyst to produce substituted cyclic ketone of formula (4), wherein X1, X2, R2, and q are as defined above;ii) intermolecular cyclization of substituted cyclic ketone of formula (4), with anthranilic acid of formula (5), wherein R1, p, and q are as defined above, to produce a compound of formula (I),wherein X1, X2, R1, R2, p, and q are as defined above.

[0052] The specific synthetic approach for the synthesis of compounds covered under the compound of formula (I) wherein R1, R2, X1, X2, Y, p, and q are as defined with respect to a compound of formula (I)] is depicted below as synthetic scheme 1-4. Scheme 1

[0053] In an embodiment of the present invention provides a process, wherein intermolecular Chan-Lam Coupling of a hydroxy or amino substituted compound of formula (2a) with appropriate boronic acid or ester of formula (3) in the presence of a suitable base and a copper catalyst in a suitable solvent afford a compound of formula (4), which on intermolecular cyclization with anthranilic acid (5) yields the compound with general formula (I) (Scheme 1). Scheme 2

[0054] In another embodiment of the present invention provides a process, wherein the reaction of the compound of formula (2b) and an aliphatic or aromatic amine undergoes a coupling reaction such as Buchwald-Hartwig coupling in the presence of a suitable base, a palladium catalyst, and a ligand in an appropriate solvent to give an amino-substituted compound of formula (4) which on intermolecular cyclization with anthranilic acid (5) yields the compound with general formula (I) (scheme 2). Scheme 3

[0055] In another embodiment of the present invention provides a process, wherein intermolecular Suzuki coupling of a compound of general formula (2c) with suitable boronic acid of formula (3) in the presence of a base and a palladium catalyst in a suitable solvent afford a compound of formula (4), which on intermolecular cyclization with anthranilic acid (5) yields the compound with general formula (I) (scheme 3). Scheme 4

[0056] Intermolecular cyclization between compound (2) and anthranilic acid (5) occur to give the compound of general formula (Ia), which further undergoes substitution reaction to afford compound of formula (I).

[0057] The compounds described herein, including compounds of general formula (Ia) and (I), can be prepared by using techniques known to one skilled in the art through the reaction sequences described in schemes 1-4 as well as by other methods. Further, in the following schemes, where specific bases, acids, reagents, solvents, etc., are mentioned, it is understood that other bases, acids, reagents, solvents, etc., known in the art may also be used and are therefore included within the scope of the present invention. Variations in reaction conditions, for example,temperature and / or duration of the reaction, which may be used as known in the art, are also within the scope of the present invention. Unless otherwise specified, all the isomers of the compound of the formula are described in these schemes and are also encompassed within the scope of this invention. Unless otherwise stated, work- up implies the following operations: distribution of the reaction mixture between the aqueous and organic phase, separation of layers, drying of the organic layer over sodium sulphate or magnesium sulphate filtration, and evaporation of the organic solvent. “Filtration" implies filtering on a celite pad on a Buchner funnel using a suitable solvent or a mixture of the appropriate polarity of solvents. Purification, unless otherwise stated, implies crystallization or purification by silica gel chromatographic techniques using ethyl acetate / petroleum ether, methanol / dichloromethane, or acetonitrile / water mixture of a suitable polarity as the mobile phase.

[0058] The intermediates and the compounds of the present invention may be obtained in pure form in a manner known per se, for example, by distilling off the solvent in vacuum and re-crystallizing the residue obtained from a suitable solvent, such as pentane, diethyl ether, isopropyl ether, chloroform, dichloromethane, ethyl acetate, acetone or their combinations or subjecting it to one of the purification methods, such as column chromatography (e.g., flash chromatography) on a suitable support material such as alumina or silica gel using eluents such as dichloromethane, ethyl acetate, hexane, methanol, acetone and their combinations in normal-phase or acetonitrile, water and methanol combinations in reverse phase. The Preparative LC-MS method is also used for the purification of molecules described herein.

[0059] Although the subject matter has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the subject matter, will become apparent to persons skilled in the art upon reference to the description of the subject matter. It is therefore contemplated that such modifications can be made without departing from the spirit or scope of the present subject matter as defined.Examples

[0060] The following examples are set forth so that the invention described herein may be more fully understood. The examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope. General Procedure:

[0061] The intermediates described below were prepared using synthetic scheme 1 depicted above. Intermediate 1: 6-phenoxy-3,4-dihydronaphthalen-1(2H)-one

[0062] The phenylboronic acid (767 mg, 2 eq.) was dissolved in 14-15 mL dichloromethane. 6-Hydroxy-3,4-dihydronaphthalen-l(2H)-one (200 mg, 1.0 eq.), triethylamine (622.3 mg, 5.0 eq.) and copper acetate (212.5 mg, 0.95 eq.) were added, and the reaction is sealed and stirred for 16 h at room temperature. The mixture was then transferred to a separatory funnel with excess dichloromethane and water. The organic layer was then washed with water and brine. The organic layer was dried with sodium sulphate and concentrated to provide 6-phenoxy-3,4- dihydronaphthalen-1(2H)-one as a brown oil. The crude compound was purified by flash column chromatography (Biotage) using eluent (10% ethyl acetate: n-hexane) to get 6-phenoxy-3,4-dihydronaphthalen-1(2H)-one (110 mg, 37.44% yield). LCMS (ESI): m / z = 239.1 (M+H)+Intermediate 2: 6-(4-trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen- 1(2H)-one

[0063] Following a similar procedure as described in the synthesis of intermediate 1 and replacing phenylboronic acid with para-trifluoromethoxyphenylboronic acid.1H NMR (500 MHz, CDCl3) δ = 7.95 (d, J = 8.7 Hz, 1H), 7.33 (t, J = 8.0 Hz, 2H), 7.03 – 6.97 (m, 2H), 6.80 (dd, J = 8.6, 2.4 Hz, 1H), 6.71 – 6.67 (m, 1H), 2.82 (t, J = 6.1 Hz, 2H), 2.58 – 2.53 (m, 2H), 2.05 (dd, J = 12.6, 6.5 Hz, 2H). Intermediate 3: 7-phenoxy-3,4-dihydronaphthalen-1(2H)-one

[0064] Following a similar procedure as described in the synthesis of intermediate 1 and replacing 6-Hydroxy-3,4-dihydronaphthalen-l(2H)-one with 7- Hydroxy-3,4-dihydronaphthalen-l(2H)-one.1H NMR (500 MHz, CDCl3) δ = 7.56 – 7.53 (m, 1H), 7.25 (t, J = 7.9 Hz, 2H), 7.17 – 7.13 (m, 1H), 7.11 – 7.06 (m, 1H), 7.03 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 8.2 Hz, 2H), 2.86 (t, J = 6.0 Hz, 2H), 2.56 (d, J = 6.4 Hz, 2H), 2.09 – 2.01 (m, 2H). Intermediate 4: 7-(4-trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen- 1(2H)-one

[0065] Following a similar procedure as described in the synthesis of intermediate 2 and replacing phenylboronic acid with para- trifluoromethoxyphenylboronic acid.1H NMR (500 MHz, CDCl3) δ = 7.55 (d, J = 2.7 Hz, 1H), 7.18 (d, J = 3.6 Hz, 1H), 7.11 – 7.09 (m, 1H), 7.09 – 7.07 (m, 2H), 6.92 – 6.88 (m, 2H), 2.87 (t, J = 6.1 Hz, 2H), 2.59 – 2.54 (m, 2H), 2.09 – 2.02 (m, 2H). Intermediate 5: 7-phenoxychroman-4-one

[0066] Following a similar procedure as described in the synthesis of intermediate 1 and replacing 6-Hydroxy-3,4-dihydronaphthalen-l(2H)-one with 7- hydroxychroman-4-one. LCMS (ESI): m / z = 241.0 (M+H)+Intermediate 6: 7-(4-(trifluoromethoxy)phenoxy)chroman-4-one

[0067] Following a similar procedure as described in the synthesis of intermediate 5 and replacing phenylboronic acid with para- trifluoromethoxyphenylboronic acid. LCMS (ESI): m / z = 325.0 (M+H)+The intermediates described below were prepared using synthetic scheme 2 depicted above. Intermediate 7: 7-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)- one

[0068] A mixture of 7-Bromo-3,4-dihydronaphthalen-1(2H)-one (100 mg, 1.0 eq.), 3,3-difluoropyrrolidine hydrochloride (63.2 mg, 1.0 eq.) and sodium tert- butoxide (126.8 mg, 3 eq.) in 1,4-dioxane (4 mL) in a sealed tube was purged with nitrogen. Then was added Pd2(dba)3(16.1 mg, 0.004 eq.) and Xantphos (41.1 mg, 0.16 eq.), and the sealed tube was then heated to 110 °C for 24 h in an oil bath. After the completion of the reaction, the reaction mixture was allowed to cool to room temperature, filtered through a celite pad, and washed with 70% ethyl acetate: hexane. The filtrate and washed down solution were combined and concentrated under vacuum to give the crude product. Further purification was carried out using flash column chromatography (Biotage) (using 30% ethyl acetate: hexane mixture) to obtain 7-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one as a light brown solid. LCMS (ESI): m / z = 252.0 (M+H)+.1H NMR (500 MHz, CDCl3) δ = 7.19 (d, J = 2.8 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 6.72 (dd, J = 8.4, 2.8 Hz, 1H),3.68 (t, J = 13.3 Hz, 2H), 3.53 (t, J = 7.1 Hz, 2H), 2.87 (t, J = 6.1 Hz, 2H), 2.65 – 2.61 (m, 2H), 2.53 – 2.43 (m, 2H), 2.13 – 2.07 (m, 2H). Intermediate 8: 6-(pyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one

[0069] To a suspension of toluene (0.58 mL) and 2-methylpropan-2-ol (0.12 mL) was added 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate (140 mg, 1.0 eq.) followed by addition of caesium carbonate (387.7 mg, 2.5 eq.), pyrrolidine (50.8 mg, 1.5 eq.), Xantphos (13.8 mg, 0.05 eq.) and palladium diacetate (2.1 mg, 0.02 eq.). The resulting reaction mixture was heated to reflux for 24 hours under a nitrogen atmosphere. The reaction solution was cooled to room temperature, filtered through a Celite pad, washed with ethyl acetate, and then the filtrate was concentrated to obtain the crude product. Further purification was carried out using flash column chromatography (Biotage) (using 15% ethyl acetate: hexane mixture) to obtain 6-(pyrrolidine-1-yl)-3,4-dihydronaphthalen-1(2H)-one as light brown oil. LCMS (ESI): m / z = 216.2 (M+H)+.1H NMR (500 MHz, CDCl3) δ = 7.87 (d, J = 8.8 Hz, 1H), 6.38 (dd, J = 8.8, 2.4 Hz, 1H), 6.20 – 6.16 (m, 1H), 3.32 – 3.24 (m, 4H), 2.79 (t, J = 6.1 Hz, 2H), 2.52 – 2.45 (m, 2H), 2.04 – 1.97 (m, 2H), 1.97 – 1.92 (m, 4H). Intermediate 9: 6-(3,3-difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)- one

[0070] Following a similar procedure as described in the synthesis of intermediate 8 and replacing pyrrolidine with 3,3-difluoroazetidine hydrochloride. LCMS (ESI): m / z = 238.1 (M+H)+Intermediate 10: 6-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen- 1(2H)-one

[0071] Following a similar procedure as described in the synthesis of intermediate 8 and replacing pyrrolidine with 3,3-difluoropyrrolidine hydrochloride. LCMS (ESI): m / z = 252.1 (M+H)+.1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.7 Hz, 1H), 6.46 (dd, J = 8.7, 2.3 Hz, 1H), 6.27 (d, J = 2.3 Hz, 1H), 3.74 (t, J = 12.9 Hz, 2H), 3.62 (t, J = 7.2 Hz, 2H), 2.89 (t, J = 6.1 Hz, 2H), 2.62 – 2.56 (m, 2H), 2.56 – 2.45 (m, 2H), 2.13 – 2.05 (m, 2H). Intermediate 11: 7-(3,3-difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)- one

[0072] Following a similar procedure as described in the synthesis of intermediate 8 and replacing 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulphonate with 8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulphonate and pyrrolidine with 3,3-difluoroazetidine hydrochloride. LCMS (ESI): m / z = 238.0 (M+H)+.1H NMR (500 MHz, CDCl3) δ = 7.16 (d, J = 8.3 Hz, 1H), 7.14 (d, J = 2.7 Hz, 1H), 6.66 (dd, J = 8.3, 2.7 Hz, 1H), 4.23 (t, J = 11.8 Hz, 4H), 2.89 (t, J = 6.1 Hz, 2H), 2.65 – 2.61 (m, 2H), 2.14 – 2.08 (m, 2H). Intermediate 12: 6-morpholino-3,4-dihydronaphthalen-1(2H)-one

[0073] Following a similar procedure as described in the synthesis of intermediate 8 and replacing pyrrolidine with morpholine. LCMS (ESI): m / z =232.1 (M+H)+.1H NMR (500 MHz, CDCl3) δ = 7.97 (d, J = 8.8 Hz, 1H), 6.81 (dd, J = 8.8, 2.6 Hz, 1H), 6.65 – 6.63 (m, 1H), 3.87 – 3.84 (m, 4H), 3.33 – 3.30 (m, 4H), 2.89 (t, J = 6.1 Hz, 2H), 2.61 – 2.57 (m, 2H), 2.13 – 2.07 (m, 2H). Intermediate 13: 7-(3,3-difluoropyrrolidin-1-yl)chroman-4-one

[0074] Following a similar procedure as described in the synthesis of intermediate 8 and replacing pyrrolidine with 3,3-difluoropyrrolidine hydrochloride and 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulphonate with chromane-4-one. LCMS (ESI): m / z = 254.0 (M+H)+.1H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 8.8 Hz, 1H), 6.23 (dd, J = 8.8, 2.3 Hz, 1H), 5.96 (d, J = 2.3 Hz, 1H), 4.51 – 4.45 (m, 2H), 3.72 (t, J = 12.9 Hz, 2H), 3.60 (t, J = 7.3 Hz, 2H), 2.76 – 2.69 (m, 2H), 2.57 – 2.45 (m, 2H). Intermediate 14: 7-(3,3-difluoroazetidin-1-yl)chroman-4-one

[0075] Following a similar procedure as described in the synthesis of intermediate 13 and replacing 3,3-difluoropyrrolidine hydrochloride with 3,3- difluoroazetidine hydrochloride. LCMS (ESI): m / z = 240.1 (M+H)+.1H NMR (500 MHz, CDCl3) δ = 7.82 (d, J = 8.6 Hz, 1H), 6.12 (dd, J = 8.6, 2.3 Hz, 1H), 5.90 (d, J = 2.3 Hz, 1H), 4.50 – 4.47 (m, 2H), 4.30 (t, J = 11.7 Hz, 4H), 2.75 – 2.71 (m, 2H). Intermediate 15: 7-(phenylamino)-3,4-dihydronaphthalen-1(2H)-one

[0076] Following a similar procedure as described in the synthesis of intermediate 11 and replacing 3,3-difluoroazetidine hydrochloride with aniline. LCMS (ESI): m / z = 238.2.1 (M+H)+.1H NMR (500 MHz, CDCl3) δ = 7.97 – 7.93(m, 1H), 7.37 – 7.32 (m, 2H), 7.20 – 7.16 (m, 2H), 7.12 – 7.06 (m, 1H), 6.85 (dd, J = 8.6, 2.4 Hz, 1H), 6.79 – 6.76 (m, 1H), 2.85 (t, J = 6.1 Hz, 2H), 2.61 – 2.57 (m, 2H), 2.12 – 2.06 (m, 2H). The intermediates described below were prepared using synthetic scheme 3 depicted above. Intermediate 16: 7-(4-(trifluoromethoxy)phenyl)chroman-4-one

[0077] A mixture of 7-bromochroman-4-one (117 mg, 1 eq.) and (4- (trifluoromethoxy)phenyl)boronic acid(128.5 mg, 1.2 eq.) in 1,4-dioxane (5 mL) was taken into a sealed tube. An aqueous solution of sodium carbonate (110.2 mg in 1.48 mL water) was added to the above mixture. The resulting solution was purged with nitrogen for 15 min, and then the catalyst Pd(dppf)Cl2(15.2 mg, 0.04 eq.) was added, and the tube was sealed pack tightly. The sealed tube was put in a pre-heated oil bath and stirred overnight at 80 °C. The resultant mixture was allowed to cool to room temperature and then filtered through a celite pad and rinsed with dichloromethane. The resulting filtrate was dried using anhydrous sodium sulphate, filtered, and then concentrated under vacuum to obtain crude product. Further purification was carried out using flash column chromatography (Biotage) (using 30% ethyl acetate: hexane mixture) to obtain 7-(4- (trifluoromethoxy)phenyl)chroman-4-one. LCMS (ESI): m / z = 307.1 (M-H)+.1H NMR (500 MHz, CDCl3) δ = 7.90 (d, J = 8.2 Hz, 1H), 7.57 – 7.52 (m, 2H), 7.25 – 7.21 (m, 2H), 7.15 (dd, J = 8.2, 1.7 Hz, 1H), 7.09 (d, J = 1.7 Hz, 1H), 4.53 – 4.49 (m, 2H), 2.80 – 2.75 (m, 2H) Synthesis of compounds Example 1: 3-bromo-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0078] Into a microwave sealed tube was added 6-Bromo-3,4- dihydronaphthalen-1(2H)-one (100 mg, 0.44 mmol) and 2-aminobenzoic acid (40.4 mg, 0.29 mmol). The reaction mixture was irradiated in a commercial microwave oven at 190 °C for 1 h. To furnish the desired product of 3-bromo-6,12- dihydrobenzo[c]acridin-7(5H)-one, the crude product was recrystallized using ether and was further purified by flash chromatography (silica gel, 60-70% EtOAc– hexane). LCMS (ESI): m / z = 325.9, 327.9 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.57 (bs, 1H), 8.19 – 8.15 (m , 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.90 – 7.84 (m, 1H), 7.77 – 7.73 (m, 1H), 7.73 – 7.69 (m, 2H), 7.40 – 7.35 (m, 1H), 2.94 – 2.87 (m, 2H), 2.83 – 2.77 (m, 2H). Example 2: 2-bromo-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0079] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- Bromo-3,4-dihydronaphthalen-1(2H)-one, the compound 2-bromo-6,12- dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 325.9, 327.9 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.49 (bs, 1H), 8.29 (d, J = 1.9 Hz, 1H), 8.12 (dd, J = 8.1, 1.2 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.69 – 7.62 (m, 2H), 7.37 (d, J = 8.1 Hz, 1H), 7.34 – 7.29 (m, 1H), 2.84 – 2.78 (m, 2H), 2.77 – 2.72 (m, 2H). Example 3: 3-hydroxy-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0080] Following a procedure analogous to the one provided for the compound of example 1 and replacing the compound 6-bromo-3,4-dihydronaphthalen-1(2H)- one with 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one, the compound 3-hydroxy- 6,12-dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 264.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.46 (bs, 1H), 10.13 (bs, 1H), 8.09 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.27 (t, J = 7.4 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 6.80 (s, 1H), 2.77 – 2.67(m, 4H). Example 4: 2-hydroxy-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0081] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- hydroxy-3,4-dihydronaphthalen-1(2H)-one, the compound 2-hydroxy-6,12- dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z =264.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.40 (bs, 1H), 9.62 (bs, 1H), 8.11 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.52 – 7.47 (m, 1H), 7.30 (t, J = 7.4 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 6.89 (dd, J = 8.1, 2.0 Hz, 1H), 2.71 (s, 4H). Example 5: 3-phenoxy-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0082] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 6- phenoxy-3,4-dihydronaphthalen-1(2H)-one, the compound 3-phenoxy-6,12- dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 340.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.44 (bs, 1H), 8.18 – 8.02 (m, 2H), 7.86– 7.76 (m, 1H), 7.60 – 7.68 (m, 1H), 7.44 – 7.51 (m, 2H), 7.34 – 7.26 (m, 1H), 7.26 – 7.19 (m, 1H), 7.18 – 7.10 (m, 2H), 7.10 – 7.05 (m, 1H), 7.01 (s, 1H), 2.89 – 2.67 (m, 4H). Example 6: 2-phenoxy-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0083] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 7- phenoxy-3,4-dihydronaphthalen-1(2H)-one, the compound 2-phenoxy-6,12- dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z =339.8 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.41 (bs, 1H), 8.13 (d, J = 7.8 Hz, 1H), 7.94 (s, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.47 – 7.36 (m, 3H), 7.31 (t, J = 7.2 Hz, 1H), 7.15 (t, J = 7.1 Hz, 1H), 7.11 – 7.01 (m, 3H), 2.88 – 2.81 (m, 2H), 2.81 – 2.75 (m, 2H). Example 7: 3-(4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin- 7(5H)-one

[0084] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 6-(4- (trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen-1(2H)-one, the compound 3- (4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 423.9 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.43 (bs, 1H), 8.14 - 8.06 (m, 2H), 7.81 (d, J = 8.2 Hz, 1H), 7.66 – 7.61 (m, 1H), 7.49 – 7.43 (m, 2H), 7.33 – 7.27 (m, 1H), 7.25 – 7.20 (m, 1H), 7.15 – 7.12 (m, 1H), 7.11 – 7.06 (m, 1H), 7.02 (d, J = 2.5 Hz, 1H), 2.86 – 2.78 (m, 2H), 2.77 – 2.71 (m, 2H).Example 8: 2-(4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin- 7(5H)-one

[0085] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7-(4- (trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen-1(2H)-one, the compound 2- (4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 423.9 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.39 (bs, 1H), 8.18 – 8.08 (m, 1H), 7.96 (s, 1H), 7.84 – 7.75 (m, 1H), 7.69 – 7.60 (m, 1H), 7.56 – 7.35 (m, 3H), 7.35 – 7.25 (m, 1H), 7.24 – 7.07 (m, 3H), 2.96 – 2.66 (m, 4H). Example 9: 2-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin- 7(5H)-one

[0086] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- (3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one, the compound 2- (3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 353.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.27 (s, 1H), 8.14 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 7.1 Hz, 1H), 7.32 (t, J = 7.1 Hz, 1H), 7.27 – 7.22 (m, 2H), 6.74 (d, J = 7.4 Hz, 1H), 3.82 (t, J = 13.2 Hz, 2H), 3.62 – 3.56 (m, 2H), 2.71 (s, 4H), 2.65 – 2.54 (m, 2H). Example 10: 2-(3,3-difluoropyrrolidin-1-yl)benzo[c]acridin-7(12H)-one

[0087] Example 10 product (2-(3,3-difluoropyrrolidin-1-yl)benzo[c]acridin- 7(12H)-one) was formed with example 9 product (2-(3,3-difluoropyrrolidin-1-yl)- 6,12-dihydrobenzo[c]acridin-7(5H)-one). LCMS (ESI): m / z = 351.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.38 (bs, 1H), 8.29 (d, J = 7.4 Hz, 1H), 8.03 – 7.95 (m, 3H), 7.94 – 7.88 (m, 1H), 7.84 – 7.79 (m, 2H), 7.77 (s, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.39 – 7.33 (m, 1H), 7.31 – 7.25 (m, 1H), 3.97 (t, J = 12.8 Hz, 2H), 3.78 – 3.72 (m, 2H), 2.74 – 2.68 (m, 2H). Example 11: 3-(pyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0088] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 6- (pyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one, the compound 3-(pyrrolidin- 1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 317.3 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.20 (bs, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 8.5 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.58 (t, J = 7.1 Hz, 1H), 7.24 (t, J = 7.4 Hz, 1H), 6.59 (d, J = 9.3 Hz, 1H), 6.53 (s, 1H), 2.79 – 2.68 (m, 4H), 2.07–1.92 (m, 4H), 1.31–1.15 (m, 4H). Example 12: 3-(3,3-difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)- one

[0089] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 6-(3,3- difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one the compound 3-(3,3- difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one was obtained. LCMS (ESI): m / z = 339.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.29 (bs, 1H), 8.09 (d, J = 7.7 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.27 (t, J = 7.5 Hz, 1H), 6.63 (d, J = 6.8 Hz, 1H), 6.58 (s, 1H), 4.39 (t, J = 12.2 Hz, 4H), 2.79 – 2.69 (m, 4H). Example 13: 3-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin- 7(5H)-one

[0090] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 6-(3,3- difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one to obtain 3-(3,3- difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one. LCMS (ESI): m / z = 353.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.25 (bs, 1H), 8.09 (dd, J = 8.0, 1.2 Hz, 1H), 7.94 (d, J = 8.6 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.63 – 7.57 (m, 1H), 7.29 – 7.23 (m, 1H), 6.68 (dd, J = 8.6, 2.4 Hz, 1H), 6.63 (d, J = 2.3 Hz, 1H), 3.81 (t, J = 13.2 Hz, 2H), 3.59 (t, J = 7.2 Hz, 2H), 2.80 – 2.70 (m, 4H), 2.63 – 2.53 (m, 2H). Example 14: 2-(3,3-difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)- one

[0091] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 7-(3,3- difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one to obtain 2-(3,3- difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one. LCMS (ESI): m / z = 339.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.35 (bs, 1H), 8.13 (dd, J = 8.1, 1.3 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.69 – 7.64 (m, 1H), 7.31 (t, J = 7.1 Hz, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.25 (d, J = 2.0 Hz, 1H), 6.69 (dd, J = 8.1, 2.2 Hz, 1H), 4.37 (t, J = 12.3 Hz, 4H), 2.72 (s, 4H). Example 15: 3-morpholino-6,12-dihydrobenzo[c]acridin-7(5H)-one

[0092] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 6- morpholino-3,4-dihydronaphthalen-1(2H)-one to obtain 3-morpholino-6,12- dihydrobenzo[c]acridin-7(5H)-one. LCMS (ESI): m / z = 333.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.27 (bs, 2H), 8.11 – 8.07 (m, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H), 7.63 – 7.58 (m, 2H), 7.29 – 7.25 (m, 2H), 7.02 (dd, J = 8.7, 2.5 Hz, 2H), 6.96 – 6.94 (m, 2H), 3.80 – 3.73 (m, 8H), 3.29 – 3.25 (m, 9H), 2.81 – 2.70 (m, 9H). Example 16: 2-(phenylamino)benzo[c]acridin-7(12H)-one

[0093] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- (phenylamino)-3,4-dihydronaphthalen-1(2H)-oneobtain(phenylamino)benzo[c]acridin-7(12H)-one. LCMS (ESI): 337.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.54 (bs, 1H), 8.80 – 8.76 (m, 2H), 8.26 – 8.22 (m, 1H),8.09 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 8.2 Hz, 1H), 7.77 – 7.72 (m, 1H), 7.53 (d, J = 2.3 Hz, 1H), 7.46 – 7.42 (m, 2H), 7.35 – 7.33 (m, 2H), 7.32 – 7.30 (m, 1H), 7.29 – 7.27 (m, 2H), 7.00 – 6.96 (m, 1H). Example 17: 3-(4-(trifluoromethoxy)phenyl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one

[0094] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7-(4- (trifluoromethoxy)phenyl)chroman-4-one to obtain 3-(4- (trifluoromethoxy)phenyl)-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one. LCMS (ESI): m / z = 410 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.71 (bs, 1H), 8.20 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 8.7 Hz, 2H), 7.84 (d, J = 8.3 Hz, 1H), 7.72 – 7.67 (m, 1H), 7.59 – 7.55 (m, 1H), 7.49 (d, J = 8.1 Hz, 2H), 7.41 – 7.38 (m, 1H), 7.35 (t, J = 7.5 Hz, 1H), 5.25 (s, 2H). Example 18: 6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one

[0095] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with chroman-4-one to obtain 6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one. LCMS (ESI): m / z =250.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.65 (bs, 1H), 8.14 - 8.07 (m, 2H), 7.83 (d, J = 8.3 Hz, 1H), 7.72 – 7.66 (m, 1H), 7.50 – 7.45 (m, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 5.19 (s, 2H). Example 19: 3-bromo-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one

[0096] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- bromochroman-4-one to obtain 3-bromo-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one. LCMS (ESI): m / z = 327.9, 329.9 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.71 (bs, 1H), 8.11 (d, J = 7.9 Hz, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.70 (t, J = 7.3 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.39 – 7.30 (m, 2H), 5.22 (s, 2H). Example 20: 2-bromo-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one

[0097] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 6- bromochroman-4-one to obtain 2-bromo-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one. LCMS (ESI): m / z = 328.0, 330.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.70 (bs, 1H), 8.33 (d, J = 2.3 Hz, 1H), 8.11 (d, J = 7.0 Hz, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.73 – 7.68 (m, 1H), 7.62 (dd, J = 8.7, 2.3 Hz, 1H), 7.39 – 7.33 (m, 1H), 7.04 (d, J = 8.7 Hz, 1H), 5.21 (s, 2H). Example 21: 3-fluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one

[0098] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- fluorochroman-4-one to obtain 3-fluoro-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one. LCMS (ESI): m / z =268.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.66 (bs, 1H), 8.18 – 8.13 (m, 1H), 8.11 (d, J = 7.9 Hz, 1H), 7.82 – 7.78 (m,1H), 7.72 – 7.66 (m, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.14 – 7.07 (m, 1H), 7.00 – 6.96 (m, 1H), 5.23 (s, 2H). Example 22: 2-fluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one

[0099] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 6- fluorochroman-4-one to obtain 2-fluoro-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one. LCMS (ESI): m / z = 268.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.66 (bs, 1H), 8.14 – 8.10 (m, 1H), 8.00 (dd, J = 9.4, 2.9 Hz, 1H), 7.82 – 7.78 (m, 1H), 7.73 – 7.68 (m, 1H), 7.36 (dd, J = 9.9, 4.4 Hz, 1H), 7.33 (dd, J = 8.6, 2.9 Hz, 1H), 7.11 (dd, J = 9.0, 4.7 Hz, 1H), 5.19 (s, 2H). Example 23: 3-hydroxy-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one[000100] Following a procedure analogous to the one provided for the compound of example 1 and 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 7- hydroxychroman-4-one to obtain 3-hydroxy-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one. LCMS (ESI): m / z = 266.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.47 (bs, 1H), 10.30 (bs, 1H), 8.11 – 8.07 (m, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.68 – 7.63 (m, 1H), 7.33 – 7.29 (m, 1H), 6.62 (dd, J = 8.6, 2.3 Hz, 1H), 6.44 (d, J = 2.3 Hz, 1H), 5.13 (s, 2H). Example 24: 3-phenoxy-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one[000101] Following a procedure analogous to the one provided for compound of example 1 and replacing 6-bromo-3,4-dihydronaphthalen-1(2H)-one with 7-phenoxychroman-4-one to obtain 3-phenoxy-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one. LCMS (ESI): m / z = 342.3 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.67 (bs, 1H), 8.16 (d, J = 8.5 Hz, 2H), 7.85 (d, J = 8.3 Hz, 1H), 7.73 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.35 (dt, J = 37.6, 7.4 Hz, 3H), 7.21 (d, J = 7.9 Hz, 2H), 6.89 (dd, J = 8.6, 2.2 Hz, 1H), 6.91 – 6.86 (m, 1H), 5.24 (s, 2H). Example 25: 3-(4-(trifluoromethoxy)phenoxy)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one[000102] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7-(4- (trifluoromethoxy)phenoxy)chroman-4-one to obtain 3-(4- (trifluoromethoxy)phenoxy)-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one. LCMS (ESI): m / z = 426.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.70 (bs, 1H), 8.21 – 8.14 (m, 2H), 7.86 (d, J = 8.3 Hz, 1H), 7.74 (m, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.42 – 7.38 (m, 1H), 7.35 – 7.31 (m, 2H), 6.96 (dd, J = 8.7, 2.4 Hz, 1H), 6.72 (d, J = 2.4 Hz, 1H), 5.26 (s, 2H). Example 26: 3-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one[000103] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- (3,3-difluoropyrrolidin-1-yl)chroman-4-one to obtain 3-(3,3-difluoropyrrolidin-1- yl)-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one. LCMS (ESI): m / z = 355.1 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.41 (bs, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.96 – 7.89 (m, 1H), 7.80 – 7.73 (m, 1H), 7.63 (t, J = 7.1 Hz, 1H), 7.29 (t, J = 7.4Hz, 1H), 6.47 (d, J = 7.1 Hz, 1H), 6.24 (s, 1H), 5.12 (s, 2H), 3.80 (t, J = 13.1 Hz, 2H), 3.57 (t, J = 6.9 Hz, 2H), 2.62 – 2.53 (m, 2H). Example 27: 3-(3,3-difluoroazetidin-1-yl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one[000104] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with 7- (3,3-difluoroazetidin-1-yl)chroman-4-one to obtain 3-(3,3-difluoroazetidin-1-yl)- 6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one. LCMS (ESI): m / z = 341.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.70 (bs, 1H), 8.21 – 8.14 (m, 2H), 7.86 (d, J = 8.3 Hz, 1H), 7.74 (m, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.42 – 7.38 (m, 1H), 7.35 – 7.31 (m, 2H), 6.96 (dd, J = 8.7, 2.4 Hz, 1H), 6.72 (d, J = 2.4 Hz, 1H), 5.26 (s, 2H). Example 28: 2-bromo-8,10-difluoro-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one[000105] Following a procedure analogous to the one provided for the compound of example 1 and replacing 6-Bromo-3,4-dihydronaphthalen-1(2H)-one with chroman-4-one and 2-aminobenzoic acid with 4,6-difluoro-2-aminobenzoic acid to obtain 2-bromo-8,10-difluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one. LCMS (ESI): m / z = 364.0, 366.0 (M+H)+.1H NMR (500 MHz, DMSO) δ = 11.82 (bs, 1H), 8.23 (d, J = 2.4 Hz, 1H), 7.60 (dd, J = 8.7, 2.2 Hz, 1H), 7.31 (d, J = 10.0 Hz, 1H), 7.11 – 7.04 (m, 1H), 7.01 (d, J = 8.7 Hz, 1H), 5.15 (s, 2H). Determination of MIC of compounds against H37Rv using microplate Alamar blue assay (MABA)[000106] The Resazurin assay is a straightforward, quick, and sensitive method for determining the viability of mammalian cells and bacteria. Alamar Blue assay is another name for it. In nature, living cells are metabolically active and use mitochondrial reductase to convert the nonfluorescent dye resazurin to the strong fluorescent dye resorufin. The quantity of fluorescence intensity is directly proportional to cell viability. Alamar Blue is nontoxic to cells; hence cells exposed to it can be returned to culture or used for other applications. Microplate Alamar Blue assay is an Alamar Blue assay performed in a MABA assay microplate. [000107] Mycobacteria employs two terminal oxidases in its oxidative cycle. One is the cytochrome bc1:aa3 type cytochrome c oxidase supercomplex, while the other is cytochrome bd-type quinol oxidase (the cytochrome bd oxidase). The experiment assessed the synthesised compounds' efficacy against cytochrome bd- type quinol oxidase by determining how crucial cytochrome bd oxidase was to maintaining ATP homeostasis in the event that a particular small molecule inhibitor (such as Q203) inhibits the cytochrome bc1:aa3 branch. Upon inhibition of the cytochrome bc1:aa3 branch with 2.5 nM of Q203, putative cytochrome bd oxidase was tested to determine the Minimum Inhibitory Concentration (MIC) of the synthesized compounds. The MIC values were determined in the presence of Q203 (“+Q203”) or in the absence of Q203 (“-Q203”). A deletion mutant devoid of the cytochrome bc1:aa3 branch was employed to validate the antimycobacterial efficacy of few selected compounds. Protocol [000108] For determination of minimum inhibitory concentration (MIC) of novel compounds against Mtb, 2 x106(100 µL OD600=0.01), mycobacterial cells were seeded in each well of a 96-well plate from running culture (OD600=0.6), and different compounds were added in triplicate with or without 2.5 nM of Q203, along with DMSO as a control. Q203 was used to inhibit the cytochrome bc1:aa3 branch of respiration. Alternatively, Mtb ^ctaE, a deletion mutant lacking cytochrome bc1:aa3 branch was used for confirming the antimycobacterial activity of the compounds of few selected compounds. Incubated the treated sample plates inBSL-3 for 7 days at 37 °C in a humidified condition of 5% CO2. Subsequently, in each well, add 40 µL of 0.02 percent Alamar Blue and incubate for 1 day. After adding 50 µL of formalin to fix the mycobacterial cells, fluorescence was monitored at Excitation 530 nm and Emission 590 nm. The MIC of drugs was then determined by comparing the fluorescence intensity of treated and control samples. Table 2: Inhibitory activity data against Mycobacterium tuberculosis[000109] Thus, the above in-vitro assay method showed that the compounds of the invention were found to have antibacterial activity against Mtb, thereby showing utility for treating diseases and disorders associated with bacterial infections, particularly in the case of tuberculosis. [000110] The compound testing results have demonstrated that the compounds of formula (I) were found to be capable of treating / reducing bacterial infections.[000111] All patents, patent applications, and publications cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent as if each patent, patent application, or publication were so individually denoted. Although certain embodiments and examples have been described in detail above, those having ordinary skill in the art will clearly understand that many modifications are possible in the embodiments and examples without departing from the teachings thereof. Pharmaceutical formulations [000112] Effective amounts of the active compounds are used with suitable carriers or excipients to prepare pharmaceutical formulations. The carriers or excipients used are suitably selected from water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, salicylic acid, fatty acids, fatty acid amines, fatty acid monoglycerides, and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone or combinations thereof. The compound of general Formula (I) can also be used with one or more antibacterial compounds. Hence formulations of the effective amounts of the active compounds of general Formula (I) with one or more antibacterial compounds are prepared.

Claims

We Claim:

1. A compound of general formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof,wherein, X1and X2are independently selected from -CR-, -CH2- and -O- , wherein both X1and X2are not simultaneously O; R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -CF3, - OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl; R1, which may be same or different at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, -CF3, -OCF3, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r-C(O)ORc, - (CRaRb)r-C(O)ORc, -NRdRe, -C(O)Rf, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, - S(O)0-2Rc, and -S(O)2NRdRe; R2is a group -A-B, wherein A is absent or a linker group of the formula -[CRgRh]- , -O-, -C(O)-, -C(O)O-, -OC(O)-, -CH(ORi)-, -N(Ri)-, N(Rj)-C(O)-, -N(Rj)-C(O)O- , -C(O)-N(Rj)-, -N(Rj)C(O)N(Ri)-, -S-, -SO-, -SO2-, -S(O)2N(Ri)-, or -N(Rj)SO2- B is independently selected from hydrogen, deuterium, halogen, cyano, nitro, -CF3, -OCF3, NH2, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C(O)ORc, -OC(O)ORc, -O(CRaRb)r- C(O)ORc, -(CRaRb)r-C(O)ORc, -C(O)Rf, NRdRe, -C(O)NRdRe, -NRdC(O)Rf, - NRdS(O)2Re, - S(O)0-2Rc, and, -S(O)2NRdRe, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, heterocyclyl, and the substituents of alkyl, aryl,cycloalkyl, heterocyclyl or heteroaryl are independently selected from halo, cyano, nitro, hydroxy, carboxy, NRkRl, C1-2alkoxy, C1-2haloalkoxy, or C1-2alkyl; wherein Ra and Rb, are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, and substituted or unsubstituted cycloalkyl; or Ra and Rb together with the carbon atom to which they are attached, may form an unsubstituted or substituted 3 to 7 membered saturated carbocyclic ring; Rc, is selected from the group consisting of hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted haloalkyl, and substituted or unsubstituted alkyl; Rdand Re, are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl; or Rd and Re can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally monosubstituted or disubstituted by oxo, halo, cyano, nitro, hydroxy, carboxy, -NRmRn, C1-4 alkoxy, C1-4 alkyl, C3-8 cycloalkyl, C3- 8 cycloalkyl-C1-3 alkyl, C1-4 alkanoyl, C1-4 alkylsulphonyl, or -C(O)NRmRn, - NRmC(O)Rn, -NRmS(O)2Rnand -S(O)2NRmRn; wherein Rmand Rnare each independently selected from hydrogen, C1-4alkyl or C3-6cycloalkyl and C3-6 cycloalkyl C1-2 alkyl; Rfis substituted or unsubstituted alkyl or substituted or unsubstituted aryl; Rgand Rh, are each independently selected from hydrogen or C1-2alkyl; Ri and Rj are each independently selected from hydrogen or C1-2 alkyl; Rk and Rl are independently selected from the group consisting of hydrogen or C1-2alkyl; 'r' is an integer ranging from 0 to 3; 'p' is an integer ranging from 0 to 4; and 'q' is an integer ranging from 0 to 4.

2. The compound of formula (I) as claimed in claim 1, wherein compound is selected from the group consisting of, 3-bromo-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-bromo-6,12-dihydrobenzo[c]acridin-7(5H)-one;3-hydroxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-hydroxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-phenoxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-phenoxy-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-(4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(4-(trifluoromethoxy)phenoxy)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(3,3-difluoropyrrolidin-1-yl)benzo[c]acridin-7(12H)-one; 3-(pyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-(3,3-difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(3,3-difluoroazetidin-1-yl)-6,12-dihydrobenzo[c]acridin-7(5H)-one; 3-morpholino-6,12-dihydrobenzo[c]acridin-7(5H)-one; 2-(phenylamino)benzo[c]acridin-7(12H)-one; 3-(4-(trifluoromethoxy)phenyl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one; 6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-bromo-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 2-bromo-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-fluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one ; 2-fluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-hydroxy-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-phenoxy-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; 3-(4-(trifluoromethoxy)phenoxy)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one; 3-(3,3-difluoropyrrolidin-1-yl)-6,12-dihydro-7H-chromeno[4,3- b]quinolin-7-one; 3-(3,3-difluoroazetidin-1-yl)-6,12-dihydro-7H-chromeno[4,3-b]quinolin- 7-one; and 2-bromo-8,10-difluoro-6,12-dihydro-7H-chromeno[4,3-b]quinolin-7-one; or a pharmaceutically acceptable salt thereof.

3. The compound as claimed in claim 1, wherein the compound is an anti- tuberculosis agent.

4. A process for preparing the compound of general formula (I) as claimed in claim 1, comprising: (i) C-C / C-N / C-O coupling of a cyclic ketone of formula (2), wherein X1and X2, are as defined in claim 1, with a boronic acid, an ester or an amine in the presence of a base and a catalyst to produce a substituted cyclic ketone of formula (4), wherein X1, X2, R2, and q are as defined in claim 1; and(ii) intermolecular cyclization of the substituted cyclic ketone of formula (4), with anthranilic acid of formula (5), wherein R1,p and q are as defined in claim 1, to produce a compound of formula (I),wherein X1, X2, R1, R2, p and q are as defined above.

5. The process as claimed in claim 4, wherein the step (i) is a C-O coupling (Chan- Lam Coupling) of the cyclic ketone of formula (2a) with a boronic acid or an ester of formula (3) in the presence of a base selected from the group consisting of NEt3, DIPEA, pyridine, Cs2CO3, NaOtBu, Na2CO3, or K2CO3 and a copper catalyst such as Cu(OAc)2to produce respective compound of formula (4);a C-N coupling (Buchwald-Hartwig Coupling) of the cyclic ketone of formula (2b) with an aliphatic or aromatic amine in the presence of a base selected from the group consisting of NEt3, DIPEA, pyridine, Cs2CO3, NaOtBu, Na2CO3, or K2CO3, and a palladium catalyst selected from Pd2(dba)3, Pd(OAc)2, Pd(Ph3)4, Pd(dppf)Cl2to produce respective compound of formula (4);a C-C coupling (Suzuki Coupling) of the cyclic ketone of formula (2c) with a boronic acid of formula (3) in the presence of a base selected from the group consisting of NEt3, DIPEA, pyridine, Cs2CO3, NaOtBu, Na2CO3, K2CO3 and a palladium catalyst selected from the group consisting of Pd2(dba)3, Pd(OAc)2, Pd (Ph3)4, Pd(dppf)Cl2to produce respective substituted cyclic ketone compound of formula (4)wherein Y, X1, X2, R1, R2, p, and q are as defined in claim 4.

6. A process for preparing the compound of general formula (I) as claimed in claim 1, comprising: (i) intermolecular cyclization of a substituted cyclic ketone of formula (2), with anthranilic acid of formula (5), wherein R1, and p are as defined in claim 1, to produce a compound of formula (Ia); and(iii)substitution reaction of (Ia) to afford the compound of formula (I) wherein X1, X2, R1, R2, p and q are as defined in claim 1.

7. An intermediate in the process for preparing the compound of general formula (I), selected from the group consisting of: 6-(4-(trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen-1(2H)-one; 7-(4-(trifluoromethoxy)phenoxy)-3,4-dihydronaphthalen-1(2H)-one; 7-(4-(trifluoromethoxy)phenoxy)chroman-4-one; 7-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 6-(3,3-difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 6-(3,3-difluoropyrrolidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 7-(4-(trifluoromethoxy)phenyl)chroman-4-one; 7-(3,3-difluoroazetidin-1-yl)-3,4-dihydronaphthalen-1(2H)-one; 6-morpholino-3,4-dihydronaphthalen-1(2H)-one; 7-(3,3-difluoropyrrolidin-1-yl)chroman-4-one; 7-(3,3-difluoroazetidin-1-yl)chroman-4-one; and 7-(phenylamino)-3,4-dihydronaphthalen-1(2H)-one.

8. A pharmaceutical composition for treating mycobacterial infections comprising: the compound of general formula (I) as claimed in claim 1 to 3 and one or more pharmaceutically acceptable excipient selected from the group consisting of water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid, lower alkyl ethers of cellulose, salicylic acid, fatty acids, fatty acid amines, fatty acid monoglycerides, diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone or combinations thereof.

9. A pharmaceutical composition, comprising: the compound of general formula (I) as claimed in claim 1 to 3 with one or more antibacterial agents.

10. A pharmaceutical composition, comprising: the compound of general formula (I) as claimed in claim 1 to 3 with one or more anti-tuberculosis agents selected from the group consisting of cytochrome bc inhibitor, NDH2inhibitor, ATP synthase inhibitor, and / or menaquinone biosynthesis inhibitor, electron transport chain dependent inhibitors such as clofazimine.

Images