Tricyclic spiro lactam compound having anti-mycobacterial activity

Abstract

The present invention relates to novel tricyclic spiro lactam (TriSLas) compounds and their use as drugs, in particular for the prevention and / or treatment of mycobacterial infections or for the treatment of diseases caused by mycobacterial infections. The tuberculosis treatment agent development pipeline ideally requires further complementation by additional candidates that act on novel targets (to minimize cross-resistance) and affect drug-resistant bacilli to shorten treatment. The inventors of the present invention have identified novel tricyclic spiro lactam (TriSLas) compounds that are particularly active against M. tuberculosis.

Description

Technical Field

[0001] Field of the Invention The present invention relates to novel tricyclic spiro lactam (TriSLas) compounds and their use as drugs, in particular for the prevention and / or treatment of mycobacterial infections or for the prevention and / or treatment of diseases caused by mycobacterial infections.

[0002] Background of the Invention Due to global efforts to eradicate tuberculosis (TB) by improving access to drugs and medication adherence, the number of deaths has decreased significantly by 29% over the past 20 years. However, TB remains the leading cause of death from infectious diseases worldwide (World Health Organization. Global tuberculosis report 2021. (2021)). The current TB treatment, which requires a multi-drug combination therapy for at least six months, is notoriously long-drawn-out. This feature is mainly due to the difficulty of eliminating a phenotypically drug-resistant subpopulation of the causative bacterium, Mycobacterium tuberculosi (Mtb) (Connolly, L. E., Edelstein, P. H. & Ramakrishnan, L. Why is long-term therapy required to cure tuberculosis? PLoS Med. 4, 435-442 (2007)). Unfortunately, due to the escalating infections caused by multi-drug resistant (MDR) TB (483,000 cases of rifampicin-resistant TB were reported in 2020 (World Health Organization. Global tuberculosis report 2021. (2021))) and extensively drug-resistant (XDR) TB (12,350 cases were reported in 2019 (World Health Organization. Global tuberculosis report 2020. (2020))), even longer treatments with less efficient and tolerable second-line drugs are required. Recognizing this global health problem, the WHO has ranked TB as the world's top priority for antibiotic-resistant bacteria to develop new antibiotics (World Health Organization. Global Priority List Of Antibiotic-Resistant Bacteria To Guide Research, Discovery And Development Of New Antibiotics. (2017) doi:10.1016 / S1473-3099(09)70222-1).

[0003] Through a coordinated effort to find alternative and better antibiotics for drug-susceptible TB and drug-resistant TB, two new classes of anti-TB drugs have been approved: bedaquiline, an ATP synthase inhibitor (Palomino, J. C. & Martin, A. TMC207 becomes bedaquiline, a new anti-TB drug. Future Microbiol. 8, 1071-1080 (2013)), and the two nitroimidazole prodrugs delamanid (Ryan, N. J. & Lo, J. H. Delamanid: First global approval. Drugs 74, 1041-1045 (2014)) and pretomanid (Keam, S. J. Pretomanid: First Approval. Drugs 79, 1797-1803 (2019)). Additional anti-TB molecules are at various stages of clinical and preclinical drug development. These may further be supplied as treatment options for us in the future (Tiberi, S. et al. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect. Dis. 18, e183-e198 (2018);Tornheim, J. A. & Dooley, K. E. The global landscape of tuberculosis therapeutics. Annu. Rev. Med. 70, 105-120 (2019);J Libardo, M. D., Boshoff, H. I. & Barry, C. E. The present state of the tuberculosis drug development pipeline. Curr. Opin. Pharmacol. 42, 81-94 (2018)).Despite these increasing efforts, it is clear that the TB drug development pipeline ideally requires further complementation by additional candidates that act on novel targets (to minimize cross-resistance) and affect drug-resistant bacteria to shorten treatment.

[0004] The inventors of the present invention have identified novel tricyclic spiro-lactam (TriSLas) compounds that are particularly active against M. tuberculosis.

[0005] Description of the Invention Accordingly, the present invention provides a compound of formula (I):

Chemical formula

[0006] The present invention further relates to a pharmaceutical composition comprising a compound represented by formula (I) as defined herein.

[0007] Also, the present invention relates to a compound according to the present invention or a pharmaceutical composition according to the present invention for use as a drug, in particular for the prevention and / or treatment of mycobacterial infections or the treatment of diseases caused by mycobacterial infections. In particular, here, the mycobacterial infection is Mycobacterium tuberculosis infection.

[0008] Furthermore, the present invention relates to the compounds or pharmaceutical compositions according to the present invention and their uses as mentioned above, in combination with at least one other anti-mycobacterial agent.

[0009] Unless otherwise specified, the terms used above or below with respect to the compounds represented by formula (I) have the meanings described below.

[0010] "Halogen" refers to a fluorine, chlorine, bromine or iodine atom, particularly a fluorine or chlorine atom.

[0011] "Alkyl", unless otherwise specified, may be straight-chain or branched-chain and represents an aliphatic hydrocarbon group having 1 to 6, particularly 1 to 3 carbon atoms in chain (C1-C6) alkyl or (C1-C3) alkyl. In particular, the alkyl group has 1 to 3 carbon atoms in chain (C1-C3) alkyl. A branched chain means that one or more alkyl groups, such as methyl, ethyl or propyl, are attached to a straight-chain alkyl chain. Exemplary alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl, n-pentyl, n-hexyl, particularly isobutyl, isopropyl, propyl, methyl or ethyl. As mentioned, the alkyl may be substituted by one or more halogen atoms.

[0012] "Haloalkyl", which may be straight-chain or branched-chain, has 1 to 6, particularly 1 to 3 carbon atoms in chain (C1-C6) haloalkyl or (C1-C3) haloalkyl, and represents an aliphatic hydrocarbon group in which one or more hydrogen atoms are replaced by halogen atoms, such as fluorine, chlorine, bromine or iodine atoms, particularly one or more fluorine atoms. Exemplary haloalkyls include trifluoromethyl or difluoroethyl.

[0013] “(C3-C6) cycloalkyl” refers to a saturated monocyclic or bicyclic non-aromatic hydrocarbon ring having 3 to 6 carbon atoms, which may contain one or more unsaturations. Specific examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl. Preferably, the cycloalkyl group is cyclohexyl, cyclobutyl or cyclopentyl.

[0014] “Alkoxy” represents an alkyl group as defined above that is bonded to oxygen at one position. Examples of straight-chain or branched-chain (C1-C6) alkoxy or (C1-C3) alkoxy include methoxy (CH3O) and ethoxy (CH3CH2O).

[0015] “Haloalkoxy” represents a haloalkyl group as defined above that is bonded to oxygen. Examples of straight-chain or branched-chain (C1-C6) haloalkoxy or (C1-C3) haloalkoxy include trifluoromethoxy (CF3O).

[0016] “Alkenyl” refers to an aliphatic hydrocarbon group containing a carbon-carbon double bond, which may be straight-chain or branched-chain, unless otherwise specified, and has 2 to 6 carbon atoms in the chain (C2-C6) alkenyl. Preferred alkenyl groups have 2 to 3 carbon atoms in the chain (C2-C3) alkenyl. Exemplary alkenyl groups include ethenyl, n-propenyl, i-propenyl, n-butenyl, i-butenyl, and in particular, ethenyl or propenyl.

[0017] "Aryl" refers to an aromatic monocyclic or polycyclic hydrocarbon ring system having 6 to 10 carbon atoms, preferably 6 carbon atoms. Exemplary aryl groups include phenyl, naphthyl, biphenyl, and in particular, phenyl. Said aryl or phenyl may be substituted by one or more halogen atoms, such as fluorine, bromine, iodine or chlorine, especially chlorine or fluorine; -OH; one or more (C1-C6) alkyl or (C1-C3) alkyl, such as methyl (said alkyl may optionally be substituted by 1 to 3 fluorine atoms, such as trifluoromethyl); one or more (C1-C3) alkoxy, such as methoxy (said alkoxy may optionally be substituted by one or more fluorine atoms, such as trifluoromethoxy); one -(C6-C 10 ) aryl, especially phenyl; one -O-(C6-C 10 ) aryl, especially -O-phenyl; and may be substituted by a heterocyclic ring defined below.

[0018] "Linear or branched (C1-C6) alkyl-(C6-C 10 ) aryl" means that the aryl is linked to the alkyl group by a carbon of the alkyl group. The alkyl group and the aryl group are as defined above. In particular, -(C1-C3) alkyl-(C6-C 10 ) aryl, especially (C1-C3) alkyl-phenyl is contemplated, and in particular, benzyl, ethylphenyl, difluoroethylphenyl or propylphenyl is contemplated. Phenyl may be substituted, as mentioned above, especially by a halogen atom, such as fluorine or chlorine, especially chlorine; methyl, trifluoromethyl, methoxy or trifluoromethoxy.

[0019] "Heterocyclic ring" or "heterocycloalkyl" refers to a saturated or partially unsaturated, non-aromatic, stable monocyclic, bicyclic or polycyclic ring having 3 to 10 members. The heteroatom may be O, S or N, particularly N. In particular, each ring contains 1 to 3 halogen atoms. Appropriate heterocyclic rings are also disclosed in the Handbook of Chemistry and Physics, 76th Edition, CRC Press, Inc., 1995 - 1996, pages 225 to 226. The said disclosure is incorporated herein by reference. Examples of heterocycloalkyl include, but are not limited to, piperazine, tetrahydropyran, tetrahydrofuran, diazepane, piperidine, pyrrolidine, morpholine, azetidine, diazabicyclooctanyl, diazabicycloheptanyl, azabicyclohexanyl, particularly piperazine, tetrahydropyran, tetrahydrofuran. The heterocyclic ring is substituted by one or more (C1 - C6) halogenoalkyl, particularly trifluoromethoxy, on a (C6 - C 10 ) aryl, particularly phenyl or by one or more (C1 - C6) halogenoalkyl, particularly trifluoromethoxy, on an -O-(C6 - C 10 ) aryl, particularly phenyl, optionally substituted.

[0020] "-O-(C6 - C 10 ) aryl" means that the aryl group is linked to the oxygen atom by the carbon of the aryl group.

[0021] "Linear or branched (C1 - C6) alkyl - heterocyclic ring" means that the heterocyclic ring is linked to the alkyl group by the carbon of the alkyl group. The alkyl and the heterocyclic ring are as defined above.

[0022] "Heteroaryl" refers to a 5- to 10-membered aromatic monocyclic, bicyclic or polycyclic ring in which at least one member of the ring is a heteroatom. The heteroatom may be O, S or N, particularly N. In particular, each ring contains 1 to 3 heteroatoms. Examples include pyrrolyl, pyridyl, oxadiazole, thiazole, oxazole, triazole, pyrazolyl, pyrimidinyl, pyrazinyl, indolyl, quinolyl, imidazolyl, particularly including pyridyl, quinolyl, imidazolyl and indolyl. The said heteroaryl may be substituted by one or more (C1-C6) alkyl or (C1-C3) alkyl, for example, methyl (the alkyl may be optionally substituted by 1 to 3 fluorine atoms, for example, trifluoromethyl); it may be substituted by one or more (C3-C6) cycloalkyl, for example, cyclopentyl.

[0023] "-S(O)2-(C6-C 10 )aryl" means that the aryl group is linked to the sulfur atom by the carbon of the aryl group. In particular, -S(O)2-(C6-C 10 )aryl is S(O)2-phenyl. Phenyl, as mentioned above, may be particularly substituted by (C1-C6) halogenoalkyl, for example, trifluoromethyl.

[0024] "-S(O)2-(C1-C6)alkyl-(C6-C 10 )aryl" means that the alkyl group is linked to the sulfur atom by the carbon of the alkyl group. In particular, -S(O)2-(C1-C6)alkyl-(C6-C 10 )aryl is S(O)2-(C1-C3)alkyl-phenyl. Phenyl, as mentioned above, may be particularly substituted by (C1-C6) halogenoalkyl, for example, trifluoromethyl.

[0025] "-C(O)-R'-(C6-C 10"Aryl" means that the aryl group is linked to R' by the carbon of the aryl group, and also means that the said R' is linked to the carbon of C(=O). Here, R' is selected from linear or branched (C1-C6) alkyl (the said alkyl may be optionally substituted by one or more halogen atoms); linear or branched O-(C1-C6) alkyl (the said alkyl may be optionally substituted by one or more halogen atoms).

[0026] Unless otherwise specified, the term "substituted" generally refers to substitution by one or more substituents. The said substituents may be the same or different and are those specified in this specification.

[0027] As mentioned above, since W may not be two Os, at least one of the two Ws is CR4R4'.

[0028] The compounds represented by formula (I) described in this specification may be provided in the form of the free base or in the form of an addition salt with an acid, and these also form part of the present invention.

[0029] These salts are preferably prepared with pharmaceutically acceptable acids, but salts with other acids useful for the purification or isolation of the compounds represented by formula (I) described in this specification, for example, also form part of the present invention.

[0030] As used herein, the expression "pharmaceutically acceptable" refers to compounds, materials, excipients, compositions or dosage forms that are within the scope of sound medical judgment, are free of excessive toxicity, irritation, allergic reaction or other problematic complications, are commensurate with a reasonable benefit / risk ratio, and are suitable for contact with human and animal tissues.

[0031] As used herein, "pharmaceutically acceptable salts" refers to derivatives of the disclosed compounds in which the parent compound is modified by formation of its acid or base salts. Pharmaceutically acceptable salts include, for example, conventional non-toxic salts or quaternary ammonium salts of the parent compound formed from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, etc. (including their mono-, di- or tri-salts) and organic acids such as formic acid, acetic acid, propionic acid, succinic acid, tartaric acid, citric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, glucoronic acid, glutamic acid, benzoic acid, salicylic acid, toluenesulfonic acid, oxalic acid, fumaric acid, maleic acid, lactic acid, etc. Further additional salts include ammonium salts such as tromethamine, meglumine, epolamine, etc., and metal salts such as sodium, potassium, calcium, zinc or magnesium.

[0032] The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing basic or acidic moieties by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds in water or an organic solvent or a mixture of the two with a stoichiometric amount of an appropriate base or acid. Generally, non-aqueous solvents such as ether, dioxane, ethyl acetate, ethanol, isopropanol or acetonitrile are preferred. A list of suitable salts can be found in Remington’s Pharmaceutical Sciences, 20 th ed., Mack Publishing Company, Easton, PA, 2000, which disclosure is incorporated herein by reference.

[0033] Compound As mentioned, the compounds according to the present invention have the formula (I):

Chemical formula

[0034] In one embodiment, Z is NR1, where R1 is linear or branched -(C1-C3)alkyl-phenyl (wherein the alkyl is optionally substituted by one or more halogen atoms, especially fluorine, and the phenyl is a halogen atom, -OH, linear or branched -(C1-C3)alkyl, especially methyl, linear or branched -(C1-C3)halogenoalkyl, especially trifluoromethyl, linear or branched -(C1-C3)alkoxy, especially methoxy, linear or branched -(C1-C3)halogenoalkoxy, especially trifluoromethoxy, phenyl, -O-phenyl; a heterocyclic ring containing 3 to 10 members and having at least one heteroatom selected from N (wherein the heterocyclic ring is optionally substituted by one or more of phenyl optionally substituted by one or more linear or branched -(C1-C3)halogenoalkoxy, especially trifluoromethoxy and -O-phenyl optionally substituted by one or more linear or branched -(C1-C3)halogenoalkoxy, especially trifluoromethoxy)); phenyl optionally substituted by one or more linear or branched -(C1-C3)halogenoalkyl or -(C1-C3)halogenoalkoxy, especially trifluoromethyl or trifluoromethoxy; linear or branched -(C1-C3)alkyl-(C6-C 10heteroaryl (said heteroaryl has at least one heteroatom selected from N and is optionally substituted by one or more of linear or branched -(C1-C3)alkyl, in particular methyl, linear or branched -(C1-C3)halogenoalkyl, in particular trifluoromethyl, -(C3-C6)cycloalkyl); linear or branched -(C1-C3)alkyl-(C3-C6)cycloalkyl; -(C3-C6)cycloalkyl; linear or branched -(C1-C3)alkyl-heterocyclic ring (said heterocyclic ring contains 3 to 10 members and has at least one heteroatom selected from O or N); -S(O)2-phenyl (said phenyl is optionally substituted by one or more linear or branched (C1-C3)halogenoalkyl, in particular trifluoromethyl); -S(O)2-(C1-C3)alkyl-phenyl (said phenyl is optionally substituted by one or more linear or branched -(C1-C3)halogenoalkyl, in particular trifluoromethyl); -C(O)-R'-phenyl (said phenyl is optionally substituted by one or more linear or branched -(C1-C3)halogenoalkyl, in particular trifluoromethoxy, where R' is selected from linear or branched -(C1-C3)alkyl (said alkyl is optionally substituted by one or more halogen atoms), linear or branched -O-(C1-C3)alkyl).

[0035] Alternatively, Z is CHNRaRb, where Ra and Rb are the same or different and are selected from H, phenyl and linear or branched -(C1-C3)alkylphenyl, said phenyl being optionally substituted by one or more linear or branched -(C1-C3)halogenoalkyl, in particular one trifluoromethyl.

[0036] In particular, R2 and R2' are -H and / or R3 and R3’ are the same or different and are selected from -H; linear or branched -(C1-C6) alkyl; linear or branched -(C2-C3) alkenyl; linear or branched -(C1-C3) haloalkyl, especially trifluoromethyl or -(C3-C6) cycloalkyl or R2 or R2’ is linked to R3 or R3’ to form cycloalkyl or aryl, and the cycloalkyl and aryl contain 3 to 6 members and / or R4 and R4’ are the same or different and are selected from -H; a halogen atom; linear or branched -(C1-C3) alkyl and linear or branched -(C2-C3) alkenyl and / or R5 and R5’ are H or they combine to form =O and / or R6 and R6’ are H or they combine to form =O.

[0037] In particular, the compound is as follows: - (3S,7aR,11aR)-9-[(4-fluorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethoxy)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[(4-chlorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[(3,4-dichlorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(p-tolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(4-methoxyphenyl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[(4-hydroxyphenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[[2,4-bis(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(4-phenylphenyl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(3-phenoxyphenyl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[4-[4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl]phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[4-[4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl]phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[4-(piperidin-1-yl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(pyridin-2-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(pyridin-3-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(pyridin-4-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[6-(trifluoromethyl)pyridin-3-yl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[5-(trifluoromethyl)pyridin-2-yl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(2-quinolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(8-quinolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(6-quinolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[(2-Cyclopropyl-4-quinolyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[2-(Trifluoromethyl)-4-quinolyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[(1-Methylimidazol-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[(3-Methyl-1H-indol-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[(1-Methylindol-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-(Cyclohexylmethyl)-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-Cyclobutyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-Cyclohexyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(tetrahydropyran-4-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(tetrahydropyran-2-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(tetrahydrofuran-2-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-phenyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[4-(trifluoromethyl)phenyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(2-phenylethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[2-[4-(trifluoromethyl)phenyl]ethyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(1-phenylethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[2,2-Difluoro-2-[4-(trifluoromethyl)phenyl]ethyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-(2-phenylacetyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[2-[4-(trifluoromethyl)phenyl]acetyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propanoyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[4-[4-(trifluoromethyl)phenyl]butanoyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[2,2-difluoro-2-[4-(trifluoromethyl)phenyl]acetyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - Benzyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - [4-(Trifluoromethyl)phenyl]methyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - 2-[4-(Trifluoromethyl)phenyl]ethyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - 3-[4-(Trifluoromethyl)phenyl]propyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - (3S,7aR,11aR)-3-isopropyl-9-[4-(trifluoromethyl)phenyl]sulfonyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methylsulfonyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]ethylsulfonyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-3-Isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propylsulfonyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-Benzyl-3-[(1S)-1-methylpropyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aS,11aS)-9-Benzyl-3-[(1S)-1-methylpropyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-Benzyl-3-[(1R)-1-methylpropyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-Benzyl-3-tert-butyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (7aR,11aR)-9-Benzylspiro[6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-3,1'-cyclohexane]-5-one; - (7aS,11aS)-9-Benzylspiro[6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-3,1'-cyclohexane]-5-one; - (7aR,11aR)-9-Benzylspiro[6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-3,1'-cyclohexane]-5-one; - (7aS,11aS)-9-Benzylspiro[6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-3,1'-cyclohexane]-5-one; - (3S,7aR,11aR)-9-Benzyl-3-cyclopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-[[4-(Trifluoromethyl)phenyl]methyl]-3-vinyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-9-Benzyl-3-ethyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aS,11aS)-9-Benzyl-3-ethyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3R,7aR,11aR)-3-(Trifluoromethyl)-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (1R,6R,11S,16S)-4-Benzyl-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1S,6S,11R,16R)-4-Benzyl-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1R,6R,11S,16S)-4-[[4-(Trifluoromethoxy)phenyl]methyl]-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1S,6S,11R,16R)-4-[[4-(Trifluoromethoxy)phenyl]methyl]-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (8aR,12aR)-10-[[4-(Trifluoromethyl)phenyl]methyl]spiro[2,4,7,8,8a,9,11,12-octahydro-[1,3]oxazino[2,3-j][1,6]naphthyridine-3,1'-cyclobutane]-6-one; - (8aS,12aS)-10-[[4-(Trifluoromethyl)phenyl]methyl]spiro[2,4,7,8,8a,9,11,12-octahydro-[1,3]oxazino[2,3-j][1,6]naphthyridine-3,1'-cyclobutane]-6-one; - (3R,8aR,12aR)-3-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (3S,8aS,12aS)-3-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (3R,8aR,12aR)-3-ethyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (3S,8aS,12aS)-3-ethyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (4R,8aR,12aR)-4-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (1S,6R,11S,16S)-4-benzyl-4,10,17-triazatetracyclo[8.7.0.01,6.011,16]heptadecane-9-one; - (1R,4S,8R)-10-Benzyl-4-isopropyl-2-oxa-5,10-diazatricyclo[6.4.0.01,5]dodecan-6-one; - (1R,4S,8R)-4-Isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,10-diazatricyclo[6.4.0.01,5]dodecan-6-one; - (3S,7aR,11aR)-9-Benzyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-thione; - (1R,4S,9R)-4-Isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2,8-dioxa-5,11-diazatricyclo[7.4.0.01,5]tridecan-6-one; - (1R,4S,8R)-4-Isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,10-diazatricyclo[6.4.0.01,5]dodecan-6-one; - (1R,4R,9R)-4-Isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecan-7-one; - (1S,4S,9S)-4-Isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecan-7-one; - (1R,4R,9R)-4-Ethyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecan-7-one; - (1R,4R,9R)-4-Ethyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecan-7-one; - (3S,7aR,11aR)-3-Isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,6,7,7a,8,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5,10-dione; - (3S,7aS,11aR)-3-Isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,6,7,7a,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5,8-dione; - (3S,7aR,9S,11aR)-9-[Bis[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one; - (3S,7aR,9R,11aR)-9-[Bis[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one; - (3S,7aR,9S,11aR)-3-Isopropyl-9-[[4-(trifluoromethyl)phenyl]methylamino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one; - (3S,7aR,9R,11aR)-3-Isopropyl-9-[[4-(trifluoromethyl)phenyl]methylamino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one; - (3S,7aR,9S,11aR)-3-Isopropyl-9-[4-(trifluoromethyl)anilino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one; - (3S,7aR,9S,11aR)-3-Isopropyl-9-[4-(trifluoromethyl)anilino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one; - (4S,9R)-4-Isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,11-diazatricyclo[7.5.0.01,5]tetradecan-6-one; - (1R,4S,9S)-4-Isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,10-diazatricyclo[7.3.0.01,5]dodecan-6-one; - (3S,6R,7aR,11aR)-3-Isopropyl-6-methyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,6R,7aR,11aR)-6-Ethyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,6R,7aR,11aR)-6-Allyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,6R,7aR,11aR)-6-Isobutyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,6S,7aR,11aR)-3-Isopropyl-6-methyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,6S,7aR,11aR)-6-Ethyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,6S,7aR,11aR)-6-Allyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-6-Fluoro-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one; - (3S,7aR,11aR)-6,6-Difluoro-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridin-5-one; Or is selected from its pharmaceutically acceptable salts.

[0038] In one embodiment, the compound represented by the formula (I) is X is O and / or Y is O and / or m has a value of 1 and / or n has a value of 1, W is CR4R4' and / or p and p' have a value of 1 and / or Z is NR1, where R1 is benzyl (the benzyl is substituted by one or more halogen atoms, linear-(C1-C6)halogenoalkyl, linear-(C1-C6)halogenoalkoxy), linear or branched-CH3-(C6-C 10 )heteroaryl (the heteroaryl has at least one heteroatom selected from O, N or S, in particular, the heteroaryl is piperidine, optionally substituted by one or more linear-(C1-C6)halogenoalkyl, (C1-C3)alkyl or-(C3-C6)cycloalkyl), linear or branched-(C1-C6)alkyl-(C6-C 10) selected from aryl (said aryl being, in particular, phenyl, said phenyl being optionally substituted by a linear - (C1 - C3) halogenoalkyl) or Z is CHNRaRb, where Ra and Rb are identical and are linear or branched - (C1 - C3) alkylphenyl, said phenyl being optionally substituted by one or more linear or branched - (C1 - C3) halogenoalkyl, in particular by one trifluoromethyl and / or R2 and R2’ are identical and are H and / or R3 and R3’ are different and are selected from H and branched - (C1 - C6) alkyl and / or R4 and R4’ are identical and are H and / or R5 and R5’ are H and / or R6 and R6’ are H, characterized in that.

[0039] In particular, said compound is the following: - (3S,7aR,11aR)-3 - isopropyl - 9 - [[4 - (trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11 octahydrooxazolo[2,3 - j][1,6]naphthyridin - 5 - one - (3S,7aR,11aR)-3 - isopropyl - 9 - [[4 - (trifluoromethoxy)phenyl]methyl]-2,3,6,7,7a,8,10,11 - octahydrooxazolo[2,3 - j][1,6]naphthyridin - 5 - one - (3S,7aR,11aR)-9 - [(4 - chlorophenyl)methyl]-3 - isopropyl - 2,3,6,7,7a,8,10,11 - octahydrooxazolo[2,3 - j][1,6]naphthyridin - 5 - one - (3S,7aR,11aR)-9 - [(3,4 - dichlorophenyl)methyl]-3 - isopropyl - 2,3,6,7,7a,8,10,11 - octahydrooxazolo[2,3 - j][1,6]naphthyridin - 5 - one - (3S,7aR,11aR)-9-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,11aR)-9-[[2,4-bis(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,11aR)-9-[(2-cyclopropyl-4-quinolyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,11aR)-3-isopropyl-9-[(1-methylindol-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]ethyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,11aR)-3-isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one - (3S,7aR,9S,11aR)-9-[bis[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one or a pharmaceutically acceptable salt thereof

[0040] In particular, in the context of the present invention, the following compounds described and named as follows in Aurora Building Blocks 9’’, 4 April 2022 (2022-04-04), Aurora Fine Chemicals Ltd, XP055972899 are excluded. - (1S,8R)-9-[(3-Hydroxyphenyl)methyl]-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; - (1S,4R,8R)-9-[(4-Methoxy-2,5-dimethylphenyl)methyl]-4-(propan-2-yl)-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; - (1S,8R)-9-([4-(2,2,2-Trifluoroethyl)phenyl]methyl)-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; - (1S,4R,8R)-9-[(5-Chloro-2-fluorophenyl)methyl]-4-(propan-2-yl)-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; - (1S,4R,8R)-9-[(3-Methylphenyl)methyl]-4-(propan-2-yl)-2-(oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; - (1S,4R,8R)-4-(propan-2-yl)-9-[(2,4,6-trimethylphenyl)methyl]-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; - (1S,4R,8R)-4-(propan-2-yl)-9-[(2,3,4-trimethoxyphenyl)methyl]-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one; and - (1S,8R)-9-[(3-Chloro-2-fluorophenyl)methyl]-2-oxa-5,9-diazatricyclo[6.3.0.0(1,5)]undecan-6-one.

[0041] As already mentioned, the present invention also relates to a combination of (a) a compound of formula (I) as defined herein and (b) at least one other anti-mycobacterial agent.

[0042] The anti-mycobacterial agent is as defined below.

[0043] The compounds provided herein can optionally be formulated into pharmaceutical compositions by mixing with one or more pharmaceutically acceptable excipients.

[0044] Accordingly, the present invention also relates to a pharmaceutical composition comprising a compound of formula (I) as defined herein and a pharmaceutically acceptable excipient.

[0045] In one embodiment, the pharmaceutical composition further comprises at least one other anti-mycobacterial agent.

[0046] Anti-mycobacterial agents are well known in the art. Anti-mycobacterial agents or anti-tuberculosis agents include rifampin, rifabutin, isoniazid, ethambutol, streptomycin, amikacin, kanamycin, moxifloxacin, pyrazinamide, bedaquiline, linezolid, stetolid, nitroimidazole. Anti-mycobacterial agents are most commonly prescribed today in combination with multiple drugs.

[0047] In one embodiment, the pharmaceutical composition comprises two, three, four, five, six or seven additional anti-tuberculosis agents. For example, in the treatment of multi-drug resistant tuberculosis, combinations of four or more drugs are generally administered to patients. For example, in the treatment of drug-susceptible tuberculosis, combinations of three or four drugs are generally administered to patients.

[0048] Such compositions can be prepared for oral administration, particularly in the form of tablets or capsules, particularly orally dispersible tablets, or for parenteral administration, particularly in the form of solutions, suspensions or emulsions.

[0049] For example, a pharmaceutical composition can be prepared by any of the methods well known in the pharmaceutical field as described in Remington: The Science and Practice of Pharmacy, 20th ed.; Gennaro, A. R., Ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2000. Pharmaceutically compatible binders and / or adjuvant materials can be included as part of the composition. Oral compositions will generally include an inert diluent carrier or an edible carrier. They can be administered in unit dosage form. Here, the term "unit dosage" means a single dosage that can be administered to a patient, is easily handled and packaged, and remains as a physically and chemically stable unit dosage containing either the active compound itself or a pharmaceutically acceptable composition.

[0050] Tablets, pills, powders, capsules, troches, etc. may contain one or more of any of the following ingredients or compounds having similar properties: binders such as microcrystalline cellulose or tragacanth gum; diluents such as starch or lactose; disintegrants such as starch and cellulose derivatives; lubricants such as magnesium stearate; glidants such as colloidal silicon dioxide; sweeteners such as sucrose or saccharin or flavoring agents such as peppermint or methyl salicylate. Capsules may be in the form of hard capsules or soft capsules, which are generally made from gelatin blends and starch capsules optionally blended with a plasticizer. In addition, dosage unit forms may contain various other materials that modify the physical form of the dosage unit, such as coatings of sugar, shellac, or enteric solvents. Other oral dosage forms such as syrups or elixirs may contain sweeteners, preservatives, dyes, colorants, and flavorings. In addition, the active compound can be incorporated into immediate-release, sustained-release, or extended-release preparations and formulations. Here, such sustained-release formulations are preferably bimodal.

[0051] The liquid preparations for administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. The liquid compositions may also include binders, buffers, preservatives, chelating agents, sweeteners, flavoring agents, coloring agents, and the like. Non-aqueous solvents include alcohols, propylene glycol, polyethylene glycol, acrylate copolymers, vegetable oils such as olive oil, and organic esters such as ethyl oleate. Aqueous carriers include mixtures of alcohol and water, hydrogels, buffered solvents, and physiological saline. In particular, biocompatible and biodegradable lactide polymers, lactide / glycolide copolymers, or polyoxyethylene-polyoxypropylene copolymers may be useful excipients for controlling the release of the active compound. Intravenous media may include body fluids and nutritional supplements, electrolyte supplements such as those based on Ringer's glucose, and the like.

[0052] Compound for use As already mentioned, the present invention also relates to compounds of formula (I) as defined herein for use as a drug.

[0053] In particular, the compound can be used to prevent and / or treat mycobacterial infections.

[0054] Mycobacterial infections are well known in the art. Mycobacterial infections are caused by infection with mycobacteria.

[0055] Mycobacteria can be members of one of the following groups of Mycobacterium: Mycobacterium tuberculosis complex (MTC), Mycobacterium avium complex (MAC), Mycobacterium gordonae lineage, Mycobacterium kansasii lineage, Mycobacterium chelonae lineage, Mycobacterium fortuitum lineage, Mycobacterium parafortuitum lineage, or Mycobacterium vaccae lineage, Mycobacterium marinum, and Mycobacterium abscessus. Mycobacteria can also be Mycobacterium ulcerans or Mycobacterium leprae.

[0056] In particular, mycobacteria are members of the Mycobacterium tuberculosis complex (MTC). Members of the Mycobacterium tuberculosis complex (MTC) include Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium marinum, Mycobacterium abscessus, and Mycobacterium pinnipedii.

[0057] These mycobacteria are the causative agents of tuberculosis in humans and animals. Mycobacterium tuberculosis is the main cause of human tuberculosis.

[0058] In particular, the infection is Mycobacterium tuberculosis infection. That is, mycobacterial infection is caused by infection with Mycobacterium tuberculosis.

[0059] In one embodiment, Mycobacterium tuberculosis is multidrug resistant.

[0060] In another aspect, the present invention relates to a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in the treatment of a disease caused by mycobacterial infection.

[0061] In particular, the mycobacteria are selected from those described hereinabove.

[0062] For example, mycobacterial infections include the following: Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium pinnipedii, Mycobacterium avium, Mycobacterium avium paratuberculosis, Mycobacterium avium silaticum, Mycobacterium avium hominissuis, Mycobacterium columbiense, Mycobacterium indicus pranii, Mycobacterium asiaticum, Mycobacterium gordonae, Mycobacterium gastri, Mycobacterium kansasii, Mycobacterium abscessus, Mycobacterium bolletii, Mycobacterium chlonae, Mycobacterium boenickei, Mycobacterium brisbanense, Mycobacterium cosmeticum, Mycobacterium fortuitum, Mycobacterium fortuitum acetamidolyticum (subspecies), Mycobacterium houstonense, Mycobacterium mageritense, Mycobacterium neworleansense, Mycobacterium peregrinum, Mycobacterium porcinum, Mycobacterium senegalense, Mycobacterium septicum, Mycobacterium austroafricanum, Mycobacterium diernhoferi, Mycobacterium frederiksbergense, Mycobacterium hodleri, MycobacteriumIt may be caused by infection with mycobacteria selected from neoaurum, Mycobacterium parafortuitum, Mycobacterium ulcerans, Mycobacterium marinum, Mycobacterium abscessus, and Mycobacterium leprae.

[0063] Diseases caused by mycobacterial infection include tuberculosis (e.g., caused by Mycobacterium tuberculosis), leprosy (e.g., caused by Mycobacterium leprae), Johne's disease (e.g., caused by Mycobacterium avium paratuberculosis (subspecies)), Buruli ulcer or Bairnsdale ulcer (e.g., caused by Mycobacterium ulcerans), Crohn's disease (e.g., caused by Mycobacterium avium paratuberculosis (subspecies)), lung diseases or lung infections, pneumonia, bursae, synovium, tendon sheaths, localized abscesses, arthritis, skin and soft tissue infections, Lady Windermere syndrome (e.g., caused by Mycobacterium avium complex (MAC)), MAC lung disease, disseminated Mycobacterium avium complex (DMAC), disseminated Mycobacterium avium intracellulare complex (DMAIC), hot tub lung (e.g., caused by Mycobacterium avium complex), MAC mastitis, MAC suppurative myositis, or granulomatosis, including but not limited to these.

[0064] In particular, in the context of the present invention, the disease is tuberculosis.

[0065] In one embodiment, therefore, the present invention also relates to a method for treating mycobacterial infection in a subject in need thereof, said treatment comprising administering to said subject a therapeutically effective amount of a compound of formula (I) described in this section or a pharmaceutically acceptable salt thereof.

[0066] As described herein, mycobacterial infection is caused by infection with mycobacteria. Mycobacteria are as described hereinabove.

[0067] In one embodiment, the present invention relates to a method for treating Mycobacterium tuberculosis infection.

[0068] In another embodiment, the present invention relates to a method for treating a disease caused by mycobacterial infection in a subject in need thereof, said treatment comprising administering to said subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

[0069] In particular, in the context of the present invention, said disease is tuberculosis.

[0070] In one embodiment, said compound is used in combination with at least one other anti-mycobacterial agent.

[0071] Anti-mycobacterial agents are well known in the art. Anti-mycobacterial agents or anti-tuberculosis agents include rifampin, rifabutin, isoniazid, ethambutol, streptomycin, amikacin, kanamycin, moxifloxacin, pyrazinamide, bedaquiline, linezolid, stetolid, nitroimidazole.

[0072] Anti-mycobacterial agents are most commonly prescribed today in combination with multiple drugs.

[0073] In one embodiment, said combination comprises 2, 3, 4, 5, 6 or 7 additional anti-tuberculosis agents. For example, in the treatment of multi-drug resistant tuberculosis, a combination of 4 or more drugs is generally administered to a patient. For example, in the treatment of drug-susceptible tuberculosis, a combination of 3 or 4 drugs is generally administered to a patient.

[0074] As used in the context of the present invention, the terms "treating," "treatment," "being treated," or "treatment" refer to therapeutic treatment aimed at removing or alleviating a symptom. Beneficial or desired clinical results include, but are not limited to, symptom removal, symptom alleviation, reduction in the degree of a condition, stabilization of a condition (i.e., not worsening), delay or blunting of the progression of a condition.

[0075] As used in the context of the present invention, the terms "preventing," "prevention," "prevention of," or "prevented" refer to preventing the onset, recurrence, or spread of a disease or disorder or infection or one or more symptoms thereof. In certain embodiments, the term particularly refers to treating or administering a compound provided herein to a patient at risk of a disease or disorder or infection provided herein prior to the onset of symptoms. The term encompasses preventing or alleviating symptoms of a particular disease or disorder or infection. In particular, in certain embodiments, a subject having a family history of a disease or disorder or infection is a candidate for a prevention regimen. Additionally, a subject having a history of recurrent symptoms may also be a candidate for prevention. In this regard, the term "prevention" can be used interchangeably with the term "preventive treatment."

[0076] In particular, a subject in need of treatment for a mycobacterial infection or a disease caused by a mycobacterial infection is a subject suffering from such a disease or infection.

[0077] In the context of the present invention, identification of a subject in need of treatment of the diseases and conditions described herein is done as mentioned above and is well within the ability and knowledge of one of ordinary skill in the art. A skilled clinician can readily identify a subject in need of such treatment using the techniques mentioned above.

[0078] A therapeutically effective amount can be readily determined by a treating diagnostician, who is a person skilled in the art, by observing the results obtained under similar circumstances using conventional techniques. When determining a therapeutically effective amount, many factors are considered by the treating diagnostician. Such factors include, but are not limited to, the species of the subject; the size, age and general health of the subject; the particular disease involved; the degree or severity of the disease; the response of the individual subject; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dosage regimen selected; the use of concomitant medications and other relevant circumstances.

[0079] As used herein, "effective amount" refers to an amount effective to reduce, eliminate, treat or control the symptoms of the diseases and conditions described herein. The term "control" is intended to refer to all processes that can slow, interrupt, prevent or stop the progression of the diseases and conditions described herein, but does not necessarily indicate complete elimination of the symptoms of all diseases and conditions, and is intended to include prophylactic treatment and chronic use.

[0080] The terms "patient" or "subject" refer to warm-blooded animals, such as mammals, particularly human males or females, having or having the potential to have one or more of the diseases and conditions described herein, unless otherwise indicated.

[0081] In particular, the compounds of the combination according to the invention are administered separately, sequentially or simultaneously.

[0082] The amount of the compound according to the invention required to achieve the desired biological effect will vary depending on many factors, including the dosage of the drug administered, the chemical properties (e.g., hydrophobicity) of the compound utilized, the potency of the compound, the type of resistance, the state of resistance in the patient and the route of administration.

[0083] The compounds provided herein can optionally be formulated into pharmaceutical compositions by mixing with one or more pharmaceutically acceptable excipients.

[0084] Such compositions can be prepared for oral administration, particularly in the form of tablets or capsules, especially orally dispersible tablets, or for parenteral administration, particularly in the form of solutions, suspensions or emulsions.

[0085] The compositions can be prepared by any of the methods well known in the pharmaceutical art, for example, as described in Remington: The Science and Practice of Pharmacy, 20th ed.; Gennaro, A. R., Ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2000. Pharmaceutically compatible binders and / or adjuvant materials can be included as part of the compositions. Oral compositions will generally include an inert diluent carrier or an edible carrier. They can be administered in unit dosage form. Here, the term "unit dosage" means a single dosage that can be administered to a patient, is easily handled and packaged, and remains as a physically and chemically stable unit dosage containing either the active compound itself or a pharmaceutically acceptable composition.

[0086] Tablets, pills, powders, capsules, troches, etc. may contain one or more of the following ingredients or compounds having similar properties: binders such as microcrystalline cellulose or tragacanth gum; diluents such as starch or lactose; disintegrants such as starch and cellulose derivatives; lubricants such as magnesium stearate; glidants such as colloidal silicon dioxide; sweeteners such as sucrose or saccharin or flavoring agents such as peppermint or methyl salicylate. Capsules may be in the form of hard capsules or soft capsules, which are generally made from gelatin blends and starch capsules optionally blended with plasticizers. In addition, dosage unit forms may contain various other materials that modify the physical form of the dosage unit, such as coatings of sugar, shellac or enteric solvents. Other oral dosage forms such as syrups or elixirs may contain sweeteners, preservatives, dyes, coloring agents and flavorings. In addition, the active compounds can be incorporated into immediate-release, sustained-release or extended-release preparations and formulations. Here, such sustained-release formulations are preferably bimodal.

[0087] Liquid preparations for administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. The liquid compositions may also include binders, buffers, preservatives, chelating agents, sweeteners, flavoring agents and coloring agents, etc. Non-aqueous solvents include alcohols, propylene glycol, polyethylene glycol, acrylate copolymers, vegetable oils such as olive oil and organic esters such as ethyl oleate. Aqueous carriers include mixtures of alcohol and water, hydrogels, buffered solvents and physiological saline. In particular, biocompatible and biodegradable lactide polymers, lactide / glycolide copolymers or polyoxyethylene-polyoxypropylene copolymers may be useful excipients for controlling the release of active compounds. Intravenous media may include body fluids and nutrient solutions, electrolyte solutions such as those based on Ringer's dextrose, etc.

[0088] Examples of administration modes include parenteral administration, for example, subcutaneous administration, intramuscular administration, intravenous administration, intradermal administration, and oral administration.

[0089] Manufacturing method Furthermore, the present invention relates to a method for manufacturing a compound represented by formula (I) described herein.

[0090] The compounds of the present invention can be prepared by many methods well-known to those skilled in the art. The compounds can be synthesized, for example, by applying or adapting the methods described below or modifications thereof understood by those skilled in the art. Appropriate modifications and substitutions will be readily apparent and well-known to those skilled in the art or will be readily available from the scientific literature.

[0091] It will be understood that the compounds of the present invention may contain one or more asymmetric substituted carbon atoms and may be isolated as optically active forms or racemates. Therefore, all diastereomeric forms of the structure are intended unless a specific stereochemistry is specifically indicated. Methods for preparing and isolating such optically active forms are well-known in the art.

[0092] For example, a mixture of stereoisomers can be separated by standard techniques including (but not limited to) resolution of racemates, normal phase, reverse phase, and chiral chromatography, preferential salt formation, recrystallization, etc. or by either synthesis from chiral starting materials or intentional synthesis of the target chiral centers.

[0093] The compounds of the present invention can be prepared by various synthetic routes. The reagents and starting materials are commercially available or can be easily synthesized by techniques well-known to those skilled in the art. Unless otherwise specified, all substituents are as defined above.

[0094] In the reactions described below, reactive functional groups, such as hydroxyl, amino, imino, thio, or carboxy groups, may need to be protected to avoid their unwanted participation in the reaction if they are desired in the final product. Conventional protecting groups can be used according to standard practice. See, for example, T.W. Greene and P.G.M. Wuts in Protective Groups in Organic Chemistry, 4th ed. (2007), John Wiley & Sons Inc., 1999; J.F.W. McOmie in Protective Groups in Organic Chemistry, Plenum Press, 1973.

[0095] The compounds thus prepared can be recovered from the reaction mixture by conventional means. For example, the compound can be recovered by distilling off the solvent from the reaction mixture or, if necessary, after distilling off the solvent from the reaction mixture, pouring the residue into water and subsequently extracting with a water-immiscible organic solvent and then distilling off the solvent from the extract. Further, if necessary, the product can be further purified by various well-known techniques, such as recrystallization, reprecipitation, or various chromatography techniques, particularly column chromatography or preparative thin-layer chromatography.

[0096] The reaction can be carried out by one skilled in the art by applying or adapting the methods exemplified in the following examples.

[0097] In particular, the compound represented by formula (I) can be prepared according to the protocol mentioned in the following experimental part.

[0098] Furthermore, the method of the present invention may include an additional step of isolating the compound represented by formula (I). This can be done by one skilled in the art by any of the known conventional means, such as the recovery methods described above.

[0099] Generally, the starting products can mainly be obtained commercially from Aldrich or Acros or other typical chemical suppliers or by applying or adapting any known method or the methods described in the examples.

[0100] In the context of the present invention, "compound for use in prevention and / or treatment" should be understood to be equivalent to "use of a compound for prevention and / or treatment" and "use of a compound for manufacturing a medicament for prevention and / or treatment".

[0101] The present invention will be further illustrated by the following examples.

[0102] Examples Part A - Synthesis of the compounds according to the present invention The following compounds according to the present invention are to be prepared.

[0103] [Table 1] TIFF2025518349000005.tif221165 TIFF2025518349000006.tif217165 TIFF2025518349000007.tif248165 TIFF2025518349000008.tif229165 TIFF2025518349000009.tif244165 TIFF2025518349000010.tif224165 TIFF2025518349000011.tif215165 TIFF2025518349000012.tif232165 TIFF2025518349000013.tif217165 TIFF2025518349000014.tif220165 TIFF2025518349000015.tif210165 TIFF2025518349000016.tif234165 TIFF2025518349000017.tif225165 TIFF2025518349000018.tif218165 TIFF2025518349000019.tif220165 TIFF2025518349000020.tif237165 TIFF2025518349000021.tif210165 TIFF2025518349000022.tif225165 TIFF2025518349000023.tif224165 TIFF2025518349000024.tif225165

[0104] 3-(1-Benzyl-4-oxo-3-piperidyl)propanoic acid (Intermediate 1)

Chemical formula

[0105] Synthesis of methyl 3-(1-benzyl-4-oxo-3-piperidyl)propanoate (Intermediate 2)

Chemical formula

[0106] The solvent was removed under vacuum, the mixture was dissolved in 0.1N HCl (100 mL), and stirred at room temperature for 1 hour. Saturated aqueous Na2CO3 solution was added until pH 10 was reached. The solution was extracted with ethyl acetate. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure to give the crude product, which was purified by silica gel chromatography (cyclohexane / ethyl acetate: 70 / 30 to 0 / 100) to give Intermediate 2 (6.73 g, 33%) as a colorless oil. [ES+ MS] m / z 276 (MH + ).

[0107] Synthesis of methyl 2-(1-benzyl-4-oxo-3-piperidyl)acetate hydrochloride (Intermediate 3) [Chemical formula] Ethyl 1-benzyl-4-oxo-piperidine-3-carboxylate; hydrochloride (0.500 g, 1.68 mmol, 1 equivalent) and Cs2CO3 (1.45 g, 4.45 mmol, 2.7 equivalents) were dissolved in dry acetone (3 mL). The reaction mixture was stirred and heated at 50 °C. Methyl 2-bromoacetate (185 μL, 2.01 mmol, 1.2 equivalents) was dissolved in dry acetone (2 mL), then added dropwise to the hot reaction mixture, and then stirred at reflux for 20 hours. The reaction mixture was filtered and the solvent was evaporated. A solution of 37% HCl (13 mL) in water (13 mL) was added.

[0108] The reaction mixture was heated at reflux for 48 hours. The solvent was removed under vacuum. Next, the pH was adjusted to 7 using 3M NaOH and saturated NaHCO3. The solvent was removed under vacuum. The mixture was dissolved in ethanol and filtered. Next, ethanol was removed under vacuum to give a dark brown oil. The resulting brown oil was dissolved in MeOH (2 mL), then SOCl2 (26.6 μL, 0.365 mmol) was added dropwise at room temperature. Next, the mixture was stirred at 55 °C for 1 hour. The solvent was removed under vacuum, the mixture was dissolved in 0.1N HCl (5 mL), and stirred at room temperature for 3 hours. The solvent was removed under reduced pressure to give Intermediate 3. [ES+MS] m / z 262 (MH+ )。

[0109] General Protocol 1: Synthesis of N-Boc Ketoester by Stork Enamine Alkylation:

Chem.

[0110]

Table 2

[0111] General Protocol 2: Synthesis of Lactam by Meyers Lactamization

Chem.

[0112]

Table 3

[0113]

Table 4

[0114] Synthesis of 4-(bromomethyl)-2-cyclopropyl-quinoline (Intermediate 20) for use in General Protocol 3

Chem.

[0115] General protocol 3: Synthesis of N-alkylated lactams from N-Boc lactams [Chemical formula]

[0116] Step 1: An appropriate N-Boc lactam was dissolved in 1,4-dioxane (0.05 M), and then an HCl solution in 1,4-dioxane (4 N, 10 equiv) was added. The mixture was stirred at room temperature for 5 - 20 h. After complete conversion (determined by TLC or LC / MS), the solvent was removed under vacuum, and the resulting crude product was carried on to the next step without any further purification.

[0117] Step 2: The crude product from Step 1 was dissolved in MeCN (0.1 N). The solution was cooled to 0 °C, and then DIEA or K2CO3 (1.5 - 3 equiv) and an appropriate alkyl bromide (1.5 equiv) were added. The mixture was warmed to room temperature and stirred for 1 - 20 h. Next, the solvent was removed under reduced pressure. The resulting residue was dissolved in H2O and extracted with dichloromethane. The organic layer was dried over MgSO4, filtered, and concentrated under vacuum to give a crude product, which was purified to give the corresponding desired lactam.

[0118] [Table 5] TIFF2025518349000042.tif195165 TIFF2025518349000043.tif204165 TIFF2025518349000044.tif191165 TIFF2025518349000045.tif200165

[0119] General Protocol 4: Deprotection of N-Boc Lactam [Chemical Structure] The appropriate N-Boc lactam was dissolved in 1,4-dioxane (0.05 M), and then an HCl solution (4 N, 10 equivalents) in 1,4-dioxane was added. The mixture was stirred at room temperature for 5 - 48 hours until complete conversion of the starting material (determined by TLC or LC / MS), the solvent was removed under vacuum, and the resulting crude product was carried on to the next step reaction without further purification.

[0120] [Table 6]

[0121] (3S,7aR,11aR)-3-Isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j][1,6]naphthyridin-5-one; Synthesis of Formic Acid (Intermediate 24) [Chemical Structure] Example 62 (655 mg, 1.99 mmol, 1 equivalent) was dissolved in methanol (20 mL), and then Pd / C 10% (127 mg, 1.20 mmol, 0.12 mmol, 10 mol%) and ammonium formate (629 mg, 9.97 mmol, 5 equivalents) were added. The mixture was refluxed for 30 minutes. The solution was filtered through celite, and then the filtrate was concentrated under reduced pressure to give Intermediate 24 as a white powder in quantitative yield. 11H NMR (300 MHz, CD2Cl2): δ 8.44 (brs, 1H), 4.13 - 3.99 (m, 2H), 3.77 (dd, J = 8.3, 5.6 Hz, 1H), 3.35 - 3.11 (m, 3H), 2.99 (td, J = 13.1, 3.2 Hz, 1H), 2.68 - 2.55 (m, 1H), 2.48 - 2.20 (m, 2H), 2.10 (td, J = 14.4, 4.6 Hz, 1H), 2.01 - 1.70 (m, 4H), 0.92 (d, J = 6.4 Hz, 3H), 0.90 (d, J = 6.4 Hz, 3H) ppm. HRMS (ESI, m / z): [M+H] + C 13 H 22 Calculated for N2O2, 239.1760; found 239.1759.

[0122] General Protocol 5: Alkylation of Deprotected Lactam

Chemical Structure

[0123]

Table 7

[0124] Synthesis of Aldehydes Used in Reductive Amination Reactions (General Protocol 8)

[0125] General Protocol 6: Oxidation of Alcohols to Aldehydes

Chem.

[0126] General Protocol 7: Synthesis of Aldehydes by Nucleophilic Aromatic Substitution

Chem.

[0127]

Table 8

[0128] General Protocol 8: Synthesis of Lactams by Reductive Amination

Chem.

[0129]

Table 9

[0130] Synthesis of Intermediates 31 - 34

Chemical Structure

Chemical Structure

Chemical formula

[0131]

Table 10

[0132] Synthesis Example 47

Chemical formula

[0133] General Protocol 9: Carbamate Synthesis

Chemical formula

[0134]

Table 11

[0135] General Protocol 10: Amide Synthesis

Chem.

[0136] Synthesis of 2,2-difluoro-2-[4-(trifluoromethyl)phenyl]acetic acid (Intermediate 35)

Chem.

[0137] Synthesis Example 42

Chem.

[0138] The solvent was removed under vacuum; then the mixture was dissolved in DCM and washed with saturated Na2CO3. The organic phase was dried over magnesium sulfate and DCM was removed under vacuum. The product was purified by flash chromatography on silica gel (cyclohexane / ethyl acetate: 100 / 0 to 0 / 100) to give the desired product (15.4 mg) (Yield = 16%).

[0139]

Table 12

[0140] General Protocol 11: Sulfonamide

Chem.

[0141]

Table 13

[0142] General Protocol 12: Buchwald Synthesis

Chem.

[0143] [Table 14]

[0144] (3S,7aR,11aR)-9-[2,2-difluoro-2-[4-(trifluoromethyl)phenyl]ethyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridin-5-one synthesis (Example 41): [Chemical formula]

[0145] Step 1: (3S,7aR,11aR)-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j][1,6]naphthyridin-5-one; hydrochloride (275 mg, 1 mmol, 1 equivalent) and 2-bromo-1-[4-(trifluoromethyl)phenyl]ethanone (267 mg, 1 mmol, 1 equivalent) dissolved in DMF (4 mL; molecular sieve) were added to a tube. Next, DIEA (0.5 mL) was added. The mixture was stirred at 100 °C for 30 minutes under microwave irradiation.

[0146] DMF was removed under vacuum. Ethyl acetate was added and the mixture was washed once with 1N aqueous HCl, once with saturated aqueous NaHCO3 and once with brine. The organic layer was dried over MgSO4, filtered and evaporated under reduced pressure. The crude product was introduced into the next step without any further treatment.

[0147] Step 2: The crude product from Step 1 (50 mg, 0.12 mmol, 1 equiv) was dissolved in dry dichloromethane (500 μL). DAST (50 μL, 0.38 mmol, 3.2 equiv) was added dropwise at 0 °C. The mixture was stirred at room temperature for 6 h. The solution changed from pale yellow to dark orange.

[0148] The reaction was quenched with saturated aqueous NaHCO3 at 0 °C; the aqueous layer was extracted three times with dichloromethane, the organic fractions were pooled and washed once with brine, dried over MgSO4, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / ethyl acetate: 100 / 0 to 0 / 100). The fractions containing the desired product were pooled and evaporated under reduced pressure. This crude product was purified by flash chromatography (dichloromethane / acetone: 100 / 0 to 80 / 20) to give the fraction of the desired product with a purity of 60%. Next, this fraction was purified by reverse-phase flash chromatography (water / MeCN: 90 / 10 to 0 / 100) to give the desired product Example 41. Yield = 3%. 11H NMR (300 MHz, MeOD): δ 7.80 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 4.05 - 3.93 (m, 2H), 3.87 - 3.76 (m, 1H), 3.04 (ddd, J = 3.0 Hz, J = 12.2 Hz, J = 15.6 Hz, 1H), 2.80 (dd, J = 3.0 Hz, J = 11.4 Hz, 1H), 2.71 - 2.57 (m, 2H), 2.56 - 2.43 (m, 2H), 2.39 - 2.23 (m, 1H), 2.07 (dd, J = 3.7 Hz, J = 8.7 Hz, 1H), 2.01 - 1.92 (m, 1H), 1.89 - 1.71 (m, 2H), 1.53 (br d, J = 15.1 Hz, 1H), 1.49 - 1.41 (m, 1H), 1.31 (br s, 1H), 0.92 (d, J = 6.9 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H) ppm. 13 13C NMR (75 MHz, MeOD, d4): δ 172.6, 140.4, 131.5 (q, J = 33 Hz), 127.7 (t, J = 6.2 Hz), 126.2 (q, J = 3.8 Hz), 124.0 (q, J = 274 Hz), 121.6 (t, J = 234 Hz), 93.2, 67.1, 63.7 (t, J = 30 Hz), 62.7, 57.1, 52.5, 41.7, 33.6, 33.0, 31.3, 30.7, 22.6, 20.2, 18.9 ppm.

[0149] General Protocol 13: Functionalization of the Lactam Ring

Chem.

[0150]

Table 15

[0151]

Table 16

[0152] General Protocol 14: Synthesis of Examples 78, 81 and 82

Chemical Structure

[0153] Step 1: An appropriate intermediate was dissolved in 1,4-dioxane (0.05 M), and then an HCl solution in 1,4-dioxane (4 N, 10 equivalents) was added. The mixture was stirred at room temperature for 5 - 20 hours. When the conversion of the starting material was complete (determined by TLC or LC / MS), the solvent was removed under vacuum, and the resulting crude product was carried on to the next step without further purification.

[0154] Step 2: The crude product of Step 1 was dissolved in MeCN (0.1 N). The solution was cooled to 0 °C, and then DIEA (1.5 - 3 equivalents) and 1-(bromomethyl)-4-(trifluoromethyl)benzene (1.5 equivalents) were added. The mixture was warmed to room temperature and stirred for 1 - 20 hours. The solvent was removed under reduced pressure. The resulting residue was dissolved in H2O and extracted with dichloromethane. The organic layer was dried over MgSO4, filtered, and concentrated under vacuum to give a crude product, which was purified by flash chromatography on a silica gel column (cyclohexane / ethyl acetate: 100 / 0 to 0 / 100) to give the corresponding trifluoromethylbenzyl-substituted lactam.

[0155]

Table 17

[0156] Synthesis of Examples 68 and 69

[0157] Step 1: Oxidation of Intermediate 9

Chemical formula

[0158] Tert-butyl (3S,7aR,11aR)-3-isopropyl-5,10-dioxo-3,6,7,7a,8,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-9-carboxylate (Intermediate 39) [ES+ MS] m / z 353 (MH + )。

[0159] Tert-butyl (3S,7aS,11aR)-3-isopropyl-5,8-dioxo-3,6,7,7a,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-9-carboxylate (Intermediate 40) [ES+ MS] m / z 353 (MH + )。

[0160] Steps 2 and 3: Conversion of Intermediate 39 and 40 to Examples 68 and 69

Chemical Structure

[0161] Step 2: A mixture of Intermediate 39 and 40 (35 mg, 0.099 mmol) was dissolved in 1,4-dioxane (2 mL), and then an HCl solution in 1,4-dioxane (4N, 0.25 mL, 1 mmol, 10 equivalents) was added. The mixture was stirred at room temperature for 20 hours. When the conversion of the starting material was judged to be complete by TLC or LC / MS, the solvent was removed under vacuum, and the resulting crude product was carried on to the next step reaction without further purification.

[0162] Procedure 3: The crude product of Procedure 1 was dissolved in THF (3 mL), and then NaH (60% suspension in oil, 96 mg, 2.49 mmol, 6 equiv) and 1-(bromomethyl)-4-(trifluoromethyl)benzene (36 mg, 0.151 mmol, 1.5 equiv) were added. The mixture was stirred at room temperature for 72 h. The solvent was removed under reduced pressure. The obtained residue was dissolved in H2O and extracted with dichloromethane. The organic layer was dried over MgSO4, filtered, and concentrated under vacuum to give a crude product, which was purified by preparative HPLC using a gradient of H2O + 0.1% HCOOH / MeCN + 0.1% HCOOH (100 / 0 to 0 / 100) to give Example 68 and Example 69.

[0163] (3S,7aR,11aR)-3-Isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,6,7,7a,8,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5,10-dione (Example 68)

Chem.

[0164] (3S,7aS,11aR)-3-Isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,6,7,7a,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5,8-dione (Example 69) [Chemical formula] Yield: 24%; colorless oil; 11H NMR (300 MHz, CDCl3): δ 7.57 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 4.68 (d, J = 15.0 Hz, 1H), 4.61 (d, J = 15.0 Hz, 1H), 4.19 - 4.04 (m, 2H), 3.70 (dd, J = 8.2, 5.9 Hz, 1H), 3.46 - 3.33 (m, 1H), 3.13 - 3.03 (m, 1H), 2.69 - 2.37 (m, 4H), 2.14 - 2.01 (m, 2H), 1.96 - 1.78 (m, 2H), 0.96 (d, J = 2.2 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H) ppm. 13 13C NMR (75 MHz, CDCl3): δ170.0, 169.7, 140.7, 129.9 (q, J = 32.2 Hz), 128.0, 125.8 (q, J = 3.8 Hz), 124.2 (q, J = 271.7 Hz), 92.2, 67.2, 61.2, 49.7, 47.3, 43.2, 33.6, 31.0, 28.7, 23.9, 20.0, 19.1 ppm. [ES+ MS] m / z 411 (MH + ).

[0165] Synthesis of 4,4 - dimethoxy - 1 - [[4 - (trifluoromethyl)phenyl]methyl]piperidin - 3 - ol (Intermediate 41):

Chemical Structure

[0166] Synthesis of methyl 2-[[4,4-dimethoxy-1-[[4-(trifluoromethyl)phenyl]methyl]-3-piperidyl]oxy]acetate (Intermediate 42)

Chem.

[0167] (1R,4S,9R)-4-Isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2,8-dioxa-5,11-diazatricyclo[7.4.0.01,5]tridecan-6-one Synthesis (Example 66)

Chemical Structure

[0168] Step 1: Intermediate 42 (300 mg, 0.767 mmol, 1 equiv) was dissolved in aqueous HCl (0.1 N, 50 mL, 5 mmol, 6 equiv). The solution was refluxed at 110 °C for 20 h. H2O was removed under vacuum, and the resulting brown oil was used in the next step reaction without further purification.

[0169] Procedure 2: The crude product for the first procedure was dissolved in DMF (2 mL), and then DIEA (525 μL, 3.07 mmol, 4 eq) and COMU (493 mg, 1.15 mmol, 1.5 eq) were added. The mixture was stirred at room temperature for 15 minutes, and then a solution of L-valinol (119 mg, 1.15 mmol, 1.5 eq) in DMF (2 mL) was added. The resulting solution was refluxed at 130 °C for 72 hours. The solvent was removed under vacuum. The obtained residue was dissolved in H2O and extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum to give a crude product. The crude product was purified by flash chromatography on a silica gel column (cyclohexane / ethyl acetate: 100 / 0 to 0 / 100) to give Example 66 (10 mg, 3%) as a yellow oil; 1 H NMR (300 MHz, CDCl3): δ 7.57 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 4.46 (d, J = 16.9 Hz, 1H), 4.11 (d, J = 16.9 Hz, 1H), 4.10 - 4.02 (m, 2H), 3.86 - 3.77 (m, 1H), 3.66 (d, J = 13.6 Hz, 1H), 3.57 (d, J = 13.6 Hz, 1H), 3.23 (dd, J = 4.3, 2.2 Hz, 1H), 3.11 - 3.03 (m, 1H), 2.79 - 2.74 (m, 1H), 2.46 (dd, J = 12.7, 2.2 Hz, 2H), 2.27 - 2.20 (m, 2H), 1.98 - 1.89 (m, 1H), 1.84 - 1.78 (m, 1H), 0.97 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.8 Hz, 3H) ppm. 1313C NMR (75 MHz, CDCl3): δ 167.5, 141.8, 129.6 (q, J = 31.2 Hz), 129.4, 125.4 (q, J = 3.6 Hz), 124.4 (q, J = 270.0 Hz), 89.1, 75.5, 68.0, 67.5, 62.0, 61.4, 54.0, 49.5, 32.9, 32.0, 20.0, 18.9 ppm. [ES+ MS] m / z 399 (MH + ).

[0170] (3S)-9-Benzyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-thione synthesis (Example 65)

Chemical Structure

[0171] General Protocol 15: Synthesis of Examples 35 and 36 by Chan-Lam Coupling

Chemical Structure

[0172]

Table 18

[0173] Part B: Activity of the compounds according to the invention Determination of MIC The minimum inhibitory concentration (MIC) of the compounds against Mtb was determined in 96-well plates using the resazurin microtiter assay (REMA). Briefly, mycobacteria were grown in complete Middlebrook 7H9 medium to mid-log phase and diluted to OD 600 0.001. Then, this bacterial suspension was added to the wells of a 96-well plate (200 μL to the wells of the first column and 100 μL to all other wells). Then, the test compound was added to the first well and serially diluted within the plate using a multichannel pipette. The plate was incubated for 8 - 10 doubling times (37 °C, 6 days), after which resazurin (10 μL of 0.025% (w / v) resazurin) was added and incubated (37 °C, overnight), and the viability of the bacteria was determined by measuring resorufin production [Ex 530 nm, Em 590 nm] using a fluorescence microplate reader. The MIC of the compounds against Mtb was considered as the lowest compound concentration at which the amount of resazurin metabolism was less than 2% of the background fluorescence.

[0174] For the MIC analysis of mycobacteria other than Mtb, the experiments were conducted in the same manner as for Mtb, but the incubation time was adjusted according to the generation time of the bacteria (5 days for M. avium and M. marinum, and 2 days for M. abscessus and M. smegmatis). In addition, M. marinum was cultured at 30 °C instead of 37 °C, and its viability was determined by visual inspection of bacterial growth in microtiter plates. For the other bacteria, the MIC was determined as the lowest compound concentration at which the resazurin metabolism was less than 10% of the background fluorescence.

[0175] Biochemical evaluation of MBP-Ndh inhibition To define the activity of compounds against purified MBP-Ndh, a biochemical assay was set up to monitor MBP-Ndh-dependent NADH oxidation in the presence of the electron acceptor menadione, as described previously (Murugesan, D. et al. 2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium tuberculosis: Structure-Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization. ACS Infect. Dis. 4, (2018)). Briefly, the IC of the compound 50To evaluate, the compound was transferred to a clear-bottom black 384-well plate using Echo liquid handling acoustic technology (Labcyte) and made up to 500 nL with DMSO. Using a Viafill liquid dispenser (INTEGRA Biosciences), 45 μL of the mixture was added to these wells containing Mtb recombinant MBP-tagged Ndh-2 enzyme (70 nM recombinant MBP-Ndh produced in E. coli; 0.66 nM recombinant MBP-Ndh produced in M. smegmatis or 30 nM recombinant MBP-NdhA produced in M. smegmatis, concentrations adjusted to have comparable NADH oxidation rates) and NADH (500 μM) in 50 mM HEPES buffer (pH 7.1 with K2HPO4). After pre-incubation (25 °C, 15 min), enzyme activity was initiated by adding menadione (5 μL, final concentration 100 μM, dispensed into the wells using ENVISION, Perkin Elmer), and the kinetics of NADH oxidation were monitored at 340 nm (measured every 60 s, ENVISION plate reader, Perkin Elmer). The rate of NADH oxidation was calculated as the slope of the linear decrease in the signal at 340 nm using Microsoft Excel, and the enzyme inhibition parameters were determined using Graphpad Prism v.9. IC 50 was reported as the mean and standard deviation of at least three independent experiments.

[0176] The results are presented in Tables 2 and 3 below.

[0177]

Table 19

[0178] The MIC activity range: +++ indicates less than 1 μM, ++ indicates 1 - 10 μM, and + indicates more than 10 μM. IC 50 Activity range: *** indicates less than 100 nM, ** indicates 0.1 - 1 μM, * indicates more than 1 μM.

[0179]

Table 20

[0180] The MIC activity range: +++ indicates less than 1 μM, ++ indicates 1 - 10 μM, and + indicates more than 10 μM. IC 50 Activity range:*** indicates less than 100 nM, ** indicates 0.1 - 1 μM, * indicates more than 1 μM.

Claims

1. Equation (I): 【Transformation 38】 [In the formula, W is O or CR ４ R ４ 'and, X is either O or S, Y is either O or N, Z is NR １ or CHNRaRb, p has a value of 0 or 1. p' has a value of 1 or 2. m and n are the same or different, and have a value of 1 or 2, where at least one W is CR ４ R ４ 'and, R １ teeth, Linear or branched -(C １ -C ６ )alkyl-(C ６ -C １０ )aryl(wherein the alkyl may be optionally substituted by one or more halogen atoms, and the aryl is a halogen atom, -OH, linear or branched -(C １ -C ６ )alkyl, linear or branched -(C １ -C ６ )halogenoalkyl, linear or branched -(C １ -C ６ )alkoxy, linear or branched -(C １ -C ６ )halogenoalkoxy, -(C ６ -C １０ )aryl, -O-(C ６ -C １０ )aryl; a heterocyclic ring containing 3 to 10 members and having at least one heteroatom selected from O, N or S (wherein the heterocyclic ring may be optionally substituted by one or more linear or branched -(C １ -C ６ )halogenoalkoxy)-(C ６ -C １０ )aryl and optionally substituted by one or more linear or branched -(C １ -C ６ )halogenoalkoxy)-(O-(C ６ -C １０ )aryl); optionally substituted by one or more of the above; one or more linear or branched -(C １ -C ６ )halogenoalkyl or -(C １ -C ６ )halogenoalkoxy)-(C ６ -C １０ )aryl; linear or branched -(C １ -C ６ )alkyl-(C[[ID=​​​​~C ６ ) Alkyl, linear or branched chain - (C １ ~C ６ ) Halogenoalkyl, -(C ３ ~C ６ (Optionally substituted with one or more cycloalkyl groups); linear or branched chain - (C １ ~C ６ ) Alkyl-(C ３ ~C ６ ) Cycloalkyl; - (C ３ ~C ６ ) Cycloalkyl; linear or branched chain - (C １ ~C ６ ) alkyl-heterocycle (the heterocycle comprises 3 to 10 members and has at least one heteroatom selected from O, N, or S); -S(O) ２ - (C ６ ~C １０ ) Aryl (The aryl is one or more linear or branched chains - (C １ ~C ６ (Optionally substituted with a halogenoalkyl); -S(O) ２ - (C １ ~C ６ ) Alkyl-(C ６ ~C １０ ) Aryl (The aryl is one or more linear or branched chains - (C １ ~C ６ (Optionally substituted with a halogenoalkyl); -C(O)-R'-(C ６ ~C １０ ) Aryl (The aryl is one or more linear or branched chains (C １ ~C ６ ) optionally substituted with a halogenoalkyl group, where R' is linear or branched-(C １ ~C ６ ) alkyl (the alkyl is optionally substituted with one or more halogen atoms), linear or branched -O-(C １ ~C ６ ) Selected from alkyl (the alkyl is optionally substituted with one or more halogen atoms) Selected from, Ra and Rb are the same or different, H, -(C ６ ~C １０ ) Aryl and linear or branched chains - (C １ ~C ６ ) Alkyl-(C ６ ~C １０ ) Selected from aryls, the aryl is one or more linear or branched chains - (C １ ~C ６ ) optionally substituted with a halogenoalkyl, R ２ and R ２ ' is -H, R ３ and R ３ ’ are the same or different and are selected from -H; straight-chain or branched-chain -(C １ ~C ６ )alkyl; straight-chain or branched-chain -(C ２ ~C ６ )alkenyl; straight-chain or branched-chain -(C １ ~C ６ )halogenoalkyl or -(C ３ ~C ６ )cycloalkyl or R ２ or R ２ ’ is R ３ or R ３ ’ is linked to form a cycloalkyl or aryl, and the cycloalkyl and aryl contain 3 to 6 members R ４ and R ４ ' is the same or different -H; halogen atom; straight chain or branched chain - (C １ ~C ６ ) Alkyl and linear or branched chain-(C ２ ~C ６ ) Selected from Alkenil, R ５ and R ５ ' is the same or different, H, linear or branched - (C １ ~C ３ ) Selected from alkyl groups or these groups together to form =O, R ６ and R ６ ' is the same or different, H, linear or branched - (C １ ~C ３ ) Selected from alkyl groups or these groups together to form =O] The compound indicated by or its pharmaceutically acceptable salt or optical isomer.

2. Z is NR １ And here, R １ However, linear or branched chains - (C １ ~C ３ ) alkyl-phenyl (the alkyl is optionally substituted with one or more halogen atoms, particularly fluorine, and the phenyl is a halogen atom, -OH, linear or branched-chain -(C) １ ~C ３ ) Alkyl, especially methyl, linear or branched-chain - (C １ ~C ３ ) Halogenoalkyl, especially trifluoromethyl, linear or branched-(C) １ ~C ３ ) Alkoxy, especially methoxy, linear or branched-chain (C) １ ~C ３ ) Halogenoalkoxys, particularly trifluoromethoxy, phenyl, -O-phenyl; a heterocycle comprising 3 to 10 members and having at least one heteroatom selected from N (the heterocycle having one or more linear or branched chains - (C １ ~C ３ ) Halogenoalkoxys, in particular phenyl and one or more linear or branched-(C) compounds optionally substituted with trifluoromethoxy. １ ~C ３ ) Halogenoalkoxys, in particular, one or more of the following (optionally substituted with trifluoromethoxy-O-phenyl); one or more linear or branched-(C) １ ~C ３ ) Halogenoalkyl or -(C １ ~C ３ ) Halogenoalkoxys, in particular phenyl optionally substituted with trifluoromethyl or trifluoromethoxy; linear or branched chain - (C １ ~C ３ ) Alkyl-(C ６ ~C １０ )heteroaryl (the heteroaryl has at least one heteroatom selected from N, and is linear or branched - (C １ ~C ３ ) Alkyl, especially methyl, linear or branched-chain - (C １ ~C ３ ) Halogenoalkyl, especially trifluoromethyl, -(C ３ ~C ６ (Optionally substituted with one or more cycloalkyl groups); linear or branched chain - (C １ ~C ３ ) Alkyl-(C ３ ~C ６ ) Cycloalkyl; - (C ３ ~C ６ ) Cycloalkyl; linear or branched chain - (C １ ~C ３ ) alkyl-heterocycle (the heterocycle comprises 3 to 10 members and has at least one heteroatom selected from O or N); -S(O) ２ - Phenyl (the phenyl is one or more linear or branched chains (C) １ ~C ３ ) Halogenoalkyl, in particular, sometimes substituted with trifluoromethyl; -S(O) ２ - (C １ ~C ３ ) Alkyl-phenyl (The phenyl is one or more linear or branched-(C) １ ~C ３ ) a halogenoalkyl, in particular optionally substituted with trifluoromethyl); -C(O)-R'-phenyl (where the phenyl is one or more linear or branched-(C) １ ~C ３ ) optionally substituted with a halogenoalkyl, particularly trifluoromethoxy, where R' is linear or branched-(C) １ ~C ３ ) alkyl (the alkyl is optionally substituted with one or more halogen atoms), linear or branched -O-(C １ ~C ３ (Selected from alkyl) A compound according to claim 1, selected from the following.

3. Z is CHNRaRb, where Ra and Rb are the same or different, and H, phenyl, and linear or branched-chain-(C) １ ~C ３ ) Selected from alkylphenyls, wherein the phenyl is one or more linear or branched-(C) １ ~C ３ The compound according to claim 1, which is optionally substituted with a halogenoalkyl, particularly one trifluoromethyl group.

4. R ２ and R ２ ' is -H and / or R ３ and R ３ ', either identical or different, -H; linear or branched chain - (C １ ~C ６ ) Alkyl; linear or branched chain - (C ２ ~C ３ ) Alkenyl; straight or branched chain - (C １ ~C ３ ) Halogenoalkyl, especially trifluoromethyl or -(C ３ ~C ６ ) Selected from cycloalkyl or R ２ Or R ２ 'But, R ３ Or R ３ ' is linked to form a cycloalkyl or aryl group, and the cycloalkyl and aryl group comprises 3 to 6 members and / or R ４ and R ４ ', identical or different, -H; halogen atom; straight chain or branched chain - (C １ ~C ３ ) Alkyl and linear or branched chain-(C ２ ~C ３ ) Selected from Alkenil and / or R ５ and R ５ ' is either H or these together form = O and / or R ６ and R ６ The compound according to claim 1, wherein ' is H or these together form =O.

5. The aforementioned compound is as follows: - (3S,7aR,11aR)-9-[(4-fluorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethoxy)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[(4-chlorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[(3,4-dichlorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(p-tolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(4-methoxyphenyl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[(4-hydroxyphenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydroxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[[2,4-bis(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(4-phenylphenyl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(3-phenoxyphenyl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidyl]phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-[4-[4-(trifluoromethoxy)phenyl]-1-piperidyl]phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(1-piperidyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(2-pyridylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(3-pyridylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(4-pyridylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(2-quinolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(8-quinolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(6-quinolylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[(2-cyclopropyl-4-quinolyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(1-methylimidazole-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(3-methyl-1H-indole-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[(1-methylindole-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-(cyclohexylmethyl)-3-isopropyl-2,3,6,7,7a,8,10,11-octahydroxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-cyclobutyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-cyclohexyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(tetrahydropyran-4-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(tetrahydropyran-2-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(tetrahydrofuran-2-ylmethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-phenyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[4-(trifluoromethyl)phenyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(2-phenylethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]ethyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(1-phenylethyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[2,2-difluoro-2-[4-(trifluoromethyl)phenyl]ethyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-(2-phenylacetyl)-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]acetyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propanoyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[4-[4-(trifluoromethyl)phenyl]butanoyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[2,2-difluoro-2-[4-(trifluoromethyl)phenyl]acetyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - Benzyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - [4-(trifluoromethyl)phenyl]methyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - 2-[4-(trifluoromethyl)phenyl]ethyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - 3-[4-(trifluoromethyl)phenyl]propyl (3S,7aR,11aR)-3-isopropyl-5-oxo-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-9-carboxylate; - (3S,7aR,11aR)-3-isopropyl-9-[4-(trifluoromethyl)phenyl]sulfonyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methylsulfonyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]ethylsulfonyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-3-isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propylsulfonyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-benzyl-3-[(1S)-1-methylpropyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aS,11aS)-9-benzyl-3-[(1S)-1-methylpropyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-benzyl-3-[(1R)-1-methylpropyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-benzyl-3-tert-butyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (7aR,11aR)-9-benzyl-3,3-dimethyl-6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5-one; - (7aS,11aS)-9-benzyl-3,3-dimethyl-6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5-one; - (7aR,11aR)-9-benzylspiro[6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-3,1'-cyclohexane]-5-one; - (7aS,11aS)-9-benzylspiro[6,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-3,1'-cyclohexane]-5-one; - (3S,7aR,11aR)-9-benzyl-3-cyclopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-[[4-(trifluoromethyl)phenyl]methyl]-3-vinyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-9-benzyl-3-ethyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aS,11aS)-9-benzyl-3-ethyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3R,7aR,11aR)-3-(trifluoromethyl)-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (1R,6R,11S,16S)-4-benzyl-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1S,6S,11R,16R)-4-benzyl-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1R,6R,11S,16S)-4-[[4-(trifluoromethoxy)phenyl]methyl]-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1S,6S,11R,16R)-4-[[4-(trifluoromethoxy)phenyl]methyl]-17-oxa-4,10-diazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (8aR,12aR)-10-[[4-(trifluoromethyl)phenyl]methyl]spiro[2,4,7,8,8a,9,11,12-octahydro-[1,3]oxazino[2,3-j][1,6]naphthyridine-3,1'-cyclobutan]-6-one; - (8aS,12aS)-10-[[4-(trifluoromethyl)phenyl]methyl]spiro[2,4,7,8,8a,9,11,12-octahydro-[1,3]oxazino[2,3-j][1,6]naphthyridine-3,1'-cyclobutan]-6-one; - (3R,8aR,12aR)-3-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (3S,8aS,12aS)-3-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (3R,8aR,12aR)-3-ethyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (3S,8aS,12aS)-3-ethyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (4R,8aR,12aR)-4-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-3,4,7,8,8a,9,11,12-octahydro-2H-[1,3]oxazino[2,3-j][1,6]naphthyridine-6-one; - (1S,6R,11S,16S)-4-benzyl-4,10,17-triazatetracyclo[8.7.0.01,6.011,16]heptadecan-9-one; - (1R,4S,8R)-10-benzyl-4-isopropyl-2-oxa-5,10-diazatricyclo[6.4.0.01,5]dodecane-6-one; - (1R,4S,8R)-4-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,10-diazatricyclo[6.4.0.01,5]dodecane-6-one; - (3S,7aR,11aR)-9-benzyl-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-thion; - (1R,4S,9R)-4-isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2,8-dioxa-5,11-diazatricyclo[7.4.0.01,5]tridecane-6-one; - (1R,4S,8R)-4-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,10-diazatricyclo[6.4.0.01,5]dodecane-6-one; - (1R,4R,9R)-4-isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecane-7-one; - (1S,4S,9S)-4-isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecane-7-one; - (1R,4R,9R)-4-ethyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecane-7-one; - (1R,4R,9R)-4-ethyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-6,11-diazatricyclo[7.4.0.01,6]tridecane-7-one; - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,6,7,7a,8,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5,10-dione; - (3S,7aS,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,6,7,7a,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5,8-dione; - (3S,7aR,9S,11aR)-9-[bis[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one; - (3S,7aR,9R,11aR)-9-[bis[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one; - (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methylamino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one; - (3S,7aR,9R,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methylamino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one; - (3S,7aR,9S,11aR)-3-isopropyl-9-[4-(trifluoromethyl)anilino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one; - (3S,7aR,9S,11aR)-3-isopropyl-9-[4-(trifluoromethyl)anilino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one; - (4S,9R)-4-isopropyl-11-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,11-diazatricyclo[7.5.0.01,5]tetradecane-6-one; - (1R,4S,9S)-4-isopropyl-10-[[4-(trifluoromethyl)phenyl]methyl]-2-oxa-5,10-diazatricyclo[7.3.0.01,5]dodecane-6-one; - (3S,6R,7aR,11aR)-3-isopropyl-6-methyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,6R,7aR,11aR)-6-ethyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,6R,7aR,11aR)-6-allyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,6R,7aR,11aR)-6-isobutyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,6S,7aR,11aR)-3-isopropyl-6-methyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,6S,7aR,11aR)-6-ethyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,6S,7aR,11aR)-6-allyl-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-6-fluoro-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one; - (3S,7aR,11aR)-6,6-difluoro-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-3,7,7a,8,10,11-hexahydro-2H-oxazolo[2,3-j][1,6]naphthyridine-5-one; The compound according to claim 1, or selected from a pharmaceutically acceptable salt or optical isomer thereof.

6. X is O and / or Y is O and / or m has a value of 1 and / or n has a value of 1, and W is CR ４ R ４ ' and / or p and p' have a value of 1 and / or Z is NR １ And R １ However, benzyl (the benzyl is one or more halogen atoms, linear-(C) １ ~C ６ ) Halogenoalkyl, linear-(C) １ ~C ６ (Substituted with a halogenoalkoxy), linear or branched-chain -CH ３ - (C ６ ~C １０ )heteroaryl (the heteroaryl has at least one heteroatom selected from O, N, or S, and in particular the heteroaryl is piperidine, and one or more linear-(C) １ ~C ６ ) Halogenoalkyl, (C １ ~C ３ ) Alkyl or -(C ３ ~C ６ (Optionally substituted with cycloalkyl groups), linear or branched chain - (C １ ~C ６ ) Alkyl-(C ６ ~C １０ )aryl (where the aryl is particularly phenyl, and the phenyl is linear-(C) １ ~C ３ (Optionally substituted with a halogenoalkyl) or Z is CHNRaRb, where Ra and Rb are the same, and it is a linear or branched chain - (C １ ~C ３ ) an alkylphenyl, wherein the phenyl is one or more linear or branched chains - (C １ ~C ３ ) Halogenoalkyl, in particular optionally substituted with one trifluoromethyl and / or R ２ and R ２ ' is H and / or R ３ and R ３ ' is different and H and branched chain - (C １ ~C ６ ) Selected from alkyl and / or R ４ and R ４ ' is the same and is H and / or R ５ and R ５ ' is H and / or R ６ and R ６ The compound according to claim 1, wherein ' is H.

7. The aforementioned compound is as follows: - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl]-2,3,6,7,7a,8,10,11 octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-3-isopropyl-9-[[4-(trifluoromethoxy)phenyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-9-[(4-chlorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-9-[(3,4-dichlorophenyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-9-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-9-[[2,4-bis(trifluoromethyl)phenyl]methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-9-[(2-cyclopropyl-4-quinolyl)methyl]-3-isopropyl-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-3-isopropyl-9-[(1-methylindole-2-yl)methyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]ethyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,11aR)-3-isopropyl-9-[3-[4-(trifluoromethyl)phenyl]propyl]-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j][1,6]naphthyridine-5-one - (3S,7aR,9S,11aR)-9-[bis[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinoline-5-one The compound according to claim 1, or selected from a pharmaceutically acceptable salt or optical isomer thereof.

8. A pharmaceutical composition comprising the compound described in any one of claims 1 to 7.

9. A pharmaceutical composition according to claim 8, for use as a drug.

10. A pharmaceutical composition for use according to claim 9, for the prevention and / or treatment of mycobacterial infections or for the treatment of diseases caused by mycobacterial infections.

11. The pharmaceutical composition for use according to claim 10, wherein the mycobacterial infection is Mycobacterium tuberculosis infection.

12. A pharmaceutical composition for use according to claim 9, for the prevention and / or treatment of tuberculosis.

13. The pharmaceutical composition for use according to claim 10, wherein the pharmaceutical composition is used in combination with at least one other anti-mycobacterial agent.

14. (a) a compound represented by formula (I) according to claim 1 or 2, and (b) a combination of at least one other anti-mycobacterial agent.

15. The pharmaceutical composition according to claim 13, wherein the at least one other anti-mycobacterial agent is an anti-tuberculosis agent.

16. The combination according to claim 14, wherein at least one other anti-mycobacterial agent is an anti-tuberculosis agent.

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