New Anti-infective tricyclic spirolactams compounds

Abstract

The present invention concerns new tricyclic spirolactams (TriSLas) compounds and their use as a drug, in particular for the prevention and / or treatment of a mycobacterial infection or for the treatment of a disease caused by infection with a mycobacterium. The tuberculosis drug development pipeline requires further supplementation with additional candidates, ideally acting on novel targets (to minimize cross-resistance) and impacting on drug-tolerant bacilli to shorten treatment. The inventors of the present invention have identified new tricyclic spirolactams (TriSLas) compounds with particular activity against M. tuberculosis.

Description

[0001] NEW ANTI-INFECTIVE TRICYCLIC SPIROLACTAMS COMPOUNDS

[0002] FIELD OF INVENTION

[0003] The present invention concerns new tricyclic spirolactams (TriSLas) compounds and their use as a drug, in particular for the prevention and / or treatment of a mycobacterial infection or for the prevention and / or treatment of a disease caused by infection with a mycobacterium.

[0004] BACKGROUND OF THE INVENTION

[0005] While global efforts to eradicate tuberculosis (TB) by improving drug accessibility and compliance have significantly decreased deaths by 29% over the last 2 decades, TB remains the leading cause of death by an infectious disease worldwide (World Health Organization. Global tuberculosis report 2021. (2021)). With a minimum of 6-months of multidrug therapy, current TB treatment is notoriously lengthy, a feature largely attributed to the difficulty of eliminating phenotypically drug-tolerant sub-populations of the causative bacteria Mycobacterium tuberculosis (Mtb) (Connolly, L. E., Edelstein, P. H. & Ramakrishnan, L. Why is long-term therapy required to cure tuberculosis? PLoS Med. 4, 435-442 (2007)). Regrettably, escalating infections by multidrug resistant (MDR) TB infections (483,000 cases of rifampicin-resistant TB reported in 2020 (World Health Organization. Global tuberculosis report 2021. (2021)) as well as extensively drug resistant (XDR) TB (12,350 cases reported in 2019 (World Health Organization. Global tuberculosis report 2020. (2020))) require even longer therapy with less efficient and tolerated second- line drugs. In recognition of this global health problem, the WHO has placed TB at the highest critical global priority of antibiotic-resistant bacteria for the development of 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 / S 1473-3099(09) 70222- 1 ) .

[0006] Concerted efforts to find alternative and better antibiotics against drug-sensitive and - resistant TB have led to the approval of two novel classes of anti-TB drugs, the ATP synthase inhibitor bedaquiline (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 levels of clinical and pre- clinical drug development that may further feed our treatment options 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 increased efforts, it is clear that the TB drug development pipeline requires further supplementation with additional candidates, ideally acting on novel targets (to minimize cross-resistance) and impacting on drug-tolerant bacilli to shorten treatment.

[0007] The inventors of the present invention identified novel tricyclic spirolactams (TriSLas) compounds with particular activity against M. tuberculosis and other mycobacterium species.

[0008] DESCRIPTION OF THE INVENTION

[0009] The present invention thus relates to a compound of formula (I):

[0010] In which : p has a value of 0 or 1 ; p’ has a value of 1 or 2; n has a value of 1 or 2;

[0011] R is: o NRaRb; or o ORc; o Ra and Rb identical or different are chosen from:

[0012] ■ H

[0013] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom; ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0014] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0015] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0016] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0017] ■ linear or branched -(C2-C6)alkene-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0018] ■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-C6)alkyl, linear or branched -(Ci- C6)halogenoalkyl, halogen atom;

[0019] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom, -OH, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0020] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0021] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1 when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; provided that: ■ Ra and Rb can not be both a linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, and

[0022] ■ when Ra is H, Rb can not be H or linear or branched -(Ci-C6)alkyl-(C6-C )aryl, said aryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , o Rc is :

[0023] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0024] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0025] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0026] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;

[0027] ■ -(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0028] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(C1- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0029] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom;

[0030] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1 when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; or

[0031] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom, cyano, methyl sulfone; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Cs-Ce) cycloalkyl ; o Z2 is H, -(Cs-Ce) cycloalkyl, linear or branched -(Ci-C6)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

[0032] In particular, the present invention relates to a compound of formula (I):

[0033] In which : p has a value of 0 or 1; p’ has a value of 1 or 2 ; n has a value of 1 or 2 ;

[0034] R is: o NRaRb; or o ORc; o Ra and Rb identical or different are chosen from:

[0035] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0036] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0037] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0038] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0039] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy; ■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci- Ce)halogenoalkyl;

[0040] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom, -OH, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0041] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0042] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZi being linked to the heterocycle by the nitrogen atom; provided that Ra and Rb can not be both a linear or branched -(Ci-Ce)alkyl-(C6- Cw)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, o Rc is :

[0043] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0044] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0045] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0046] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;

[0047] ■ -(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0048] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0049] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom;

[0050] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; or

[0051] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Ca-Ce) cycloalkyl ; o Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

[0052] The present invention further relates to a pharmaceutical composition comprising a compound of formula (I) as defined herein.

[0053] It also relates to a compound according to the invention or to a pharmaceutical composition according to the invention for use as a drug, in particular for the prevention and / or treatment of a mycobacterial infection or for the treatment of a disease caused by infection with a mycobacterium, more particularly wherein the mycobacterial infection is a Mycobacterium tuberculosis infection.

[0054] It further relates to a compound or a pharmaceutical composition according to the invention in combination with at least one other anti-mycobacterial agent and to their use as mentioned above.

[0055] Unless specified otherwise, the terms used hereabove or hereafter as regards to the compounds of formula (I) have the meaning ascribed to them below: “halogen” refers to fluorine, chlorine, bromine or iodine atom, in particular fluorine atom.

[0056] "alkyl" represents an aliphatic-hydrocarbon group which may be straight or branched, having 1 to 6, especially 1 to 3 carbon atoms in the chain (Ci-Ce)alkyl or (Ci-C3)alkyl, unless specified otherwise. In particular, alkyl groups have 1 to 3 carbon atoms in the chain (Ci-C3)alkyl. Branched means that one or more alkyl groups such as methyl, ethyl or propyl are attached to a linear alkyl chain. Exemplary alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i- butyl, n-pentyl, n-hexyl, in particular isobutyl, isopropyl, propyl, methyl or ethyl. As mentioned, the alkyl chain can be interrupted by a SO2 group or by an oxygen atom.

[0057] “alkene” represents an aliphatic-hydrocarbon group containing at least a carboncarbon double bond, which may be straight or branched, having 2 to 6, especially 2 to 3 carbon atoms in the chain (C2-Ce)alkene or (C2-C3)alkene, unless specified otherwise. In particular, alkene groups have 2 to 3 carbon atoms in the chain (C2- C3)alkene. Branched means that one or more alkene groups are attached to a linear alkene chain. Exemplary alkene groups include allyle.

[0058] “cyano” represents -C=N.

[0059] “methyl sulfone” represents -S(O)2-CH3.

[0060] “halogenoalkyl” represents an aliphatic-hydrocarbon group which may be straight or branched, having 1 to 6, especially 1 to 3 carbon atoms in the chain (C1- Ce)halogenoalkyl or (Ci-C3)halogenoalkyl and in which one or more hydrogen atoms has been replaced by a halogen atom such as fluorine, chlorine, bromine or iodine atom, in particular by one or more fluorine atoms. Exemplary halogenoalkyl include trifluoromethyl, trifluoropropyl, trifluorobutyl, fluoropropyl or fluoroethyl.

[0061] “alkoxy” represents an alkyl group as previously defined singular bonded to oxygen. Examples of linear or branched (C1-C6)alkoxy or (C1-C3)alkoxy includes methoxy (CH3O) and ethoxy (CH3CH2O).

[0062] “halogenoalkoxy” represents an halogenoalkyl group as previously defined bonded to oxygen. Examples of linear or branched (C1-C6)halogenoalkoxy or (C1- C3)halogenoalkoxy includes trifluoromethoxy (CF3O).

[0063] “(C3-C6)cycloalkyl” refers to a saturated monocyclic or bicyclic non-aromatic hydrocarbon ring of 3 to 6 carbon atoms, which can comprise one or more unsaturation. Specific examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl. Preferably, the cycloalkyl group is cyclopropyl or cyclohexyl.

[0064] “linear or branched (Ci-C6)alkyl-(C3-C6)cycloalkyl” means that the cycloalkyl is linked to the alkyl group by a carbon of the alkyl group; alkyl and cycloalkyl are as defined previously.

[0065] "-(C6-C )aryl" refers to an aromatic monocyclic or multicyclic hydrocarbon ring system of 6 to 10 carbon atoms, preferably of 6 carbon atoms. Exemplary aryl groups include phenyl, naphthyl, biphenyl, in particular phenyl. Said aryl or phenyl can be substituted by one or more halogen atoms such as fluorine, bromine, iodine or chlorine, in particular chlorine or fluorine; cyano; methyl sulfone;-OH; one or more (Ci-Ce)alkyl or (Ci-C3)alkyl such as a methyl, said alkyl being optionally substituted by one to 3 fluorine atoms such as trifluoromethyl; one or more (Ci- C3)alkoxy such as methoxy, said alkoxy being optionally substituted by one or more fluorine atoms such as trifluoromethoxy.

[0066] “linear or branched (Ci-C6)alkyl-(C6-C )aryl ” means that the aryl is linked to the alkyl group by a carbon of the alkyl group; alkyl and aryl group are as defined previously; in particular -(Ci-C3)alkyl-(C6-C )aryl and more particularly (Ci- C3)alkyl-phenyl are contemplated, more particularly benzyl. Phenyl can be substituted as above mentioned, in particular by a halogen atom such as fluorine or chlorine, in particular chlorine; a methyl, a trifluoromethyl, a methoxy or trifluorometoxy.

[0067] “linear or branched -(Ci-C6)alkene-(C6-C )aryl” means that the aryl is linked to the alkene group by a carbon of the alkene group; alkene and aryl group are as defined previously; in particular -(C2-C3)alkene-(C6-C )aryl and more particularly (C2-C3)alkene-phenyl are contemplated, more particularly allyl-phenyl. Phenyl can be substituted as above mentioned, in particular by a trifluoromethyl.

[0068] "heterocycle" or "heterocycloalkyl" refers to a saturated or partially unsaturated non aromatic stable 3 to 10-membered mono, bi or multicyclic rings. Hetero atoms can be O, S or N, in particular N. In particular, each ring comprises from 1 to 3 hetero atoms. Suitable heterocycles are also disclosed in the Handbook of Chemistry and Physics, 76th Edition, CRC Press, Inc., 1995-1996, pages 225 to 226, the disclosure of which is hereby incorporated by reference. Examples of heterocycloalkyl include, but are not limited to piperazine, oxetane, tetrahydropyrane, tetrahydrofurane, diazepane, piperidine, pyrrolidine, morpholine, azetidine, diazabicyclo octanyl, diazabicycloheptanyl, azabicyclohexanyl, in particular oxetane, azetidine, piperidine, pyrrolidine. Said heterocycle is optionally substituted by one or more linear or branched -(Ci- Ce)halogenoalkyl, in particular fluoroalkyl such as fluoroethyl, trifluoropropyl or fluoropropyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom, with Z1 being as defined herein, in particular being C(CH3)3, with Z2 being as defined herein, in particular being (C3-C6)cycloalkyl such as cyclopropyl, an alkyl chain that can be interrupted by an oxygen atom such as CH2-O-CH3, a hydrogen, a (Ci-C3)alkyl such as methyl.

[0069] “linear or branched (Ci-C6)alkyl-heterocycle” means that the heterocycle is linked to the alkyl group by a carbon of the alkyl group; alkyl and heterocycle are as defined previously.

[0070] "heteroaryl" refers to a 5 to 10, aromatic mono-, bi- or multicyclic ring wherein at least one member of the ring is a hetero atom. Hetero atoms can be O, S or N, in particular N. In particular, each ring comprises from 1 to 3 hetero atoms. Examples include pyrrolyl, pyridyl, oxadiazol, thiazol, oxazol, triazol, pyrazolyl, pyrimidinyl, pyrazinyl, indolyl, quinolyl, imidazolyl, in particular pyridyl. Said heteroaryl can be substituted by one or more halogen atoms such as fluorine, bromine, iodine or chlorine, in particular chlorine or fluorine ; -OH; one or more (Ci-Ce)alkyl or (C1- C3)alkyl such as a methyl, said alkyl being optionally substituted by one to 3 fluorine atoms such as trifluoromethyl; one or more (Ci-C3)alkoxy such as methoxy, said alkoxy being optionally substituted by one or more fluorine atoms such as trifluoromethoxy.

[0071] “linear or branched (Ci-C6)alkyl-heteroaryl” means that the heteroaryl is linked to the alkyl group by a carbon of the alkyl group; alkyl and heteroaryl are as defined previously.

[0072] The term “substituted” generally refers to, unless specified otherwise, a substitution with one or more substituents, which may be identical or different, and which are identified herein.

[0073] In the context of the invention, Ra and Rb can not be at the same time a linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl. Ra and Rb can not also be at the same time H or if Ra is H, Rb can not be linear or branched -(Ci-C6)alkyl-(C6-C )aryl, said aryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl.

[0074] The compounds of formula (I) as described herein can be provided in the form of a free base or in the form of addition salts with acids, which also form part of the invention. These salts are advantageously prepared with pharmaceutically acceptable acids, but salts with other acids, useful for example for the purification or for the isolation of the compounds of formula (I) as described herein, also form part of the invention.

[0075] As used herein, the expression “pharmaceutically acceptable” refers to those compounds, materials, excipients, compositions or dosage forms which are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response or other problem complications commensurate with a reasonable benefit / risk ratio.

[0076] As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from nontoxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like, including mono, di or tri-salts thereof; and the salts prepared from organic acids such as formic, acetic, propionic, succinic, tartaric, citric, methanesulfonic, trifluoromethanesulfonic, benzenesulfonic, trifluoroacetic, glucoronic, glutamic, benzoic, salicylic, toluenesulfonic, oxalic, fumaric, maleic, lactic and the like. Further addition salts include ammonium salts such as tromethamine, meglumine, epolamine, etc., metal salts such as sodium, potassium, calcium, zinc or magnesium.

[0077] The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two. Generally, non-aqueous media like ether, dioxane, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington’s Pharmaceutical Sciences, 20thed., Mack Publishing Company, Easton, PA, 2000, the disclosure of which is hereby incorporated by reference.

[0078] Compounds

[0079] As mentioned, the compounds according to the invention are compounds of formula (I):

[0080] In which : p has a value of 0 or 1 ; p’ has a value of 1 or 2; n has a value of 1 or 2;

[0081] R is: o NRaRb; or o ORc; o Ra and Rb identical or different are chosen from:

[0082] ■ H

[0083] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0084] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0085] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0086] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0087] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0088] ■ linear or branched -(C2-C6)alkene-(C6-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy; ■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci- Ce)halogenoalkyl, halogen atom;

[0089] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom, -OH, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0090] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0091] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZi being linked to the heterocycle by the nitrogen atom; provided that:

[0092] ■ Ra and Rb can not be both a linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, and

[0093] ■ when Ra is H, Rb can not be H or linear or branched -(Ci-C6)alkyl-(C6-C )aryl, said aryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , o Rc is :

[0094] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0095] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0096] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0097] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; ■ -(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0098] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0099] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom;

[0100] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; or

[0101] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom, cyano, methyl sulfone; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Ca-Ce) cycloalkyl ; o Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

[0102] In particular, the compounds according to the invention are compounds of formula (I):

[0103]

[0104] In which : p has a value of 0 or 1 ; p’ has a value of 1 or 2 ; n has a value of 1 or 2 ;

[0105] R is: o NRaRb; or o ORc; o Ra and Rb identical or different are chosen from:

[0106] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0107] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0108] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0109] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0110] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0111] ■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-C6)alkyl, linear or branched -(Ci- C6)halogenoalkyl;

[0112] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom, -OH, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;

[0113] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0114] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZi being linked to the heterocycle by the nitrogen atom; provided that Ra and Rb can not be both a linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, o Rc is :

[0115] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0116] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0117] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0118] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;

[0119] ■ -(C6-Cw)heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0120] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(C1- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0121] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom;

[0122] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; or

[0123] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Cs-Ce) cycloalkyl ; o Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

[0124] In particular: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ;

[0125] R is: o NRaRb; or o ORc; o Ra is:

[0126] ■ H

[0127] ■ linear or branched -(Ci-Ce)alkyl-(Ce-Cio)aryl; or

[0128] ■ linear or branched -(Ci-Ce)alkyl-(Ce-Cio)heteroaryl, said heteroaryl having at least one nitrogen atom, said aryl and heteroaryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy; o Rb is :

[0129] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0130] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0131] ■ linear or branched -(Ci-C6)halogenoalkyl ; ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0132] ■ linear or branched -(C2-C6)alkene-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;

[0133] ■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(C1- Ce)halogenoalkyl;

[0134] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom;

[0135] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0136] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1 when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom;

[0137] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0138] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0139] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0140] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;

[0141] ■ -(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0142] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0143] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0144] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom ;or

[0145] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Ca-Ce) cycloalkyl o Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

[0146] In particular: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ;

[0147] R is: o NRaRb; or o ORc; o Ra is:

[0148] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl; or

[0149] ■ linear or branched -(Ci-C6)alkyl-(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom, said aryl and heteroaryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy; o Rb is : ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0150] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0151] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0152] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0153] ■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(C1- Ce)halogenoalkyl;

[0154] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0155] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0156] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1 when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom;

[0157] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0158] ■ -(Cs-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0159] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0160] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; ■ -(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0161] ■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;

[0162] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0163] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom ;or

[0164] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Ca-Ce) cycloalkyl o Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

[0165] In particular, compounds according to the invention are those in which: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:

[0166] ■ H

[0167] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl; or

[0168] ■ linear or branched -(Ci-C6)alkyl-(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom, said aryl and heteroaryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl ; and / or o Rb is :

[0169] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0170] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0171] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0172] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0173] ■ linear or branched -(C2-C6)alkene-(C6-C )aryl substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;

[0174] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0175] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1 when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Cs-Ce) cycloalkyl o Z2 is H, -(Cs-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; and / or o Rc is :

[0176] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atoms; or its pharmaceutically acceptable salts or optical isomers.

[0177] In particular, compounds according to the invention are those in which: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is: linear or branched -(Ci-C6)alkyl-(C6-C )aryl; or ■ linear or branched -(Ci-C6)alkyl-(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom, said aryl and heteroaryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl ; and / or o Rb is :

[0178] ■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;

[0179] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0180] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0181] ■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;

[0182] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or

[0183] ■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1 when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Cs-Ce) cycloalkyl o Z2 is H, -(Cs-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; and / or o Rc is :

[0184] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; or its pharmaceutically acceptable salts or optical isomers.

[0185] More particularly, compounds according to the invention are those in which: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is: ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl, optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl ; and / or o Rb is :

[0186] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0187] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0188] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl;

[0189] ■ linear or branched -(Ci-C3)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; or o Rc is :

[0190] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; or

[0191] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom; or its pharmaceutically acceptable salts or optical isomers.

[0192] More particularly, compounds according to the invention are those in which: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:

[0193] ■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl, optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl ; and / or o Rb is :

[0194] ■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;

[0195] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0196] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl; or o Rc is : linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; or its pharmaceutically acceptable salts or optical isomers.

[0197] Even more particularly, compounds according to the invention are those in which: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:

[0198] ■ linear or branched -(Ci-C3)alkyl-(C6-C )aryl, optionally substituted by one or more linear or branched -(C1-C3) halogenoalkyl ; and / or o Rb is :

[0199] ■ linear or branched -(Ci-C3)alkyl-(C3-C6)cycloalkyl;

[0200] ■ linear or branched -(Ci-C6)halogenoalkyl ;

[0201] ■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C3)halogenoalkyl; linear or branched -(Ci-C3)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N;; and / or o Rc is :

[0202] ■ linear or branched -(Ci-C3)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(C1-C3) halogenoalkyl; or

[0203] ■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom; or its pharmaceutically acceptable salts or optical isomers.

[0204] Even more particularly, compounds according to the invention are those in which: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:

[0205] ■ linear or branched -(Ci-C3)alkyl-(C6-C )aryl, optionally substituted by one or more linear or branched -(C1-C3) halogenoalkyl ; and / or o Rb is :

[0206] ■ linear or branched -(Ci-C3)alkyl-(C3-C6)cycloalkyl;

[0207] ■ linear or branched -(Ci-C6)halogenoalkyl ; heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C3)halogenoalkyl;

[0208] ; and / or o Rc is :

[0209] ■ linear or branched -(Ci-C3)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(C1-C3) halogenoalkyl; or its pharmaceutically acceptable salts or optical isomers.

[0210] In one embodiment, said compound if chosen from:

[0211] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0212] 3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0213] 3S,7aR,9R,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0214] 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0215] (3S,7aR,9S,11aR)-9-[cyclohexylmethyl-[[4-

[0216] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-

[0217] 2H-oxazolo[2,3-j]quinolin-5-one;

[0218] (3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[4-

[0219] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-

[0220] 2H-oxazolo[2,3-j]quinolin-5-one;

[0221] (3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-yl-[[4-

[0222] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one; tert-butyl 3-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro-

[0223] 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4-

[0224] (trifluoromethyl)phenyl]methyl]amino]azetidine-1-carboxylate; tert-butyl 3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro-

[0225] 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]azetidine-1 -carboxylate; tert-butyl (2R)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4-

[0226] (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl (2S)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; - tert-butyl 3-[(1 R)-1-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]ethyl]azetidine-1 -carboxylate;

[0227] - tert-butyl 3-[(1S)-1-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]ethyl]azetidine-1 -carboxylate; tert-butyl (3R)-3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl (3S)-3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl 4-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl (2R)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]pyrrolidine-1 -carboxylate; tert-butyl (2S)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]pyrrolidine-1 -carboxylate;

[0228] (3S,7aR,9S,11aR)-9-[azetidin-3-yl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0229] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-2-piperidyl]methyl-[[4-

[0230] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0231] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-2-piperidyl]methyl-[[4-

[0232] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0233] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2R)-2-piperidyl]methyl-[[4-

[0234] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0235] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(3S)-3-piperidyl]methyl-[[4-

[0236] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one; ((3S,7aR,9S,11aR)-3-isopropyl-9-[[(3R)-3-piperidyl]methyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;dihydrochloridej]quinolin-5-one;

[0237] (3S,7aR,9S,11aR)-3-isopropyl-9-[4-piperidylmethyl-[[4-

[0238] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0239] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2R)-pyrrolidin-2-yl]methyl-[[4-

[0240] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0241] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-pyrrolidin-2-yl]methyl-[[4-

[0242] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0243] (3S,7aR,9S,11aR)-9-[(4-hydroxy-4-methyl-cyclohexyl)-[[4-

[0244] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0245] (3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[6-(trifluoromethyl)-3- pyridyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one; tert-butyl 3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[6-(trifluoromethyl)-3- pyridyl]methyl]amino]methyl]azetidine-1 -carboxylate; tert-butyl 3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[5-(trifluoromethyl)-2- pyridyl]methyl]amino]methyl]azetidine-1 -carboxylate;

[0246] - (3S,7aR,9S,11aR)-9-[[1-(2-fluoroethyl)azetidin-3-yl]-[[4-

[0247] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0248] 3S,7aR,9S,11aR)-9-[[1-(3-fluoropropyl)azetidin-3-yl]-[[4-

[0249] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0250] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl-[1-(3,3,3- trifluoropropyl)azetidin-3-yl]amino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;

[0251] (3S,7aR,9S,11aR)-9-[[1-(cyclopropanecarbonyl)azetidin-3-yl]-[[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-[[1-(2-methoxyacetyl)azetidin-3-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0252] - (3S,7aR,9S,11aR)-9-[(1-acetylazetidin-3-yl)-[[4-

[0253] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0254] 3-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro-2H- oxazolo[2,3-j]quinolin-9-yl]-[[4-(trifluoromethyl)phenyl]methyl]amino]azetidine-1- carbaldehyde; tert-butyl 4-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4-

[0255] (trifluoromethyl)phenyl]methyl]amino]piperidine-1 -carboxylate;

[0256] (3S,7aR,9S,11aR)-3-isopropyl-9-[4-piperidyl-[[4-

[0257] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0258] 3S,7aR,9S,11aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-

[0259] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0260] (3S,7aR,9S,11aR)-9-[2-fluoroethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0261] (3S,7aR,9S,11aR)-3-isopropyl-9-[3-methylsulfonylpropyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0262] - (3S,7aR,9S,11aR)-9-[(4,4-difluorocyclohexyl)-[[4-

[0263] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0264] (3S,7aR,9S,11aR)-9-[3-fluoropropyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0265] (3S,7aR,9S,11aR)-9-[cyclopropyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0266] (3S,7aR,9S,11aR)-9-[cyclobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0267] (3S,7aR,9R, 11 aR)-9-[2-fluoroethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0268] (3S,7aR,9R, 11 aR)-9-[3-fluoropropyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one; (3S,7aR,9R, 11 a / ?)-3- isopropyl-9- [4, 4, 4-trif I uorobuty l-[[4-

[0269] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one;

[0270] (3S,7aR,9R, 11 aR)-9-[4-fluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0271] (3S,7aR,9S,11aR)-9-[4-fluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0272] (3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-ylmethyl-[[4-

[0273] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one;

[0274] (3S,7aR,9S,11aR)-9-[[(1R)-2,2-difluorocyclopropyl]methyl-[[4-

[0275] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0276] (3S,7aR,9S,11aR)-9-[[(1S)-2,2-difluorocyclopropyl]methyl-[[4-

[0277] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0278] (3S,7aR,9S,11aR)-3-isopropyl-9-[(1-methylindol-2-yl)methylamino]- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0279] (3S,7aR,9S,11aR)-3-isopropyl-9-[[1-(4,4,4-trifluorobutyl)azetidin-3-yl]-[[4-

[0280] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one;

[0281] (3S,7aR,9S,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]allylamino]- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0282] (3S,7aR,9R,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]allylamino]- 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0283] (3S,7aR,9S,11aR)-9-[[8-fluoro-2-(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0284] (3S,7aR,9S,11aR)-9-[[2,8-bis(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0285] (3S,7aR,9S,11aR)-9-[[7-fluoro-2-(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0286] (3S,7aR,9S,11aR)-9-[[6,7-difluoro-2-(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0287] (3S,7aR,9S,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methylamino]- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one; (3S,7aR,9R,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methylamino]- 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0288] (3S,7aR,9R, 11 aR)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0289] (3S,7aR,9S,11aR)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0290] (3S,7aR,9R, 11 aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0291] (3S,7aR,9S,11aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0292] (3S,7aR,9R, 11 aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0293] (3S,7aR,9S,11aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one; or its pharmaceutically acceptable salts or optical isomers.

[0294] In one embodiment, said compound if chosen from:

[0295] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0296] 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0297] 3S,7aR,9R,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0298] 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0299] (3S,7aR,9S,11aR)-9-[cyclohexylmethyl-[[4-

[0300] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0301] (3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[4-

[0302] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0303] (3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-yl-[[4-

[0304] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one; tert-butyl 3-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]azetidine-1-carboxylate; tert-butyl 3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]azetidine-1 -carboxylate; tert-butyl (2R)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl (2S)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate;

[0305] - tert-butyl 3-[(1 R)-1-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]ethyl]azetidine-1 -carboxylate;

[0306] - tert-butyl 3-[(1S)-1-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]ethyl]azetidine-1 -carboxylate; tert-butyl (3R)-3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl (3S)-3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl 4-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate; tert-butyl (2R)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]pyrrolidine-1 -carboxylate; tert-butyl (2S)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]pyrrolidine-1 -carboxylate;

[0307] (3S,7aR,9S,11aR)-9-[azetidin-3-yl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0308] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-2-piperidyl]methyl-[[4-

[0309] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0310] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-2-piperidyl]methyl-[[4-

[0311] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one; (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2R)-2-piperidyl]methyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0312] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(3S)-3-piperidyl]methyl-[[4-

[0313] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0314] ((3S,7aR,9S,11aR)-3-isopropyl-9-[[(3R)-3-piperidyl]methyl-[[4-

[0315] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;dihydrochloridej]quinolin-5-one;

[0316] (3S,7aR,9S,11aR)-3-isopropyl-9-[4-piperidylmethyl-[[4-

[0317] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0318] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2R)-pyrrolidin-2-yl]methyl-[[4-

[0319] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0320] (3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-pyrrolidin-2-yl]methyl-[[4-

[0321] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0322] (3S,7aR,9S,11aR)-9-[(4-hydroxy-4-methyl-cyclohexyl)-[[4-

[0323] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0324] (3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[6-(trifluoromethyl)-3- pyridyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one; tert-butyl 3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[6-(trifluoromethyl)-3- pyridyl]methyl]amino]methyl]azetidine-1 -carboxylate; tert-butyl 3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[5-(trifluoromethyl)-2- pyridyl]methyl]amino]methyl]azetidine-1 -carboxylate;

[0325] - (3S,7aR,9S,11aR)-9-[[1-(2-fluoroethyl)azetidin-3-yl]-[[4-

[0326] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0327] 3S,7aR,9S,11aR)-9-[[1-(3-fluoropropyl)azetidin-3-yl]-[[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]methyl-[1-(3,3,3- trifluoropropyl)azetidin-3-yl]amino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;

[0328] (3S,7aR,9S,11aR)-9-[[1-(cyclopropanecarbonyl)azetidin-3-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0329] (3S,7aR,9S,11aR)-3-isopropyl-9-[[1-(2-methoxyacetyl)azetidin-3-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0330] - (3S,7aR,9S,11aR)-9-[(1-acetylazetidin-3-yl)-[[4-

[0331] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0332] 3-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro-2H- oxazolo[2,3-j]quinolin-9-yl]-[[4-(trifluoromethyl)phenyl]methyl]amino]azetidine-1- carbaldehyde; tert-butyl 4-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10, 11 -octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]piperidine-1 -carboxylate;

[0333] (3S,7aR,9S,11aR)-3-isopropyl-9-[4-piperidyl-[[4-

[0334] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0335] 3S,7aR,9S,11aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-

[0336] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0337] (3S,7aR,9S,11aR)-9-[2-fluoroethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0338] (3S,7aR,9S,11aR)-3-isopropyl-9-[3-methylsulfonylpropyl-[[4-

[0339] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one; or its pharmaceutically acceptable salts or optical isomers.

[0340] In a particular embodiment, said compound if chosen from:

[0341] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0342] 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0343] 3S,7aR,9R,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0344] 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one; (3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[4-

[0345] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0346] (3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-yl-[[4-

[0347] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0348] - (3S,7aR,9S,11aR)-9-[[1-(2-fluoroethyl)azetidin-3-yl]-[[4-

[0349] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0350] 3S,7aR,9S,11aR)-9-[[1-(3-fluoropropyl)azetidin-3-yl]-[[4-

[0351] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0352] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl-[1-(3,3,3- trifluoropropyl)azetidin-3-yl]amino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;

[0353] 3S,7aR,9S,11aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-

[0354] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0355] (3S,7aR,9S,11aR)-9-[2-fluoroethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0356] (3S,7aR,9S,11aR)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-3-isopropyl- 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0357] (3S,7aR,9R,11aR)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0358] (3S,7aR,9S,11aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0359] (3S,7aR,9R, 11 aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0360] (3S,7aR,9S,11aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0361] (3S,7aR,9R, 11 aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;

[0362] (3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-ylmethyl-[[4-

[0363] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one; or its pharmaceutically acceptable salts or optical isomers. In a particular embodiment, said compound if chosen from:

[0364] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]- 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0365] 3S,7aR,9R,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-

[0366] 3,6, 7, 7a, 8, 9, 10, 11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one;

[0367] (3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[4-

[0368] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0369] (3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-yl-[[4-

[0370] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0371] - (3S,7aR,9S,11aR)-9-[[1-(2-fluoroethyl)azetidin-3-yl]-[[4-

[0372] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0373] 3S,7aR,9S,11aR)-9-[[1-(3-fluoropropyl)azetidin-3-yl]-[[4-

[0374] (trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;

[0375] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methyl-[1-(3,3,3- trifluoropropyl)azetidin-3-yl]amino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;

[0376] 3S,7aR,9S,11aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-

[0377] (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;

[0378] (3S,7aR,9S,11aR)-9-[2-fluoroethyl-[[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 its pharmaceutically acceptable salts or optical isomers.

[0379] As previously 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.

[0380] The anti-mycobacterial agent is as defined below.

[0381] Compounds provided herein can be formulated into pharmaceutical compositions, optionally by admixture with one or more pharmaceutically acceptable excipients.

[0382] The present invention thus also relates to a pharmaceutical composition comprising a compound of formula (I) as defined herein, and a pharmaceutically acceptable excipient. In one embodiment, said pharmaceutical composition further comprises at least one other anti-mycobacterial agent.

[0383] Anti-mycobacterial agents are well known in the art. Antimycobacterial, or antituberculosis, agents include rifampin, rifabutin, isoniazid, ethambutol, streptomycin, amikacin, kanamycin, moxifloxacin, pyrazinamide, bedaquiline, linezolid, sutezolid, nitroimidazole . Antimycobacterial agents are most commonly prescribed today in multidrug combinations.

[0384] In one embodiment, the pharmaceutical composition comprises two, three, four, five, six or seven additional anti- tuberculosis agents. For example, in the treatment of multidrugresistant tuberculosis, it is common that combinations of four or more drugs are administered to patients. For example, in the treatment of drug-sensitive tuberculosis, it is common that combinations of three or four drugs are administered to patients.

[0385] Such compositions may be prepared for use in oral administration, particularly in the form of tablets or capsules, in particular orodispersible (lyoc) tablets; or parenteral administration, particularly in the form of liquid solutions, suspensions or emulsions.

[0386] It may 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 binding agents 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 dose forms, wherein the term “unit dose” means a single dose which is capable of being administered to a patient, and which can be readily handled and packaged, remaining as a physically and chemically stable unit dose comprising either the active compound itself, or as a pharmaceutically acceptable composition.

[0387] The tablets, pills, powders, capsules, troches and the like can contain one or more of any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, or gum tragacanth; a diluent such as starch or lactose; a disintegrant such as starch and cellulose derivatives; a lubricant such as magnesium stearate; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, or methyl salicylate. Capsules can be in the form of a hard capsule or soft capsule, which are generally made from gelatin blends optionally blended with plasticizers, as well as a starch capsule. In addition, dosage unit forms can contain various other materials that modify the physical form of the dosage unit, for example, coatings of sugar, shellac, or enteric agents. Other oral dosage forms syrup or elixir may contain sweetening agents, preservatives, dyes, colorings, and flavorings. In addition, the active compounds may be incorporated into fast dissolve, modified-release or sustained-release preparations and formulations, and wherein such sustained-release formulations are preferably bi-modal.

[0388] 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, sweetening, flavoring and 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 alcohols and water, hydrogels, buffered media, and saline. In particular, biocompatible, biodegradable lactide polymer, lactide / glycolide copolymer, or polyoxyethylene-polyoxypropylene copolymers may be useful excipients to control the release of the active compounds. Intravenous vehicles can include fluid and nutrient replenishers, electrolyte replenishers, such as those based on Ringer's dextrose, and the like.

[0389] Compounds for use

[0390] As already mentioned, the present invention also relates to a compound of formula (I) as defined herein for use as a drug.

[0391] In particular, said compound can be used to prevent and / or treat a mycobacterial infection.

[0392] Mycobacterial infections are well known in the art. A mycobacterial infection is one caused by infection with a mycobacterium.

[0393] The mycobacterium may be a member of one of the following groups of mycobacterium: Mycobacterium tuberculosis complex (MTC), Mycobacterium avium comp / ex (MAC), Mycobacterium gordonae clade, Mycobacterium kansasii clade, Mycobacterium chelonae clade, Mycobacterium fortuitum clade, Mycobacterium parafortuitum clade or Mycobacterium vaccae clade, Mycobacterium marinum and Mycobacterium abscessus. The mycobacterium may also be Mycobacterium ulcerans or Mycobacterium leprae.

[0394] In particular, the mycobacterium is a member of the Mycobacterium tuberculosis complex (MTC). Members of 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. These mycobacteria are causative agents of human and animal tuberculosis. Mycobacterium tuberculosis is the major cause of human tuberculosis.

[0395] Still particularly, the infection is a Mycobacterium tuberculosis infection. In other words, the mycobacterial infection is caused by infection with Mycobacterium tuberculosis.

[0396] In one embodiment, the Mycobacterium tuberculosis is multidrug-resistant.

[0397] In another aspect, the 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 infection with a mycobacterium.

[0398] In particular, the mycobacterium is selected from those hereinbefore described.

[0399] For example, the mycobacterial infection may be caused by infection with a mycobacterium selected from the following: Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium pinnipedii, Mycobacterium avium, Mycobacterium avium paratuberclosis, 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, include Mycobacterium boenickei, Mycobacterium brisbanense, Mycobacterium cosmeticum, Mycobacterium fortuitum, Mycobacterium fortuitum subspecies acetamidolyticum, Mycobacterium houstonense, Mycobacterium mageritense, Mycobacterium neworleansense, Mycobacterium peregrinum, Mycobacterium porcinum, Mycobacterium senegalense, Mycobacterium septicum, Mycobacterium austroafricanum, Mycobacterium diernhoferi, Mycobacterium frederiksbergense, Mycobacterium hodleri, Mycobacterium neoaurum, Mycobacterium parafortuitum, Mycobacterium ulcerans, Mycobacterium marinum, Mycobacterium abscessus and Mycobacterium leprae.

[0400] Diseases caused by infection with a mycobacterium include, but are not limited to, tuberculosis (e.g. from Mycobacterium tuberculosis), leprosy (e.g. from Mycobacterium leprae), Johne's disease (e.g. from Mycobacterium avium subspecies paratuberculosis), Buruli or Bairnsdale ulcer (e.g. from Mycobacterium ulcerans), Crohn's disease (e.g. from Mycobacterium avium subspecies paratuberculosis), pulmonary disease or pulmonary infection, pneumonia, bursa, synovial, tendon sheaths, localized abscess, lymphadenitis, skin and soft tissue infections, Lady Windermere syndrome (e.g. from Mycobacterium avium complex (MAC)), MAC lung disease, disseminated Mycobacterium avium complex (DMAC), disseminated Mycobacterium avium intracellulare complex (DMAIC), hot-tub lung (e.g. from Mycobacterium avium complex), MAC mastitis, MAC pyomyositis, or granuloma disease. In particular, in the context of the invention, the disease is tuberculosis.

[0401] In one embodiment, the invention thus also relates to a method of treatment of a 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) as described in this section, or pharmaceutically acceptable salt thereof.

[0402] As described herein, a mycobacterial infection is one caused by infection with a mycobacterium. The mycobacterium is as hereinbefore described.

[0403] In one embodiment, the invention relates to a method of treatment of a Mycobacterium tuberculosis infection.

[0404] In another embodiment, the invention relates to a method of treatment of a disease caused by infection with a mycobacterium 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.

[0405] In particular in the context of the invention, the disease is tuberculosis.

[0406] In one embodiment, said compound is used in combination with at least one other anti-mycobacterial agent.

[0407] Anti-mycobacterial agents are well known in the art. Antimycobacterial, or antituberculosis, agents include rifampin, rifabutin, isoniazid, ethambutol, streptomycin, amikacin, kanamycin, moxifloxacin, pyrazinamide, bedaquiline, linezolid, sutezolid, nitroimidazole.

[0408] Antimycobacterial agents are most commonly prescribed today in multidrug combinations.

[0409] In one embodiment, the combination comprises two, three, four, five, six or seven additional anti- tuberculosis agents. For example, in the treatment of multidrug-resistant tuberculosis, it is common that combinations of four or more drugs are administered to patients. For example, in the treatment of drug-sensitive tuberculosis, it is common that combinations of three or four drugs are administered to patients.

[0410] The terms "treat", “treating”, “treated” or "treatment", as used in the context of the invention, refer to therapeutic treatment wherein the object is to eliminate or lessen symptoms. Beneficial or desired clinical results include, but are not limited to, elimination of symptoms, alleviation of symptoms, diminishment of extent of condition, stabilized (i.e., not worsening) state of condition, delay or slowing of progression of the condition. The terms “prevent”, “prevention”, “preventing” or “prevented”, as used in the context of the present invention, refer to the prevention of the onset, recurrence or spread of a disease or disorder or infection, or of one or more symptoms thereof. In certain embodiments, the terms refer to the treatment with or administration of a compound provided herein prior to the onset of symptoms, particularly to patients at risk of disease or disorder or infection provided herein. The terms encompass the inhibition or reduction of a symptom of the particular disease or disorder or infection. Subjects with familial history of a disease or disorder or infection in particular are candidates for preventive regimens in certain embodiments. In addition, subjects who have a history of recurring symptoms are also potential candidates for the prevention. In this regard, the term “prevention” may be interchangeably used with the term “prophylactic treatment”.

[0411] In particular, the subject in need of a treatment against mycobacterial infection or a disease caused by infection with a mycobacterium is a subject afflicted with such disease or infection.

[0412] In the context of the present invention, the identification of the subjects who are in need of treatment of herein-described diseases and conditions is conducted as above mentioned and is well within the ability and knowledge of the man skilled in the art. A clinician skilled in the art can readily identify, by the above-mentioned technics, those subjects who are in need of such treatment.

[0413] A therapeutically effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of conventional techniques and by observing results obtained under analogous circumstances. In determining the therapeutically effective amount, a number of factors are considered by the attending diagnostician, including, but not limited to: the species of subject; its size, age, and general health; the specific disease involved; the degree of involvement or the severity of the disease; the response of the individual subject; the particular compound administered; the mode of administration; the bioavailability characteristic of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances.

[0414] As used herein, an «effective amount” refers to an amount which is effective in reducing, eliminating, treating or controlling the symptoms of the herein-described diseases and conditions. The term "controlling" is intended to refer to all processes wherein there may be a slowing, interrupting, arresting, or stopping of the progression of the diseases and conditions described herein, but does not necessarily indicate a total elimination of all disease and condition symptoms, and is intended to include prophylactic treatment and chronic use. The term “patient" or “subject” refers to a warm-blooded animal such as a mammal, in particular a human, male or female, unless otherwise specified, which is afflicted with, or has the potential to be afflicted with one or more diseases and conditions described herein.

[0415] In particular, the compounds of the combination according to the invention are administered separately, sequentially or simultaneously.

[0416] The amount of the compound according to the invention, which is required to achieve the desired biological effect, will vary depending upon a number of factors, including the dosage of the drug to be administered, the chemical characteristics (e.g. hydrophobicity) of the compounds employed, the potency of the compounds, the type of resistance, the state of resistance in the patient, and the route of administration.

[0417] Compounds provided herein can be formulated into pharmaceutical compositions, optionally by admixture with one or more pharmaceutically acceptable excipients.

[0418] Such compositions may be prepared for use in oral administration, particularly in the form of tablets or capsules, in particular orodispersible (lyoc) tablets; or parenteral administration, particularly in the form of liquid solutions, suspensions or emulsions.

[0419] It may 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, 20thed.; Gennaro, A. R., Ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2000. Pharmaceutically compatible binding agents 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 dose forms, wherein the term “unit dose” means a single dose which is capable of being administered to a patient, and which can be readily handled and packaged, remaining as a physically and chemically stable unit dose comprising either the active compound itself, or as a pharmaceutically acceptable composition.

[0420] The tablets, pills, powders, capsules, troches and the like can contain one or more of any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, or gum tragacanth; a diluent such as starch or lactose; a disintegrant such as starch and cellulose derivatives; a lubricant such as magnesium stearate; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, or methyl salicylate. Capsules can be in the form of a hard capsule or soft capsule, which are generally made from gelatin blends optionally blended with plasticizers, as well as a starch capsule. In addition, dosage unit forms can contain various other materials that modify the physical form of the dosage unit, for example, coatings of sugar, shellac, or enteric agents. Other oral dosage forms syrup or elixir may contain sweetening agents, preservatives, dyes, colorings, and flavorings. In addition, the active compounds may be incorporated into fast dissolve, modified-release or sustained-release preparations and formulations, and wherein such sustained-release formulations are preferably bi-modal.

[0421] 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, sweetening, flavoring and 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 alcohols and water, hydrogels, buffered media, and saline. In particular, biocompatible, biodegradable lactide polymer, lactide / glycolide copolymer, or polyoxyethylene-polyoxypropylene copolymers may be useful excipients to control the release of the active compounds. Intravenous vehicles can include fluid and nutrient replenishers, electrolyte replenishers, such as those based on Ringer's dextrose, and the like.

[0422] Examples of modes of administration include parenteral e.g. subcutaneous, intramuscular, intravenous, intradermal, as well as oral administration.

[0423] Process of preparation

[0424] The present invention is also concerned with the process of preparation of the compounds of formula (I) as described herein.

[0425] The compounds of the present invention may be prepared in a number of ways well known to those skilled in the art. The compounds can be synthesized, for example, by application or adaptation of the methods described below, or variations thereon as appreciated by the skilled artisan. The appropriate modifications and substitutions will be readily apparent and well known or readily obtainable from the scientific literature to those skilled in the art.

[0426] It will be appreciated that the compounds of the present invention may contain one or more asymmetrically substituted carbon atoms, and may be isolated in optically active or racemic forms. Thus, all diastereomeric forms of a structure are intended, unless the specific stereochemistry - is specifically indicated. It is well known in the art how to prepare and isolate such optically active forms.

[0427] For example, mixtures of stereoisomers may be separated by standard techniques including, but not limited to, resolution of racemic forms, normal, reverse-phase, and chiral chromatography, preferential salt formation, recrystallization, and the like, or by chiral synthesis either from chiral starting materials or by deliberate synthesis of target chiral centers.

[0428] Compounds of the present invention may be prepared by a variety of synthetic routes. The reagents and starting materials are commercially available, or readily synthesized by well-known techniques by one of ordinary skill in the arts. All substituents, unless otherwise indicated, are as previously defined.

[0429] In the reactions described hereinafter, it may be necessary to protect reactive functional groups, for example hydroxyl, amino, imino, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups may be used in accordance with standard practice, for examples see 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.

[0430] The compound thus prepared may be recovered from the reaction mixture by conventional means. For example, the compounds may 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 followed by extraction with a water- immiscible organic solvent and distilling off the solvent from the extract. Additionally, the product can, if desired, be further purified by various well-known techniques, such as recrystallization, reprecipitation or the various chromatography techniques, notably column chromatography or preparative thin layer chromatography.

[0431] The reactions can be carried out by the skilled person by applying or adapting the methods illustrated in the examples hereinafter.

[0432] In particular, compounds of formula (I) can be prepared according to protocols mentioned in the experimental part below.

[0433] Further, the process of the invention may also comprise the additional step of isolating the compound of formula (I). This can be done by the skilled person by any of the known conventional means, such as the recovery methods described above.

[0434] Generally, the starting products are commercially available mainly from Aldrich or Acros or other typical chemicals supplier or may be obtained by applying or adapting any known methods or those described in the examples.

[0435] In the context of the present invention, it should be understood that "a compound for use for the prevention and / or treatment of" is equivalent to "the use of a compound for the prevention and / or treatment of" and to "the use of a compound for the manufacture of a medicament for the prevention and / or treatment of ”. The invention will be further illustrated by the following examples.

[0436] Examples

[0437] Part A - Synthesis of compounds according to the invention

[0438] Synthesis of methyl 3-(8-oxo-1,4-dioxaspiro[4.5]decan-7-yl)propanoate (intermediate 1)

[0439] In a round bottom flask charged with 1 ,4-dioxaspiro[4.5]decan-8-one (1 g, 6.4 mmol, 1 eq) dissolved in 35 mL of anhydrous toluene. Then morpholine (2.8 mL, 32 mmol, 5 eq) was added dropwise. The mixture was refluxed under Dean-Stark apparatus at 150 °C for 5h. Then methyl prop-2-enoate (2.9 mL, 32 mmol, 5 eq) was added. The mixture was stirred at 120 °C overnight. The solvent was removed under reduced pressure; then an aqueous solution of HCI 0.1 N (10 mL) was added as well as 5 mL of acetonitrile. The mixture was stirred for 1h. DCM was added, layers were separated. Organic layer was washed with water, once with brine, dried over MgSO4, filtered and evaporated under reduced pressure. The crude was purified though flash chromatography (Cyclohexane / ethyl acetate: 100 / 0 to 0 / 100) to afford the desired product 1 (476 mg, 31 %) as a colorless oil. NMR (300 MHz, CDCI3): 5 4.06 - 3.94 (m, 4H), 3.63 (s, 3H), 2.72 - 2.53 (m, 2H), 2.38 - 2.19 (m, 3H), 2.10 - 1.93 (m, 4H), 1.69 (t, J = 13.1 Hz, 1 H), 1.57 - 1.42 (m, 1 H) ppm. [ES+ MS] m / z 243 (MH+).

[0440] Synthesis of (3'S,7'aR,1 TaR)-3'-isopropylspiro[1,3-dioxolane-2,9'- 2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j]quinoline]-5,-one (intermediate 2) via meyers lactamization (intermediate 2)

[0441] A solution of pivalic acid (238 mg, 2.33 mmol, 1.2 equiv) in toluene (10 mL) was added to intermediate 1 (470 mg, 1.94 mmol, 1 eq). To this mixture was added a solution of L- valinol (240 mg, 2.33 mmol, 1.2 eq). The resulting mixture was refluxed at 150 °C for 5h. The solvent was removed under in vacuo. The oil obtained was dissolved in DCM and water. The layers were separated. The aqueous layer was extracted 3 times with DCM. The combined organic layer was dried over MgSC>4, filtered, then concentrated under reduced pressure to give the crude material which was purified by flash chromatography column over silica gel (cyclohexane / ethyl acetate: 100 / 0 to 0 / 100) to afford intermediate 2 (440 mg, 77%) as a white powder, as a single diastereoisomer.1H NMR (300 MHz, CDCI3): 6 4.13 - 3.96 (m, 2H), 3.97 - 3.85 (m, 4H), 3.73 (dd, J = 8.1 Hz, J = 6.1 Hz, 1 H), 2.61 - 2.47 (m, 1 H), 2.39 - 2.14 (m, 3H), 2.05 - 1.73 (m, 6H), 1.72 - 1.56 (m, 3H), 0.94 (d, J = 6.9 Hz, 3H), 0.90 (d, J = 6.9 Hz, 3H) ppm.13C NMR (75 MHz, CDCI3): 5 170.6, 107.7, 93.7, 66.6, 64.6, 64.1 , 61.2, 40.3, 36.3, 33.1 , 31.7, 31.3, 28.8, 23.5, 20.0, 18.9 ppm. [ES+MS] m / z 296 (MH+).

[0442] Deprotection of acetal group of (S'S.T'aR.H'aRJ-S'-isopropylspiron.S- dioxolane-2,9'-2,3,6,7,7a,8,10,11-octahydrooxazolo[2,3-j]quinoline]-5'-one (intermediate 3)

[0443] Intermediate 2 (100 mg, 0.339 mmol, 1 eq) was dissolved in THF (0.5 mL) then an aqueous solution of HCI (1 N) (3.39 mL, 3.39 mmol, 10 equiv) was added. The solution was stirred at room temperature for 4h. Aqueous solution saturated with Na2COs was added until pH 7. The solvent was removed using a freeze dryer to afford a white solid. The solid obtained was dissolved in DCM and H2O. The layers were separated, then the aqueous layer was extracted three times with DCM. The combined organic layer was dried over MgSCL, filtered then concentrated in vacuo to afford the desired product (3S,7aR,11aR)-3- isopropyl-2,3,6,7,7a,8, 10, 11 -octahydrooxazolo[2,3-j]quinoline-5, 9-dione, intermediate 3 (90 mg, quantitative yield) as a white solid.1H NMR (300 MHz, CDCI3): 6 4.18-4.02 (m, 2H), 3.88 (dd, J = 8.6 Hz and J = 5.7 Hz, 1 H), 2.98 (dd, J = 14.5 Hz, J = 6.4 Hz, 1 H), 2.73- 2.57 (m, 1 H), 2.54 (dd, J = 8.7 Hz, J = 2.2 Hz, 1 H), 2.48-2.36 (m, 1 H), 2.30-2.00 (m, 6H), 1.90-1.78 (m, 1 H), 1.70-1.53 (m, 1 H), 0.94 (d, J = 6.9 Hz, 3H), 0.92 (J = 6.7 Hz, 3H) ppm. [ES+MS] m / z 252 (MH+).

[0444] Synthesis of Examples 1 and 2 from intermediate 3 First step: Reduction of ketone from intermediate 3

[0445] Int 3 Int 4

[0446] Intermediate 3 (200 mg, 0.796 mmol, 1 eq) was dissolved in anhydrous THF (5 mL), then NaBH4 (60 mg, 1.59 mmol, 2 eq) was added. The mixture was stirred at room temperature for 3 h. The mixture was quenched with H2O and let stirred at room temperature overnight. Then the solution was extracted with ethyl acetate. The layers were separated, then the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried on MgSCU, filtered, and concentrated in vacuo to afford the desired product intermediate 4 (200 mg) in quantitative yield, as two diastereoisomers, as a colorless oil.

[0447] Second step: Alkylation of intermediate 4 with trifluoromethyl benzyl bromide

[0448] Ex 1 Ex 2

[0449] Intermediate 4 (200 mg, 0.789 mmol, 1 equiv) was dissolved in THF (5 mL). The solution was cooled down to 0 °C (ice bath), then NaH (60% in suspension in oil) (121 mg, 3.16 mmol, 4 equiv), 1-(bromomethyl)-4-(trifluoromethyl)benzene (566 mg, 2.37 mmol, 3 equiv), and TBAI (292 mg, 0.789 mmol, 1 equiv) were added. The ice bath was removed and the resulting solution was stirred at room temperature overnight. The solution was placed at 0 °C, then quenched with H2O. The resulting solution was extracted three times with ethyl acetate. The combined organic layers were dried over MgSC>4, filtered and concentrated under vacuum to give the crude material which was purified by flash chromatography column (cyclohexane / ethyl acetate: 1 / 0 to 0 / 1) to afford examples 1 (76 mg, 23%, colorless oil) and 2 (123 mg, 38% of yield, colorless oil) as two separated diastereoisomers.

[0450] (3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]- 3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one (example 1):1H NMR (300 MHz, CDCI3): 7.58 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 4.58 (s, 2H), 4.12-3.97 (m, 2H), 3.75 (dd, J = 8.2 Hz, and J = 6.1 Hz, 1 H), 3.64-3.52 (m, 1 H), 2.61-2.49 (m, 1 H), 2.45-2.30 (m, 1 H), 2.07-1.58 (m, 10H), 0.94 (d, J = 6.9 Hz, 3H), 0.90 ( = 6.9 Hz, 3H) ppm.13C NMR (75 MHz, CDCI3): 170.0, 143.1 , 129.9 (q, J = 32.8 Hz), 127.5, 125.5 (q, J = 3.7 Hz), 124.2 (q, J = 272.1 Hz), 93.5, 72.9, 64.6, 66.5, 61.4, 40.3, 34.1 , 32.8, 31.3, 29.8, 28.6, 23.2, 20.0, 18.8 ppm. [ES+MS] m / z 412 (MH+).

[0451] (3S,7aR,9R,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]- 3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one (example 2):1H NMR (300 MHz, CDCI3): 7.60 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 4.54 (s, 2H), 4.15-3.98 (m, 2H), 3.79-3.65 (m, 2H), 2.61-2.48 (m, 1 H), 2.40-2.23 (m, 2H), 2.05-1.66 (m, 10H), 0.96 (d, J = 6.8 Hz, 3H), 0.91 (J = 6.8 Hz, 3H) ppm.13C NMR (75 MHz, CDCI3): 170.8, 143.1 , 130.0 (q, J = 36.9 Hz), 127.2, 125.5 (q, J = 3.8 Hz), 124.4 (q, J = 271.5 Hz), 94.4, 72.7, 69.6, 66.7, 61.2, 39.3, 33.5, 32.3, 31.5, 26.6, 25.9, 24.8, 20.2, 19.0 ppm. [ES+MS] m / z 412 (MH+).

[0452] Synthesis of methyl 3-(5-benzyloxy-2-oxo-cyclohexyl)propanoate (intermediate 5)

[0453] Under Ar, 4-benzyloxycyclohexanone (2.3 g, 11.3 mmol, 1 eq) was dissolved in toluene then pyrrolidine (4.4 mL, 52.9 mmol, 4.7 eq) was added at room temperature. The flask was equipped with a Dean Stark apparatus and the mixture was heated to 150 °C and stirred for 5 h. Methyl prop-2-enoate (1.9 mL, 21.4 mmol, 1.9 eq) was added and the resulting mixture was stirred at 130 °C for 16 h. The solvent was evaporated and the crude was dissolved in DCM (37 mL). HCI 1 M (12 mL) was added and the mixture was stirred for 5 h at room temperature. After completion of the reaction, brine was added. The aqueous layer was extracted with DCM (2 x). The combined organic layers were dried over MgSC>4, filtered and concentrated under reduced pressure. The crude was purified by flash chromatography using cyclohexane / EtOAc (1 :0 to 6:4) as eluent to give intermediate 5 (2.23 g, 7.67 mmol, 68%) as a mixture of two diastereoisomers and a yellow oil.1H NMR (300 MHz, CDCI3) 6 7.41 - 7.27 (m, 5H), 4.60 (s, 2H), 3.91 - 3.79 (m, 1 H), 3.67 - 3.63 (m, 3H), 2.87 - 2.65 (m, 1 H), 2.50 - 2.20 (m, 6H), 2.15 - 1.98 (m, 1 H), 1.87 - 1.68 (m, 1 H), 1.66 - 1.42 (m, 2H) ppm.

[0454] Synthesis of (3S,7a / ?,9 / ?,11a / ?)-9-benzyloxy-3-isopropyl-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-5-one (intermediate 6) and (3S,7a / ?,9S,11a / ?)-9- benzyloxy-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one (intermediate 7)

[0455] Under Ar, intermediate 5 (2.2 g, 7.58 mmol, 1 eq) was dissolved in anhydrous toluene (22 mL) then (2S)-2-amino-3-methyl-butan-1-ol (938 mg, 9.09 mmol, 1.2 eq) and 2,2- dimethylpropanoic acid (929 mg, 9.09 mmol, 1.2 eq) were added at room temperature. The mixture was heated to reflux and stirred overnight. The solvent was evaporated and the residue was dissolved in DCM and brine. The aqueous layer was extracted with DCM (3 x). The combined organic layers were dried over MgSCU, filtered and concentrated under reduced pressure. The crude was purified by flash chromatography using cyclohexane / EtOAc (1 :0 to 1 :1) to give the desired intermediate 6 and 7 (1.93 g, 5.61 mmol, 74%) as a colorless solid for intermediate 6 and a brown oil for intermediate 7.

[0456] Intermediate 6:1H NMR (300 MHz, CDCI3) 6 7.39 - 7.24 (m, 5H), 4.49 (d, J = 1.3 Hz, 2H), 4.15 - 4.05 (m, 1 H), 4.02 (t, J = 8.0 Hz, 1 H), 3.74 (dd, J = 8.3, 6.4 Hz, 1 H), 3.70 - 3.64 (m, 1 H), 2.61 - 2.49 (m, 1 H), 2.49 - 2.23 (m, 2H), 2.08 - 1.85 (m, 5H), 1.82 - 1.64 (m, 4H), 0.96 (d, J = 6.9 Hz, 3H), 0.91 (d, J = 6.7 Hz, 3H) ppm.

[0457] Intermediate ?:1H NMR (300 MHz, CDCh) 6 7.38 - 7.23 (m, 5H), 4.54 (s, 2H), 4.13 - 4.04 (m, 1 H), 4.07 - 3.97 (m, 1 H), 3.80 - 3.71 (m, 1 H), 3.64 - 3.50 (m, 1 H), 2.61 - 2.48 (m, 1 H), 2.44 - 2.29 (m, 1 H), 2.08 - 1.87 (m, 5H), 1.87 - 1.75 (m, 2H), 1.75 - 1.59 (m, 3H), 0.94 (d, J = 6.90 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H) ppm.

[0458] Synthesis of (3S,7aR, 9R, 11aR)-9-hydroxy-3-isopropyl-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-5-one (intermediate 8) and (3S,7aR, 9S, 11aR)-9- hydroxy-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-5-one (intermediate 9)

[0459] General procedure 1 : Deprotection of benzyl group lnt 6-7

[0460] Intermediate 6-7 was dissolved in analytical grade MeOH (C = 0.05 mol / L). The mixture was hydrogenated using H-Cube® in continuous flow using a 10% Pd / C or 20% Pd(OH)2 cartridge. MeOH was evaporated under reduced pressure to give the desired intermediates 8-9.

[0461] General procedure 2: preparation of [4-[(4-substitutedphenyl)-(2,2,2- trichloroethanimidoyl)oxy-methyl]phenyl] intermediates 13-15

[0462] 10, R1 = CF3Int 13, R1 = CF3

[0463] 11, R1 = F I nt 14, R1 = F

[0464] 12, R1 = Cl Int 15, R1 = Cl

[0465] Under Ar, intermediate 10-12 (1 eq) was dissolved in dry DCM (C = 0.5 mol / L) then trichloroacetonitrile (10 eq) was added followed by DBU (0.1 eq). The mixture was stirred for 4 h at room temperature. The solvent was evaporated and the residue was purified by flash chromatography using 3% Et3N in cyclohexane / EtOAc (80:1) as eluent to give the desired intermediates 13-15.

[0466] General procedure 3: Functionalization step

[0467]

[0468] Int 14, R1 = F

[0469] Int 15, R1 = Cl Ex 3 and 4, R1 = CF3

[0470] Ex 5 and 6, R1 = F

[0471] Ex 7 and 8, R1 = Cl

[0472] Under Ar, intermediate 8-9 (1 eq) and intermediate 13-15 (1.2 equiv) were dissolved in dry toluene. TMSOTf (0.5 eq) was added and the mixture was heated to 110 °C and stirred for 2 h to overnight. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography to give the desired exemples 3-8. Synthesis of Tert-butyl N-[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo- 3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]carbamate (intermediate 16)

[0473] Int 16

[0474] Intermediate 16 was prepared according to the procedure described by our team (Tangara S, FaTon L, Piveteau C, Capet F, Godelier R, Michel M, Flipo M, Deprez B, Willand N, Villemagne B. Pharmaceuticals. 2023, 16(3), 413. https: / / doi.org / 10.3390 / ph16030413).

[0475] Deprotection of Boc group from intermediate 16

[0476] Int 16

[0477] Intermediate 16 was dissolved in 1 ,4-dioxane (0.05 M), then HCI in solution in 1 ,4- dioxane (4N, 10 eq) was added. The mixture was stirred at room temperature until full conversion of the starting material following by TLC or LC-MS. The solvent was removed under vacuum to afford intermediate 17 in a quantitative yield as a white amorphous solid. The crude product obtained was engaged into the next step reaction without any further purification.

[0478] (3S,7aR,9S,11aR)-9-amino-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H- oxazolo[2,3-j]quinolin-5-one;hydrochloride (intermediate 17)1H NMR (300 MHz, D2O): 5 4.04 (dd, J = 7.2 Hz, J = 8.4 Hz, 1 H), 3.92 (ddd, J = 1 .7 Hz, J = 6.4 Hz; J = 14.5 Hz, 1 H), 3.82 (dd, J = 6.4 Hz, J = 8.4 Hz, 1 H), 3.46 - 3.31 (m, 1 H), 2.52 (dd, J = 5.1 Hz, J = 18.5 Hz, 1 H), 1.41 - 2.24 (m, 1 H), 2.11 - 1.42 (m, 10H), 0.82 - 0.75 (m, 6H) ppm. [ES+MS] m / z 253 (MH+- HCI). Synthesis of (3S,7aR,9R,11aR)-9-amino-3-isopropyl-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-5-one (Intermediate 18)

[0479] NaHB(OAc)3 (1.5 eq) was slowly added to a solution of intermediate 3 (1 eq) and benzylamine (1.1 eq) in DCE and the reaction was stirred at 70°C for 4 h. The mixture was quenched with water, extracted with DCM, dried over MgSC>4, filtrated and evaporated to dryness. The crude was dissolved in dry MeOH, ammonium formate (10 eq) and PD / C (10%, 0.1 eq) were added and the mixture was refluxed 4 h. The reaction was filtrated through a pad of silica, washed with DCM and evaporated to dryness. Purification over silica gel using flash chromatography (DCM / MeOH 10 / 0 to 8 / 2) afforded the desired intermediate 18 as a white powder (660 mg, 75%).

[0480] 1H NMR (300 MHz, CDCI3) 6 4.14 - 3.98 (m, 2H), 3.76 - 3.68 (m, 1 H), 3.33 (s, 1 H), 2.63 - 2.40 (m, 2H), 2.37 - 2.20 (m, 1 H), 2.08 (m, 2H), 1.95 (m, 1 H), 1.91 - 1.78 (m, 1 H), 1.78 - 1 .43 (m, 7H), 0.96 (d, J = 6.9 Hz, 3H), 0.90 (d, J = 6.7 Hz, 3H).

[0481] Functionalization of intermediates 17-18

[0482] General procedure 4: preparation of monoalkylated intermediates from intermediate 17-18 via reductive amination

[0483] Int 19-31

[0484] Ex 9-19

[0485] Intermediate 17-18 (1 eq) was dissolved in methanol. Then appropriate carbonyl (1- 3 eq) (ketone or aldehyde), tetraisopropoxytitanium (0-3 eq) and DIEA (2 eq) were added. The mixture was stirred at 70°C overnight. The reaction was allowed to cool to room temperature, then NaBH4 (3 eq) was added, the mixture was stirred for 1h. The reaction mixture was either directly purified by flash chromatography or extracted with dichloromethane and water, washed with brine, dried over MgSC>4 before purification.

[0486] Second functionalization step:

[0487]

[0488] General procedure 5: preparation of dialkylated compounds from monalkylated intermediates via nucleophilic substitution

[0489] The appropriate intermediate was dissolved in ACN, the appropriate halogenated reactant (1-2 eq), TEA (3 eq) or DI PEA (1.5-3 eq), and Nal (if needed, 1.5 -3 eq) were added. The mixture was stirred overnight at room temperature or heated at 70 °C until complete conversion of the monoalkylated intermediate. The solvent was removed in vacuo. The mixture was then quenched with water, extracted with AcOEt, washed with brine, dried over MgSC>4, filtrated and evaporated to dryness under vacuum to give the crude compound which was purified by flash chromatography.

[0490] General procedure 6: preparation of dialkylated compounds from monalkylated intermediates via reductive amination

[0491] The appropriate intermediate was dissolved in 1 ,2-dichloroethane, then appropriate carbonyl (2 eq) (ketone or aldehyde), Ti(O / Pr)4 (2 eq), (CHsCOCOsBHNa (2eq) and TEA (3 eq) were added and the mixture was stirred at reflux overnight. The reaction was quenched with water, extracted with dichloromethane, dried over MgSC>4, filtrated and evaporated to dryness under vacuum to give the crude compound which was purified by flash chromatography.

[0492]

[0493] General procedure 7: deprotection of Boc protecting group of piperidines and pyrrolidines analogs

[0494] Ex 25, 27-30, 35

[0495] The appropriate N-Boc lactam was dissolved in 1 ,4-dioxane (0.05 M), then HCI in solution in 1 ,4-dioxane (4N, 10 eq) was added. The mixture was stirred at room temperature for 5-48 h. When the conversion of the starting material was judged complete by TLC or LC-MS, the solvent was removed under vacuum, the crude product was triturated with Et20, filtrated and dried to obtained the desired product without any further purification.

[0496] General procedure 8: deprotection of Boc protecting group of azetidine analogs

[0497] Example 23 or example 24 (1 eq) was dissolved in DCM (0.01 M), then 2,6-lutidine (6 eq) and TMSOTf (14 eq) were added. The solution was stirred at room temperature until complete conversion of the starting material judged by LC-MS. The mixture was concentrated under vacuum to give the crude product which was purified by reverse phase preparative HPLC using H2O + 0.1 % HCOOH / MeCN + 0.1% HCOOH gradient from 90 / 10 to 0 / 100 to afford the corresponding desired product.

[0498] Substitution of azetidine ring

[0499] General procedure 9: acylation of the azetidine

[0500] Example 23 (1 eq) was dissolved in a 1 :1 mixture DCM / TFA (2 mL) and the solution was stirred 3 h at room temperature. The solvent was removed under vacuum, the crude was dissolved in THF, the appropriate acyl chloride (2 eq) and TEA (3 eq) were added at 0°C and the mixture was stirred 5 h at room temperature. The reaction was quenched with water, extracted with AcOEt, washed with brine, dried over MgSCU, filtrated and evaporated to dryness under vacuum.

[0501] General procedure 10: alkylation of azetidine by nucleophilic substitutions using alkyl halides Example 23 (1 eq) was dissolved in a 1 :1 mixture DCM / TFA (2 mL) and the solution was stirred 3 h at room temperature. The solvent was removed under vacuum, the crude was dissolved in ACN, the appropriate halogenated reactant (2 eq) and TEA (3 eq) were added and the mixture was stirred overnight at 70°C. The reaction was quenched with water, extracted with AcOEt, washed with brine, dried over MgSO4, filtrated and evaporated to dryness under vacuum.

[0502] General procedure 11 : alkylation of azetidine by reductive aminations

[0503] Example 23 (1 eq) was dissolved in a 1 :1 mixture DCM / TFA (2 mL) and the solution was stirred 3 h at room temperature. The solvent was removed under vacuum, the crude was dissolved in 1 ,2-dichloroethane, the appropriate carbonyl (2 eq) (ketone or aldehyde), Ti(OPr)4 (2 eq), (CHsCOO^BHNa (2 eq) and TEA (3 eq) were added and the mixture was stirred at reflux overnight. The reaction was quenched with water, extracted with dichloromethane, dried over MgSO4, filtrated and evaporated to dryness under vacuum.

[0504]

[0505] Part B: Activity of the compounds according to the invention

[0506] Determination of MICs

[0507] The minimum inhibitory concentration (MIC) of compounds against Mtb was determined using the resazurin microtiter assay (REMA) in multiwell plates. Briefly, mycobacteria were grown to mid-log phase in complete Middlebrook 7H9 media and diluted to an ODeoo of 0.001. The bacterial suspension was then added to the wells of a 96-well plate (200 pL to the first column of wells and 100 pL to all other wells). Test compounds were then spiked into the first well, and serially diluted down the plate using a multichannel pipette. Plates were incubated for 8-10 doubling times (37°C, 6 days) and bacterial viability was determined by OD600 measurement, GFP fluorescence measurement (where mycobacterium is expressing GFP), or by subsequent addition of resazurin (10 pL of 0.025% (w / v) resazurin). For the late resazurin assay, bacteria were incubated (37°C, overnight) and viability determined by measuring resorufin production [Ex 530nm, Em 590nm] using a fluorescence microplate reader. The MIC of compounds against Mtb was considered to be the lowest compound concentration where resazurin turnover was less than 2%, 5% or 10% (depending on assay readout) of the background fluorescence.

[0508] Results are mentioned in Table 7.

[0509] Table 7: activity of compounds according to the invention - MIC activity range : +++ indicates <0.5 pM, ++ indicates between 0.5-5 pM, + indicates > 5 pM. MIC determined using resazurin reduction assay as a surrogate for bacterial viability.

Claims

CLAIMS1. A compound of formula (I):In which : p has a value of 0 or 1 ; p’ has a value of 1 or 2; n has a value of 1 or 2;R is: o NRaRb; or o ORc; o Ra and Rb identical or different are chosen from:■ H■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;■ linear or branched -(Ci-C6)halogenoalkyl ;■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogenatom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;■ linear or branched -(C2-C6)alkene-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched - (C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-C6)alkyl, linear or branched -(Ci- C6)halogenoalkyl, halogen atom;■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom, -OH, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZi being linked to the heterocycle by the nitrogen atom; provided that:■ Ra and Rb can not be both a linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, and■ when Ra is H, Rb can not be H or linear or branched -(Ci-C6)alkyl-(C6-C )aryl, said aryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , o Rc is :■ linear or branched -(Ci-C6)halogenoalkyl ;■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;■ -(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom;■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; or■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom, cyano, methyl sulfone; o Z1 is chosen from linear or branched -(Ci-Ce)alkyl, -(Cs-Ce) cycloalkyl ; o Z2 is H, -(Cs-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

2. A compound according to claim 1 wherein: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ;R is: o NRaRb; or o ORc; o Ra is:■ H■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl; or■ linear or branched -(Ci-C6)alkyl-(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom, said aryl and heteroaryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl , halogen atom, -OH, linear or branched -(C1-C6)alkyl, linear or branched -(C1-C6)alkoxy, linear or branched -(C1-C6) halogenoalkoxy; o Rb is :■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;■ linear or branched -(Ci-C6)halogenoalkyl ;■ linear or branched -(Ci-C6)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;■ linear or branched -(C2-C6)alkene-(C6-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;■ -(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(C1- Ce)halogenoalkyl;■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl, halogen atom;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom;■ linear or branched -(Ci-C6)halogenoalkyl ;■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;■ -(C6-Cw)heteroaryl, said heteroaryl having at least one nitrogen atom and being optionally substituted by one or more linear or branched - (Ci-Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;■ linear or branched -(Ci-C6)alkyl-(Cs-Cio)heteroaryl, said heteroaryl having at least one hetero atom chosen from O, N or S, and being optionally substituted by one or more linear or branched -(C1- Ce)alkyl, linear or branched -(Ci-C6)halogenoalkyl;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZi or COZ2, said substituents COOZi or COZ2 being linked to the heterocycle by the nitrogen atom; or■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZi when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom ;or■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom; en from linear or branched -(Ci-Ce)alkyl, -(Cs-Ce) cycloalkylo Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; or its pharmaceutically acceptable salts or optical isomers.

3. A compound according to claim 1 or 2, wherein: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:■ H■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl; or■ linear or branched -(Ci-C6)alkyl-(C6-C )heteroaryl, said heteroaryl having at least one nitrogen atom, said aryl and heteroaryl being optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl ; and / or o Rb is :■ -(Ca-Ce) cycloalkyl optionally substituted by one or more linear or branched -(Ci-C3)alkyl, OH, halogen atom;■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;■ linear or branched -(Ci-C6)halogenoalkyl ;■ linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is interrupted by a SO2 group ;■ linear or branched -(C2-C6)alkene-(C6-C )aryl substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl, or when the heterocycle comprises a nitrogen atom, by COOZ1 or COZ2, said substituents COOZ1 or COZ2 being linked to the heterocycle by the nitrogen atom; or■ linear or branched -(Ci-C6)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more COOZ1when the heterocycle comprises a nitrogen atom, said COOZ1 being linked to the heterocycle by the nitrogen atom; o Zi is chosen from linear or branched -(Ci-Ce)alkyl, -(Ca-Ce) cycloalkyl o Z2 is H, -(Ca-Ce) cycloalkyl, linear or branched -(Ci-Ce)alkyl, wherein the alkyl chain is eventually interrupted by a O; and / or o Rc is :■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atoms; or its pharmaceutically acceptable salts or optical isomers.

4. A compound according to any one of claims 1 to 3, wherein said compound if chosen from :(3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-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]methoxy]-3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[cyclohexylmethyl-[[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)-9-[cyclopropylmethyl-[[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-[oxetan-3-yl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;- tert-butyl 3-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]azetidine-1-carboxylate;- tert-butyl 3-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]azetidine-1 -carboxylate;- tert-butyl (2R)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate;- tert-butyl (2S)-2-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate;- tert-butyl 3-[(1 R)-1-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]ethyl]azetidine-1 -carboxylate;- tert-butyl 3-[(1 S)-1-[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]ethyl]azetidine-1 -carboxylate;- tert-butyl (3R)-3-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate;- tert-butyl (3S)-3-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate;- tert-butyl 4-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]piperidine-1-carboxylate;- tert-butyl (2R)-2-[[[(3S,7aR,9S, 11 aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9, 10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]pyrrolidine-1 -carboxylate;- tert-butyl (2S)-2-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11- octahydro-2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]methyl]pyrrolidine-1 -carboxylate; (3S,7aR,9S,11aR)-9-[azetidin-3-yl-[[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-[[(2S)-2-piperidyl]methyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-2-piperidyl]methyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[(2R)-2-piperidyl]methyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[(3S)-3-piperidyl]methyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;((3S,7aR,9S,11aR)-3-isopropyl-9-[[(3R)-3-piperidyl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;dihydrochloridej]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[4-piperidylmethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[(2R)-pyrrolidin-2-yl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[(2S)-pyrrolidin-2-yl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[(4-hydroxy-4-methyl-cyclohexyl)-[[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)-9-[cyclopropylmethyl-[[6-(trifluoromethyl)-3- pyridyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;- tert-butyl 3-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[6-(trifluoromethyl)-3- pyridyl]methyl]amino]methyl]azetidine-1 -carboxylate;- tert-butyl 3-[[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[5-(trifluoromethyl)-2- pyridyl]methyl]amino]methyl]azetidine-1 -carboxylate;- (3S,7aR,9S,11aR)-9-[[1-(2-fluoroethyl)azetidin-3-yl]-[[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)-9-[[1-(3-fluoropropyl)azetidin-3-yl]-[[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]methyl-[1-(3,3,3- trifluoropropyl)azetidin-3-yl]amino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[1-(cyclopropanecarbonyl)azetidin-3-yl]-[[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-[[1-(2-methoxyacetyl)azetidin-3-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;- (3S,7aR,9S,11aR)-9-[(1-acetylazetidin-3-yl)-[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-5-one;3-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro-2H- oxazolo[2,3-j]quinolin-9-yl]-[[4-(trifluoromethyl)phenyl]methyl]amino]azetidine-1- carbaldehyde;- tert-butyl 4-[[(3S,7aR,9S,11aR)-3-isopropyl-5-oxo-3,6,7,7a,8,9,10,11-octahydro- 2H-oxazolo[2,3-j]quinolin-9-yl]-[[4- (trifluoromethyl)phenyl]methyl]amino]piperidine-1 -carboxylate;(3S,7aR,9S,11aR)-3-isopropyl-9-[4-piperidyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;3S,7aR,9S,11aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[2-fluoroethyl-[[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-[3-methylsulfonylpropyl-[[4- (trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;- (3S,7aR,9S,11aR)-9-[(4,4-difluorocyclohexyl)-[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[3-fluoropropyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[cyclopropyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[cyclobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[2-fluoroethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[3-fluoropropyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[4-fluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[4-fluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-ylmethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[(1R)-2,2-difluorocyclopropyl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[(1S)-2,2-difluorocyclopropyl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3-isopropyl-3,6,7,7a,8,9,10,11-octahydro- 2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[(1-methylindol-2-yl)methylamino]- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[1-(4,4,4-trifluorobutyl)azetidin-3-yl]-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]allylamino]- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R,11aR)-3-isopropyl-9-[2-[4-(trifluoromethyl)phenyl]allylamino]-3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[8-fluoro-2-(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[2,8-bis(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[7-fluoro-2-(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[[6,7-difluoro-2-(trifluoromethyl)-4-quinolyl]methylamino]-3- isopropyl-3,6,7,7a,8,9, 10, 11 -octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methylamino]- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R,11aR)-3-isopropyl-9-[[2-(trifluoromethyl)-4-quinolyl]methylamino]- 3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one; (3S,7aR,9S,11aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one; or its pharmaceutically acceptable salts or optical isomers.

5. A compound according to any one of claims 1 to 3, wherein: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl, optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl ; and / or o Rb is :■ linear or branched -(Ci-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by one or more halogen atom;■ linear or branched -(Ci-C6)halogenoalkyl ;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C6)halogenoalkyl;■ linear or branched -(Ci-C3)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; oro Rc is :■ linear or branched -(Ci-C6)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl; or■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom; or its pharmaceutically acceptable salts or optical isomers.

6. A compound according to any one of claims 1-3 or 5, wherein: p has a value of 1 ; p’ has a value of 1 ; n has a value of 2 ; o Ra is:■ linear or branched -(Ci-C3)alkyl-(C6-C )aryl, optionally substituted by one or more linear or branched -(C1-C3) halogenoalkyl ; and / or o Rb is :■ linear or branched -(Ci-C3)alkyl-(C3-C6)cycloalkyl;■ linear or branched -(Ci-C6)halogenoalkyl ;■ heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N; said heterocycle being optionally substituted by one or more linear or branched -(Ci-C3)halogenoalkyl; linear or branched -(Ci-C3)alkyl-heterocycle comprising 3 to 10 members and having at least one hetero atom chosen from O, N;; and / or o Rc is :■ linear or branched -(Ci-C3)alkyl-(C6-C )aryl optionally substituted by one or more linear or branched -(C1-C3) halogenoalkyl; or■ CHY1Y2 with Y1 and Y2 being a -(Ce-Cio)aryl substituted by one or more linear or branched -(Ci-Ce) halogenoalkyl, halogen atom; or its pharmaceutically acceptable salts or optical isomers.

7. A compound according to any of the preceding claims, wherein said compound if chosen from :(3S,7aR,9S,11aR)-3-isopropyl-9-[[4-(trifluoromethyl)phenyl]methoxy]-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]methoxy]-3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[cyclopropylmethyl-[[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-[oxetan-3-yl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;- (3S,7aR,9S,11aR)-9-[[1-(2-fluoroethyl)azetidin-3-yl]-[[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)-9-[[1-(3-fluoropropyl)azetidin-3-yl]-[[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]methyl-[1-(3,3,3- trifluoropropyl)azetidin-3-yl]amino]-3,6,7,7a,8,9,10,11-octahydro-2H-oxazolo[2,3- j]quinolin-5-one;3S,7aR,9S,11aR)-3-isopropyl-9-[4,4,4-trifluorobutyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11 -octahydro-2 H- oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[2-fluoroethyl-[[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)-9-[bis[4-(trifluoromethyl)phenyl]methoxy]-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]methoxy]-3-isopropyl-3,6, 7, 7a, 8, 9, 10, 11 -octahydro-2H-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[bis(4-fluorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9R, 11 aR)-9-[bis(4-chlorophenyl)methoxy]-3-isopropyl- 3,6,7,7a,8,9,10,11-octahydro-2 / 7-oxazolo[2,3-j]quinolin-5-one;(3S,7aR,9S,11aR)-3-isopropyl-9-[oxetan-3-ylmethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-3,6,7,7a,8,9, 10, 11-octahydro-2 / 7- oxazolo[2,3-j]quinolin-5-one; or its pharmaceutically acceptable salts or optical isomers.

8. A pharmaceutical composition comprising a compound according to any of claims 1 to 7.

9. A compound according to any of claims 1 to 7 or a pharmaceutical composition according to claim 8 for use as a drug.

10. A compound or a pharmaceutical composition for use according to claim 9, for the prevention and / or treatment of a mycobacterial infection or for the treatment of a disease caused by infection with a mycobacterium.

11. A compound or a pharmaceutical composition for use according to claim 10, wherein the mycobacterial infection is a Mycobacterium tuberculosis infection.

12. A compound or a pharmaceutical composition for use according to any of claims 9 to 11 , for the prevention and / or treatment of tuberculosis.

13. A compound or a pharmaceutical composition for use according to any of claims 9 to 12, wherein said compound or pharmaceutical composition is used in combination with at least one other anti-mycobacterial agent.

14. A combination of (a) a compound of Formula (I) as defined in any one of claims 1 to 7 and (b) at least one other anti-mycobacterial agent.

15. A pharmaceutical composition according to claim 8, a compound or pharmaceutical composition for use according to any of claims 9 to 13, or combination according to claim 14, wherein said at least one other anti- mycobacterial agent is an anti-tuberculosis agent.

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