Novel benzothiazepine derivatives, processes for their preparation and therapeutic uses thereof

Abstract

Disclosed herein are compounds of the formula (I) or a pharmaceutically acceptable salt thereof (I) wherein X1 represents a -NH- or -O- group, X3-X2 represents a =CH-CH=C- group, a =CH- N=C- group, or a =N-N- group, Z represents a bridged (C5-C8)cycloalkyl group, R1 represents an oxadiazole group, which may be optionally substituted and partially saturated, a tetrazolyl group, a -COOR7 group, a -OCOR8 group, a hydroxy group or a (C1-C6)alkoxy group, a -NRaRb group, a hetero(C3-C8)cycloalkyl group, a -CONHSO2R9 group, a halogen atom, a -NHCOR8 group, a -CONR8R8' group or a -COR8' group, R2 represents a halogen atom or a hydrogen atom, R4 represents a hydrogen atom, R5 represents various groups or alternatively R4 and R5 form together with the atoms to which they are attached a 5- or 6- membered ring optionally comprising a heteroatom, R represents a halogen atom, and n is 0, 1 or 2. Further disclosed are process for preparing the same, pharmaceutical compositions comprising them as well as said compounds of formula (I) for use in the treatment of cancer and infectious disease caused by viruses or bacteria.

Description

[0001] NOVEL BENZOTHIAZEPINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION AND THERAPEUTIC USES THEREOF Disclosed herein are novel substituted benzothiazepine derivatives, the processes for their preparation, as well as the therapeutic uses thereof, in particular as agents suitable for the treatment of neoplastic and / or infectious diseases, and more particularly as anticancer agents. Documents WO2016 / 139181 and WO2022 / 171745 disclose some substituted bicyclic tetrahydrothiazepine derivatives useful for the treatment of neoplastic and / or infectious diseases. The inventors have now found novel compounds able to treat neoplastic and / or infectious diseases. The compounds according to the present invention also present the advantage of reducing the risk of occurrence of and even avoiding drug-drug interaction. As it will be apparent in the experimental part, the compounds of the present invention have indeed been tested in a functional assay to assess their potency to enhance the cytokine production of sub-optimal-activated T cells as well as in test for evaluating their mechanism-based inactivation potential (MBI) in human hepatic microsomal fractions on Cytochrome P4503A4. Disclosed herein are compounds of the formula (I), or pharmaceutically acceptable salts thereof: wherein: - X1 represents a -NH- or -O- group, - X3-X2 represents a =CH-CH=C- group, a =CH-N=C- group, or a =N-N- group, - Z represents a bridged (C5-C8)cycloalkyl group, - R1 represents a group, wherein R3 represents a hydrogen atom or a group selected from ^ a hydroxy group or a (C1-C6)alkoxy group, ^ a -NRaRb group, wherein Ra and Rb independently represent a hydrogen atom or a (C1-C6)alkyl group, ^ a (C1-C6)alkyl group, optionally substituted by a -COOH group, by a -O-C(O)CH3group, by a hydroxy group, by a (C1-C4)alkoxy group, by a tetrazolyl group or by a benzyltetrazolyl group, ^ a fluoro(C1-C6)alkyl group, ^ a -COR6 group, wherein R6 represents a (C1-C4)alkyl group or a (C1-C4)alkoxy group, ^ a (C3-C7)cycloalkyl group, optionally substituted by a methyl group, by an amino group or by a halogen atom, ^ a bridged (C4-C8)cycloalkyl group, ^ a spiro(C5-C11)bicyclic ring, ^ a hetero(C3-C8)cycloalkyl group, optionally substituted by a (C1-C4)alkyl group, and ^ a hetero(C5-C6)aryl group, a group, wherein R3’ represents a group selected from ^ a (C1-C6)alkyl group, optionally substituted by a -COOH group, by a hydroxy group, or ^ a fluoro(C1-C6)alkyl group, a group, wherein R3” represents a hydrogen atom or a (C1-C6)alkyl group, a tetrazolyl group, a -COOR7 group, wherein R7 represents ^ a hydrogen atom, ^ a (C1-C6)alkyl group optionally substituted by a (C3-C7)cycloalkyl group, ^ a fluoro(C1-C6)alkyl group, ^ a (C3-C7)cycloalkyl group, ^ a hetero(C3-C8)cycloalkyl group, optionally substituted by a methyl group, or ^ a group , o a -OCOR8 group, wherein R8 represents a (C1-C6)alkyl group or a fluoro(C1-C6)alkyl group, o a hydroxy group, o a -NRaRb group, wherein Ra and Rb are as defined above, o a (C1-C4)alkoxy group, optionally substituted by a COOR7 group as defined above, o a hetero(C3-C8)cycloalkyl group, optionally substituted by one or two halogen atoms, o a -CONHSO2R9 group, wherein R9 represents a (C1-C4)alkyl group or a (C3-C7)cycloalkyl group, o a halogen atom, o a -NHCOR8 group, wherein R8 is as defined above, o a -CONR8R8’ group, wherein R8 is as defined above and R8’ is a hetero(C3-C8)cycloalkyl group, a hydrogen atom or a (C1-C4)alkyl group, or o a -COR8’ group, wherein R8’ is as defined above, - R2 represents a halogen atom or a hydrogen atom, - R4 represents a hydrogen atom, - R5 represents o a halogen atom, o a hydroxy group, o a (C1-C6)alkoxy group optionally substituted by a -COOH group, o a fluoro(C1-C6)alkoxy group, o a (C3-C7)cycloalkyl, optionally substituted by a (C1-C3)alkyl group, itself optionally substituted by a hydroxy group, o a (C3-C7)cycloalkyloxy group, o a hetero(C3-C8)cycloalkyl group, optionally substituted by a methyl group or by a -COOH group, o a hetero(C5-C6)aryl group, optionally substituted by a halogen atom, o a bridged hetero(C5-C8)cycloalkyl group, - or alternatively R4 and R5 form together with the atoms to which they are attached a 5- or 6-membered ring optionally comprising a heteroatom, and thus forming an optionally partially saturated (C5-C11)heteroaromatic bicyclic ring with the aryl or heteroaryl group to which they are attached, - R represents a halogen atom, and - n is 0, 1 or 2, provided that - (1) when R1 represents a and R3 is a tertiobutyl group, then R2 and R5 are not simultaneously respectively a hydrogen or fluorine atom and a - O-CH(CH3)2 group, - (2) R5 does not represent a -O-CH(CH3)2 group, when R1 represents o a group and R3 is a 1-methylcyclobutyl group, o a group and R3 is a tetrahydropyranyl group, o a 3-methyloxetan-3-yloxycarbonyl group, o a 1-methylcyclopropyloxycarbonyl group, o a tert-butoxycarbonyl group, or o a dimethylcarbamoyl group, - (3) when R1 represents a cyclohexoxycarbonyl group or a cyclopentoxycarbonyl group, then X1 does not represent a -NH- group, and - (4) when R1 is a fluorine atom, then R5 is not a dioxanyl group. The compounds of formula (I) can contain one or more asymmetric carbon atoms. They may therefore exist in the form of enantiomers. The compounds of formula (I) may be present as well under tautomer forms. The compounds of formula (I) may exist in the form of bases, acids, zwitterion or of addition salts with acids or bases. Hence, herein are provided compounds of formula (I) or pharmaceutically acceptable salts thereof, like in form of their hydrochlorides, oxalates, succinates, sulfates, tosylates, citrates, trifluoroacetates. These salts may be prepared with pharmaceutically acceptable acids or bases, although the salts of other acids or bases useful, for example, for purifying or isolating the compounds of formula (I) are also provided. As used herein, the terms below have the following definitions unless otherwise mentioned throughout the instant specification: - a halogen atom: a fluorine, a chlorine, a bromine or an iodine atom, and in particular a fluorine and a chlorine atom; - an alkyl group: a linear or branched saturated hydrocarbon-based aliphatic group comprising, unless otherwise mentioned, from 1 to 6 carbon atoms (noted “(C1-C6)-alkyl”). By way of examples, mention may be made of, but not limited to: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl and isohexyl groups, and the like; - a cycloalkyl group: a monocyclic alkyl group comprising, unless otherwise mentioned, from 3 to 7 carbon atoms, saturated or partially unsaturated and unsubstituted or substituted. By way of examples, mention may be made of, but not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclobutenyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, groups and the like, in particular a cyclopentyl, a cyclohexyl, a cycloheptyl, a cycloheptenyl, or a cyclohexenyl; - a heterocycloalkyl group: a 3 to 8-membered heterocycloalkyl, in particular a 3 to 6-membered cycloalkyl group, saturated or partially unsaturated, comprising 1 to 2 heteroatoms independently selected from oxygen, nitrogen and sulfur, in particular being oxygen or nitrogen. By way of examples, mention may be made of, but not limited to: azetidinyl, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, aziridinyl, oxanyl, oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, oxepanyl, diazepanyl, dioxanyl, dihydropyranyl, tetrahydropyranyl, and tetrahydrothiopyranyl. The heterocycloalkyl is advantageously aztidinyl, oxetanyl, piperidinyl, morpholinyl, dioxanyl, tetrahydropyranyl or tetrahydrofuranyl; - a fluoroalkyl group: an alkyl group as previously defined where the alkyl group is substituted with at least one fluorine atom. In other terms, at least one hydrogen atom of the alkyl group is replaced by a fluorine atom. By way of example, mention may be made of -CH2F, -CHF2, CH2CHF2, -CH2CH2F and the like. When all the hydrogen atoms belonging to the alkyl group are replaced by fluorine atoms, the fluoroalkyl group can be named perfluoroalkyl group. By way of example, mention may be made of trifluoromethyl group or trifluoroethyl group and the like; - an alkoxy group: an -O-alkyl group where the alkyl group is as previously defined. By way of examples, mention may be made of, but not limited to: methoxy, ethoxy, propoxy, isopropoxy, linear, secondary or tertiary butoxy, isobutoxy, pentoxy or hexoxy groups, and the like; - a fluoroalkoxy group: an -O-alkyl group where the alkyl group is as previously defined and where the alkyl group is substituted with at least one fluorine atom. In other terms, at least one hydrogen atom of the alkyl group is replaced by a fluorine atom. By way of example, mention may be made of -OCH2F, -OCHF2, -OCH2CH2F and the like. When all the hydrogen atoms belonging to the alkyl group are replaced by fluorine atoms, the fluoroalkoxy group can be named perfluoroalkoxy group. By way of example, mention may be made of trifluoromethoxy group and the like; - a heteroaryl group: a cyclic 5 to 10-membered aromatic group containing between 2 and 9 carbon atoms and containing between 1 and 4 heteroatoms, such as nitrogen, oxygen or sulfur, in particular a cyclic 5 to 6-membered aromatic group containing between 1 and 5 carbon atoms and containing between 1 and 4 heteroatoms selected from nitrogen and oxygen. Such nitrogen atom may be substituted with an oxygen atom in order to form a –N- O bond. Such -N-O bond can be in a form of a N-oxide (-N+-O-). Said heteroaryl group may be monocyclic or bicyclic. By way of examples of heteroaryl groups, mention may be made of, but not limited to: thiophene, furan, thiadiazole, thiazole, imidazole, tetrazole, pyridazine, triazine, pyrazine, oxadiazole, pyrazole, isothiazole, oxazole, isoxazole, pyridine, pyrimidine, benzotriazole, benzoxazole, pyrrolo[2,3-b]pyridine, benzimidazole, benzoxadiazole, benzothiazole, benzothiadiazole, benzofuran, indole, isoquinoline, indazole, benzisoxazole, benzisothiazole, pyridone groups and the like. The heteroaryl group is advantageously pyridine, pyrrole, imidazole, tetrazole, pyrazine, furane, thiazole, pyrazole, thiadiazole, pyridazine, pyridone and pyrimidine, and more particularly imidazole, tetrazole, pyrazole, and pyrimidine; - a “spirobicyclic ring”. Such spiro bicyclic alkyl generally comprises 5 to 11 carbon atoms referring to a “spiro(C5-C11)bicyclic ring”. The rings may be saturated or partially unsaturated. Such spirobicyclic ring may be unsubstituted or substituted, in particular by at least one (C1-C3)alkyl group such as methyl or a fluorine. In Addition, one to three carbon atoms may be replaced by a heteroatom selected from an oxygen atom and a nitrogen atom. By way of examples of spiro(C5-C11)bicyclic ring as for the definition of R6, mention may be made of, but not limited to: spiro[2.3]hexane, spiro[3.3]heptane, spiro[3.3]heptene, spiro[2.5]octane, 4,7-diazaspiro[2.5]octan-7-yl and 7-azaspiro[3.5]nonane. The spiro(C5- C11)bicyclic ring is advantageously azabicyclo[2.2.1]heptan-2-yl; - a “bridged (C5-C8)cycloalkyl” group, the rings share three or more atoms and the bridge contains at least one atom, for example 1, 2 or 3 atoms and preferentially 1 atom. By way of examples of such bridged cycloalkyl groups, mention may be made of, but not limited to bicyclo[3.2.1]octan-3-yl, bicyclo[2.2.2]octan-1-yl, bicyclo[2.1.1]hexan-1-yl, norpinan-1-yl, bicyclo[1.1.1]pentan-1-yl; bicyclo[2.2.1]heptan-2-yl and cubane; - a “bridged hetero(C5-C8)cycloalkyl” group, the rings have 2 to 4 carbon atoms replaced by a heteroatom selected from an oxygen atom and a nitrogen atom and share three or more atoms and the bridge contains at least one atom, for example 1, 2 or 3 atoms and preferentially 1 atom. By way of examples of such bridged cycloalkyl groups, mention may be made of azabicyclo[2.2.1]heptan-2-yl, oxabicyclo[2.2.2]octanyl and the like, and in particular of azabicyclo[2.2.1]heptan-2-yl; - a “heteroaromatic bicyclic ring”: a bicyclic ring having from 9 to 11 carbon atoms. Said bicyclic ring may be saturated or partially saturated. The rings have 1 to 4 carbon atoms replaced by a heteroatom selected from a sulfur, an oxygen atom and a nitrogen atom. By way of examples of such heteroaromatic bicyclic ring, mention may be made of indanyl, indolyl benzothiazolyl, indazolyl, benzotriazole, benzoxazole, pyrrolo[2,3-b]pyridine, benzimidazole, benzoxadiazole, benzothiazole, benzothiadiazole, benzisothiazole, benzisoxazole, indazole, pyrrolo[2,3-b]pyridine, quinoline, benzofuran and the like, and in particular of benzofuran. In one embodiment, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is characterized in that X3-X2 represents a =CH-CH=C- group. In one embodiment, the compound of formula (I), or a pharmaceutically In one embodiment, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is characterized in that Z represents a bicyclo[2.2.2]octan-1-yl, a bicyclo[2.1.1]hexan-1-yl, a norpinan-1-yl or a bicyclo[1.1.1]pentan-1-yl. In one embodiment, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is characterized in that R1 represents o a group group, wherein R3 represents a hydrogen atom or a group selected from ^ a hydroxy group, ^ a -CH(CH3)2COOH group, a tertiobutyl group, a 1-methyl-1-(2H- tetrazol-5-yl)ethyl group, a 1-(2-benzyltetrazol-5-yl)-1-methyl-ethyl group, a 2-hydroxy-1,1-dimethyl-ethyl group, a -CH(CH3)2COOCH3group, a 1-hydroxy-1-methyl-ethyl group, a hydroxymethyl group, a tert-butoxymethyl group, a methoxymethyl group, a ethyl group, a methyl group, ^ a 1-fluoro-1-methyl-ethyl group, a trifluoromethyl group, ^ a acetyl group, a ethoxycarbonyl group, ^ a 1-aminocyclobutyl group, a 3-fluorocyclobutyl group, a 1-methylcyclobutyl group, a cyclobutyl group, a cyclopropyl group, ^ a 1-bicyclo[1.1.1]pentanyl group, ^ a 4,7-diazaspiro[2.5]octan-7-yl group, ^ a morpholinyl group, a dioxanyl group, a piperidinyl group, a 1- methyl-4-piperidyl group, a tetrahydrofuranyl group, an oxetanyl group, a tetrahydropyranyl group, ^ a pyrimidinyl group, an imidazolyl group, o a group, wherein R3’ represents a group selected from ^ a (C1-C6)alkyl group, optionally substituted by a -COOH group, by a hydroxy group, or ^ a fluoro(C1-C6)alkyl group, group, wherein R3” represents a hydrogen atom or a tertio butyl group, o a tetrazolyl group, o a cyclohexoxycarbonyl group, a oxetan-3-yloxycarbonyl group, a tert- butoxycarbonyl group, a -COOH group, a 3-methyloxetan-3-yloxycarbonyl group, a 2,2,2-trifluoro-1,1-dimethyl-ethoxycarbonyl group, a group a methoxycarbonyl group, a 2- morpholinoethoxycarbonyl group, a tetrahydrofuranyloxycarbonyl group, a ethoxycarbonyl group, a tetrahydropyranyloxycarbonyl group, a cyclobutyloxycarbonyl group, a cyclopropyloxycarbonyl group, o a -O-COC(CH3)3group, a -O-COCH2CF3group, o a -OCH2COOC(CH3)3 group, o a 4,4-difluoro-1-piperidyl group, o a cyclopropylsulfonylcarbamoyl group, o a halogen atom, in particular a fluorine atom, o a propanoylamino group, o a N-methyl(tetrahydropyran-4-yl)carbamoyl group, an ethylcarbamoyl group, a N-diethylcarbamoyl group, a morpholinylcarbonyl group, or o a N-piperidine-1-carbonyl group, an azetidine-1-carbonyl group. In one embodiment, the compound of formula (I), or a pharmaceutically acceptable salt thereof, characterized in that R4 represents a hydrogen atom and R5 represents o a halogen atom, in particular a fluorine atom or a chlorine atom, o a hydroxy group, o an isopropoxy group, a methoxy group, a butoxy group, a carboxymethoxy group, o a 2,2,2-trifluoro-1-methyl-ethoxy group, a 2,2-difluoroethoxy group, o a hydroxymethylcyclopropyl group, a 1-methylcyclopropyl group, a cyclohexyl group, o a cyclobutoxy group, a cyclopropoxy group, o a 1-methyl-4-piperidyl group, a morpholinyl group, a 4-methylpiperazinyl group, a 1,4-dioxanyl group, a carboxypiperidinyl group, a tetrahydropyranyl group, o a 4-fluoropyrazolyl group, or o a azabicyclo[2.2.1]heptan-2-yl group. In one embodiment, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is characterized in that R4 and R5 form together with the atoms to which they are attached a benzofuranyl group. The compound of formula (I), or a pharmaceutically acceptable salt thereof, is characterized in that when R1 represents a cyclohexoxycarbonyl group or a cyclopentoxycarbonyl group, then X1 represents a -O- group. Among the compounds of formula (I) described herein, mention may be made in particular of the following compounds or a pharmaceutically acceptable salt thereof, in particular hydrochloride salt thereof: - 2-[5-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]-1,2,4- oxadiazol-3-yl]-2-methyl-propanoic acid; hydrochloride (1) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-[1-(hydroxymethyl)cyclopropyl]phenyl]methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (2) - (3R)-3-amino-N-[4-[3-(1-aminocyclobutyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (3) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-[1-methyl-1-(2H- tetrazol-5-yl)ethyl]-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide; acetate (4) - (3R)-3-amino-N-[4-[3-[1-(2-benzyltetrazol-5-yl)-1-methyl-ethyl]-1,2,4-oxadiazol- 5-yl]-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (5) - 2-[3-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]-1,2,4- oxadiazol-5-yl]-2-methyl-propanoic acid (6) - (3R)-3-amino-N-[4-[3-(4,7-diazaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (7) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(3-morpholin-2-yl- 1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (8) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(3- pyrimidin-5-yl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (9) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(3-morpholin-3-yl- 1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (10) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-(1-methyl-4-piperidyl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (11) - (3R)-3-amino-N-[4-[3-(1,4-dioxan-2-yl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (12) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-morpholinophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (13) - (3R)-3-amino-8-fluoro-5-[(4-methoxyphenyl)methyl]-N-[4-(3-morpholino-1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (14) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-[3-(1- piperidyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (15) - (3R)-3-amino-N-[4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (16) - (3R)-3-amino-8-fluoro-N-[4-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-3- yl]-1-bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (17) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-(4-fluoropyrazol-1-yl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (18) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-1,1,4-trioxo-5-[[4-(trideuteriomethoxy)phenyl]methyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (19) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-fluorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carboxamide (20) - (3R)-3-amino-N-[4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; trifluoroacetate (21) - (3R)-3-amino-8-fluoro-N-[4-[3-(3-fluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (22) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-(1-methyl-4- piperidyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (23) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (24) - (3R)-3-amino-8-fluoro-N-[4-[3-(1H-imidazol-5-yl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (25) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-hydroxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (26) - (3R)-3-amino-N-[4-[(4S)-4-tert-butyl-4,5-dihydrooxazol-2-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (27) - (3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro-N-[4-[3-(1- methylcyclobutyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (28) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(2-oxo- 3H-1,3,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (29) - [1-[5-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]-1,2,4- oxadiazol-3-yl]-1-methyl-ethyl] acetate (30) - (3R)-3-amino-N-[4-[3-(1-bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (31) - (3R)-3-amino-8-fluoro-N-[4-[3-(1-fluoro-1-methyl-ethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (32) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-5- [[4-(1,4-dioxan-2-yl)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (33) - (3R)-3-amino-N-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (34) - [4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxylate (35) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (36) - (3R)-N-[4-(3-acetyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-3-amino-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (37) - (3R)-3-amino-8-fluoro-N-[4-[3-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-5-yl]- 1-bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (38) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (39) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(3- tetrahydrofuran-2-yl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide isomer 1 (40) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(3- tetrahydrofuran-2-yl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide isomer 2 (41) - [4-(cyclohexoxycarbonyl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (42) - (3R)-3-amino-8-fluoro-1,1,4-trioxo-N-[4-[3-[(2R)-tetrahydrofuran-2-yl]-1,2,4- oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (43) - (3R)-3-amino-8-fluoro-1,1,4-trioxo-N-[4-[3-[(2S)-tetrahydrofuran-2-yl]-1,2,4- oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (44) - [4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl] 2,2- dimethylpropanoate (45) - [4-(oxetan-3-yloxycarbonyl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (46) - (3R)-3-amino-N-[4-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (47) - (3R)-3-amino-8-fluoro-N-[4-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (48) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-(oxetan-3-yl)- 1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (49) - (3R)-3-amino-N-[4-[3-(tert-butoxymethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (50) - ethyl 5-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]- 1,2,4-oxadiazole-3-carboxylate (51) - (3R)-3-amino-N-[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]- 8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (52) - (3R)-3-amino-8-fluoro-N-[4-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (53) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-1,1,4-trioxo-5-[[4- [(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxylate (54) - 4-[(3R)-3-amino-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]oxybicyclo[2.2.2]octane-1-carboxylic acid (55) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-8-fluoro-5-[(4- methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (56) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (57) - [4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl] 3,3,3- trifluoropropanoate; hydrochloride (58) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-8-fluoro-1,1,4- trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxylate (59) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]- 2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (60) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (61) - (3R)-3-amino-8-fluoro-1,1,4-trioxo-N-[4-(3-tetrahydropyran-4-yl-1,2,4-oxadiazol- 5-yl)-1-bicyclo[2.2.2]octanyl]-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (62) - tert-butyl 2-[[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1- bicyclo[2.2.2]octanyl]oxy]acetate (63) - (3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-N-[4-[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (64) - tert-butyl 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[6-[(1R)-2,2,2-trifluoro-1- methyl-ethoxy]-3-pyridyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (65) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-[3- (trifluoromethyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (66) - [4-(cyclohexoxycarbonyl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (67) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (68) - tert-butyl 4-[[(3R)-3-amino-5-[[4-[(2S)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (69) - tert-butyl 4-[[(3R)-3-amino-8-fluoro-5-[[4-(4-methylpiperazin-1- yl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (70) - tert-butyl 4-[[(3R)-3-amino-5-[[6-(2,2-difluoroethoxy)-3-pyridyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (71) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[[4-[(2R)-1,4- dioxan-2-yl]phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxylate (72) - (3-methyloxetan-3-yl) 4-[[(3R)-3-amino-5-[[4-(1,4-dioxan-2-yl)phenyl]methyl]-8- fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (73) - oxetan-3-yl 4-[[(3R)-3-amino-5-[[4-(1,4-dioxan-2-yl)phenyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (74) - (2,2,2-trifluoro-1,1-dimethyl-ethyl) 4-[[(3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2- yl]phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (75) - (3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro-N-[4-(1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (76) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(1,2,4-oxadiazol-5- yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide (77) - (2,2,2-trifluoro-1,1-dimethyl-ethyl) 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (78) - 4-[[(3R)-3-amino-5-[[4-(cyclobutoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (79) - 4-[[(3R)-3-amino-5-(benzofuran-5-ylmethyl)-8-fluoro-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (80) - tert-butyl 4-[[(3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (81) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-(methoxymethyl)- 1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (82) - (3R)-3-amino-N-[4-(4,4-difluoro-1-piperidyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5- [(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (83) - 4-[[(3R)-3-amino-5-[[4-(cyclopropoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (84) - 4-[[(3R)-3-amino-8-fluoro-5-[[4-(1-methylcyclopropyl)phenyl]methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylic acid; hydrochloride (85) - tert-butyl 4-[[(3R)-3-amino-1,1,4-trioxo-5-[[4-[(1S)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (86) - 4-[[(3R)-3-amino-5-[(4-butoxyphenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (87) - 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]norbornane-1-carboxylic acid; hydrochloride (88) - 4-[[(3R)-3-amino-5-[(2-chloro-4-methoxy-phenyl)methyl]-8-fluoro-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (89) - (3R)-3-amino-N-[4-(cyclopropylsulfonylcarbamoyl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (90) - (3-methyloxetan-3-yl) 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (91) - tert-butyl 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(2,2,2-trifluoro-1-methyl- ethoxy)phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (92) - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (93) - (3R)-1-[4-[[(3R)-3-amino-7-[(4-fluoro-1-bicyclo[2.2.2]octanyl)oxycarbonyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepin-5-yl]methyl]phenyl]piperidine-3- carboxylic acid (94) - 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.1.1]hexane-1- carboxylic acid (95) - (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (96) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4- (propanoylamino)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (97) - (4-methoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (98) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4- [methyl(tetrahydropyran-4-yl)carbamoyl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (99) - oxetan-3-yl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylate (100) - 4-[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carbonyl]oxybicyclo[2.2.2]octane-1-carboxylic acid (101) - 4-[[(3R)-3-amino-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (102) - 4-[[(3R)-3-amino-5-[(3,4-dichlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (103) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4- (piperidine-1-carbonyl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (104) - 2-morpholinoethyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (105) - [(3R)-tetrahydrofuran-3-yl] 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (106) - [(3S)-tetrahydrofuran-3-yl] 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (107) - (3R)-3-amino-N-[4-(3-ethyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (108) - (4-ethoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (109) - (3R)-3-amino-N-[4-(azetidine-1-carbonyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (110) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(5-methyl-1,3,4- oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (111) - (3R)-3-amino-N-[4-(ethylcarbamoyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide (112) - tetrahydropyran-4-yl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (113) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(3-methyl-1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (114) - cyclobutyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylate (115) - cyclopropyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylate (116) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(2H- tetrazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (117) - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(morpholine-4- carbonyl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carboxamide; hydrochloride (118) - tert-butyl 4-[[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate (119) - (3R)-3-amino-N-[4-(diethylcarbamoyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (120) - 5-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]norpinane-1-carboxylic acid (121) - ethyl 4-[[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (122) - tert-butyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate (123) - ethyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate; hydrochloride (124) - 4-[[(3R)-3-amino-5-[[4-[(1S,4R)-2-azabicyclo[2.2.1]heptan-2-yl]phenyl]methyl]-8- fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (125) - 2-[4-[[(3R)-3-amino-8-fluoro-7-[(4-fluoro-1-bicyclo[2.2.2]octanyl)carbamoyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepin-5-yl]methyl]phenoxy]acetic acid; hydrochloride (126) - 3-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[1.1.1]pentane-1- carboxylic acid; hydrochloride (127) - 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[(4-tetrahydropyran-4-ylphenyl)methyl]- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (128) - methyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate; hydrochloride (129) - 4-[[(3R)-3-amino-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (130) - 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (131) - 4-[[(3R)-3-amino-5-[(1-cyclohexylpyrazol-3-yl)methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (132) - 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (133) - 4-[[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (134) - (3R)-1-[4-[[(3R)-3-amino-8-fluoro-7-[(4-fluoro-1- bicyclo[2.2.2]octanyl)carbamoyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepin-5- yl]methyl]phenyl]piperidine-3-carboxylic acid; hydrochloride (135) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; succinate (salt of compound (61) above) (136) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; citrate (salt of compound (61) above) (137) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; sulfate (salt of compound (61) above) (138) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; tosylate (salt of compound (61) above) (139) - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (salt of compound (61) above) (140) or - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; oxalate (salt of compound (61) above) (141). Another embodiment is a compound selected from the above list, or a pharmaceutically acceptable salt thereof, for use in therapy, in particular in the treatment of neoplastic and / or infectious diseases, especially in the treatment of cancer. Another embodiment is a method of treating neoplastic and / or infectious diseases, especially of treating cancer, comprising administering to a subject in need thereof, in particular a human, a therapeutically effective amount of a compound selected from the above list, or a pharmaceutically acceptable salt thereof. Another embodiment is the use of a compound selected from the above list, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament useful in treating neoplastic and / or infectious diseases, especially in treating cancer. Another embodiment is a pharmaceutical composition comprising as active principle an effective dose of a compound selected from the above list, or a pharmaceutically acceptable salt thereof, and also at least one pharmaceutically acceptable excipient. The compounds of the formula (I) can be prepared by the following processes. The compounds of the formula (I) and other related compounds having different substituents are synthesized using techniques and materials described below or otherwise known by the skilled person in the art. In addition, solvents, temperatures and other reaction conditions presented below may vary as deemed appropriate to the skilled person in the art. General below methods for the preparation of compounds of formula (I) optionally modified by the use of appropriate reagents and conditions for the introduction of the various moieties found in the formula (I) are described below. The following abbreviations and empirical formulae are used: Boc Tert-butyloxycarbonyl Cbz Carboxybenzyle DCM Dichloromethane DCC N,N'-Dicyclohexylcarbodiimide DIAD Diisopropyl azodicarboxylate DIPEA N,N-diisopropylethylamine DMAP 4-dimethylaminopyridine DMF N,N-dimethylformamide DMSO Dimethyl sulfoxide EtOAc Ethyl acetate EtOH Ethanol H2 Hydrogen HCl Hydrochloric acid iPrOAc Isopropyl acetate LiOH Lithium hydroxide MeCN Acetonitrile MeOH Methanol MgSO4 Magnesium sulfate N2Nitrogen NaH Sodium hydride NaHCO3 Sodium bicarbonate Na2SO4Sodium sulfate Pd / C Palladium on carbon Pg Protecting group PPh3Triphenylphosphine RT Room temperature Rt Retention time TBDMS Tert-Butyldimethylsilyl TBTU 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate TEA Triethylamine TFA Trifluoroacetic acid THF Tetrahydrofuran T3P (PPAA) Propanephosphonic acid anhydride SCHEME 1: Preparation of compounds of formula (I), wherein X1 represents a -NH-

[0002] group – General process – method A According to SCHEME 1, in which R1, R2, R4, R5, X2, X3, R, Z and n are as defined above and Pg is a protecting group (Pg), wherein Pg is for example a Boc group or a Cbz group, intermediate (A) can be converted in STEP 1 to intermediate (C) by treatment with TBTU in the presence of TEA by reacting with intermediate (B), and stirred for example at RT. Alternatively, said coupling STEP 1 may be performed with other reactants such as T3P, in presence of DIPEA in a solvent such as DCM. Intermediate (C) can be converted in STEP 2 to compound of formula (I), wherein X1 represents a -NH- group in a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane typically when Pg is a Boc group. Alternatively, when Pg is a Cbz group, which may be particularly useful for the obtention of compounds of formula (I), wherein R1 comprises a carbonyl or carbamoyl function, then the deprotection step may be performed by treatment with Pd / C in MeOH in H2 atmosphere. SCHEME 2: Preparation of compounds of formula (I), wherein X1 represents a -NH- R1 – – B According to SCHEME 2, in which R1, R2, R4, R5, X2, X3, R, Z and n are as defined above and Pg is a protecting group (Pg), wherein Pg is for example a Boc group or a Cbz group, intermediate (A) can be converted in STEP 1 to intermediate (E) by treatment with T3P in the presence of DIPEA in a solvent such as DCM by reacting with intermediate (D), and stirred for example at RT. Intermediate (E) can be converted in STEP 2 to intermediate (F) by treatment with Pd / C in a solvent such as MeOH in H2 atmosphere. Intermediate (F) can be converted in STEP 3 to intermediate (H) by treatment by T3P, in presence of DIPEA in a solvent such as DCM with intermediate (G). Intermediate (H) can be converted in STEP 4 to intermediate (J) by a cyclization step by treatment with Burgess reactant (CAS 29684-56-8). The reaction mixture can be heated under microwaves. Intermediate (J) may be converted in STEP 5 to compound of formula (I), wherein X1 represents a -NH- group and R1 represents group by a deprotection step as in STEP 2 of SCHEME 1. SCHEME 3: Preparation of compounds of formula (I), wherein X1 represents a -O- group – General process – method C According to SCHEME 3, in which R1, R2, R4, R5, X2, X3, R, Z and n are as defined above and Pg is a protecting group (Pg), wherein Pg is for example a Boc group or a Cbz group, intermediate (A) can be converted in STEP 1 to intermediate (C’) by treatment with DCC in the presence of DL-10-camphorsulfonic acid and DMAP by reacting with intermediate (B’), and stirred for example at RT. Intermediate (C’) can be converted in STEP 2 to compound of formula (I), wherein X1 represents a -O- group, in a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane. The intermediate (A) may be obtained by all methods known by the person skilled in the art. Typically, when group in formula (I) represents a group then intermediate (A) may be obtained according to SCHEME 4 below. SCHEME 4: Preparation of intermediate (A), wherein group in formula (I) represents a group – General process According to SCHEME 4, in which R2, R5, R, Z and n are as defined above and Pg is a protecting group (Pg), wherein Pg is for example a Boc group, intermediate (K), which is obtainable according to known procedures, can be converted in STEP 1 to intermediate (M) by reacting with intermediate (L) by treatment with PPh3 and DIAD in a solvent such as THF. The reaction mixture may be stirred at RT before adding an aqueous solution of LiOH. Intermediate (M) may be converted in STEP 2 to compound of formula (I),wherein treatment by an alumina / H2O mixture and potassium peroxymonosulfate. The intermediate (B) may be prepared according to methods known from the person skilled in the art. Typically, when R1 is a group , intermediate (B) may be obtained according to SCHEME 5 below. SCHEME 5: Preparation of intermediate (B), wherein R1 is a group According to SCHEME 5, in which R3 and Z are as defined above and Pg is a protecting group (Pg), wherein Pg is for example a Boc group, intermediate (M), which is obtainable according to known procedures, can be converted in STEP 1 to intermediate (N) by treatment with TBTU with R3CH(NH2)NOH in a solvent such as DMF in presence of TEA. Intermediate (N) may be converted in STEP 2 to intermediate (P) at reflux temperature in a solvent such as dioxane. Intermediate (P) may be converted in STEP 3 to intermediate (B1) by treatment with an acid, for example HCl or TFA in a solvent such as dioxane. Typically, when R1 is a group , intermediate (B’) may be obtained according to SCHEME 6 below. SCHEME 6: Preparation of intermediate (B’), wherein R1 is a group According to SCHEME 6, in which R3 and Z are as defined above and Pg is a protecting group (Pg), wherein Pg is for example a TBDMS group, intermediate (M’), which is obtainable according to known procedures, can be converted in STEP 1 to intermediate (N’) by treatment with TBTU with R3CH(NH2)NOH in a solvent such as DMF in presence of TEA. Intermediate (N’) may be converted in STEP 2 to intermediate (P’) at reflux temperature in a solvent such as dioxane. Intermediate (P’) may be converted in STEP 3 to intermediate (B’1) by treatment with tetrabutyl ammonium fluoride in a solvent such as THF. In one embodiment, herein is disclosed a process for preparing a compound of formula (I), wherein X1 represents a -NH- as described above, wherein it comprises a first step wherein an intermediate (A) wherein R2, R4, R5, X2, X3, R and n are as defined above and Pg is a protecting group, is converted to intermediate (C) by treatment with TBTU in the presence of TEA by reacting with intermediate are as defined above, and wherein it comprises a second step, wherein said intermediate (C) is converted to compound of formula (I) wherein X1 represents a -NH-, in a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane when Pg is a Boc group and with Pd / C in MeOH in H2 atmosphere, when Pg is a Cbz group. In another embodiment, herein is disclosed a process for preparing a compound of formula (I) wherein X1 represents a -NH- group and R1 represents a group as described above, wherein it comprises a first step, wherein an intermediate (H) wherein R1, Z, R2, X2, X3, R4, R5, R and n are as defined above, and Pg is a protecting group, is converted to an intermediate (J) by a cyclization step by treatment with Burgess reactant, optionally by heating under microwaves, and wherein it comprises a second step, wherein said intermediate (J) is converted to compound of formula (I), wherein X1 represents a -NH- group and R1 represents a group by a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane when Pg is a Boc group and with Pd / C in MeOH in H2atmosphere, when Pg is a Cbz group. In another embodiment, herein is disclosed a process for preparing a compound of formula (I) as described above, wherein X1 represents a -O- group, wherein an intermediate (A) wherein R2, X2, X3, R4, R5, R and n are as described above and Pg is a protecting group, is converted to intermediate (C’) by treatment with DCC in the presence of DL-10-camphorsulfonic acid and DMAP by reacting with intermediate (B’) , wherein Z and R1 are as defined above, and wherein it comprises a second step, wherein said intermediate (C’) is converted to compound of formula (I), wherein X1 represents a -O- group, in a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane. The liquid chromatography / mass spectra (LC / MS) were obtained by different Liquid Chromatography analytical methods (A, B, C, D, E or F) as described below. Method A: LC / MS system: Waters UPLC-SQD2; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition: 85 to 1500 uma; UV detection : DAD from 195 to 380 nm; ELS detection. Chromatographic conditions: Column : ACQUITY CSH C18 - 1.7 µm - 2.1 x 50 mm at 60°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid); Flow rate: 1 mL / min.3 min gradient: 0 to 0.1 min 3% of B - 0.1 to 2.1 min, from 3 to 97% of B - 2.1 to 2.45 min 97% of B - 2.45 to 2.5 min, from 97 to 3% of B - 2.5 to 3 min 3% of B. Method B: LC / MS system: Waters UPLC-SQD; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition : 85 to 1000 uma; UV detection : DAD from 191 to 499 nm; ELS detection. Chromatographic conditions: Column: ACQUITY Cortecs C18+ - 1.6 µm - 2.1 x 50 mm at 40°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid); Flow rate: 1 mL / min. 3 min gradient: 0 to 2 min, from 2% to 100% of B - 2 to 2.6 min, 100% of B - 2.6 to 2.7 min, 100% to 2% of B - from 2.7 to 3 min 2% of B. Method C: LC / MS system: Waters UPLC-SQD2; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition : 120 to 900 uma; UV detection : DAD from 210 to 380 nm; ELS detection. Chromatographic conditions: Column: ACQUITY Cortecs C18+ - 1.6 µm - 2.1 x 50 mm at 55°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid); Flow rate: 0.8 mL / min.3 min gradient: 0 to 2.5 min, from 2% to 100% of B – 2.5 to 2.9 min, 100% of B - 2.9 to 2.95 min, 100% to 2% of B - from 2.95 to 3 min 2% of B. Method D: LC / MS system: Waters UPLC-SQD; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition : 50 to 900 uma; UV detection : DAD from 210 to 400 nm; ELS detection. Chromatographic conditions: Column: ACQUITY Cortecs C18+ - 1.6 µm - 2.1 x 50 mm at 50°C; Solvents: A : H2O (0.1 % trifluoroacetic acid) - B : CH3CN (0.1 % trifluoroacetic acid); Flow rate: 1 mL / min. 2 min gradient: 0 to 0.5 min, from 5% to 6% of B – 0.5 to 1.5 min, from 6 to 99% of B – 1.5 to 1.9 min, 99% of B – 1.9 to 1.95 min, 99% to 5% of B - from 1.95 to 2 min 5% of B. Method E: LC / MS system: Waters UPLC-SQD; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition: 85 to 1100 uma; UV detection : DAD from 195 to 380 nm; ELS detection. Chromatographic conditions: Column : ACQUITY CSH C18 - 1.7 µm - 2.1 x 35 mm at 35°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid); Flow rate: 0.7 mL / min. 4 min gradient: 0 to 0.18 min 5% of B - 0.18 to 3.2 min, from 5 to 99% of B – 3.2 to 3.4 min 99% of B - 3.4 to 3.55 min, from 99 to 5% of B - 3.55 to 4 min 5% of B. Method F: LC / MS system: Waters UPLC-SQD2; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition : 85 to 1500 uma; UV detection : DAD from 195 to 380 nm; ELS detection. Chromatographic conditions: Column: ACQUITY CSH C18 - 1.7 µm - 2.1 x 35 mm at 60°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid) – C (isopropanol); Flow rate: 1 mL / min. 3 min gradient: 0 to 0.1 min 2% of B, 2% of C – 0.1 to 2.1 min, from 2% to 97% of B, 2% of C – 2.1 to 2.45 min, 97% of B, 2% of C - 2.45 to 2.5 min, from 97 to 2% of B, 2% of C - from 2.5 to 3 min 2% of B, 2% of C. Method G: LC / MS system: Waters UPLC-SQD2; Ionisation: electrospray in positive and negative mode (ES+ / -); Acquisition: 85 to 1000 uma; UV detection : DAD from 191 to 499 nm; ELS detection. Chromatographic conditions: Column : ACQUITY Cortecs C18 - 1.7 µm - 2.1 x 50 mm at 40°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid); Flow rate: 1 mL / min.3 min gradient: 0 min, 2% of B - 0 to 2 min, from 2 to 100% of B - 2 to 2.6 min 100% of B - 2.6 to 2.7 min, from 100 to 2% of B - 2.7 to 3 min, 2% of B. Method H: LC / MS system: Waters UPLC-LCT Premier; Ionisation: electrospray in positive mode (ES+); Acquisition: 100 to 1500 uma; UV detection : DAD from 210 to 400 nm; ELS detection. Chromatographic conditions: Column : ACQUITY Cortecs C18 - 1.7 µm - 2.1 x 50 mm at 40°C; Solvents: A : H2O (0.1 % formic acid) - B : CH3CN (0.1 % formic acid); Flow rate: 1 mL / min. 3 min gradient: 0 min, 2% of B - 0 to 2 min, from 2 to 100% of B - 2 to 2.6 min 100% of B - 2.6 to 2.7 min, from 100 to 2% of B - 2.7 to 3 min, 2% of B. The following table 1 comprises respectively specific compounds of formula (I) (structure) in accordance with the present disclosure as well as their characterization (liquid chromatography / mass). Table 1: MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) O O FSH NH N 1 N 698.4 1.34 A O O N HO N O O O 2 680.3 1.41 A 3 681.3 1.03 A

[0003] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) CH3COOH O O F S H NH N N 4 O N O 722.4 1.31 A N N O N N O N H 5 812.5 1.61 A 6 698.1 1.37 A OOF S H NH N N 7 O N O 694.2 0.95 A HN N N O O MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 8 697.4 0.99 A 9 690.2 1.37 A 10 697.3 1.01 A 11 707.2 1.08 A MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 12 698.3 1.33 A 13 695.1 1.42 A OOF S H NH N N 14 O N O 669.1 1.26 A O N N O O 15 695.4 1.57 A MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 16 640.5 1.29 A 17 684.3 1.33 A 18 694.2 1.50 A

[0004] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 19 643.3 1.44 A 20 628.3 1.47 A CF3COOH 21 668.2 1.41 A

[0005] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 22 684.2 1.46 A 23 709.2 0.99 A 24 708.3 1.04 A

[0006] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 25 678.3 1.12 A 26 626.1 1.31 A 27 669.2 1.28 A

[0007] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 28 708.1 1.45 A 29 628.1 1.18 A 30 712.3 1.44A MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) O N F O H S N O N NH2 31 O N 678.1 1.54AO O 32 672.1 1.47 A 33 696.2 1.43 A MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 34 668.2 1.58 A 35 669.1 1.73 A 36 680.2 1.52 A MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 37 654.2 1.36 A 38 670.3 1.26 A 39 640.4 1.04 G

[0008] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 40 682.6 0.98 G Isomer 1 41 682.6 0.98 G Isomer 2 O O F S NH2 O N 42 O O O 671.5 1.38 G O O MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 43 736.5 1.04 G 44 736.6 1.04 G 45 644.3 1.59 A

[0009] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 46 645.5 1.01 B 47 666.3 1.52 A 48 642.2 1.19 A

[0010] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 49 668.2 1.29 A 50 698.5 1.50 A 51 684.5 1.40 A MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 52 652.2 1.44 A 53 710.5 0.98 G 54 681.5 1.28 G MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 55 625.4 0.92 G 56 617.4 1.16 G 57 645.4 1.28 G 58 670.4 1.05 B MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 59 699.4 1.31 G 60 722.4 1.19B61 668.2 1.57 A 62 750.5 1.02 G MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 63 674.5 1.04 B 64 734.4 1.18 G 65 699.4 1.18 G

[0011] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H]) FFF N N FO OO H S N 66 NH 680.4 1.13 G N 2 O O O 67 653.4 1.35 B 68 599.4 1.55 A

[0012] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 69 672.3 1.02 G 70 684.3 0.70 G 71 667.2 1.08 G

[0013] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 72 673.2 1.14 G 73 686.3 0.83 B 74 672.2 0.78 G

[0014] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 75 726.3 1.06 B 76 640.3 0.78 G 77 612.3 0.9 G

[0015] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 78 698.3 1.18 G 79 600.2 0.83 G 80 570.2 0.73 G

[0016] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 81 672.3 1.02 G 82 656.4 0.92 G 83 663.3 0.59 B

[0017] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 84 586.2 0.78 G 85 584.2 0.85 G 86 680.3 1.15 G

[0018] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 87 602.2 0.88 G 88 574.3 0.77 G 89 594.2 0.76 G

[0019] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 90 691.5 0.85 B 91 658.3 0.95 G 92 698.5 1.18 B

[0020] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 93 627.3 1.25 B 94 614.2 1.24 A 95 560.3 0.75 G

[0021] MS Rt LC / MS Compound Structure (m / z, (min) method [M+H]+) 96 700.4 0.97 B 97 615.5 0.82 B 98 585.2 1.41 A

[0022] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 99 685.5 0.86 B 100 644.4 0.89 B 101 571.2 1.25 A

[0023] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 102 560.3 0.60 G 103 598.2 0.83 B 104 655.5 0.94B

[0024] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 105 701.5 0.61BO O FSH NH2 N N 106 O O O 658.5 0.92 B O O O 107 658.4 0.92 B 108 640.4 0.98 G MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 109 599.4 1.10 G 110 627.4 0.81 B 111 626.5 0.83 G

[0025] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 112 615.5 0.79 G 113 672.5 0.96 B 114 615.5 0.80 G O O FSH NH N 2 N 115 O O O 642.4 1.10 G O O MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) O O FSH NH N 2 N 116 O O O 628.4 1.01 G O O 117 612.4 0.75 B 118 657.4 0.82B

[0026] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 119 626.4 1.11 G 120 643.0 0.92 H 121 574.0 0.77 G

[0027] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 122 598.4 1.03 G 123 644.4 1.14 B 124 616.2 1.00 G

[0028] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 125 625.2 0.82 B 126 578.1 0.81B127 546.1 0.80 B

[0029] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 128 614.2 0.82 B OOF S H NH2 N 129 N O 602.2 0.92 H O O O O 130 610.1 0.75 G

[0030] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 131 642.2 0.84 H 132 602.2 0.74 H 133 588.3 0.80 B

[0031] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 134 570.2 0.76 G 135 631.2 0.75B136

[0032] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 137 H2SO4 138 139

[0033] MS Rt LC / MS Compound Structure (m / z, + (min) method [M+H] ) 140 141 The following table 2 comprises the NMR characterization of compounds of formula (I) in accordance with the present disclosure. Table 2: Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.50 (s, 6 H) 1.99 (br s, 12 H) 3.92 - 4.05 (m, 1 H) 4.09 - 4.20 (m, 1 H) 4.39 (br dd, J=10.7, 7.7 1 Hz, 1 H) 4.54 - 4.68 (m, 2 H) 5.25 (br d, J=15.3 Hz, 1 H) 6.86 (d, J=8.6 Hz, 2 H) 7.27 (d, J=8.6 Hz, 2 H) 7.42 (d, J=5.5 Hz, 1 H) 7.78 (d, J=8.0 Hz, 1 H) 8.21 (s, 1 H) 8.23 - 9.31 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 0.67 - 0.74 (m, 2 H) 0.79 - 0.90 (m, 2 H) 1.28 (s, 9 H) 1.90 - 2.07 (m, 14 H) 3.52 (d, J=5.6 Hz, 2 H) 3.59 - 3.75 (m, 2 2 H) 3.84 - 3.95 (m, 1 H) 4.52 (br d, J=15.5 Hz, 1 H) 4.64 (t, J=5.6 Hz, 1 H) 5.28 (br d, J=15.5 Hz, 1 H) 7.22 - 7.30 (m, 4 H) 7.34 (d, J=5.4 Hz, 1 H) 7.69 (d, J=8.3 Hz, 1 H) 8.13 (s, 1 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6H) 1.69 - 1.82 (m, 1 H) 1.86 - 2.13 (m, 17 H) 2.15 - 2.30 (partially hidden m, 2 H) 2.37 - 2.46 (m, 3 2 H) 3.60 - 3.70 (m, 2 H) 3.82 - 3.94 (m, 1 H) 4.51 (d, J=15.3 Hz, 1 H) 4.59 (spt, J=6.0 Hz, 1 H) 5.24 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.7 Hz, 2 H) 7.24 (br d, J=8.7 Hz, 2 H) 7.33 (d, J=5.5 Hz, 1 H) 7.68 (d, J=8.3 Hz, 1 H) 8.14 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, AcOD, 30°C) δ ppm 1.23 (d, J=6.0 Hz, 6H) 1.76 4 (br s, 6 H) 1.97 (br s, 12 H) 3.68 - 3.80 (m, 1 H) 3.86 - 3.97 (m, 2 H) 4.49 - 4.62 (m, 2 H) 5.23 (d, J=15.3 Hz, 1 H) 6.84 (br d, J=8.7 Hz, 2 H) 7.23 (br d, J=8.7 Hz, 2 H) 7.35 (d, J=5.5 Hz, 1 H) 7.69 (d, J=8.3 Hz, 1 H) 8.09 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.76 (s, 6 H) 1.89 - 2.11 (m, 14 H) 3.58 - 3.71 (m, 2 H) 3.81 - 3.94 (m, 1 H) 4.51 (d, J=15.3 Hz, 5 1 H) 4.58 (spt, J=6.0 Hz, 1 H) 5.23 (d, J=15.3 Hz, 1 H) 5.92 (s, 2 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.28 - 7.42 (m, 6 H) 7.67 (d, J=8.3 Hz, 1 H) 8.12 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.42 (s, 6 H) 1.87 - 1.99 (m, 12 H) 3.59 - 3.72 (m, 2 H) 3.80 - 3.94 (m, 1 H) 4.49 (d, J=15.0 Hz, 6 1 H) 4.59 (spt, J=6.0 Hz, 1 H) 5.25 (d, J=15.0 Hz, 1 H) 6.86 (br d, J=7.9 Hz, 2 H) 7.25 (br d, J=7.9 Hz, 2 H) 7.31 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.3 Hz, 1 H) 8.08 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.93 - 2.19 (m, 14 H) 2.69 - 2.75 (m, 2 H) 2.82 (dd, J=12.5, 9.5 Hz, 1 H) 2.97 (dd, J=12.5, 2.8 8 Hz, 1 H) 3.51 - 3.72 (m, 3 H) 3.77 - 3.84 (m, 1 H) 3.84 - 3.92 (m, 1 H) 4.50 (d, J=15.3 Hz, 1 H) 4.53 - 4.65 (m, 2 H) 5.24 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.8 Hz, 2 H) 7.23 (br d, J=8.8 Hz, 2 H) 7.31 (d, J=5.8 Hz, 1 H) 7.67 (d, J=8.5 Hz, 1 H) 8.13 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.90 - 2.18 (m, 14 H) 3.59 - 3.74 (m, 2 H) 3.82 - 3.96 (m, 1 H) 4.51 (d, J=15.3 Hz, 1 H) 4.55 - 9 4.65 (m, 1 H) 5.24 (d, J=15.3 Hz, 1 H) 6.86 (br d, J=8.6 Hz, 2 H) 7.25 (br d, J=8.6 Hz, 2 H) 7.34 (d, J=5.5 Hz, 1 H) 7.68 (d, J=8.3 Hz, 1 H) 8.17 (s, 1 H) 9.32 (s, 2 H) 9.40 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.28 (s, 9 H) 1.58 - 1.77 (m, 4 H) 1.86 - 2.14 (m, 16 H) 2.18 (s, 3 H) 2.38 - 2.54 (m partially hidden, 1 H) 2.85 (br d, 11 J=11.3 Hz, 2 H) 3.60 - 3.75 (m, 2 H) 3.89 (dd, J=11.6, 5.3 Hz, 1 H) 4.46 (d, J=15.5 Hz, 1 H) 5.32 (d, J=15.5 Hz, 1 H) 7.17 - 7.24 (m, 2 H) 7.25 - 7.32 (m, 3 H) 7.68 (d, J=8.3 Hz, 1 H) 8.09 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.90 - 2.10 (m, 14 H) 3.57 - 3.78 (m, 6 H) 3.81 - 3.98 (m, 3 H) 4.50 (d, J=15.0 Hz, 1 H) 4.59 12 (spt, J=6.0 Hz, 1 H) 4.78 (dd, J=9.1, 2.9 Hz, 1 H) 5.24 (d, J=15.0 Hz, 1 H) 6.85 (br d, J=8.7 Hz, 2 H) 7.24 (br d, J=8.7 Hz, 2 H) 7.32 (d, J=5.5 Hz, 1 H) 7.68 (d, J=8.0 Hz, 1 H) 8.14 (br s, 1 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.29 (s, 9 H) 1.91 - 2.08 (m, 14 H) 13 3.04 - 3.17 (m, 4 H) 3.58 - 3.70 (m, 2 H) 3.70 - 3.75 (m, 4 H) 3.81 - 3.94 (m, 1 H) 4.50 (d, J=15.3 Hz, 1 H) 5.22 (d, J=15.3 Hz, 1 H) 6.88 (br d, J=8.6 Hz, 2 H) 7.20 (br d, J=8.6 Hz, 2 H) 7.33 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.3 Hz, 1 H) 8.12 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.28 (s, 6 H) 1.87 - 2.05 (m, 14 H) 3.53 (d, J=5.5 Hz, 2 H) 3.59 - 3.71 (m, 2 H) 3.83 - 3.93 (m, 17 1 H) 4.49 (d, J=15.5 Hz, 1 H) 4.59 (spt, J=6.0 Hz, 1 H) 5.01 (t, J=5.5 Hz, 1 H) 5.25 (d, J=15.5 Hz, 1 H) 6.85 (br d, J=8.5 Hz, 2 H) 7.24 (br d, J=8.5 Hz, 2 H) 7.31 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.0 Hz, 1 H) 8.06 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.28 (s, 9 H) 1.90 - 2.06 (m, 14 H) 3.59 - 3.76 (m, 2 H) 3.83 - 3.94 (m, 1 H) 4.79 (d, J=15.4 Hz, 1 H) 5.26 (d, J=15.4 18 Hz, 1 H) 7.43 (d, J=5.5 Hz, 1 H) 7.45 (br d, J=8.6 Hz, 2 H) 7.68 (d, J=8.3 Hz, 1 H) 7.74 (br d, J=8.6 Hz, 2 H) 7.82 (d, J=4.5 Hz, 1 H) 8.10 (s, 1 H) 8.69 (d, J=4.5 Hz, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.29 (s, 9 H) 1.95 - 2.05 (m, 14 H) 19 3.57 - 3.73 (m, 2 H) 3.80 - 3.95 (m, 1 H) 4.61 (d, J=15.1 Hz, 1 H) 5.19 (d, J=15.1 Hz, 1 H) 6.86 (br d, J=8.8 Hz, 2 H) 7.26 (br d, J=8.8 Hz, 2 H) 7.37 (d, J=5.6 Hz, 1 H) 7.66 (d, J=8.3 Hz, 1 H) 8.10 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.28 (s, 9 H) 1.94 - 2.07 (m, 14 H) 20 3.58 - 3.75 (m, 2 H) 3.82 - 3.95 (m, 1 H) 4.77 (d, J=15.5 Hz, 1 H) 5.18 (d, J=15.5 Hz, 1 H) 7.14 (br t, J=8.9 Hz, 2 H) 7.38 (br dd, J=8.7, 5.6 Hz, 2 H) 7.44 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.4 Hz, 1 H) 8.12 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.99 (s, 14 H) 2.45 - 2.77 (m partially hidden, 4 H) 3.58 - 3.73 (m, 3 H) 3.81 - 3.94 (m, 1 H) 22 4.50 (d, J=15.1 Hz, 1 H) 4.53 - 4.66 (m, 1 H) 5.17 - 5.42 (m, 2 H) 6.85 (br d, J=8.8 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.32 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.1 Hz, 1 H) 8.11 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.29 (s, 9 H) 1.94 - 2.07 (m, 14 H) 2.21 (s, 3 H) 2.39 - 2.46 (m, 4 H) 3.06 - 3.15 (m, 4 H) 3.58 - 3.71 (m, 2 H) 3.81 - 24 3.94 (m, 1 H) 4.45 (d, J=15.1 Hz, 1 H) 5.24 (d, J=15.1 Hz, 1 H) 6.87 (d, J=8.6 Hz, 2 H) 7.18 (d, J=8.6 Hz, 2 H) 7.30 (d, J=5.5 Hz, 1 H) 7.66 (d, J=8.4 Hz, 1 H) 8.08 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.97 - 2.14 (m, 12 H) 4.00 (br dd, J=13.2, 11.1 Hz, 2 H) 4.11 - 4.23 (m, 1 H) 4.36 - 4.45 (m, 1 25 H) 4.54 - 4.68 (m, 2 H) 5.26 (d, J=15.3 Hz, 1 H) 6.87 (br d, J=8.8 Hz, 2 H) 7.28 (br d, J=8.8 Hz, 2 H) 7.42 (d, J=5.5 Hz, 1 H) 7.79 (d, J=8.1 Hz, 1 H) 8.06 (s, 1 H) 8.23 (s, 1 H) 8.51 - 8.59 (m, 1 H) 8.61 - 8.85 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.49 (s, 3 H) 1.84 - 2.13 (m, 18 H) 28 2.36 - 2.50 (m partially hiddden, 2 H) 3.22 - 3.36 (m partially hiddden, 1 H) 3.51 - 3.96 (m, 8 H) 4.53 - 4.64 (m, 2 H) 5.29 (d, J=15.6 Hz, 1 H) 7.28 - 7.38 (m, 5 H) 7.68 (d, J=8.1 Hz, 1 H) 8.12 (s, 1 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.67 (s, 6 H) 1.95 - 2.00 (m, 15 H) 1.99 - 2.05 (m, 2 H) 3.58 - 3.71 (m, 2 H) 3.82 - 3.93 (m, 1 H) 30 4.51 (d, J=15.1 Hz, 1 H) 4.59 (spt, J=6.0 Hz, 1 H) 5.24 (d, J=15.1 Hz, 1 H) 6.85 (br d, J=8.8 Hz, 2 H) 7.24 (br d, J=8.8 Hz, 2 H) 7.33 (d, J=5.6 Hz, 1 H) 7.67 (d, J=8.3 Hz, 1 H) 8.13 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.31 (d, J=6.0 Hz, 6 H) 1.78 (d, J=22.0 Hz, 6 H) 2.00 - 2.15 (m, 14 H) 3.63 - 3.79 (m, 2 H) 3.87 - 4.01 (m, 1 H) 32 4.57 (br d, J=15.3 Hz, 1 H) 4.60 - 4.71 (m, 1 H) 5.30 (br d, J=15.3 Hz, 1 H) 6.91 (br d, J=8.6 Hz, 2 H) 7.30 (br d, J=8.6 Hz, 2 H) 7.39 (d, J=5.5 Hz, 1 H) 7.74 (d, J=8.1 Hz, 1 H) 8.21 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.28 (s, 9 H) 1.85 - 2.11 (m, 14 H) 33 3.19 - 3.39 (m partially hidden, 1 H) 3.48 - 4.06 (m, 8 H) 4.49 - 4.69 (m, 2 H) 5.29 (br d, J=15.8 Hz, 1 H) 7.33 (s, 5 H) 7.68 (d, J=8.3 Hz, 1 H) 8.12 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.22 - 1.28 (m, 6 H) 1.29 (s, 9 H) 1.95 - 2.06 (m, 2 H) 2.08 - 2.12 (m, 12 H) 3.62 - 3.81 (m, 2 H) 3.87 (dd, J=12.2, 35 5.8 Hz, 1 H) 4.40 (d, J=15.1 Hz, 1 H) 4.56 - 4.68 (m, 1 H) 5.32 (br d, J=15.1 Hz, 1 H) 6.89 (br d, J=8.5 Hz, 2 H) 7.25 (br d, J=8.5 Hz, 2 H) 7.57 (d, J=5.9 Hz, 1 H) 7.74 (d, J=9.1 Hz, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.93 - 2.04 36 (m, 14 H) 3.58 - 3.70 (m, 2 H) 3.80 - 3.94 (m, 1 H) 4.49 (d, J=15.5 Hz, 1 H) 4.58 (spt, J=6.0 Hz, 1 H) 5.24 (d, J=15.5 Hz, 1 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.7 Hz, 2 H) 7.31 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.0 Hz, 1 H) 8.11 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.90 - 2.15 (m, 14 H) 2.60 (s, 3 H) 3.58 - 3.77 (m, 2 H) 3.80 - 3.94 (m, 1 H) 4.50 (br d, J=15.3 37 Hz, 1 H) 4.54 - 4.65 (m, 1 H) 5.24 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.32 (d, J=5.5 Hz, 1 H) 7.68 (d, J=8.4 Hz, 1 H) 8.16 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.46 (s, 6 H) 1.94 - 2.05 (m, 14 H) 3.59 - 3.71 (m, 2 H) 3.82 - 3.93 (m, 1 H) 4.50 (d, J=15.2 Hz, 38 1 H) 4.59 (spt, J=6.0 Hz, 1 H) 5.24 (d, J=15.2 Hz, 1 H) 5.49 (s, 1 H) 6.85 (br d, J=8.7 Hz, 2 H) 7.24 (br d, J=8.7 Hz, 2 H) 7.32 (d, J=5.6 Hz, 1 H) 7.68 (d, J=8.3 Hz, 1 H) 8.13 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.08 (s, 9 H) 1.25 (d, J=6.1 Hz, 6 H) 2.00 (br s, 14 H) 3.59 - 3.69 (m, 2 H) 3.83 - 3.91 (m, 1 H) 4.48 (d, J=15.5 Hz, 1 H) 45 4.58 (spt, J=6.1 Hz, 1 H) 5.23 (d, J=15.5 Hz, 1 H) 6.84 (br d, J=8.6 Hz, 2 H) 7.23 (br d, J=8.6 Hz, 2 H) 7.29 (d, J=5.5 Hz, 1 H) 7.66 (br d, J=8.5 Hz, 1 H) 8.04 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (br d, J=6.0 Hz, 3 H) 1.26 (br d, J=6.0 Hz, 3 H) 1.88 - 2.17 (m, 14 H) 3.59 - 3.80 (m, 2 H) 3.81 - 3.91 (m, 1 H) 4.37 46 (d, J=15.0 Hz, 1 H) 4.43 (dd, J=8.3, 5.3 Hz, 2 H) 4.60 (spt, J=6.0 Hz, 1 H) 4.75 - 4.81 (m, 2 H) 5.28 - 5.39 (m, 2 H) 6.88 (br d, J=8.5 Hz, 2 H) 7.24 (br d, J=8.5 Hz, 2 H) 7.53 (d, J=6.0 Hz, 1 H) 7.72 (d, J=9.0 Hz, 1 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.85 - 2.11 (m, 16 H) 2.17 - 2.36 (m, 4 H) 3.55 - 3.72 (m, 3 H) 3.80 - 3.95 (m, 1 H) 4.50 (d, 47 J=15.3 Hz, 1 H) 4.53 - 4.67 (m, 1 H) 5.24 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.32 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.3 Hz, 1 H) 8.11 (s, 1 H) 1H NMR (400 MHz, DMSO-d6 with trifluoroacetic acid-d, 30°C) δ ppm 1.26 (d, 48 J=6.0 Hz, 6 H) 2.04 (s, 14 H) 3.96 - 4.14 (m, 1 H) 4.42 - 4.65 (m, 1 H) 4.52 (s, 2 H) 5.30 (d, J=15.3 Hz, 1 H) 6.89 (br d, J=8.7 Hz, 2 H) 7.30 (br d, J=8.7 Hz, 2 H) 7.45 (d, J=5.4 Hz, 1 H) 7.79 (d, J=8.2 Hz, 1 H) 8.19 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.20 (s, 9 H) 1.24 (d, J=6.0 Hz, 6 H) 1.93 - 2.08 (m, 14 H) 3.57 - 3.74 (m, 2 H) 3.80 - 3.95 (m, 1 H) 4.45 (s, 2 H) 4.50 50 (d, J=15.1 Hz, 1 H) 4.53 - 4.67 (m, 1 H) 5.24 (d, J=15.1 Hz, 1 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.32 (d, J=5.6 Hz, 1 H) 7.67 (d, J=8.3 Hz, 1 H) 8.11 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.32 (t, J=7.1 Hz, 3 H) 1.94 - 2.11 (m, 14 H) 3.58 - 3.74 (m, 2 H) 3.81 - 3.95 (m, 1 H) 4.40 (q, 51 J=7.1 Hz, 2 H) 4.50 (d, J=15.3 Hz, 1 H) 4.54 - 4.65 (m, 1 H) 5.24 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.32 (d, J=5.6 Hz, 1 H) 7.68 (d, J=8.3 Hz, 1 H) 8.13 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 0.81 - 0.90 (m, 2 H) 0.98 - 1.07 (m, 2 H) 1.24 (d, J=6.0 Hz, 6 H) 1.89 - 2.11 (m, 15 H) 3.58 - 3.73 (m, 2 H) 3.79 - 3.95 52 (m, 1 H) 4.50 (d, J=15.1 Hz, 1 H) 4.53 - 4.65 (m, 1 H) 5.24 (d, J=15.1 Hz, 1 H) 6.85 (br d, J=8.6 Hz, 2 H) 7.24 (br d, J=8.6 Hz, 2 H) 7.32 (d, J=5.5 Hz, 1 H) 7.67 (d, J=8.4 Hz, 1 H) 8.10 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=5.9 Hz, 6 H) 2.03 (br s, 12 H) 3.56 (q, J=11.2 Hz, 2 H) 3.90 - 4.03 (m, 1 H) 4.03 - 4.16 (m, 1 H) 4.29 - 4.41 58 (m, 1 H) 4.52 - 4.65 (m, 2 H) 5.25 (d, J=14.9 Hz, 1 H) 6.86 (br d, J=8.6 Hz, 2 H) 7.26 (br d, J=8.6 Hz, 2 H) 7.37 (d, J=5.4 Hz, 1 H) 7.77 (d, J=8.1 Hz, 1 H) 8.09 - 8.57 (m, 3 H) 8.16 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.41 (s, 9 H) 1.62 - 1.73 (m, 6 H) 1.90 - 1.99 (m, 6 H) 1.99 - 2.24 (m, 2 H) 3.57 - 3.69 (m, 2 H) 63 3.81 - 3.92 (m, 3 H) 4.46 (d, J=15.1 Hz, 1 H) 4.58 (spt, J=6.0 Hz, 1 H) 5.24 (d, J=15.1 Hz, 1 H) 6.84 (br d, J=8.7 Hz, 2 H) 7.23 (br d, J=8.7 Hz, 2 H) 7.27 (d, J=5.6 Hz, 1 H) 7.65 (d, J=8.4 Hz, 1 H) 7.98 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (br d, J=6.0 Hz, 3 H) 1.26 (br d, J=6.0 Hz, 3 H) 1.29 - 1.49 (m, 6 H) 1.55 - 1.75 (m, 4 H) 1.83 - 2.26 (m, 14 H) 3.58 67 - 3.74 (m, 2 H) 3.79 - 3.92 (m, 1 H) 4.32 (d, J=15.0 Hz, 1 H) 4.60 (spt, J=6.0 Hz, 1 H) 4.63 - 4.71 (m, 1 H) 5.40 (br d, J=15.0 Hz, 1 H) 6.89 (br d, J=8.6 Hz, 2 H) 7.25 (br d, J=8.6 Hz, 2 H) 7.60 (d, J=1.5 Hz, 1 H) 7.94 - 8.02 (m, 2 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.58 (s, 3 H) 1.78 - 1.91 (m, 12 H) 73 1.96 - 2.04 (m, 2 H) 3.53 - 3.95 (m, 9 H) 4.39 - 4.43 (m, 2 H) 4.54 - 4.61 (m, 4 H) 5.28 (d, J=15.6 Hz, 1 H) 7.29 - 7.35 (m, 5 H) 7.67 (d, J=8.4 Hz, 1 H) 8.02 (s, 1 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.57 - 1.63 (m, 6 H) 1.74 - 1.92 (m, 12 H) 3.26 - 3.30 (partially hidden m, 1 H) 3.53 - 3.62 (m, 1 H) 3.69 - 3.90 (m, 4 75 H) 3.99 (dd, J=13.6, 11.0 Hz, 1 H) 4.08 - 4.17 (m, 1 H) 4.39 - 4.46 (m, 1 H) 4.58 (dd, J=10.0, 2.5 Hz, 1 H) 4.65 (d, J=15.8 Hz, 1 H) 5.31 (d, J=15.8 Hz, 1 H) 7.31 - 7.41 (m, 5 H) 7.77 (d, J=8.5 Hz, 1 H) 8.09 (br s, 1 H) 8.35 - 8.66 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.95 - 2.07 (m, 12 H) 2.20 - 3.06 (partially hidden m, 6 H) 3.58 - 3.75 (m, 2 H) 3.99 (dd, 83 J=13.4, 11.1 Hz, 1 H) 4.14 (dd, J=13.4, 7.4 Hz, 1 H) 4.38 (dd, J=11.1, 7.4 Hz, 1 H) 4.54 - 4.66 (m, 2 H) 5.23 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.7 Hz, 2 H) 7.26 (br d, J=8.7 Hz, 2 H) 7.43 (d, J=5.5 Hz, 1 H) 7.78 (d, J=8.2 Hz, 1 H) 8.25 (s, 1 H) 8.64 (br s, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.00 - 1.13 (m, 4 H) 1.25 (d, J=6.0 Hz, 6 H) 1.75 - 1.94 (m, 12 H) 2.90 - 2.98 (m, 1 H) 3.97 (dd, J=13.2, 11.1 Hz, 1 H) 90 4.10 (dd, J=13.2, 7.5 Hz, 1 H) 4.39 (dd, J=11.1, 7.5 Hz, 1 H) 4.54 - 4.65 (m, 2 H) 5.25 (d, J=15.2 Hz, 1 H) 6.86 (br d, J=8.7 Hz, 2 H) 7.26 (br d, J=8.7 Hz, 2 H) 7.40 (d, J=5.5 Hz, 1 H) 7.77 (d, J=8.2 Hz, 1 H) 8.10 (br s, 1 H) 8.20 - 8.98 (m, 3 H) 10.74 - 11.57 (m, 1 H) 1H NMR (500 MHz, DMSO-d6, 27°C) δ ppm 1.37 (br s, 9 H) 1.39 (br d, J=6.3 Hz, 3 H) 1.72 - 1.78 (m, 6 H) 1.83 - 1.88 (m, 6 H) 1.94 - 2.08 (m, 2 H) 3.60 - 3.70 (m, 92 2 H) 3.83 - 3.92 (m, 1 H) 4.57 (d, J=15.1 Hz, 1 H) 5.17 - 5.26 (m, 2 H) 7.02 (br d, J=8.8 Hz, 2 H) 7.29 (br d, J=8.8 Hz, 2 H) 7.33 (d, J=5.0 Hz, 1 H) 7.66 (d, J=8.2 Hz, 1 H) 8.02 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.50 - 1.63 (m, 2 H) 1.68 - 1.78 (m, 1 H) 1.89 - 2.00 (m, 7 H) 2.08 - 2.19 (m, 6 H) 2.52 - 2.58 (partially hidden m, 1 H) 94 2.71 - 2.82 (m, 1 H) 2.91 (dd, J=12.3, 9.8 Hz, 1 H) 3.38 - 3.53 (partially hidden m, 3 H) 3.59 - 3.71 (m, 3 H) 3.77 - 3.93 (m, 1 H) 4.22 (d, J=15.2 Hz, 1 H) 5.41 (d, J=15.2 Hz, 1 H) 6.92 (br d, J=8.7 Hz, 2 H) 7.20 (br d, J=8.7 Hz, 2 H) 7.60 (d, J=1.3 Hz, 1 H) 7.94 - 8.04 (m, 2 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.77 - 1.92 (m, 12 H) 1.94 - 2.12 (m, 2 H) 2.15 (s, 3 H) 3.57 - 3.71 (m, 2 H) 3.80 - 3.94 (m, 1 96 H) 4.48 (d, J=15.2 Hz, 1 H) 4.58 (spt, J=6.0 Hz, 1 H) 4.93 (s, 2 H) 5.24 (d, J=15.2 Hz, 1 H) 6.84 (br d, J=8.8 Hz, 2 H) 7.23 (br d, J=8.8 Hz, 2 H) 7.29 (d, J=5.6 Hz, 1 H) 7.66 (d, J=8.3 Hz, 1 H) 8.03 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 0.93 (t, J=7.6 Hz, 3 H) 1.25 (d, J=6.0 Hz, 6 H) 1.90 (br d, J=1.8 Hz, 12 H) 2.00 (q, J=7.6 Hz, 2 H) 3.94 (dd, J=13.2, 11.0 97 Hz, 1 H) 4.04 - 4.14 (m, 1 H) 4.30 (dd, J=11.0, 7.5 Hz, 1 H) 4.51 - 4.65 (m, 2 H) 5.26 (d, J=15.3 Hz, 1 H) 6.86 (br d, J=8.8 Hz, 2 H) 7.21 - 7.30 (m, 3 H) 7.35 (d, J=5.5 Hz, 1 H) 7.75 (d, J=8.3 Hz, 1 H) 7.82 - 8.30 (m, 4 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.21 - 1.31 (m, 6 H) 1.84 - 2.05 (m, 98 14 H) 3.59 (s, 3 H) 3.59 - 3.75 (m, 2 H) 3.86 (dd, J=11.7, 5.2 Hz, 1 H) 4.33 (d, J=15.2 Hz, 1 H) 4.54 - 4.66 (m, 1 H) 5.39 (d, J=15.2 Hz, 1 H) 6.89 (br d, J=8.6 Hz, 2 H) 7.26 (br d, J=8.6 Hz, 2 H) 7.62 (d, J=1.0 Hz, 1 H) 7.93 - 8.03 (m, 2 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.37 - 1.47 (m, 2 H) 1.68 - 1.83 (m, 2 H) 1.83 - 2.00 (m, 12 H) 2.77 (br s, 3 H) 3.35 - 3.46 99 (partially hidden m, 2 H) 3.82 - 4.02 (m, 3 H) 4.05 - 4.14 (m, 1 H) 4.22 - 4.34 (m, 1 H) 4.38 (dd, J=10.9, 7.4 Hz, 1 H) 4.53 - 4.66 (m, 2 H) 5.26 (d, J=15.1 Hz, 1 H) 6.86 (br d, J=8.8 Hz, 2 H) 7.26 (br d, J=8.8 Hz, 2 H) 7.39 (d, J=5.5 Hz, 1 H) 7.76 (d, J=8.3 Hz, 1 H) 8.09 (br s, 1 H) 8.73 (s, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.22 - 1.32 (m, 6 H) 1.84 - 2.04 (m, 101 12 H) 3.89 - 4.11 (m, 2 H) 4.34 - 4.45 (m, 2 H) 4.57 - 4.67 (m, 1 H) 5.42 (d, J=15.4 Hz, 1 H) 6.92 (br d, J=8.6 Hz, 2 H) 7.30 (br d, J=8.6 Hz, 2 H) 7.64 (s, 1 H) 8.03 - 8.10 (m, 2 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.74 - 1.97 (m, 12 H) 3.98 (dd, J=13.3, 11.0 Hz, 1 H) 4.10 - 4.20 (m, 1 H) 4.41 (dd, J=11.0, 7.4 Hz, 1 H) 4.91 (d, 103 J=15.6 Hz, 1 H) 5.19 (d, J=15.6 Hz, 1 H) 7.34 (dd, J=8.3, 2.0 Hz, 1 H) 7.57 (d, J=5.5 Hz, 1 H) 7.60 (d, J=8.3 Hz, 1 H) 7.67 (d, J=2.0 Hz, 1 H) 7.78 (d, J=8.0 Hz, 1 H) 7.88 - 9.71 (m, 3 H) 8.13 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.38 - 1.48 (m, 4 H) 1.53 - 1.63 (m, 2 H) 1.80 - 1.96 (m, 12 H) 3.43 - 3.55 (m, 4 H) 3.98 (dd, 104 J=13.3, 11.0 Hz, 1 H) 4.07 - 4.16 (m, 1 H) 4.39 (dd, J=11.0, 7.3 Hz, 1 H) 4.51 - 4.70 (m, 2 H) 5.27 (d, J=15.3 Hz, 1 H) 6.86 (br d, J=8.8 Hz, 2 H) 7.27 (br d, J=8.8 Hz, 2 H) 7.38 (d, J=5.8 Hz, 1 H) 7.76 (d, J=8.3 Hz, 1 H) 8.08 (br s, 1 H) 8.27 - 8.76 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.77 - 1.98 (m, 12 H) 2.96 - 3.57 (partially hidden m, 6 H) 3.76 - 4.06 (m, 5 H) 4.11 - 4.21 (m, 105 1 H) 4.34 - 4.44 (m, 3 H) 4.54 - 4.65 (m, 2 H) 5.26 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.8 Hz, 2 H) 7.27 (br d, J=8.8 Hz, 2 H) 7.39 (d, J=5.5 Hz, 1 H) 7.77 (d, J=8.2 Hz, 1 H) 8.13 (s, 1 H) 8.72 (br s, 3 H) 10.99 - 11.69 (m, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.74 - 1.93 (m, 13 H) 1.95 - 2.06 (m, 2 H) 2.06 - 2.16 (m, 1 H) 3.57 - 3.81 (m, 6 H) 3.82 - 3.92 106 (m, 1 H) 4.48 (d, J=15.2 Hz, 1 H) 4.58 (spt, J=6.0 Hz, 1 H) 5.14 - 5.20 (m, 1 H) 5.24 (d, J=15.2 Hz, 1 H) 6.84 (br d, J=8.7 Hz, 2 H) 7.23 (br d, J=8.7 Hz, 2 H) 7.29 (d, J=5.6 Hz, 1 H) 7.66 (d, J=8.3 Hz, 1 H) 8.02 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.24 (d, J=6.0 Hz, 6 H) 1.76 - 1.92 (m, 13 H) 1.95 - 2.05 (m, 2 H) 2.05 - 2.18 (m, 1 H) 3.55 - 3.81 (m, 6 H) 3.82 - 3.92 107 (m, 1 H) 4.48 (d, J=15.2 Hz, 1 H) 4.58 (spt, J=6.0 Hz, 1 H) 5.15 - 5.21 (m, 1 H) 5.24 (d, J=15.2 Hz, 1 H) 6.84 (br d, J=7.5 Hz, 2 H) 7.23 (br d, J=7.5 Hz, 2 H) 7.29 (d, J=5.6 Hz, 1 H) 7.66 (d, J=8.3 Hz, 1 H) 8.02 (br s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.72 - 1.94 (m, 12 H) 2.08 - 2.25 (m, 2 H) 3.71 - 3.87 (m, 2 H) 3.95 (dd, J=13.3, 11.3 Hz, 1 H) 110 4.05 - 4.17 (m, 1 H) 4.22 - 4.44 (m, 3 H) 4.50 - 4.69 (m, 2 H) 5.26 (d, J=15.1 Hz, 1 H) 6.86 (br d, J=8.8 Hz, 2 H) 7.26 (br d, J=8.8 Hz, 2 H) 7.37 (d, J=5.5 Hz, 1 H) 7.76 (d, J=8.3 Hz, 1 H) 8.05 (br s, 1 H) 8.08 - 8.60 (m, 3 H) Compound NMR 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.1 Hz, 6 H) 1.39 - 1.59 (m, 2 H) 1.73 - 1.95 (m, 14 H) 3.44 - 3.52 (m, 2 H) 3.63 - 3.81 (m, 4 H) 3.89 (dd, 113 J=12.4, 6.3 Hz, 1 H) 4.49 (d, J=15.3 Hz, 1 H) 4.59 (spt, J=6.1 Hz, 1 H) 4.83 (tt, J=7.9, 3.9 Hz, 1 H) 5.25 (d, J=15.3 Hz, 1 H) 6.85 (br d, J=8.7 Hz, 2 H) 7.24 (br d, J=8.7 Hz, 2 H) 7.30 (d, J=5.6 Hz, 1 H) 7.67 (d, J=8.3 Hz, 1 H) 8.03 (s, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.90 - 2.10 (m, 12 H) 3.95 - 4.04 (m, 1 H) 4.09 - 4.17 (m, 1 H) 4.41 (dd, J=11.0, 7.3 Hz, 1 H) 117 4.53 - 4.68 (m, 2 H) 5.27 (d, J=15.1 Hz, 1 H) 6.87 (br d, J=8.8 Hz, 2 H) 7.27 (br d, J=8.8 Hz, 2 H) 7.42 (d, J=5.5 Hz, 1 H) 7.78 (d, J=8.0 Hz, 1 H) 8.17 (s, 1 H) 8.37 - 8.88 (m, 3 H) 15.44 - 16.71 (m, 1 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.25 (d, J=6.0 Hz, 6 H) 1.80 - 1.99 (m, 12 H) 3.50 - 3.62 (m, 8 H) 3.97 (dd, J=13.3, 11.0 Hz, 1 H) 4.05 - 4.17 (m, 1 H) 118 4.37 (dd, J=11.0, 7.4 Hz, 1 H) 4.52 - 4.69 (m, 2 H) 5.26 (d, J=15.3 Hz, 1 H) 6.86 (br d, J=8.7 Hz, 2 H) 7.27 (br d, J=8.7 Hz, 2 H) 7.39 (d, J=5.5 Hz, 1 H) 7.76 (d, J=8.0 Hz, 1 H) 8.09 (br s, 1 H) 8.15 - 9.27 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.21 - 1.32 (m, 1 H) 1.45 - 1.72 (m, 5 H) 1.73 - 1.93 (m, 12 H) 2.52 - 2.68 (partially hidden m, 3 H) 3.99 (dd, J=13.4, 125 11.0 Hz, 1 H) 4.06 - 4.20 (m, 2 H) 4.33 - 4.41 (m, 1 H) 4.44 (d, J=14.9 Hz, 1 H) 5.25 (d, J=14.9 Hz, 1 H) 6.46 (br d, J=8.3 Hz, 2 H) 7.13 (br d, J=8.3 Hz, 2 H) 7.34 (d, J=5.6 Hz, 1 H) 7.75 (d, J=8.2 Hz, 1 H) 8.05 (s, 1 H) 8.58 - 8.73 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.79 - 2.14 (m, 12 H) 3.98 (dd, J=13.3, 11.0 Hz, 1 H) 4.08 - 4.15 (m, 1 H) 4.34 - 4.46 (m, 1 H) 4.65 (s, 2 H) 4.69 126 (d, J=15.3 Hz, 1 H) 5.20 (d, J=15.3 Hz, 1 H) 6.86 (br d, J=8.8 Hz, 2 H) 7.29 (br d, J=8.8 Hz, 2 H) 7.47 (d, J=5.5 Hz, 1 H) 7.76 (d, J=8.0 Hz, 1 H) 8.14 (br s, 1 H) 8.20 - 9.36 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.60 - 1.72 (m, 4 H) 1.73 - 1.91 (m, 12 H) 2.72 - 2.83 (m, 1 H) 3.38 - 3.47 (m, 2 H) 3.91 - 4.03 (m, 3 H) 4.08 - 4.17 (m, 128 1 H) 4.42 (dd, J=11.0, 7.5 Hz, 1 H) 4.55 (d, J=15.6 Hz, 1 H) 5.33 (d, J=15.6 Hz, 1 H) 7.24 (br d, J=8.5 Hz, 2 H) 7.31 - 7.36 (m, 3 H) 7.78 (d, J=8.0 Hz, 1 H) 8.07 (s, 1 H) 8.12 - 9.20 (m, 3 H) 1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.51 - 2.09 (m, 16 H) 2.01 - 2.65 (partially hidden m, 1 H) 2.78 - 3.10 (m, 2 H) 3.37 - 3.72 (partially hidden m, 2 H) 135 3.99 (dd, J=13.2, 11.2 Hz, 1 H) 4.08 - 4.17 (m, 1 H) 4.34 - 4.47 (m, 1 H) 4.54 (br d, J=15.2 Hz, 1 H) 5.26 (d, J=15.2 Hz, 1 H) 6.89 - 7.09 (m, 2 H) 7.25 (br d, J=8.1 Hz, 2 H) 7.36 (d, J=5.5 Hz, 1 H) 7.76 (d, J=8.0 Hz, 1 H) 8.13 (br s, 1 H) 8.55 - 8.73 (m, 3 H) The examples which follow describe the preparation of some compounds of formula (I) described herein. The numbers of the compounds exemplified below match those given in the Table 1 above. All reactions are performed under inert atmosphere, unless otherwise stated. In the following examples, when the source of the starting products is not specified, it should be understood that said products are known compounds. EXAMPLES methods used NMR: The proton magnetic resonance spectra (1H NMR), are recorded at 400 MHz, or 500 MHz in DMSO-d6, using the DMSO-d6 peak as reference. The chemical shifts (δ) are expressed in parts per million (ppm). The signals observed are expressed as follows: s = singlet; d = doublet; t = triplet; m = multiplet or br s = broad singlet; br m = broad multiplet; q = quartet; dd = doublet of doublets; tt = triplet of triplets; spt = septet; br d = broad doublet; br t = broad triplet; br dd = broad doublet of doublets. LCMS: The LCMS characteristics were obtained by different Liquid Chromatography analytical methods (A to H) as described above. Intermediates: Intermediate 6: Step 1: To a solution of starting material 1, 4-difluoro-5-nitrobenzoate (200 g, 1 mol, 1.00 eq) and (tert-butoxycarbonyl)-L-cysteine (222.23 g, 1 mol, 1.00 eq) in toluene (2321 mL) was added dropwise DIPEA (351.05 mL, 2.01 mol, 2.00 eq) at 25 °C under N2. The reaction was stirred at 25 °C for 12 hours. The reaction was diluted with water (1.0 L) and the toluene phase extracted 3 times with 1L of water. The combined aqueous phase was then extracted with 1.0 L ethyl ether before being acidified to pH=2 with a 2M solution of aqueous HCl (850 mL). The combined aqueous phase was extracted 3 times with DCM. The combined organic layers (DCM) were washed twice with brine (5.0 L), dried over Mg2SO4, filtered, concentrated under reduced pressure and dried 2 hours in a drying oven to afford intermediate 2 N-(tert-butoxycarbonyl)-S-(4-(methoxycarbonyl)-2-nitrophenyl)-L-cysteine (392.85 g; 970 mmol) as yellow solid. (yield 97%). ES-MS m / z 401 [M+H]+, Retention time: 1.56 min. (Method F) Step 2: To a solution of intermediate 2 N-(tert-butoxycarbonyl)-S-(4-(methoxycarbonyl)-2- nitrophenyl)-L-cysteine (145,5g, 363.38 mmol) in 2.9 L of acetone was added an aqueous buffer solution 4M ammonium acetate (1.82 L, 7.27 mol). The reaction was cooled down to 10°C before adding slowly Titanium(III) Chloride (1.96 L, 2.54 mol). During the addition, the temperature of the reaction was maintained between 9 and 13°C. After 30 minutes the reaction mixture was extracted twice with 3L of EtOAc. The combined organic layers were washed twice with water (2.0 L), with brine (2.0 L), dried over Mg2SO4, filtered, concentrated under reduced pressure. The resulting solid was then redissolved twice in 500mL of toluene and reconcentrated under reduced pressure to get an orange solid intermediate 3 (144 g, 363mmol) S-(2-amino-4-(methoxycarbonyl)phenyl)-N-(tert- butoxycarbonyl)-L-cysteine as yellow solid. (yield 100%) ES-MS m / z 371 [M+H]+, Retention time: 1.42 min. (Method F) Step 3: intermediate 3 S-(2-amino-4-(methoxycarbonyl)phenyl)-N-(tert-butoxycarbonyl)- L-cysteine (73g, 197.07 mmol) was dissolved in THF (1.6 L) in a 3-neck round bottom flask. 1-propanephosphonic anhydride (234.63 mL, 394.15 mmol) was first added before the dropwise addition of N,N-diisopropylethylamine (172.21 mL, 985.37 mmol) under vigorous stirring. The reaction temperature was maintained under 25°C and the mixture was stirred overnight (20 hours). The reaction was diluted with water (1.5 L). The aqueous phase was then extracted with 1.0L EtOAc. The combined organic layers were washed twice with water (1.0 L), with a saturated solution of Na2CO3(1.0 L), dried over Mg2SO4, filtered, and concentrated under reduced pressure. The resulting solid was than triturated with 350mL of diisopropylether and filtered. The resulting solid was dried in a drying oven to get intermediate 4 (57.4 g, 162.7 mmol) methyl (R)-3-((tert-butoxycarbonyl)amino)-4-oxo- 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylate as yellow solid. (yield 82.6%). ES-MS m / z 353 [M+H]+, Retention time: 1.50 min. (Method F) Step 4: Intermediate 4 methyl (R)-3-((tert-butoxycarbonyl)amino)-4-oxo-2,3,4,5- tetrahydrobenzo[b][1,4]thiazepine-7-carboxylate (31 g, 87.97 mmol) was dissolved in THF (600 mL) in a 3-neck round bottom flask. [4-(propan-2-yloxy)phenyl]methanol (18.47 g, 105.56 mmol), and triphenylphosphine (36.12 g, 136,35 mmol) were added to the reaction mixture under vigorous stirring. Then diisopropyl azodicarboxylate (27.29 mL, 131.95 mmol) was added dropwise to the reaction mixture over a 5 minutes period as temperature raised to 41°C. The reaction mixture was stirred 40 minutes at room temperature before adding an aqueous solution of LiOH (439.83 mL, 87.97 mmol) dropwise. The reaction was than stirred 35 hours at room temperature. The reaction was diluted with water (700 mL) and diisopropylether (200 mL). After vigorous shaking, the organic layers were washed with water (2 x 250 mL). Then all the combined aqueous layers were washed with diisopropylether (2 x 200mL) and iPrOAc (2x 200 mL). The aqueous phase was acidified to pH 2-3 with an aqueous solution of HCl 1N. After 30 minutes of stirring this aqueous phase was extracted with 1.0 L EtOAc. The combined organic layers were washed twice with brine (200 mL), dried over Mg2SO4, filtered, and concentrated under reduced pressure to afford intermediate 5 (37 g, 75.6 mmol) (R)-3-((tert-butoxycarbonyl)amino)-5-(4- isopropoxybenzyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylic acid as yellow solid. (yield 86%). ES-MS m / z 487 [M+H]+, Retention time: 1.79 min. (Method A) Step 5: intermediate 5 (R)-3-((tert-butoxycarbonyl)amino)-5-(4-isopropoxybenzyl)-4-oxo- 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylic acid (36 g, 73.99 mmol) was dissolved in chloroform (250 mL) in a 3-neck round bottom flask. An alumina / H2O (80 / 20) mixture was prepared in a beaker. Under mechanic stirring, standard alumina (128 g) et water (32.04 mL), potassium peroxymonosulfate (185.64 g, 295.94 mmol) were added to the reaction mixture and stirred during 24 hours. The alumina was filtered and washed 3 times with 250 mL of DCM. All the filtered solutions were concentrated, the resulting cake was suspended and stirred in 200 mL of diisopropylether for 2 hours. The solid in suspension was than filtered of and washed twice with heptane (50m L) to get intermediate 6 (24 g, 0.46mmol) (3R)-3-(tert- butoxycarbonylamino)-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5- benzothiazepine-7-carboxylic acid as white solid. (yield 62 %). ES-MS m / z 519 [M+H]+, Retention time: 1.67 min. (Method A) Intermediate 15: Intermediate 3: Step 1: To a solution of starting material 10 methyl 2,4-difluoro-5-nitrobenzoate (200 g, 921.12 mmol) and (tert-butoxycarbonyl)-L-cysteine (203.82 g, 921,12 mmol) in toluene (2L) was added dropwise DIPEA (313.29 mL, 1.84 mol) at 25 °C under N2. The reaction was stirred at 25 °C for 20 h. The reaction was diluted with water (1.5 L) and the toluene phase extracted 3 times with 1.L of water. The combined aqueous phase was then washed twice with 1.0L terbutylether before being acidified to pH=2 with a 5M aqueous solution of HCl (150mL). The combined aqueous phase was extracted 3 times with EtOAc. The combined organic layers (EtOAc, 1.5L) were washed with brine (1.5L), dried over Mg2SO4, filtered, concentrated under reduced pressure to get intermediate 11 N-(tert- butoxycarbonyl)-S-(5-fluoro-4-(methoxycarbonyl)-2-nitrophenyl)-L-cysteine (365 g, 874mmol) as yellow oil. (yield 95%). ES-MS m / z 418 [M+H]+, Retention time: 1.21 min. (Method A) Step 2: To a solution of intermediate 11 N-(tert-butoxycarbonyl)-S-(5-fluoro-4- (methoxycarbonyl)-2-nitrophenyl)-L-cysteine (175 g, 418.27 mmol) in 3.5 L of acetone was added 4M ammonium acetate buffer (2.1 L, 8.37 mol). The reaction was cooled down to 10°C before adding slowly Titanium(III) Chloride (2.25 L, 2.93 mol). During the addition, the temperature of the reaction was maintained between 9 and 13°C. After 30 minutes the reaction mixture was extracted twice with 2.5 L of EtOAc. The combined organic layers were washed twice with water (2.5 L), with brine (2.5 L), dried over Mg2SO4, filtered, concentrated under reduced pressure. The resulting solid was then redissolved 4 times in 500mL of toluene and concentrated under reduced pressure to get as a white solid intermediate 12 S-(2-amino-5-fluoro-4-(methoxycarbonyl)phenyl)-N-(tert- butoxycarbonyl)-L-cysteine (134 g, 345mmol) as yellow solid. (yield 82.5%). ES-MS m / z 388 [M+H]+, Retention time: 1.64 min. (Method A) Step 3: Intermediate 12 S-(2-amino-5-fluoro-4-(methoxycarbonyl)phenyl)-N-(tert- butoxycarbonyl)-L-cysteine (134 g, 345 mmol) was dissolved in THF (3L) in a 3-neck round bottom flask. 1-propanephosphonic anhydride (410.74 mL, 689.99 mmol) was first added before the dropwise addition of N,N-diisopropylethylamine (301.47 mL, 1.72 mol) under vigorous stirring. The reaction temperature was maintained under 25°C and the mixture was stirred overnight (20 hours). The reaction was diluted with water (2.5 L). The aqueous phase was then extracted twice with 2.0 L EtOAc. The combined organic layers were washed twice with water (2.0 L), with brine (2.0 L), dried over Mg2SO4, filtered, and concentrated under reduced pressure. The resulting solid was than triturated with 350 mL of diisopropylether and filtered. The resulting solid was dried in a drying oven to get intermediate 13 methyl (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-4-oxo-3,5-dihydro-2H-1,5-benzothiazepine-7- carboxylate (105.7 g, 285mmol) as yellow solid. (yield 82.7%). ES-MS m / z 371 [M+H]+, Retention time: 1.59 min. (Method E) Step 4: Intermediate 13 methyl (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-4-oxo-3,5- dihydro-2H-1,5-benzothiazepine-7-carboxylate (60 g, 162 mmol) was dissolved in THF (1L) in a 3-neck round bottom flask. [4-(propan-2-yloxy)phenyl]methanol (26.93 g, 162 mmol), and triphenylphosphine (65.86 g, 251 mmol) were added to the reaction mixture under vigorous stirring. Then diisopropyl azodicarboxylate (47.84 mL, 243 mmol) was added dropwise to the reaction mixture over a 5 minutes period and temperature raised to 31°C. The reaction mixture was stirred 24 hours at room temperature before adding an aqueous solution of lithium hydroxide (4.66 g, 194 mmol) dropwise. The reaction was then stirred 48 hours at room temperature. The reaction was diluted with water (920 mL) and extracted 3 times with diisopropylether (360mL). The aqueous phase was acidified to pH 2-3 with a solution of HCl 2N. After 30 minutes of stirring this aqueous phase were extracted twice with 750mL EtOAc. The combined organic layers were washed twice with brine (200mL), dried over Mg2SO4, filtered, and concentrated under reduced pressure to get intermediate 14 (3R)-3-(tert- butoxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-4-oxo-2,3-dihydro-1,5- benzothiazepine-7-carboxylic acid (56.55 g, 112mmol) as yellow solid. (yield 69%). ES-MS m / z 505 [M+H]+, Retention time: 2.21 min. (Method E) Step 5: Intermediate 14 (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-4-oxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (56.55 g, 112 mmol) was dissolved in chloroform (720 mL) in a 3 neck round bottom flask. An alumina / H2O (80 / 20) mixture was prepared in a beaker. Under mechanic stirring, standard alumina (195 g), water (51 mL), and potassium peroxymonosulfate (275.6 g, 450 mmol) were added to the reaction mixture and stirred at 50°C during 48 hours. LC / MS shows that there is still some sulfoxide remaining. Standard alumina (98 g), water (26 mL), and potassium peroxymonosulfate (138 g) were added to the reaction mixture and stirred at 60°C during 24 hours. The alumina was filtered and washed 3 times with 200 mL of DCM. All the filtered solutions were concentrated, and the resulting cake was suspended and stirred in 200 mL of diisopropylether for 2 hours. The solid in suspension was than filtered of and washed twice with diisopropylether (30mL) to get intermediate 15 (3R)-3-(tert-butoxycarbonylamino)-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7- carboxylic acid (24 g, 44.7mmol) as white solid. (yield 39.91 %). ES-MS m / z 537 [M+H]+, Retention time: 2.14 min. (Method E) Intermediate 24: butoxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylic acid (13.48 g, 50.05 mmol) in 135mL of DMF, were added N'-hydroxy-2,2-dimethyl-propanamidine (6.39 g, 55.05 mmol) and TBTU (19.28 g, 60.06 mmol). Triethylamine (15.1 g, 150.1 mmol) was added dropwise to the reaction mixture in 5 minutes under vigorous stirring. The temperature of the reaction raised from 21°C to 34°C and the reaction mixture was stirred for 2 hours. The reaction mixture is poured into 1.3L of water and a white precipitate appears. The mixture is vigorously stirred during 2 hours and then filtered. The white residue is washed with water and dried in a drying oven at 50°C overnight. White solid intermediate 22 tert-butyl N-[4- [[(E)-C-tert-butyl-N-hydroxy-carbonimidoyl]carbamoyl]-1- bicyclo[2.2.2]octanyl]carbamate (14.54 g, 39.5mmol). (yield 79%). ES-MS m / z 368 [M+H]+, Retention time: 1.76 min. (Method E) Step 2: In a round bottom flask equipped with a cooling chiller, intermediate 22 -tert-butyl N-[4-[[(E)-C-tert-butyl-N-hydroxy-carbonimidoyl]carbamoyl]-1- bicyclo[2.2.2]octanyl]carbamate (14.5 g, 39.5 mmol) was dissolved in 270 mL 1,4-dioxane. The reaction mixture was refluxed for 3.5 hours. The mixture was then concentrated under reduced pressure to get intermediate 23 tert-butyl N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)- 1-bicyclo[2.2.2]octanyl]carbamate (14.54 g, 39.5mmol). (yield 100 %). ES-MS m / z 350 [M+H]+, Retention time: 2.49 min. (Method E) Step 3: To intermediate 23 -tert-butyl N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1- bicyclo[2.2.2]octanyl]carbamate (13.8 g, 39.5 mmol) in a round bottom flask were added 98.7 mL of a solution of HCl in dioxane (4M). The reaction mixture was stirred overnight at room temperature. Overnight a beige precipitate appeared. The reaction mixture was filtered, and the solid residue washed with pentane. After drying in a drying oven overnight a beige solid was obtained: intermediate 24 4-(3-tert-butyl-1,2,4-oxadiazol-5- yl)bicyclo[2.2.2]octan-1-amine;hydrochloride (11.3 g, 39.5mmol). (yield 100 %). ES-MS m / z 250 [M+H]+, Retention time: 1.03 min. (Method E) Examples Example 1: preparation of compound (61) Step 1: To a solution of intermediate 15 (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (402 mg, 0.7492 mmol) in 4 mL of DMF were added intermediate 244-(3-tert-butyl-1,2,4- oxadiazol-5-yl)bicyclo[2.2.2]octan-1-amine;hydrochloride (170 mg, 0.59mmol), TBTU (402 mg, 1.25 mmol) and triethylamine (0.57 mL, 4.1 mmol). Addition of triethylamine was slightly exothermic. The reaction mixture was stirred at room temperature for 1.5 hour. Then the reaction mixture was poured into 40 mL of water and stirred for another 15 minutes. A solid residue was formed, filtered of and washed with water and pentane. After drying overnight in a drying oven a beige solid was obtained intermediate 16 tert-butyl N-[(3R)-7- [[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate. (457 mg, 0.65mmol) (yield 88.45 %). ES-MS m / z 768 [M+H]+, Retention time: 2.14 min. (Method A) Step 2: To a solution of intermediate 16 -tert-butyl N-[(3R)-7-[[4-(3-tert-butyl-1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (400 mg, 0.52 mmol) in 3 mL of dioxane were added 1.3 mL of HCl 4 M in dioxane (1.25 mL, 5 mmol, 4 mol / L). The reaction mixture was stirred overnight at room temperature. As the reaction wasn’t finished, 1.3mL of HCl 4M in dioxane (5.2 mmol, 4 mol / L) were added the next morning and the reaction stirred for 5 hours more. Then the reaction mixture was concentrated, treated with a saturated solution of NaHCO3and extracted with 2x30 mL EtOAc. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The resulting solid was washed with ethylether and pentane before being dried in a drying oven overnight to obtain Compound (61) (3R)-3-amino-N-[4-(3-tert-butyl- 1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (277 mg, 0.41 mmol) (yield 80 %). ES-MS m / z 668 [M+H]+, Retention time: 1.57 min. (Method A)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.24 (d, J=6.0 Hz, 6 H) ; 1.28 (s, 9 H) ; 1.88 - 2.10 (m, 14 H) ; 3.59 - 3.72 (m, 2 H) ; 3.81 - 3.94 (m, 1 H) ; 4.51 (d, J=15.3 Hz, 1 H) ; 4.59 (spt, J=6.0 Hz, 1 H) ; 5.24 (d, J=15.3 Hz, 1 H) ; 6.85 (d, J=8.5 Hz, 2 H) ; 7.24 (d, J=8.5 Hz, 2 H) ; 7.33 (d, J=5.8 Hz, 1 H) ; 7.67 (d, J=8.3 Hz, 1 H) ; 8.13 (br s, 1 H). Example 2: preparation of compound (133) Step 1: To a solution of intermediate 15 (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (350 mg, 0.65 mmol) and tert-butyl-4-aminobicyclo[2.2.2]octane-1-carboxylate (160 mg, 0.71 mmol) in 5 mL of DCM were added 1-propanephosphonic anhydride (0.78 mL, 1.3 mmol) and dropwise N,N-diisopropylethylamine (0.45 mL, 2.6 mmol). The reaction mixture was stirred 2 hours at room temperature. The reaction was diluted with DCM (30 mL). The organic layers were washed twice with water (30 mL), dried over Mg2SO4, filtered, and concentrated under reduced pressure. After purification by flash chromatography intermediate 17 tert-butyl 4-[[(3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-16,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate was obtained as a white solid. (330 mg, 0.44 mmol) (yield 68%). ES-MS m / z 744 [M+H]+, Retention time: 2.5 min. (Method C) Step 2: To a solution of intermediate 17 tert-butyl 4-[[(3R)-3-(tert-butoxycarbonylamino)- 8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (330 mg, 0.44 mmol) in 3 mL of dioxane were added 5.5mL of HCl 4M in dioxane (22 mmol). The reaction mixture was stirred overnight at room temperature. Then the reaction mixture was concentrated. The resulting white solid was triturated with diethyl ether twice and after filtration dried overnight in a drying oven to obtain Compound (133) 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (255 mg, 0.41mmol)(yield 93.8 %). ES-MS m / z 588 [M+H]+, Retention time: 0.80 min. (Method B)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.25 (d, J=6.0 Hz, 6 H) ; 1.72 - 1.93 (m, 12 H) ; 3.98 (dd, J=13.3, 11.0 Hz, 1 H) ; 4.12 (dd, J=13.3, 7.4 Hz, 1 H) ; 4.38 (dd, J=11.0, 7.4 Hz, 1 H) ; 4.53 - 4.64 (m, 2 H) ; 5.26 (d, J=15.2 Hz, 1 H) ; 6.85 (d, J=8.8 Hz, 2 H) ; 7.26 (d, J=8.8 Hz, 2 H) ; 7.38 (d, J=5.5 Hz, 1 H) ; 7.77 (d, J=8.2 Hz, 1 H) ; 8.07 (br s, 1 H) ; 8.20 - 8.80 (m, 3 H). Example 3: preparation of compound (127) Step 1: Same procedure than for preparation of intermediate 17. Starting from of intermediate 15 (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (1.05g, 2.4 mmol) and tert-butyl 4 aminobicyclo(2.2.2) pentane1 carboxylate (325 mg, 2.6 mmol) to afford intermediate 18 tert-butyl 3-[[(3R)-3-(tert-butoxycarbonylamino)-8-fluoro- 5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7- carbonyl]amino]bicyclo[1.1.1]pentane-1-carboxylate (1.14g, 1.76mmol, white solid) (yield 73%). ES-MS m / z 702 [M+H]+, Retention time: 1.22 min. (Method D) Step 2: Same procedure than for preparation of compound (133). Starting from tert-butyl 3- [[(3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1,5-benzothiazepine-7-carbonyl]amino]bicyclo[1.1.1]pentane-1- carboxylate (340mg, 0.45mmol) to afford- 3-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[1.1.1]pentane-1-carboxylic acid, hydrochloride (230mg, 0.42 mmol, white solid) (yield 92.4%). ES-MS m / z 546 [M+H]+, Retention time: 0.80 min. (Method B)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.24 (d, J=6.0 Hz, 6 H) ; 2.27 (s, 6 H) ; 3.98 (dd, J=13.3, 11.1 Hz, 1 H) ; 4.14 (dd, J=13.3, 7.5 Hz, 1 H) ; 4.40 (dd, J=11.1, 7.5 Hz, 1 H) ; 4.58 (spt, J=6.0 Hz, 1 H) ; 4.79 (d, J=15.3 Hz, 1 H) ; 5.14 (d, J=15.3 Hz, 1 H) ; 6.83 (d, J=8.8 Hz, 2 H) ; 7.24 (d, J=8.8 Hz, 2 H) ; 7.65 (d, J=5.7 Hz, 1 H) ; 7.79 (d, J=8.5 Hz, 1 H) ; 8.13 - 9.21 (m, 3 H) ; 9.27 (br s, 1 H). Example 4: preparation of compound (123) Step 1: To a solution of intermediate 17 tert-butyl 4-[[(3R)-3-(tert-butoxycarbonylamino)- 8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (198 mg, 0.27 mmol) in 5 mL of dioxane was added 0.25mL of HCl 4M in dioxane (1 mmol). The reaction mixture was stirred overnight at room temperature. The next day, 1mL of HCl 4M in dioxane (4 mmol) was added and the reaction mixture stirred overnight. Then the reaction mixture was concentrated without heating at room temperature. The reaction mixture is then poured in 50mL of DCM. The organic layers are washed twice with a saturated solution of NaHCO3, dried over Na2SO4, filtered and concentrated. After purification by flash chromatography compound (123) tert-butyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1- 6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate was obtained as a white solid (25 mg, 0.043 mmol) (yield 16%). ES-MS m / z 644 [M+H]+, Retention time: 1.14 min. (Method B)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.25 (d, J=6.0 Hz, 6 H) ; 1.37 (s, 9 H) ; 1.69 - 1.92 (m, 12 H) ; 1.98 - 2.03 (m, 2 H) ; 3.57 - 3.71 (m, 2 H) ; 3.82 - 3.92 (m, 1 H) ; 4.47 (d, J=15.2 Hz, 1 H) ; 4.58 (spt, J=6.0 Hz, 1 H) ; 5.24 (d, J=15.2 Hz, 1 H) ; 6.85 (d, J=8.8 Hz, 2 H) ; 7.23 (d, J=8.8 Hz, 2 H) ; 7.28 (d, J=5.7 Hz, 1 H) ; 7.66 (d, J=8.4 Hz, 1 H) ; 7.99 (br s, 1 H). preparation of compound (93) Step 1: To a solution of intermediate 6 (3R)-3-(tert-butoxycarbonylamino)-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (250 mg, 0.65 mmol) in 20 mL of DCM were added 213 mg of tert-butyl 4- hydroxybicyclo[2.2.2]octane-1-carboxylate, dicyclohexylcarbodiimide (139 mg), 4- dimethylaminopyridine (27mg) and DL-10-camphorsulfonic acid (13 mg) . The reaction mixture was stirred during 18 hours at room temperature. After dilution with 50mL of water, the reaction mixture is extracted 3 times with DCM (50mL). The combined organic layers are then dried over Na2SO4, filtered and concentrated. After purification by flash chromatography intermediate 19 was obtained (205 mg, 0.28 mmol). (4-tert- butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-(tert-butoxycarbonylamino)-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylate. ES-MS m / z 727.5 [M+H]+, Retention time: 1.91min. (Method B) Step 2: To a solution of intermediate 19, 4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-(tert-butoxycarbonylamino)-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1,5-benzothiazepine-7-carboxylate (205mg, 0.28mmol) in 5 mL of dioxane were added) in 4 mL of dioxane were added 3 mL of HCl 4M in dioxane (12 mmol). The reaction mixture was stirred 15 hours at room temperature. The reaction mixture was concentrated without heating at room temperature. The reaction mixture was then poured in 20mL of DCM. The organic layers were washed twice with a saturated solution of NaHCO3, dried over Na2SO4, filtered and concentrated. After purification by flash chromatography compound (93) (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxylate was obtained as a white solid (33 mg, 0.052 mmol) (yield 19%). ES-MS m / z: 627 [M+H]+, Retention time: 1.25. (Method B)1H NMR (400 MHz, DMSO-d6, 30°C) δ ppm 1.26 (d, J=6.0 Hz, 3 H) 1.26 (d, J=6.0 Hz, 6 H) 1.37 (s, 9 H) 1.79 - 1.89 (m, 6 H) 1.92 - 2.07 (m, 8 H) 3.56 - 3.76 (m, 2 H) 3.80 - 3.90 (m, 1 H) 4.32 (d, J=15.1 Hz, 1 H) 4.60 (spt, J=6.0 Hz, 1 H) 5.39 (d, J=15.1 Hz, 1 H) 6.89 (d, J=8.8 Hz, 2 H) 7.25 (d, J=8.8 Hz, 2 H) 7.61 (d, J=1.3 Hz, 1 H) 7.95 (br dd, J=8.3, 1.3 Hz, 1 H) 7.99 (d, J=8.3 Hz, 1 H). Example 6: preparation of compound (60) Step 1: Intermediate 13 methyl (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-4-oxo-3,5- dihydro-2H-1,5-benzothiazepine-7-carboxylate (2 g, 5.4mmol) was dissolved in THF (70mL) in a 3-neck round bottom flask. [4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methanol (1.43 g, 6.47 mmol), triphenylphosphine (2.2 g, 8.37mmol) were added to the reaction mixture under vigorous stirring. Then diisopropyl azodicarboxylate (1.64 g, 8.1 mmol) was added dropwise to the reaction mixture over a 5 minutes period and temperature raised to 25°C. The reaction mixture was stirred 1 hour at room temperature. The reaction mixture was then diluted with EtOAc (150mL). The organic layer was washed with water and brine, dried with Na2SO4, filtered and evaporated. The resulting solid was dissolved in THF (55 mL) and a LiOH hydrate solution (3.8 mmol in 20mL of water) was added dropwise to the reaction mixture with stirring. The reaction was stirred overnight at room temperature. THF was then concentrated and the reaction mixture acidified with 2.5 mL of HCl 3N in water. After addition of water (30 mL), the white residue was filtered of, washed with water twice and dried in a drying oven overnight to obtain intermediate 30 (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-4-oxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (1.63 g, 2.72 mmol) (yield 54%). ES-MS m / z 559 [M+H]+, Retention time: 1.79 min. (Method C) Step 2: To a solution of (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-4-oxo-5-[[4-[(1R)- 2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro-1,5-benzothiazepine-7- carboxylic acid1 (1.63 g, 2.72 mmol) in DCM (60 mL) were added 3-Cl perbenzoic acid (1.68 g, 7.3 mmol). The reaction mixture was stirred overnight at room temperature. 0.75g (3.2 mmol) of 3-Cl perbenzoic acid was added the next day and the reaction stirred for another 48 hours. Then the reaction mixture was concentrated and after purification by flash chromatography a white solid was isolated to obtain intermediate 31 (tertbutoxycarbonylamino)-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro- 1methylethoxy]phenyl]methyl]-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (1.5 g, 2.36 mmol) (yield 87%). ES-MS m / z 591 [M+H]+, Retention time: 1.66 min. (Method C) Step 3: Same procedure than for preparation of intermediate 17. Starting from intermediate 31 tertbutoxycarbonylamino)-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro- 1methylethoxy]phenyl]methyl]-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (236 mg, 0.4mmol) to afford tert-butyl N-[(3R)-7-[[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1- bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1- methyl-ethoxy]phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (196 mg, 0.24 mmol) (yield 59.5%). ES-MS m / z 866 [M+HCOO]-, Retention time: 2.22 min. (Method C) Step 4: To a solution intermediate 32 tert-butyl N-[(3R)-7-[[4-(3-tert-butyl-1,2,4-oxadiazol- 5-yl)-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro- 1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (196 mg, 0.24 mmol) in 4 mL of DCM were added (0.55 mL, 7.15 mmol) of TFA. The reaction mixture was stirred 3 hours at room temperature. The reaction was then concentrated, treated with 20mL of saturated solution of NaHCO3, extracted with EtOAc twice. The combined organic layers were washed with water, dried with Na2SO4, filtered and evaporated. The white residue was washed with ether and pentane to get compound (60) (3R)-3-amino-N- [4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-1,1,4-trioxo-5-[[4- [(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine- 7-carboxamide(120 mg, 0.17mmol) (yield 71.5%). ES-MS m / z 722 [M+H]+, Retention time: 1.19 min. (Method B)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.28 (s, 9 H) ; 1.39 (d, J=6.4 Hz, 3 H) ; 1.90 - 2.09 (m, 14 H) ; 3.59 - 3.70 (m, 2 H) ; 3.81 - 3.94 (m, 1 H) ; 4.60 (d, J=15.4 Hz, 1 H) ; 5.16 - 5.29 (m, 2 H) ; 7.03 (d, J=8.6 Hz, 2 H) ; 7.30 (d, J=8.6 Hz, 2 H) ; 7.37 (d, J=5.4 Hz 1 H) ; 7.68 (d, J=8.3 Hz, 1 H) ; 8.14 (br s, 1 H). Example 7: preparation of compound (34) Step 1: To a solution of tert-butyl N-(4-cyano-1-bicyclo[2.2.2]octanyl)carbamate (279 mg, 1.1 mmol) in 5 mL of EtOH were added (0.66mL, 11.15mmol) hydroxyl amine (50% in water). The reaction mixture was heterogenous and was heated at 80°C for 4 hours. After evaporation, the white solid is solubilized in EtOAc (25 mL). The organic phase was washed 3 time with water (10 mL), 3 times with brine (10 mL), dried with Na2SO4, filtered and evaporated to afford intermediate 42 tert-butyl N-[4-[(Z)-N'-hydroxycarbamimidoyl]-1- bicyclo[2.2.2]octanyl]carbamate as a white solid (301 mg, 1.mmol) (yield 95%). ES-MS m / z 284 [M+H]+, Retention time: 0.96 min. (Method E) Step 2: Intermediate 42, tert-butyl N-[4-[(Z)-N'-hydroxycarbamimidoyl]-1- bicyclo[2.2.2]octanyl]carbamate (100 mg, 0.35mmol), imidazole hydrochloride (92 mg) and NNdimethyl pivalamide (0.35mL) were heated together at 120°C with stirring. The reaction mixture was ten poured in a solution of EtOAc / NaCl saturated solution (30 mL). The mixture was extracted with EtOAc (2 times 15mL). The combined organic layers were washed twice with brine, dried with MgSO4, filtered and evaporated to an oil. After purification by flash chromatography intermediate 43 tert-butyl N-[4-(5-tert-butyl-1,2,4- oxadiazol-3-yl)-1-bicyclo[2.2.2]octanyl]carbamate was isolated as a white solid. (87 mg, 0.25 mmol) (yield 70%). ES-MS m / z 350 [M+H]+, Retention time: 2.42 min. (Method E) Step 3: Same procedure than for preparation of compound (60). Staring from intermediate 43 tert-butyl N-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[2.2.2]octanyl]carbamate (172 mg, 0.49 mmol) to afford intermediate 44 as a white solid: 4-(5-tert-butyl-1,2,4- oxadiazol-3-yl)bicyclo[2.2.2]octan-1-amine (116mg, 0.46mmol) (yield 94%). ES-MS m / z 250 [M+H]+, Retention time: 0.90 min. (Method A) Step 4: Same procedure than for preparation of intermediate 16. Starting from intermediate 15 (3R)-3-(tertbutoxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxylic acid (194 mg, 0.36 mmol) and intermediate 44 4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)bicyclo[2.2.2]octan-1-amine (90 mg, 0.36 mmol) to afford intermediate 45 as a yellow powder: tert-butyl N-[(3R)-7-[[4-(5-tert- butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (244 mg, 0.32 mmol) (yield 88%). ES-MS m / z 768 [M+H]+, Retention time: 2.17 min. (Method A) Step 5: Same procedure than for preparation of compound (60) Starting from intermediate 45 tert-butyl N-[(3R)-7-[[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1- bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (242 mg, 032mmol) to afford (3R)-3- amino-N-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carboxamide compound (34) (192 mg, 0.29 mmol) (yield 91%) white solid. ES-MS m / z 668 [M+H]+, Retention time: 1.58 min. (Method A)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.25 (d, J=6.0 Hz, 6 H) ; 1.35 (s, 9 H) ; 1.86 - 2.03 (m, 14 H) ; 3.58 - 3.72 (m, 2 H) ; 3.81 - 3.94 (m, 1 H) ; 4.49 (d, J=15.0 Hz, 1 H) ; 4.59 (spt, J=6.0 Hz, 1 H) ; 5.25 (d, J=15.0 Hz, 1 H) ; 6.85 (d, J=8.6 Hz, 2 H) ; 7.24 (d, J=8.6 Hz, 2 H) ; 7.31 (d, J=5.6 Hz, 1 H) ; 7.67 (d, J=8.2 Hz, 1 H) ; 8.06 (br s, 1 H). preparation of compound (21) Step 1: Same procedure than intermediate 17. From intermediate 15 (3R)-3- (tertbutoxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1,5-benzothiazepine-7-carboxylic acid (2g, 3.73mmol) to afford intermediate 50 benzyl 4-[[(3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate (2.56 g, 3.2 mmol ) (yield 88%). ES-MS m / z 778 [M+H]+, Retention time: 1.34 min. (Method D) Step 2: To a solution of intermediate 50 benzyl 4-[[(3R)-3-(tert-butoxycarbonylamino)-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (2.56 g, 3.2 mmol ) in 15mL of MeOH were added 48mg of Pd / C 10%) in a flask under H2atmosphere. The reaction mixture was stirred at 50psi during 2.5 hours. After filtration the organic layers were evaporated and the resulting solid dried overnight in a drying oven to get a white solid intermediate 51.4-[[(3R)- 3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid (2.14 g, 3.1 mmol) (yield 97%). ES-MS m / z 688 [M+H]+, Retention time: 1.99 min. (Method C) Step 3: Same procedure than for preparation of intermediate 17. Starting from intermediate 51 (275 mg, 0.47 mmol) 4-[[(3R)-3-(tert-butoxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid to get intermediate 52 (370mg, 0.47mmol)(yield 100%) (crude intermediate used in the next step) tert-butyl N-[(3R)-7-[[4- [(2,2-dimethylpropanoylamino)carbamoyl]-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro- 5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3- yl]carbamate. ES-MS m / z 786 [M+H]+, Retention time: 1.13 min. (Method E) Step 4: To a solution of intermediate 52 tert-butyl N-[(3R)-7-[[4-[(2,2- dimethylpropanoylamino)carbamoyl]-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (370 mg, 0.47 mmol) in 5 mL THF was added Burgess reagent (CAS 29684-56-8, 448mg, 1.88 mmol). The reaction mixture was heated at 100°C under microwaves during 1 hour. Then the reaction mixture was poured into a 50 mL mixture of water and EtOAc 50 / 50. The mixture was extracted with EtOAc (2 times 25 mL). The combined organic layers were washed with water and brine, dried with MgSO4, filtered and evaporated. After purification by flash chromatography intermediate 53 was isolated as a white solid. tert-butyl N-[(3R)- 7-[[4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5- [(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate (237 mg, 0.31 mmol) (yield 65.6%). ES-MS m / z 767 [M+H]+, Retention time: 2.01 min. (Method E) Step 5: Same procedure than for preparation of compound (60). From intermediate 53 (237 mg, 0.31 mmol) tert-butyl N-[(3R)-7-[[4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1- bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate to afford compound (21) (3R)-3-amino-N- [4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide as a trifluoroacetate salt (184 mg, 0.3 mmol) (yield 97%). ES-MS m / z 668 [M+H]+, Retention time: 1.41 min. (Method A) 1.25 (d, J=6.0 Hz, 6 H) ; 1.33 (s, 9 H) ; 1.91 - 2.08 (m, 12 H) ; 3.92 - 4.13 (m, 2 H) ; 4.42 (dd, J=11.0, 7.5 Hz, 1 H) ; 4.54 - 4.65 (m, 2 H) ; 5.27 (d, J=15.5 Hz, 1 H) ; 6.87 (d, J=8.7 Hz, 2 H) ; 7.27 (d, J=8,7 Hz, 2 H) ; 7.41 (d, J=5.5 Hz, 1 H) ; 7.77 (d, J=8.0 Hz, 1 H) ; 8.15 (br s, 1 H) ; 8.25 - 8.70 (m, 3 H). Example 9: preparation of compound (31) Step 1: Same procedure than for preparation of intermediate 42. Starting from bicyclo(1.1.1)pentan-1-carbonitrile (150 mg, 1.53 mmol) to afford intermediate 60 N’- hydroxybicyclo (1.1.1)pentan-1carboxamidine (115 mg, 0.91mmol) (yield 60%). ES-MS m / z 127 [M+H]+, Retention time: 0.16 min. (Method A) Step 2: Same procedure than for preparation of intermediate 16 followed by flash chromatography. Starting from 4-(tert-butoxycarbonylamino)bicyclo[2.2.2]octane-1- carboxylic acid (170mg, 0.63mmol) to afford intermediate 61 (126 mg, 0.33mmol)(yield 52%) tert-butyl N-[4-[[(Z)-C-(1-bicyclo[1.1.1]pentanyl)-N- hydroxycarbonimidoyl]carbamoyl]-1-bicyclo[2.2.2]octanyl]carbamate. Step 3: A solution of intermediate 61 tert-butyl N-[4-[[(Z)-C-(1-bicyclo[1.1.1]pentanyl)-N- hydroxycarbonimidoyl]carbamoyl]-1-bicyclo[2.2.2]octanyl]carbamate (126 mg, 0.33 mmol) in 8 mL of dioxane was refluxed during 4 hours. The reaction mixture was concentrated, and treated with 25 mL of DCM and 25 mL of an aqueous NaHCO3 solution. The aqueous solution was extracted 3 times with DCM (20mL). The combined organic layers were washed 3 times with brine, dried with MgSO4, filtered and evaporated. After purification by flash chromatography intermediate 62 tert-butyl N-[4-[3-(1- bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]carbamate was isolated as a white solid (120 mg, 0.3 mmol) (yield 100%). ES-MS m / z 360 [M+H]+, Retention time: 1.96 min. (Method A) Step 4: Same procedure than for preparation of compound (60). Starting from intermediate 62 tert-butyl N-[4-[3-(1-bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]carbamate (120 mg, 0.3 mmol) to afford intermediate 63 (91 mg, 0.3 mmol) (yield 100%) 4-[3-(1-bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5- yl]bicyclo[2.2.2]octan-1-amine. ES-MS m / z 260 [M+H]+, Retention time: 0.87 min. (Method A) Step 5: Same procedure than for preparation of intermediate 16 followed by flash chromatography. Starting from intermediate 15 (3R)-3-(tertbutoxycarbonylamino)-8-fluoro- 5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7- carboxylic acid (188 mg, 0.35 mmol) to afford intermediate 64 (232 mg, 0.3 mmol) (yield 87%) tert-butyl N-[(3R)-7-[[4-[3-(1-bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]carbamoyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1,5-benzothiazepin-3-yl]carbamate ES-MS m / z 778 [M+H]+, Retention time: 2.14 min. (Method A) Step 6: Same procedure than for preparation of compound (60) followed by flash chromatography. Starting from intermediate 64 tert-butyl N-[(3R)-7-[[4-[3-(1- bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]carbamoyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepin-3- yl]carbamate (232 mg, 0.3mmol) to afford compound (31) (3R)-3-amino-N-[4-[3-(1- bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (173 mg, 0.26 mmol) (yield 88%). ES-MS m / z 678 [M+H]+, Retention time: 1.54 min. (Method A)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.24 (d, J=6.0 Hz, 6 H) ; 1.93 - 2.07 (m, 14 H) ; 2.15 (s, 6 H) ; 2.57 (s, 1 H) ; 3.58 - 3.72 (m, 2 H) ; 3.80 - 3.94 (m, 1 H) ; 4.51 (d, J=15.1 Hz, 1 H) ; 4.59 (spt, J=6.0 Hz, 1 H) ; 5.24 (d, J=15.1 Hz, 1 H) ; 6.85 (d, J=8.7 Hz, 2 H) ; 7.24 (d, J=8.7 Hz, 2 H) ; 7.32 (d, J=5.6 Hz, 1 H) ; 7.67 (d, J=8.3 Hz, 1 H) ; 8.13 (br s, 1 H). Example 10: preparation of compound (100) Step 1: To a solution of 4-(benzyloxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylic acid (350 mg, 1.12 mmol,) in 6mL of DCM were added DCC (254 mg, 1.23 mmol), DMAP (14 mg, 0.11 mmol), and oxetan3-ol (105 mg, 1.34 mmol). The reaction mixture was stirred at room temperature overnight. The precipitate was filtered of and washed with 10mL of DCM. The combined organic layers were evaporated, and the residue purified by flash chromatography to afford intermediate 70 as a white solid (3-methyloxetan-3-yl) 4- (benzyloxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylate (281 mg, 0.78mmol) (yield 70%). ES-MS m / z 360 [M+H]+, Retention time: 1.86 min. (Method C) Step 2: Same procedure than for preparation of intermediate 51. Starting from intermediate 70 (3-methyloxetan-3-yl) 4-(benzyloxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylate (241mg, 0.64 mmol) to afford intermediate 71 (131mg, 0.54mmol)(yield 85%) oxetan-3-yl 4-aminobicyclo[2.2.2]octane-1-carboxylate. ES-MS m / z 226 [M+H]+, Retention time: 0.3 min. (Method C) Step 3: Same procedure than for preparation of compound (60). Starting from intermediate 13 (5g, 13.5 mmol) methyl (3R)-3-(tert-butoxycarbonylamino)-8-fluoro-4-oxo-3,5-dihydro- 2H-1,5-benzothiazepine-7-carboxylate to afford intermediate 72 methyl (R)-3-amino-8- fluoro-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylate (3.4 g, 12.58 mmol) (yield 93.2%). ES-MS m / z 271 [M+H]+, Retention time: 0.72 min. (Method D) Step 4: To a solution of intermediate 72 (3.4g, 12.58mmol) methyl (R)-3-amino-8-fluoro-4- oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylate in 33 mL of DCM was added N-benzyloxy-carbonyloxy-succinimide (3.84 g, 15.1 mmol) and DIPEA (4.84 mL, 27.7 mmol) dropwise. The reaction mixture was stirred at room temperature overnight. After hydrolysis with water (30mL) the reaction mixture was extracted 3 times with DCM (30mL). The combined organic layers were washed with water and brine, dried with MgSO4, filtered and evaporated. The residue was purified by flash chromatography to afford intermediate 73 methyl (R)-3-(((benzyloxy)carbonyl)amino)-8-fluoro-4-oxo-2,3,4,5- tetrahydrobenzo[b][1,4]thiazepine-7-carboxylate (4.5g, 11.07mmol) (yield 88%). ES-MS m / z 405 [M+H]+, Retention time: 1.44 min. (Method C) Step 5: Same procedure than for preparation of intermediate 14. Starting from intermediate 73 (4.6g, 11.4mmol) methyl (R)-3-(((benzyloxy)carbonyl)amino)-8-fluoro-4-oxo-2,3,4,5- tetrahydrobenzo[b][1,4]thiazepine-7-carboxylate to afford intermediate 74 (2.64 g, 4.9 mmol) (yield 43%) (R)-3-(((benzyloxy)carbonyl)amino)-8-fluoro-5-(4-isopropoxybenzyl)- 4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylic acid. ES-MS m / z 539 [M+H]+, Retention time: 1.74 min. (Method C) Step 6: Same procedure than for preparation of intermediate 15. Starting from intermediate 74 (2.64 g, 4.9 mmol) (R)-3-(((benzyloxy)carbonyl)amino)-8-fluoro-5-(4- isopropoxybenzyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-7-carboxylic acid to afford intermediate 75 (2.2 g, 3.8 mmol) (yield 78%) (3R)-3-(benzyloxycarbonylamino)-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1,5-benzothiazepine-7- carboxylic acid. ES-MS m / z 571 [M+H]+, Retention time: 1.64 min. (Method C) Step 7: Same procedure than for preparation of intermediate 17. From intermediate 75 (3R)- 3-(benzyloxycarbonylamino)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1,5-benzothiazepine-7-carboxylic acid (320mg, 0.56 mmol) to afford intermediate 76 (206 mg, 0.26 mmol) (yield 47.2%) oxetan-3-yl 4-[[(3R)-3-(benzyloxycarbonylamino)- 8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate. ES-MS m / z 778 [M+H]+, Retention time: 2.18 min. (Method C) Step 8: Same procedure than for preparation of intermediate 51. Starting from intermediate 76 oxetan-3-yl 4-[[(3R)-3-(benzyloxycarbonylamino)-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (206 mg, 0.26 mmol) to afford compound (100) (93 mg, 0.14 mmol)(yield 56%) oxetan-3-yl 4-[[(3R)-3-amino-8-fluoro-5- [(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate. ES-MS m / z 644 [M+H]+, Retention time: 0.89 min. (Method B)1H NMR (400 MHz, DMSO-d6, 30°C) δ 1.25 (d, J=6.0 Hz, 6 H) ; 1.80 – 1.92 (m, 12 H) ; 1.95 – 2.05 (m, 2 H) ; 3.59 – 3.72 (m, 2 H) ; 3.81 – 3.93 (m, 1 H) ; 4.40 – 4.45 (m, 2 H) ; 4.48 (d, J=15.3 Hz, 1 H) ; 4.59 (spt, J=6.0 Hz, 1 H) ; 4.75 – 4.80 (m, 2 H) ; 5.24 (d, J=15.3 Hz, 1 H) ; 5.28 – 5.37 (m, 1 H) ; 6.84 (d, J=8.7 Hz, 2 H) ; 7.23 (d, J=8.7 Hz, 2 H) ; 7.30 (d, J=5.7 Hz, 1 H) ; 7.66 (d, J=8.3 Hz, 1 H) ; 8.04 (br s, 1 H). The compounds according to table 1 above were subjected to pharmacological tests. Test: cytokine production of sub-optimal-activated T cells The purpose of this assay is to determine the potency of compounds of formula (I) to enhance the cytokine production of sub-optimal-activated T cells in a functional assay. Cell preparation Buffy Coat (Healthy donors, EFS) was diluted with an equal volume of D-PBS (at room temperature), transferred on a Sepmate tube (STEMCELL) containing 15 mL with Ficoll-Paque Plus (GE Healthcare) then centrifuged (1200 × g, 20 min, RT) with an Eppendorf centrifuge (Eppendorf, 5910R). PBMCs were collected from the Ficoll-Paque- plasma interface into a 50 mL tube and washed twice (300 g, 10 min, 4°C) with cold PBS (Life Technology) before being resuspended in 10 mL cold PBS. PBMCs were enumerated and assessed for viability, using trypan blue with a VI-CELL BLUE Analyzer (Beckman Coulter). Then T Lymphocytes were isolated from PBMCs by immunomagnetic negative selection using the EasySep™ Direct Human Total Lymphocyte Isolation Kit (STEMCELL). T Lymphocytes were enumerated and assessed for viability, using trypan blue with a VI-CELL BLUE Analyzer (Beckman Coulter). Purity was assessed by Flow- cytometry with anti-CD3 BUV395 (Clone UCHT-1, Becton-Dickinson), anti-CD4-BV711 (clone RPA-T4, Biolegend) and anti-CD8 BV786 (clone RPA-T8, Biolegend). Fixable Viability Dye-eFluor-780 (eBioscience) was used to exclude dead cells. Data acquisition was performed using a FORTESSA X20 flow cytometer (Becton Dickinson) and data analysis with FlowJo software (FlowJO, LLC). T-Cell activation with compounds Eighty thousand T lymphocytes per well were seeded in a 96-well microplate (U-shape, Greiner) under a total volume of 110 µL X-VIVOTM15 medium (Lonza). 40 µL of anti-CD3 at 5 µg / mL in X-VIVOTM15 medium (clone OKT3, Functional Grade, 1 mg / mL, eBioscience) and 40 µL of anti CD28 at 5µg / mL in X-VIVOTM15 medium (clone CD28.2, Functional Grade, 1 mg / mL, eBioscience) were added to each well. Compounds to be tested were first diluted in 100 % DMSO (SIGMA) with a 1:3 serial dilution (96 well V Bottom, Polypropylene, non-treated, sterile, COSTAR) then diluted 1:16,6 in X-VIVO medium. 10 µL of each serial dilution in X-VIVOTM15 medium were added per well. 10 µL 6% DMSO were added to negative control wells. Cells were incubated for 18 hours at 37°C under 5% CO2. 150 µL supernatant were removed and stored at -80°C. Cytokine titration Cytokine titration was performed using the HTRF human IL-2 kit (CisBio) according to the manufacturer. Fluorescence was measured with a PHERASTAR (BMG) by selecting the channel A (665 nm) and channel B (620nm) then a ratio was calculated with the formula signal A / signal B x 10000. Data analysis A Delta ratio was calculated according to the formula Ratio [standard or sample] – Ratio [negative control]. Delta-F ratio was transferred into Excel template and the cytokine levels (pg / mL) were calculated from the standard curve of IL-2 according to guidelines of the manufacturer. The duplicate values for each donor were combined and a curve was fitted to a 4-parameter logistic model (XLfit software). Relative EC50was calculated for each compound and the Table 3 below provides the EC50values in nM. Table 3: Compound EC50 (nM) No. 1 2449 2 528 3 1151 5 64 6 306 7 8114 10 214 11 1645 12 6091 13 707 14 1470 15 1300 16 92 17 1812 18 844 19 227 Compound EC50 (nM) No. 20 255 21 440 22 513 23 104 24 1684 25 1432 26 1453 28 107 29 1566 30 4335 31 199 32 48 33 68 34 843 35 32 36 18 37 119 38 956 39 1216 40 173 41 479 42 356 43 30 44 351 45 273 46 98 47 157 48 251 49 4261 50 578 51 210 53 242 54 560 55 144 58 55 59 158 60 138 61 33 62 46 63 483 64 511 65 221 66 266 67 49 Compound EC50 (nM) No. 68 91 69 1062 70 760 71 2986 72 447 73 1127 76 352 78 649 79 61 82 1617 83 607 84 456 87 166 88 2195 92 830 93 160 94 189 98 2814 99 170 100 4118 101 1708 105 518 106 1857 107 559 108 1074 109 361 110 265 112 4147 114 731 115 742 116 282 117 260 120 513 121 1129 123 887 124 97 125 248 128 8436 129 4148 130 537 131 4411 132 1318 134 2096 135 3642 Compound EC50 (nM) No. 136 26 137 31 138 19 139 121 140 44 141 65 It is therefore apparent that most of the compounds of formula (I) of the present invention have an EC50of less than 8500 nM, in particular of less than 1800 nM, more particularly of less than 500 nM, and for example less than 180 nM, such as between 15 and 180 nM. The compounds of formula (I) can therefore be used for preparing medicaments, especially medicaments which are suitable for the treatment of neoplastic and / or infectious diseases, especially for the treatment of cancer. A further test for evaluating the risk of drug-drug interactions on co-administered drugs was carried out. Test: CYP3A MBI - Evaluation of the mechanism-based inactivation potential (MBI) of the compounds of the invention in human hepatic microsomal fractions The present test evaluates the potential of compounds of formula (I) to be a perpetrator of drug-drug interactions, by mechanism-based inactivation (MBI) of cytochromes P4503A (CYP3A). Modulation of CYP activity via induction or inhibition by drugs can lead to clinical drug–drug interactions with consequences ranging from loss of efficacy to the introduction of adverse effects, respectively, for coadministered drugs. The drug that causes changes in CYP activity is referred to as the “perpetrator”. For this purpose, early-kinact (eKinact, inactivation rate constant at saturating concentration of the NCE) and early-KI (eKi, inhibitor concentration required to achieve half maximal inactivation) were determined on CYP3A4 midazolam 1’-hydroxylase activity in human hepatic microsomal fractions after two times of pre-incubation (0 and 20 minutes). A - EXPERIMENTAL CONDITIONS Human hepatic microsomal fractions (0.5 mg / mL) were preincubated in phosphate buffer 0.1 M, pH 7.4 with 1 mM NADPH and 11 concentrations of compounds of formula (I), plus vehicle, for 0 and 20 minutes at 37°C. Samples were diluted (1 / 10) and incubated for 10 minutes at 37°C with 50 µM Midazolam (more than 10 fold its Km). The final solvent concentration in incubation was 0.35% DMSO. Enzyme activity was stopped with 1 volume of acetonitrile containing internal standard. Following protein precipitation and their removal by centrifugation, supernatant fluids were analyzed by LC-mass- spectrometry or equivalent analytical method for assessment of 1’-hydroxymidazolam formation. Mifepristone^was used as positive control. CALCULATIONS Inactivation plot (natural logarithm of the corrected % remaining activity versus pre-incubation time) at the different concentrations of compounds of formula (I) allowed the determination of the different Kobs (slope).^And a non-linear regression analysis of the negative slopes versus concentration of a compound of formula (I) (in the pre-incubation) was performed to obtain eKinact^and eKi^values. When eKinact < 0.01 min-1, eKinact and eKi are set to “No MBI”. It may be considered that the risks of drug-drug interactions are limited when the MBI is below 0.03. B - RESULTS The Table 4 below provides the eKi and eKinact values. Table 4 Compound eKinact eKi No. 1 No MBI No MBI 2 No MBI No MBI 3 0.4 0.016 4 No MBI No MBI 5 0.3 0.025 6 5.7 0.016 7 0.2 0.08 8 0.4 0.026 9 0.2 0.028 10 0.3 0.025 11 No MBI No MBI Compound eKinact eKi No. 12 0.3 0.023 13 0.3 0.012 14 No MBI No MBI 15 0.5 0.027 16 2.5 0.019 17 No MBI No MBI 18 1.1 0.017 19 2.9 0.016 20 No MBI No MBI 21 1.6 0.012 22 0.9 0.017 23 1 0.024 24 10 0.016 25 0.2 0.016 26 30 0.025 27 12 0.016 28 1.9 0.07 29 1.1 0.019 30 0.5 0.027 31 1.8 0.018 32 2.2 0.025 33 1.3 0.011 34 1.6 0.023 35 No MBI No MBI 36 1.4 0.017 37 3.2 0.012 38 No MBI No MBI 39 No MBI No MBI 40 0.7 0.018 41 0.7 0.024 42 7.5 0.02 43 0.8 0.011 44 0.1 0.012 45 1.2 0.02 46 5.7 0.024 47 30 0.021 48 1 0.023 49 0.8 0.025 50 0.6 0.024 51 No MBI No MBI 52 1.4 0.02 53 1.2 0.022 54 30 0.011 55 No MBI No MBI Compound eKinact eKi No. 56 30 0.028 57 4.4 0.012 58 0.4 0.019 59 1.8 0.014 60 No MBI No MBI 61 No MBI No MBI 62 0.4 0.027 63 0.6 0.023 64 1.1 0.025 65 0.5 0.026 66 0.8 0.019 67 No MBI No MBI 68 No MBI No MBI 69 No MBI No MBI 70 0.1 0.016 71 1 0.015 72 No MBI No MBI 73 No MBI No MBI 74 No MBI No MBI 75 1.2 0.011 76 No MBI No MBI 77 GT 30 GT 0.024 78 No MBI No MBI 79 No MBI No MBI 80 No MBI No MBI 81 30 0.012 82 0.8 0.022 83 No MBI No MBI 84 No MBI No MBI 85 No MBI No MBI 86 0.4 0.022 87 30 0.015 88 No MBI No MBI 89 30 0.012 90 No MBI No MBI 91 0.3 0.018 92 0.3 0.02 93 3.5 0.02 94 No MBI No MBI 95 No MBI No MBI 96 No MBI No MBI 97 0.9 0.028 98 0.6 0.013 99 1.1 0.022 Compound eKinact eKi No. 100 2 0.021 101 No MBI No MBI 102 No MBI No MBI 103 No MBI No MBI 104 4.2 0.04 105 1.2 0.03 106 0.9 0.015 107 19 0.026 108 30 0.02 109 0.3 0.011 110 1.4 0.025 111 30 0.028 112 30 0.025 113 0.8 0.028 114 1.2 0.022 115 2.4 0.018 116 0.3 0.011 117 5 0.01 118 3 0.018 119 0.9 0.031 120 8.5 0.027 121 No MBI No MBI 122 0.7 0.017 123 2.1 0.029 124 2.9 0.15 125 No MBI No MBI 126 11 0.019 127 10 0.015 128 No MBI No MBI 129 5.6 0.023 130 No MBI No MBI 131 No MBI No MBI 132 No MBI No MBI 133 No MBI No MBI 134 No MBI No MBI 135 18 0.023 It is therefore apparent that most of the compounds of formula (I) of the present invention present a limited risk of drug-drug interaction. Accordingly, also provided herein are medicaments which comprise a compound of the formula (I), or a pharmaceutically acceptable salt thereof. Herein are also provided the compounds of formula (I) defined above, or pharmaceutically acceptable salts thereof, for use as medicines. Herein are also provided the compounds of formula (I) defined above, or pharmaceutically acceptable salt thereof, for use in therapy, especially as agents suitable for the treatment of neoplastic and / or infectious diseases, especially as anticancer agents. Herein are also provided the compounds of formula (I) defined above, or a pharmaceutically acceptable salts thereof, for use in the treatment of neoplastic and / or infectious diseases, and in particular in the treatment of cancer. A particular aspect is a compound of formula (I) defined above, or a pharmaceutically acceptable salt thereof, for use in the treatment of neoplastic and / or infectious diseases, in particular in the treatment of cancer. In a particular embodiment, the neoplastic disease is cancer. Cancer may be understood in the broadest sense as any malignant neoplastic disease, i.e., the presence of one or more malignant neoplasm(s) in the patient. Cancer may be solid or hematologic malignancy. Subtypes of cancer may be classified in different ways such as by the location in the body the main or only tumor bulk is found or by the tissue of origin the tumor(s) is / are derived from. Exemplarily, such malignant neoplasm according to the present invention may be located on or in the lip, oral cavity and pharynx, on or in the digestive organs, on or in the respiratory system and intrathoracic organs, on or in the bone and articular cartilage, on or in the skin , on or in the connective and soft tissue, on or in the breast and female genital organs, on or in the male genital organs, on or in the urinary organs, on or in the eye, brain and central nervous system, on or in the endocrine glands and related structures, may be secondary and ill-defined neoplasms, may be stated or presumed to be primary, of lymphoid, haematopoietic and related tissue neoplasms, and / or may be neoplasms of independent (primary) multiple sites. Preferably, cancer may be the formation of one or more solid tumor(s). Alternatively, cancer may be the formation of one or more hematopoietic tumor(s). In an alternative preferred embodiment, the disease may be an infectious disease. As used in the context of the present invention, the term "infectious disease" may be understood in the broadest sense as any pathologic condition caused by the invasion of a patient's body by one or more biological agent(s) foreign to the body able to provoke an immune reaction in the patient's body. An infectious disease may or may not be accompanied by an inflammatory response (inflammation). Exemplarily, such immune reaction in the patient's body may be in more detail caused by a biological agent itself (e.g., by the presence of surface antigens thereof), by antigens originating from a biological agent provided on a major histocompatibility complex I or II (MHC I or MHC II), by the multiplication of a biological agent, by the reaction of host tissues to such biological agent, by compounds produced or caused by such biological agent (e.g., toxines, semiochemicals, cytokines, etc.), or by the formation of an antigen from a haptene originating from such biological agent. Such biological agents may be non-living or living agents. Exemplarily, an infectious disease may be caused by biological agents selected from the group consisting of viruses, viroids, prions, microorganisms such as bacteria, nematodes such as roundworms and pinworms, arthropods (e.g., ticks, mites, fleas, and lice), fungi, ringworms, and tapeworms. Preferably, an infectious disease according to the present invention is caused by viruses or bacteria. A viral infection in the context of the present invention may be an infection by any virus. The viral infection may be an acute viral infection or a chronic viral infection. According to another aspect, herein is provided a method of treating the pathological conditions indicated above, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof. In an embodiment of this method of treatment, the subject is a human. Herein is also provided the use of a compound of the formula (I), or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament useful in treating any of the pathological conditions indicated above, more particularly useful in treating neoplastic and / or infectious diseases, especially in treating cancer. Herein are also provided the pharmaceutical compositions comprising as active principle a compound of formula (I) or one of its pharmaceutically acceptable salts. These pharmaceutical compositions comprise an effective dose of at least one compound of formula (I), or a pharmaceutically acceptable salt thereof, and also at least one pharmaceutically acceptable excipient. The said excipients are selected, in accordance with the pharmaceutical form and method of administration desired, from the customary excipients, which are known to a person skilled in the art. In the pharmaceutical compositions for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intra-tracheal, intranasal, transdermal or rectal administration, the active principle of formula (I) above, or its base, acid, zwitterion or salt thereof, may be administered in a unit administration form, in a mixture with conventional pharmaceutical excipients, to animals and to human beings for the treatment of the above disorders or diseases. The unit administration forms appropriate include oral forms such as tablets, soft or hard gel capsules, powders, granules and oral solutions or suspensions, sublingual, buccal, intra-tracheal, intra-ocular and intra-nasal administration forms, forms for inhalative, topical, transdermal, subcutaneous, intra-muscular or intravenous administration, rectal administration forms and implants. For topical application it is possible to use the compounds of formula (I) in creams, gels, ointments or lotions. There may be particular cases in which higher or lower dosages are appropriate. According to usual practice, the dosage that is appropriate for each patient is determined by the doctor according to the mode of administration and the weight and response of the said patient.

Claims

CLAIMS 1. A compound of the formula (I) or a pharmaceutically acceptable salt thereof:wherein: - X1 represents a -NH- or -O- group, - X3-X2 represents a =CH-CH=C- group, a =CH-N=C- group, or a =N-N- group, - Z represents a bridged (C5-C8)cycloalkyl group, - R1 representso a groupgroup, wherein R3 represents a hydrogen atom or a group selected from ^ a hydroxy group or a (C1-C6)alkoxy group, ^ a -NRaRb group, wherein Ra and Rb independently represent a hydrogen atom or a (C1-C6)alkyl group, ^ a (C1-C6)alkyl group, optionally substituted by a -COOH group, by a -O-C(O)CH3 group, by a hydroxy group, by a (C1-C4)alkoxy group, by a tetrazolyl group or by a benzyltetrazolyl group, ^ a fluoro(C1-C6)alkyl group, ^ a -COR6 group, wherein R6 represents a (C1-C4)alkyl group or a (C1-C4)alkoxy group, ^ a (C3-C7)cycloalkyl group, optionally substituted by a methyl group, by an amino group or by a halogen atom, ^ a bridged (C4-C8)cycloalkyl group, ^ a spiro(C5-C11)bicyclic ring,^ a hetero(C3-C8)cycloalkyl group, optionally substituted by a (C1-C4)alkyl group, and ^ a hetero(C5-C6)aryl group,a group, wherein R3’ represents a group selected from ^ a (C1-C6)alkyl group, optionally substituted by a -COOH group, by a hydroxy group, or ^ a fluoro(C1-C6)alkyl group, agroup, wherein R3” represents a hydrogen atom or a (C1-C6)alkyl group, a tetrazolyl group, a -COOR7 group, wherein R7 represents ^ a hydrogen atom, ^ a (C1-C6)alkyl group optionally substituted by a (C3-C7)cycloalkyl group, ^ a fluoro(C1-C6)alkyl group, ^ a (C3-C7)cycloalkyl group, ^ a hetero(C3-C8)cycloalkyl group, optionally substituted by a methyl group, or ^ a group , a -OCOR8 group, wherein R8 represents a (C1-C6)alkyl group or a fluoro(C1-C6)alkyl group, a hydroxy group, a -NRaRb group, wherein Ra and Rb are as defined above, a (C1-C4)alkoxy group, optionally substituted by a COOR7 group as defined above,o a hetero(C3-C8)cycloalkyl group, optionally substituted by one or two halogen atoms, o a -CONHSO2R9 group, wherein R9 represents a (C1-C4)alkyl group or a (C3-C7)cycloalkyl group, o a halogen atom, o a -NHCOR8 group, wherein R8 is as defined above, o a -CONR8R8’ group, wherein R8 is as defined above and R8’ is a hetero(C3-C8)cycloalkyl group, a hydrogen atom or a (C1-C4)alkyl group, or o a -COR8’ group, wherein R8’ is as defined above, - R2 represents a halogen atom or a hydrogen atom, - R4 represents a hydrogen atom, - R5 represents o a halogen atom, o a hydroxy group, o a (C1-C6)alkoxy group optionally substituted by a -COOH group, o a fluoro(C1-C6)alkoxy group, o a (C3-C7)cycloalkyl, optionally substituted by a (C1-C3)alkyl group, itself optionally substituted by a hydroxy group, o a (C3-C7)cycloalkyloxy group, o a hetero(C3-C8)cycloalkyl group, optionally substituted by a methyl group or by a -COOH group, o a hetero(C5-C6)aryl group, optionally substituted by a halogen atom, o a bridged hetero(C5-C8)cycloalkyl group, - or alternatively R4 and R5 form together with the atoms to which they are attached a 5- or 6-membered ring optionally comprising a heteroatom, and thus forming an optionally partially saturated (C5-C11)heteroaromatic bicyclic ring with the aryl or heteroaryl group to which they are attached, - R represents a halogen atom, and - n is 0, 1 or 2, provided that- (1) when R1 represents a group and R3 is a tertiobutyl group, then R2 and R5 are not simultaneously respectively a hydrogen or fluorine atom and a - O-CH(CH3)2group, - (2) R5 does not represent a -O-CH(CH3)2group, when R1 representso a group and R3 is a 1-methylcyclobutyl group,o a group and R3 is a tetrahydropyranyl group, o a 3-methyloxetan-3-yloxycarbonyl group, o a 1-methylcyclopropyloxycarbonyl group, o a tert-butoxycarbonyl group, or o a dimethylcarbamoyl group, - (3) when R1 represents a cyclohexoxycarbonyl group or a cyclopentoxycarbonyl group, then X1 does not represent a -NH- group, and - (4) when R1 is a fluorine atom, then R5 is not a dioxanyl group.

2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that X3-X2 represents a =CH-CH=C- group.

3. The compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that Z represents a bicyclo[2.2.2]octan-1-yl, a bicyclo[2.1.1]hexan-1-yl, a norpinan-1-yl or a bicyclo[1.1.1]pentan-1-yl.

4. The compound of formula (I) according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that R1 representso a groupgroup, wherein R3 represents a hydrogen atom or a group selected from^ a hydroxy group, ^ a -CH(CH3)2COOH group, a tertiobutyl group, a 1-methyl-1-(2H- tetrazol-5-yl)ethyl group, a 1-(2-benzyltetrazol-5-yl)-1-methyl-ethyl group, a 2-hydroxy-1,1-dimethyl-ethyl group, a -CH(CH3)2COOCH3group, a 1-hydroxy-1-methyl-ethyl group, a hydroxymethyl group, a tert-butoxymethyl group, a methoxymethyl group, a ethyl group, a methyl group, ^ a 1-fluoro-1-methyl-ethyl group, a trifluoromethyl group, ^ a acetyl group, a ethoxycarbonyl group, ^ a 1-aminocyclobutyl group, a 3-fluorocyclobutyl group, a 1-methylcyclobutyl group, a cyclobutyl group, a cyclopropyl group, ^ a 1-bicyclo[1.1.1]pentanyl group, ^ a 4,7-diazaspiro[2.5]octan-7-yl group, ^ a morpholinyl group, a dioxanyl group, a piperidinyl group, a 1- methyl-4-piperidyl group, a tetrahydrofuranyl group, an oxetanyl group, a tetrahydropyranyl group, ^ a pyrimidinyl group, an imidazolyl group,a group, wherein R3’ represents a group selected from ^ a (C1-C6)alkyl group, optionally substituted by a -COOH group, by a hydroxy group, or ^ a fluoro(C1-C6)alkyl group, agroup, wherein R3” represents a hydrogen atom or a tertio butyl group, a tetrazolyl group, a cyclohexoxycarbonyl group, a oxetan-3-yloxycarbonyl group, a tert- butoxycarbonyl group, a -COOH group, a 3-methyloxetan-3-yloxycarbonyl group, a 2,2,2-trifluoro-1,1-dimethyl-ethoxycarbonyl group, a group, a methoxycarbonyl group, a 2- morpholinoethoxycarbonyl group, a tetrahydrofuranyloxycarbonyl group, a ethoxycarbonyl group, a tetrahydropyranyloxycarbonyl group, a cyclobutyloxycarbonyl group, a cyclopropyloxycarbonyl group, o a -O-COC(CH3)3group, a -O-COCH2CF3group, o a -OCH2COOC(CH3)3group, o a 4,4-difluoro-1-piperidyl group, o a cyclopropylsulfonylcarbamoyl group, o a halogen atom, in particular a fluorine atom, o a propanoylamino group, o a N-methyl(tetrahydropyran-4-yl)carbamoyl group, an ethylcarbamoyl group, a N-diethylcarbamoyl group, a morpholinylcarbonyl group, or o a N-piperidine-1-carbonyl group, an azetidine-1-carbonyl group.

5. The compound of formula (I) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, characterized in that R4 represents a hydrogen atom and R5 represents o a halogen atom, in particular a fluorine atom or a chlorine atom, o a hydroxy group, o an isopropoxy group, a methoxy group, a butoxy group, a carboxymethoxy group, o a 2,2,2-trifluoro-1-methyl-ethoxy group, a 2,2-difluoroethoxy group, o a hydroxymethylcyclopropyl group, a 1-methylcyclopropyl group, a cyclohexyl group, o a cyclobutoxy group, a cyclopropoxy group, o a 1-methyl-4-piperidyl group, a morpholinyl group, a 4-methylpiperazinyl group, a 1,4-dioxanyl group, a carboxypiperidinyl group, a tetrahydropyranyl group, o a 4-fluoropyrazolyl group, oro a azabicyclo[2.2.1]heptan-2-yl group.

6. The compound of formula (I) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, characterized in that R4 and R5 form together with the atoms to which they are attached a benzofuranyl group.

7. The compound of formula (I) according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, characterized in that said compound is selected from the following compounds: - -2-[5-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]-1,2,4- oxadiazol-3-yl]-2-methyl-propanoic acid; hydrochloride (1), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-[1-(hydroxymethyl)cyclopropyl]phenyl]methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (2), - (3R)-3-amino-N-[4-[3-(1-aminocyclobutyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (3), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-[1-methyl-1-(2H- tetrazol-5-yl)ethyl]-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide; acetate (4), - (3R)-3-amino-N-[4-[3-[1-(2-benzyltetrazol-5-yl)-1-methyl-ethyl]-1,2,4-oxadiazol- 5-yl]-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (5), - 2-[3-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]-1,2,4- oxadiazol-5-yl]-2-methyl-propanoic acid (6), - (3R)-3-amino-N-[4-[3-(4,7-diazaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (7),- (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(3-morpholin-2-yl- 1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (8), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(3- pyrimidin-5-yl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (9), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(3-morpholin-3-yl- 1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (10), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-(1-methyl-4-piperidyl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (11), - (3R)-3-amino-N-[4-[3-(1,4-dioxan-2-yl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (12), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-morpholinophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (13), - (3R)-3-amino-8-fluoro-5-[(4-methoxyphenyl)methyl]-N-[4-(3-morpholino-1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (14), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-[3-(1- piperidyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (15), - (3R)-3-amino-N-[4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (16), - (3R)-3-amino-8-fluoro-N-[4-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-3- yl]-1-bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (17),- (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-(4-fluoropyrazol-1-yl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (18), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-1,1,4-trioxo-5-[[4-(trideuteriomethoxy)phenyl]methyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (19), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-fluorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carboxamide (20), - (3R)-3-amino-N-[4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; trifluoroacetate (21), - (3R)-3-amino-8-fluoro-N-[4-[3-(3-fluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (22), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-(1-methyl-4- piperidyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (23), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (24), - (3R)-3-amino-8-fluoro-N-[4-[3-(1H-imidazol-5-yl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (25), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-hydroxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (26), - (3R)-3-amino-N-[4-[(4S)-4-tert-butyl-4,5-dihydrooxazol-2-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (27),- (3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro-N-[4-[3-(1- methylcyclobutyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (28), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(2-oxo- 3H-1,3,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (29), - [1-[5-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]-1,2,4- oxadiazol-3-yl]-1-methyl-ethyl] acetate (30), - (3R)-3-amino-N-[4-[3-(1-bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (31), - (3R)-3-amino-8-fluoro-N-[4-[3-(1-fluoro-1-methyl-ethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (32), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-5- [[4-(1,4-dioxan-2-yl)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (33), - (3R)-3-amino-N-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (34), - [4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxylate (35), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (36), - (3R)-N-[4-(3-acetyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-3-amino-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (37),- (3R)-3-amino-8-fluoro-N-[4-[3-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-5-yl]- 1-bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (38), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (39), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(3- tetrahydrofuran-2-yl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (40), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(3- tetrahydrofuran-2-yl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (41), - [4-(cyclohexoxycarbonyl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (42), - (3R)-3-amino-8-fluoro-1,1,4-trioxo-N-[4-[3-[(2R)-tetrahydrofuran-2-yl]-1,2,4- oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (43), - (3R)-3-amino-8-fluoro-1,1,4-trioxo-N-[4-[3-[(2S)-tetrahydrofuran-2-yl]-1,2,4- oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (44), - [4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl] 2,2- dimethylpropanoate (45), - [4-(oxetan-3-yloxycarbonyl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (46), - (3R)-3-amino-N-[4-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (47),- (3R)-3-amino-8-fluoro-N-[4-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxamide (48), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-(oxetan-3-yl)- 1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (49), - (3R)-3-amino-N-[4-[3-(tert-butoxymethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carboxamide (50), - ethyl 5-[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl]- 1,2,4-oxadiazole-3-carboxylate (51), - (3R)-3-amino-N-[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]- 8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (52), - (3R)-3-amino-8-fluoro-N-[4-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (53), - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-1,1,4-trioxo-5-[[4- [(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxylate (54), - 4-[(3R)-3-amino-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]oxybicyclo[2.2.2]octane-1-carboxylic acid (55), - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-8-fluoro-5-[(4- methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (56), - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (57),- [4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1-bicyclo[2.2.2]octanyl] 3,3,3- trifluoropropanoate; hydrochloride (58), - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-8-fluoro-1,1,4- trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]-2,3-dihydro- 1λ6,5-benzothiazepine-7-carboxylate (59), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl-ethoxy]phenyl]methyl]- 2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (60), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (61), - (3R)-3-amino-8-fluoro-1,1,4-trioxo-N-[4-(3-tetrahydropyran-4-yl-1,2,4-oxadiazol- 5-yl)-1-bicyclo[2.2.2]octanyl]-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide (62), - tert-butyl 2-[[4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]-1- bicyclo[2.2.2]octanyl]oxy]acetate (63), - (3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-N-[4-[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]-1- bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (64), - tert-butyl 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[6-[(1R)-2,2,2-trifluoro-1- methyl-ethoxy]-3-pyridyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (65), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-[3- (trifluoromethyl)-1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (66), - [4-(cyclohexoxycarbonyl)-1-bicyclo[2.2.2]octanyl] (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (67),- (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (68), - tert-butyl 4-[[(3R)-3-amino-5-[[4-[(2S)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (69), - tert-butyl 4-[[(3R)-3-amino-8-fluoro-5-[[4-(4-methylpiperazin-1- yl)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (70), - tert-butyl 4-[[(3R)-3-amino-5-[[6-(2,2-difluoroethoxy)-3-pyridyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (71), - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[[4-[(2R)-1,4- dioxan-2-yl]phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxylate (72), - (3-methyloxetan-3-yl) 4-[[(3R)-3-amino-5-[[4-(1,4-dioxan-2-yl)phenyl]methyl]-8- fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (73), - oxetan-3-yl 4-[[(3R)-3-amino-5-[[4-(1,4-dioxan-2-yl)phenyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (74), - (2,2,2-trifluoro-1,1-dimethyl-ethyl) 4-[[(3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2- yl]phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (75), - (3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro-N-[4-(1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (76), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(1,2,4-oxadiazol-5- yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide (77),- (2,2,2-trifluoro-1,1-dimethyl-ethyl) 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (78), - 4-[[(3R)-3-amino-5-[[4-(cyclobutoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (79), - 4-[[(3R)-3-amino-5-(benzofuran-5-ylmethyl)-8-fluoro-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (80), - tert-butyl 4-[[(3R)-3-amino-5-[[4-[(2R)-1,4-dioxan-2-yl]phenyl]methyl]-8-fluoro- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (81), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-[3-(methoxymethyl)- 1,2,4-oxadiazol-5-yl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide (82), - (3R)-3-amino-N-[4-(4,4-difluoro-1-piperidyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5- [(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (83), - 4-[[(3R)-3-amino-5-[[4-(cyclopropoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (84), - 4-[[(3R)-3-amino-8-fluoro-5-[[4-(1-methylcyclopropyl)phenyl]methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylic acid; hydrochloride (85), - tert-butyl 4-[[(3R)-3-amino-1,1,4-trioxo-5-[[4-[(1S)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (86), - 4-[[(3R)-3-amino-5-[(4-butoxyphenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (87),- 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]norbornane-1-carboxylic acid; hydrochloride (88), - 4-[[(3R)-3-amino-5-[(2-chloro-4-methoxy-phenyl)methyl]-8-fluoro-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (89), - (3R)-3-amino-N-[4-(cyclopropylsulfonylcarbamoyl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (90), - (3-methyloxetan-3-yl) 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (91), - tert-butyl 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(2,2,2-trifluoro-1-methyl- ethoxy)phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (92), - (4-tert-butoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (93), - (3R)-1-[4-[[(3R)-3-amino-7-[(4-fluoro-1-bicyclo[2.2.2]octanyl)oxycarbonyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepin-5-yl]methyl]phenyl]piperidine-3- carboxylic acid (94), - 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.1.1]hexane-1- carboxylic acid (95), - (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (96), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4- (propanoylamino)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (97),- (4-methoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (98), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4- [methyl(tetrahydropyran-4-yl)carbamoyl]-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carboxamide; hydrochloride (99), - oxetan-3-yl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylate (100), - 4-[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carbonyl]oxybicyclo[2.2.2]octane-1-carboxylic acid (101), - 4-[[(3R)-3-amino-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (102), - 4-[[(3R)-3-amino-5-[(3,4-dichlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (103), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4- (piperidine-1-carbonyl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (104), - 2-morpholinoethyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (105), - [(3R)-tetrahydrofuran-3-yl] 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (106), - [(3S)-tetrahydrofuran-3-yl] 4-[[(3R)-3-amino-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (107), - (3R)-3-amino-N-[4-(3-ethyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (108),- (4-ethoxycarbonyl-1-bicyclo[2.2.2]octanyl) (3R)-3-amino-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxylate (109), - (3R)-3-amino-N-[4-(azetidine-1-carbonyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (110), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(5-methyl-1,3,4- oxadiazol-2-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (111), - (3R)-3-amino-N-[4-(ethylcarbamoyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide (112), - tetrahydropyran-4-yl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate (113), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(3-methyl-1,2,4- oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (114), - cyclobutyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylate (115), - cyclopropyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4- trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane- 1-carboxylate (116), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-N-[4-(2H- tetrazol-5-yl)-1-bicyclo[2.2.2]octanyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (117), - (3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-N-[4-(morpholine-4- carbonyl)-1-bicyclo[2.2.2]octanyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine- 7-carboxamide; hydrochloride (118),- tert-butyl 4-[[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate (119), - (3R)-3-amino-N-[4-(diethylcarbamoyl)-1-bicyclo[2.2.2]octanyl]-8-fluoro-5-[(4- isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carboxamide; hydrochloride (120), - 5-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]norpinane-1-carboxylic acid (121), - ethyl 4-[[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro- 1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylate; hydrochloride (122), - tert-butyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate (123), - ethyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate; hydrochloride (124), - 4-[[(3R)-3-amino-5-[[4-[(1S,4R)-2-azabicyclo[2.2.1]heptan-2-yl]phenyl]methyl]-8- fluoro-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (125), - 2-[4-[[(3R)-3-amino-8-fluoro-7-[(4-fluoro-1-bicyclo[2.2.2]octanyl)carbamoyl]- 1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepin-5-yl]methyl]phenoxy]acetic acid; hydrochloride (126), - 3-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[1.1.1]pentane-1- carboxylic acid; hydrochloride (127), - 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[(4-tetrahydropyran-4-ylphenyl)methyl]- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (128),- methyl 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylate; hydrochloride (129), - 4-[[(3R)-3-amino-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo- 2,3-dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (130), - 4-[[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-[(1R)-2,2,2-trifluoro-1-methyl- ethoxy]phenyl]methyl]-2,3-dihydro-1λ6,5-benzothiazepine-7- carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (131), - 4-[[(3R)-3-amino-5-[(1-cyclohexylpyrazol-3-yl)methyl]-8-fluoro-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (132), - 4-[[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3- dihydro-1λ6,5-benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1- carboxylic acid; hydrochloride (133), - 4-[[(3R)-3-amino-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid; hydrochloride (134), - (3R)-1-[4-[[(3R)-3-amino-8-fluoro-7-[(4-fluoro-1- bicyclo[2.2.2]octanyl)carbamoyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5-benzothiazepin-5- yl]methyl]phenyl]piperidine-3-carboxylic acid; hydrochloride (135), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; succinate (136), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; citrate (137), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; sulfate (138),- (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; tosylate (139), - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; hydrochloride (140), and - (3R)-3-amino-N-[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]-8- fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1λ6,5- benzothiazepine-7-carboxamide; oxalate (141).

8. A process for preparing a compound of formula (I), wherein X1 represents a -NH- as described in any one of claims 1 to 7, comprising a first step wherein an intermediate (A)wherein R2, R4, R5, X2, X3, R and n are as defined in any one of claims 1 to 6 and Pg is a protecting group, is converted to intermediate (C)by treatment with TBTU in the presence of TEA by reacting with intermediate wherein Z and R1 are as defined in any one of claims 1 to 6, and comprising a second step, wherein said intermediate (C) is converted to a compound of formula (I) wherein X1 represents a -NH-, in a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane when Pg is a Boc group and with Pd / C in MeOH in H2 atmosphere, when Pg is a Cbz group.

9. A process for preparing a compound of formula (I) wherein X1 represents a - NH- group and R1 representsgroup as described in any one of claims 1 to 7, comprising a first step, wherein an intermediate (H)wherein R1, Z, R2, X2, X3, R4, R5, R and n are as defined in any one of claims 1 to 6, and Pg is a protecting group, is converted to an intermediate (J)by a cyclization step by treatment with Burgess reactant, optionally by heating under microwaves,and comprising a second step, wherein said intermediate (J) is converted to compound of formula (I), wherein X1 represents a -NH- group and R1 represents agroup by a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane when Pg is a Boc group and with Pd / C in MeOH in H2atmosphere, when Pg is a Cbz group.

10. A process for preparing a compound of formula (I) as described in any one of claims 1 to 7, wherein X1 represents a -O- group, comprising a first step, wherein an intermediate (A)wherein R2, X2, X3, R4, R5, R and n are as described in any one of claims 1 to 6 and Pg is a protecting group, is converted to intermediate (C’)by treatment with DCC in the presence of DL-10-camphorsulfonic acid andDMAP by reacting with intermediate (B’) , wherein Z and R1 are as defined in any one of claims 1 to 6, and comprising a second step, wherein said intermediate (C’) is converted to compound of formula (I), wherein X1 represents a -O- group, in a deprotection step by treatment with an acid, for example HCl or TFA in a solvent such as dioxane.

11. A medicament, characterized in that it comprises a compound of formula (I) according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition, characterized in that it comprises a compound of formula (I) according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

13. A compound of formula (I) according to any one of claims 1 to 7, for use in the treatment of neoplastic and / or infectious diseases, especially - of malignant neoplasm which is located on or in the lip, oral cavity and pharynx , on or in the digestive organs, on or in the respiratory system and intrathoracic organs, on or in the bone and articular cartilage, on or in the skin , on or in the connective and soft tissue, on or in the breast and female genital organs, on or in the male genital organs, on or in the urinary organs, on or in the eye, brain and central nervous system, on or in the endocrine glands and related structures, which is secondary and ill-defined neoplasms, which is stated or presumed to be primary, of lymphoid, haematopoietic and related tissue neoplasms, and / or which is neoplasms of independent (primary) multiple sites, or - of infectious disease caused by viruses or bacteria.

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