Spirocyclohexane derivatives, pharmaceutical compositions containing them and their uses as Anti-apoptotic inhibitors

Abstract

Compounds of Formula (I) wherein R1, R3, R11, R12, X, Y1, Y2, Y3, Y4 and formula (II) are as defined in the description. Medicaments.

Description

FIELD OF THE INVENTION The present invention relates to new spirocyclohexane derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their uses as anti-apoptotic inhibitors. The compounds of the present invention inhibit the activity of the Mcl-1 protein and may be of interest in the treatment of cancer, immune and autoimmune diseases. BACKGROUND OF THE INVENTION Apoptosis, or programmed cell death, is a physiological process that is crucial for embryonic development and maintenance of tissue homeostasis. Apoptotic-type cell death involves morphological changes such as condensation of the nucleus and DNA fragmentation, but also biochemical phenomena such as caspases activation, which causes damage to key structural components of the cell, thus inducing its disassembly and death. Regulation of apoptosis process is complex and involves the activation or repression of several intracellular signaling pathways (Singh etal, Nature Rev. Mol. Cell. Biol. 2019, 20, 175-193). Apoptosis deregulation is involved in several pathologies. Increased apoptosis is associated with neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and ischemia. Conversely, deficits in apoptosis implementation play a significant role in the development of cancers and their chemoresistance, in auto-immune diseases, inflammatory diseases and viral infections. Accordingly, absence of apoptosis is one of the hallmarks of cancer (Hanahan and Weinberg, Cell 2011, 5, 646-674). The anti-apoptotic proteins of the Bcl-2 family are associated with numerous pathologies. The involvement of proteins of the Bcl-2 family is described in numerous types of cancer, such a colon cancer, breast cancer, small-cell lung cancer, non-small-cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphoid leukemia, lymphoma, myeloma, acute myeloid leukemia, pancreatic cancer etc. Overexpression of apoptotic proteins of the Bcl-2 family is involved in tumorigenesis, in resistance to chemotherapy and in the poorer clinical prognosis of patients affected by cancer. Notably, the gene encoding Mcl-1, an anti-apoptotic Bcl-2 family member, is located in one of the most frequently amplified chromosome regions in cancer (Beroukhim et al, Nature 2010, 463, 899-905; Zack et al, Nature Genetics 2013, 45, 1134-1140). In addition, an increasing body of evidences indicates that Mcl-1 is highly expressed in multiple cancer subtypes, including hematological malignancies (reviewed in Wei et al. Blood Rev. 2020, 44, 100672), melanoma (Sale et al, Nat. Commun. 2019, 10, 5167), hepatocellular carcinoma (Sieghart et al, J. Hepatol. 2006, 44, 151-157), breast cancer (Campbell et al, Cell Death Dis. 2018, 9, 19), pancreatic cancer (Castillo et al, Oncogene 2019, 39, 1821-1829), small-cell lung cancer (Yasuda et al, Cell Death Dis. 2020, 11, 177), nonsmall-cell lung cancer (Wen et al, Diagn. Pathol. 2019, 14, 108), prostate cancer (Reiner et al, Oncoscience 2015, 8, 703-715), urothelial carcinoma (Hong et al, Mol. Cancer Res. 2019, 17, 1294-1304), testicular germ cell tumors (Sano et al, Histopathology 2005, 46, 532-539), etc. In addition, upregulation of Mcl-1 has been implicated in inappropriate survival of virally or bacterially infected cells and in inflammatory conditions, suggesting that interfering with Mcl-1 might be therapeutically beneficial in many other disease settings such as in the diseases of the immune system and autoimmune diseases (Michels et al, Int. J. Biochem. Cell. Biol. 2005, 37, 267-271; Carrington et al, Immunol. Cell Biol. 2017, 95, 870-877; Cottier et al, Rheumatology 2014, 53, 1539-1546). These findings indicated above motivated the discovery and development of a new class of drugs named BH3 mimetics. These molecules are able to disrupt the interaction between the pro-apoptotic and anti-apoptotic members of the Bcl-2 family and are potent inducers of apoptosis. Particularly, selective inhibitors of Mcl-1, such as A-1210477, S63845, S64315, AMG-176 or AZD-5991, have been discovered (Leverson etal, Cell Death Dis. 2015, 6, el590; Kotschy et al, Nature 2016, 538, 477-482; Maragno et al, AACR 2019, Poster #4482; Kotschy et al, WO 2015 / 097123; Caenepeel et al, Cancer Discov. 2018, 8, 1582-1597; Tron et al, Nat. Commun. 2018, 9, 5341) and have shown promising in vivo activity in several types of hematological cell malignancies in preclinical models and three of them - S64315, AMG176 and AZD5991 - are currently being investigated in clinical trials (Yang et al, Eur. J. Med. Chern. 2019, 177, 63-75). Consequently, BH3 mimetics represent a highly attractive approach for the development of novel therapies in oncology and in the field of immune and autoimmune diseases. There is, therefore, a high therapeutic need for compounds inhibiting the anti-apoptotic activity of the proteins of the Bcl-2 family and, particularly, there is a high therapeutic need for compounds inhibiting the anti-apoptotic activity of Mcl-1. SUMMARY OF THE INVENTION The present invention provides potent selective Mcl-1 inhibitors of Formula (I) as defined below. We have shown that compounds of Formula (I) have a strong binding affinity on Mcl-1 receptor and are cytotoxic. Moreover, compounds of Formula (I) can induce apoptosis in in vivo cancer models, triggering tumor regression in mice. Based on their ability to induce the apoptosis, the compounds of the invention could be of interest for the treatment of pathologies involving a deregulation in apoptosis, such as, for example, cancer, auto-immune diseases and diseases of the immune system. In a first aspect of the invention, the present invention relates to compounds of Formula (I): O wherein: ♦ X represents -S-, -O-, -CH2- or -N(R2)-, ♦ Yi represents -C(Ri)(R5)- or -N(R6)-, ♦ Y2 represents -N(R7)-, -C(R8)(R9)-, or -C(R8)(R9)-C(Ri4)(Ri5)-, ♦           means a single bond or a double bond, ♦ Y3 represents -C(Rio)- or -N-, ♦ Y4 represents -C(Ri3)- or -N-, ♦ Ri represents an aryl group or a heteroaryl group, ♦ R2 represents a hydrogen atom or a linear or branched (Ci-Ce)alkyl group, or the pair (Ri,R2) together with the nitrogen atom to which they are attached forms a non-aromatic or aromatic mono- or bicyclic ring composed of from 5 to 12 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen, sulphur and nitrogen, wherein said ring may be substituted by from 1 to 2 groups representing a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ R3 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-O-C(O)-R3a, -Wi-NR3aR3b, -Wi-C(O)-NR3aR3b,         -Wi-O-C(O)-OR3a,         -Wi-O-C(O)-NR3AR3b, -Wi-O-P(O)(OR3a)2, -W1-SO2-OR3A, or -Wi-Cyi, wherein: - Wi represents a bond or a linear or branched (Ci-C4)alkylene group, - R3a and R3b independently of one another, represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, or a cycloalkyl group, or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen and nitrogen, - Cyi represents an aryl group or a heteroaryl group, ♦ R4 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkyl group substituted by 2 linear or branched (Ci-Ce)alkoxy groups, a linear or branched (C2-Ce)alkenyl group, a linear or branched (C2-Ce)alkynyl group, a linear or branched (Ci-C6)alkoxy group, a linear or branched (C2-C6)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkoxy(C2-C6)alkenyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)haloalkyl group, a hydroxy group, a linear or branched (Ci-Ce)hydroxyalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein: - W2 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-C6)alkenylene group, or a linear or branched (C2-Ce)alkynylene group, - W3 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-Ce)alkenylene group, a linear or branched (C2-Cs)alkynylene group, a linear or branched (Ci-Ce)alkoxylene group, a linear or branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2- group, - W4 represents a linear or branched (Ci-C4)alkylene group, - L represents -O-, -S-, or -SO2-, - R4A and R4B independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an aryl group, a heteroaryl group, or an arylalkyl group, - Ric and R4D independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a heteroarylalkyl group, - R4e represents -Cy4 or -CH2-O-Cy4, - Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group, - Cy3 represents an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group, - Cy4 represents an aryl group, a heteroaryl group, an arylalkyl group, or a heterocycloalkylalkyl group, ♦ R5 represents a hydrogen atom or a linear or branched (Ci-C6)alkyl group, or the pair (R4,Rs) represents an oxo group, or a cycloalkylidene group, or the pair (R4,Rs) together with carbon atoms to which they are attached forms a nonaromatic ring composed of from 3 to 6 ring members, ♦ Re represents an aryl group, a -SO2-aryl group, or a -Ws-O-Cys group, wherein: - W5 represents a linear or branched (Ci-C4)alkylene group, - Cys represents an aryl group, or a heteroaryl group, ♦ R7 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a formyl group, ♦ Rs represents a hydrogen atom, or a linear or branched (Ci-C6)alkyl group, or the pair (R4,Rs) together with carbon atoms to which they are attached forms a nonaromatic or aromatic ring composed of from 3 to 7 ring members, ♦ R9 represents a hydrogen atom, or the pair (Rs,Rg) represents an oxo group, ♦ Rio represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, or the pair (R?,Rio) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members, ♦ Rn represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, or a linear or branched (Ci-Ce)alkoxy group, ♦ Rn represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-C6)alkenyl group, a linear or branched (Ci-Ce)alkynyl group, a linear or branched (Ci-C6)alkoxy group, a linear or branched (Ci-Ce)alkenyloxy group, a linear or branched halo(Ci-C6)alkyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl    group, a   linear or   branched (Ci-C6)alkoxy(Ci-Ce)alkoxy group, a hydroxy group, a linear or branched hydroxy(Ci-Ce)alkyl group, an    acetyl    group, a formyl group, a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?, wherein: - Cye represents an aryl group, a heteroaryl group, a cycloalkyl group, an arylalkyl group, or an arylalkenyl group, - Cy? represents an aryl group, cycloalkyl group, or a cycloalkylalkyl group, or the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms wherein said ring may be substituted by Ris and Ris’, ♦ R13 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl group, ♦ Rm and R15 independently of one another, represent a hydrogen atom or a linear or branched (Ci-Ce)alkyl group, ♦ Rie represents a -O-R3 group or a -NR17R17’ group, ♦ R17 and R17’ independently of one another, represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a -SO2-CF3 group, or a -SO2-CH3 group, ♦ Ris and Ris’ independently of one another, represent a hydrogen atom, halogen atom, or a linear or branched (Ci-Ce)alkyl group, or the pair (Ris,Ris’) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 3 to 5 ring members, it being possible for the aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, arylalkyl, arylalkenyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl groups so defined to be substituted by from 1 to 4 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkylidene, linear or branched (Ci-Ce)alkoxy, linear or branched (Ci-C6)alkoxy(Ci-Ce)alkoxy, a linear or branched halo (Ci-Ce)alkyloxy group, hydroxy, a linear or branched hydroxy(Ci-Ce)alkyl group, cyano, oxo, -NR’R”, -C(O)-OR’, cyclopropyl, 2,2-dimethylcyclopropyl, phenyl, pyridinyl, benzyl, (2,3,6-trifluorophenyl)methyl, -CHi-pyridinyl, -O-phenyl, -O-benzyl, -O-pyridinyl, -O-CHi-cyclopropyl, -O-CFh-pyridinyl, aryloxyalkyl or heteroaryloxyalkyl, wherein R’ and R’ ’ independently of one another represent a hydrogen atom or linear or branched (Ci-C6)alkyl, their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. In another aspect, the invention provides compounds of Formula (I) as described herein, for use in the treatment of cancer, autoimmune diseases and the disease of immune system. In a further aspect, the invention provides a pharmaceutical composition comprising the compounds of Formula (I) as described herein, and at least one pharmaceutically acceptable excipient. DEFINITIONS Among the pharmaceutically acceptable acids there may be mentioned, without implying any limitation, hydrochloric acid, hydrobromic acid, sulphuric acid, phosphonic acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulphonic acid, camphoric acid, etc. Among the pharmaceutically acceptable bases there may be mentioned, without implying any limitation, sodium hydroxide, potassium hydroxide, tri ethylamine, / e / V-butyl amine, etc. “aryl” means a monocyclic or a fused bicyclic group composed of from 5 to 10 ring members, having at least one aromatic moiety. Among the aryl groups, there may be mentioned, without implying any limitation, phenyl, indanyl, naphthyl, etc. In a particular embodiment, an aryl group can be deuterated, more particularly a phenyl group can be tetradeuterated. “heteroaryl” means a monocyclic, a fused bicyclic, or a bridged bicyclic group composed of from 5 to 12 ring members, having at least one aromatic moiety and containing from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen. Among the heteroaryl groups, there may be mentioned, without implying any limitation, furyl, thienyl, thiazolyl, isoxazolyl, pyrazolyl, pyridinyl (also known as pyridyl), pyrimidinyl, pyridinonyl, indolyl, dihydroindolyl, indazolyl, tetrahydroindazolyl, benzofuranyl, dihydrobenzofuranyl, benzimidazolyl, benzopyranyl, benzodioxolyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, tetrahydroquinazolinyl, pyrrolopyridinyl, thienopyrimidinyl, furopyridinyl, cyclopentapyridinyl, cyclopentapyrimidinyl, benzothiazolyl, hexahydropentalenopyridinyl, cycloheptapyridinyl, pyranopyridinyl, tetrahydronaphthyridinyl,     tetrahydro-5,8- ethanoquinolinyl, pyrrolyl, isothiazolyl, oxazolyl, imidazolyl, pyrazinyl, pyridazinyl, dihydroisoindolyl, dihydrocyclopentathienyl, benzothienyl, tetrahydrobenzothienyl, imidazopyridinyl, benzotri azolyl, dihydrobenzodioxinyl, isoquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, dihydroquinoxalinyl, dihydrothienodioxinyl, quinazolinonyl, pyrrolopyridazinyl, dihydropyrrolizinyl, tetrahydroindolizinyl, etc. “cycloalkyl” means a monocyclic, a fused bicyclic, or a bridged bicyclic non-aromatic carbocyclic group composed of from 3 to 7 ring members. Among the cycloalkyl groups, there may be mentioned, without implying any limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. “cycloalkenyl” means a monocyclic, a fused bicyclic, or a bridged bicyclic non-aromatic carbocyclic group composed of from 3 to 7 ring members and having one or more double bonds. Among the cycloalkenyl groups, there may be mentioned, without implying any limitation, cyclohexenyl, bicyclo[2.2.1]heptenyl, cyclopentenyl, etc. “heterocycloalkyl” means a monocyclic or fused bicyclic non-aromatic group composed of from 3 to 10 ring members, containing from 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen, and may have one double bond. Among the heterocycloalkyl groups, there may be mentioned, without implying any limitation, azetidinyl, tetrahydropyranyl, tetrahydropyridinyl, piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, etc. “alkylene” or “(Ci-C6)alkylene” means a divalent linear or branched, saturated hydrocarbon radical having from 1 to 6 carbon atoms. Among the alkylene radicals, there may be mentioned, without implying any limitation, -CH2-, -(012)2-, -(012)3-, -(012)4-, -CH(CH3)-, -CH2-CH(CH3)-,   -CH(CH3)-CH2-,   -CH2-CH(CH3)-CH2-,   -CH2-CH(CH2-CH3)-CH2-, -CH2-CH[CH(CH3)2]-CH2-, -CH2-C(CH3)2-CH2-, -CH2-CH(CH3)-CH(CH3)-, etc. “alkenylene” or “(C2-C6)alkenylene” means a divalent linear or branched, hydrocarbon radical having from 2 to 6 carbon atoms and one or more double bonds. More preferably, “alkenylene” refers to a divalent linear or branched hydrocarbon chain having 2 to 6 carbon atoms and one double bond. Among the alkenylene radicals, there may be mentioned, without implying any limitation, -CH-CH-, -CH=CH-CH2-, -CH2-CH-CH-5 etc. “alkynylene” or “(C2-Cg)alkylene” means a divalent linear or branched, hydrocarbon radical having from 2 to 8 carbon atoms and one or more triple bonds. More preferably, “alkynylene” refers to a divalent linear or branched hydrocarbon chain having 2 to 8 carbon atoms and one triple bond. Among the alkynylene radicals, there may be mentioned, without implying any limitation, -C=C-, -C=C-CH2-, -CH2-C=C-, -CH2-CH(C=C<CH2)2<H3)-CH2-, etc. “hydroxyalkylene” or “(Ci-C4)hydroxyalkylene” means a divalent linear or branched, saturated hydrocarbon radical having from 1 to 4 carbon atoms, and one or more hydroxy groups. More preferably, “hydroxyalkylene” refers to a divalent linear or branched hydrocarbon chain having 1 to 4 carbon atoms and one hydroxy group. Among the hydroxyalkylene radicals, there may be mentioned, without implying any limitation, -CH(OH)-, -CH2-CH(OH)-, -CH(OH)-CH2-, -CH2-CH(CH2-OH)-CH2-, etc. “haloalkylene” or “(Ci-C4)haloalkylene” means a divalent linear or branched, saturated hydrocarbon radical having from 1 to 4 carbon atoms, and one or more halogens atoms. More preferably, “haloalkylene” refers to a divalent linear or branched hydrocarbon chain having 1 to 4 carbon atoms and one or more halogens atoms selected from fluorine, chlorine or bromine, more preferably fluorine. Among the haloalkylene radicals, there may be mentioned, without implying any limitation, -CHF-,. -CF2-, -CH2-CHF-, -CHF-CH2-, -CH2-CF2-CH2-, -CH2-CHF-CH2-, -CH2-CH(CH2F)-CH2-, -CH2-CH(CHF2)-CH2-, -CH2-CF(CH3)-CH2-, etc. “alkoxylene” or “(Ci-C6)alkoxylene” means a divalent linear or branched, saturated hydrocarbon radical having from 1 to 6 carbon atoms, and one or more oxygen atoms. More preferably, “alkoxylene” refers to a divalent linear or branched hydrocarbon chain having 1 to 6 carbon atoms and one oxygen atom. Among the alkoxylene radicals, there may be mentioned, without implying any limitation, -CH2-O-, -CH2OCH2-, ~O-(CH2)3-, -CH2-CH(CH2-O-CH3)-CH2-, etc. The term “cycloalkylalkyl” used herein refers to a linear or branched -(Ci-C4)alkyl-Zi group, wherein “Zi” is a cycloalkyl group, preferably a cyclopropyl group, which can be substituted by 0, 1, or 2 substituents independently selected from halogen, (Ci-C6)alkyl, or (Ci-C6)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the cycloalkylalkyl groups, there may be mentioned, without implying any limitation, -CH2-cyclopropyl, -(CH2)2-cyclopropyl, etc. The term “arylalkyl” used herein refers to a linear or branched -(Ci-C4)alkyl-Z2 group, wherein “Z2” is an aryl group, preferably a phenyl group, which can be substituted by 0, 1, 2, or 3 substituents independently selected from halogen, (Ci-C6)alkyl, or (Ci-Ce)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the arylalkyl groups, there may be mentioned, without implying any limitation, -CH2-phenyl (also known as benzyl), -(CH2)2-phenyl, -(CH2)3-phenyl, -CH(CH3)-phenyl, etc. The term “arylalkenyl” used herein refers to a linear or branched -(C2-C4)alkenyl-Z3 group, wherein “Z3” is an aryl group, preferably a phenyl group, which can be substituted by 0, 1, or 2 substituents independently selected from halogen, (Ci-Ce)alkyl, or (Ci-Ce)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the arylalkenyl groups, there may be mentioned, without implying any limitation, -CH=CH-phenyl, -CH=CH-CH2-phenyl, etc. The term “heteroarylalkyl” used herein refers to a linear or branched -(Ci-C4)alkyl-Z4 group, wherein “Z4” is a heteroaryl group, preferably a pyridinyl group, which can be substituted by 0, 1, or 2 substituents independently selected from halogen, (Ci-C6)alkyl, or (Ci-Ce)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the heteroarylalkyl groups, there may be mentioned, without implying any limitation, -Cfh-pyridinyl, -(CH2)2-pyridinyl, -(CH2)3-pyridinyl, etc. The term “heterocycloalkylalkyl” used herein refers to a linear or branched -(Ci-C4)alkyl-Z5 group, wherein “Z5” is a heterocycloalkyl group, preferably a morpholinyl group, which can be substituted by 0, 1, or 2 substituents independently selected from halogen, (Ci-Ce)alkyl, or (Ci-Ce)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the heterocycloalkylalkyl groups, there may be mentioned, without implying any limitation, -CHi-morpholinyl, -(CH2)2-morpholinyl, etc. The term “aryloxyalkyl” used herein refers to a linear or branched -(Ci-C4)alkyl-O-Z6, wherein “Ze” is an aryl group, preferably a phenyl group, which can be substituted by 0, 1, or 2 substituents independently selected from halogen, (Ci-Ce)alkyl, or (Ci-Ce)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the aryloxyalkyl groups, there may be mentioned, without implying any limitation, -CH2-O-phenyl, -(CH2)2-O-phenyl, etc. The term “heteroaryloxyalkyl” used herein refers to a linear or branched -(Ci-C4)alkyl-O-Z7, wherein “Z7” is a heteroaryl group, preferably a pyridinyl group or a thienopyridinyl group, each can be substituted by 0, 1, or 2 substituents independently selected from halogen, (Ci-Ce)alkyl, or (Ci-Ce)alkoxy, preferably fluorine, chlorine, methyl, or methoxy. Among the heteroaryloxyalkyl groups, there may be mentioned, without implying any limitation, -CH2-O-pyridinyl, -(CH2)2-O-pyridinyl, -CH2-O-thienopyridinyl, -(CH2)2-O-thienopyridinyl, etc. “spirocyclohexane compounds” or “spirocyclohexane derivatives” or “spirocyclohexane scaffolds” mean compounds having at least two molecular rings with only one common atom (Moss, Pure AppL Chern. 1999, 71, 531 -558). The common atom that connects the two rings is called the spiro atom which is a quaternary carbon in the present case. For compounds according to the invention, the 1,1,4,4-tetrasubstituted spirocyclohexane allows the formation of two diastereoisomers which are represented as follows: or represented as follows: wherein the -C(=O)-Ri6 group is located to the same side of the benzene-type ring (as shown above on the left), or wherein the -X-Ri group is located to the same side of the benzene-type ring (as shown above on the right). Preferred diastereoisomer of spirocyclohexane derivatives 5 according to the invention is represented as follows: O or represented as follows: O wherein the -C(=O)-Ri6 group is located to the same side of the benzene-type ring. 10 The symbol “ * ” close to two substituted asymmetric carbon atoms (chiral centers) drawn on a molecule scheme means relative stereochemistry. The real configuration of these chiral centers can be either the one drawn or the one where all stereocenters with “ * ” have opposite configuration compared to the drawn. For example, rac-(57?,85)-4-chloro-5-methyl-5,6,7,8-tetrahydroquinolin-8-ol while (57?*, 85*)-4-chloro-5-methyl-5,6,7,8-tetrahydroquinolin-8-ol, enantiomer 1 Among the pharmaceutical compositions according to the invention there may be mentioned more especially those that are suitable for oral, parenteral, nasal, per- or trans-cutaneous, rectal, perlingual, ocular or respiratory administration, especially tablets or dragees, sublingual tablets, sachets, paquets, capsules, glossettes, lozenges, suppositories, creams, ointments, dermal gels, and drinkable or injectable ampoules. The pharmaceutical compositions according to the invention comprise one or more excipients or carriers selected from diluents (such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycerol...), lubricants (such as silica, talc, stearic acid and its magnesium and calcium salts, polyethylene glycol...), binders (such as magnesium aluminum silicate, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidone...), disintegration agents (such as agar, alginic acid and its sodium salt, effervescent mixtures...), stabilizers, preservatives, absorbents, colorants, sweeteners, flavorings, etc. The administration route is preferably the oral route or the intravenous route, and the corresponding pharmaceutical compositions may allow the instantaneous or delayed release of the active ingredients. Among the combinations of a compound of Formula (I) with an anticancer agent according to the invention, there may be mentioned more especially those that are suitable for a simultaneous administration or a sequential administration. The combinations according to the invention comprise a compound of Formula (I) combined to anti-cancer agents selected from genotoxic agents, mitotic poisons, anti-metabolites, proteasome inhibitors, kinase inhibitors, proteinprotein interaction inhibitors, immunomodulators, E3 ligase inhibitors, chimeric antigen receptor T-cell therapy and antibodies. The compounds of the combination may moreover be administered in the form of two separate pharmaceutical compositions, each containing one of the active ingredients, or in the form of a single pharmaceutical composition, in which the active ingredients are in admixture. As used herein, the term “treat”, “treating” or “treatment” of any disease or disorder refers in one embodiment, to ameliorating the disease or disorder (i.e., slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In another embodiment “treat”, “treating” or “treatment” refers to alleviating or ameliorating at least one physical parameter including those which may not be discernible by the patient. In yet another embodiment, “treat”, “treating” or “treatment” refers to modulating the disease or disorder, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both. Among the cancer treatments envisaged there may be mentioned, without implying any limitation, the treatment of haematological malignancies and solid tumors. Haematological malignancies include myeloma, especially multiple myeloma, lymphoma, especially NonHodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), and leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (TALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML). Solid tumors include the bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer. Among the treatments of autoimmune diseases envisaged there may be mentioned, without implying any limitation, the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the rate and extent of absorption, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A suitable daily dose of a compound of the invention will depend upon the factors described above and may range from 0.01 mg to 2.5 g per day in one or more administration(s). DETAILED DESCRIPTION Advantageously, X represents -O- or -N(R2)-. Preferably, X represents -N(R2)-. More preferably, X represents -NH-. In one preferred embodiment, ........ represents a single bond. In one another preferred embodiment, when ........ represents a single bond, independently of one another, Yi represents -C(R4)(Rs)- or -N(R6)- and Y2 represents -N(R?)-, -C(Rs)(R9)-, or -C(R8)(R9)-C(Ri4)(Ri5)-. Preferably, Yi represents -C(R4)(Rs)-. More preferably, Yi represents -N(Re)-. In one preferred embodiment, Y2 represents -N(R?)-. In one another preferred embodiment, Y2 represents -C(R8)(R9)-. In one preferred embodiment, Y2 represents -C(R8)(R9)-C(Ri4)(Ri5)-. Preferably, Yi represents -QRiXRs)- and Y2 represents -C(R8)(R9)-. In one another embodiment, Yi represents -C(R4)(Rs)- and Y2 represents -N(R?)-. In one another embodiment, Yi represents -N(R6)- and Y2 represents -C(R8)(R<j)-. In another embodiment, Yi represents -C(R4)(Rs)- and Y2 represents -C(R8)(R9)-C(Ri4)(Ri5)-. Preferably, when           represents a double bond, independently of one another, Yi represents -C(R4)- and Y2 represents -N= or -C(R8)-. In a preferred embodiment, Y1-Y2 represents -C(R4)=N-. In another embodiment, Y1-Y2 represents -C(R4)=C(R8)-. In preferred embodiment, Y3 represents -C(Rio)-. Preferably, Y4 represents -C(Ri3)-. Advantageously, Y3 represents -C(Rw)- and Y4 represents -C(Ri3)-. An advantageous possibility consists of compounds of Formula (I-a): 10 wherein Ri, R4, Rs, R7, Rio, R11, R12, R13, Ri6 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-a): wherein: 15        ♦ X represents-N(R2)-, ♦ Ri represents an aryl group, ♦ R2, R3, R11 and R13 represent a hydrogen atom, ♦ Rie represents a -O-R3 group, ♦ R4 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, or a -Wi-Cyz group, wherein: - W2 represents a linear or branched (Ci-Ce)alkylene group, - Cy2 represents an aryl group, ♦ R5 represents a hydrogen atom, or the pair (R^Rs) represents an oxo group, ♦ R7 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a formyl group, ♦ Rio represents a hydrogen atom, or a linear or branched (Ci-Ce)alkyl group, or the pair (R?,Rio) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members, ♦ R12 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-C6)alkenyl group, a linear or branched (Ci-C6)alkynyl group, or -Cye, wherein: - Cye represents an aryl group, a cycloalkyl group, an arylalkyl group, or an arylalkenyl group. Another advantageous possibility consists of compounds of Formula (I-b): 0 Rio wherein Ri, R4, Rio, R11, R12, R13, Rie and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-b): O Rio wherein: ♦ X represents -N(R2)-, ♦ Ri represents an aryl group, 5        ♦ R2, R3, Rio, Ru and R13 represent a hydrogen atom, ♦ Rie represents a -O-R3 group, ♦ R4 represents a linear or branched (Ci-Ce)alkyl group, ♦ R12 represents a hydrogen atom or a halogen atom. Another advantageous possibility consists of compounds of Formula (I-c): 0 wherein Ri, Rs, Rs, R9, Rio, R11, R12, R13, Ri6 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-c): wherein: ♦ X represents -N(R2)-, ♦ Ri represents an aryl group, ♦ Rie represents a -O-R3 group, ♦ R2, R3, Rs, R9, Rio and R13 represent a hydrogen atom, or the pair (Rs,R9) represents an oxo group, ♦ Re represents an aryl group, a -SO2-aryl group, or a -Ws-O-Cys group, wherein: - W5 represents a linear or branched (Ci-C4)alkylene group, - Cys represents an aryl group, or a heteroaryl group, ♦ R11 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ R12 represents a hydrogen atom, a linear or branched (Ci-C6)alkoxy group, or a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl group, or the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms. Another advantageous possibility consists of compounds of Formula (I-d): wherein Ri, R4, Rs, Rio, R11, R12, R13, Rie and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-d): wherein: ♦ X represents -N(R2)-, ♦ Ri represents an aryl group or a heteroaryl group, ♦ R2 represents a hydrogen atom or a linear or branched (Ci-C6)alkyl group, ♦ Rie represents a -O-R3 group, ♦ R3 represents a hydrogen atom, ♦ R4 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkyl group substituted by 2 linear or branched (Ci-Ce)alkoxy groups, a linear or branched (C2-Ce)alkenyl group, a linear or branched (Ci-C6)alkoxy(C2-Ce)alkenyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein: - W2 represents a bond, a linear or branched (Ci-C6)alkylene group, a linear or branched (C2-C6)alkenylene group, or a linear or branched (C2-Ce)alkynylene group, - W3 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-C8)alkynylene group, a linear or branched (Ci-Ce)alkoxylene group, a linear or branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2- group, - W4 represents a linear or branched (Ci-C4)alkylene group, - L represents -O-, - R4A and R4B independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an aryl group, or an arylalkyl group, - R4C and R4D independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a heteroarylalkyl group, - R4E represents -Cy4 or -CH2-O-Cy4, - Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group, - Cy3 represents an aryl group, a heteroaryl group, an arylalkyl group, or a heteroarylalkyl group, 5               - Cy4 represents a heteroaryl group, or an arylalkyl group, ♦ Rg represents a hydrogen atom, or a linear or branched (Ci-C6)alkyl group, ♦ Rio represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl group, ♦ Rn represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl 10            group, or a linear or branched (Ci-C6)alkoxy group, ♦ R12 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkoxy group, a linear or branched hydroxy(Ci-C6)alkyl group, or an acetyl group, ♦ R13 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl 15            group. Another advantageous possibility consists of compounds of Formula (I-e): wherein Ri, R4, R5, Rs, R9, Rio, R11, R12, R13, Rie and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-e): O wherein: ♦ X represents -S-, -0-, -CH2- or -N(R2)-, ♦ Ri represents an aryl group or a heteroaryl group, ♦ R2 represents a hydrogen atom, or the pair (Ri,R2) together with the nitrogen atom to which they are attached forms a non-aromatic or aromatic mono- or bicyclic ring composed of from 5 to 12 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen, sulphur and nitrogen, wherein said ring may be substituted by from 1 to 2 groups representing a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ R3 represents a hydrogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-0-C(0)-R3A, -Wi-NRsaRsb, -Wi-C(O)-NR3aR3b,         -Wi-0-C(0)-0R3a,         -Wi-O-C(O)-NR3aR3b, -Wi-O-P(O)(OR3a)2, -W1-SO2-OR3A, or -Wi-Cyi, wherein: - Wi represents a bond or a linear or branched (Ci-C4)alkylene group, - R3A and R3B independently of one another, represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl group, or a cycloalkyl group, or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen and nitrogen, - Cyi represents an aryl group or a heteroaryl group, ♦ R4 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched (C2-Ce)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)haloalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein: - W2 represents a bond, a linear or branched (Ci-Ce)alkylene group, - W3 represents a bond, a linear or branched (Ci-C6)alkylene group, a linear or branched (Ci-Ce)alkoxylene group, a linear or branched (Ci-C4)hydroxy alkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2-group, - W4 represents a linear or branched (Ci-C4)alkylene group, - L represents -O-, -S-, or -SO2-, - R4A and R4B independently of one another represent a hydrogen atom, or a heteroaryl group, - Rte and R4D independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a heteroarylalkyl group, - R4E represents -Cy4 or -CH2-O-Cy4, - Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, or a heterocycloalkyl group, - Cy3 represents an aryl group, a heteroaryl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group, - Cy4 represents an aryl group, a heteroaryl group, an arylalkyl group, or a heterocycloalkylalkyl group, ♦ R5 represents a hydrogen atom or a linear or branched (Ci-Ce)alkyl group, or the pair (R4,Rs) represents a cycloalkylidene group, or the pair (R4,Rs) together with carbon atoms to which they are attached forms a nonaromatic ring composed of from 3 to 7 ring members, ♦ Rs represents a hydrogen atom, or a linear or branched (Ci-C6)alkyl group, or the pair (R4,Rs) together with carbon atoms to which they are attached forms a nonaromatic or aromatic ring composed of from 3 to 7 ring members, ♦ R9 represents a hydrogen atom, ♦ Rio represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ Rn represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, or a linear or branched (Ci-Ce)alkoxy group, ♦ Rn represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-C6)alkoxy group, a linear or branched (Ci-Ce)alkenyloxy group, a linear or branched halo(Ci-Ce)alkyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl    group, a   linear or branched (Ci-C6)alkoxy(Ci-C6)alkoxy group, a hydroxy group, a linear or branched hydroxy(Ci-Ce)alkyl group, an acetyl group, a formyl group, a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?, wherein: - Cye represents an aryl group, a heteroaryl group, a cycloalkyl group, or an arylalkyl group, - Cy? represents an aryl group, a cycloalkyl group, or a cycloalkylalkyl group, or the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms wherein said ring may be substituted by Ris and Ris’, ♦ R13 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ Rie represents a -O-R3 group or a -NR17R17’ group, ♦ R17 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a -SO2-CF3 group, or a -SO2-CH3 group, ♦ R17’ represents a hydrogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ Ris and Ris’ independently of one another, represent a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl group, or the pair (Ris,Ris’) together with the carbon atoms to which they are attached forms a cyclopropyl ring or a cyclobutyl ring. Preferably, compounds of Formula (I-e) are: wherein Ri, R4, Rs, Rs, R9, Rio, R11, R12, R13, Rie and X are as defined previously. More preferably, compounds of Formula (I-e) are: wherein Ri, R4, R5, Rs, R% Rio, R11, R12, R13, Ri6 and X are as defined previously. Another advantageous possibility consists of compounds of Formula (I-f): wherein Ri, R4, Rs, Rs, R9, Rio, R11, R12, R13, R14, Ris, Ri6 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-f): wherein: 10        ♦ X represents-N(R2)-, ♦ Ri represents an aryl group, ♦ Rie represents a -O-R3 group, ♦ R2, R3, R4, Rs, Rs, R9, Rio, R11, R12, R13, R14 and R15 represent a hydrogen atom. Another advantageous possibility consists of compounds of Formula (I-g): 0 r8 5 wherein Ri, R4, Rs, R11, R12, R13, Ri6 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-g): 0 r8 wherein: ♦ X represents -N(R2)-, 10         ♦ Ri represents an aryl group, ♦ Rie represents a -O-R3 group, ♦ R2, R3, R4, Rs, R11, R12 and R13 represent a hydrogen atom. Another advantageous possibility consists of compounds of Formula (I-h): wherein Ri, R4, Rs, R% Rio, R11, R12, Ri6 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-h): 5 wherein: ♦ X represents -N(R2)-, ♦ Ri represents an aryl group, ♦ Rie represents a -O-R3 group, ♦ R2, R3, R4, Rs, Rio, R11 and R12 represent a hydrogen atom. 10 In particular embodiments of compounds of Formulae (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g) and (I-h) above-mentioned, it being possible for the aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, arylalkyl, arylalkenyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl groups so defined to be substituted by from 1 to 4 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkyl, linear or 15 branched halo(Ci-C6)alkylidene, linear or branched (Ci-Ce)alkoxy, linear or branched (Ci-C6)alkoxy(Ci-Ce)alkoxy, a linear or branched halo(Ci-C6)alkyloxy group, hydroxy, a linear or branched hydroxy(Ci-Ce)alkyl group, cyano, oxo, -NR’R”, -C(O)-OR’, cyclopropyl, 2,2-dimethylcyclopropyl, phenyl, pyridinyl, benzyl, (2,3,6-trifluorophenyl)methyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-pyridinyl, -O-CH2-cyclopropyl, -O-CH2-pyridinyl, aryl oxyalkyl or heteroaryloxyalkyl, wherein R’ and R’ ’ independently of one another represent a hydrogen atom or linear or branched (Ci-C6)alkyl. In a preferred embodiment of the invention, the present invention relates to compounds of Formula (I) wherein Ri represents an aryl group, more preferably a phenyl group. Preferably, Ri represents an aryl group, more preferably a phenyl group, which is substituted by from 1 to 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched (Ci-Ce)alkoxy, cyano, or hydroxy. More preferably, Ri represents an aryl group, preferably a phenyl group, which is substituted by from 1 to 3 groups selected from fluorine, chlorine, bromine, methyl, difluoromethyl, trifluoromethyl, methoxy, cyano, or hydroxy. Preferably, Ri represents a 3-chloro-phenyl group, a 3-chloro-4-fluoro-phenyl group, a 3-chloro-2-fluoro-phenyl group, or a 3-chloro-2-methyl-phenyl group. Preferably, Ri represents a 3-chloro-phenyl group. Ri preferably represents a deuterated aryl group, preferably a deuterated phenyl group. In a preferred embodiment, Ri represents a heteroaryl group, preferably a pyridinyl group, more preferably a pyridin-2-yl group, a pyridin-3-yl group or a pyridin-4-yl group. In another preferred embodiment, Ri represents a heteroaryl group, preferably a pyridinyl group, which is substituted by from 1 to 2 groups selected from halogen or (Ci-C6)alkoxy(Ci-Ce)alkoxy. Preferably, Ri represents a heteroaryl group, more preferably a pyridinyl group, which is substituted by from 1 to 2 groups selected from bromine, chlorine, or methoxyethoxy. Advantageously, R2 represents a hydrogen atom or a methyl group, preferably a hydrogen atom. Preferably, the pair (Ri,R2) together with the nitrogen atom to which they are attached forms an indolinyl group. More preferably, the pair (Ri,R2) together with the nitrogen atom to which they are attached forms an indolinyl group which is substituted by a halogen atom, preferably a chlorine atom. Advantageously, Ri6 represents a -O-R3 group. In one embodiment, Rie represents a -NR17R17’ group. In one preferred embodiment, Rie represents a -NH2 group, a -NH-CH3 group, a -N(CH3)2 group, a -NH-SO2-CF3 group, or a -NH-SO2-CH3 group. R3 preferably represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-0-C(0)-R3A, -Wi-NR3AR3B, -Wi-C(O)-NR3aR3b, -Wi-O-C(O)-OR3A, -Wi-O-C(O)-NR3AR3b, -Wi-O-P(O)-(OR3a)2, -Wi-SO2-OR3A, or -Wi-Cyi, wherein: - Wi represents a bond, a -CH2- group, a -(CH2)2- group, a -(CH2)3- group, or a -CH(CH3)- group, - R3a and R3b independently of one another, represent a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxymethyl group, a methoxyethyl group, or a cyclopentyl group, or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a morpholinyl group, - Cyi represents an indanyl group or a 5-methyl-2-oxo-l,3-dioxol-4-yl group. More preferably, R3 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-Ce)alkyl group, -(CH2)2-OR3a, -CH(CH3)-O-C(O)-R3a, -CH2-O-C(O)-R3a, -(CH2)2-NR3aR3b, -CH2-C(O)-NR3aR3b, -CH(CH3)-O-C(O)-OR3a, -CH2-O-C(O)-OR3A, -CH(CH3)-O-C(O)-NR3AR3b, -CH2-O-C(O)-NR3aR3b, -CH2-O-P(O)-(OR3A)2, -(CH2)3-SO2-OR3A, -Cyi, or -CH2-Cyi. Even more preferably, R3 represents a hydrogen atom or a group selected from methyl, ethyl, isopropyl, 2,2,2-trifluoroethyl, methoxyethoxyethyl, methoxyethyl, N,N-dimethylaminoethyl, N,N-dimethylamidomethyl, indan-5-yl, (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl, -CH(CH3)-O-C(O)-CH3, -CH(CH3)-O-C(O)-CH2CH3, -CH(CH3)-O-C(O)-CH2-O-CH3, -CH2-O-C(O)-C(CH3)3, -CH(CH3)-O-C(O)-O-CH3, -CH(CH3)-O-C(O)-O-CH(CH3)2, -CH(CH3)-O-C(O)-O-cyclopentyl, -CH(CH3)-O-C(O)-NH-(CH2)2-O-CH3, -CH2-O-C(O)-O-CH3, -CH(CH3)-O-C(O)-N-morpholinyl, -CH(CH3)-O-C(O)-N(CH2CH3)2, -CH2-O-C(O)-N(CH2CH3)2, -CH2-O-P(O)(O-C(CH3)3)2, -CH2-O-P(O)(OH)2, or -(CH2)3-SO2-OH. Preferably, R3 represents a hydrogen atom. Advantageously, R4 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, a branched (Ci-C6)alkyl group substituted by 2 linear (Ci-C6)alkoxy groups, a linear or branched (C2-Ce)alkenyl group, a linear or branched (C2-C6)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-C6)alkoxy(C2- C6)alkenyl group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)haloalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein - W2 represents a bond, a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group, - W3 represents a bond, a linear or branched (Ci-C6)alkylene group, a linear or branched (C2-Cs)alkynylene group, a linear or branched (Ci-Ce)alkoxylene group, a branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene, or a -CH2-CH(R4e)-CH2- group, - L represents -O-, -S-, or -SO2-, - Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group, - Cy3 represents an aryl group, a heteroaryl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group. Preferably, R4 represents a hydrogen atom, a bromine atom, a iodine atom, a methyl group, an ethyl group, a propyl group, a 3-methoxy-2-(methoxymethyl)propyl, a prop-l-en-l-yl group, a (prop-2-en-l-yl)oxy group, a methoxypropyl group, an ethoxy propyl group, a 3-ethoxy prop-1-en-lyl group, a 2,2-difluoro-3-methoxypropyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NRacRad group. In one preferred embodiment, R4 represents a -W2-Cy2 group. Preferably, W2 represents a bond, a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group. More preferably, W2 represents a bond, a -CH2- group, a -(CH2)2- group, a -(CH2)3- group, a -(CH2)4- group, a -CH2-CH(CH3)- group, a -CH2-CH(CH3)-CH2- group, a -CH=CH- group, a -CH=CH-CH2- group, or a -C=C- group. Cy2 preferably represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydroquinolinyl group, a tetrahydropyridinyl group, an azetidinyl group, a pyridinyl group, a pyrimidinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, a cyclopentenyl group, or a cyclohexyl group. More preferably, Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched (Ci-Ce)alkoxy, hydroxy, oxo, trifluoromethoxy, methoxy ethoxy, -C(O)-OR’, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxyalkyl, wherein R’ represents a linear or branched (Ci-C6)alkyl group. Even more preferably, Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydroquinolinyl group, a tetrahydropyridinyl group, an azetidinyl group, a pyridinyl group, a pyrimidinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, a cyclopentenyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched (Ci-C6)alkoxy, hydroxy, oxo, trifluoromethoxy, methoxyethoxy, -C(O)-OR’, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxyalkyl, wherein R’ represents a linear or branched (Ci-Ce)alkyl group. Advantageously, Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydroquinolinyl group, a tetrahydropyridinyl group, an azetidinyl group, a pyridinyl group, a pyrimidinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, a cyclopentenyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from chlorine, fluorine, methyl, -CF3, -CH2-CF3, methoxy, ethoxy, hydroxy, oxo, trifluoromethoxy, methoxy ethoxy, -CO-O-C(CH3)3, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, -CH2-O-phenyl, -CH2-O-pyridinyl, or -CH2-O-thienopyridinyl. Preferably, R4 represents a -W2-Cy2 group wherein W2 represents a bond and Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydropyridinyl group, an azetidinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, or a cyclopentenyl group. More preferably, R4 represents a -W2-Cy2 group wherein W2 represents a bond and Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydropyridinyl group, an azetidinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, or a cyclopentenyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched (Ci-C6)alkoxy, hydroxy, trifluoromethoxy, methoxyethoxy, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxy alkyl. Even more preferably, R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group. Advantageously, R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group. More advantageously, R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched (Ci-Ce)alkoxy, oxo, -C(O)-OR’, or phenyl, wherein R’ represents a linear or branched (Ci-Ce)alkyl group. In one preferred embodiment, R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched (Ci-Ce)alkoxy, oxo, -C(O)-OR’, or phenyl, wherein R’ represents a linear or branched (Ci-C6)alkyl group. In another preferred embodiment, R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from chlorine, methyl, methoxy, oxo, -CO-O-C(CH3)3, or phenyl. In another preferred embodiment, R4 represents a -W3-L-Cy3 group. W3 preferably represents a bond, a linear or branched (Ci-C6)alkylene group, a linear or branched (C2-Cg)alkynylene group, a linear or branched (Ci-C6)alkoxylene group, a branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2- group. More preferably, W3 represents a bond, a -CH2- group, a -(CH2)2- group, a -(CH2)3- group, a -(CH2)4- group, a -CH2-CH(CH3)-CH2- group, a -CH2-CH(CH2-CH3)-CH2- group, a -CH2-CH[CH(CH3)2]-CH2- group, a -CH2-CH(CH3)-CH(CH3)- group, a -CH2-C(CH3)2-CH2- group, a -O-(CH2)3- group, a -CH2-CH(CH2-OH)-CH2- group, a -CH2-CH(CH2-OCH3)-CH2- group, a -CH2-CF2-CH2- group, a -CH2-CHF-CH2- group, a -CH2-CH(CH2F)-CH2- group, a -CH2-CH(CHF2)-CH2- group, a -CH2-CF(CH3)-CH2- group, a -CH2-CH(C=C-CH2-CH2-CH3)-CH2-group, a -C=C-CH2- group, a -OC-CH2-CH2- group, or a -CH2-CH(R4e)-CH2- group. Even more preferably, W3 represents a -CH2-CH(CH3)-CH2- group. Preferably, L represents -O-. In a preferred embodiment, L represents -S- or -SO2-. Cy3 preferably represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, a benzothiazolyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group, a benzyl group, a -(CH2)2-phenyl group, a -(CH2)3-phenyl group, or a -(CH2)3-pyridinyl group. Advantageously, Cy3 represents an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkylidene, linear or branched (Ci-C6)alkoxy, -NR’R”, cyclopropyl, 2,2-dimethylcyclopropyl, a linear or branched (Ci-C6)hydroxyalkyl, hydroxy, oxo, or difluoromethoxy, wherein R’ and R’ ’ independently of one another represent a hydrogen atom or a linear or branched (Ci-C6)alkyl group. More preferably, Cy3 represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, a benzothiazolyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group, a benzyl group, a -(CH2)2-phenyl group, a -(CH2)3-phenyl group, or a -(CH2)3-pyridinyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched halo(Ci-C6)alkylidene, linear or branched (Ci-Ce)alkoxy, -NR’R”, cyclopropyl, 2,2-dimethylcyclopropyl, a linear or branched (Ci-Ce)hydroxyalkyl, hydroxy, oxo, or difluoromethoxy, wherein R’ and R” independently of one another represent a hydrogen atom or a linear or branched (Ci-C6)alkyl group. Even more preferably, Cy3 represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, a benzothiazolyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group, a benzyl group, a -(CH2)2-phenyl group, a -(CH2)3-phenyl group, or a -(CH2)3-pyridinyl group which are substituted by 1, 2 or 3 groups selected from fluorine, chlorine, methyl, ethyl, isopropyl, -CHF2, -CF3, -CH2CF3, =CHF, methoxy, -NH2, -NH(CH3), cyclopropyl, 2,2-dimethylcyclopropyl, hydroxymethyl, hydroxy, oxo, or difluoromethoxy. Preferably, R4 represents a -W3-L-Cy3 group wherein W3 represents a bond, L represents -O-and Cy3 represents an arylalkyl group or a heteroarylalkyl group. In a preferred embodiment, R4 represents a -W3-L-Cy3 group wherein W3 represents a bond, L represents -O- and Cy3 represents a -(CH2)3-phenyl group or a -(CH2)3-pyridinyl group. In another preferred embodiment, R4 represents a -Ws-L-Cys group wherein W3 represents a linear or branched (Ci-Ce)alkylene group, L represents -O- and Cy3 represents an aryl group, a heteroaryl group, a heterocycloalkyl group, or an arylalkyl group. Advantageously, R4 represents a -Ws-L-Cys group wherein W3 represents a linear or branched (Ci-Ce)alkylene group, L represents -O- and Cy3 represents a phenyl group, a pyridinyl group, a thienopyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a benzothiazolyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group a benzyl group, or a -(CH2)2-phenyl group. In another preferred embodiment, R4 represents a -W3-L-Cy3 group wherein W3 represents a - CH2-CH(CH3)-CH2- group, L represents -O- and Cy3 represents a tetrahydroquinolinyl group. Preferably, R4 represents a -W3-L-Cy3 group wherein W3 represents a -CH2-CH(CH3)-CH2-group, L represents -O- and Cy3 represents a tetrahydroquinolinyl group which is substituted by 1 or 2 groups selected from halogen, preferably a fluorine atom, linear or branched (Ci-5 Ce)alkyl, preferably a methyl group, or hydroxy. Advantageously, R4 represents wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. 10 Preferably, R4 represents wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. More advantageously, R4 represents wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. Preferably, R4 represents wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. Even more advantageously, R4 represents wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. R4 preferably represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (C2-Cs)alkynylene group, L represents -O- and Cy3 represents a phenyl group, or a thienopyridinyl group. In another preferred embodiment, R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (Ci-C4)alkoxylene group, L represents -O- and Cy3 represents a pyridinyl group, or a cyclopentapyridinyl group. In another preferred embodiment, R4 represents a -W3-L-Cy3 group wherein W3 represents a branched (Ci-C4)hydroxyalkylene group, L represents -O- and Cy3 represents a thienopyridinyl group, or a cyclopentapyridinyl group. In another preferred embodiment, R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (Ci-C4)haloalkylene group, L represents -O- and Cys represents a cyclopentapyridinyl group, a tetrahydroquinolinyl group, or a thienopyridinyl group. In another preferred embodiment, R4 represents a -Ws-L-Cys group wherein W3 represents a -CH2-CH(R4E)-CH2- group, L represents -O- and Cys represents a phenyl group, a thienopyridinyl group, a cyclopentapyridinyl group, a pyridinyl group, or a tetrahydroquinolinyl group. Preferably, R4e represents -Cy4. More preferably, Rie represents -CH2-O-Cy4. Preferably, Cy4 represents a phenyl group, a benzyl group, a pyridinyl group, a thienopyridinyl group, a cyclopentapyridinyl group, or a -(CH2)2-morpholinyl group. Advantageously, Rie represents -Cy4 wherein Cy4 represents a phenyl group, a benzyl group, or a pyridinyl group. Advantageously, Rie represents -CH2-O-Cy4 wherein Cy4 represents a thienopyridinyl group, a cyclopentapyridinyl group, or a -(CH2)2-morpholinyl group. Preferably, R4 represents a -W4-NR4aR4b group. Preferably, W4 represents a -CH2- group, a -(CH2)2- group, or a -CH2-CH(CH3)-CH2- group. Preferably, Ria and Rm independently of one another represent a hydrogen atom, a methyl group, a phenyl group, a pyridinyl group, a thienopyridinyl group, a tetrahydroquinolinyl group, or a benzyl group. Preferably, R4a represents a phenyl group, a pyridinyl group, a thienopyridinyl group, a tetrahydroquinolinyl group, or a benzyl group. Preferably, R4b represents a hydrogen atom, or a methyl group. Preferably, R4 represents a -CO-NR4cR4d group. Preferably, R4c and R4d independently of one another represent a hydrogen atom, a methyl group, a benzyl group, a -(CH2)2-phenyl group, or a -(CH2)2-pyridinyl group. Preferably, R4c represents a benzyl group, a -(CH2)2-phenyl group, or a -(CH2)2-pyridinyl group. Preferably, R4D represents a hydrogen atom, or a methyl group. Preferably, Rs represents a hydrogen atom or a methyl group, more preferably a hydrogen atom. Preferably, the pair (R^Rs) represents an oxo group, or a cyclopentylidene group. More preferably, the pair (R4,Rs) together with carbon atoms to which they are attached forms a cyclopentyl ring. Preferably, Re represents a phenyl group, a -SCh-phenyl group, or a -Ws-O-Cys group. Preferably, Ws represents a -(CH2)3- group, or a -CH2-CH(CH3)-CH2- group, more preferably a -CH2-CH(CH3)-CH2- group. Preferably, Cys represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, or a tetrahydroquinolinyl group, more preferably a tetrahydroquinolinyl group, even more preferably, a tetrahydroquinolinyl group which is substituted by 1 or 2 groups selected from linear or branched (Ci-C6)alkyl, preferably a methyl group. More preferably, Re represents h3c*^ wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. Preferably, R? represents a hydrogen atom, a methyl group, an ethyl group, a benzyl group, or a formyl group. Preferably, Rs represents a hydrogen atom, a methyl group, an ethyl group, or an isopropyl group. More preferably, Rs represents a hydrogen atom. Preferably, the pair (R^Rs) together with carbon atoms to which they are attached forms a cyclopropyl ring or a phenyl ring. Preferably, R9 represents a hydrogen atom. Preferably, Rio represents a hydrogen atom, a chlorine atom, a fluorine atom, a bromine atom, or a methyl group. More preferably, Rio represents a hydrogen atom. Preferably, the pair (R?,Rio) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of 6 ring members. Preferably, Ru represents a hydrogen atom, a chlorine atom, a fluorine atom, a bromine atom, a methyl group, or a methoxy group. More preferably, R11 represents a hydrogen atom, a chlorine atom, a fluorine atom, or a methyl group. Even more preferably, R11 represents a hydrogen atom. R12 preferably represents a hydrogen atom, a fluorine atom, a bromine atom, a iodine atom, a chlorine atom, a methyl group, an ethyl group, a prop-l-enyl group, a -C=CH group, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, an isobutyloxy group, a 2-methoxypropan-2-yl group, a prop-2-en-l-yloxy group, a 2,2,2-trifluoroethoxy group, a methoxymethyl group, a methoxyethoxy group, a methoxypropoxy group, a hydroxy group, a hydroxymethyl group, a 1-hydroxyethyl group, an acetyl group, a formyl group, a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?. More preferably, R12 represents a hydrogen atom, a methyl group, a methoxy group, an ethoxy group, an isopropoxy group, a 2-methoxypropan-2-yl group, a methoxymethyl group, a methoxy ethoxy group or a 1-hydroxyethyl group. Even more preferably, R12 represents -Cye which is selected from a phenyl group, a cyclopropyl group, a thienyl group, a pyrrolyl group, a -(CH2)2-phenyl group, a -CH(CH3)-phenyl group, a -CH=CH-phenyl group, or a -CH=CH-CH2-phenyl group. Advantageously, R12 represents -Cye which is selected from a phenyl group, a cyclopropyl group, a thienyl group, a pyrrolyl group, a -(CH2)2-phenyl group, a -CH(CH3)-phenyl group, a -CH=CH-phenyl group, or a -CH=CH-CH2-phenyl group which are substituted by 1, 2 or 3 groups selected from linear or branched (Ci-Ce)alkyl, linear or branched (Ci-Ce)alkoxy, linear or branched (Ci-Ce)alkoxy(Ci-Ce)alkyl, or hydroxy. More advantageously, R12 represents -Cye which is selected from a phenyl group, a cyclopropyl group, a thienyl group, a pyrrolyl group, a -(CH2)2-phenyl group, a -CH(CHs)-phenyl group, a -CH=CH-phenyl group, or a -CH=CH-CH2-phenyl group which are substituted by 1, 2 or 3 groups selected from methyl, methoxy, methoxymethyl, or hydroxy. 5 In a preferred embodiment, R12 represents -O-Cy? wherein Cy- represents a phenyl group, a cyclopentyl group, or a -CH2-cyclopropyl group. Preferably, the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms, wherein said ring may be substituted by Ris and Ris’. 10 More preferably, the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: wherein Ris and Ris’ are as defined for Formula (I). 15 Even more preferably, the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: Advantageously, the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: More advantageously, the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: Preferably, R13 represents a hydrogen atom, a fluorine atom, a bromine atom, or a methyl group. More preferably, R13 represents a hydrogen atom. Preferably, Rm and R15 represent a hydrogen atom. Preferably, R17 and R17’ independently of one another, represent a hydrogen atom, a methyl group, a -SO2-CF3 group, or a -SO2-CH3 group. In one embodiment, R17 represents a hydrogen atom, a methyl group, a -SO2-CF3 group, or a -SO2-CH3 group. In one embodiment, R17’ represents a hydrogen atom or a methyl group. Preferably, Ris and Ris’ independently of one another, represent a hydrogen atom, a fluorine atom, a methyl group, an ethyl group, a w-propyl group or an isopropyl group. In a preferred embodiment, Ris represents a hydrogen atom, a methyl group, an ethyl group, a w-propyl group or an isopropyl group and Ris’ represents a hydrogen atom. More preferably, Ris and Ris’ represent both a hydrogen atom. In another embodiment, Ris and Ris’ represent both a fluorine atom. In another embodiment, Ris and Ris’ represent both a methyl group. In another embodiment, the pair (Ris,Ris’) together with the carbon atoms to which they are attached forms a cyclopropyl ring or a cyclobutyl ring. Preferred compounds according to the invention are: - (15,45)-4-(3-chi oroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-isoindole]-4-carboxylic acid; -   (l.s,45)-4-(3-chloro-4-fluoroanilino)-5'-fluoro-2'-[(2 / ?)-2-methyl-3-{[(5 / ?)-5-methyl- 5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-isoindole]-4-carboxylic acid; - (ls,45)-4-(3-chloroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-2' / / -spiro[cyclohexane-l,5'-[l,3]dioxolo[4,5- / |isoindole]-4-carboxylic acid; -   (15,45)-4-(3-chl oro-4-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8- tetrahydroquinolin-4-yl]oxy}propyl]-6,,7'-dihydro-2'7 / -spiro[cyclohexane-l,5'-[l,3]dioxolo[4,5- / ]isoindole]-4-carboxylic acid; - (lr,2'5,4S)-4-(3-chloro-2-methylanilino)-2'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'£,4S)-4-(3-chloroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'£,4S)-4-(3-chloroanilino)-5'-fluoro-2'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l, l'-indene]-4-carboxylic acid; - (lr,2'£,4S)-5'-chloro-4-(3-chloroanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-6'-methoxy-2'-[(2J?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-6'-ethoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'£,45)-4-(3-chloroanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6'-[(propan-2-yl)oxy]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,2'£,45)-4-(3-chloroanilino)-6'-(2-methoxyethoxy)-2'-[(2 / ?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,2'£,45)-5'-chloro-4-(3-chloroanilino)-6'-methoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,4£,8'5)-4-(3-chloroanilino)-8'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-3\4\8',9'-tetrahydro-277-spiro[cyclohexane-1 J'-indeno[5,6- / >][l,4]dioxepine]-4-carboxylic acid; - (lr,41S',7'1S)-4-(3-chloroanilino)-7'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5,-indeno[5,6-<7][l,3]dioxole]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloro-4-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(5??)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-tZ][l,3]dioxole]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloro-2-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(5??)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-tZ][l,3]dioxole]-4-carboxylic acid; - (lr,4£,6'S)-4-(3-chloro-2-methylanilino)-6'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-27Z-spiro[cyclohexane-l,5'-indeno[5,6-t / ][l,3]dioxole]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloroanilino)-2\2'-dimethyl-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-t / ][l,3]dioxole]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-5',6'-dimethyl-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,27?,47?)-4-(3-chloroanilino)-5\6'-dimethyl-2'-[(2 / ?)-2-methyl-3-{[(5J?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; -   (Ir,2'5,45)-4-(3-chl oroanilino)-6'-(l-hydroxyethyl)-2'-[(27?)-2-methyl-3-{[(57?)-5- methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; -   (lr,2'£,45)-4-(3-chloroanilino)-6'-(2-methoxypropan-2-yl)-2'-[(27?)-2-methyl-3- {[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-6'-(methoxymethyl)-2'-[(2A)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,41S',6'1S)-4-(3-chloroanilino)-6'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-6l,7,-dihydro-2, / / -spiro[cyclohexane-l,5'-indeno[5,6-t / ][l,3]dioxole]-4-carboxylic acid; - (lr,45,7'5)-4-(3-chloroanilino)-7'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; - (lr,3'5,45,7'5)-4-(3-chloroanilino)-3'-methyl-7'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; - (lr,37?,4£,7\S)-4-(3-chloroanilino)-3'-methyl-7'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; - (lr,45,4'5,8'5)-4-(3-chloroanilino)-4'-methyl-8'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6J,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-27 / -spiro[cyclohexane-l,7'-indeno[5,6-6][l,4]dioxepine]-4-carboxylic acid; - (lr,45,47?,8'5)-4-(3-chloroanilino)-4'-methyl-8'-[(2.Z?)-2-methyl-3-{[(5J?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-277-spiro[cyclohexane-l,7'-indeno[5,6-6][l,4]dioxepine]-4-carboxylic acid. Another aspect of the invention concerns a compound of Formula (IIIA): O wherein Rn, Rn, Yi, Y2, Y3, Y4 and          are as defined in Formula (I). Advantageously, compound of Formula (IIIA) can be used as synthesis intermediate for the preparation of compounds of Formula (I). Preferably, compound of Formula (IIIA) is 6'-bromo- 277-spiro[cyclohexane-l,5'-indeno[5,6-d][l,3]dioxol]-4-one. Another aspect of the invention concerns a compound of Formula (VA): O wherein Ri, Rn, R12, X, Y2, Y3, Y4 and ........ are as defined in El, and Hal represents a halogen atom and PG represents a protecting group of the carboxylic acid function. Advantageously, compound of Formula (VA) can be used as synthesis intermediate for the preparation of compounds of Formula (I). Preferably, compound of Formula (VA) is: - methyl (ls,4s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,l'-indene]-4-carboxylate; - methyl (ls,4s)-6'-bromo-4-(3-chloroanilino)-27 / -spiro[cyclohexane-l,5'-indeno[5,6-d\ [ 1,3 ] di oxol e] -4-carb oxyl ate. Described below are a number of embodiments of the invention, where for convenience El is identical to the first aspect of the invention hereinabove. Further enumerated embodiments (E) of the invention are described herein. It will be recognized that features specified in each embodiment may be combined with other specified features to provide further embodiments of the present invention. E2. Compounds according to El wherein X represents -O- or -N(R2)-. E3. Compounds according to El wherein X represents -N(R2)-. E4. Compounds according to El wherein X represents -NH-. E5. Compounds according to El wherein          represents a single bond. E6. Compounds according to El wherein, when           represents a single bond, independently of one another, Yi represents -C(R4)(Rs)- or -N(R6)- and Y2 represents -N(R?)-, -C(R8)(R9)-, or -C(R8)(R9)-C(Ri4)(Ri5)-. E7. Compounds according to El wherein Yi represents -C(R4)(Rs)-. E8. Compounds according to El wherein Yi represents -N(Re)-. E9. Compounds according to El wherein Y2 represents -N(R?)-. E10. Compounds according to El wherein Y2 represents -C(R8)(R9)-. Ell. Compounds according to El wherein Y2 represents -C(R8)(R9)-C(Ri4)(Ri5)-. Ell. Compounds according to El wherein Yi represents -C(R4)(Rs)- and Y2 represents -C(R8)(R9)-. E13. Compounds according to El wherein Yi represents -C(R4)(Rs)- and Y2 represents -N(R7)-. E14. Compounds according to El wherein Yi represents -N(R6)- and Y2 represents -C(R8)(R9)-. E15. Compounds according to El wherein Yi represents -C(R4)(Rs)- and Y2 represents -C(R8)(R9)-C(Ri4)(Ri5)-. E16. Compounds according to El wherein, when           represents a double bond, independently of one another, Yi represents -C(R4)- and Y2 represents -N= or -C(Rs)-. E17. Compounds according to El wherein Y1-Y2 represents -C(R4)=N-. El8. Compounds according to El wherein Y1-Y2 represents -C(R4)=C(Rs)-. E19. Compounds according to El wherein Y3 represents -C(Rio)-. E20. Compounds according to El wherein Y4 represents -C(Ri3)-. Ell. Compounds according to El wherein Y3 represents -C(Rio)- and Y4 represents -C(Ri3)-. Ell. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-a): (I-a) wherein Ri, R4, R5, R7, Rio, R11, R12, R13, Ri6 and X are as defined for Formula (I). E13. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-b): 10 wherein Ri, R4, Rio, R11, R12, R13, Rie and X are as defined for Formula (I). E14. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-c): wherein Ri, Re, Rs, R9, Rio, Rn, R12, R13, Ri6 and X are as defined for Formula (I). E25. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-d): wherein Ri, R4, Rs, Rio, R11, R12, R13, Rie and X are as defined for Formula (I). E26. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-e): 10 wherein Ri, R4, R5, Rs, R9, Rio, R11, R12, R13, Rie and X are as defined for Formula (I). E27. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-f): wherein Ri, R4, R5, Rs, R9, Rio, R11, R12, R13, R14, R15, Ri6 and X are as defined for Formula (I). E28. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-g): wherein Ri, R4, Rs, R11, R12, R13, Ri6 and X are as defined for Formula (I). E29. Compounds according to El wherein an advantageous possibility consists of compounds of Formula (I-h): 10 wherein Ri, R4, Rs, R9, Rio, R11, R12, Rie and X are as defined for Formula (I). E30. Compounds according to El wherein Ri represents an aryl group, preferably a phenyl group. E31. Compounds according to El wherein Ri represents an aryl group, preferably a phenyl group, which is substituted by from 1 to 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched (Ci-C6)alkoxy, cyano, or hydroxy. E32. Compounds according to El wherein Ri represents an aryl group, preferably a phenyl group, which is substituted by from 1 to 3 groups selected from fluorine, chlorine, bromine, methyl, difluoromethyl, trifluoromethyl, methoxy, cyano, or hydroxy. E33. Compounds according to El wherein Ri represents a 3-chloro-phenyl group, a 3-chloro-4-fluoro-phenyl group, a 3-chloro-2-fluoro-phenyl group, ora3-chloro-2-methyl-phenyl group. E34. Compounds according to El wherein Ri represents a 3-chloro-phenyl group. E35. Compounds according to El wherein Ri represents a deuterated aryl group, preferably a deuterated phenyl group. E36. Compounds according to El wherein Ri represents a heteroaryl group, preferably a pyridinyl group, more preferably a pyridin-2-yl group, a pyridin-3-yl group or a pyridin-4-yl group. E37. Compounds according to El wherein Ri represents a heteroaryl group, preferably a pyridinyl group, which is substituted by from 1 to 2 groups selected from halogen or (Ci-C6)alkoxy(Ci-Ce)alkoxy. E38. Compounds according to El wherein Ri represents a heteroaryl group, preferably a pyridinyl group, which is substituted by from 1 to 2 groups selected from bromine, chlorine, or methoxy ethoxy. E39. Compounds according to El wherein R2 represents a hydrogen atom or a methyl group, preferably a hydrogen atom. E40. Compounds according to El wherein the pair (Ri,R2) together with the nitrogen atom to which they are attached forms an indolinyl group. E41. Compounds according to El wherein the pair (Ri,R2) together with the nitrogen atom to which they are attached forms an indolinyl group which is substituted by a halogen atom, preferably a chlorine atom. E42. Compounds according to El wherein R3 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-O-C(O)-R3a, -Wi-NR3aR3b, -Wi-C(O)-NR3aR3b, -Wi-O-C(O)-OR3A, -Wi-O-C(O)-NR3aR3b, -Wi-O-P(O)-(OR3a)2, -W1-SO2-OR3A, or-Wi-Cyi, wherein: - Wi represents a bond, a -CH2- group, a -(012)2- group, a -(012)3- group, or a -CH(CH3)- group, - R3A and R3B independently of one another, represent a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxymethyl group, a methoxyethyl group, or a cyclopentyl group, or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a morpholinyl group, - Cyi represents an indanyl group or a 5-methyl-2-oxo-l,3-dioxol-4-yl group. E43. Compounds according to El wherein R3 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-Ce)alkyl group, -(CH2)2-OR3a, -CH(CH3)-O-C(O)-R3a,   -CH2-O-C(O)-R3a,   -(CH2)2-NR3aR3b, -CH2-C(O)-NR3aR3b, -CH(CH3)-O-C(O)-OR3a,       -CH2-O-C(O)-OR3a, -CH(CH3)-O-C(O)-NR3aR3b, -CH2-O-C(O)-NR3aR3b, -CH2-O-P(O)-(OR3a)2, -(CH2)3-SO2-OR3a, -Cyi, or -CH2-Cyi. E44. Compounds according to El wherein R3 represents a hydrogen atom or a group selected from methyl, ethyl, isopropyl, 2,2,2-trifluoroethyl, methoxyethoxyethyl, methoxyethyl, N,N-dimethylaminoethyl, N,N-dimethylamidomethyl, indan-5-yl, (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl, -CH(CH3)-O-C(O)-CH3, -CH(CH3)-O-C(O)-CH2CH3, -CH(CH3)-O-C(O)-CH2-O-CH3, -CH2-O-C(O)-C(CH3)3, -CH(CH3)-O-C(O)-O-CH3, -CH(CH3)-O-C(O)-O-CH(CH3)2, -CH(CH3)-O-C(O)-O-cyclopentyl, -CH(CH3)-O-C(O)-NH-(CH2)2-O-CH3, -CH2-O-C(O)-O-CH3, -CH(CH3)-O-C(O)-N-morpholinyl, -CH(CH3)-O-C(O)-N(CH2CH3)2, -CH2-O-C(O)-N(CH2CH3)2, -CH2-O-P(O)(O-C(CH3)3)2, -CH2-O-P(O)(OH)2, or -(CH2)3-SO2-OH. E45. Compounds according to El wherein R3 represents a hydrogen atom. E46. Compounds according to El wherein R4 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, a branched (Ci-C6)alkyl group substituted by 2 linear (Ci-Ce)alkoxy groups, a linear or branched (C2-Ce)alkenyl group, a linear or branched (C2-Ce)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-C6)alkoxy(C2-C6)alkenyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)haloalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein - W2 represents a bond, a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group, - W3 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-Cs)alkynylene group, a linear or branched (Ci-C6)alkoxylene group, a branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene, or a -CH2-CH(R4e)-CH2- group, - L represents -O-, -S-, or -SO2-, - Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group, - Cy3 represents an aryl group, a heteroaryl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group. E47. Compounds according to El wherein R4 represents a hydrogen atom, a bromine atom, a iodine atom, a methyl group, an ethyl group, a propyl group, a 3-methoxy-2-(methoxymethyl)propyl, a prop-l-en-l-yl group, a (prop-2-en-l-yl)oxy group, a methoxypropyl group, an ethoxypropryl group, a 3-ethoxy prop-1-en-lyl group, a 2,2-difluoro-3-methoxypropyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group. E48. Compounds according to El wherein R4 represents a -W2-Cy2 group. E49. Compounds according to El wherein W2 represents a bond, a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group. E50. Compounds according to El wherein W2 represents a bond, a -CH2- group, a -(CH2)2-group, a -(CH2)3- group, a -(CH2)4- group, a -CH2-CH(CH3)- group, a -CH2-CH(CH3)-CH2-group, a -CH=CH- group, a -CH=CH-CH2- group, or a -C=C- group. E51. Compounds according to El wherein Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydroquinolinyl group, a tetrahydropyridinyl group, an azetidinyl group, a pyridinyl group, a pyrimidinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, a cyclohexenyl group, a bicyclo[2.2. l]heptenyl group, a cyclopentenyl group, or a cyclohexyl group. E52. Compounds according to El wherein Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched (Ci-Ce)alkoxy, hydroxy, oxo, trifluoromethoxy, methoxy ethoxy, -C(O)-OR’, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxyalkyl, wherein R’ represents a linear or branched (Ci-Ce)alkyl group. E53. Compounds according to El wherein Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydroquinolinyl group, a tetrahydropyridinyl group, an azetidinyl group, a pyridinyl group, a pyrimidinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, a cyclopentenyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched (Ci-C6)alkoxy, hydroxy, oxo, trifluoromethoxy, methoxyethoxy, -C(O)-OR’, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxyalkyl, wherein R’ represents a linear or branched (Ci-Ce)alkyl group. E54. Compounds according to El wherein Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydroquinolinyl group, a tetrahydropyridinyl group, an azetidinyl group, a pyridinyl group, a pyrimidinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, a cyclopentenyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from chlorine, fluorine, methyl, -CF3, -CH2-CF3, methoxy, ethoxy, hydroxy, oxo, trifluoromethoxy, methoxyethoxy, -CO-O-C(CH3)3, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-CH2-cyclopropyl, -O-pyridinyl, -O-CH2-pyridinyl, -CH2-O-phenyl, -CH2-O-pyridinyl, or -CH2-O-thienopyridinyl. E55. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a bond and Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydropyridinyl group, an azetidinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, or a cyclopentenyl group. E56. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a bond and Cy2 represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a phenyl group, a pyrazolyl group, a thiazolyl group, an isoxazolyl group, a thienyl group, a furyl group, a benzofuranyl group, an indolyl group, a dihydrobenzofuranyl group, a tetrahydropyridinyl group, an azetidinyl group, a cyclohexenyl group, a bicyclo[2.2.1]heptenyl group, or a cyclopentenyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched (Ci-Ce)alkoxy, hydroxy, trifluoromethoxy, methoxy ethoxy, phenyl, benzyl, (2,3,6-trifluorophenyl)methyl, pyridinyl, -CEE-pyridinyl, -O-phenyl, -O-benzyl, -O-CHi-cyclopropyl, -O-pyridinyl, -0-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxyalkyl. E57. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group. E58. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group. E59. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Cg)alkyl, linear or branched (Ci-Ce)alkoxy, oxo, -C(O)-OR’, or phenyl, wherein R’ represents a linear or branched (Ci-Ce)alkyl group. E60. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched (Ci-Ce)alkoxy, oxo, -C(O)-OR’, or phenyl, wherein R’ represents a linear or branched (Ci-Ce)alkyl group. E61. Compounds according to El wherein R4 represents a -W2-Cy2 group wherein W2 represents a linear or branched (Ci-C4)alkylene group, a linear (C2-C4)alkenylene group, or a linear (C2-C4)alkynylene group and Cy2 represents a cyclopentyl group, a phenyl group, an indolyl group, a pyridinyl group, a pyrimidinyl group, a tetrahydroquinolinyl group, a piperidinyl group, a morpholinyl group, a piperazinyl group, or a cyclohexyl group which are substituted by 1, 2 or 3 groups selected from chlorine, methyl, methoxy, oxo, -CO-O-C(CH3)3, or phenyl. E62. Compounds according to El wherein R4 represents a -W3-L-Cy3 group. E63. Compounds according to El wherein W3 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-Cg)alkynylene group, a linear or branched (Ci-Ce)alkoxylene group, a branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2- group. E64. Compounds according to El wherein W3 represents a bond, a -CH2- group, a -(CH2)2-group, a -(012)3- group, a -(012)4- group, a -CH2-CH(CH3)-CH2- group, a -CH2-CH(CH2-CH3)-CH2- group, a -CH2-CH[CH(CH3)2]-CH2- group, a -CH2-CH(CH3)-CH(CH3)- group, a -CH2-C(CH3)2-CH2- group, a -O-(CH2)3- group, a -CH2-CH(CH2-OH)-CH2- group, a -CH2-CH(CH2-OCH3)-CH2- group, a -CH2-CF2-CH2-group, a -CH2-CHF-CH2- group, a -CH2-CH(CH2F)-CH2- group, a -CH2-CH(CHF2)-CH2-group, a -CH2-CF(CH3)-CH2- group, a -CH2-CH(C=C-CH2-CH2-CH3)-CH2- group, a -C=C-CH2- group, a -C=C-CH2-CH2- group, or a -CH2-CH(R4e)-CH2- group. E65. Compounds according to El wherein W3 represents a -CH2-CH(CH3)-CH2- group. E66. Compounds according to El wherein L represents -O-. E67. Compounds according to El wherein L represents -S- or -SO2-. E68. Compounds according to El wherein Cy3 represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, a benzothiazolyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group, a benzyl group, a -(CH2)2-phenyl group, a -(CH2)3-phenyl group, or a -(CH2)3-pyridinyl group. E69. Compounds according to El wherein Cy3 represents an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group which are substituted by 1,2 or 3 groups selected from halogen, linear or branched (Ci-C6)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkylidene, linear or branched (Ci-Ce)alkoxy, -NR’R”, cyclopropyl, 2,2-dimethylcyclopropyl, a linear or branched (Ci-Ce)hydroxyalkyl, hydroxy, oxo, or difluoromethoxy, wherein R’ and R” independently of one another represent a hydrogen atom or a linear or branched (Ci-C6)alkyl group. E70. Compounds according to El wherein Cy3 represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, a benzothiazolyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group, a benzyl group, a -(CH2)2-phenyl group, a -(CH2)3-phenyl group, or a -(CH2)3-pyridinyl group which are substituted by 1, 2 or 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-C6)alkyl, linear or branched halo(Ci-Ce)alkylidene, linear or branched (Ci-Ce)alkoxy, -NR’R”, cyclopropyl, 2,2-dimethylcyclopropyl, a linear or branched (Ci-Ce)hydroxyalkyl, hydroxy, oxo, or difluoromethoxy, wherein R’ and R” independently of one another represent a hydrogen atom or a linear or branched (Ci-C6)alkyl group. E71. Compounds according to El wherein Cy3 represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, a benzothiazolyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl group, a dihydroquinolinyl group, a benzyl group, a -(CH2)2-phenyl group, a -(CH2)3-phenyl group, or a -(CH2)3-pyridinyl group which are substituted by 1, 2 or 3 groups selected from fluorine, chlorine, methyl, ethyl, isopropyl, -CHF2, -CF3, -CH2CF3, =CHF, methoxy, -NH2, -NH(CH3), cyclopropyl, 2,2-dimethylcyclopropyl, hydroxymethyl, hydroxy, oxo, or difluoromethoxy. E72. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a bond, L represents -O- and Cy3 represents an arylalkyl group or a heteroarylalkyl group. E73. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a bond, L represents -O- and Cy3 represents a -(CH2)3-phenyl group or a -(CH2)3-pyridinyl group. E74. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (Ci-C6)alkylene group, L represents -O- and Cya represents an aryl group, a heteroaryl group, a heterocycloalkyl group, or an arylalkyl group. E75. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (Ci-Ce)alkylene group, L represents -O- and Cys represents a phenyl group, a pyridinyl group, a thienopyridinyl group, an indolyl group, a benzodioxolyl group, a tetrahydroindazolyl group, an indanyl group, a thienopyrimidinyl group, a pyrimidinyl group, a quinolinyl group, a pyrrolopyridinyl group, a furopyridinyl group, a tetrahydroquinolinyl group, a cyclopentapyridinyl group, an indazolyl group, a cyclopentapyrimidinyl group, a tetrahydroquinazolinyl group, a tetrahydropyranyl group, a benzimidazolyl group, a dihydroindolyl group, a benzopyranyl group, a pyridinonyl group, a hexahydropentalenopyridinyl group, a benzothiazolyl group, a cycloheptapyridinyl group, a pyranopyridinyl group, a tetrahydronaphthyridinyl group, a tetrahydro-5,8-ethanoquinolinyl 5 group, a dihydroquinolinyl group a benzyl group, or a -(CH2)2-phenyl group. E76. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a -CH2-CH(CH3)-CH2- group, L represents -O- and Cy3 represents a tetrahydroquinolinyl group. E77. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 10 represents a -CH2-CH(CH3)-CH2- group, L represents -O- and Cy3 represents a tetrahydroquinolinyl group which is substituted by 1 or 2 groups selected from halogen, preferably a fluorine atom, linear or branched (Ci-Ce)alkyl, preferably a methyl group, or hydroxy. E78. Compounds according to El wherein R4 represents 15 wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. E79. Compounds according to El wherein R4 represents wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. E80. Compounds according to El wherein R4 represents Ch3 JL J h3ct — wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. E81. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (C2-Cg)alkynylene group, L represents -O- and Cy3 represents a phenyl group, or a thienopyridinyl group. E82. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (Ci-C4)alkoxylene group, L represents -O- and Cy3 represents a pyridinyl group, or a cyclopentapyridinyl group. E83. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a branched (Ci-C4)hydroxyalkylene group, L represents -O- and Cya represents a thienopyridinyl group, or a cyclopentapyridinyl group. E84. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a linear or branched (Ci-C4)haloalkylene group, L represents -O- and Cys represents a cyclopentapyridinyl group, a tetrahydroquinolinyl group, or a thienopyridinyl group. E85. Compounds according to El wherein R4 represents a -W3-L-Cy3 group wherein W3 represents a -CH2-CH(R4e)-CH2- group, L represents -O- and Cy3 represents a phenyl group, a thienopyridinyl group, a cyclopentapyridinyl group, a pyridinyl group, or a tetrahydroquinolinyl group. E86. Compounds according to El wherein Rie represents -Cy4. E87. Compounds according to El wherein Rie represents -CH2-O-Cy4. E88. Compounds according to El wherein Cy4 represents a phenyl group, a benzyl group, a pyridinyl group, a thienopyridinyl group, a cyclopentapyridinyl group, or a -(CH2)2-morpholinyl group. E89. Compounds according to El wherein R4E represents -Cy4 wherein Cy4 represents a phenyl group, a benzyl group, or a pyridinyl group. E90. Compounds according to El wherein Rie represents -CH2-O-Cy4 wherein Cy4 represents a thienopyridinyl group, a cyclopentapyridinyl group, or a -(CH2)2-morpholinyl group. E91. Compounds according to El wherein R4 represents a -W4-NR4AR4B group. E92. Compounds according to El wherein W4 represents a -CH2- group, a -(CH2)2- group, or a -CH2-CH(CH3)-CH2- group. E93. Compounds according to El wherein R4A and R4B independently of one another represent a hydrogen atom, a methyl group, a phenyl group, a pyridinyl group, a thienopyridinyl group, a tetrahydroquinolinyl group, or a benzyl group. E94. Compounds according to El wherein R4A represents a phenyl group, a pyridinyl group, a thienopyridinyl group, a tetrahydroquinolinyl group, or a benzyl group. E95. Compounds according to El wherein R4B represents a hydrogen atom, or a methyl group. E96. Compounds according to El wherein R4 represents a -CO-NR4CR4D group. E97. Compounds according to El wherein R4C and R4D independently of one another represent a hydrogen atom, a methyl group, a benzyl group, a -(CH2)2-phenyl group, or a -(CEbh-pyridinyl group. E98. Compounds according to El wherein R4C represents a benzyl group, a -(CH2)2-phenyl group, or a -(CH2)2-pyridinyl group. E99. Compounds according to El wherein R4D represents a hydrogen atom, or a methyl group. E100. Compounds according to El wherein R5 represents a hydrogen atom or a methyl group, preferably a hydrogen atom. E101. Compounds according to El wherein the pair (R^Rs) represents an oxo group, or a cyclopentylidene group. E102. Compounds according to El wherein the pair (R4,Rs) together with carbon atoms to which they are attached forms a cyclopentyl ring. E103. Compounds according to El wherein Re represents a phenyl group, a -SO2-phenyl group, or a -Ws-O-Cys group. El04. Compounds according to El wherein W5 represents a -(012)3- group, or a -CH2-CH(CH3)-CH2- group, more preferably a -CH2-CH(CH3)-CH2- group. E105. Compounds according to El wherein Cys represents a phenyl group, a thienopyridinyl group, a pyridinyl group, an indolyl group, or a tetrahydroquinolinyl group, more preferably a tetrahydroquinolinyl group, even more preferably, a tetrahydroquinolinyl group which is substituted by 1 or 2 groups selected from linear or branched (Ci-C6)alkyl, preferably a methyl group. E106. Compounds according to El wherein Re represents Ch3 3 wherein the wavy line indicates the covalent attachment site to the spirocyclohexane scaffold. E107. Compounds according to El wherein R7 represents a hydrogen atom, a methyl group, an ethyl group, a benzyl group, or a formyl group. E108. Compounds according to El wherein Rs represents a hydrogen atom, a methyl group, an ethyl group, or an isopropyl group, preferably a hydrogen atom. E109. Compounds according to El wherein the pair (R^Rs) together with carbon atoms to which they are attached forms a cyclopropyl ring or a phenyl ring. E110. Compounds according to El wherein R9 represents a hydrogen atom. Elll. Compounds according to El wherein Rio represents a hydrogen atom, a chlorine atom, a fluorine atom, a bromine atom, or a methyl group, preferably a hydrogen atom. El 12. Compounds according to El wherein the pair (R?,Rio) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of 6 ring members. E113. Compounds according to El wherein Rn represents a hydrogen atom, a chlorine atom, a fluorine atom, a bromine atom, a methyl group, or a methoxy group. El 14. Compounds according to El wherein Rn represents a hydrogen atom, a chlorine atom, a fluorine atom, or a methyl group, preferably a hydrogen atom. El 15. Compounds according to El wherein R12 represents a hydrogen atom, a fluorine atom, a bromine atom, a iodine atom, a chlorine atom, a methyl group, an ethyl group, a prop-l-enyl group, a -C=CH group, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, an isobutyloxy group, a 2-methoxypropan-2-yl group, a prop-2-en-l-yloxy group, a 2,2,2-trifluoroethoxy group, a methoxymethyl group, a methoxyethoxy group, a methoxypropoxy group, a hydroxy group, a hydroxymethyl group, a 1-hydroxyethyl group, an acetyl group, a formyl group, a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?. E116. Compounds according to El wherein R12 represents a hydrogen atom, a methyl group, a methoxy group, an ethoxy group, an isopropoxy group, a 2-methoxypropan-2-yl group, a methoxymethyl group, a methoxy ethoxy group or a 1-hydroxy ethyl group. E117. Compounds according to El wherein R12 represents -Cy6 which is selected from a phenyl group, a cyclopropyl group, a thienyl group, a pyrrolyl group, a -(CH2)2-phenyl group, a -CH(CH3)-phenyl group, a -CH=CH-phenyl group, or a -CH=CH-CH2-phenyl group. E118. Compounds according to El wherein R12 represents -Cy6 which is selected from a phenyl group, a cyclopropyl group, a thienyl group, a pyrrolyl group, a -(CH2)2-phenyl group, a -CH(CH3)-phenyl group, a -CH=CH-phenyl group, or a -CH=CH-CH2-phenyl group which are substituted by 1, 2 or 3 groups selected from linear or branched (Ci-C6)alkyl, linear or branched (Ci-Ce)alkoxy, linear or branched (Ci-Ce)alkoxy(Ci-C6)alkyl, or hydroxy. E119. Compounds according to El wherein R12 represents -Cye which is selected from a phenyl group, a cyclopropyl group, a thienyl group, a pyrrolyl group, a -(CH2)2-phenyl group, a -CH(CH3)-phenyl group, a -CH=CH-phenyl group, or a -CH=CH-CH2-phenyl group which are substituted by 1, 2 or 3 groups selected from methyl, methoxy, methoxymethyl, or hydroxy. E120. Compounds according to El wherein R12 represents -O-Cy? wherein Cy? represents a phenyl group, a cyclopentyl group, or a -CH2-cyclopropyl group. E121. Compounds according to El wherein the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms, wherein said ring may be substituted by Ris and Ris’. E122. Compounds according to El wherein the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: wherein Ris and Ris’ are as defined for Formula (I). E123. Compounds according to El wherein the pair (Rn,Ri2) together with the carbon atoms 5 to which they are attached forms a non-aromatic ring as follows: E124. Compounds according to El wherein the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: E125. Compounds according to El wherein the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows: 10 E126. Compounds according to El wherein R13 represents a hydrogen atom, a fluorine atom, a bromine atom, or a methyl group, preferably a hydrogen atom. E127. Compounds according to El wherein Rm and R15 represent a hydrogen atom. E128. Compounds according to El wherein Rie represents a -O-R3 group. E129. Compounds according to El wherein Rie represents a -NR17R17’ group. E130. Compounds according to El wherein Rie represents a -NH2 group, a -NH-CH3 group, a -N(CH3)2 group, a -NH-SO2-CF3 group, or a -NH-SO2-CH3 group. E131. Compounds according to El wherein R17 and R17’ independently of one another, represent a hydrogen atom, a methyl group, a -SO2-CF3 group, or a -SO2-CH3 group. E132. Compounds according to El wherein R17 represents a hydrogen atom, a methyl group, a -SO2-CF3 group, or a -SO2-CH3 group. E133. Compounds according to El wherein R17’ represents a hydrogen atom or a methyl group. E134. Compounds according to El wherein Ris and Ris’ independently of one another, represent a hydrogen atom, a fluorine atom, a methyl group, an ethyl group, a / / -propyl group or an isopropyl group. E135. Compounds according to El wherein Ris represents a methyl group, an ethyl group, a / / -propyl group or an isopropyl group and Ris’ represents a hydrogen atom. E136. Compounds according to El wherein Ris and Ris’ represent both a methyl group. E137. Compounds according to El wherein Ris and Ris’ represent both a fluorine atom. E138. Compounds according to El wherein the pair (Ris,Ris’) together with the carbon atoms to which they are attached forms a cyclopropyl ring or a cyclobutyl ring. E139. Compounds according to E24. wherein: ♦ X represents -N(R2)-, ♦ Ri represents an aryl group, ♦ R2, Rs, R9, Rio and Rn represent a hydrogen atom, or the pair (Rs,R9) represents an oxo group, ♦ Re represents an aryl group, a -SO2-aryl group, or a -Ws-O-Cys group, wherein: - W5 represents a linear or branched (Ci-Chalkylene group, - Cys represents an aryl group, or a heteroaryl group, ♦ Ru represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl group, ♦ R12 represents a hydrogen atom, a linear or branched (Ci-C6)alkoxy group, or a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl group, or the pair (Ru,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms ♦ Rie represents a -O-R3 group wherein R3 represents a hydrogen atom. El40. Compounds according to E26. wherein: ♦ X represents -S-, -O-, -CH2- or -N(R2)-, ♦ Ri represents an aryl group or a heteroaryl group, ♦ R2 represents a hydrogen atom, or the pair (Ri,R2) together with the nitrogen atom to which they are attached forms a non-aromatic or aromatic mono- or bicyclic ring composed of from 5 to 12 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen, sulphur and nitrogen, wherein said ring may be substituted by from 1 to 2 groups representing a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ Rie represents a -O-R3 group, ♦ R3 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-0-C(0)-R3A, -W1-NR3AR3B, -Wi-C(O)-NR3aR3b,         -Wi-0-C(0)-0R3a,         -Wi-O-C(O)-NR3aR3b, -Wi-O-P(O)(OR3a)2, -W1-SO2-OR3A, -Wi-Cyi, wherein: - Wi represents a bond or a linear or branched (Ci-C4)alkylene group, - R3A and Rsb independently of one another, represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl group, a cycloalkyl group, or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen and nitrogen, - Cyi represents an aryl group or a heteroaryl group, ♦ R4 represents a hydrogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (C2-Ce)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)haloalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein: - W2 represents a bond, a linear or branched (Ci-C6)alkylene group, - W3 represents a bond, a linear or branched (Ci-C6)alkylene group, a linear or branched (Ci-Ce)alkoxylene group, a linear or branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2-group, - W4 represents a linear or branched (Ci-C4)alkylene group, - L represents -O-, -S-, or -SO2-, - R4A and Rib independently of one another represent a hydrogen atom, or a heteroaryl group, - R4C and R4D independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a heteroarylalkyl group, - R4E represents -Cy4 or -CH2-O-Cy4, - Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, or a heterocycloalkyl group, - Cy3 represents an aryl group, a heteroaryl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group, - Cy4 represents an aryl group, a heteroaryl group, an arylalkyl group, or a heterocycloalkylalkyl group, ♦ R5 represents a hydrogen atom or a linear or branched (Ci-Ce)alkyl group, or the pair (R4,Rs) represents a cycloalkylidene group or the pair (R4,Rs) together with carbon atoms to which they are attached forms a nonaromatic ring composed of from 3 to 7 ring members, ♦ Rs represents a hydrogen atom, a linear or branched (Ci-C6)alkyl group, or the pair (R4,Rx) together with carbon atoms to which they are attached forms a nonaromatic or aromatic ring composed of from 3 to 7 ring members, ♦ R9 represents a hydrogen atom, ♦ Rio represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, ♦ R11 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl group, or a linear or branched (Ci-C6)alkoxy group, ♦ R12 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkoxy group, a linear or branched (Ci-Ce)alkenyloxy group, a linear or branched halo(Ci-C6)alkyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl group, a   linear or   branched (Ci-C6)alkoxy(Ci-Ce)alkoxy group, a hydroxy group, a linear or branched hydroxy(Ci-Ce)alkyl group, an acetyl group, a formyl group, a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?, wherein: - Cye represents an aryl group, a heteroaryl group, a cycloalkyl group, or an arylalkyl group, - Cy? represents an aryl group, a cycloalkyl group, or a cycloalkylalkyl group, or the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms wherein said ring may be substituted by Ris and Ris’, ♦ R13 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group; ♦ Ris and Ris’ independently of one another, represent a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group, or the pair (Ris,Ris’) together with the carbon atoms to which they are attached forms a cyclopropyl ring or a cyclobutyl ring. E141. Compounds according to E26. or E140. wherein compounds of Formula (I-e) are: O wherein Ri, R4, R5, Rs, R% Rio, R11, R12, R13, Ri6 and X are as defined in E26. or E140. E142. Compounds according to E141. wherein compounds of Formula (I-e) are: 0 5 wherein Ri, R4, Rs, Rs, R9, Rio, R11, R12, R13, Ri6 and X are as defined in E141. E143. Compounds according to El which are: -   (15,45)-4-(3-chloroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8- tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-isoindole]-4-carboxylic acid; 10         -   (15,45)-4-(3-chloro-4-fluoroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl- 5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-isoindole]-4-carboxylic acid; - (15,45)-4-(3-chi oroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'- 15            [l,3]dioxolo[4,5- / |isoindole]-4-carboxylic acid; - (15,45)-4-(3-chl oro-4-fluoroanilino)-6'-[(2J?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-[l,3]dioxolo[4,5- / |isoindole]-4-carboxylic acid; - (Ir, 2'5,45)-4-(3-chi oro-2 -methylanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl- 5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-5'4duoro-2'-[(22?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-5'-fluoro-2'-[(27?)-3-{[(57?,8 / ?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l, l'-indene]-4-carboxylic acid; - (lr,2'5,45)-5'-chloro-4-(3-chloroanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-6'-methoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-6'-ethoxy-2'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; -   (lr, 2'S, 45)-4-(3-chloroanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8- tetrahydroquinolin-4-yl]oxy}propyl]-6'-[(propan-2-yl)oxy]-2',3'-dihydrospiro[cyclohexane-l, l'-indene]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-6'-(2-methoxyethoxy)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,2'5,45)-5'-chloro-4-(3-chloroanilino)-6'-methoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,45,8'5)-4-(3-chloroanilino)-8'-[(27?)-2-methyl-3-{[(5J?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-277-spiro[cyclohexane-l,7'-indeno[5,6-6][l,4]dioxepine]-4-carboxylic acid; - (lr,45,7'5)-4-(3-chloroanilino)-7'-[(27?)-2-methyl-3-{[(5J?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; -   (Ir, 45,6'5)-4-(3-chloroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8- tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-t / ][l,3]dioxole]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloro-4-fluoroanilino)-6'-[(2A)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-<7][l,3]dioxole]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloro-2-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(5??)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-tZ][l,3]dioxole]-4-carboxylic acid; - (lr,4£,6'S)-4-(3-chloro-2-methylanilino)-6'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-tZ][l,3]dioxole]-4-carboxylic acid; - (lr,45,6'5)-4-(3-chloroanilino)-2',2'-dimethyl-6'-[(27?)-2-methyl-3-{[(5J?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-tZ][l,3]dioxole]-4-carboxylic acid; - (lr,2'5,45)-4-(3-chloroanilino)-5',6'-dimethyl-2'-[(27?)-2-methyl-3-{[(5J?)-5-methyl-5,6J,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; - (lr,27?3^)-4-(3-chloroanilino)-5',6'-dimethyl-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid; -   (Ir,2'53^-4-(3-chloroanilino)-6'-(l-hydroxyethyl)-2'-[(27?)-2-methyl-3-{[(57?)-5- methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; -   (lr,2'£,45)-4-(3-chloroanilino)-6'-(2-methoxypropan-2-yl)-2'-[(27?)-2-methyl-3- {[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,2'£,45)-4-(3-chloroanilino)-6'-(methoxymethyl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid; - (lr,4£,6'5)-4-(3-chloroanilino)-6'-[(27?)-3-{[(57?,8J?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-d][l,3]dioxole]-4-carboxylic acid; - (lr,4£,7'5)-4-(3-chloroanilino)-7'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8- tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-^][l,4]dioxine]-4-carboxylic acid; - (lr,3'5,45,7'S)-4-(3-chloroanilino)-3'-methyl-7'-[(2.R)-2-methyl-3-{[(5.K)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; - (lr,3'7?,45',7'5)-4-(3-chloroanilino)-3'-methyl-7'-[(27?)-2-methyl-3-{[(5A)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid; - (lr,45,4'5,8'5)-4-(3-chloroanilino)-4'-methyl-8'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6J,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-27 / -spiro[cyclohexane-l,7'-indeno[5,6-Z>][l,4]dioxepine]-4-carboxylic acid; - (lr,4£,47?,8'S)-4-(3-chloroanilino)-4'-methyl-8'-[(2.Z?)-2-methyl-3-{[(57?)-5-methyl-5,6J,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-27 / -spiro[cyclohexane-l,7'-indeno[5,6-Z>][l,4]dioxepine]-4-carboxylic acid. E144. A compound of Formula (IIIA): O wherein Rn, Rn, Yi, Y2, Y3, Y4 and          are as defined in El, as synthesis intermediate for the preparation of compounds of Formula (I) according to El. E145. A compound of Formula (IIIA) according to E144. which is 6'-bromo-2' / / -spiro[cyclohexane-l,5'-indeno[5,6-<7][l,3]dioxol]-4-one. E146. A compound of Formula (IIIA) according to E144. or E145. for use as synthesis intermediate for the preparation of compounds of Formula (I) according to El. E147. A compound of Formula (VA): 0 wherein Ri, Rn, R12, X, Y2, Y3, Y4 and ........ are as defined in El, and Hal represents a halogen atom and PG represents a protecting group of the carboxylic acid function, as synthesis intermediate for the preparation of compounds of Formula (I) according to El. 5   E148. A compound of Formula (VA) according to E147. which is: - methyl (ls,4s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,l'-indene]-4-carboxylate; - methyl (ls,4s)-6'-bromo-4-(3-chloroanilino)-277-spiro[cyclohexane-l,5'-indeno[5,6-d\ [ 1,3 ] di oxol e] -4-carb oxy 1 ate. 10   E149. Pharmaceutical composition comprising a compound of Formula (I) according to any one of embodiments El to E143. or an addition salt thereof with a pharmaceutically acceptable acid or base in combination with one or more pharmaceutically acceptable excipients. E150. Pharmaceutical composition according to E149. for use as anti-apoptotic inhibitors. E151. Pharmaceutical composition according to E149. for use in the treatment of cancer and 15   of auto-immune and immune system diseases. E152. Pharmaceutical composition according to El 51. wherein the cancer is an haematological malignancy or a solid tumor. E153. Pharmaceutical composition according to E151. or El 52. wherein the cancer is chemoresistant or radio-resistant. E154. Pharmaceutical composition according to El52. wherein the haematological malignancy is myeloma, especially multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), and leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML). E155. Pharmaceutical composition according to El52. wherein the solid tumor is selected from bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially nonsmall-cell lung cancer and small-cell lung cancer. E156. Pharmaceutical composition according to E151. wherein the auto-immune and immune system diseases are rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). E157. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use as anti-apoptotic inhibitors. E158. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use in the treatment of cancer and of auto-immune and immune system diseases. E159. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use according to E158. wherein the cancer is an haematological malignancy or a solid tumor. E160. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use according toE158. wherein the cancer is chemo-resistant or radio-resistant. E161. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use according to El 59. wherein the haematological malignancy is myeloma, especially multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), and leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML). E162. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use according to El 59. wherein the solid tumor is selected from bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer. E163. Compound of Formula (I) according to any one of embodiments El to E143. , or an addition salt thereof with a pharmaceutically acceptable acid or base, for use according to E158. wherein the auto-immune and immune system diseases are rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). E164. Combination of a compound of Formula (I) according to any one of embodiments El to E143. with anti-cancer agents selected from genotoxic agents, mitotic poisons, anti-metabolites, proteasome inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators, E3 ligase inhibitors, chimeric antigen receptor T-cell therapy and antibodies. E165. Pharmaceutical composition comprising a combination according to E164. in combination with one or more pharmaceutically acceptable excipients. E166. Combination according to E165. for use in the treatment of cancer. E167. Combination according to El66. wherein the cancer is chemo-resistant or radioresistant. E168. Combination according to E166. or E167. wherein the cancer is selected from myeloma, especially multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML), bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer. E169. Compound of Formula (I) according to any one of embodiments El to E143. for use in the treatment of cancer requiring radiotherapy. Pharmacological studies of the compounds of the invention have shown that they have pro-apoptotic properties. The ability to reactivate the apoptotic process in cancerous cells is of major therapeutic interest in the treatment of cancer and of immune and auto-immune diseases. The present invention relates also to pharmaceutical compositions comprising at least one compound of Formula (I) or an addition salt thereof with a pharmaceutically acceptable acid or base in combination with one or more pharmaceutically acceptable excipients. In particular, these pharmaceutical compositions are interesting for use as anti-apoptotic inhibitors, particularly, in the treatment of cancer (haematological malignancy and solid tumor) and of auto-immune and immune system diseases. Particularly, these pharmaceutical compositions are interesting for use as anti-apoptotic inhibitors in the treatment of cancer chemo-resistant or radio-resistant. Preferably, these pharmaceutical compositions can be used in the treatment of cancer (haematological malignancy and solid tumor) and of auto-immune and immune system diseases selected from myeloma, especially multiple myeloma, lymphoma, especially NonHodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (TALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML), bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, lung cancer, especially non-small-cell lung cancer and small-cell lung cancer, rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Furthermore, the present invention relates also to the combination of a compound of Formula (I) with an anticancer agent selected from genotoxic agents, mitotic poisons, anti-metabolites, proteasome inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators, E3 ligase inhibitors, chimeric antigen receptor T-cell therapy and antibodies, and also to pharmaceutical compositions comprising that type of combination and their use in the manufacture of medicaments for use in the treatment of cancer, particularly, haematological malignancy and solid tumors selected from myeloma, especially multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML), bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer. Alternatively, the compounds of the invention may be linked to monoclonal antibodies. Antibody Drug Conjugates (ADCs) represent a class of therapeutics that is formed by chemically linking a cytotoxic drug to a monoclonal antibody through a linker. The monoclonal antibody of an ADC selectively binds to a target antigen of a cell (e.g. cancer cell) and releases the drug into the cell or in the cell environment. ADCs have therapeutic potential because they combine the specificity of the antibody and the cytotoxic potential of the drug. Nonetheless, developing ADCs as therapeutic agents has thus far met with limited success owing to a variety of factors such as unfavorable toxicity profiles, low efficacies and poor pharmacological parameters. Accordingly, there is still a need for new ADCs that overcome these problems and can selectively deliver Mcl-1 inhibitors to target cancer cells. In another aspect, the compounds of the invention may be linked to monoclonal antibodies or fragments thereof or linked to scaffold proteins that can be related or not to monoclonal antibodies. Antibody fragments must be understood as fragments of Fv, scFv, Fab, F(ab')2, F(ab'), scFv-Fc type or diabodies, which generally have the same specificity of binding as the antibody from which they are descended. According to the present invention, antibody fragments of the invention can be obtained starting from antibodies by methods such as digestion by enzymes, such as pepsin or papain, and / or by cleavage of the disulfide bridges by chemical reduction. In another manner, the antibody fragments comprised in the present invention can be obtained by techniques of genetic recombination likewise well known to the person skilled in the art or else by peptide synthesis by means of, for example, automatic peptide synthesizers such as those supplied by the company Applied Biosystems, etc. Scaffold proteins that can be related or not to monoclonal antibodies are understood to mean a protein that contains or not an immunoglobulin fold and that yields a binding capacity similar to a monoclonal antibody. The man skilled in the art knows how to select the protein scaffold. More particularly, it is known that, to be selected, such a scaffold should display several features as follows (Skerra, J. Mol. Recogn. 2000, 13, 167-187): phylogenetically good conservation, robust architecture with a well-known three-dimensional molecular organization (such as, for example, crystallography or NMR), small size, no or only a low degree of post-translational modifications, easy to produce, express and purify. Such a protein scaffold can be, but without limitation, a structure selected from the group consisting in fibronectin and preferentially the tenth fibronectin type III domain (FNfnlO), lipocalin, anticalin (Skerra, J. Biotechnol. 2001, 74, 257-75), the protein Z derivative from the domain B of staphylococcal protein A, thioredoxin A or any protein with a repeated domain such as an “ankyrin repeat” (Kohl et al, PNAS 2003, 100, 1700-1705), “armadillo repeat”, “leucine-rich repeat” or “tetratricopeptide repeat”. There could also be mentioned a scaffold derivative from toxins (such as, for example, scorpion, insect, plant or mollusc toxins) or protein inhibitors of neuronal nitric oxide synthase (PIN). EXAMPLES The compounds of the present disclosure can be prepared in a number of ways well known to those skilled in the art of organic synthesis. By way of example, compounds of the invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. It is understood that at any moment considered appropriate during the processes described below, some groups (halogen, hydroxy, amino...) of the starting reagents or of the synthesis intermediates can be protected, subsequently deprotected and functionalized, as required by the synthesis. Preferred methods include but are not limited to those methods described below. Compounds of the present invention can be synthesized by following the steps outlined in General Schemes 1, 2, 3, 4, 5, 6, 7 and 8 which comprise different sequences of preparing intermediates IIA, IIB, IIC, IIIA, IIIC, IVA, IVD, VA, VA’, VB, VIA, VIA’, VIB, VIB’, VIB”, VIIA and VIIA’. Starting materials IA, IB, IC and ID are either commercially available or made by known procedures in the reported literature or as illustrated. General Scheme 1 ib                                     nB wherein Yi, Y2, Y3, Y4, Rn, R12 and ........ are as defined in Formula (I). The general way of preparing key-intermediate ketone IIIA containing spirocyclohexane 5 scaffold by using intermediates IIA and IIB is outlined in General Scheme 1. Spirocyclization of starting material IA with (1,3-di oxolane-2,2-diyl)di(ethane-2,l-diyl)methanesulfonate or 2,2-bis(2-bromoethyl)-l,3-dioxolane using a strong base (such as NaH or LIHDMS) at low temperatures and ketal cleavage under acidic conditions provides intermediate ketone IIIA. Alternatively, preparation of key-intermediate ketone IIIA can be performed by 10 spirocyclization of starting material IB with methyl vinyl ketone (also known as but-3-en-2-one) under acidic conditions (for example, using PTSA) at elevated temperatures providing intermediate IIB. Finally, hydrogenation of IIB using catalytic amount ofPd / C and dihydrogen (or other known reagents for hydrogenation reaction) provides mA. General Scheme 2 wherein Y2, Y3, Y4, Re, R11 and R12 are as defined in Formula (I). Even if spirocyclohexane derivatives wherein Yi represents -N(Re)- can be prepared through synthetic pathway as outlined in General Scheme 1 above, an alternative way for preparing these specific compounds is outlined in General Scheme 2. Spirocyclization of starting material IC using a Pd salt (such as Pd(OAc)2) at high temperatures provides intermediate IIC. Finally, hydrogenation of IIC using catalytic amount of Pd / C in presence of ammonium formate followed by ketal cleavage under acidic conditions provides intermediate ketone IIIC. General Scheme 3 IIIA                                                 IVA wherein X, Yi, Y2, Y3, Y4, Ri, Ru, R12 and          are as defined in Formula (I). The general way of preparing IVA containing spirocyclohexane scaffold by using intermediate ketone IIIA is outlined in General Scheme 3. In one embodiment, ketone’s functionalization was performed via Bargellini reaction using appropriate reactant Ri-X-H in presence of NaOH and CHCh at low temperatures providing IVA. In a particular embodiment for the preparation of IVA wherein X represents -N(R2)-, ketone IIIA is subjected to Strecker reaction using appropriate reactant R1-NH2 in presence of cyanide salt yielding a cyano intermediate which is transformed to the corresponding amide derivative and the latter is finally hydrolyzed to yield IVA. In another embodiment for the preparation of IVA wherein X represents -N(R2)-, ketone IHA is subjected to Bucherer-Bergs reaction using ammonium carbonate and potassium cyanide at elevated temperatures yielding a hydantoin intermediate which is then hydrolyzed to provide an amino acid intermediate and the latter is finally subjected to Ullmann reaction in presence 5 of copper and Ri-Z wherein Z is a halogen atom to yield IVA. General Scheme 4 wherein X, Y2, Y3, Y4, Ri, Re, R11, R12 and Rie are as defined in Formula (I). Even if spirocyclohexane derivatives wherein Yi represents -N(Re)- can be prepared through 10 synthetic pathway as outlined in General Scheme 3 above, an alternative way for preparing these specific compounds is outlined in General Scheme 4. Spirocyclization of starting material ID under acidic conditions provides IVD. VIIA wherein X, Y2, Y3, Y4, Ri, R4, R11, R12 and ........ are as defined in Formula (I), and Hal represents a halogen atom and PG represents a protecting group of the carboxylic acid function. In one preferred embodiment, a synthetic pathway for preparing VIIA is outlined in General Scheme 5. Starting material IVA wherein Yi represents -C(Hal)= or -C(Hal)(Rs)- and Hal represents a halogen atom, was esterified to provide key-intermediate VA wherein PG represents a protecting group of the carboxylic acid function such as methyl ester, ethyl ester, etc. Then, R4 group was introduced according to classical chemical reactions using the corresponding reactants (for example, metal-catalyzed cross coupling using R4-ZnBr reactant such as Negishi reaction) to provide VIA. In one embodiment, when          represents a double bond, an intermediate hydrogenation step of indene VIA can be performed to provide corresponding indane. Finally, VIIA is obtained after removal of carboxylic acid protecting group (for example, by ester hydrolysis). General Scheme 6 VIIA' wherein Cy3, L, W3, X, Y2, Y3, Y4, Ri, R11, R12 and ........ are as defined in Formula (I), and PG represents a protecting group of the carboxylic acid function. 5 In one preferred embodiment, a synthetic pathway for preparing VIIA’ is outlined in General Scheme 6. Starting material IVA wherein Yi represents -C(Br)= or -C(Br)(Rs)- was esterified to provide VA’ wherein PG represents a protecting group of the carboxylic acid function such as methyl ester, ethyl ester, etc. Metal-catalyzed cross-coupling reaction in presence of W3-OH reactant was performed to provide VIA’. In one embodiment, when ........ represents a 10 double bond, an intermediate hydrogenation step of indene VIA’ is possible to provide corresponding indane. Finally, VIIA’ is obtained after coupling Cy3-L-H on intermediate VIA’ (for example, through Mitsunobu reaction) and removal of carboxylic acid protecting group (for example, by ester hydrolysis). General Scheme 7 wherein X, Y2, Y3, Y4, Ri, R11 and ........ are as defined in Formula (I), and Hal represents a halogen atom and PG represents a protecting group of the carboxylic acid 5 function. In one another embodiment, a synthetic pathway for preparing VIB, VIB’ and VIB” is outlined in General Scheme 7. Starting material IVA wherein Yi represents -C(Hal)= or -C(Hal)(Rs)-, R12 represents a hydrogen atom and Hal represents a halogen atom, was esterified to provide VB wherein PG represents a protecting group of the carboxylic acid function such as methyl 10 ester, ethyl ester, etc. From intermediate VB, among existing chemical reactions, there may be mentioned Friedel-Crafts acylation providing VIB, formylation reaction providing VIB’, or halogenation reaction providing VIB”. In one embodiment, intermediate VIB can be transformed through Baeyer-Villiger rearrangement which can further provide, after hydrolysis, hydroxylated analogues, ether analogues or aryl derivatives. Finally, group R4 is introduced 15 according to General Schemes 5 or 6. In one another embodiment, intermediate VIB’ can be transformed through a reduction reaction to provide hydroxymethyl analogues. Finally, group R4 is introduced according to General Schemes 5 or 6. In one another embodiment, intermediate VIB” can be transformed through an alkylation reaction on the benzene ring. Finally, group R4 is introduced according to General Schemes 5 or 6. It is understood that IVA, IVD, VA, VA’, VB, VIA, VIB, VIB’, VIB”, VIIA and VIIA’ can represent particular compounds of Formula (I) or can represent intermediates for the preparation of compounds of Formula (I). For example, as shown in General Scheme 8, transformation of carboxylic acid of VIIA can be performed for the preparation of VIIIA or for the preparation ofIXA. General Scheme 8 0                                      0 vmA                                         IXA wherein X, Y2, Y3, Y4, Ri, R4, R11, R12, R17, R17’ and ........ are as defined in Formula (I), and R3’ represents a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-O-C(O)-R3a, -W1-NR3AR3B, -Wi-C(O)-NR3aR3b, -Wi-0-C(0)-0R3a, -Wi-O-C(O)-NR3aR3b, -Wi-O-P(O)(OR3a)2,   -W1-SO2-OR3A, or-Wi-Cyi. A mixture of enantiomers, diastereoisomers resulting from the processes described above can be separated into their single components by chiral salt technique, chromatography using normal phase, reverse phase or chiral column, depending on the nature of the separation. ABBREVIATIONS abbreviation name 2-Me-THF Ac AcCl 2-methyl-tetrahydrofuran acetyl acetyl chloride AcOH AtaPhos aq. acetic acid bis(di-tert-butyl(4- dimethylaminophenyl)phosphine)dichloropalladium(II) aqueous 5 B2pin2 bis(pinacolato)diboron BBr3 boron tribromide BF3xEt2O boron trifluoride diethyl etherate BH3x SMe2 borane dimethyl sulfide complex BH3xTHF borane tetrahydrofuran complex 10 BOC2O di-tert-butyl di carb onate Bn benzyl BnBr benzyl bromide BnOH benzyl alcohol cataCXium® A di(l-adamantyl)-«-butylphosphine 15 cc. concentrated CHCh chloroform Cui copper (I) iodide Cu(OAc)2 copper(II) acetate Cu(OTf)2 copper(II) trifluoromethane sulfonate 20 DAST diethylaminosulfur trifluoride DBU 1,8 -di azabi cyl co [5.4.0]undec-7-ene DCM methylene chloride DDQ 4,5-dichloro-3,6-dioxo-cyclohexa-l,4-diene-l,2-di carbonitrile DEA diethylamine 25 DIAD diisopropyl azodicarboxylate DIBAL-H diisobutyl aluminium hydride DIPA diisopropylamine DIPE diisopropyl ether DIPEA diisopropylethylamine 30 DMA A,A-di methyl acetamide DMAP 4-dimethylaminopyridine DME 1,2-dimethoxy ethane DMF A, A-di methyl form amide DMP Dess-Martin periodinane dimethyl sulfoxide DMSO dppp 1,3 -bi s(diphenylphosphino)propane DTBAD di-tert-butyl azodi carboxyl ate 5 eq. equivalent EDCxHCl A-(3-dimethylaminopropyl)-A"-ethylcarbodiimide hydrochloride Et ethyl Et20 diethyl ether Etl iodoethane 10 EtMgCl ethyl magnesium chloride EtOAc ethyl acetate EtOH ethanol EtSH ethanethiol h hour(s) 15 HBTU 2-(lH-benzotriazole-l-yl)-l, 1,3,3- tetramethylaminium hexafluorophosphate Herrmann’s catalyst trans-bi. s(acetato)b i s [o-(di -o- tolylphosphino)benzyl]dipalladium(II) HOBt hydroxybenzotriazole 20 zPrMgCl isopropyl magnesium chloride zPrOH / IPA isopropyl alcohol Josiphos SL-J009 (7?)-l-[(SP)-2-(dicyclohexylphosphino) ferrocenyl]ethyldi-tert-butylphosphine KOAc potassium acetate 25 KO / Bu potassium tert-butoxide LAH lithium aluminiumhydride LDA lithium diisopropylamide LiHMDS [bis(trimethylsilyl)amino]lithium zzzCPBA 3-chloroperoxybenzoic acid 30 Me methyl MeCN acetonitrile Mel iodomethane MeLi methyl lithium MeMgCl MeMgBr MeOH MeReO3 methyl magnesium chloride methyl magnesium bromide methanol methyltrioxorhenium (VII) 5 MgSO4 magnesium sulfate min minute(s) MnO2 manganese (IV) oxide MOM-CI chloromethyl methyl ether MsCl methanesulphonyl chloride 10 MVK methyl vinyl ketone NaBH4 sodium borohydride NaCN sodium cyanide NaH sodium hydride NaHCO3 sodium bicarbonate 15 NaOMe sodium methoxide Na2SO4 sodium sulfate NBS V-bromosuccinimide / ?BuLi / / -butyl lithium «PrOH propanol 20 NCS V-chlorosuccinimide NF SI V-fluorobis(phenylsulfonyl)amine NIS V-iodosuccinimide nh3 ammonia nh4ci ammonium chloride 25 NH4HCO3 ammonium bicarbonate nh4hco2 ammonium formate NiC12xglyme nickel(II)chloride ethylene glycol dimethyl ether complex Ni(dppp)C12 [l,3-bis(diphenylphosphino)propane]dichloronickel(II) Pd / C palladium on activated charcoal 30 Pd(dppf)Cl2 [l,l’-bis(diphenylphosphino)ferrocene] di chloropalladium (II) Pd(dppf)Cl2xDCM [ 1,1’ -bis(diphenylphosphino)ferrocene] di chloropalladium (II), complex with dichloromethane Pd2(dba)3 tris(dibenzylideneacetone)dipalladium (0) Pd(OAc)2 palladium (II) acetate Pd(PPh3)2Cl2 bis(triphenylphosphine)palladium(II) dichloride PE petroleum ether PhNTf2 bis(trifluoromethanesulfonyl)aniline 5 Ph2O diphenyl ether PPh3 triphenylphosphine PMB 4-methoxybenzyl PMB-Br 4-methoxybenzyl bromide PMB-C1 4-methoxybenzyl chloride 10 POC13 phosphorus (V) oxychloride PPA polyphosphoric acid PPTS pyridinium / ?-toluenesulfonate Pt / C platinum on activated charcoal PTFE polytetrafluoroethylene 15 PtO2 platinum (IV) oxide PTSA / ?-toluenesulfonic acid monohydrate Rh2(OAc)4 rhodium(II) acetate dimer rt room temperature RuPhos 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl 20 RuPhos Pd G2 chloro(2-dicyclohexylphosphino-2',6'-diisopropoxy-l, 1 biphenyl)[2-(2'-amino-l, 1 '-biphenyl)]palladium(II) sat. saturated SOC12 thionyl chloride STAB sodium triacetoxyborohydride 25 TBAB tetrabutyl ammonium bromide TBAC1 tetrabutyl ammonium chloride TBAF tetrabutyl ammonium fluoride TBAI tetrabutyl ammonium iodide / Bu Zc / 7-butyl 30 / BuBr tert-butylbromide / BuOH tert-butanol / BuXPhos 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl TBDMS-C1 tert-butyldimethyl silyl chloride TBDMS-OTf / c' / 7-butyl di methyl silyl triflate TBDPS-C1 Zert-butyldiphenylchlorosilane TBTU G-(b enzotri azol e-1 -yl)-A, N, N \N ’-tetramethyluronium tetrafluoroborate TEA tri ethylamine TFA trifluoroacetic acid TFAA trifluoroacetic acid anhydride Tf2O trifluoromethanesulphonic anhydride THF tetrahydrofuran TMSCHNN diazomethyl(trimethyl)silane TMS-C1 trimethylchorosilane TMS-CN trimethylsilylcyanide TsCl p^ra-toluenesulfonyl chloride Urotropin 1,3,5,7-tetrazatri cyclo[3.3.1.13,7]decane GENERAL SYNTHETIC REMARKS All reagents obtained from commercial sources were used without further purification. Anhydrous solvents were obtained from commercial sources and used without further drying. The reactions were monitored using LCMS and GCMS instruments and / or TLC. Thin layer chromatography was conducted with 5 cm x 10 cm plates coated with Merck Type 60 F254 silica-gel. Analytical LC-MS: The compounds of the present invention were characterized by high performance liquid chromatography-mass spectroscopy (HPLC-MS) using the following instruments: • Agilent HP 1200 LC with Agilent MSD 6140 single quadrupole, operating in positive or negative ion electrospray ionisation mode. Molecular weight scan range is 100 to 1350 m / z. Parallel UV detection was done at 210 nm and 254 nm. Samples were supplied as a 1 mM solution in MeCN, or in THF / water (1:1) with 5 pL loop injection. LCMS analyses were performed on 2 instruments, one of which was operated with basic, and the other with acidic eluents. Basic LCMS: Gemini-NX, 3 pm, C18, 50 mm x 3.00 mm i.d. column at 23°C, at a flow rate of 1 mL min'1 using 5 mM aq. NH4HCO3 solution (Solvent A) and MeCN (Solvent B) with a gradient starting from 100% Solvent A and finishing at 100% Solvent B over various duration of time. Acidic LCMS: ZORB AX Eclipse XDB-C18, 1.8 pm, 50 mm x 4.6 mm i.d. column at 40°C, at a flow rate of 1 mL min'1 using 0.02% V / V aq. HCOOH solution (Solvent A) and 0.02% V / V HCOOH solution in MeCN (Solvent B) with a gradient starting from 100% Solvent A and finishing at 100% Solvent B over various duration of time. • Agilent 1200 SL series instrument linked to an Agilent MSD 6140 single quadrupole with an ESI-APCI multimode source or using an Agilent 1290 Infinity II series instrument connected to an Agilent TOF 6230 with an ESI-jet stream source; column: Thermo Accucore 2.6 pm, Cl8, 50 mm x 2.1 mm at 55°C or Agilent Zorbax Eclipse plus 3.5 pm, C18, 30 mm x 2.1 mm at 35°C; eluents: Solvent A: 10 mM aq. NH4OAC solution + 0.08% (v / v) HCOOH; Solvent B: MeCN + 5% (v / v) Solvent A + 0.08% (v / v) HCCOH, with a gradient starting from 95% Solvent A and finishing at 95% Solvent B or starting from 60% Solvent A and finishing at 98% Solvent B over various duration of time; ionisation is recorded in positive mode, negative mode, or positive-negative switching mode. Combination gas chromatography and low-resolution mass spectrometry (LRMS) were performed on Agilent 6850 gas chromatograph and Agilent 5975C mass spectrometer using 15 m x 0.25 mm column with 0.25 pm HP-5MS coating and helium as carrier gas. Ion source: EI+, 70 eV, 230°C, quadrupole: 150°C, interface: 300°C. Microwave heating was performed in an Anton Parr MonoWave or CEM Discover® instrument. Flash chromatography was performed on ISCO CombiFlash Rf 200, Rf 200i and Rf+ Lumen™ with pre-packed silica-gel cartridges (RediSep® Rf Normal-phase Silica Flash Columns (3570pm, 60 A), RediSep Rf Gold® Normal-phase Silica High Performance Columns (20-40pm, 60 A), RediSep® Rf Reversed-phase C18 Columns (40-63 pm, 60 A), or RediSep Rf Gold® Reversed-phase C18 High Performance Columns (20-40 pm, 100 A). Preparative HPLC purifications were performed on the following instruments: 1. Armen Spot Liquid Chromatography system with a Gemini-NX® 10 pM Cl 8, 250 mm x 50 mm i.d. column running at a flow rate of 118 mL min'1 with UV diode array detection (210-400 nm) using 25 mM aq. NH4HCO3 solution and MeCN as eluents unless specified otherwise. 2. CombiFlash EZ Prep (Teledyne ISCO) system with a Gemini-NX® 10 pM C18, 250 mm x 50 mm i.d. column running at a flow rate of 118 mL min’1 with UV detection (210-400 nm) using 25 mM aq. NH4HCO3 solution and MeCN as eluents unless specified otherwise. 3. Waters FractionLynx MS autopurification system, with a Gemini® 5 pm C18(2), 100 mm x 20 mm i.d. column from Phenomenex, running at a flow rate of 20 mL min’1 with UV diode array detection (210-400 nm) and mass-directed collection. The mass spectrometer was a Waters Micromass ZQ2000 spectrometer, operating in positive or negative ion electrospray ionisation modes, with a molecular weight scan range of 150 to 1000. pH4 eluents: Solvent A: 10 mM aq. NFLOAc solution + 0.08% (v / v) HCOOH; Solvent B: MeCN + 5% (v / v) Solvent A + 0.08% (v / v) HCCOH. pH9 eluents: Solvent A: 10 mM aq. NFLOAc solution + 0.08% (v / v) cc. aq. NEL solution; Solvent B: MeCN + 5% (v / v) Solvent A + 0.08% (v / v) cc. aq. NH3 solution. 4. AccQPrep HP 125 (Teledyne ISCO) system, with a Gemini® NX 5 pm Cl8(2), 150 mm x 21.2 mm i.d. column from Phenomenex, running at a flow rate of 20 mL min’1 or Gemini® NX 5 pm Cl8(2), 250 mm x 30 mm i.d. column from Phenomenex, running at a flow rate of 40 mL min’1 with UV (214 and 254 nm) and ELS detection. pH4 eluents: Solvent A: water + 0.08% (v / v) HCOOH; solvent B: MeCN + 0.08% (v / v) HCOOH. pH9 eluents: Solvent A: water + 0.08% (v / v) cc. aq. NH3 solution; solvent B: MeCN + 0.08% (v / v) cc. aq. NH3 solution. Neutral eluents: Solvent A: water; Solvent B: MeCN. 'H-NMR measurements were performed on Bruker Avance III 500 MHz spectrometer, Bruker Avance III 400 MHz spectrometer, Bruker DPX 400 MHz spectrometer and Bruker Avance NEO 400 MHz spectrometer, using DMSO-de or CDCI3 as solvent. 1H NMR data is in the form of delta values, given in part per million (ppm), using the residual peak of the solvent (2.50 ppm for DMSO-de and 7.26 ppm for CDCI3) as internal standard. Splitting patterns are designated as: s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), sept (septet), m (multiplet), br (broad), br s (broad singlet), br d (broad doublet), br t (broad triplet), br m (broad multiplet), dd (doublet of doublets), td (triplet of doublets), dt (doublet of triplets), tt (triplet of triplets), tm (triplet of multiplets), qd (quartet of doublets), ddd (doublet of doublet of doublets), dm (doublet of multiplets). HRMS were determined on a Shimadzu IT-TOF, ion source temperature 200°C, ESI + / -, ionization voltage: (+-)4.5 kV. Mass resolution min. 10000. Chemical names were generated using ACD / Labs 2019.1.2. (File version: C05H41, Build: 111302, 27 Aug 2019). GENERAL PROCEDURES General procedure 1: LAH reduction of esters LAH (3 eq.) was added portionwise to dry THF (2 mL / mmol ester) under N2 atmosphere. The mixture was stirred at 40-50°C for 15 min. Then the appropriate ester (1 eq.) in dry THF (1 mL / mmol ester) was added dropwise while maintaining the temperature between 55 and 60°C. The mixture was stirred at reflux temperature for 3 h, then it was allowed to cool to rt and stirred overnight. The reaction mixture was cooled to 0°C. Water (2 mL / g LAH) was added dropwise, followed by the dropwise addition of 15% aq. NaOH solution (2 mL / g LAH) at 0-10°C. The mixture was stirred for 15 min, then water (6 mL / g LAH) was added and the mixture was stirred at rt for 1 h. The precipitate was filtered off. The filtrate was concentrated under reduced pressure, then DCM and water were added. The layers were separated and the aq. layer was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was used without further purification. General procedure 2: monoprotection of the diols The appropriate diol (1 eq.) was dissolved in MeCN (3 mL / mmol diol), then KI (1 eq.) and K2CO3 (1.1 eq.) were added, followed by the addition of 2-diphenylboranyloxyethanamine (0.08 eq.). The mixture was stirred for 5 min, then PMB-C1 (1.5 eq.) was added and the mixture was stirred at 60°C until no further conversion was observed. The mixture was allowed to cool to rt, diluted with EtOAc and washed with water. The layers were separated and the aq. layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 3: bromination of alcohols PPhs (1.1 eq.) was dissolved in DCM (0.25 mL / mmol alcohol) and cooled to 0°C. Bn (1.2 eq.) dissolved in DCM (0.25 mL / mmol alcohol) was added dropwise. The mixture was stirred at rt for 1 h then it was cooled to 0°C. The mixture of the appropriate alcohol (1 eq.) and TEA (1.25 eq.) in DCM (1.5 mL / mmol alcohol) was added dropwise at 0°C. After stirring at 0°C for 30 min the mixture was allowed to warm to rt and stirred overnight. Then it was quenched with sat. aq. Na2S2O3 solution and water, the layers were separated, the aq. layer was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Heptane was added, and the mixture was stirred and sonicated. The precipitate was filtered and washed with heptane. The filtrate was concentrated under reduced pressure and purified via flash chromatography using heptane and EtOAc as eluents. General procedure 4: Zn reagent formation To an oven-dried flask zinc (1.4 eq.) was added and the vessel was heated at 160°C for 1 h under vacuum then allowed to cool to rt and placed under N2 atmosphere. DMA (0.7 mL / mmol bromo compound) was added followed by the addition of I2 (0.05 eq.). The mixture was stirred at rt for 5 min, then the appropriate bromo compound (1 eq.) in DMA (0.6 mL / mmol bromo compound) was added and the mixture was stirred at 75°C for 18 h, then it was allowed to cool to rt. Cannulation through a filter (cotton-wool / Celite / cotton-wool) into a dry Schlenk tube afforded the desired product as a solution (concentration determined by titration with a 0.5 M solution of I2) that was used without further characterization. General procedure 5: bromination of indan-1-ones The appropriate indan-l-one (1 eq.) was dissolved in DCM (1.5 mL / mmol indan-l-one), then NBS (1.1 eq.) and PTSA (0.1 eq.) were added at rt. The mixture was stirred at reflux temperature until no further conversion was observed. The mixture was allowed to cool to rt. It was quenched with water and brine and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 6: oxo reduction of bromo-indan-1-ones The appropriate bromo-indan-1-one (1 eq.) was dissolved in DCM or MeOH (3.5 mL / mmol bromo-indan-1-one), cooled to 0°C, then NaBH4 (1-2 eq.) was added portionwise. The mixture was stirred at rt until no further conversion was observed. The mixture was quenched with water and brine. The layers were separated and the aq. layer was extracted with DCM. The combined organic layers were dried over Na2SO4, fdtered and the filtrate was concentrated under reduced pressure. The crude intermediate was used without further purification. General procedure 7: Water elimination from indanes The appropriate indane (1 eq.) was dissolved in toluene (50 mL / mmol indane) in a flask equipped with a Dean Stark apparatus. PTSA (0.64 eq.) was added and the mixture was stirred at reflux temperature until no further conversion was observed. The mixture was allowed to cool to rt. Sat. aq. NaHCO3 solution was added and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and DCM or heptane and EtOAc as eluents. General procedure 8a: spirocyclization with NaH in DMF The appropriate indene (1 eq.) and Preparation lb (or Preparation la, where noted, 1.1 eq.) were dissolved in dry DMF (4 mL / mmol indene) and cooled to 0°C under N2 atmosphere. NaH (2.2 eq., 60% dispersion in mineral oil) was added. After stirring for 1 h at 0°C, the mixture was allowed to warm to rt, and stirred until no further conversion was observed. Then it was quenched with sat. aq. NH4CI solution and stirred for 30 min. Sat. aq. NaHCOs solution was added and the mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc or DCM and MeOH as eluents. General procedure 8b: spirocyclization with LiHMDS in THF The appropriate indene or isoindolin-l-one (1 eq.) was dissolved in dry THF (10 mL / mmol indene or isoindolin-l-one) and cooled to -78°C under N2 atmosphere. LiHMDS (1 M solution in THF, 2.2 eq.) was added, and the mixture was stirred at -78°C for 30 min under N2 atmosphere. Preparation lb (1.2 eq.) was dissolved in dry THF (1 mL / mmol indene or isoindolin-l-one) and was added dropwise at -78°C. Then it was allowed to warm to rt and stirred until no further conversion was observed. Then it was quenched with sat. aq. NH4CI solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 9: Ketal cleavage The appropriate ketal (or acetal, 1 eq.) was dissolved in acetone (6.2 mL / mmol ketal), then 2 M aq. HC1 solution (4.4 mL / mmol ketal) was added. The mixture was stirred at 45°C until no further conversion was observed. Then it was allowed to cool to rt. The pH was adjusted to 7 with sat. aq. NaHCO3 solution and acetone was removed under reduced pressure. Then it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents or DCM and MeOH (1.2% NH3) as eluents. General procedure 10: Bargellini reaction with ketones The appropriate ketone (1 eq.) was dissolved in THF (5 mL / mmol ketone), then it was cooled to 0°C. The appropriate aniline or phenol or thiol (1-3 eq.) and solid NaOH (3-5 eq.) were added, followed by the dropwise addition of CHCh (3-5 eq.). The mixture was stirred at 0°C for 30 min, then it was allowed to warm to rt and it was stirred at rt until no further conversion was observed. Then it was quenched with water, and the pH was adjusted to 3-4 with 2 M aq. HC1 solution. Then it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 11: Strecker reaction with ketones The appropriate ketone (1 eq.) and the appropriate aniline or pyridine-amine (1.2 eq.) were dissolved in AcOH (10 mL / mmol ketone), then TMS-CN (1.2 eq.) was added dropwise. The mixture was stirred at rt until no further conversion was observed. The pH was adjusted to 10 with 25% aq. NH3 solution. Then it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 12a: hydrolysis of nitriles with acetaldoxime / InCh The appropriate nitrile (1 eq.) was dissolved in dry toluene (4 mL / mmol nitrile), then acetaldoxime (4.5 eq.) and InCh (0.07 eq.) were added. The mixture was stirred at 75°C until no further conversion was observed. The mixture was allowed to cool to rt. Toluene was removed under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtO Ac or EtOAc and MeOH or DCM and MeOH as eluents. General procedure 12b: hydrolysis of nitriles with H2O2 The appropriate nitrile (1 eq.) was dissolved in MeOH (70 mL / mmol nitrile), then 1 M aq. NaOH solution (5 mL / mmol nitrile) was added. H2O2 solution (30%, 10 mL / mmol nitrile) was added at 10°C in portions. After 30 min stirring at rt, the mixture was heated to 35°C-50°C and stirred until no further conversion was observed. Sat. aq. Na2S2O3 solution was added under cooling, then MeOH was removed under reduced pressure. Water was added and it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 13: hydrolysis of amides The appropriate amide (1 eq.) was dissolved in 2-methoxy-ethanol (8 mL / mmol amide), then NaOH (15 eq.) and water (0.8 mL / mmol amide) were added. The mixture was stirred at 120°C-200°C with or without microwave irradiation until no further conversion was observed. The mixture was allowed to cool to rt. The pH was set to 2-3 with 2 M aq. HC1 solution. The mixture was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc or DCM and MeOH as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 14: Bucherer-Bergs reaction with ketones A flask was charged with the appropriate ketone (1 eq.), (NH4)2CO3 (4 eq.), KCN (or NaCN where noted, 2 eq.), EtOH (5 mL / mmol ketone) and water (6 mL / mmol ketone). The mixture was stirred at 60°C until no further conversion was observed. The mixture was allowed to cool to rt. A mixture of water and ice was added and it was stirred for 15 min. The precipitation was filtered, washed with water and dried under reduced pressure. General procedure 15: hydrolysis of hydantoins A teflon flask was charged with the appropriate hydantoin (1 eq.), then LiOHxHiO (10 eq.) and water (3 mL / mmol hydantoin) were added. The mixture was stirred in an oil bath heated to 140°C until no further conversion was observed. Then it was allowed to cool to rt. The pH was set to 7 with cc. aq. HC1 solution. The formed precipitation was filtered, washed with water and dried under reduced pressure. General procedure 16: Ullmann coupling A flask was charged with the appropriate amino acid (1 eq.), the appropriate iodobenzene or bromobenzene (1.2 eq.), Cui (0.1 eq.), ethyl-2-oxocyclohexanecarboxylate (0.4 eq.), CS2CO3 (2 eq.) and DMF (10 mL / mmol amino acid) under N2 atmosphere. The mixture was stirred at 105°C until no further conversion was observed. Then it was allowed to cool to rt. DMF was removed under reduced pressure. Water and brine were added and it was extracted with DCM or EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 17a: esterification of acids with TMS-CHNN The appropriate amino acid (1 eq.) was dissolved in DCM (5 mL / mmol amino acid) and MeOH (5 mL / mmol amino acid), then TMS-CHNN (2-4 eq.) was added. The mixture was stirred at rt until no further conversion was observed. The solvents were removed under reduced pressure and the crude intermediate was purified via flash chromatography using heptane and EtOAc or DCM and MeOH as eluents. General procedure 17b: esterification of acids with Mel The appropriate amino acid (1 eq.) was dissolved in DMF (8 mL / mmol amino acid), then cooled to 0°C. CS2CO3 (1 eq.) and Mel (1.3 eq.) were added. The mixture was stirred at 0°C until no further conversion was observed. DMF was removed under reduced pressure, then water and brine were added and it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 18: Suzuki coupling with 2-bromo-indenes A microwave vial was charged with the appropriate 2-bromo-indene derivative (1 eq.), the appropriate boronic acid or ester (1.5-3 eq.), CS2CO3 (3 eq.) and 1,4-dioxane (10 mL / mmol indene) and water (3 mL / mmol indene). The vial was purged with N2, followed by the addition of Pd(PPh3)4 (0.1 eq.). The mixture was heated at 120°C for 30 min under microwave irradiation. Then it was diluted with water, the pH was set to 3 with 2 M aq. HC1 solution. It was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 19: hydrogenation of indenes The appropriate indene (1 eq.) was dissolved in EtOAc (15 mL / mmol indene). 10% Pt / C (0.1 g catalyst / g indene) was added and the flask was evacuated and backfilled with N2 (x3), then evacuated and filled with H2. Then the mixture was stirred at rt until no further conversion was observed. Then it was filtered, washed with EtOAc, and the filtrate was concentrated under reduced pressure. When the reduction stopped at low conversion, the hydrogenation procedure was repeated using fresh catalyst. The crude product was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 20: coupling with NaAuCh Preparation 7b (1 eq.), the appropriate alcohol (5 eq.) and NaAuCUx2H2O (0.05 eq.) were measured into a vial, sealed and stirred at 70°C until no further conversion was observed. Then the mixture was diluted with DCM and MeOH, filtered and the filtrate was concentrated. The crude product was purified via flash chromatography using heptane and EtOAc as eluents, and then via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 21: amide formation from carboxylates The appropriate carboxylic acid (1 eq.) was dissolved in pyridine (12 mL / mmol carboxylic acid). The appropriate amine (1.1 eq.) and EDCxHCl (3 eq.) were added and the mixture was stirred at rt under N2 atmosphere until no further conversion was observed. Then it was concentrated under reduced pressure and purified via flash chromatography using heptane and EtOAc as eluents. General procedure 22: TFA amide formation The appropriate indene (1 eq.) was dissolved in 2-Me-THF (2.25 mL / mmol indene), then TEA (5 eq.) and DMAP (0.1 eq.) were added, then cooled to 0°C. TFAA (20 eq.) was added dropwise at 0°C (keeping the temperature of the mixture below 10°C), then it was stirred at 50°C until no further conversion was observed. Then it was cooled to 0°C and stirred for 2 h. The precipitate was filtered, taken up in DIPE and sonicated. The precipitate was filtered, washed with DIPE and dried. General procedure 23: Friedel Crafts acylation of indenes To a suspension of AlCh (3 eq.) in DCM (6 mL / mmol indene) a solution of AcCl (2 eq.) in DCM (2 mL / mmol indene) was added at 0°C under N2 atmosphere and the mixture was stirred at 0°C for 30 min. Then a solution of the appropriate indene (1 eq.) in DCM (2 mL / mmol indene) was added dropwise and the mixture was stirred at 0°C until no further conversion was observed. Then it was poured onto ice-water and stirred for 15 min. The layers were separated and the aq. layer was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 24: Baeyer-Villiger oxidation of acetyl-indenes The appropriate indene (1 eq.) was dissolved in DCM (10 mL / mmol), then Na2HPO4 (10 eq.) and mCPBA (2.05 eq.) were added. The mixture was stirred at rt until no further conversion was observed. Then it was diluted with water, and stirred for 20 min. The precipitation was filtered, and the filtrate was extracted with DCM. The combined organic layers were washed with water, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 25: Acetyl cleavage of acetoxy-indenes The appropriate indene (1 eq.) was dissolved in MeOH (6 mL / mmol indene), then NaOMe (1.65 eq.) was added under N2 atmosphere. The mixture was stirred at rt until no further conversion was observed. Then it was diluted with water, the pH was set to 6 with 2 M aq. HC1 solution and it was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 26: formylation of indenes The appropriate indene (1 eq.) was dissolved in TFA (5 mL / mmol indene), then urotropine (3 eq.) was added. The mixture was stirred at reflux temperature until no further conversion was observed. The reaction mixture was concentrated under reduced pressure and purified via flash chromatography using heptane and EtOAc as eluents. General procedure 27a: Negishi coupling with AtaPhos An oven-dried round-bottom flask, equipped with a PTFE-coated magnetic stirring bar was charged with the appropriate 2-bromo-indene derivative (1 eq.) and AtaPhos (0.02 eq.), then dry THF (6 mL / mmol indene) was added under N2 atmosphere. 1-Methylimidazole (1.7 eq.) and the appropriate Zn reagent (2 eq.) were added and the mixture was stirred at 50°C or at 120°C under microwave irradiation until no further conversion was observed. The mixture was allowed to cool to rt, then diluted with sat. aq. NH4CI solution and water, then extracted with EtOAc. The combined organic layers were washed with brine, then dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 27b: Negishi coupling with Pd(I)-I-dimer An oven-dried round-bottom flask, equipped with a PTFE-coated magnetic stirring bar was charged with the appropriate 2-bromo-indene derivative (1 eq.), then dry toluene (10 mL / mmol indene) was added under N2 atmosphere. Di-p-iodobis(tri-Zert-butylphosphino)dipalladium (I) (0.02 eq.) was added under N2 flow. The appropriate Zn reagent (1.25 eq.) was added at 50°C and the mixture was stirred at 50-105°C until no further conversion was observed. The mixture was allowed to cool to rt. The mixture was diluted with sat. aq. NH4CI solution and water, then filtered through a pad of Celite. The filtrate was extracted with EtOAc and the combined organic layers were washed with brine, then dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 28a: PMB cleavage with DDQ The appropriate PMB derivative (1 eq.) was dissolved in DCM (5 mL / mmol PMB derivative) and water (0.5 mL / mmol PMB derivative), then cooled to 0°C. DDQ (1.2 eq.) was added and the mixture was stirred at rt until no further conversion was observed. Then it was diluted with water and brine, then extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 28b: PMB cleavage with TfOH The appropriate PMB derivative (1 eq.) was dissolved in DCM (10 mL / mmol PMB derivative), then 1,3-dimethyoxybenzene (3 eq.) and TfOH (1.2 eq.) were added. The mixture was stirred at rt until no further conversion was observed. Then it was diluted with sat. aq. NaHCOs solution and water, then extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc or DCM and MeOH (1.2% NH3) as eluents. General procedure 29: silyl protecting group cleavage The appropriate silyl derivative (1 eq.) was dissolved in THF (10 mL / mmol silyl derivative), then TBAF (1.1 eq.) was added. The mixture was stirred at rt until no further conversion was observed. Then it was diluted with sat. aq. NaHCO3 solution and water, then extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 30a: Mitsunobu coupling with DTABD The appropriate indene or indane or isoindoline (1 eq.), PPh3 (2-3 eq.) and the appropriate alcohol (2-3 eq.) were dissolved in THF or in toluene (10 mL / mmol indane). DTBAD (2-3 eq.) was added and the mixture was stirred at 50°C until no further conversion was observed. The solvent was removed under reduced pressure and the crude intermediate was purified via flash chromatography using heptane and EtOAc as or EtOAc and MeOH as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 30b: Mitsunobu coupling with DIAD To a solution of the appropriate alcohol (1.5 eq.) and PPh3 (2-3 eq.) dissolved in THF (5-10 mL / mmol alcohol) was added DIAD (1.5 eq.) dropwise at 0°C or rt and the resulting solution was stirred for 5 min. The appropriate indene or indane or isoindoline (1 eq.) in THF (10 mL / mmol) was added and the mixture stirred at rt until no further conversion was observed. Then it was diluted with DCM, washed with sat. aq. NaHCO3 solution and the organic phase was dried (PTFE phase separator) and concentrated in vacuo. The crude intermediate was purified via flash chromatography using heptane and EtOAc or MeOH and DCM as eluents. General procedure 31a: coupling of aryl chlorides with Josiphos The appropriate alcohol (1 eq.) was dissolved in toluene (5-10 mL / mmol alcohol), then Josiphos SL-J009 (0.1 eq.), the appropriate aryl chloride (1.2 eq.), CS2CO3 (3 eq.) and allylpalladium(II) chloride dimer (0.05 eq.) were added. The mixture was sparged with N2 and stirred at 90°C until no further conversion was observed. The mixture was allowed to cool to rt. The mixture was partitioned between DCM and sat. aq. NaHCOs solution and the organic phase was washed with brine, dried (PTFE phase separator) and concentrated in vacuo. The crude intermediate was purified via flash chromatography using heptane and EtOAc or MeOH and DCM as eluents. General procedure 31b: alkylation of aryl chlorides The appropriate alcohol (1 eq.) was dissolved in DMF (10 mL / mmol alcohol), then NaH (60% dispersion; 3 eq.) was added portionwise and the mixture was allowed to stir for 5 min at 0°C or rt. The appropriate aryl chloride (1.5-2 eq.) in DMF (10 mL / mmol alcohol) was added. The mixture was stirred at 90°C until no further conversion was observed, then it was allowed to cool to rt. It was quenched with water, then extracted with DCM. The combined organic extracts were washed with 1 M aq. HC1 solution, brine, dried (PTFE phase separator) and concentrated in vacuo. The crude intermediate was purified via flash chromatography using heptane and EtOAc or MeOH and DCM as eluents or via prep RP-HPLC using MeCN and water as eluents. General procedure 31c: alkylation of aryl chlorides To a solution of the appropriate alcohol (1 eq.) dissolved in DMSO (6 mL / mmol alcohol) was added KO / Bu (3-4 eq.) and the mixture was stirred at rt for 5 min before the addition of the appropriate aryl chloride (1.3-2.3 eq.) in DMSO (2-5 mL / mmol aryl chloride). The mixture was stirred at rt or at 50°C until no further conversion was observed. Then it was partitioned between DCM and water, and the organic phase was washed with 0.1 M aq. HC1 solution, brine, dried (PTFE phase separator) and concentrated in vacuo. The crude intermediate was purified via flash chromatography using heptane and EtOAc or MeOH and DCM as eluents or via prep RP-HPLC using MeCN and water as eluents. General procedure 32: Mitsunobu coupling followed by hydrolysis Step A-Mistunobu coupling The appropriate indene or indane or isoindoline (1 eq.), PPh3 (2-3 eq.) and the appropriate alcohol or amine (2-3 eq.) were dissolved in THF or in toluene (10 mL / mmol indane). DTBAD (2-3 eq.) was added and the mixture was stirred at 50°C until no further conversion was observed. The solvent was removed under reduced pressure and the crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. Step B-hydrolysis The obtained intermediate (1 eq.) was dissolved in 1,4-dioxane (10 mL / mmol ester), then water (10 mL / mmol ester) and LiOHxH2O (10-20 eq.) were added and the mixture was stirred at 60°C until no further conversion was observed. The mixture was allowed to cool to rt. The pH was set to 6-8 with 2 M aq. HC1 solution, and then it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 33a: hydrolysis The appropriate ester (1 eq.) was dissolved in 1,4-dioxane or MeOH (10 mL / mmol for the ester), then water (10 mL / mmol ester) and LiOHxH2O (10-20 eq.) were added and the mixture was stirred at 60°C until no further conversion was observed. The mixture was allowed to cool to rt. The pH was set to 6-8 with 2 M aq. HC1 solution, and it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents or via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 33b: hydrolysis in microwave reactor To the appropriate ester (1 eq.) dissolved in MeOH (10 mL / mmol for the ester) was added LiOH><H2O (5-10 eq.) and the mixture was heated at 110-130°C under microwave irradiation until no further conversion was observed. The mixture was allowed to cool to rt. Then it was diluted with water, acidified with 2 M aq. HC1 solution and then extracted with DCM. The combined organic layers were dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc, or MeOH and DCM as eluents or via prep RP-HPLC using MeCN and water as eluents. General procedure 34: Suzuki coupling with triflates Preparation 16a (1 eq.), the appropriate boronic ester or acid (1.2-2 eq.), CS2CO3 (2 eq.) and Pd(dppf)Ch (0.1 eq.) were measured into a vial, the vial was purged with N2. THF (5 mL / mmol triflate) and water (1.5 mL / mmol triflate) were added. The vial was sealed and the mixture was stirred at 85°C until no further conversion was observed. Then the mixture was cooled to rt, and it was directly injected in the loop of the prep RP-HPLC and purified using 25 mM aq. NH4HCO3 solution and MeCN as eluents. General procedure 36: carbonyl reduction with NaBH4 The appropriate acetyl or formyl derivative (1 eq.) was dissolved in MeOH (20 mL / mmol acetyl compound) and cooled to 0°C. NaBH4 (2 eq.) was added portionwise, and the mixture was stirred at 0°C until no further conversion was observed. Then it was quenched with sat. aq. NH4CI solution, and extracted with DCM. It was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using DCM and MeOH as eluents. General procedure 37: alkylation of isoindolin-l-ones The appropriate isoindolin-l-one (1 eq.) was dissolved in dry DMF (2.5 mL / mmol isoindolin-1-one) and cooled to 0°C under N2 atmosphere. NaH (60% dispersion in mineral oil, 1.2 eq.) was added, then allowed to warm to rt and stirred at rt for 20 min. The appropriate alkyl bromide (1.5 eq.) was added dropwise and the mixture was stirred at rt until no further conversion was observed. Then it was quenched with sat. aq. NH4CI solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 38: reduction of isoindolin-l-ones The appropriate isoindolin-l-one (1 eq.) was dissolved in dry THF (3 mL / mmol isoindolin-1-one) and cooled to 0°C under N2 atmosphere. LAH in THF (1 M, 1.5-2.0 eq.) was added dropwise at 0°C and the mixture was stirred at 0°C-50°C until no further conversion was observed. Then water (1 mL / g LAH) was added dropwise, followed by the dropwise addition of 15% aq. NaOH solution (1 mL / g LAH) at 0-10°C. The mixture was stirred for 15 min, then water (3 mL / g LAH) was added again and the mixture was stirred at rt for 1 h. Then it was filtered through a pad of Celite, washed with EtOAc. The filtrate was washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 39: Pd catalysed synthesis of isoindolin-l-ones The appropriate benzamide (1 eq.) was dissolved in MeCN (10 mL / mmol benzamide). PPhs (0.5 eq.), K2CO3 (3 eq.), TBAC1 (1.5 eq.) andPd(OAc)2 (0.15 eq.) were added and the mixture was stirred under N2 atmosphere at 80°C until no further conversion was observed. Then it was diluted with sat. aq. NaHCO3 solution, brine and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 40: alkylation with mesylates To a solution of the appropriate mesylate (1 eq) in MeCN (10-20 mL / mmol) was added K2CO3 or CS2CO3 (2-3 eq) and the appropriate alcohol or amine (1.2 eq). The mixture was heated at 70°C until no further conversion was observed and then cooled to rt. The mixture was partitioned between DCM and water, and the organic phase was washed with brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified via flash chromatography using heptane and EtOAc or MeOH and DCM as eluents. General procedure 41a: silyl protection of alcohols, NaH base To a solution of the appropriate alcohol (1 eq.) in THF (5-10 mL / mmol) cooled to 0°C under N2 was added NaH (60% as a dispersion in mineral oil, 1-1.2 eq.) in portions and the mixture was stirred for 15 min. The appropriate silyl chloride (1-1.2 eq.) in THF (1-5 mL / mmol) was added dropwise, cooling removed, and the mixture was stirred at rt until no further conversion was observed. The mixture was quenched by the addition of sat. aq. NH4CI solution and partitioned between EtOAc and water. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 41b: silyl protection of alcohols, imidazole base To a solution of the appropriate alcohol (1 eq.) and imidazole (2 eq.) in DMF (5-10 mL / mmol) the appropriate silyl chloride (1.1-1.4 eq.) was added dropwise and the mixture was stirred at rt until no further conversion was observed. The mixture was quenched by the addition of sat. aq. NH4CI solution and partitioned between EtOAc and water. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 42: tosyl protection of diols To a solution of the appropriate alcohol (1 eq.) in DCM (1-2 mL / mmol) was added DMAP (0.1 eq), TEA (2.5-3.5 eq) and TsCl (2.5-3.5 eq). The mixture was stirred at 25-40°C until no further conversion was observed. Then it was quenched with 2 M aq. HC1 solution and the layers were separated. The organic layer was washed with sat. aq. NaHCO? solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents. General procedure 43: double alkylation with bis-tosylates To a solution of the appropriate catechol derivative (1 eq) in DMF (15 mL / mmol) was added CS2CO3 (2-3 eq) and the appropriate bis-tosylate (1-1.5 eq). The mixture was heated under N2 at 80°C until no further conversion was observed and then cooled to rt. The mixture was filtered, and the filtrate was purified via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN and / or IP A as eluents. PREPARATIONS Preparation la (1,3-di oxolane-2,2-diyl)di(ethane-2,l-diyl) dimethanesulfonate To a solution of 2-[2-(2-hydroxyethyl)-l,3-dioxolan-2-yl]ethan-l-ol (13.5 g, 83.2 mmol) in DCM (500 mL) was added TEA (35.4 mL, 25.6 g, 254 mmol) and cooled to -40°C. A solution of MsCl (16.1 mL, 23.8 g, 208.1 mmol) in DCM (500 mL) was added dropwise and stirring continued at -40°C for 30 min. The reaction was warmed to 0°C and quenched by the addition of sat. aq. NaHCO3 solution. The organics were separated and the aq. phase was extracted with another portion of DCM. The combined organic extracts were washed with water, brine, dried (MgSO4), filtered and the filtrate was concentrated in vacuo to give Preparation la as a white crystalline solid (25.5 g, 80.1 mmol, 96%). ^NMR (400 MHz, CDCh) 8 ppm: 4.36 (t, J= 6.8 Hz, 4H), 4.00 (s, 4H), 3.05 (s, 6H), 2.17 (t, J= 6.8 Hz, 4H). Preparation lb 2,2-bis(2-bromoethyl)-l,3-dioxolane Using General procedure 3 and 2-[2-(2-hydroxyethyl)-l,3-dioxolan-2-yl]ethanol as the appropriate alcohol, Preparation lb was obtained. 'H NMR (400 MHz, DMSO-de) 8 ppm: 3.9 (s, 4H), 3.44 (m, 4H), 2.19 (m, 4H). LRMS calculated for C7Hi2Br2O2: 285.92; found 207.0 (M-HBr). Preparation 2al and Preparation 2a2 Preparation 2aA 5-[(E)-2-(2-bromo-5-methyl-anilino)vinyl]-2,2-dimethyl-l,3-dioxane-4,6-di one O To the solution of 2-bromo-5-methyl-aniline (24.4 g, 131 mmol) in EtOH (610 mL), 5-(methoxymethylene)-2,2-dimethyl-l,3-dioxane-4,6-dione (26.9 g, 144.0 mmol) was added at rt and the mixture was stirred at rt for 45 min. Then it was concentrated under reduced pressure. The residue was digerated with DIPE. The precipitate was filtered and washed with DIPE. The precipitate was dried under reduced pressure at 40°C to give Preparation 2aA. *H NMR (400 MHz, DMSO-de) 8 ppm: 11.51 (d, 1H), 8.76 (d, 1H), 7.76 (s, 1H), 7.61 (d, 1H), 7.04 (d, 1H), 2.33 (s, 3H), 1.69 (s, 6H). Preparation 2aB 8-bromo-5-methyl-quinolin-4-ol The solution of Preparation 2aA (78.5 g, 231.0 mmol) in Ph2O (393 mL) in a 2 L 3-necked flask equipped with N2 inlet, overhead stirrer and air cooled reflux condenser was put in a preheated bath, and it was stirred at 270°C for 40 min. During the reaction slow N2 stream was applied. The reaction mixture was allowed to cool to 100°C, and it was poured into 1.6 L well stirred heptane. The precipitate was filtered off, and taken up in the mixture of DIPE (320 mL) and heptane (160 mL). It was refluxed for 15 min, then it was allowed to cool to rt. The mixture was filtered and the precipitate was washed with DIPE. This reflux-crystallisation process was repeated. The solids were dried under reduced pressure to give Preparation 2aB. *H NMR (400 MHz, DMSO-de) 8 ppm: 10.77 (br s, 1H), 7.80 (d, 1H), 7.73 (dd, 1H), 6.96 (d, 1H), 6.04 (d, 1H), 2.75 (s, 3H). Preparation 2al (57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-ol and Preparation 2a2 (55)-5-methyl-5,6,7,8-tetrahydroquinolin-4-ol Preparation 2aB (120 g, 504 mmol) was dissolved in AcOH (1100 mL) and MeOH (500 mL). CHaCOONa^SHiO (103 g, 756 mmol) and 10% Pd / C (12.0 g, 0.1 g / g quinolin-4-ol) was added to the mixture. The autoclave was evacuated and backfilled with N2 (x3), then evacuated and filled with H2. The reaction mixture was stirred under 10 bar H2 at 50°C for 1.5 h. The flask was evacuated and backfilled with N2 and PtO2 (12.0 g, 0.1 g / g quinolin-4-ol) was added in TFA (116 mL). The flask was evacuated and filled with H2. The reaction mixture was stirred under 10 bar H2 at 50°C for 4 h. The reaction mixture was filtered through a pad of silica gel and washed with MeOH. The filtrate was concentrated under reduced pressure. MeOH was added and concentrated under reduced pressure to remove traces of AcOH and TFA. 6 M NH3 solution in MeOH (90 mL) was added and the mixture was concentrated under reduced pressure. The residue was taken up in DCM-MeOH mixture (4:1) and evaporated onto silica gel. The crude product was purified via flash chromatography using NH3 / MeOH and EtOAc as eluents. The resulting intermediate was taken up in MeOH (240 mL) and zPrOH (640 mL) and stirred at 60°C for 20 min, then heptane (250 mL) was added. The precipitate was filtered and washed with zPrOH (50 mL). The filtrate was allowed to cool to rt and the precipitate was filtered. The filtrate was concentrated under reduced pressure. The residue was taken up in DIPE (250 mL), stirred at 45°C for 20 min, then heptane was added (250 mL) and the precipitate was filtered and dried to give a racemate. The enantiomers were separated by chiral chromatography. Column: AS-V, 100^500 mm, 20 pm, Eluents: 3:15:82 MeOH / zPrOH / heptane + 0.05% DEA. The enantiomer eluting earlier was collected as Preparation 2a2. *HNMR (500 MHz, DMSO-d6) 8 ppm: 11.05 (br s, 1H), 7.43 (d, 1H), 5.90 (d, 1H), 2.83 (m, 1H), 2.54-2.42 (m, 2H), 1.79-1.63 (m, 2H), 1.64-1.49 (m, 2H), 1.04 (d, 3H). HRMS calculated for C10H13NO: 163.0997; found 164.1071 (M+H). The enantiomer eluting later was collected and purified via flash chromatography using MeOH and EtOAc as eluents to give Preparation 2al. HRMS calculated for C10H13NO: 163.0997; found 163.09939 (M+). Preparation 3a Preparation 3aA 2-(4-methoxyphenyl)-5-methyl-l,3-dioxane l-(dimethoxymethyl)-4-methoxy-benzene (10.0 g, 55.0 mmol) was dissolved in dry DCM (330 mL). 2-methylpropane-l,3-diol (4.07 mL, 46.2 mmol) and PPTS (1.38 g, 5.5 mmol) were added and the mixture was stirred at rt for 3 h. Then NaHCOs (924 mg, 11.0 mmol) was added and it was stirred at rt for 30 min. Then it was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 3aA. NMR (400 MHz, DMSO-d6) 5 ppm: 7.35-7.31 (m, 2H), 6.93-6.88 (m, 2H), 5.43 / 5.37 (s, 1H), 4.11-4.02 (m, 2H), 3.80 / 3.46 (dm / t, 2H), 3.75 (s, 3H), 3.48-3.43 (m, 2H), 2.09-1.99 / 1.68-1.62 (m, 1H), 1.23 / 0.70 (d, 3H). Preparation 3aB (27?)-3-[(4-methoxyphenyl)methoxy]-2-methyl-propan-l-ol and Preparation 3aC (25)-3-[(4-methoxyphenyl)methoxy]-2-methyl-propan-1 -ol Preparation 3aA (78.0 g, 374 mmol) was dissolved in DCM (750 mL) and cooled to 0°C. 1 M DIBAL-H solution in DCM (800 mL) was added dropwise at 0°C, then it was allowed to warm to rt and stirred for 1 h. Then it was cooled to 0°C, MeOH (200 mL) was added dropwise at 0°C, then water (200 mL) was added. The mixture was stirred at rt for 1 h, then it was diluted with water (600 mL). The layers were separated. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via distillation (bp: 190°C, 0.45 mbar) to give a racemate. The enantiomers were separated by chiral chromatography. Column: AS-V, 10x500 mm, 20 pm, Eluents: 10:90 EtOH / heptane. The enantiomer eluting earlier was collected as Preparation 3aB. 'H NMR (500 MHz, DMSO-d6) 6 ppm: 7.23 (m, 2H), 6.9 (m, 2H), 4.4 (t, 1H), 4.36 (s, 2H), 3.74 (s, 3H), 3.35 / 3.2 (dd+dd, 2H), 3.34 / 3.26 (t+t, 2H), 1.78 (m, 1H), 0.84 (d, 3H). HRMS calculated for C12H18O3: 210.1256; found 210.12478 (M+). The enantiomer eluting later was collected as Preparation 3aC. HRMS calculated for C12H18O3: 210.1256; found 210.12489 (M+). Preparation 3aD Zer^butyl-[(2J?)-3-[(4-methoxyphenyl)methoxy]-2-methyl-propoxy]-diphenyl-silane Preparation 3aC (420 mg, 2.0 mmol) was dissolved in dry THF (6 mL). Imidazole (143 mg, 2.1 mmol) and TBDPS-C1 (537 pL, 2.1 mmol) was added to the mixture and stirred at rt overnight. The reaction mixture was diluted with sat. aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 3aD. *H NMR (500 MHz, DMSO-d6) 8 ppm: 7.62-7.36 (m, 10H), 7.19 (m, 2H), 6.87 (m, 2H), 4.35 / 4.34 (d+d, 2H), 3.72 (s, 3H), 3.59 / 3.56 (dd+dd, 2H), 3.41 / 3.31 (dd+dd, 2H), 1.92 (m, 1H), 0.97 (s, 9H), 0.89 (d, 3H). HRMS calculated for C28H36O3Si: 448.2434; found 471.23248 (M+Na). Preparation 3aE (27?)-3-[ter / -butyl(diphenyl)silyl]oxy-2-methyl-propan-l -ol Using General procedure 28a and Preparation 3aD as the appropriate PMB derivative, Preparation 3aE was obtained. !H NMR (500 MHz, DMSO-de) 8 ppm: 7.61 (m, 4H), 7.45 (dd, 2H), 7.43 (m, 4H), 4.42 (t, 1H), 3.62 / 3.5 (dd+dd, 2H), 3.41 / 3.31 (dd+dd, 2H), 1.77 (m, 1H), 0.99 (s, 9H), 0.87 (d, 3H). HRMS calculated for C2oH2802Si: 328.1859; found 329.1927 (M+H). Preparation 3a [(2S)-3-bromo-2-methyl-propoxy]-tert-butyl-diphenyl-silane Using General procedure 3 and Preparation 3aE as the appropriate alcohol, Preparation 3a was obtained. ’H NMR (500 MHz, DMSO-d6) 8 ppm: 7.62 (m, 4H), 7.47 (dd, 2H), 7.45 (m, 4H), 3.62 (m, 2H), 3.57 (m, 2H), 2.03 (m, 1H), 1 (s, 9H), 0.95 (d, 3H). HRMS calculated for C20H27BrOSi: 390.1015; found 333.03048 (M- / Bu). Preparation 3b bromo-[(25)-3-[fert-butyl(diphenyl)silyl]oxy-2-methyl-propyl]zinc Using General procedure 4 and Preparation 3a as the appropriate bromo compound, Preparation 3b was obtained. Preparation 3c l-[[(25)-3-bromo-2-methyl-propoxy]methyl]-4-methoxy-benzene Br^ O O— Using General procedure 3 and Preparation 3aB as the appropriate alcohol, Preparation 3c was obtained. JH NMR (500 MHz, DMSO-d6) 8 ppm: 7.25 (m, 2H), 6.9 (m, 2H), 4.39 (s, 2H), 3.74 (s, 3H), 3.54 (m, 2H), 3.31 (d, 2H), 2.05 (m, 1H), 0.94 (d, 3H). HRMS calculated for Ci2Hi7BrO2: 272.0412; found 272.04064 (M+). Preparation 3d bromo-[(25)-3-[(4-methoxyphenyl)methoxy]-2-methyl-propyl]zinc Zn^ O Br   )— / O— Using General procedure 4 and Preparation 3c as the appropriate bromo compound, Preparation 3d was obtained. Preparation 3e Preparation 3eA 2-[(2A>)-3-[(4-methoxyphenyl)methoxy]-2-methyl-propyl]isoindoline-l,3-di one O o— Preparation 3c (54.6 g, 200 mmol) was dissolved in DMF (220 mL). Potassium phthalimide (42.6 g, 230 mmol) was added to the mixture and stirred at 50°C for 3 h. The mixture was allowed to cool to rt. EtOAc was added to the mixture and stirred at rt for 10 min, then it was washed with water. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 3eA. *H NMR (500 MHz, DMSO-d6) 8 ppm: 7.88-7.78 (m, 4H), 7.14 (m, 2H), 6.81 (m, 2H), 4.31 / 4.28 (d+d, 2H), 3.71 (s, 3H), 3.61 / 3.44 (dd+dd, 2H), 3.31 / 3.29 (dd+dd, 2H), 2.18 (m, 1H), 0.86 (d, 3H). Preparation 3e (27?)-3-[(4-methoxyphenyl)methoxy]-2-methyl-propan-l -amine H2N—\  O O— Preparation 3eA (688 mg, 2.03 mmol) was dissolved in EtOH (8 mL). Hydrazine hydrate (105 pL, 2.13 mmol) was added to the mixture and stirred under N2 atmosphere at 75°C for 3 h. The mixture was allowed to cool to rt and washed with sat. aq. NH4CI solution. The organic layer was dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 3e. XH NMR (500 MHz, DMSO-de) 8 ppm: 7.23 (dm, 2H), 6.90 (dm, 2H), 4.35 (s, 2H), 3.74 (s, 3H), 3.32 / 3.20 (dd+dd, 2H), 2.52 / 2.37 (dd+dd, 2H), 1.65 (m, 1H), 1.32 (m, 2H), 0.83 (d, 3H). HRMS calculated for C12H19NO2: 209.1416; found 210.1492 (M+H). Preparation 4a Preparation 4aA 2"-bromodispiro[[l,3]dioxolane-2,r-cyclohexane-4',l"-indene] Using General procedure 8a and 2-bromo-l / 7-indene as the appropriate indene, Preparation 4aA was obtained. ^NMR (500 MHz, DMSO-d6) 5 ppm: 7.68 (dm, 1H), 7.36 (dm, 1H), 7.28 (m, 1H), 7.20 (m, 1H), 7.04 (s, 1H), 3.99-3.92 (m, 4H), 2.11 / 1.17 (m+m, 4H), 2.11 / 1.87 (m+m, 4H). HRMS calculated for C16 H17 Br 02: 320.0412; found 321.0484 (M+H). Preparation 4a 2'-bromospiro[cyclohexane-l,l'-inden]-4-one Using General procedure 9 and Preparation 4aA as the appropriate ketal. Preparation 4a was obtained. *HNMR (400 MHz, DMSO-d6) 5 ppm: 7.91 (dm, 1H), 7.40 (dm, 1H), 7.32 (m, 1H), 7.22 (m, 1H), 7.11 (s, 1H), 2.93 / 2.49 (m+m, 4H), 2.22 / 1.58 (m+m, 4H). LRMS calculated for Ci4Hi3BrO: 276.02; found 276.1 (M+). Preparation 5a Preparation 5aA (rs,l"s)-2"-bromodispiro[imidazolidine-4,r-cyclohexane-4',l"-indene]-2,5-di one Using General procedure 14 and Preparation 4a as the appropriate ketone, a 4:1 mixture of diastereoisomers was obtained. DME (7.5 mL / mmol) was added and the mixture was stirred at 82°C for 2 h, then slowly cooled to 20°C and stirred for 2 h. Then it was filtered and the filtrate was concentrated under reduced pressure. Heptane (1.4 mL / mmol) was added and it was stirred at rt for 1 h. The precipitate was filtered, washed with heptane to obtain Preparation 5aA as a single diastereoisomer. 'HNMR (500 MHz, DMSO-de) 3 ppm: 10.80 (br s, 1H), 8.96 (s, 1H), 7.72 (dm, 1H), 7.38 (m, 1H), 7.25 (m, 1H), 7.06 (m, 2H), 2.38 / 1.76 (m+m, 4H), 2.12 / 1.17 (m+m, 4H). HRMS calculated for Ci6Hi5BrN2O2: 346.0317; found 347.0392 (M+H). Preparation 5a (ls,4s)-4-amino-2'-bromospiro[cyclohexane-l,l'-indene]-4-carboxylic acid Using General procedure 15 and Preparation 5aA as the appropriate hydantoin, Preparation 5a was obtained as a single diastereoisomer. *H NMR (400 MHz, DMSO-de) 6 ppm: 8.05 (d, J = 7.60 Hz, 1H), 7.81 (br s, 2H), 7.37 (dd, J= 7.4, 1.3 Hz, 1H), 7.30 (td, J = 7.4, 1.0 Hz, 1H), 7.22 (td, J = 7.5, 1.4 Hz, 1H), 7.05 (s, 1H), 2.65 (td, J= 14.7, 5.0 Hz, 2H), 2.06 (td, J= 14.1, 4.4 Hz, 2H), 1.82-1.72 (m, 2H), 1.11-1.02 (m, 2H). HRMS calculated for Ci5Hi6NO2Br: 321.0364; found 322.0435 (M+H). Preparation 5b Preparation 5bA 6-bromo-6,7-dihydro-277,57 / -indeno[5,6-t / ][l,3]dioxol-5-one O Using General procedure 5 and 5,6-dihydrocyclopenta[ / ][l,3]benzodioxol-7-one as the appropriate indan-l-one, Preparation 5bA was obtained. 'HNMR (500 MHz, DMSO-de) 8 ppm: 7.13 (s, 1H), 7.08 (d, 1H), 6.21 / 6.20 (d+d, 2H), 4.97 (dd, 1H), 3.76 / 3.19 (dd+dd, 2H). HRMS calculated for CioH7Br03: 253.9579; found 254.9645 (M+H). Preparation 5bB 6-bromo-6,7-dihydro-2 / 7,5 / / -indeno[5,6-d\ [1,3]dioxol-5-ol OH Preparation 5bA (69.0 g, 271 mmol) was dissolved in MeOH (740 mL) and cooled with icebath (0-5°C). NaBH4 (10.2 g, 271 mmol) was added to the mixture portionwise, then the mixture was stirred at 0°C for 30 min. The reaction mixture was diluted with water (800 mL). The precipitate was filtered, washed with water and dried to give Preparation 5bB. *H NMR (500 MHz, DMSO-d6) 8 ppm: 6.82 (s, 1H), 6.81 (s, 1H), 5.98 (d, 2H), 4.82 (dd, 1H), 4.79 (d, 1H), 3.28 / 3.08 (dd+dd, 2H). HRMS calculated for CioH9Br03: 255.9735; found 255.97248 (M+). Preparation 5bC 6-bromo-277,577-indeno[5,6-d][l,3]dioxole Using General procedure 7 and Preparation 5bB as the appropriate indane and dry CHC13 instead of toluene, Preparation 5bC was obtained. !H NMR (500 MHz, DMSO-de) 6 ppm: 7.03 (t, 1H), 6.97 (t, 1H), 6.95 (s, 1H), 5.99 (s, 2H), 3.58 (d, 2H). HRMS calculated for CioH7Br02: 237.9629; found 237.95976 (M+). Preparation 5bD 6"-bromo-2"77-dispiro[[l,3]dioxolane-2,r-cyclohexane-4',5"-indeno[5,6- <7][l,3]dioxole] Using General procedure 8a and Preparation 5bC as the appropriate indene, Preparation 5bD was obtained. XH NMR (500 MHz, DMSO-d6) 5 ppm: 7.22 (s, 1H), 6.96 (s, 1H), 6.90 (s, 1H), 6.01 (s, 2H), 3.98-3.91 (m, 4H), 2.06 / 1.18 (m+m, 4H), 2.04 / 1.86 (m+m, 4H). HRMS calculated for Ci7Hi7BrO4: 364.031; found 365.0383 (M+H). Preparation 5bE 6'-bromo-277-spiro[cyclohexane-l,5'-indeno[5,6-<7][l,3]dioxol]-4-one Using General procedure 9 and Preparation 5bD as the appropriate ketal, Preparation 5bE was obtained. *HNMR (500 MHz, DMSO-d6) 5 ppm: 7.63 (s, 1H), 6.99 (s, 1H), 6.96 (s, 1H), 6.02 (s, 2H), 2.90 / 2.47 (m+m, 4H), 2.15 / 1.59 (m+m, 4H). HRMS calculated for Ci5Hi3BrO3: 320.0048; found 320.0024 (M+). Preparation 5bF 6"-bromo-2'77-dispiro[imidazolidine-4, ^-cyclohexane-4,,5"-indeno[5,6-£ / ] [ 1,3 ] di oxol e] -2,5 -di one Using General procedure 14 and Preparation 5bE as the appropriate ketone, Preparation 5bF was obtained as a 4:1 mixture of diastereoisomers. !H NMR (500 MHz, DMSO-de) 5 ppm: 10.81 (s, 1H), 8.95 (s, 1H), 7.23 (s, 1H), 6.99 (s, 1H), 6.92 (s, 1H), 6.03 (s, 2H), 2.3 / 1.75 (td+d, 4H), 2.07 / 1.16 (td+d, 4H). HRMS calculated for Ci7Hi5BrN2O4: 390.0215; found 391.0286 and 391.0258 (M+H). Preparation 5b 4-amino-6'-bromo-27f-spiro[cyclohexane-l,5'-indeno[5,6-£Z][l,3]dioxole]-4- carboxylic acid Using General procedure 15 and Preparation 5bF as the appropriate hydantoin, Preparation 5b was obtained as a 4:1 mixture of diastereoisomers. ’H NMR (500 MHz, DMSO-de) 5 ppm: 7.70 / 7.69 (s / s, 1H), 6.96 / 6.92 (s / s, 1H), 6.89 / 6.85 (s / s, 1H), 6.01 / 6.00 (s / s, 2H), 2.63-0.97 (m, 8H). HRMS calculated for Ci6Hi6BrNO4: 365.0263; found 366.0644 and 366.0337 (M+H). Preparation 6a and Preparation 6b and Preparation 6c Preparation 6aA (ls,4s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l, l'-indene]-4-carbonitrile and Preparation 6bA (lr,4r)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,T-indene]-4-carbonitrile Using General procedure 11 and Preparation 4a as the appropriate ketone and 3-chloroaniline as the appropriate aniline, a mixture of diastereoisomers was obtained. The diastereoisomers were separated via flash chromatography using heptane and EtOAc as eluents. The diastereoisomer eluting earlier was collected as Preparation 6aA. *H NMR (500 MHz, DMSO-de) 8 ppm: 7.82-7.17 (m, 4H), 7.24 (t, 1H), 7.12 / 7.06 (s, 1H), 6.96 / 6.94 (t, 1H), 6.92 / 6.90 (dm, 1H), 6.79 (dm, 1H), 6.59 / 6.57 (s, 1H), 2.64-1.19 (m, 8H). HRMS calculated for C2iHi8BrClN2: 412.0342; found 413.0415 (M+H). The diastereoisomer eluting later was collected as Preparation 6bA. 'H NMR (500 MHz, DMSO-de) 8 ppm: 7.82-7.17 (m, 4H), 7.24 (t, 1H), 7.12 / 7.06 (s, 1H), 6.96 / 6.94 (t, 1H), 6.92 / 6.90 (dm, 1H), 6.79 (dm, 1H), 6.59 / 6.57 (s, 1H), 2.64-1.19 (m, 8H). HRMS calculated for C2iHi8BrClN2: 412.0342; found 413.0401 (M+H). Preparation 6aB (ls,4s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,r-indene]-4-carb oxamide Using General procedure 12b and Preparation 6aA as the appropriate nitrile, Preparation 6aB was obtained. ’H NMR (500 MHz, DMSO-d6) 5 ppm: 7.76 (d, 1H), 7.36 (dd, 1H), 7.33 / 7.25 (br+br, 2H), 7.29 (td, 1H), 7.23 (td, 1H), 7.12 (t, 1H), 7.02 (s, 1H), 6.70 (t, 1H), 6.62 (dm, 1H), 6.60 (dm, 1H), 2.46 / 2.10 (td+d, 4H), 2.13 / 0.94 (t+d, 4H). HRMS calculated for C2iH20BrClN2O: 430.0447; found 431.0517 (M+H). Preparation 6a (ls,4s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l, l'-indene]-4-carboxylic acid Using General procedure 13 and Preparation 6aB as the appropriate amide, Preparation 6a was obtained. NMR (500 MHz, DMSO-d6) 8 ppm: 7.77 (d, 1H), 7.35 (dd, 1H), 7.28 (t, 1H), 7.21 (td, 1H), 7.01 (t, 1H), 7.01 (s, 1H), 6.62 (t, 1H), 6.56 (dd, 1H), 6.46 (dd, 1H), 2.40 / 2.17 (t+d, 4H), 2.16 / 0.92 (t+d, 4H). HRMS calculated for C2iHi9BrClNO2: 431.0288; found 432.0358 (M+H). Preparation 6bB (lr,4r)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l, l'-indene]-4-carb oxamide Using General procedure 12b and Preparation 6bA as the appropriate nitrile, Preparation 6bB was obtained. XH NMR (500 MHz, DMSO-d6) 8 ppm: 7.77 (d, 1H), 7.49 / 7.16 (br+br, 2H), 7.33 (dd, 1H), 7.26 (td, 1H), 7.20 (td, 1H), 7.09 (t, 1H), 7.02 (s, 1H), 6.74 (t, 1H), 6.65 (dm, 1H), 6.60 (dm, 1H), 6.23 (s, 1H), 2.56 / 2.02 (m+m, 4H), 2.08 / 1.36 (m+m, 4H). HRMS calculated for C2iH2oBrClN20: 430.0447; found 431.0526 (M+H). Preparation 6b (lr,4r)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,r-indene]-4-carboxylic acid Using General procedure 13 and Preparation 6bB as the appropriate amide, Preparation 6b was obtained. NMR (500 MHz, DMSO-d6) 5 ppm: 7.70 (d, 1H), 7.34 (dd, 1H), 7.27 (td, 1H), 7.21 (td, 1H), 7.09 (t, 1H), 7.03 (s, 1H), 6.75 (t, 1H), 6.66 (dd, 1H), 6.54 (dd, 1H), 6.39 (br, 1H), 2.62 / 2.06 (m+m, 4H), 2.04 / 1.32 (m+m, 4H). HRMS calculated for C2iHi9BrClNO2: 431.0288; found 432.0363 (M+H). Preparation 6c methyl (ls,4s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,r-indene]-4-carb oxy late Using General procedure 17a and Preparation 6a as the appropriate amino acid, Preparation 6c was obtained. 'H NMR (500 MHz, DMSO-d6) 5 ppm: 7.71 (d, 1H), 7.37 (dd, 1H), 7.30 (t, 1H), 7.23 (td, 1H), 7.10 (t, 1H), 7.04 (s, 1H), 6.61 (t, 1H), 6.60 (dm, 1H), 6.48 (dm, 1H), 3.69 (s, 3H), 2.40 / 2.27 (td+br d, 4H), 2.21 / 0.99 (td+br d, 4H). HRMS calculated for C22H2iBrClNO2: 445.0444; found 446.0506 (M+H). Preparation 7a (ls,4s)-4-(3-chloroanilino)-4-(methoxycarbonyl)spiro[cyclohexane-l,T-indene]-2'-carboxylic acid Preparation 6c (230 mg, 0.55 mmol) was dissolved in DMF (6 mL) and water (2 mL). Pd(OAc)2 (11.2 mg, 0.05 mmol), dppp (24.8 mg, 0.06 mmol) and TEA (210 pL, 1.5 mmol) were added. The mixture was placed into an autoclave. The autoclave was evacuated and filled with 10 bar CO. The mixture was stirred at 80°C overnight. The reaction mixture was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 7a. 'H NMR (500 MHz, DMSO-d6) 8 ppm: 12.42 (br s, 1H), 7.79 (m, 1H), 7.64 (s, 1H), 7.59 (m, 1H), 7.37 (m, 2H), 7.08 (t, 1H), 6.62 (t, 1H), 6.58 (dd, 1H), 6.45 (dd, 1H), 6.32 (br s, 1H), 3.69 (s, 3H), 2.79 / 0.94 (td+d, 4H), 2.37 / 2.23 (td+d, 4H). HRMS calculated for C23H22CINO4: 411.1237; found 412.1312 (M+H). Preparation 7b methyl (ls,4s)-4-(3-chloroanilino)-2'-(hydroxymethyl)spiro[cyclohexane-1, l'-indene]-4-carboxylate Preparation 7a (6.80 g, 16.5 mmol) was dissolved in THF (100 mL). BH3xSMe2 (3.90 mL, 41.3 mmol) was added to the mixture and stirred at rt for 80 min. The reaction was quenched by the addition of MeOH, water and AcOH. The mixture was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 7b. JH NMR (500 MHz, DMSO-de) 8 ppm: 7.63 (dm, 1H), 7.32 (dm, 1H), 7.23 (m, 1H), 7.12 (m, 1H), 7.09 (t, 1H), 6.63 (t, 1H), 6.61 (t, 1H), 6.60 (dm, 1H), 6.46 (dm, 1H), 6.39 (s, 1H), 5.00 (t, 1H), 4.27 (dd, 2H), 3.69 (s, 3H), 2.39 / 2.18 (m+m, 4H), 2.11 / 1.00 (m+m, 4H). HRMS calculated for C23H24CINO3: 397.1445; found 398.1532 (M+H). Preparation 8a Preparation 8aA methyl (lr,4r)-4-(3-chloroanilino)-2'-[(E)-2-ethoxy ethenyl] spiro[cy cl ohexane-l,l'-indene]-4-carboxylate To a solution of Preparation 6c (1.47 g, 3 .29 mmol, 1 eq) in 1,4-di oxane (25 mL) and water (5 mL) was added 2-[(£)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (0.91 mL, 4.28 mmol, 1.3 eq) and K3PO4 (2.79 g, 13.16 mmol, 4 eq). The mixture was sparged with N2 (10 min), then Pd(dppf)C12xDCM (134 mg, 0.16 mmol, 0.05 eq) was added and the mixture was heated at 80°C for 2 h. Then the reaction was partitioned between EtOAc and brine. The organic phase was separated, and the aq. phase was extracted with another portion of EtOAc. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by automated flash chromatography (CombiFlash Rf, 24 gRediSep™ silica cartridge) eluting with a gradient of 0-40% EtOAc in heptane afforded Preparation 8aA as a pale yellow powder (1.25 g, 2.86 mmol, 87%). LRMS calculated for C26H28CINO3: 437; found 438 (M+H). Preparation 8a methyl (lr,4r)-4-(3-chloroanilino)-2'-(2-hydroxyethyl)spiro[cyclohexane-1, l'-indene]-4-carboxylate To a solution of Preparation 8aA (470 mg, 1.07 mmol, 1 eq) in acetone (10 mL) was added 2 M aq. HC1 solution (3 mL, 6 mmol, 5.6 eq) and the mixture was heated at 45°C for 45 min. After cooling, the mixture was partitioned between DCM and 2 M aq. NaOH solution. The organic phase was separated and the aq. phase was extracted with further portions of DCM. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was dissolved in THF (10 mL), then NaBH4 (56 mg, 1.49 mmol, 1.4 eq) was added and the mixture was stirred at rt for 2 h. After quenching with water, the mixture was partitioned between EtOAc and water. The organic phase was separated and the aq. phase was extracted with further portions of EtOAc. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by automated flash column chromatography (CombiFlash Rf, 12 g RediSep™ silica cartridge) eluting with a gradient of 0-60% EtOAc in heptane afforded Preparation 8a. LRMS calculated for C24H26CINO3: 411; found 412 (M+H). ‘HNMR (400 MHz, DMSO-d6) 8 ppm: 7.65 (d, J= 7.5 Hz, 1H), 7.28 (dd, J= 7.4, 1.3 Hz, 1H), 7.23 (td, J= 1A, 0.9 Hz, 1H), 7.14-7.08 (m, 2H), 6.65 (t, J= 2.1 Hz, 1H), 6.60 (ddd, J= 7.8, 2.0, 0.8 Hz, 1H), 6.51-6.45 (m, 3H), 4.71 (t, J= 52 Hz, 1H), 3.73-3.65 (m, 5H), 2.46-2.35 (m, 4H), 2.27-2.06 (m, 4H), 0.93-0.86 (m, 2H). Preparation 8b Preparation 8bA methyl (lr,4r)-4-(3-chloroanilino)-2'-(2-hydroxyethyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General Procedure 19 and Preparation 8a (150 mg, 0.36 mmol, 1 eq) as the appropriate indene and EtOH instead of EtOAc, Preparation 8bA was obtained as a racemate, isolated as a colourless gum (148 mg, 0.36 mmol, 98%). LRMS calculated for C24H28CINO3: 413; found 414 (M+H). ^NMR (400 MHz, DMSO-d6) 5 ppm: 7.43-7.35 (m, 1H), 7.24-7.11 (m, 3H), 7.07 (t, J= 8.1 Hz, 1H), 6.62-6.55 (m, 2H), 6.48-6.43 (m, 1H), 6.34 (s, 1H), 4.49 (t, J= 52 Hz, 1H), 3.66 (s, 3H), 3.59-3.50 (m, 1H), 3.50-3.40 (m, 1H), 2.95 (dd, J = 15.7, 7.3 Hz, 1H), 2.58-2.38 (m, 2H), 2.15-1.86 (m, 5H), 1.78-1.64 (m, 2H), 1.49-1.40 (m, 1H), 1.37-1.22 (m, 2H). Preparation 8b methyl (lr,4r)-4-(3-chloroanilino)-2'-{2-[(methanesulfonyl)oxy]ethyl}-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate To a solution of Preparation 8bA (83 mg, 0.2 mmol, 1 eq) in DCM (3 mL) was added TEA (34 pL, 0.24 mmol, 1.2 eq) followed by the dropwise addition of MsCl (31 pL, 0.4 mmol, 2 eq) and the mixture was stirred at rt for 2 h. Then it was partitioned between DCM and water, and the organic phase was washed with with sat. aq. NaHCOs solution, brine, dried (PTFE phase separator) and concentrated in vacuo to afford Preparation 8b. LRMS calculated for C25H30CINO5S: 491; found 492 (M+H). ’H NMR (400 MHz, DMSO-d6) 5 ppm: 7.46-7.39 (m, 1H), 7.25-7.14 (m, 3H), 7.08 (t, J = 8.1 Hz, 1H), 6.63-6.55 (m, 2H), 6.49-6.43 (m, 1H), 6.34 (s, 1H), 4.38-4.25 (m, 2H), 3.66 (s, 3H), 3.20 (s, 3H), 3.00 (dd, J = 15.7, 7.2 Hz, 1H), 2.62 (dd, J = 15.7, 8.6 Hz, 1H), 2.49-2.39 (m, 1H), 2.15-1.89 (m, 6H), 1.75-1.64 (m, 1H), 1.64-1.44 (m, 2H), 1.38-1.29 (m, 1H). Preparation 9a Preparation 9aA bromido(3-{[ter / -butyl(dimethyl)silyl]oxy}propyl)zinc Br Zn O-Si Using General procedure 4 with (3-bromopropoxy)(ter / -butyl)dimethylsilane as the appropriate bromo compound, Preparation 9aA was obtained. Preparation 9aB methyl (lr,4r)-2'-(3-{[ter / -butyl(dimethyl)silyl]oxy}propyl)-4-(3-chloroanilino)spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 27a and Preparation 6c as the appropriate 2-bromo-indene and Preparation 9aA as the appropriate zinc reagent, Preparation 9aB was isolated as a colourless gum (152 mg, 0.28 mmol, 63%). LRMS calculated for C3iH42ClNO3Si: 539; found 540 (M+H). Preparation 9a methyl (lr,4r)-4-(3-chloroanilino)-2'-(3-hydroxypropyl)spiro[cyclohexane-1, l'-indene]-4-carboxylate Using General procedure 29 and Preparation 9aB as the appropriate silyl derivative, Preparation 9a was isolated as a white foam (79 mg, 0.19 mmol, 63%). LRMS calculated for C25H28CINO3: 425; found 426 (M+H). *HNMR (400 MHz, DMSO-d6) 8 ppm: 7.65 (d, J= 7.5 Hz, 1H), 7.29 (dd, J= 7.4, 1.2 Hz, 1H), 7.23 (td, J= 7.4, 0.9 Hz, 1H), 7.14-7.07 (m, 2H), 6.64 (t, J= 2.1 Hz, 1H), 6.62-6.58 (m, 1H), 6.51-6.43 (m, 3H), 4.50 (t, J= 5.1 Hz, 1H), 3.70 (s, 3H), 3.55-3.48 (m, 2H), 2.48-2.36 (m, 2H), 2.28-2.08 (m, 6H), 1.83-1.74 (m, 2H), 0.94-0.86 (m, 2H). Preparation 9b methyl (lr,4r)-4-(3-chloroanilino)-2'-(3-hydroxypropyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate To a solution of Preparation 9a (675 mg, 1.58 mmol, 1 eq) in EtOH (30 mL) was added 5% Pt / C (300 mg, 0.08 mmol, 0.05 eq) under a N2 atmosphere. The mixture was evacuated and backfilled with N2 (x3), then evacuated and backfilled with H2 and shaken for 7.5 h at rt under an atmosphere of H2. The reaction was filtered through celite, washed with EtOH. The filtrate was concentrated under reduced pressure. Purification by automated flash chromatography (CombiFlash Rf, 12g Gold RediSep™silica cartridge) eluting with a gradient of 15-50% EtOAc in heptane afforded a racemate, Preparation 9b as a white foam (421 mg, 0.98 mmol, 62%). LRMS calculated for C25H30CINO3: 427; found 428 (M+H). 'H NMR (400 MHz, DMSO-d6) 8 7.40-7.33 (m, 1H), 7.24-7.11 (m, 3H), 7.07 (t, J= 8.0 Hz, 1H), 6.62-6.55 (m, 2H), 6.49-6.44 (m, 1H), 6.32 (s, 1H), 4.40 (t, J = 5.1 Hz, 1H), 3.66 (s, 3H), 3.48-3.37 (m, 2H), 2.97 (dd, J = 15.7, 7.2 Hz, 1H), 2.58-2.50 (m, 1H), 2.49-2.38 (m, 1H), 2.19-2.08 (m, 1H), 2.04-1.84 (m, 4H), 1.80-1.69 (m, 1H), 1.64-1.31 (m, 5H), 1.22-1.07 (m, 1H). Preparation 9bl methyl (lr,27?,47?)-4-(3-chloroanilino)-2'-(3-hydroxypropyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate and Preparation 9b2 methyl (lr,2'5,4S)-4-(3-chloroanilino)-2'-(3-hydroxypropyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate The enantiomers of Preparation 9b were separated by chiral chromatography. Column: AD, 100x500 mm, 20 pm, Eluents: 10:90 EtOH / heptane. The enantiomer eluting earlier was collected as Preparation 9bl. HRMS calculated for C25H30CINO3: 427.1914; found 428.1990 (M+H). The enantiomer eluting later was collected as Preparation 9b2. HRMS calculated for C25H30CINO3: 427.1914; found 428.1988 (M+H). Preparation 9c methyl (lr,4r)-4-(3-chloroanilino)-2'-{3-[(methanesulfonyl)oxy]propyl}-2,,3'- dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate To a solution of Preparation 9b (390 mg, 0.91 mmol, 1 eq) in DCM (10 mL) was added TEA (253 pL, 1.82 mmol, 2 eq). The mixture was cooled to 0°C before the dropwise addition of MsCl (92 pL, 1.18 mmol, 1.3 eq) and then stirred at rt for 1 h. The reaction was partitioned between DCM and water, and the organic phase was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by automated flash chromatography (CombiFlash Rf, 12g RediSep™ silica cartridge) eluting with a gradient of 0-50% EtOAc in heptane afforded a racemate, Preparation 9c. LRMS calculated for C26H32CINO5S: 505.17; found 506.18 (M+H). ’H NMR (400MHz, DMSCM,) 8 ppm: 7.42-7.35 (m, 1H), 7.24-7.12 (m, 3H), 7.07 (t, J= 8.0 Hz, 1H), 6.61-6.55 (m, 2H), 6.49-6.44 (m, 1H), 6.32 (s, 1H), 4.23 (t, J= 6.4 Hz, 2H), 3.66 (s, 3H), 3.17 (s, 3H), 2.99 (dd, J = 15.7, 7.2 Hz, 1H), 2.55 (dd, J = 15.7, 7.8 Hz, 1H), 2.48-2.38 (m, 1H), 2.19-2.08 (m, 1H), 2.06-1.53 (m, 8H), 1.51-1.33 (m, 2H), 1.29-1.16 (m, 1H). Preparation 10a Preparation lOaA methyl (lr,4J?)-4-(3-chloroanilino)-2'-{(27?)-3-[(4- methoxyphenyl)methoxy]-2-methylpropyl}spiro[cyclohexane-l,r-indene]-4-carboxylate Using General procedure 27a and Preparation 6c as the appropriate 2-bromo-indene derivative and Preparation 3d as the appropriate Zn reagent, Preparation lOaA was obtained. NMR (500 MHz, DMSO-d6) 5 ppm: 7.70-7.03 (m, 4H), 7.22 (m, 2H), 7.09 (t, 1H), 6.85 (d, 2H), 6.64 (t, 1H), 6.59 (dd, 1H), 6.48 (dd, 1H), 6.43 (s, 1H), 6.43 (s, 1H), 4.40 / 4.37 (d, 2H), 3.72 (s, 3H), 3.69 (s, 3H), 3.33 / 3.30 (m, 2H), 2.47-0.78 (m, 8H), 2.35 / 1.99 (m, 2H), 2.17 (m, 1H), 0.94 (d, 3H). HRMS calculated for C34H38CINO4: 559.249; found 560.2557 (M+H). Preparation 10a methyl (lr,47?)-4-(3-chloroanilino)-2'-[(2 / ?)-3-hydroxy-2-methylpropyl]spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 28b and Preparation lOaA as the appropriate PMB derivative, Preparation 10a was obtained. ’H NMR (500 MHz, DMSO-de) 5 ppm: 7.69-7.07 (m, 4H), 7.09 (t, 1H), 6.63 (t, 1H), 6.59 (dm, 1H), 6.47 (dm, 1H), 6.46 (s, 1H), 6.43 (s, 1H), 4.54 (t, 1H), 3.69 (s, 3H), 3.35 / 3.30 (m+m, 2H), 2.48-0.81 (m, 8H), 2.36 / 1.91 (dd+dd, 2H), 1.97 (m, 1H), 0.90 (t, 3H). HRMS calculated for C26H30CINO3: 439.1914; found 440.1983 (M+H). Preparation 10b methyl (lr,47?)-4-(3-chloroanilino)-2'-[(27?)-3-hydroxy-2-methylpropyl]- 2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Using General procedure 19 and Preparation 10a as the appropriate indene. Preparation 10b was obtained as a mixture of diastereoisomers. HRMS calculated for C26H32CINO3: 441.2071; found 442.2147 and 442.2133 (M+H). Preparation lObl methyl (lr,2'5,45)-4-(3-chloroanilino)-2'-[(27?)-3-hydroxy-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate and Preparation 10b2 methyl (lr,27?,47?)-4-(3-chloroanilino)-2'-[(27?)-3-hydroxy-2- methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate The diastereoisomers of Preparation 10b were separated by chiral chromatography. Column: AD, 100x500 mm, 20 pm, Eluents: 15:85 zPrOH / heptane. The diastereoisomer eluting earlier was collected as Preparation 10b2. 'HNMR (500 MHz, DMSO-de) 5 ppm: 7.37 (d, 1H), 7.20 (d, 1H), 7.15 (t, 1H), 7.13 (t, 1H), 7.06 (t, 1H), 6.59 (dd, 1H), 6.56 (dd, 1H), 6.45 (dd, 1H), 6.30 (s, 1H), 4.39 (br s, 1H), 3.64 (s, 3H), 3.42 / 3.20 (dd+dd, 2H), 2.96 / 2.53 (dd+dd, 2H), 2.43 / 1.99 / 1.88 / 1.45 (td+dt / td+dt, 4H), 2.08 / 1.90 / 1.71 / 1.34 (t+d / t+t, 4H), 2.07 (m, 1H), 1.61 (m, 1H), 1.45 / 1.02 (t+t, 2H), 0.91 (d, 3H). HRMS calculated for C26H32CINO3: 441.2071; found 442.2143 (M+H). The diastereoisomer eluting later was collected as Preparation lObl. 'H NMR (500 MHz, DMSO-d6) 8 ppm: 7.36 (d, 1H), 7.20 (d, 1H), 7.15 (t, 1H), 7.13 (t, 1H), 7.06 (t, 1H), 6.59 (dd, 1H), 6.56 (dd, 1H), 6.45 (dd, 1H), 6.31 (s, 1H), 4.45 (t, 1H), 3.64 (s, 3H), 3.22 (t, 2H), 2.93 / 2.51 (dd+dd, 2H), 2.44 / 1.97 / 1.88 / 1.44 (td+dt / td+dt, 4H), 2.12 / 1.89 / 1.71 / 1.36 (t+d / t+d, 4H), 2.07 (m, 1H), 1.56 (m, 1H), 1.35 / 1.07 (t+t, 2H), 0.85 (d, 3H). HRMS calculated for C26H32CINO3: 441.2071; found 442.2139 (M+H). Preparation Ila Preparation IlaA 5-(bromomethyl)-2,2-dimethyl-l,3-dioxane Br To a stirred solution of (2,2-dimethyl-l,3-dioxan-5-yl)methanol (3.07 g, 21 mmol, 1 eq) in DCM (4 mL) and pyridine (2 mL) was added CBn (3.24 mL, 31.9 mmol, 1.52 eq), followed by PPh3 (5.51 g, 21 mmol, 1 eq) in DCM (5 mL) over 1.5 h. The mixture was stirred at rt for 18 h, then filtered and concentrated in vacuo. Purification by automated flash column chromatography (CombiFlash Rf, 80 g RediSep™ silica cartridge) eluting with a gradient of 0100% DCM in heptane afforded Preparation IlaA as a cream oil (1.96 g, 9.36 mmol, 45%). XH NMR (400 MHz, DMSO-d6) 8 ppm: 3.99-3.90 (m, 2H), 3.73-3.63 (m, 2H), 3.58 (d, J= 7.2 Hz, 2H), 2.00-1.86 (m, 1H), 1.36-1.30 (m, 6H). Preparation HaB bromido[(2,2-dimethyl-l,3-dioxan-5-yl)methyl]zinc Using General procedure 4 and Preparation IlaA as the appropriate bromo compound, Preparation HaB was obtained. Preparation Ila methyl (lr,4r)-4-(3-chloroanilino)-2'-[3-hydroxy-2-(hydroxymethyl)propyl]spiro[cyclohexane-l,T-indene]-4-carboxylate To an oven-dried flask was added Preparation 6c (112 mg, 0.25 mmol, 1 eq) and AtaPhos (4 mg, 5 pmol, 0.02 eq) in THF (3 mL). 1-methylimidazole (40 pL, 0.5 mmol, 2 eq) was added followed by Preparation llaB (1 mL, 0.5 M, 0.5 mmol, 2 eq) and then stirred at rt for 18 h. The mixture was filtered through celite, washed with DCM and the organic phase was washed with 1 M aq. HC1 solution, brine, dried (MgSO4) and concentrated in vacuo. The residue was taken up in MeOH (10 mL) and PTSA (4 pL, 0.04 mmol, 0.2 eq) was added and the mixture was stirred at rt for 1 h, then neutralized with K2CO3. The mixture was partitioned between DCM and sat. aq. NaHCO3 solution. The organic phase was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by automated flash column chromatography (CombiFlash Rf, 12 g RediSep™ silica cartridge) eluting with a gradient of 0-10% MeOH in DCM afforded Preparation Ila as a white solid (63 mg, 0.14 mmol, 55%). LRMS calculated for C26H30CINO4: 455; found 456 (M+H). JH NMR (400 MHz, DMSO-d6) 5 ppm: 7.68-7.62 (m, 1H), 7.32-7.27 (m, 1H), 7.26-7.20 (m, 1H), 7.14-7.07 (m, 2H), 6.65-6.57 (m, 2H), 6.526.51 (m, 2H), 6.44 (s, 1H), 4.44 (t, J= 5.1 Hz, 2H), 3.69 (s, 3H), 3.51-3.39 (m, 4H), 2.48-2.35 (m, 2H), 2.26-2.07 (m, 6H), 2.02-1.91 (m, 1H), 0.93-0.83 (m, 2H). Preparation 11b methyl (lr,4r)-4-(3-chloroanilino)-2'-[3-hydroxy-2- (hydroxymethyl)propyl]-2',3'-dihydrospiro[cyclohexane-l,T-indene]-4-carboxylate Using General procedure 19 and Preparation Ila as the appropriate indene, Preparation 11b was obtained. LRMS calculated for C26H32CINO4: 457; found 458 (M+H). Preparation 12a methyl (ls,4s)-4-(3-chloroanilino)-2'-(4-hydroxyphenyl)spiro[cyclohexane-1, l'-indene]-4-carboxylate Using General procedure 18 and Preparation 6c as the appropriate 2-bromo-indene and (4-hydroxyphenyl)boronic acid as the appropriate boronic acid, Preparation 12a was obtained. NMR (500 MHz, DMSO-d6) 5 ppm: 9.62 (s, 1H), 7.75 (dm, 1H), 7.68 (m, 2H), 7.38 (dm, 1H), 7.27 (m, 1H), 7.16 (m, 1H), 7.13 (t, 1H), 7.10 (s, 1H), 6.79 (m, 2H), 6.71 (t, 1H), 6.65 (s, 1H), 6.63 (dm, 1H), 6.55 (dm, 1H), 3.71 (s, 3H), 2.50 / 1.01 (m+m, 4H), 2.44 / 2.30 (m+m, 4H). HRMS calculated for C28H26CINO3: 459.1601; found 460.1667 (M+H). Preparation 12b methyl (ls,4s)-4-(3-chloroanilino)-2'-(3-hydroxyphenyl)spiro[cyclohexane-1, l'-indene]-4-carboxylate Using General procedure 18 and Preparation 6c as the appropriate 2-bromo-indene and (3-hydroxyphenyl)boronic acid as the appropriate boronic acid, Preparation 12b was obtained. *HNMR (500 MHz, DMSO-d6) 5 ppm: 9.41 (s, 1H), 7.80-7.16 (m, 4H), 7.19 (m, 1H), 7.18 (m, 1H), 7.10 (t, 1H), 7.10 (s, 1H), 7.10 (m, 1H), 6.75 (dm, 1H), 6.69 (t, 1H), 6.60 (dm, 1H), 6.56 (s, 1H), 6.51 (dm, 1H), 3.70 (s, 3H), 2.50 / 1.04 (m+m, 4H), 2.44 / 2.28 (m+m, 4H). HRMS calculated for C28H26CINO3: 459.1601; found 460.1675 (M+H). Preparation 12c methyl (lr,4r)-4-(3-chloroanilino)-2'-(3-hydroxyphenyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate, enantiomer 1 Using General procedure 19 and Preparation 12b as the appropriate indene and using AcOH instead of EtOAc, a racemate was obtained. The enantiomers were separated by chiral chromatography. Column: IA, 100x500 mm, 20 pm, eluents: heptane / THF / zPrOH. The enantiomer eluting earlier was collected as Preparation 12c. !H NMR (500 MHz, DMSO-de) 3 ppm: 9.17 (s, 1H), 7.31-7.17 (m, 4H), 7.02 (t, 1H), 6,98 (t, 1H), 6.56 (dm, 1H), 6.54 (dm, 1H), 6.51 (t, 1H), 6.46 (dm, 1H), 6.40 (t, 1H), 6.39 (dm, 1H), 6.17 (s, 1H), 3.62 (s, 3H), 3.36 / 2.92 (dd, 2H), 3.32 (dd, 1H), 2.44-1.33 (m, 8H). HRMS calculated for C28H28C1NO3: 461.1758; found 462.1833 (M+H). Preparation 13a Preparation 13aAA methyl (ls,4s)-2'-bromo-4-[(3- chl orophenyl)(trifluoroacetyl)amino]spiro[cy cl ohexane-1,1'-indene]-4-carboxylate Preparation 6c (112 g, 251 mmol) was dissolved in 2-Me-THF (564 mL). TEA (175 mL, 1254 mmol) and DMAP (3.06 g, 25.1 mmol) were added to the mixture and cooled to 0°C. TFAA (697 mL, 5013 mmol) was added dropwise at 0°C (keeping the temperature of the reaction mixture below 10°C), then it was stirred at 50°C for 18 h. Then it was cooled to 0°C and stirred at 0°C for 2 h. The precipitate was filtered, taken up in DIPE (200 mL) and sonicated. The precipitate was filtered, washed with DIPE and dried to obtain Preparation 13aAA. 'H NMR (500 MHz, DMSO-d6) 6 ppm: 7.81 (m, 1H), 7.68 (m, 2H), 7.62 (t, 1H), 7.49 (dm, 1H), 7.32 (dm, 1H), 7.27 (m, 1H), 7.23 (m, 1H), 7.02 (s, 1H), 3.84 (s, 3H), 2.55-0.93 (m, 8H). HRMS calculated for C24H2oBrClF3N03: 541.0267; found 542.0328 (M+H). Preparation 13aA methyl (l.s,4.s)-2'-bromo-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-foimylspiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 26 and Preparation 13aAA as the appropriate indene, Preparation 13aA was obtained. NMR (500 MHz, DMSO-d6) 5 ppm: 10.00 (d, 1H), 7.97 (br s, 1H), 7.88 (dd, 1H), 7.82 (m, 1H), 7.73-7.6 (m, 3H), 7.55 (d, 1H), 7.19 (s, 1H), 3.87 (s, 3H), 2.58-1.40 (m, 5   8H). HRMS calculated for C25H2oBrClF3N04: 569.0216; found 587.0559 (M+NH4). Preparation 13aB methyl (lr,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6,-formyl-2,-{(27?)-3-[(4-methoxyphenyl)methoxy]-2-methylpropyl}spiro[cyclohexane-l,r-indene]-4- carboxylate F F 10 Using General procedure 27b and Preparation 13aA as the appropriate 2-bromo-indene derivative and Preparation 3d as the appropriate Zn reagent, Preparation 13aB was obtained. XH NMR (500 MHz, DMSO-d6) 6 ppm: 9.95 (s, 1H), 7.99 (d, 1H), 7.93-7.48 (m, 4H), 7.81 (d, 1H), 7.45 (dd, 1H), 7.25 / 7.24 (m, 2H), 6.89 (m, 2H), 6.58 / 6.57 (s, 1H), 4.47-4.33 (d+d, 2H), 15   3.86 (s, 3H), 3.72 (s, 3H), 3.42-3.25 (m, 2H), 2.66-1.02 (m, 11H), 0.95 / 0.93 (d, 3H). HRMS calculated for C37H37CIF3NO6: 683.2261; found 706.21591 (M+Na). Preparation 13aC (lr,47?)-4-(3-chloroanilino)-6'-formyl-2'-{(27?)-3-[(4- methoxyphenyl)methoxy]-2-methylpropyl}spiro[cyclohexane-l,r-indene]-4-carboxylic acid Using General Procedure 33a and Preparation 13aB as the appropriate ester. Preparation 13aC was obtained. ^NMR (500 MHz, DMSO-d6) 5 ppm: 12.83 (br s, 1H), 9.97 (s, 1H), 8.12 (br s, 1H), 7.84 (dd, 1H), 7.49 (d, 1H), 7.22 (dm, 2H), 7.10 (t, 1H), 6.85 (dm, 2H), 6.66 (t, 1H), 6.61 (s, 1H), 6.58 (m, 2H), 6.36 (br s, 1H), 4.40 / 4.37 (d+d, 2H), 3.72 (s, 3H), 3.34 / 3.30 (dd+dd, 2H), 2.46-2.01 (m, 8H), 2.42 / 2.06 (dd+dd, 2H), 2.20 (m, 1H), 0.94 (d, 3H). HRMS calculated for C34H36CINO5: 573.2282; found 574.2344 (M+H). Preparation 13aD methyl (lr,47?)-4-(3-chloroanilino)-6'-formyl-2'-{(27?)-3-[(4- methoxyphenyl)methoxy]-2-methylpropyl} spiro[cyclohexane-l, 1 '-indene]-4-carboxylate Using General procedure 17a and Preparation 13aC as the appropriate amino acid, Preparation 13aD was obtained. XHNMR (500 MHz, DMSO-de) 8 ppm: 9.98 (s, 1H), 8.12 (s, 1H), 7.83 (dd, 1H), 7.48 (d, 1H), 7.21 (d, 2H), 7.10 (t, 1H), 6.85 (d, 2H), 6.66 (dd, 1H), 6.60 (dd, 1H), 6.60 (s, 1H), 6.49 (dd, 1H), 6.45 (s, 1H), 4.40 / 4.36 (d+d, 2H), 3.72 (s, 3H), 3.71 (s, 3H), 3.33 / 3.29 (dd+dd, 2H), 2.46-0.87 (m, 8H), 2.42 / 2.05 (dd+dd, 2H), 2.19 (m, 1H), 0.94 (d, 3H). HRMS calculated for C35H38CINO5: 587.2438; found 588.2521 (M+H). Preparation 13aE methyl (lr,47?)-4-(3-chloroanilino)-6'-formyl-2'-[(27?)-3-hydroxy-2- methylpropyl]spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 28a and Preparation 13aD as the appropriate PMB derivative, Preparation 13aE was obtained. *HNMR (500 MHz, DMSO-de) 5 ppm: 9.98 (s, 1H), 8.13 (br s, 1H), 7.84 (dd, 1H), 7.51 (d, 1H), 7.10 (t, 1H), 6.65 (t, 1H), 6.63 (s, 1H), 6.60 (dm, 1H), 6.49 (dm, 1H), 6.45 (s, 1H), 4.59 (t, 1H), 3.71 (s, 3H), 3.33 (m, 2H), 2.47-0.87 (m, 8H), 2.43 / 1.97 (m+m, 2H), 1.99 (m, 1H), 0.90 (d, 3H). HRMS calculated for C27H30CINO4: 467.1863; found 468.1924 (M+H). Preparation 13aF methyl (lr,47?)-4-(3-chloroanilino)-6'-(l,3-dioxan-2-yl)-2'-[(2A)-3- hydroxy-2-methylpropyl]spiro[cyclohexane-l,r-indene]-4-carboxylate Preparation 13aE (1.39 g, 2.97 mmol) was dissolved in toluene (44.5 mL). Propane-1,3-diol (2.15 mL, 29.7 mmol) and PPTS (60 mg, 0.24 mmol) were added and the mixture was stirred at reflux temperature for 1 h using a Dean-Stark apparatus. Then it was concentrated under reduced pressure and purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 13aF. ’H NMR (500 MHz, DMSO-de) 8 ppm: 7.73 (br s, 1H), 7.26 (dd, 1H), 7.24 (d, 1H), 7.10 (t, 1H), 6.63 (t, 1H), 6.59 (dm, 1H), 6.47 (dm, 1H), 6.46 (s, 1H), 6.41 (s, 1H), 5.52 (s, 1H), 4.54 (t, 1H), 4.15 / 3.96 (dm+tm, 4H), 3.71 (s, 3H), 3.34 / 3.29 (m+m, 2H), 2.44-0.80 (m, 8H), 2.35 / 1.90 (m+m, 2H), 2.00 / 1.45 (m+dm, 2H), 1.96 (m, 1H), 0.89 (d, 3H). HRMS calculated for C30H36CINO5: 525.2282; found 526.23491 (M+H). Preparation 13aG methyl (lr,27?,4A)-4-(3-chloroanilino)-6'-(l,3-dioxan-2-yl)-2'-[(27?)-3-hydroxy-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,T-indene]-4-carboxylate and Preparation 13aH methyl (1^2^,45)-4-(3-011^03011100)-6^(1,3^^30-2^1)-2^(2.^)-3- hydroxy-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 19 and Preparation 13aF as the appropriate indene, a mixture of diastereoisomers was obtained. The diastereoisomers were separated by chiral chromatography. Column: AD, 100x500 mm, 20 pm, Eluents: 15:85 EtOH / heptane. The diastereoisomer eluting earlier was collected as Preparation 13aG. *H NMR (500 MHz, DMSO-de) 5 ppm: 7.35 (s, 1H), 7.17 (m, 2H), 7.07 (t, 1H), 6.60 (t, 1H), 6.57 (dd, 1H), 6.46 (dd, 1H), 6.29 (s, 1H), 5.48 (s, 1H), 4.39 (t, 1H), 4.13 / 3.93 (dd+dd, 4H), 3.65 (s, 3H), 3.42 / 3.19 (m+m, 2H), 2.95 / 2.53 (dd+dd, 2H), 2.41-1.36 (m, 8H), 2.14 (m, 1H), 1.99 / 1.44 (m, 2H), 1.60 (m, 1H), 1.41 / 0.94 (m+m, 2H), 0.89 (d, 3H). HRMS calculated for C30H38CINO5: 527.2438; found 528.2505 (M+H). The diastereoisomer eluting later was collected as Preparation 13aH. 'H NMR (500 MHz, DMSO-d6) 6 ppm: 7.34 (s, 1H), 7.17 (m, 2H), 7.07 (t, 1H), 6.60 (t, 1H), 6.56 (dd, 1H), 6.46 (dd, 1H), 6.31 (s, 1H), 5.48 (s, 1H), 4.43 (t, 1H), 4.14 / 3.93 (dd+dd, 4H), 3.66 (s, 3H), 3.20 (m, 2H), 2.94 / 2.49 (dd+dd, 2H), 2.42-1.37 (m, 8H), 2.13 (m, 1H), 1.99 / 1.44 (m+m, 2H), 1.56 (m, 1H), 1.25 / 1.03 (m+m, 2H), 0.85 (d, 3H). HRMS calculated for C30H38CINO5: 527.2438; found 528.2507 (M+H). Preparation 13al methyl (lr,2'5,4S)-4-(3-chloroanilino)-6'-(l,3-dioxan-2-yl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 30a and Preparation 13aH as the appropriate indane and Preparation 2al as the appropriate aryl-alcohol, Preparation 13al was obtained. *H NMR (500 MHz, DMSO-d6) 8 ppm: 8.13 (d, 1H), 7.36 (d, 1H), 7.18 (dd, 1H), 7.17 (d, 1H), 7.05 (t, 1H), 6.75 (d, 1H), 6.59 (t, 1H), 6.56 (dm, 1H), 6.45 (dm, 1H), 6.33 (s, 1H), 5.48 (s, 1H), 4.173.88 (m, 4H), 3.89 / 3.83 (dd+dd, 2H), 3.66 (s, 3H), 3.03 (m, 1H), 3.01 / 2.53 (dd+dd, 2H), 2.76 / 2.64 (m+m, 2H), 2.50-1.36 (m, 14H), 2.20 (m, 1H), 1.99 (m, 1H), 1.42 / 1.31 (m+m, 2H), 1.05 (d, 3H), 1.02 (d, 3H). HRMS calculated for C40H49CIN2O5: 672.333; found 673.3389 (M+H). Preparation 13a methyl (lr,2'5,45)-4-(3-chloroanilino)-6'-formyl-2,-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-1, l'-indene]-4-carboxylate Preparation 13al (430 mg, 0.64 mmol) was dissolved in acetone (4.8 mL), then 2 M aq. HC1 solution (3.2 mL) was added. The mixture was stirred at 45°C until no further conversion was observed. The mixture was allowed to cool to rt. The pH was adjusted to 7 with sat. aq. NaHCOa solution and acetone was removed under reduced pressure. The mixture was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 13a. 1H NMR (500 MHz, DMSO-d6) 8 ppm: 9.98 (s, 1H), 8.14 (d, 1H), 7.85 (br, 1H), 7.75 (dd, 1H), 7.45 (d, 1H), 7.06 (t, 1H), 6.76 (d, 1H), 6.60 (t, 1H), 6.56 (dd, 1H), 6.46 (dd, 1H), 6.35 (s, 1H), 3.87 (m, 2H), 3.66 (s, 3H), 3.11 / 2.63 (dd+dd, 2H), 3.02 (m, 1H), 2.75 / 2.63 (m+m, 2H), 2.46-1.46 (m, 8H), 2.24 (m, 1H), 2.01 (m, 1H), 1.77 / 1.70 (m+m, 2H), 1.65 / 1.58 (m+m, 2H), 1.46 / 1.34 (m+m, 2H), 1.05 (d, 3H), 1.00 (d, 3H). HRMS calculated for C37H43CIN2O4: 614.2911; found 615.29814 (M+H). Preparation 13b Preparation 13bA methyl (lr,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-formyl-2'-[(27?)-3-hydroxy-2-methylpropyl]spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 28a and Preparation 13aB as the appropriate PMB derivative. Preparation 13bA was obtained as a white solid. LRMS calculated for C29H29CIF3NO5: 563; found: 564 (M+H). Preparation 13bB methyl (lr,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-(l,3-dioxan-2-yl)-2'-[(27?)-3-hydroxy-2-methylpropyl]spiro[cyclohexane-l,r-indene]-4-carboxylate To a solution of Preparation 13bA (26.58 g, 47.13 mmol, 1 eq) in toluene (650 mL) was added propane-1,3-diol (34.2 mL, 471 mmol, 10 eq) and PPTS (0.95 g, 3.77 mmol, 0.08 eq). The mixture was heated at reflux for 1 h using Dean-Stark apparatus (pre-filled with toluene) and then allowed to cool to rt. The mixture was partitioned between DCM and water, and the organic phase was washed with brine, dried (PTFE phase separator) and concentrated in vacuo. Purification by automated flash chromatography (CombiFlash Rf, 330g RediSep™ silica cartridge) eluting with a gradient of 0-50% EtOAc in heptane afforded Preparation 13bB as a white foam (26.4 g, 42.4 mmol, 90%). LRMS calculated for C32H35CIF3NO6: 621; found: 622 (M+H). Preparation 13bC methyl (Ir^lRXTTM-fQ-chlorophenylXtrifluoroacetyOaminoJ^'-Q^-dioxan-2-yl)-2'-[(27?)-3-hydroxy-2-methylpropyl]-2',3l-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate F F Cl f-Y and Preparation 13bD methyl (lr,2'5,45)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6,-(l,3-dioxan-2-yl)-2'-[(27?)-3-hydroxy-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate F F Using General procedure 19 and Preparation 13bB as the appropriate indene, a mixture of di stereoisomers was obtained. They were purified and separated by automated flash chromatography (CombiFlash Rf, 330g RediSep™ silica cartridge) eluting with a gradient of 0-45% EtOAc in heptane. The diastereoisomer eluting earlier was collected as Preparation 13bC, isolated as a white solid. LRMS calculated for C32H37CIF3NO6: 623; found: 624 (M+H). 'H NMR (400 MHz, DMSO-d6) 6 ppm: 7.70-7.50 (m, 4H), 7.17-7.05 (m, 3H), 5.46 (s, 1H), 4.43-4.35 (m, 1H), 4.18-4.09 (m, 2H), 3.97-3.87 (m, 2H), 3.79 / 3.78 (s, 3H), 3.44-3.36 (m, 1H), 3.15-2.92 (m, 2H), 2.54-2.46 (m, 1H), 2.30-1.93 (m, 5H), 1.73-1.40 (m, 7H), 1.16-1.04 (m, 1H), 0.85-0.77 (m, 3H), 0.68-0.57 (m, 1H). The diastereoisomer eluting later was collected as Preparation 13bD, isolated as a white solid. LRMS calculated for C32H37CIF3NO6: 623; found: 624 (M+H). ’H NMR (400 MHz, DMSO-d6) 8 ppm: 7.76-7.44 (m, 4H), 7.16-7.00 (m, 3H), 5.46 (s, 1H), 4.39-4.32 (m, 1H), 4.17-4.09 (m, 2H), 3.97-3.87 (m, 2H), 3.79 / 3.79 (s, 3H), 3.17-2.90 (m, 3H), 2.54-1.36 (m, 13H), 1.025   0.52 (m, 5H). Preparation 13bE methyl (lr,2'5,45)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6,-(l,3-dioxan-2-yl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 30a and Preparation 13bD as the appropriate indene and Preparation 2al as the appropriate alcohol, Preparation 13bE was obtained as a white solid. LRMS calculated for C42H48CIF3N2O6: 768; found: 769 (M+H). 15 Preparation 13b methyl (lr,2\S,45)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6,-formyl-2,-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate A solution of Preparation 13bE (6.04 g, 7.85 mmol, 1 eq) in a mixture of AcOH (24.3 mL, 20   424 mmol, 54 eq) and water (25 mL) was heated at 90°C for 1 h. The mixture was allowed to cool to rt and partitioned between EtOAc and water. The phases were separated, and the organic phase was washed with sat. aq. NaHCOs solution, brine, dried (MgSO4) and concentrated in vacuo. Purification by automated flash chromatography (CombiFlash Rf, 120g RediSep™ silica cartridge) eluting with a gradient of 0-100% EtOAc in heptane afforded Preparation 13b as a white foam (4.8 g, 6.76 mmol, 86%). LRMS calculated for C39H42CIF3N2O5: 710; found: 711 (M+H). Preparation 13c methyl (lr,2'5',45)-4-(3-chloroanilino)-6'-(hydroxymethyl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 36 and Preparation 13a as the appropriate formyl derivative, Preparation 13c was obtained. *HNMR (500 MHz, DMSO-de) 5 ppm: 8.14 (d, 1H), 7.32 (br s, 1H), 7.13 (d, 1H), 7.08 (dd, 1H), 7.05 (t, 1H), 6.76 (d, 1H), 6.60 (t, 1H), 6.56 (dm, 1H), 6.46 (dm, 1H), 6.32 (s, 1H), 5.12 (t, 1H), 4.46 (d, 2H), 3.90 / 3.84 (dd+dd, 2H), 3.65 (s, 3H), 3.05 (m, 1H), 2.97 / 2.50 (dd+dd, 2H), 2.76 / 2.67 (m+m, 2H), 2.50-1.36 (m, 8H), 2.15 (m, 1H), 2.00 (m, 1H), 1.84-1.66 (m, 2H), 1.66 / 1.60 (m+m, 2H), 1.45 / 1.33 (m+m, 2H), 1.05 (d, 3H), 1.04 (d, 3H). HRMS calculated for C37H45CIN2O4: 616.3068; found: 617.3141 (M+H). Preparation 13d Preparation 13dA methyl (lr,27?,4J?)-4-(3-chloroanilino)-6'-(l,3-dioxan-2-yl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 30a and Preparation 13aG as the appropriate indane and Preparation 2al as the appropriate alcohol, Preparation 13dA was obtained. £H NMR (500 MHz, DMSO-d6) 8 ppm: 8.13 (d, 1H), 7.39 (d, 1H), 7.18 (dd, 1H), 7.17 (d, 1H), 7.05 (t, 1H), 6.78 (d, 1H), 6.58 (t, 1H), 6.57 (dm, 1H), 6.41 (dm, 1H), 6.23 (s, 1H), 5.47 (s, 1H), 4.17-3.88 (m, 4H), 4.00 / 3.87 (dd+dd, 2H), 3.64 (s, 3H), 3.00 (m, 1H), 3.00 / 2.58 (dd+dd, 2H), 2.73 / 2.59 (m+m, 2H), 2.45-1.28 (m, 14H), 2.13 (m, 1H), 2.06 (m, 1H), 1.66 / 1.18 (m+m, 2H), 1.08 (d, 3H), 1.08 (d, 3H). HRMS calculated for C40H49CIN2O5: 672.3330; found: 673.3408 (M+H). Preparation 13dB methyl (lr,2'7?,47?)-4-(3-chloroanilino)-6'-formyl-2,-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-1, l'-indene]-4-carboxylate Using General procedure 9 and Preparation 13dA as the appropriate acetal, Preparation 13dB was obtained. ‘HNMR (500 MHz, DMSO-d6) 8 ppm: 9.97 (s, 1H), 8.15 (d, 1H), 7.88 (d, 1H), 7.74 (dd, 1H), 7.45 (d, 1H), 7.06 (t, 1H), 6.77 (d, 1H), 6.59 (t, 1H), 6.57 (dd, 1H), 6.43 (dd, 1H), 6.28 (s, 1H), 4.01 / 3.88 (dd+dd, 2H), 3.66 (s, 3H), 3.12 / 2.70 (dd+dd, 2H), 3.07 (m, 1H), 2.72 / 2.60 (m+m, 2H), 2.44-1.40 (m, 8H), 2.15 (m, 1H), 2.07 (m, 1H), 1.76 / 1.64 (m+m, 2H), 1.70 / 1.23 (m+m, 2H), 1.48 (m, 2H), 1.10 (d, 3H), 1.08 (d, 3H). HRMS calculated for C37H43CIN2O4: 614.2911; found: 615.2981 (M+H). Preparation 13d methyl (lr,27?,47?)-4-(3-chloroanilino)-6'-(hydroxymethyl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 36 and Preparation 13dB as the appropriate formyl derivative, Preparation 13d was obtained. *HNMR (500 MHz, DMSO-de) 8 ppm: 8.13 (d, 1H), 7.34 (br s, 1H), 7.14 (d, 1H), 7.07 (br d, 1H), 7.05 (t, 1H), 6.78 (d, 1H), 6.59 (t, 1H), 6.56 (dm, 1H), 6.42 (dm, 1H), 6.23 (s, 1H), 5.11 (t, 1H), 4.45 (d, 2H), 4.00 / 3.87 (dd+dd, 2H), 3.64 (s, 3H), 3.00 (m, 1H), 2.97 / 2.56 (dd+dd, 2H), 2.73 / 2.60 (m+m, 2H), 2.48-1.32 (m, 8H), 2.10 (br, 1H), 2.07 (m, 1H), 1.76-1.66 (m, 2H), 1.68 / 1.21 (m+m, 2H), 1.52 / 1.47 (m+m, 2H), 1.09 (d, 3H), 1.09 (d, 3H). HRMS calculated for C37H45CIN2O4: 616.3068; found: 617.3140 (M+H). Preparation 14a and Preparation 14b Preparation 14aA methyl (ls,4s)-6'-acetyl-2'-bromo-4-[(3- chl orophenyl)(trifluoroacetyl)amino]spiro[cy cl ohexane-1,1'-indene]-4-carboxylate Using General procedure 23 and Preparation 13aAA as the appropriate indene, Preparation 14aA was obtained. THNMR (500 MHz, DMSO-d6) 5 ppm: 8.10 (d, 1H), 7.94 (dd, 1H), 7.83 (m, 1H), 7.73-7.60 (m, 3H), 7.46 (d, 1H), 7.15 (s, 1H), 3.86 (s, 3H), 2.65-1.28 (m, 8H), 2.60 (s, 3H). HRMS calculated for C26H22BrClF3NO4: 583.0373; found 584.0438 (M+H). Preparation 14aB methyl (ls,4s)-6'-(acetyloxy)-2'-bromo-4-[(3- chlorophenyl)(trifluoroacetyl)amino] spiro [cyclohexane-1,1 '-indene] -4-carboxylate Using General procedure 24 and Preparation 14aA as the appropriate indene, Preparation 14aB was obtained. ’H NMR (500 MHz, DMSO-d6) 5 ppm: 7.81-7.59 (m, 4H), 7.34 (d, 1H), 7.17 (d, 1H), 7.04 (dd, 1H), 7.03 (s, 1H), 3.82 (s, 3H), 2.45-1.44 (m, 8H), 2.30 (s, 3H). HRMS calculated for C26H22BrClF3NO5: 599.0322; found 617.0654 (M+NH4). Preparation 14aC methyl (ls,4s)-2'-bromo-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-hy droxy spiro [cy cl ohexane-1,1' -indene] -4 -carb oxy 1 ate Using General procedure 25 and Preparation 14aB as the appropriate indene, Preparation 14aC was obtained. ^NMR (500 MHz, DMSO-d6) 5 ppm: 9.53 (s, 1H), 7.77 (br s, 1H), 7.687.59 (m, 3H), 7.08 (d, 1H), 6.92 (d, 1H), 6.85 (s, 1H), 6.65 (dd, 1H), 3.84 (s, 3H), 2.40-1.50 (m, 8H). HRMS calculated for C24H20BrClF3NO4: 557.0216; found 575.0545 (M+NH4). Preparation 14aD methyl (15,45)-2'-bromo-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6,- (methoxymethoxy)spiro[cyclohexane-l,l'-indene]-4-carboxylate Preparation 14aC (111 g, 199 mmol) was dissolved in DCM (993 mL) and cooled to 0°C under N2 atmosphere. DIPEA (138 mL, 795 mmol) and MOM-CI (60 mL, 795 mmol) were added at 0°C, then the mixture was allowed to warm to rt and stirred overnight. Then it was diluted with water and sat. aq. NaHCO3 solution and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 14aD. 'HNMR (500 MHz, DMSO-de) 5 ppm: 7.83-7.58 (m, 4H), 7.23 (d, 1H), 7.17 (d, 1H), 6.95 (dd, 1H), 6.94 (s, 1H), 5.19 (s, 2H), 3.83 (s, 3H), 3.40 (s, 3H), 2.55-1.30 (m, 8H). HRMS calculated for C26H24BrClF3NO5: 601.0479; found 619.0823 (M+NH4). Preparation 14aE methyl (lr,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'- (methoxymethoxy)-2'-{(2J?)-3-[(4-methoxyphenyl)methoxy]-2- m ethylpropyl} spiro[cyclohexane-1,1 '-indene]-4-carboxylate Using General procedure 27b and Preparation 14aD as the appropriate 2-bromo-indene derivative and Preparation 3d as the appropriate Zn reagent, Preparation 14aE was obtained. NMR (500 MHz, DMSO-d6) 5 ppm: 7.85 / 7.78 (s / s, 1H), 7.70-7.63 (m, 2H), 7.55 / 7.50 (t / t, 1H), 7.25 / 7.23 (d / d, 2H), 7.20 (d, 1H), 7.13 / 7.12 (d / d, 1H), 6.89 (d, 2H), 6.88 (d, 1H), 6.34 / 6.33 (s / s, 1H), 5.16 (s, 2H), 4.43 / 4.41 / 4.38 / 4.35 (d+d / d+d, 2H), 3.82 (s, 3H), 3.73 (s, 3H), 3.40 (s, 3H), 3.33 / 3.28 (dd+dd, 2H), 2.60-1.00 (m, 8H), 2.27 / 2.17 / 1.89 / 1.80 (dd+dd / dd+dd, 2H), 2.10 (m, 1H), 0.93 / 0.91 (d / d, 3H). HRMS calculated for C38H41CIF3NO7: 715.2524; found 733.2882 (M+NH4). Preparation 14aF methyl (lr,2'5,45)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-(methoxymethoxy)-2'-{(27?)-3-[(4-methoxyphenyl)methoxy]-2-methylpropyl}-2',31-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate and Preparation 14bF methyl (lr,27?,4J?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-(methoxymethoxy)-2'-{(27?)-3-[(4-methoxyphenyl)methoxy]-2-methylpropyl}-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 19 and Preparation 14aE as the appropriate indene and toluene instead of EtOAc, a mixture of diastereoisomers was obtained. The diastereoisomers were separated by flash chromatography using heptane and EtOAc as eluents. The diastereoisomer eluting earlier was collected as Preparation 14bF. *H NMR (500 MHz, DMSO-de) 6 ppm: 7.67-7.41 (m, 4H), 7.22 (dm, 2H), 7.05 (d, 1H), 6.89 (dm, 2H), 6.77 (dm, 1H), 6.69 (d, 1H), 5.11 (s, 2H), 4.41 / 4.36 (d+d, 2H), 3.78 (s, 3H), 3.73 (s, 3H), 3.36 (s, 3H), 3.32 / 3.10 / 3.07 (m+dd / dd, 2H), 2.89 / 2.46 (dd+dd, 2H), 2.29-1.35 (m, 8H), 2.17 (m, 1H), 1.73 (m, 1H), 1.12 / 0.83 (m+m, 2H), 0.87 / 0.85 (d / d, 3H). HRMS calculated for C38H43CIF3NO7: 717.268; found 735.2976 (M+NH4). The diastereoisomer eluting later was collected as Preparation 14aF. 'H NMR (500 MHz, DMSO-d6) 8 ppm: 7.74-7.40 (m, 4H), 7.16 / 7.14 (dm / dm, 2H), 7.05 (d, 1H), 6.86 / 6.85 (dm / dm, 2H), 6.77 (dm, 1H), 6.67 / 6.66 (d / d, 1H), 5.11 (s, 2H), 4.31 / 4.28 (s / s, 2H), 3.78 (s, 3H), 3.72 (s, 3H), 3.36 (s, 3H), 3.17-2.99 (m, 2H), 2.90 / 2.87 / 2.40 (dd / dd+d, 2H), 2.44-1.18 (m, 8H), 2.20 / 2.15 (m / m, 1H), 1.65 (m, 1H), 1.03 / 0.94 / 0.75 / 0.65 (m / m+m / m, 2H), 0.77 / 0.74 (d / d, 3H). HRMS calculated for C38H43CIF3NO7: 717.268; found 735.2977 (M+NH4). Preparation 14aG methyl (lr,2W,4S)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-2'-[(2.R)-3-hydroxy-2-methylpropyl]-6'-(methoxymethoxy)-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Preparation 14bG methyl (lr,2'J?,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-2'-[(27?)-3-hydroxy-2-methylpropyl]-6'-(methoxymethoxy)-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Using General procedure 28a and Preparation 14aF as the appropriate PMB derivative, Preparation 14aG was obtained. !H NMR (500 MHz, DMSO-de) 5 ppm: 7.74-7.42 (m, 4H), 7.05 (d, 1H), 6.77 / 6.76 (dd, 1H), 6.67 / 6.66 (d, 1H), 5.11 (s, 2H), 4.37 / 4.34 (br t, 1H), 3.79 (s, 3H), 3.36 (s, 3H), 3.19-2.96 (m, 2H), 2.88 / 2.40 (dd+dd, 2H), 2.47-1.17 (m, 8H), 2.21 / 2.16 (m, 1H), 1.45 (m, 1H), 1.04 / 0.95 / 0.70 / 0.59 (m+m, 2H), 0.73 / 0.70 (d, 3H). HRMS calculated for C30H35CIF3NO6: 597.2105; found 615.2434 (M+NH4). Using General procedure 28a and Preparation 14bF as the appropriate PMB derivative, Preparation 14bG was obtained. *H NMR (500 MHz, DMSO-d6) 3 ppm: 7.70-7.48 (m, 4H), 7.05 (d, 1H), 6.77 (dd, 1H), 6.68 (d, 1H), 5.11 (s, 2H), 4.38 / 4.36 (t / t, 1H), 3.78 (s, 3H), 3.38 / 3.07 (m+m, 2H), 3.36 (s, 3H), 2.90 / 2.43 (dm+d, 2H), 2.22-1.40 (m, 8H), 2.21 (m, 1H), 1.51 (m, 1H), 1.12 / 0.69 (m+m, 2H), 0.82 (d, 3H). HRMS calculated for C30H35CIF3NO6: 597.2105; found 615.2440 (M+NH4). Preparation 14aH methyl (lr,2N,45)-4-[(3-chlorophenyl)(trifLuoroacetyl)amino]-6'-(methoxymethoxy)-2'-[(2A>)-2-methyl-3-j [(5 / ?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate and Preparation 14bH methyl (lr,2W3^-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-(methoxymethoxy)-2'-[(2J?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 30a and Preparation 14aG as the appropriate indane and Preparation 2al as the appropriate alcohol, Preparation 14aH was obtained. *H NMR (500 MHz, DMSO-d6) 8 ppm: 8.12 / 8.10 (d / d, 1H), 7.79-7.42 (m, 4H), 7.04 (d, 1H), 6.78 / 6.77 (dd / dd, 1H), 6.71 / 6.68 (d / d, 1H), 6.66 (d, 1H), 5.11 (s, 2H), 3.79 (s, 3H), 3.74 (m, 2H), 3.35 (s, 3H), 2.94 / 2.44 (m+m, 2H), 2.90 (m, 1H), 2.74 / 2.63 (m+m, 2H), 2.51-1.20 (m, 8H), 2.30 / 2.25 (m / m, 1H), 1.89 (m, 1H), 1.77 / 1.73 (m+m, 2H), 1.60 (m, 2H), 1.23-0.81 (m, 2H), 0.91 / 0.86 (d / d, 3H), 0.91 / 0.90 (d / d, 3H). Using General procedure 30a and Preparation 14aG as the appropriate indane and Preparation 2a2 as the appropriate alcohol, Preparation 14bH was obtained. 'H NMR (500 MHz, DMSO-de) 8 ppm: 8.11 / 8.09 (d / d, 1H), 7.81-7.45 (m, 4H), 7.05 (d, 1H), 6.78 / 6.77 (dd / dd, 1H), 6.66 (d, 1H), 6.65 / 6.63 (d / d, 1H), 5.11 / 5.10 (s / s, 2H), 3.81 / 3.78 / 3.68 / 3.64 (dd+dd / dd+dd, 2H), 3.80 (s, 3H), 3.35 / 3.34 (s / s, 3H), 2.95 / 2.48 (m+m, 2H), 2.83 / 2.77 (m / m, 1H), 2.73 / 2.62 (m+m, 2H), 2.58-1.18 (m, 8H), 2.34 / 2.27 (m / m, 1H), 1.90 (m, 1H), 1.78 / 1.72 (m+m, 2H), 1.60 (m, 2H), 1.02 / 0.97 (d / d, 3H), 1.00 / 0.94 (m+m, 2H), 0.92 (d, 3H). HRMS calculated for C40H46N2O6F3CI: 742.2996; found: 743.3049 (M+H). Preparation 14a methyl (lr,2'5,45)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-hydroxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Preparation 14aH (3.30 g, 4.44 mmol) was dissolved in DCM (44 mL). 1.25 M HC1 solution in EtOH (10.6 mL, 13.3 mmol) was added and the mixture was stirred at rt overnight. Then it was diluted with water, sat. aq. NaHCOa solution and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using MeOH and DCM as eluents to obtain Preparation 14a. *HNMR (500 MHz, DMSO-de) 6 ppm: 9.04 / 9.03 (s / s, 1H), 8.12 / 8.10 (d / d, 1H), 7.80-7.40 (m, 4H), 6.90 (d, 1H), 6.71 / 6.68 (d / d, 1H), 6.49 (dd, 1H), 6.45 / 6.43 (d / d, 1H), 3.81-3.68 (m, 2H), 3.78 (s, 3H), 2.91 (m, 1H), 2.88 / 2.37 (m+d, 2H), 2.74 / 2.63 (m+m, 2H), 2.50-1.35 (m, 8H), 2.25 / 2.20 (m / m, 1H), 1.87 (m, 1H), 1.77 / 1.73 (m+m, 2H), 1.60 (m, 2H), 1.24-0.80 (m, 2H), 0.91 / 0.87 (d / d, 3H), 0.91 / 0.89 (d / d, 3H). HRMS calculated for C38H42CIF3N2O5: 698.2734; found 699.2800 (M+H). Preparation 14b methyl (b;2'5’,41S')-4-[(3-chlorophenyl)(trifluoroacetyr)amino]-6'-hydroxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Preparation 14bH (2.294 g, 33.09 mmol) was dissolved in DCM (330 mL). 1.25 M HC1 solution in EtOH (15.4 mL, 19.3 mmol) was added and the mixture was stirred at rt for 1 h. Then it was diluted with water, sat. aq. NaHCO3 solution and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using MeOH and DCM as eluents to obtain Preparation 14b. 'H NMR (500 MHz, DMSO-de) 6 ppm: 9.05 / 9.04 (s / s, 1H), 8.11 / 8.09 (d / d, 1H), 7.82-7.42 (m, 4H), 6.91 (d, 1H), 6.66 / 6.63 (d / d, 1H), 6.49 (dd, 1H), 6.44 / 6.42 (d / d, 1H), 3.85-3.60 (m, 2H), 3.79 (s, 3H), 2.90 / 2.42 (m+dd, 2H), 2.85 / 2.79 (m / m, 1H), 2.56-0.86 (m, 14H), 2.29 / 2.22 (br / br, 1H), 1.88 (m, 1H), 1.78 / 1.72 (m+m, 2H), 1.02 / 0.98 (d / d, 3H), 0.92 (d, 3H). HRMS calculated for C38H42N2O5F3CI: 698.2734; found: 699.2799 (M+H). Preparation 14c methyl (lr,27?,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-hydroxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 30a and Preparation 14bG (4 g, 6.69 mmol, 1 eq) as the appropriate indane and Preparation 2al (1.64 g, 10 mmol, 1.5 eq) as the appropriate alcohol, an intermediate was obtained which was purified by loading onto a DCM-wet SCX cartridge (70g), washing successively with DCM, MeOH and eluting with 10% NHs / MeOH in DCM, then further purified by automated flash chromatography (CombiFlash Rf, 40g RediSep™ silica cartridge) eluting with a gradient of 0-20% MeOH in EtOAc to obtain Preparation 14c as a white solid (2.48 g, 3.55 mmol, 53%). LRMS calculated for C38H42CIF3N2O5: 698; found: 699 (M+H). ’H NMR (400 MHz, DMSO-d6) 5 ppm: 9.09 (s, 1H), 8.26 / 8.21 (d, J= 5.6 Hz, 1H), 7.62-6.83 (m, 6H), 6.53-6.47 (m, 2H), 4.11-3.98 (m, 1H), 3.87-3.70 (m, 4H), 3.09-2.95 (m, 1H), 2.94-2.73 (m, 2H), 2.73-2.57 (m, 1H), 2.49-2.41 (m, 1H), 2.36-1.36 (m, 15H), 1.14-1.08 (m, 3H), 1.06-0.83 (m, 4H). Preparation 15a Preparation 15aA methyl (lr,2'£,4S)-5'-chloro-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-2'-[(27?)-3-hydroxy-2-methylpropyl]-6'-(methoxymethoxy)-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Preparation 14aG (5.0 g, 8.36 mmol) was dissolved in MeCN (100 mL). l,3-Dichloro-5,5-dimethyl-imidazolidine-2,4-dione (873 mg, 4.43 mmol) was added and the mixture was stirred at rt for 2 days in the dark. Then it was diluted with sat. aq. NaHCOa solution and extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents to obtain Preparation 15aA. *H NMR (500 MHz, DMSO-d6) 8 ppm: 7.75-7.43 (m, 4H), 7.22 (s, 1H), 6.90 / 6.88 (s, 1H), 5.26-5.19 (d+d, 2H), 4.38 / 4.35 (t, 1H), 3.79 / 3.78 (s, 3H), 3.42 / 3.41 (s, 3H), 3.19-2.96 (m, 2H), 2.90 / 2.41 (dd+dd, 2H), 2.49-0.53 (m, 10H), 2.24 / 2.18 (m, 1H), 1.44 (m, 1H), 0.73 / 0.70 (d, 3H). HRMS calculated for C30H34CI2F3NO6: 631.1715; found 649.2039 (M+NH4). Preparation 15aB methyl (lr,2'JS’,48)-5'-chloro-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-(methoxymethoxy)-2'-[(2JR)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Using General procedure 30a and Preparation 15aA as the appropriate indane and Preparation 2al as the appropriate alcohol, Preparation 15aB was obtained. 'H NMR (500 MHz, DMSO-d6) 8 ppm: 8.12 / 8.10 (d / d, 1H), 7.81-7.42 (m, 4H), 7.20 (s, 1H), 6.89 / 6.88 (s / s, 1H), 6.70 / 6.68 (d / d, 1H), 5.22 (m, 2H), 3.82-3.64 (m, 2H), 3.79 (s, 3H), 3.40 (s, 3H), 2.96 / 2.45 (m+d, 2H), 2.89 (m, 1H), 2.74 / 2.64 (dm+m, 2H), 2.54-0.78 (m, 14H), 2.33 / 2.27 (m / m, 1H), 1.87 (m, 1H), 0.89 (d, 3H), 0.86 / 0.81 (d / d, 3H). HRMS calculated for C40H45CI2F3N2O6: 776.2607; found 777.2665 (M+H). Preparation 15a methyl (lr,2'>S’,45)-5'-chloro-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-6'-hydroxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Preparation 15aB (2.12 g, 2.73 mmol) was dissolved in DCM (27 mL). 1.25 M HC1 solution in EtOH (6.5 mL, 8.18 mmol) was added and the mixture was stirred at rt overnight. Then it was diluted with water and sat. aq. NaHCOs solution. It was extracted with DCM. The combined organic layers were dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 15a. *H NMR (500 MHz, DMSO-dg) 6 ppm: 9.80 (br s, 1H), 8.12 / 8.10 (d / d, 1H), 7.84-7.41 (m, 4H), 7.06 (s, 1H), 6.71 / 6.68 (d / d, 1H), 6.66 / 6.64 (s / s, 1H), 3.83-3.60 (m, 2H), 3.78 (s, 3H), 2.89 (m, 1H), 2.89 / 2.39 (m+d, 2H), 2.74 / 2.64 (dm+m, 2H), 2.50-0.76 (m, 14H), 2.28 / 2.22 (m / m, 1H), 1.86 (m, 1H), 0.90 / 0.88 (d / d, 3H), 0.87 / 0.82 (d / d, 3H). HRMS calculated for C38H41CI2F3N2O5: 732.2344; found 733.2423 (M+H). Preparation 16a methyl (lr,2W,4S)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-2'-[(2.R)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6'-[(trifluoromethanesulfonyl)oxy]-2',3'-dihydrospiro[cyclohexane-l,T-indene]-4-carboxylate Preparation 14a (1.15 g, 1.64 mmol) was dissolved in DCM (16 mL). Pyridine (265 pL, 3.28 mmol) was added and the mixture was cooled to 0°C. 1 M Tf20 solution in DCM (1.97 mL, 1.97 mmol) was added at 0°C, then it was allowed to warm to rt and stirred for 30 min. Then it was cooled to 0°C, the pH was set to 7 with 0.1 M aq. HC1 solution and the layers were separated. The aq. layer was extracted with DCM. The combined organic layers were dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using EtOAc and MeOH as eluents to obtain Preparation 16a. !H NMR (500 MHz, DMSO-d6) 5 ppm: 8.34 / 8.33 (d / d, 1H), 7.82-7.44 (m, 4H), 7.34 (d, 1H), 7.23 (dd, 1H), 7.10 / 7.09 (d / d, 1H), 7.03 / 7.01 (d / d, 1H), 3.96-3.80 (m, 2H), 3.80 / 3.79 (s / s, 3H), 3.08 / 2.58 (m+d, 2H), 2.82 / 2.73 (m+m, 2H), 2.55-1.19 (m, 8H), 2.41 / 2.35 (br / br, 1H), 1.93 (m, 1H), 1.76 (m, 2H), 1.69-1.54 (m, 1H), 1.69-1.54 (m, 2H), 1.21-0.82 (m, 2H), 0.92 / 0.91 (d / d, 3H), 0.85 / 0.79 (d / d, 3H). HRMS calculated for C39H41CIF6N2O7S: 830.2227; found 831.2292 (M+H). Preparation 16b methyl (lr,2'7?,47?)-4-[(3-chlorophenyl)(trifluoroacetyl)amino]-2,-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6'-[(trifluoromethanesulfonyl)oxy]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate F F To a solution of Preparation 14c (1.21 g, 1.73 mmol, 1 eq) in DCM (15 mL), cooled to 0°C, was added pyridine (279 pL, 3.46 mmol, 2 eq) followed by Tf2O (341 pL, 2.08 mmol, 1.2 eq) and the mixture was stirred at rt for 2 h. The mixture was partitioned between DCM and 0.1 M aq. HC1 solution, and the organic phase was washed with sat. aq. NaHCOs solution, brine, dried (MgSO4) and concentrated in vacuo. Purification by automated flash chromatography (CombiFlash Rf, 24g RediSep™ silica cartridge) eluting with a gradient of 0-4% MeOH in EtOAc afforded Preparation 16b as an off-white solid (731 mg, 0.88 mmol, 51%). LRMS calculated for C39H41CIF6N2O7S: 830; found: 831 (M+H). Preparation 17a and Preparation 17b Preparation 17aA methyl (15,45)-6'-acetyl-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane- 1, l'-indene]-4-carboxylate Using General procedure 33a and Preparation 14aA as the appropriate ester, an intermediate was obtained which was treated as described in General procedure 17a to obtain Preparation 17aA. ‘HNMR (500 MHz, DMSO-d6) 5 ppm: 8.27 (br s, 1H), 7.99 (dd, 1H), 7.51 (d, 1H), 7.18 (s, 1H), 7.10 (t, 1H), 6.61 (m, 1H), 6.60 (dm, 1H), 6.53 (s, 1H), 6.47 (dm, 1H), 3.72 (s, 3H), 2.61 (s, 3H), 2.44 / 2.31 (td+br d, 4H), 2.22 / 1.03 (td+br d, 4H). HRMS calculated for C24H23BrClNO3: 487.055; found 488.0618 (M+H). Preparation 17aB methyl (lr,47?)-6'-acetyl-4-(3-chloroanilino)-2'-{(27?)-3-[(4- methoxyphenyl)methoxy]-2-methylpropyl} spiro[cyclohexane-l, 1 '-indene]-4-carboxylate Using General procedure 27b and Preparation 17aA as the appropriate 2-bromo-indene derivative and Preparation 3d as the appropriate Zn reagent, Preparation 17aB was obtained. 'HNMR (400 MHz, DMSO-d6) 5 ppm: 8.24 (s, 1H), 7.91 (dd, 1H), 7.38 (d, 1H), 7.21 (d, 2H), 7.09 (t, 1H), 6.85 (d, 2H), 6.66 (t, 1H), 6.60 (dd, 1H), 6.56 (s, 1H), 6.48 (dd, 1H), 6.45 (s, 1H), 4.38 (m, 2H), 3.72 (s, 3H), 3.72 (s, 3H), 3.30 (m, 2H), 2.58 (s, 3H), 2.43 / 2.24 (m+m, 4H), 2.41 / 2.03 (m+m, 2H), 2.18 (m, 1H), 2.12 / 0.88 (m+m, 4H), 0.93 (d, 3H). HRMS calculated for C36H4oC1N05: 601.2595; found 602.26625 (M+H). Preparation 17aC methyl (lr,4J?)-6'-acetyl-4-(3-chloroanilino)-2'-[(2R)-3-hydroxy-2- methylpropyl]spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 28a and Preparation 17aB as the appropriate PMB derivative. Preparation 17aC was obtained. 'HNMR (500 MHz, DMSO-de) 6 ppm: 8.26 (br s, 1H), 7.93 (dd, 1H), 7.42 (d, 1H), 7.11 (t, 1H), 6.65 (t, 1H), 6.61 (dm, 1H), 6.60 (s, 1H), 6.48 (dm, 1H), 6.46 (s, 1H), 4.59 (t, 1H), 3.73 (s, 3H), 3.34 (m, 2H), 2.60 (s, 3H), 2.50-0.84 (m, 8H), 2.43 / 1.97 (m+m, 2H), 2.00 (m, 1H), 0.91 (d, 3H). HRMS calculated for C28H32CINO4: 481.202; found 482.2088 (M+H). Preparation 17a methyl (lr,2'5,45)-6'-acetyl-4-(3-chloroanilino)-2,-[(2 / ?)-3-hydroxy-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate and Preparation 17b methyl (lr,2'7?,47?)-6'-acetyl-4-(3-chloroanilino)-2'-[(27?)-3-hydroxy-2- methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 19 and Preparation 17aC as the appropriate indene and toluene instead of EtOAc, a mixture of diastereoisomers was obtained. The diastereoisomers were separated by chiral chromatography. Column: AD, 100x500 mm, 20 pm. Eluents: 50:50 z'PrOH / heptane. The diastereoisomer eluting earlier was collected as Preparation 17b. 'H NMR (500 MHz, DMSO-d6) 8 ppm: 7.91 (br s, 1H), 7.81 (dd, 1H), 7.35 (d, 1H), 7.07 (t, 1H), 6.59 (t, 1H), 6.57 (dm, 1H), 6.45 (dm, 1H), 6.32 (s, 1H), 4.41 (t, 1H), 3.66 (s, 3H), 3.41 / 3.21 (m+m, 2H), 3.05 / 2.61 (dd+dd, 2H), 2.56 (s, 3H), 2.52-1.30 (m, 8H), 2.16 (m, 1H), 1.61 (m, 1H), 1.47 / 1.00 (m+td, 2H), 0.90 (d, 3H). HRMS calculated for C28H34CINO4: 483.2176; found 484.2245 (M+H). The diastereoisomer eluting later was collected as Preparation 17a. 1H NMR (500 MHz, DMSO-de) 8 ppm: 7.90 (br s, 1H), 7.81 (dd, 1H), 7.35 (d, 1H), 7.07 (t, 1H), 6.60 (t, 1H), 6.57 (dm, 1H), 6.45 (dm, 1H), 6.34 (s, 1H), 4.46 (t, 1H), 3.66 (s, 3H), 3.24 / 3.20 (m+m, 2H), 3.02 / 2.57 (dd+dd, 2H), 2.56 (s, 3H), 2.52-1.36 (m, 8H), 2.16 (m, 1H), 1.57 (m, 1H), 1.32 / 1.07 (m+m, 2H), 0.86 (d, 3H). HRMS calculated for C28H34CINO4: 483.2176; found 484.2250 (M+H). Preparation 18a Preparation 18aA 6-methoxy-177-indene 5-methoxy-2,3-dihydro-17 / -inden-l-one (50.7 g, 313 mmol) was dissolved in MeOH (500 mL) and cooled to 0°C. NaBH4 (24.8 g, 655 mmol) was added portionwise and then the mixture was allowed to warm to rt and stirred for 1 h. Then it was concentrated under reduced pressure. The residue was diluted with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was taken up in THF (300 mL). PTSA (3.0 g, 15.6 mmol) was added and the mixture was stirred at 75°C overnight. Then it was washed with sat. aq. NaHCOs solution and brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 18aA. ’H NMR (500 MHz, DMSO-d6) 6 ppm: 7.30 (d, 1H), 7.11 (d, 1H), 6.84 (dt, 1H), 6.83 (dd, 1H), 6.44 (dt, 1H), 3.75 (s, 3H), 3.36 (t, 2H). HRMS calculated for C10H10O: 146.0732; found 146.07341 (M+). Preparation 18aB 2-bromo-6-methoxy-1 / / -indene Preparation 18aA (12.0 g, 82.4 mmol) was dissolved in DMSO (100 mL) and cooled to 0°C. Water (2.8 mL) and then NBS (15.0 g, 84.4 mmol) were added portionwise. Then it was allowed to warm to rt and stirred for 30 min. Then it was poured onto ice and the precipitate was filtered. The precipitate was taken up in EtOAc, dried over NaiSCU, filtered and the filtrate was concentrated under reduced pressure. The residue was taken up in toluene (800 mL). PTSA (1.7 g, 8.9 mmol) was added and the mixture was stirred at 80°C overnight. Then it was cooled to rt, washed with sat. aq. NaHCO3 solution and brine. The aq. layer was extracted with toluene. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 18aB. *H NMR (500 MHz, DMSO-de) 6 ppm: 7.25 (d, 1H), 7.04 (m, 1H), 7.02 (td, 1H), 6.82 (dd, 1H), 3.75 (s, 3H), 3.64 (s, 2H). HRMS calculated for CioH9BrO: 223.9837; found 223.98418 (M+). Preparation 18aC 2"-bromo-6"-methoxydispiro[[l,3]dioxolane-2,r-cyclohexane-4', 1"-indene] and Preparation 18aD 2"-bromo-5"-methoxydispiro[[l,3]dioxolane-2,l'-cyclohexane-4', 1"-indene] Using General procedure 8a and Preparation 18aB as the appropriate indene, a mixture of regioisomers was obtained. The regioisomers were separated via flash chromatography using heptane and EtOAc as eluents. The regioisomer eluting earlier was collected as Preparation 18aD ’H NMR (500 MHz, DMSO-d6) 8 ppm: 7.56 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.75 (dd, 1H), 3.95 (m, 4H), 3.75 (s, 3H), 2.15-1.07 (m, 8H). HRMS calculated for Ci7Hi9BrO3: 350.0518; found 351.0593 (M+H). The regioisomer eluting later was collected as Preparation 18aC. ’H NMR (500 MHz, DMSO-d6) 8 ppm: 7.27 (d, 1H), 7.15 (d, 1H), 6.95 (s, 1H), 6.88 (dd, 1H), 3.95 (m, 4H), 3.77 (s, 3H), 2.15-1.07 (m, 8H). HRMS calculated for Ci7Hi9BrO3: 350.0518; found 351.0596 (M+H). Preparation 18aE 2'-bromo-6'-methoxyspiro[cyclohexane-l,l'-inden]-4-one Using General procedure 9 and Preparation 18aC as the appropriate ketal, Preparation 18aE was obtained. NMR (400 MHz, DMSO-d6) 8 ppm: 7.44 (d, 1H), 7.29 (d, 1H), 7.01 (s, 1H), 6.88 (dd, 1H), 3.79 (s, 3H), 2.91 / 2.52 (m, 4H), 2.17 / 1.66 (m, 4H). LRMS calculated for Ci5Hi5BrO2: 306.0; found 306.0 (M+). Preparation 18aF (ls,4s)-2'-bromo-4-(3-chloroanilino)-6'-methoxyspiro[cyclohexane-l,T-indene]-4-carbonitrile Using General procedure 11 and Preparation 18aE as the appropriate ketone and 3-chloroaniline as the appropriate aniline, a mixture of diastereoisomers was obtained. The diastereoisomers were separated via flash chromatography using heptane and EtOAc as eluents. The diastereoisomer eluting earlier was collected as Preparation 18aF. ’H NMR (500 MHz, DMSO-d6) 8 ppm: 7.28 (d, 1H), 7.24 (t, 1H), 7.22 (d, 1H), 6.97 (s, 1H), 6.92 (t, 1H), 6.89 (m, 2H), 6.79 (dm, 1H), 6.59 (s, 1H), 3.80 (s, 3H), 2.55 / 2.47 (m+m, 4H), 2.06 / 1.35 (m+m, 4H). HRMS calculated for C22H2oBrClN20: 442.0447; found 443.0526 (M+H). Preparation 18aG (ls,4s)-2'-bromo-4-(3-chloroanilino)-6'-methoxyspiro[cyclohexane-l,r-indene]-4-carboxamide Using General procedure 12b and Preparation 18aF as the appropriate nitrile, Preparation 18aG was obtained. NMR (500 MHz, DMSO-d6) 8 ppm: 7.37 (d, 1H), 7.34 / 7.24 (d+d, 2H), 7.26 (d, 1H), 7.12 (t, 1H), 6.93 (s, 1H), 6.88 (dd, 1H), 6.69 (t, 1H), 6.62 (dm, 1H), 6.60 (dm, 1H), 6.23 (s, 1H), 3.78 (s, 3H), 2.47 / 2.09 (m+m, 4H), 2.09 / 0.95 (m+m, 4H). HRMS calculated for C22H22BrClN2O2: 460.0553; found 461.0639 (M+H). Preparation 18aH (ls,4s)-2'-bromo-4-(3-chloroanilino)-6'-methoxyspiro[cyclohexane-l,V-indene]-4-carboxylic acid Using General procedure 13 and Preparation 18aG as the appropriate amide, Preparation 18aH was obtained. JH NMR (500 MHz, DMSO-d6) 8 ppm: 7.34 (d, 1H), 7.26 (d, 1H), 7.03 (t, 1H), 6.92 (s, 1H), 6.88 (dd, 1H), 6.60 (t, 1H), 6.54 (dm, 1H), 6.50 (dm, 1H), 6.26 (br s, 1H), 3.77 (s, 3H), 2.40 / 2.17 (m+m, 4H), 2.14 / 0.95 (m+m, 4H). HRMS calculated for C22H2iBrClNO3: 461.0393; found 462.0465 (M+H). Preparation 18al methyl (ls,4s)-2'-bromo-4-(3-chloroanilino)-6'-methoxyspiro[cyclohexane-1, l'-indene]-4-carboxylate Using General procedure 17a and Preparation 18aH as the appropriate amino acid, Preparation 18al was obtained. *HNMR (500 MHz, DMSO-de) 8 ppm: 7.28 (d, 1H), 7.26 (s, 1H), 7.09 (t, 1H), 6.95 (s, 1H), 6.90 (dd, 1H), 6.60 (t, 1H), 6.59 (dm, 1H), 6.49 (s, 1H), 6.46 (dm, 1H), 3.79 (s, 3H), 3.69 (s, 3H), 2.40 / 2.24 (m+m, 4H), 2.18 / 1.00 (m+m, 4H). HRMS calculated for C23H23BrClNO3: 475.055; found 476.0620 (M+H). Preparation 18aJ methyl (lr,4r)-4-(3-chloroanilino)-6'-methoxy-2'-(3-phenoxyphenyl)spiro[cyclohexane-l,r-indene]-4-carboxylate Using General procedure 18 and Preparation 18al as the appropriate 2-bromo-indene and (3-phenoxyphenyl)boronic acid as the appropriate boronic acid, Preparation 18aJ was obtained. ^NMR (500 MHz, DMSO-d6) 5 ppm: 7.54 (dm, 1H), 7.45 (t, 1H), 7.37 (t, 1H), 7.36 (m, 2H), 7.35 (d, 1H), 7.32 (d, 1H), 7.20 (s, 1H), 7.12 (m, 1H), 7.04 (t, 1H), 7.02 (m, 2H), 6.92 (dd, 1H), 6.89 (dm, 1H), 6.66 (t, 1H), 6.66 (s, 1H), 6.59 (dm, 1H), 6.52 (dm, 1H), 3.81 (s, 3H), 3.70 (s, 3H), 2.51 / 1.07 (m+m, 4H), 2.43 / 2.28 (m+m, 4H). HRMS calculated for C35H32C1NO4: 565.202; found 566.2099 (M+H). Preparation 18aK methyl (lr,4r)-4-(3-chloroanilino)-6'-methoxy-2'-(3-phenoxyphenyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate, enantiomer 1 and Preparation 18aL methyl (lr,4r)-4-(3-chloroanilino)-6'-methoxy-2'-(3-phenoxyphenyl)-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate, enantiomer 2 Using General procedure 19 and Preparation 18aJ as the appropriate indene and AcOH instead of EtOAc, a racemate was obtained. The enantiomers were separated by chiral chromatography. Column: AD, 100x500 mm, 20 pm. Eluents: 50:50 zPrOH / heptane. The enantiomer eluting earlier was collected as Preparation 18aK. 'H NMR (500 MHz, DMSO-d6) 6 ppm: 7.24 (t, 1H), 7.23 (m, 2H), 7.15 (d, 1H), 7.04 (m, 1H), 7.04 (t, 1H), 6.88 (dm, 1H), 6.87 (m, 2H), 6.81 (dm, 1H), 6.81 (d, 1H), 6.76 (dd, 1H), 6.72 (br s, 1H), 6.56 (dm, 1H), 6.48 (t, 1H), 6.37 (dm, 1H), 6.13 (s, 1H), 3.74 (s, 3H), 3.63 (s, 3H), 3.40 (dd, 1H), 3.25 / 2.92 (dd+dd, 2H), 2.43-1.25 (m, 8H). HRMS calculated for C35H34CINO4: 567.2177; found 568.2242 (M+H). The enantiomer eluting later was collected as Preparation 18aL. LRMS calculated for C35H34CINO4: 567.2; found 568.3 (M+H). Preparation 18a methyl (lr,4r)-4-(3-chloroanilino)-6'-hydroxy-2'-(3-phenoxyphenyl)-2',3'-dihydrospiro[cyclohexane-l, l'-indene]-4-carboxylate, enantiomer 1 Preparation 18aK (97 mg, 0.17 mmol) was dissolved in DCM (2 mL). 1 M BBn solution in DCM (340 pL, 0.34 mmol) was added and the mixture was stirred at rt for 30 min. Then it was diluted with water and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was taken up in DCM (1 mL) and MeOH (1 mL). 2 M TMS-CHNN solution in Et2O (170 pL, 0.34 mmol) was added and the mixture was stirred at rt for 30 min. Then it was concentrated under reduced pressure and purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 18a. *HNMR (500 MHz, DMSO-d6) 6 ppm: 9.17 (s, 1H), 7.23 (m, 3H), 7.04 (t, 1H), 7.03 (m, 1H), 7.01 (d, 1H), 6.87 (dm, 1H), 6.86 (m, 2H), 6.80 (dm, 1H), 6.74 (br s, 1H), 6.71 (d, 1H), 6.57 (dd, 1H), 6.56 (dm, 1H), 6.48 (t, 1H), 6.37 (dm, 1H), 6.12 (s, 1H), 3.63 (s, 3H), 3.37 (dd, 1H), 3.20 / 2.87 (dd+dd, 2H), 2.39-1.25 (m, 8H). HRMS calculated for C34H32CINO4: 553.202; found 554.2091 (M+H). Preparation 19a and Preparation 19b Preparation 19aA 5-(benzyloxy)-2,3-dihydro-177-inden-l-one O 5-hydroxyindan-l-one (444 mg, 3.0 mmol) was dissolved in MeCN (6 mL). K2CO3 (912 mg, 6.6 mmol) and bromomethylbenzene (392 gL, 3.3 mmol) was added and the mixture was stirred at rt for 5.5 h. Then it was diluted with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 19aA. !H NMR (500 MHz, DMSO-de) 8 ppm: 7.56 (d, 1H), 7.49-7.32 (m, 5H), 7.19 (d, 1H), 7.03 (dd, 1H), 5.22 (s, 2H), 3.04 (m, 2H), 2.58 (m, 2H). HRMS calculated for C16H14O2: 238.0994; found 239.1071 (M+H). Preparation 19aB 5-(benzyloxy)-2-bromo-2,3-dihydro-177-inden-l-one Preparation 19aA (119 mg, 0.5 mmol) was dissolved in CHCh (2 mL) and EtOAc (2 mL). CuBr2 (223 mg, 1.0 mmol) was added portionwise and the mixture was stirred at 60°C for 8 h. Then it was filtered through a pad of Celite, washed with EtOAc and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 19aB. rH NMR (500 MHz, DMSO-de) 8 ppm: 7.69 (d, 1H), 7.47 (d, 2H), 7.41 (t, 2H), 7.36 (t, 1H), 7.20 (d, 1H), 7.12 (dd, 1H), 5.25 (s, 2H), 4.97 (dd, 1H), 3.84 / 3.27 (dd+dd, 2H). HRMS calculated for Ci6Hi3BrO2: 316.0099; found 317.0182 (M+H). Preparation 19aC 5 -(benzyloxy)-2-bromo-2,3 -dihydro- 17 / -i nden -1 -ol OH Using General procedure 6 and Preparation 19aB as the appropriate bromo-indan-1-one and MeOH as solvent, Preparation 19C was obtained. ’H NMR (500 MHz, DMSO-de) 8 ppm: 7.44 (d, 2H), 7.39 (t, 2H), 7.32 (t, 1H), 7.21 (d, 1H), 6.91 (d, 1H), 6.87 (dd, 1H), 5.64 (br s, 1H), 5.10 / 5.07 (d+d, 2H), 4.84 (m, 1H), 4.83 (m, 1H), 3.36 / 3.15 (dd+dd, 2H). HRMS calculated for CieHi5BrO2: 318.0255; found 318.02499 (M+). Preparation 19aD 6-(benzyloxy)-2-bromo-l / / -indene Using General procedure 7 and Preparation 19aC as the appropriate indane. Preparation 19aD was obtained. NMR (500 MHz, DMSO-d6) 5 ppm: 7.44 (d, 2H), 7.39 (t, 2H), 7.33 (t, 1H), 7.25 (d, 1H), 7.13 (d, 1H), 7.02 (dd, 1H), 6.90 (dd, 1H), 5.09 (s, 2H), 3.65 (dd, 2H). HRMS calculated for Ci6Hi3BrO: 300.0150; found 300.01360 (M+). Preparation 19aE 6"-(benzyloxy)-2"-bromodispiro[[ 1,3 ]di oxolane-2, l'-cyclohexane-4',l"-indene] Using General procedure 8b and Preparation 19aD as the appropriate indane, a mixture of regioisomers was obtained. The regioisomers were separated via flash chromatography using heptane and EtOAc as eluents. The regioisomer eluting earlier was collected as Preparation 19aE ’H NMR (500 MHz, DMSO-d6) 8 ppm: 7.47 (d, 2H), 7.40 (t, 2H), 7.33 (t, 1H), 7.27 (d, 1H), 7.23 (d, 1H), 6.96 (dd, 1H), 6.95 (s, 1H), 5.12 (s, 2H), 3.95 (t, 4H), 2.08 / 1.19 (t+d, 4H), 2.03 / 1.85 (t+d, 4H). HRMS calculated for C23H23BrO3: 426.0831; found 427.0900 (M+H). Preparation 19aF 6'-(benzyloxy)-2'-bromospiro[cyclohexane-l,l'-inden]-4-one Using General procedure 9 and Preparation 19aE as the appropriate ketal, Preparation 19aF was obtained. *HNMR (500 MHz, DMSO-d6) 6 ppm: 7.54 (d, 1H), 7.47 (d, 2H), 7.39 (t, 2H), 7.33 (t, 1H), 7.29 (d, 1H), 7.01 (s, 1H), 6.97 (dd, 1H), 5.14 (s, 2H), 2.91 / 2.47 (dd+dt, 4H), 2.18 / 1.62 (td+dt, 4H). HRMS calculated for C2iHi9BrO2: 382.0569; found 382.05629 (M+). Preparation 19aG (15,45)-6'-(benzyloxy)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-1,1 '-indene]-4-carbonitrile Using General procedure 11 and Preparation 19aF as the appropriate ketone and 3-chloroaniline as the appropriate aniline, a mixture of diastereoisomers was obtained. The diastereoisomers were separated by flash chromatography using heptane and EtOAc as eluents. The diastereoisomer eluting earlier was collected as Preparation 19aG. *H NMR (500 MHz, DMSO-d6) 8 ppm: 7.50 (dm, 2H), 7.41 (tm, 2H), 7.35 (tm, 1H), 7.28 (d, 1H), 7.26 (d, 1H), 7.24 (t, 1H), 6.97 (dd, 1H), 6.96 (s, 1H), 6.92 (t, 1H), 6.88 (dm, 1H), 6.79 (dm, 1H), 6.57 (s, 1H), 5.17 (s, 2H), 2.51 / 2.41 (d+tm, 4H), 2.06 / 1.27 (td+d, 4H). HRMS calculated for C28H24BrClN2O: 518.076; found 519.0821 (M+H). Preparation 19aH (ls,4s)-6'-(benzyloxy)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-1,1 '-indene]-4-carboxamide Using General procedure 12a and Preparation 19aG as the appropriate nitrile, Preparation 19aH was obtained. ’H NMR (500 MHz, DMSO-d6) 6 ppm: 7.53-7.30 (m, 5H), 7.42 (d, 1H), 7.34 / 7.25 (br+br, 2H), 7.25 (d, 1H), 7.12 (t, 1H), 6.95 (dd, 1H), 6.92 (s, 1H), 6.69 (t, 1H), 6.62 (dm, 1H), 6.60 (dm, 1H), 6.22 (s, 1H), 5.12 (s, 2H), 2.45 / 2.07 (td+d, 4H), 2.10 / 0.94 (br t+d, 4H). HRMS calculated for C28H26BrClN2O2: 536.0866; found 537.0938 (M+H). Preparation 19al (ls,4s)-6'-(benzyloxy)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,r-indene]-4-carboxylic acid Using General procedure 13 and Preparation 19aH as the appropriate amide, Preparation 19al was obtained. NMR (500 MHz, DMSO-d6) 6 ppm: 12.83 (br s, 1H), 7.48 (d, 2H), 7.40 (t, 2H), 7.34 (d, 1H), 7.33 (t, 1H), 7.26 (d, 1H), 7.07 (t, 1H), 6.96 (dd, 1H), 6.93 (s, 1H), 6.61 (dd, 1H), 6.56 (dd, 1H), 6.54 (dd, 1H), 6.38 (br s, 1H), 5.12 (s, 2H), 2.35 / 2.20 (t+d, 4H), 2.16 / 0.96 (t+d, 4H). HRMS calculated for C28H25BrClNO3: 537.0706; found 538.0786 (M+H). Preparation 19aJ methyl (ls,4s)-6'-(benzyloxy)-2'-bromo-4-(3- chloroanilino)spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 17a and Preparation 19al as the appropriate amino acid, Preparation 19aJ was obtained. 'H NMR (500 MHz, DMSO-de) 8 ppm: 7.50-7.32 (m, 5H), 7.30 (d, 1H), 7.27 (d, 1H), 7.09 (t, 1H), 6.97 (dd, 1H), 6.94 (s, 1H), 6.60 (t, 1H), 6.59 (dm, 1H), 6.48 (s, 1H), 6.46 (dm, 1H), 5.13 (s, 2H), 3.68 (s, 3H), 2.35 / 2.23 (m+m, 4H), 2.17 / 0.98 (m+m, 4H). HRMS calculated for C29H27BrClNO3: 551.0863; found 552.0935 (M+H). Preparation 19aK methyl (lr,4J?)-6'-(benzyloxy)-4-(3-chloroanilino)-2'-{(2R)-3-[(4- methoxyphenyl)methoxy]-2-methylpropyl}spiro[cyclohexane-l,r-indene]-4-carboxylate Using General procedure 27a and Preparation 19aJ as the appropriate 2-bromo-indene derivative and Preparation 3d as the appropriate Zn reagent, Preparation 19aK was obtained. LRMS calculated for C41H44CINO5: 665; found 666 (M+H). TH NMR (400 MHz, DMSO-d6) 8 ppm: 7.50-7.45 (m, 2H), 7.44-7.38 (m, 2H), 7.38-7.31 (m, 1H), 7.27 (d, J = 2.2 Hz, 1H), 7.247.19 (m, 2H), 7.16 (d, J= 8.2 Hz, 1H), 7.10 (t, J= 8.1 Hz, 1H), 6.90 (dd, J= 8.2, 2.2 Hz, 1H), 6.89-6.84 (m, 2H), 6.64 (t, J= 2.1 Hz, 1H), 6.62-6.58 (m, 1H), 6.50-6.46 (m, 1H), 6.42 (s, 1H), 6.37-6.34 (m, 1H), 5.11 (s, 2H), 4.42-4.34 (m, 2H), 3.73 (s, 3H), 3.69 (s, 3H), 3.36-3.24 (m, 2H), 2.41-2.27 (m, 3H), 2.22-2.01 (m, 5H), 1.99-1.89 (m, 1H), 0.93 (d, J =6.6 Hz, 3H), 0.900.82 (m, 2H). Preparation 19aL methyl (lr,47?)-6'-(benzyloxy)-4-(3-chloroanilino)-2'-[(27?)-3-hydroxy-2- methylpropyl]spiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 28b and Preparation 19aK as the appropriate PMB derivative, Preparation 19aL was obtained. LRMS calculated for C33H36CINO4: 545; found 546 (M+H). !H NMR (400 MHz, DMSO-d6) 5 ppm: 7.51-7.45 (m, 2H), 7.45-7.38 (m, 2H), 7.38-7.31 (m, 1H), 7.27 (d, J= 2.2 Hz, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.10 (t, J= 8.1 Hz, 1H), 6.90 (dd, J = 8.2, 2.2 Hz, 1H), 6.65-6.57 (m, 2H), 6.50-6.45 (m, 1H), 6.42 (s, 1H), 6.39-6.36 (m, 1H), 5.11 (s, 2H), 4.53 (t, J= 5.2 Hz, 1H), 3.69 (s, 3H), 3.40-3.24 (m, 2H), 2.43-2.27 (m, 3H), 2.24-2.02 (m, 4H), 2.01-1.81 (m, 2H), 0.95-0.81 (m, 5H). Preparation 19aM methyl (lr,2'5,45)-6'-(benzyloxy)-4-(3-chloroanilino)-2'-[(2J?)-3-hydroxy- 2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate and Preparation 19bM methyl (lr,27?,4J?)-6'-(benzyloxy)-4-(3-chloroanilino)-2'-[(27?)-3- hydroxy-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Using General procedure 19 and Preparation 19aL as the appropriate indene, a mixture of diastereoisomers was obtained. The diastereoisomers were separated by chiral chromatography. Column: AD, 100x500 mm, 20 pm. Eluents: 30:70 zPrOH / heptane. The diastereoisomer eluting earlier was collected as Preparation 19bM. !H NMR (400 MHz, DMSO-de) 5 ppm: 7.47 (m, 2H), 7.42-7.39 (m, 2H), 7.36-7.32 (m, 1H), 7.11-7.05 (m, 2H), 6.96 (d, 1H), 6.80 (dd, 1H), 6.60-6.56 (m, 2H), 6.47-6.44 (m, 1H), 6.29 (s, 1H), 5.07 (s, 2H), 4.39 (br s, 1H), 3.65 (s, 3H), 3.41 (m, 1H), 3.19 (m, 1H), 2.89 / 2.36 (m+m, 2H), 2.09 (m, 1H), 2.46-1.40 (m, 8H), 1.59 (m, 1H), 1.27 / 1.00 (m+m, 2H), 0.91 (d, 3H). LRMS calculated for C33H38CINO4: 547.25; found 548.4 (M+H). The diastereoisomer eluting later was collected as Preparation 19aM. !H NMR (500 MHz, DMSO-d6) 8 ppm: 7.45 (m, 2H), 7.39 (m, 2H), 7.33 (m, 1H), 7.09 (d, 1H), 7.06 (t, 1H), 6.95 (d, 1H), 6.79 (dd, 1H), 6.59 (t, 1H), 6.56 (dd, 1H), 6.54 (dd, 1H), 6.30 (s, 1H), 5.07 (s, 2H), 4.44 (br s, 1H), 3.65 (s, 3H), 3.21 (d, 2H), 2.86 / 2.41 (m+m, 2H), 2.40-1.32 (m, 8H), 2.08 (m, 1H), 1.54 (m, 1H), 1.33 / 1.04 (m+m, 2H), 0.84 (d, 3H). HRMS calculated for C33H38CINO4: 547.249; found 548.25578 (M+H). Preparation 19aN methyl (lr,2'<S,45)-6'-(benzyloxy)-4-(3-chloroanilino)-2'-{(27?)-2-methyl-3-[(thieno[3,2-Z>]pyridin-7-yl)oxy]propyl}-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Preparation 19aM (955 mg, 1.74 mmol), thieno[3,2- / >]pyridin-7-ol (527 mg, 3.48 mmol) and PPhs (914 mg, 3.48 mmol) were dissolved in dry THF (17 mL) and cooled to 0°C. 40% DEAD solution in toluene (1.52 mL, 3.48 mmol) was added and the mixture was stirred at 0°C for 2 h. Then it was diluted with water and sat. aq. NaHCOs solution. It was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 19aN. 'H NMR (500 MHz, DMSO-d6) 8 ppm: 8.50 (d, 1H), 8.00 (d, 1H), 7.50 (d, 1H), 7.48-6.42 (m, 12H), 6.99 (d, 1H), 6.32 (s, 1H), 4.16 / 4.10 (dd+dd, 2H), 3.65 (s, 3H), 2.92 / 2.47 (dd+dd, 2H), 2.48-1.28 (m, 8H), 2.14 (m, 1H), 2.05 (m, 1H), 1.46 / 1.35 (m+m, 2H), 1.06 (d, 3H). HRMS calculated for C40H41CIN2O4S: 680.2476; found 681.25477 (M+H). Preparation 19a methyl (lr,2'5,45)-4-(3-chloroanilino)-6'-hydroxy-2'-{(27?)-2-methyl-3- [(thieno[3,2-Z>]pyridin-7-yl)oxy]propyl}-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4- carboxylate Preparation 19aN (845 mg, 1.24 mmol) was dissolved in DCM (25 mL) and EtSH (25 mL). BF3xEt2O (3.8 mL, 30.5 mmol) was added and the mixture was stirred at rt overnight. Then it was diluted with sat. aq. NaHCOi solution and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using DCM and MeOH as eluents to obtain Preparation 19a. XH NMR (500 MHz, DMSO-de) 8 ppm: 9.09 (s, 1H), 8.51 (d, 1H), 8.01 (d, 1H), 7.50 (d, 1H), 7.05 (t, 1H), 6.99 (d, 1H), 6.96 (d, 1H), 6.82 (d, 1H), 6.60 (t, 1H), 6.56 (dm, 1H), 6.53 (dd, 1H), 6.45 (dm, 1H), 6.32 (s, 1H), 4.16 / 4.10 (dd+dd, 2H), 3.64 (s, 3H),2.88 / 2.41 (dd+dd, 2H), 2.46-1.28 (m, 8H),2.10(m, lH),2.04(m, 1H), 1.47 / 1.34 (m+m, 2H), 1.06 (d, 3H). HRMS calculated for C33H35CIN2O4S: 590.2006; found 591.2070 (M+H). Preparation 19bN methyl (lr,27?,4 / ?)-6'-(benzyloxy)-4-(3-chloroanilino)-2'-{(27?)-2-methyl-3-[(thieno[3,2-Z>]pyridin-7-yl)oxy]propyl}-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylate Preparation 19bM (990 mg, 1.81 mmol), thieno[3,2-Z>]pyridin-7-ol (546 mg, 3.61 mmol) and PPh3 (947 mg, 3.61 mmol) were dissolved in dry THF (18 mL) and cooled to 0°C. 40% DEAD solution in toluene (1.57 mL, 3.61 mmol) was added and the mixture was stirred at 0°C for 1 h. Then it was diluted with water and sat. aq. NaHCO3 solution. It was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 19bN. *H NMR (500 MHz, DMSO-d6) 8 ppm: 8.50 (d, 1H), 7.90 (d, 1H), 7.48 (d, 1H), 7.42 (d, 2H), 7.39 (t, 2H), 7.33 (t, 1H), 7.10 (d, 1H), 7.05 (t, 1H), 6.98 (d, 1H), 6.92 (d, 1H), 6.80 (dd, 1H), 6.57 (m, 2H), 6.42 (dd, 1H), 6.22 (s, 1H), 5.06 (s, 2H), 4.23 / 4.12 (dd+dd, 2H), 3.64 (s, 3H), 2.97 / 2.52 (dd+dd, 2H), 2.42-1.27 (m, 8H), 2.17 (dd, 1H), 2.12 (m, 1H), 1.67 / 1.28 (dd+dd, 2H), 1.09 (d, 3H). HRMS calculated for C40H41CIN2O4S: 680.2476; found 681.2549 (M+H). Preparation 19b methyl (lr,27?,47?)-4-(3-chloroanilino)-6'-hydroxy-2'-{(2A)-2-methyl-3- [(thieno[3,2-Z>]pyridin-7-yl)oxy]propyl}-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4- carboxylate Preparation 19bN (864 mg, 1.27 mmol) was dissolved in DCM (25 mL) and EtSH (25 mL). BF3xEt2O (3.8 mL, 30.5 mmol) was added and the mixture was stirred at rt overnight. Then it was diluted with sat. aq. NaHCOs solution and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to obtain Preparation 19b. ’H NMR (500 MHz, DMSO-de) 8 ppm: 9.09 (s, 1H), 8.50 (d, 1H), 7.90 (d, 1H), 7.47 (d, 1H), 7.04 (t, 1H), 6.99 (d, 1H), 6.96 (d, 1H), 6.83 (d, 1H), 6.57 (m, 2H), 6.53 (dd, 1H), 6.42 (dm, 1H), 6.22 (s, 1H), 4.23 / 4.12 (dd+dd, 2H), 3.64 (s, 3H), 2.91 / 2.47 (dd+dd, 2H), 2.42-1.24 (m, 8H), 2.14 (m, 1H), 2.12 (m, 1H), 1.67 / 1.28 (m+m, 2H), 1.09 (d, 3H). HRMS calculated for C33H35CIN2O4S: 590.2006; found 591.2072 (M+H). Preparation 20a methyl (lr,2'JS',4*S)-4-(3-chloroanilino)-5',6,-dihydroxy-2'-[(27?)-3-hydroxy- 2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylate Example 839E (5.00 g, 10.3 mmol, 1 eq) was dissolved in DCM (103 mL) and cooled to 0°C. BBr3 (2.97 mL, 30.9 mmol, 3 eq) was added in one portion and the mixture was stirred at 0°C for 30 min. Then MeOH was added and the mixture was concentrated under reduced pressure. MeOH was added again and the mixture was concentrated under reduced pressure. The residue was dissolved in THF and washed with brine. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to obtain catechol derivative Preparation 20a (4.84 g, 10.2 mmol, 99%). ‘HNMR (400 MHz, DMSO-d6) 8 ppm: 8.54 (s, 2H), 7.06 (t, 1H), 6.79 (s, 1H), 6.59 (t, 1H), 6.57 (dm, 1H), 6.55 (s, 1H), 6.44 (dm, 1H), 6.28 (s, 1H), 4.43 (t, 1H), 3.64 (s, 3H), 3.21 (m, 2H), 2.74 / 2.31 (dd+dd, 2H), 2.43-1.15 (m, 8H), 1.98 (m, 1H), 1.53 (m, 1H), 1.33 / 1.02 (m+m, 2H), 0.83 (d, 3H). HRMS calculated for C26H32CINO5: 473.1969; found: 474.2031 (M+H). Preparation 20b methyl (lr,2'5,4S)-4-(3-chloroanilino)-5',6'-dihydroxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-1, l'-indene]-4-carboxylate Example 839 (3.77 g, 5.97 mmol, 1 eq) was dissolved in DCM (60 mL) and cooled to 0°C. BBr3 (1.72 mL, 17.9 mmol, 3 eq) was added in one portion and the mixture was stirred at 0°C for 30 min. Partial hydrolysis of the carboxylate ester was also observed. MeOH was added and the mixture was concentrated under reduced pressure. MeOH was added again and the mixture was concentrated under reduced pressure. The residue was dissolved in THF and washed with brine. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was treated as described in General procedure 17a then, instead flash chromatography the crude product was purified via prep RP-HPLC using 25 mM aq. NH4HCO3 solution and MeCN as eluents to obtain catechol derivative Preparation 20b (3.25 g, 5.25 mmol, 88%). !H NMR (500 MHz, DMSO-d6) 5 ppm: 8.55 (s, 1H), 8.54 (s, 1H), 8.18 (d, 1H), 7.04 (t, 1H), 6.82 (d, 1H), 6.81 (s, 1H), 6.57 (t, 1H), 6.56 (s, 1H), 6.55 (dm, 1H), 6.43 (dm, 1H), 6.30 (s, 1H), 3.93 / 3.86 (dd+dd, 2H), 3.64 (s, 3H), 3.06 (m, 1H), 2.80 / 2.34 (dd+dd, 2H), 2.77 / 2.67 (dm+m, 2H), 2.41-1.20 (m, 14H), 2.02 (m, 1H), 1.98 (m, 1H), 1.07 (d, 3H), 1.03 (d, 3H). HRMS calculated for C36H43CIN2O5: 618.2861; found: 619.2909 (M+H). EXAMPLES Example 1 (lr,4r)-4-(3-bromoanilino)-2'-oxo-T,2'-dihydrospiro[cyclohexane-l,3'-indole]-4-carboxylic acid A solution of l'H-spiro[cyclohexane-l,3'-indole]-2',4-dione (137 mg, 0.64 mmol, 1.5 eq) in THF (6 mL), cooled in an ice bath, was treated as described in General procedure 10 using 3-bromoaniline (46 pL, 0.42 mmol, 1 eq) and the mixture stirred at rt for 48 h. The mixture was diluted with water, acidified with 2 M aq. HC1 solution and then extracted with DCM. The organic phase was loaded onto a DCM-wet PE-AX cartridge (10 g) and washed successively with DCM, MeOH and eluted with 5% HCOOH in DCM, and then concentrated in vacuo. The residue was suspended in DCM and the precipitate collected by filtration, washed with DCM and dried in vacuo to afford a single diastereoisomer, Example 1 as a white powder (10.7 mg, 0.03 mmol, 6%). LRMS calculated for C2oHi9N203Br: 414; found: 415 (M+H). XH NMR (400 MHz, DMSO-d6) 6 ppm: 12.69 (br s, 1H), 10.31 (s, 1H), 7.25 (d, J= 7.3 Hz, 1H), 7.17 (td, J= 7.7, 1.2 Hz, 1H), 7.03 (t,7=8.1 Hz, 1H), 6.97 (td, J= 7.6, 1.1 Hz, 1H), 6.85 (t, 7= 2.1 Hz, 1H), 6.83 (d, 7= 7.6 Hz, 1H), 6.71 (ddd, 7=7.9, 1.9, 0.8 Hz, 1H), 6.65-6.61 (m, 1H), 6.28 (brs, 1H), 2.62-2.54 (m, 2H), 2.03-1.87 (m, 4H), 1.66-1.57 (m, 2H). Example 2 Example 2A l'-ethylspiro[cyclohexane-l,3'-indole]-2',4-dione To a solution of rH-spiro[cyclohexane-l,3'-indole]-2',4-dione (150 mg, 0.7 mmol, 1 eq) in MeCN (4 mL) was added CS2CO3 (454 mg, 1.39 mmol, 2 eq) and Etl (62 pL, 0.77 mmol, 1.1 eq) and the mixture stirred at rt under a N2 atmosphere for 18 h. The reaction was diluted with water, extracted with EtOAc and the organic phase dried (MgSCU) and concentrated in vacuo to afford Example 2A as a yellow solid (97.4 mg, 0.4 mmol, 57%). *H NMR (400 MHz, DMSO-d6) 5 ppm: 7.53 (dd, J= 7.5, 1.0 Hz, 1H), 7.31 (td, J= 1.2 Hz, 1H), 7.11 (d, J = 1.1, 1H), 7.06 (td, J= 7.5, 1.0 Hz, 1H), 3.74 (q, J= 12 Hz, 2H), 2.88 (ddd, J= 15.6, 10.2, 5.9 Hz, 2H), 2.43 (dt, J= 14.9, 5.7 Hz, 2H), 2.16 (ddd, J= 14.9, 10.1, 5.2 Hz, 2H), 1.98 (dt, J= 12.6, 5.9 Hz, 2H), 1.18 (t, 7= 7.1 Hz, 3H). Example 2 (lr,4r)-4-(3-bromoanilino)-T-ethyl-2'-oxo-r,2'-dihydrospiro[cyclohexane-l,3'-indole]-4-carboxylic acid A solution of Example 2A (97.4 mg, 0.4 mmol, 1 eq) in THF (4 mL) was treated as described in General procedure 10 using 3-bromoaniline (44 pL, 0.4 mmol, 1 eq) and the mixture stirred at rt for 18 h. The mixture was diluted with water, acidified with 2 M aq. HC1 solution and then extracted with EtOAc. The organic phase was loaded onto a DCM-wet PE-AX cartridge (10 g) and washed successively with DCM, MeOH and eluted with 5% HCOOH in DCM, and then concentrated in vacuo. Purification by flash chromatography (5g silica cartridge) eluting with a stepped gradient of 0-40% EtOAc in heptane, followed by trituration with DCM, afforded a single diastereoisomer, Example 2 as a white powder (9.5 mg, 0.02 mmol, 5%). LRMS calculated for C22H23N2O3Br: 442; found: 443 (M+H). *HNMR (400 MHz, DMSO-d6) 8 ppm: 12.71 (br s, 1H), 7.33-7.24 (m, 2H), 7.08-6.99 (m, 3H), 6.85 (t, J= 2.1 Hz, 1H), 6.73-6.68 (m, 1H), 6.65-6.60 (m, 1H), 6.29 (br s, 1H), 3.69 (q, J = 7.0 Hz, 2H), 2.64-2.54 (m, 2H), 2.05-1.91 (m, 4H), 1.62-1.53 (m, 2H), 1.14 (t, J = 7.1 Hz, 3H). Example 3 Example 3A l"H-dispiro[l,3-dioxolane-2,r-cyclohexane-4',3"-indole]-2"-one To a suspension of rH-spiro[cyclohexane-l,3'-indole]-2',4-dione (250 mg, 1.16 mmol, 1 eq) and 4A molecular sieves in anhydrous toluene (10 mL), was added PTSA (11 mg, 0.06 mmol, 0.05 eq) and ethylene glycol (0.13 mL, 2.32 mmol, 2 eq) and the reaction refluxed for 18 h. The mixture was di...

Claims

1. Compound of Formula (I):wherein:♦ X represents -S-, -O-, -CH2- or -N(R2)-,♦ Yi represents -C(R4)(Rs)- or -N(Re)-,♦ Y2 represents -N(R?)-, -C(Rs)(R9)-, or -C(Rs)(R9)-C(Ri4)(Ri5)-,♦   ........ means a single bond or a double bond,♦ Y3 represents -C(Rio)- or -N-,♦ Y4 represents -C(Ri3)- or -N-,♦ Ri represents an aryl group or a heteroaryl group,♦ R2 represents a hydrogen atom, or a linear or branched (Ci-C6)alkyl group,or the pair (Ri,R2) together with the nitrogen atom to which they are attached forms a non-aromatic or aromatic mono- or bicyclic ring composed of from 5 to 12 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen, sulphur and nitrogen, wherein said ring may be substituted by from 1 to 2 groups representing a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group,♦ R3 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-C6)alkyl group, -W1-OR3A, -Wi-0-C(0)-R3A, -W1-NR3AR3B, -Wi-C(O)-NR3aR3b,         -Wi-0-C(0)-0R3a,         -Wi-O-C(O)-NR3aR3b,-Wi-O-P(O)(OR3a)2, or -W1-SO2-OR3A, -Wi-Cyi, wherein:- Wi represents a bond or a linear or branched (Ci-C4)alkylene group,- R3A and R3B independently of one another, represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkylgroup, or a cycloalkyl group,or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members, which may contain in addition to the nitrogen a second heteroatom selected from oxygen and nitrogen,- Cyi represents an aryl group or a heteroaryl group,♦ R4 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkyl group substituted by 2 linear or branched (Ci-Ce)alkoxy groups, a linear or branched (C2-Ce)alkenyl group, a linear or branched (C2-Ce)alkynyl group, a linear or branched (Ci-C6)alkoxy group, a linear or branched (C2-Ce)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-Ce)alkoxy(C2-C6)alkenyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)haloalkyl group, a hydroxy group, a linear or branched (Ci-Ce)hydroxyalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein:- W2 represents a bond, a linear or branched (Ci-C6)alkylene group, a linear or branched (C2-C6)alkenylene group, or a linear or branched (C2-Ce)alkynylene group,- W3 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-Ce)alkenylene group, a linear or branched (C2-Cs)alkynylene group, a linear or branched (Ci-C6)alkoxylene group, a linear or branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene group, or a -CH2-CH(R4e)-CH2- group,- W4 represents a linear or branched (Ci-C4)alkylene group,- L represents -O-, -S-, or -SO2-,- R4E represents -Cy4 or -CH2-O-Cy4,- R4A and R4B independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an aryl group, a heteroaryl group, or an arylalkyl group,- R4C and R4D independently of one another represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a heteroarylalkyl group,- Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group,- Cy3 represents an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group,- Cy4 represents an aryl group, a heteroaryl group, an arylalkyl group, or a heterocycloalkylalkyl group,♦ R5 represents a hydrogen atom or a linear or branched (Ci-Ce)alkyl group,or the pair (R4,Rs) represents an oxo group, a cycloalkylidene group,or the pair (R4,Rs) together with carbon atoms to which they are attached forms a nonaromatic ring composed of from 3 to 6 ring members,♦ Re represents an aryl group, a -SO2-aryl group, or a -Ws-O-Cys group, wherein:- W5 represents a linear or branched (Ci-C4)alkylene group,- Cys represents an aryl group, or a heteroaryl group,♦ R7 represents a hydrogen atom, a linear or branched (Ci-Ce)alkyl group, an arylalkyl group, or a formyl group,♦ Rs represents a hydrogen atom, or a linear or branched (Ci-C6)alkyl group, or the pair (R^Rs) together with carbon atoms to which they are attached forms a nonaromatic or aromatic ring composed of from 3 to 7 ring members,♦ R9 represents a hydrogen atom,or the pair (Rs,R9) represents an oxo group,♦ Rio represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group,or the pair (R?,Rio) together with the nitrogen atom to which they are attached forms a non-aromatic ring composed of from 4 to 7 ring members,♦ Rn represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, or a linear or branched (Ci-Ce)alkoxy group,♦ R12 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, a linear or branched (Ci-C6)alkenyl group, a linear or branched (Ci-Ce)alkynyl group, a linear or branched (Ci-C6)alkoxy group, a linear or branched (Ci-Ce)alkenyloxy group, a linear or branched halo(Ci-Ce)alkyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-Ce)alkyl    group, a   linear or   branched(Ci-C6)alkoxy(Ci-Ce)alkoxy group, a hydroxy group, a linear or branched hydroxy(Ci-Ce)alkyl group, an    acetyl    group, a   formyl group,a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?, wherein:- Cye represents an aryl group, a heteroaryl group, a cycloalkyl group, an arylalkyl group, or an arylalkenyl group,- Cy? represents an aryl group, cycloalkyl group, or a cycloalkylalkyl group, or the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms wherein said ring may be substituted by Ris and Ris’,♦ R13 represents a hydrogen atom, a halogen atom, or a linear or branched (Ci-C6)alkyl group,♦ R14 and R15 independently of one another, represent a hydrogen atom or a linear or branched (Ci-Ce)alkyl group,♦ Rie represents a -O-R3 group or a -NR17R17’ group,♦ R17 and R17’ independently of one another, represent a hydrogen atom, a linear or branched (Ci-Ce)alkyl, -SO2-CF3 group, or a -SO2-CH3 group,♦ Ris and Ris’ independently of one another, represent a hydrogen atom, a halogen atom, or a linear or branched (Ci-Ce)alkyl group,or the pair (Ris,Ris’) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 3 to 5 ring members,it being possible for the aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, arylalkyl, arylalkenyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl groups so defined to be substituted by from 1 to 4 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched halo(Ci-Ce)alkylidene, linear or branched (Ci-Ce)alkoxy, linear or branched (Ci-C6)alkoxy(Ci-Ce)alkoxy, a linear or branched halo(Ci-C6)alkyloxy group, hydroxy, a linear or branched hydroxy(Ci-C6)alkyl group, cyano, oxo, -NR’R”, -C(O)-OR’, cyclopropyl, 2,2-dimethylcyclopropyl, phenyl, pyridinyl, benzyl, (2,3,6-trifluorophenyl)methyl, -CH2-pyridinyl, -O-phenyl, -O-benzyl, -O-pyridinyl, -O-CH2-cyclopropyl, -O-CH2-pyridinyl, aryloxyalkyl, or heteroaryloxyalkyl, wherein R’ and R’ ’ independently of one another represent a hydrogen atom or linear or branched (Ci-C6)alkyl,their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base.

2. Compound according to claim 1, wherein X represents -O- or -N(R2)-.

3. Compound according to claim 1, wherein ........ represents a single bond.

4. Compound according to claim 1, wherein Yi represents -C(R4)(R5)-.

5. Compound according to claim 1, wherein Y2 represents -C(Rs)(R9)-5   6. Compound according to claim 1, which is a compound of Formula (I-e):owherein Ri, R4, R5, Rs, R9, Rio, Ru, R12, R13, Rie and X are as defined in claim 1.

7. Compound according to claim 1, wherein Ri represents an aryl group.

8. Compound according to claim 1, wherein Ri represents an aryl group which is substituted 10 by from 1 to 3 groups selected from halogen, linear or branched (Ci-Ce)alkyl, linear or branched halo(Ci-Ce)alkyl, linear or branched (Ci-Ce)alkoxy, cyano, or hydroxy.

9. Compound according to claim 1, wherein R2 represents a hydrogen atom or a methyl group.

10. Compound according to claim 1, wherein Rie represents a -O-R3 group.

11. Compound according to claim 1, wherein R3 represents a hydrogen atom, a linear or 15 branched (Ci-Ce)alkyl group, a linear or branched halo(Ci-Ce)alkyl group, -W1-OR3A, -Wi-0-C(0)-R3a, -Wi-NR3aR3b, -Wi-C(O)-NR3AR3b, -Wi-0-C(0)-0R3a, -Wi-O-C(O)-NR3aR3b, -Wi-O-P(O)-(OR3a)2, -W1-SO2-OR3A, or -Wi-Cyi, wherein:- Wi represents a bond, a -CH2- group, a -(CH2)2- group, a -(CH2)3- group, ora-CH(CH3)- group,- R3A and R3B independently of one another, represent a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxymethyl group, a methoxyethyl group, or a cyclopentyl group,or the pair (R3a,R3b) together with the nitrogen atom to which they are attached forms a morpholinyl group,- Cyi represents an indanyl group or a 5-methyl-2-oxo-l,3-dioxol-4-yl group.

12. Compound according to claim 1, wherein R3 represents a hydrogen atom.

13. Compound according to claim 1, wherein R4 represents a hydrogen atom, a halogen atom, a linear or branched (Ci-Ce)alkyl group, a branched (Ci-C6)alkyl group substituted by 2 linear (Ci-Ce)alkoxy groups, a linear or branched (C2-Ce)alkenyl group, a linear or branched (C2-Ce)alkenyloxy group, a linear or branched (Ci-C6)alkoxy(Ci-C6)alkyl group, a linear or branched (Ci-C6)alkoxy(C2-Ce)alkenyl group, a linear or branched (Ci-C6)alkoxy(Ci-C6)haloalkyl group, a -W2-Cy2 group, a -W3-L-Cy3 group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group, wherein- W2 represents a bond, a linear or branched (Ci-C4)alkylene group, a linear or branched (C2-C4)alkenylene group, or a linear or branched (C2-C4)alkynylene group,- W3 represents a bond, a linear or branched (Ci-Ce)alkylene group, a linear or branched (C2-Cs)alkynylene group, a linear or branched (Ci-C6)alkoxylene group, a branched (Ci-C4)hydroxyalkylene group, a linear or branched (Ci-C4)haloalkylene, or a -CH2-CH(R4e)-CH2- group,- L represents -O-, -S-, or -SO2-,- Cy2 represents an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, or a heterocycloalkyl group,- Cy3 represents an aryl group, a heteroaryl group, a heterocycloalkyl group, an arylalkyl group, or a heteroarylalkyl group.

14. Compound according to claim 1, wherein R4 represents a hydrogen atom, a bromine atom, a iodine atom, a methyl group, an ethyl group, a propyl group, a 3-methoxy-2-(methoxymethyl)propyl, a prop-l-en-l-yl group, a (prop-2-en-l-yl)oxy group, a methoxypropyl group, an ethoxypropryl group, a 3-ethoxyprop-1-en-lyl group, a 2,2-difluoro-3-methoxypropyl group, a -W2-Cy2 group, a -Wi-L-Cy? group, a -W4-NR4AR4B group, or a -CO-NR4CR4D group.5   15. Compound according to claim 1, wherein R4 represents a -W3-L-Cy3 group.

16. Compound according to claim 1, wherein R4 representswherein the wavy line indicates the covalent attachment site to the spirocyclohexane10 scaffold.

17. Compound according to claim 1, wherein R5 represents a hydrogen atom, or a methyl group.

18. Compound according to claim 1, wherein R& represents a phenyl group, a -SO2-phenyl group, or a -Ws-O-Cys group.15   19. Compound according to claim 1, wherein R7 represents a hydrogen atom, a methyl group,an ethyl group, a benzyl group, or a formyl group.

20. Compound according to claim 1, wherein Rs represents a hydrogen atom, a methyl group, an ethyl group, or an isopropyl group.

21. Compound according to claim 1, wherein R9 represents a hydrogen atom.

22. Compound according to claim 1, wherein Rio represents a hydrogen atom, a chlorine atom, a fluorine atom, a bromine atom, or a methyl group.

23. Compound according to claim 1, wherein Rn represents a hydrogen atom, a chlorine atom, a fluorine atom, a bromine atom, a methyl group, or a methoxy group.

24. Compound according to claim 1, wherein R12 represents a hydrogen atom, a fluorine atom, a bromine atom, a iodine atom, a chlorine atom, a methyl group, an ethyl group, a prop-1-enyl group, a -C=CH group, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, an isobutyloxy group, a 2-methoxypropan-2-yl group, a prop-2-en-l-yloxy group, a 2,2,2-trifluoroethoxy group, a methoxymethyl group, a methoxyethoxy group, a methoxypropoxy group, a hydroxy group, a hydroxymethyl group, a 1-hydroxyethyl group, an acetyl group, a formyl group, a -CH2-O-tetrahydrofuranyl group, -Cye, or -O-Cy?.

25. Compound according to claim 1, wherein the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring composed of from 5 to 8 ring members, which may contain 1 or 2 oxygen atoms, wherein said ring may be substituted by Ris and Ris’.

26. Compound according to claim 1, wherein the pair (Rn,Ri2) together with the carbon atoms to which they are attached forms a non-aromatic ring as follows:wherein Ri8 and Ris’ are as defined in claim 1.

27. Compound according to claim 1, wherein R13 represents a hydrogen atom, a fluorine atom,a bromine atom, or a methyl group.

28. Compounds according to claim 1, which are:-   (15,45)-4-(3-chl oroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-isoindole]-4-carboxylic acid;- (15,4S)-4-(3-chloro-4-fluoroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-isoindole]-4-carboxylic acid;- (15,4S)-4-(3-chloroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-[l,3]dioxolo[4,5- / |isoindole]-4-carboxylic acid;- (15,4S)-4-(3-chloro-4-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-[l,3]dioxolo[4,5- / |isoindole]-4-carboxylic acid;- (lr,2'5,45)-4-(3-chloro-2-methylanilino)-2'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;- (lr,2'(S',4(S)-4-(3-chloroanilino)-5'-fluoro-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;- (lr,2'5,45)-4-(3-chloroanilino)-5'-fluoro-2'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid;- (lr,2'5,45)-5'-chloro-4-(3-chloroanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;- (lr,2'5,45)-4-(3-chloroanilino)-6'-methoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;- (lr,2'£,45)-4-(3-chloroanilino)-6'-ethoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;-   (Ir,2'5,45)-4-(3-chl oroanilino)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6'-[(propan-2-yl)oxy]-2',3'-dihydrospiro[cyclohexane-l, l'-indene]-4-carboxylic acid;- (lr,2'5,45)-4-(3-chloroanilino)-6'-(2-methoxyethoxy)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid;- (lr,2'5,45)-5'-chloro-4-(3-chloroanilino)-6'-methoxy-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid;- (lr,45,8'5)-4-(3-chloroanilino)-8'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-277-spiro[cyclohexane-l,7'-indeno[5,6-Z>][l,4]dioxepine]-4-carboxylic acid;- (lr,45,7'5)-4-(3-chloroanilino)-7'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid;- (lr,45,6'5)-4-(3-chloroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-27Z-spiro[cyclohexane-l,5'-indeno[5,6-t / ][l,3]dioxole]-4-carboxylic acid;- (lr,45,6'5)-4-(3-chloro-4-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-t / ][l,3]dioxole]-4-carboxylic acid;-   (Ir,45,6'5)-4-(3-chl oro-2-fluoroanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-d][l,3]dioxole]-4-carboxylic acid;-   (Ir,45,6'5)-4-(3-chl oro-2-methylanilino)-6'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-d][l,3]dioxole]-4-carboxylic acid;- (lr,45,6'5)-4-(3-chloroanilino)-2',2'-dimethyl-6'-[(2J?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-d][l,3]dioxole]-4-carboxylic acid;- (lr,2'5,45)-4-(3-chloroanilino)-5',6'-dimethyl-2'-[(2J?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;- (lr,27?,4J?)-4-(3-chloroanilino)-5',6'-dimethyl-2'-[(2 / ?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2\3'-dihydrospiro[cyclohexane-l,r-indene]-4-carboxylic acid;-   (Ir,2'5,45)-4-(3-chl oroanilino)-6'-(l-hydroxyethyl)-2'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid;- (lr,2'5,4S)-4-(3-chloroanilino)-6'-(2-methoxypropan-2-yl)-2'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l, l'-indene]-4-carboxylic acid;- (lr,2'£,4S)-4-(3-chloroanilino)-6'-(methoxymethyl)-2'-[(2??)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3'-dihydrospiro[cyclohexane-l,l'-indene]-4-carboxylic acid;- (lr,4£,6'S)-4-(3-chloroanilino)-6'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-6',7'-dihydro-277-spiro[cyclohexane-l,5'-indeno[5,6-tZ][l,3]dioxole]-4-carboxylic acid;- (lr,4£,7'S)-4-(3-chloroanilino)-7'-[(27?)-3-{[(57?,87?)-8-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}-2-methylpropyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-^][l,4]dioxine]-4-carboxylic acid;- (lr,3'5,45,7'5)-4-(3-chloroanilino)-3,-methyl-7'-[(2J?)-2-methyl-3-{[(5^)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-^][l,4]dioxine]-4-carboxylic acid;- (lr,37?,45,7'5)-4-(3-chloroanilino)-3'-methyl-7'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2',3',7',8'-tetrahydrospiro[cyclohexane-l,6'-indeno[5,6-Z>][l,4]dioxine]-4-carboxylic acid;- (lr,45,4'5,8'S)-4-(3-chloroanilino)-4'-methyl-8'-[(27?)-2-methyl-3-{[(5J?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-27 / -spiro[cyclohexane-l,7'-indeno[5,6-Z>][l,4]dioxepine]-4-carboxylic acid;- (lr,4£,47?,8'5)-4-(3-chloroanilino)-4'-methyl-8'-[(27?)-2-methyl-3-{[(57?)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-3',4',8',9'-tetrahydro-27 / -spiro[cyclohexane-l,7'-indeno[5,6-Z>][l,4]dioxepine]-4-carboxylic acid.

29. A compound of Formula (IIIA):(mA)wherein Rn, R12, Yi, Y2, Y3, Y4 and ........ are as defined in claim 1,for use as synthesis intermediate for the preparation of compounds of Formula (I) according to claim 1.5   30. Compound of Formula (IIIA) according to claim 29 which is 6'-bromo-27 / -spiro[cyclohexane-1,5'-indeno[5,6<7] [ 1,3 ]dioxol]-4-one.

31. A compound of Formula (VA):Owherein Ri, Rn, R12, X, Y2, Y3, Y4 and           are as defined in claim 1, and Halrepresents a halogen atom and PG represents a protecting group of the carboxylic acid 10 function,as synthesis intermediate for the preparation of compounds of Formula (I) according to claim 1.

32. Compound of Formula (VA) according to claim 31 which is methyl (Ls,4.s)-2'-bromo-4-(3-chloroanilino)spiro[cyclohexane-l,r-indene]-4-carboxylate or methyl (ls,4s)-6'-bromo-4-15 (3-chloroanilino)-277-spiro[cyclohexane-l,5'-indeno[5,6-£ / ][l,3]dioxole]-4-carboxylate.

33. Pharmaceutical composition comprising a compound of Formula (I) according to any one of claims 1 to 28 or an addition salt thereof with a pharmaceutically acceptable acid or base in combination with one or more pharmaceutically acceptable excipients.

34. Pharmaceutical composition according to claim 33 for use as anti-apoptotic inhibitors.

35. Pharmaceutical composition according to claim 33 for use in the treatment of cancer and of auto-immune and immune system diseases.

36. Pharmaceutical composition according to claim 35 wherein the cancer is an haematological malignancy or a solid tumor.

37. Pharmaceutical composition according to claim 36 wherein the haematological malignancy is selected from myeloma, multiple myeloma, lymphoma, Non-Hodgkin Lymphoma (NHL), Diffuse Large B-cell Lymphoma (DLBCL), leukemia, Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML).

38. Pharmaceutical composition according to claim 36 wherein the solid tumor is selected from bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer.

39. Compound of Formula (I) according to any one of claims 1 to 28, or an addition salt thereof with a pharmaceutically acceptable acid or base, for use as anti-apoptotic inhibitor.

40. Compound of Formula (I) according to any one of claims 1 to 28, or an addition salt thereof with a pharmaceutically acceptable acid or base, for use in the treatment of myeloma, multiple myeloma, lymphoma, Non-Hodgkin Lymphoma (NHL), Diffuse Large B-cell Lymphoma (DLBCL), leukemia, Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML) bladder, brain, breast, uterus, oesophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer,pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer.

41. Combination of a compound of Formula (I) according to any one of claims 1 to 28 with anti-cancer agents selected from genotoxic agents, mitotic poisons, anti-metabolites, 5 proteasome inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators, E3 ligase inhibitors, chimeric antigen receptor T-cell therapy and antibodies.

42. Pharmaceutical composition comprising a combination according to claim 41 in combination with one or more pharmaceutically acceptable excipients.10   43. Combination according to claim 41 for use in the treatment of cancer.