Arylalkyloxyindole compounds and derivatives and their use

Abstract

The inventors have now succeeded in developing alkyloxyindole and arylalkyloxyindole compounds, in particular 5-alkyloxyindole, 4-arylalkyloxyindole, 5- arylalkyloxyindole and 6-arylalkyloxyindole compounds, and derivatives. These compounds have the advantage of modulating, in particular inhibiting, the YAP(TAZ)- TEAD interaction, in particular targeting the palmitate pocket. The present invention relates to alkyloxyindole and arylalkyloxyindole compounds and derivatives, including their pharmaceutically acceptable salts and solvates, which are useful as modulators, in particular as inhibitors, of the YAP(TAZ)-TEAD interaction targeting the palmitate pocket, and are useful as therapeutic compounds, particularly in the treatment of cancer.

Description

[0001] ARYLALKYLOXYINDOLE COMPOUNDS AND DERIVATIVES AND THEIR

[0002] USE

[0003] The present invention relates to alkyloxyindole and arylalkyloxyindole compounds and derivatives, including their pharmaceutically acceptable salts and solvates, which are useful as modulators, in particular as inhibitors, of the YAP(TAZ)-TEAD interaction targeting the palmitate pocket, and are useful as therapeutic compounds, particularly in the treatment of cancer.

[0004] BACKGROUND OF THE INVENTION

[0005] The Hippo pathway is involved in organ size control and tissue homeostasis by regulating cell growth, proliferation and apoptosis. It consists in a cascade of kinases including Mstl / 2 (mammalian ste20-like protein kinase), Savl (scaffold protein Salvador), Latsl / 2 (large tumor suppressor kinase) and Mob proteins (mps one binder kinase), which regulates the phosphorylation of the transcription co-activator YAP (Yes associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif) in order to control their nuclear import and their interaction with TEAD (Transcriptional Enhanced Associated Domain) (Piccolo et al., Physiol. Rev., 2014, 94, 1287-1312).

[0006] The phosphorylation of S127 of YAP (S89 in TAZ) promotes its cytoplasmic retention by the protein 14-3-3 and the phosphorylation of S381 (S311 in TAZ) induces its degradation. Conversely, unphosphorylated, YAP and TAZ enter into the nucleus, interact with TEAD and drive the target gene expressions in charge of cell proliferation and apoptosis avoidance such as CTGF (connective tissue growth factor), Cyr61 (cysteine-rich angiogenic protein), Survivin (also known as Birc-5) and AXL.

[0007] In the nucleus, YAP and TAZ compete with other natural TEAD ligands, namely VGLL (Transcriptional cofactor Vestigial like protein family) which are nuclear regulators of the transcriptional activity of TEAD s (Pobbati et al., Cancer Biol. Then, 2013, 14, 390-398). More recently FAM181A and FAM181B, two new TEAD interactors have been identified (Bokhovchuk et al., Protein Sci. Publ. Protein Soc., 2020, 29, 509-520). These proteins are expressed most prominently in neural tissues, where Faml81A is exclusively expressed during embryonic development (Marks et al., Gene, 2016, 575, 438-451). Several stimuli such as mechanical force, cell adhesion, serum starvation, or energy stress promote activation of kinases and regulate YAP / TAZ localization. In contrast, osmotic stress, high cell density and cell detachment induce cytoplasmic translocation of TEAD (Lin et al., Trends Biochem. Sci., 2017, 42, 862-872). A dysregulation of this equilibrium brings to abnormal and excessive proliferation leading to cancer where YAP / TAZ and TEAD are overexpressed (Wang et al., Cell Rep., 2018, 25, 1304-1317. e5). Thus, inhibition of YAP / TAZ-TEAD complexes is a pertinent strategy for regenerative therapies with activators, in particular for cancer therapy (Dey et al., Nat. Rev. Drug Discov., 2020, 19, 480-494), more particularly for the treatment of breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers.

[0008] YAP / TAZ and TEADs form a complex through the interaction of the N-terminal domain of YAP (and TAZ) (TEAD Binding Domain: TBD) and the C-terminal domain of TEAD (YAP / TAZ Binding Domain: Y / TBD). In their pioneer work, Li et al. (Li et al., Genes Dev., 2010, 24, 235-240) defined the three interfaces of contact between TEADI209-426 and YAP50- 171 and their respective importance in the binding. In 2016, was reported for the first time, that Y / TBD of TEAD2 and TEAD3 are palmitoylated in an internal hydrophobic pocket (Noland et al., Structure, 2016, 24, 179-186; Chan et al., Nat. Chem. Biol., 2016, 12, 282- 289). This palmitoylation is required for the stability of TEAD, the interaction with YAP or TAZ and regulates the output of the Hippo pathway. This internal pocket clearly appears as the third druggable site of TEAD.

[0009] Chemical control of the Hippo pathway can be divided into three main strategies: (i) favor the phosphorylation (Song et al., Eur. J. Med. Chem., 2020, 203, 112618) or the nuclear import of YAP or TAZ, (ii) physically inhibit YAP / TAZ-TEAD interaction, (iii) interfer on the YAP / TAZ-TEAD transcriptional targets (Pobbati et al., Theranostics, 2020, 10, 3622- 3635).

[0010] Considering the second strategy, modified linear and cyclic YAP-like peptides and a peptide composed of the VGLL4 interface 2 domain and the YAP interface 3 domain (super- TDU) were firstly developed to compete with YAP for binding TEADs (Zhang et al., ACS Med. Chem. Lett., 2014, 5, 993-998; Jiao et al., Cancer Cell, 2014, 25, 166-180; Zhou et al., FASEB J., 2015, 29, 724-732). These modified peptides present high affinity for TEAD. Only recently, the first non-peptidic inhibitor, CPD3.1, targeting the interface 3 was published (Smith et al., J. Med. Chem., 2019, 62, 1291-1305). As a non-selective YAP- TEAD inhibitor, CPD3.1 has an IC50 ranging between 33 and 44 μM on the four members of TEAD family as measured in HeLa cells transfected by a Gal4-luc reporter together with the vectors for Gal4-TEADx. Prior to the discovery of the presence of palmitate in the internal pocket of TEAD, identified niflumic, bromoflufenamic and flufenamic acids were identified as TEAD ligands of the central pocket (Pobbati et al., Structure, 2015, 23, 2076- 2086). While niflumic acid has a KD of 28 μM for TEAD4 (measured by isothermal calorimetry), it only presents cellular effect at 150 μM. A small molecule inhibiting YAP- TEAD complex transcriptional activity through the presumed formation of a covalent bond with the cysteine residue in the central pocket was also reported (Bum-Erdene et al., Cell Chem. Biol., 2019, 26, 378-389. el3). Using fluorescence polarization experiments, the authors were able to measure the inhibitory activity of their compounds for the YAP-TEAD4 interaction. TED-347 possessed an EC50 of 5.9 μM and a similar IC50 in a HEK293 cellbased assay. TEAD-347 was found to be toxic in EGFR-mutant NSCLC cell lines and replaced by another covalent TEAD ligand which bears an acrylamide moiety (Kurpa et al., Cancer Cell, 2020, 37, 104-122. el2). This new compound bearing a vinylamide moiety (MYF-01-037) is supposed to covalently bind to C359 (TEAD1) in the palmitate pocket as another vinylsulfamide: DCTEAD-02 (Lu et al., Eur. J. Med. Chem., 2019, 184, 111767) and K-379 (Kaneda et al., Am. J. Cancer Res., 2020, 10, 4399-4415). But the first ligand of the palmitate pocket reported so far is MGH-CP1 (Li et al., Cell Stem Cell, 2020, 26, 675- 692. e8; WO 2017 / 053706 Al) which was very recently followed by two new compounds (Holden et al., Cell Rep., 2020, 31, 107809).

[0011] WO 2018 / 204532 Al and WO 2020 / 097389 Al disclose inhibitors of hTEAD autopalmitoylation. VT103 is the first selective inhibitor of hTEADl autopalmitoylation while VT107 is 50 fold less active than its enantiomer (Tang et al., Mol. Cancer Ther., 2021, 20, 986-998).

[0012] However, there is still a need for compounds having an activity as modulators, in particular as inhibitors, associated with one or more members of the Hippo pathway network, such as compounds that modulate the interaction between YAP / TAZ and TEAD, and that may be of therapeutic value in the treatment of cancer, in particular cancers that are modulated by the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket.

[0013] SUMMARY OF THE INVENTION

[0014] The inventors have now succeeded in developing alkyloxyindole and arylalkyloxyindole compounds, in particular 5-alkyloxyindole, 4-arylalkyloxyindole, 5-arylalkyloxyindole and 6-arylalkyloxyindole compounds, and derivatives. These compounds have the advantage of modulating, in particular inhibiting, the YAP(TAZ)-TEAD interaction, in particular targeting the palmitate pocket.

[0015] The invention therefore relates to compounds of general Formula I, their pharmaceutically acceptable salts and solvates as well as methods of use of such compounds or compositions comprising such compounds for the treatment of cancer, in particular cancers that are modulated by the YAP(TAZ)-TEAD interaction, in particular targeting the palmitate pocket.

[0016] In a general aspect, the invention provides compounds of general Formula I:

[0017] I, a pharmaceutically acceptable salt or a solvate thereof, wherein

[0018] R1is selected from benzyl, (l,l’-biphenyl)-4-ylmethyl, (adamantan-l-yl)methyl and (halogenocyclohexyl)methyl;

[0019] R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, C1- C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6- alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, C1-C4-alkyloxy carbonylaryl, C1-C4- alkyl oxy carbonylheteroaryl, vinylsulfonamidoaryl, haloaryl-C1-C4-alkyl, nitroaryl-C1- C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4- alkyl amidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinyl sulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl- C1-

[0020] R3is selected from H, cyanovinyl, 3 -amino-3 -carb oxy propyl, hydroxy-C1-C6-alkyl, C1- C4-alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4- alkyl oxy oxopropenyl and oxo-C1-C6-alkyl;

[0021] A is C-R4or CH-R4wherein R4is H, or

[0022] R3and R4form together a group selected from wherein

[0023] R5and R6are independently selected from H, OH, C(O)OH, C1-C4- alkyloxycarbonyl, NO2, NH2, CN and vinylsulfonamido;

[0024] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl;

[0025] > is a single bond or a double bond; with the proviso that:

[0026] R2and R3are not both H when R1is benzyl,

[0027] R2is not t-butyloxycarbonyl, carboxyethyl, methoxycarbonylmethyl, 2-

[0028] (m ethoxy carbonyl)phenyl, 3-(ethoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 3- cyanophenyl, benzyl, 4-chlorobenzyl, 4-fluorobenzyl, 3 -fluorobenzyl, 4- trifluoromethylbenzyl or 3-methoxycarbonylbenzyl when R1is benzyl and R3is H,

[0029] R3is not hydroxyethyl when R1is benzyl and R2is H,

[0030] R5is not NO2 or OH when R6and R7are H and R1is benzyl,

[0031] R6is not NO2 or methoxy when R5and R7are H and R1is benzyl, R7is not H when R5and R6are H; and

[0032] ! is a double bond when A is C-R4.

[0033] The invention also relates to a compound of Formula I:

[0034] I, a pharmaceutically acceptable salt or solvate thereof, wherein

[0035] R1is selected from C1-C6-alkyl, halo-C1-C6-alkyl, aryl-C1-C4-alkyl, haloaryl-C1-C4- alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl- C1-C4-alkyl; R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido- C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6- alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6-alkyloxy carbonyl, aryl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl, C1-C4-alkyloxy carbonylaryl, C1-C4-alkyloxy carbonylheteroaryl, vinylsulfonamidoaryl, aryl-C1-C4-alkyl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C 1 - C4-alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl;

[0036] R3is selected from H, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6- alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1-C4- alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy - C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, formyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3 -amino-3 -carboxypropyl, C1-C6-alkyl, carboxy- C1-C6-alkyl and C1-C4-alkyloxycarbonyl-C1-C6-alkyl;

[0037] A is N or C-R4or CH-R4wherein R4is H, or

[0038] R3and R4form together a group selected from wherein R5and R6are independently selected from H, OH, C(O)OH, C1-C4- alkyloxycarbonyl, NO2, NH2, CN and vinylsulfonamido;

[0039] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl;

[0040] ! is a single bond or a double bond; with the proviso that:

[0041] R7is not H when R5and R6are H; and

[0042] I is a double bond when A is N or C-R4;for use use in treating cancer.

[0043] The invention also relates to the use of compounds of Formula I, or their pharmaceutically acceptable salts and solvates, for modulating, in particular for inhibiting, the YAP(TAZ)- TEAD interaction.

[0044] DETAILED DESCRIPTION OF THE INVENTION

[0045] As detailed above, the invention relates to a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof.

[0046] Particular compounds of Formula I, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and A are defined as follows:

[0047] R1is selected from benzyl, (l,l’-biphenyl)-4-yl-methyl, (adamantan-l-yl)methyl and (halogenocyclohexyl)methyl; in particular R1is selected from benzyl, (l,l’-biphenyl)-4- ylmethyl, (adamantan-l-yl)methyl and (4,4-difluorocyclohexyl)methyl;

[0048] R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, C1-C4- alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, C1-C4-alkyloxy carbonylaryl, C1-C4- alkyl oxy carbonylheteroaryl, vinylsulfonamidoaryl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4- alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C 1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C1-C4- alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from H, carboxy-C3-C6-alkyl, C1-C4-alkyloxycarbonyl-C2-C6-alkyl, C1-C4- alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carb oxy phenyl, carboxypyridinyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, halo- C1-C4-alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, halophenyl-C1-C4-alkyl, nitrophenyl-C1-C4-alkyl, aminophenyl-C1-C4-alkyl, C1-C4- alkylamidophenyl-C1-C4-alkyl, halo-C1-C4-alkylamidophenyl-C1-C4-alkyl, C1-C4- alkylsulfonamidophenyl-C1-C4-alkyl, vinylsulfonamidophenyl-C1-C4-alkyl, cyanophenyl- C1-C4-alkyl, halo-C1-C4-alkylphenyl-C1-C4-alkyl, carboxyphenyl-C1-C4-alkyl and C1- C4-alkyloxycarbonylphenyl-C1-C4-alkyl; more particularly R2is selected from H, carboxy - C3 -C6-alkyl, C1-C4-alkyloxycarbonyl-C2-C6-alkyl, C1-C2-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C2-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido- C1-C6-alkyl, vinylsulfonamido-C l-C6-alkyl, C1-C6-alkyloxy carbonyl, carboxyphenyl, carboxypyridinyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, halo-C 1-C2- alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4- alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, halophenyl-C1-C2-alkyl, nitrophenyl- C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C 1- C4-alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, halo-C1-C4-alkylphenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C2- alkyl; still more particularly R2is selected from H, carboxy-C3-C4-alkyl, methoxy carbonyl- C2-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, haloacetamido-C1-C4- alkyl, C1-C2-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4- alkyloxycarbonyl, carboxyphenyl, carboxypyridinyl, 3-halophenyl, 3 -hydroxyphenyl, 3- nitrophenyl, 3 -aminophenyl, halo-C l-C2-alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, bromophenyl-C1-C2-alkyl, 2-fluorophenyl-C1-C2-alkyl, nitrophenyl-C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C1-C2- alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, halo-C1-C4-alkylphenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl, 2-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl and 4-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl; still more particularly R2is selected from H, carboxy-C3-C4-alkyl, methoxycarbonyl-C2-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, chloroacetamido-C1-C4-alkyl, C1-C2-alkylsulfonamido-C1-C4- alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4-alkyloxy carbonyl, carboxyphenyl, carboxypyridinyl, 3-halophenyl, 3 -hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 3-halo- C1-C2-alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4- alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, bromophenyl-C l-C2-alkyl, 2- fluorophenyl-C1-C2-alkyl, nitrophenyl-C l-C2-alkyl, aminophenyl-C l-C2-alkyl, C1-C4- alkylamidophenyl-C1-C2-alkyl, chloro-C1-C2-alkylamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, halo-C1-C2-alkylphenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl, 2-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl and 4-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl; even more particularly R2is selected from H, 3 -carboxypropyl, 4-carboxybutyl, 4-(m ethoxy carbonyl)butyl, acetamidoethyl, acetamidopropyl, acrylamidoethyl, aery 1 amidopropyl, chloroacetamidoethyl, chloroacetamidopropyl, methanesulfonamidoethyl, methanesulfonamidopropyl, vinylsulfonamidoethyl, vinylsulfonamidopropyl, tert-butyloxycarbonyl, 2-carboxyphenyl, 3 -carb oxy phenyl, 4-carboxyphenyl, 3-carboxypyridin-2-yl, 6-carboxypyri din-2 -yl, 3- fluorophenyl, 3 -chlorophenyl, 3 -bromophenyl, 3 -iodophenyl, 3 -hydroxyphenyl, 3- nitrophenyl, 3 -aminophenyl, 3 -trifluom ethylphenyl, 2-ethoxy carbonylphenyl, 3- methoxycarbonylphenyl, 4-methoxycarbonylphenyl; 3-vinylsulfonamidophenyl, 3- methoxycarbonylpyridin-2-yl, 5-methoxycarbonylpyridin-2-yl, 5-carboxypyridin-2-yl, 2- nitrobenzyl, 2-aminobenzyl, 2-(chloromethylacetamido)benzyl, 2-vinylsulfonamidobenzyl,

[0049] 3 -nitrobenzyl, 3 -aminobenzyl, 3-(chloromethylacetamido)benzyl, 3- vinylsulfonamidobenzyl, 4-nitrobenzyl, 4-aminobenzyl, 4-(chloromethylacetamido)benzyl,

[0050] 4-vinylsulfonamidobenzyl, 2-cyanobenzyl, 3 -cyanobenzyl, 4-cyanobenzyl, 2-bromobenzyl, 3 -bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 2-trifluoromethylbenzyl, 3- trifluoromethylbenzyl, 4-methoxycarbonylbenzyl, 4-carboxybenzyl, 3 -carboxybenzyl, 2- methoxycarbonylbenzyl, and 2-carboxybenzyl;

[0051] R3is selected from H, cyanovinyl, 3 -amino-3 -carb oxy propyl, hydroxy-C1-C6-alkyl, C1-C4- alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4- alkyl oxy oxopropenyl and oxo-C1-C6-alkyl; in particular R3is selected from H, cyanovinyl, 3 -amino-3 -carboxypropyl, hydroxy-C1-C4-alkyl, C1-C4-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4-alkyloxy oxopropenyl and oxo-C1-C4-alkyl; more particularly R3is selected from H, cyanovinyl, 3 -amino-3 -carboxypropyl, hydroxy-C 1-C4- alkyl, C1-C2-alkyl sulfonamido-C1-C4-alkyl, vinylsulfonamido-C l-C2-alkyl, C1-C4- alkyl oxy oxopropenyl and oxo-C1-C4-alkyl; still more particularly R3is selected from H, cyanovinyl, 3 -hydroxybutyl, methylsulfonamidoethyl, vinylsulfonamidoethyl, tert- butyloxy-3-oxopro-l-pen-l-yl and 3-oxobutyl;

[0052] A is C-R4or CH-R4, in particular A is C-R4wherein R4is H, or

[0053] R3and R4form together a group selected from wherein

[0054] R5and R6are independently selected from H, OH, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(0)0me, NO2, NH2, CN and vinylsulfonamido; still more particularly R5is selected from H, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido, and R6is selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido;

[0055] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; particularly R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, C1-C2-alkyl and C1-C4-alkyloxy carbonyl; still more particularly R7is selected from H, methyl and tert-butyloxy carbonyl;

[0056] I is a single bond or a double bond; particularly is a single bond; with the proviso that:

[0057] R2and R3are not both H when R1is benzyl;

[0058] R2is not t-butyloxycarbonyl, carboxyethyl, methoxycarbonylmethyl, 2- (m ethoxy carbonyl)phenyl, 3-(ethoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 3- cyanophenyl, benzyl, 4-chlorobenzyl, 4-fluorobenzyl, 3 -fluorobenzyl 4- trifluoromethylbenzyl or 3-methoxycarbonylbenzyl when R1is benzyl and R3is H;

[0059] R3is not hydroxyethyl when R1is benzyl and R2is H;

[0060] R5is not NO2 or OH when R6and R7are H and R1is benzyl;

[0061] R6is not NO2 or methoxy when R5and R7are H and R1is benzyl;

[0062] R7is not H when R5and R6are H; and

[0063] ' is a double bond when A is C-R4.

[0064] Halogens include a fluorine atom, an iodine atom, a chlorine atom and a bromine atom. C1-C6-alkyl include hexyl, in particular n-hexyl, neohexyl, isohexyl, sec-hexyl or tert-hexyl; pentyl, in particular n-pentyl, neopentyl, isopentyl, sec-pentyl or tert-pentyl; butyl, in particular n-butyl, isobutyl, sec-butyl or tert-butyl; propyl, in particular n-propyl or isopropyl; ethyl or methyl. C1-C4-alkyl include butyl, in particular n-butyl, isobutyl, sec-butyl or tert-butyl; propyl, in particular n-propyl or isopropyl; ethyl or methyl.

[0065] In the formula I as used herein, the atoms of the central core are numbered as follows:

[0066] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 4, 5 or 6 of the central core.

[0067] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 4 or 5 of the central core.

[0068] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 4 or 6 of the central core.

[0069] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 5 or 6 of the central core.

[0070] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 4 of the central core.

[0071] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 5 of the central core.

[0072] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 6 of the central core. In one embodiment, the compounds of Formula I are those wherein I is a double bond.

[0073] In one embodiment, the compounds of Formula I are those wherein I is a single bond.

[0074] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 4 of the central core and I is a double bond.

[0075] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 5 of the central core and ! is a double bond.

[0076] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 6 of the central core and I is a double bond.

[0077] In one embodiment, the compounds of Formula I are those wherein the group -O-R1is located in position 5 of the central core and I is a single bond.

[0078] In one embodiment, the compounds of Formula I are those wherein R1is benzyl.

[0079] In one embodiment, the compounds of Formula I are those wherein R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarboxy-C1-C6-alkyl, C1-C4-alkylamido-C 1 -C6- alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, vinylsulfonamido- C1-C6-alkyl, C1-C6-alkyloxy carbonyl, carboxyaryl, carboxyheteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, C1-C4-alkyloxy carbonylaryl, C1- C4-alkyl oxy carb oxy heteroaryl, vinylsulfonamidoaryl, haloaryl-C1-C4-alkyl, nitroaryl-C1- C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C 1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C 1 -C4- alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from H, carboxy-C l-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido- C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl and halo-C1-C4-alkylaryl.

[0080] In one embodiment, the compounds of Formula I are those wherein R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarboxy-C1-C6-alkyl, C1-C4-alkylamido-C 1 -C6- alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, vinylsulfonamido- C1-C6-alkyl, C1-C6-alkyloxy carbonyl, carboxyaryl, carboxyheteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, C1-C4-alkyloxy carbonylaryl, C1- C4-alkyl oxy carb oxy heteroaryl, vinylsulfonamidoaryl, haloaryl-C1-C4-alkyl, nitroaryl-C1- C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C 1 -C4- alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl.

[0081] In one embodiment, the compounds of Formula I are those wherein R2is H.

[0082] In one embodiment, the compounds of Formula I are those wherein R1is benzyl and R2is H.

[0083] In one embodiment, the compounds of Formula I are those wherein R3is selected from methylsulfonamido-C1-C6-alkyl, cyanovinyl, 3 -amino-3 -carboxypropyl, hydroxy-C1-C6- alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4-alkyloxy oxopropenyl and oxo-C1-C6-alkyl.

[0084] In one embodiment, the compounds of Formula I are those wherein R3is H.

[0085] In one embodiment, the compounds of Formula I are those wherein R1is benzyl and R3is H.

[0086] In one embodiment, the compounds of Formula I are those wherein R2is C1-C6- alkyl oxy carbonyl or carboxyaryl and R3is C1-C4-alkyloxy oxopropenyl, oxo-C1-C6-alkyl or cyanovinyl.

[0087] In one embodiment, the compounds of Formula I are those wherein A is CH. In one embodiment, the compounds of Formula I are those wherein R1is benzyl and A is

[0088] CH.

[0089] In one embodiment, the compounds of Formula I are those wherein R1is benzyl, R2is H and A is CH.

[0090] In one embodiment, the compounds of Formula I are those wherein R1is benzyl, R3is H and A is CH.

[0091] In one embodiment, the compounds of Formula I are those wherein R2and R3are not H.

[0092] In one embodiment, the compounds of Formula I are those wherein R1is benzyl and R2and R3are not H.

[0093] In one embodiment, the compounds of Formula I are those wherein A is C-R4and R3and R4form together the following group:

[0094] In one embodiment, the compounds of Formula I are those wherein R1is benzyl, A is C-R4and R3and R4form together the following group:

[0095] In one embodiment, the compounds of Formula I are those wherein R1is benzyl, R2is H, A is C-R4and R3and R4form together the following group:

[0096] In one embodiment, the compounds of Formula I are those wherein A is C-R4and R3and R4form together the following group: wherein

[0097] R5and R6are independently selected from H, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(O)Ome, NO2, NH2, CN and vinylsulfonamido; still more particularly R5is selected from H, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido, and R6is selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido; and

[0098] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; particularly R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, C1-C2-alkyl and C1-C4-alkyloxy carbonyl; still more particularly R7is selected from H, methyl and tert-butyloxycarbonyl; with the proviso that: R5is not NO2 or OH when R6and R7are H and R1is benzyl;

[0099] R6is not NO2 or methoxy when R5and R7are H and R1is benzyl; and

[0100] R7is not H when R5and R6are H.

[0101] In one embodiment, the compounds of Formula I are those wherein R1is benzyl, A is C-R4and R3and R4form together the following group: wherein

[0102] R5and R6are independently selected from H, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(O)Ome, NO2, NH2, CN and vinylsulfonamido; still more particularly R5is selected from H, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido, and R6is selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido; and

[0103] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; particularly R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, C1-C2-alkyl and C1-C4-alkyloxy carbonyl; still more particularly R7is selected from H, methyl and tert-butyloxycarbonyl; with the proviso that:

[0104] R5is not NO2 or OH when R6and R7are H; R6is not NO2 or methoxy when R5and R7are H; and

[0105] R7is not H when R5and R6are H.

[0106] In one embodiment, the compounds of Formula I are those wherein R1is benzyl, R2is H, A is C-R4and R3and R4form together the following group: wherein

[0107] R5and R6are independently selected from H, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(O)Ome, NO2, NH2, CN and vinylsulfonamido; still more particularly R5is selected from H, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido, and R6is selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido; and;

[0108] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; particularly R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, C1-C2-alkyl and C1-C4-alkyloxy carbonyl; still more particularly R7is selected from H, methyl and tert-butyloxycarbonyl; with the proviso that:

[0109] R5is not NO2 or OH when R6and R7are H;

[0110] R6is not NO2 or methoxy when R5and R7are H; and R7is not H when R5and R6are H.

[0111] In one embodiment, the compounds of Formula I are those of Formula II:

[0112] II, or pharmaceutically acceptable salts or solvates thereof, wherein

[0113] R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments.

[0114] Preferred compounds of Formula II, or pharmaceutically acceptable salts or solvates thereof, are those wherein the group -O-R1is located in position 4, 5 or 6 of the central core. In one embodiment, the compounds of Formula I are those of Formula III: or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments. In one embodiment, the compounds of Formula I are those of Formula IV:

[0115] IV, or pharmaceutically acceptable salts or solvates thereof, wherein

[0116] R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments.

[0117] Preferred compounds of Formula IV, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0118] R1is benzyl; R2is carboxyaryl or carb oxy heteroaryl; in particular R2is carboxyphenyl or carb oxy pyridyl; more particularly R2is selected from 2-carboxyphenyl, 3 -carboxyphenyl, 4-carboxyphenyl and 6-carboxypyridin-2-yl;

[0119] R3is H; and

[0120] R4is H. In one embodiment, the compounds of Formula I are those of Formula V:

[0121] or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments.

[0122] Preferred compounds of Formula V, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0123] R1is benzyl;

[0124] R2is carboxyaryl or carb oxy heteroaryl; in particular R2is carboxyphenyl or carb oxy pyridyl; more particularly R2is selected from 2-carboxyphenyl, 3 -carboxyphenyl, 4-carboxyphenyl and 6-carboxypyridin-2-yl;

[0125] R3is H; and

[0126] R4is H.

[0127] In one embodiment, the compounds of Formula I are those of Formula VI: or pharmaceutically acceptable salts or solvates thereof, wherein

[0128] R1, R2and R3are as defined above with respect to Formula I and any of its embodiments.

[0129] In one embodiment, the compounds of Formula I are those of Formula VII:

[0130] VII, or pharmaceutically acceptable salts or solvates thereof, wherein

[0131] R1and R2are as defined above with respect to Formula I and any of its embodiments.

[0132] Preferred compounds of Formula VII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0133] R1is benzyl; and

[0134] R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, C1-C4- alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, C1-C4-alkyloxy carbonylaryl, C1-C4- alkyl oxy carbonylheteroaryl, vinylsulfonamidoaryl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4- alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C 1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C 1 -C4- alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from carboxy-C3-C6-alkyl, C1-C4-alkyloxycarbonyl-C2-C6-alkyl, C1-C4- alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carb oxy phenyl, carboxypyridinyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, halo-C1-C4-alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, halophenyl-C1-C4-alkyl, nitrophenyl-C1-C4-alkyl, aminophenyl-C1-C4-alkyl, C1-C4- alkylamidophenyl-C1-C4-alkyl, halo-C1-C4-alkylamidophenyl-C1-C4-alkyl, C1-C4- alkylsulfonamidophenyl-C1-C4-alkyl, vinylsulfonamidophenyl-C1-C4-alkyl, cyanophenyl- C1-C4-alkyl, halo-C1-C4-alkylphenyl-C1-C4-alkyl, carboxyphenyl-C1-C4-alkyl and C1- C4-alkyloxycarbonylphenyl-C1-C4-alkyl; more particularly R2is selected from carboxy - C3 -C6-alkyl, C1-C4-alkyloxycarbonyl-C2-C6-alkyl, C1-C2-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C2-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido- C1-C6-alkyl, vinylsulfonamido-C l-C6-alkyl, C1-C6-alkyloxy carbonyl, carboxyphenyl, carboxypyridinyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, halo-C 1-C2- alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4- alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, halophenyl-C1-C2-alkyl, nitrophenyl- C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C 1- C4-alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, halo-C1-C4-alkylphenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C2- alkyl; still more particularly R2is selected from carboxy-C3-C4-alkyl, methoxycarbonyl- C2-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, haloacetamido-C1-C4- alkyl, C1-C2-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4- alkyloxycarbonyl, carboxyphenyl, carboxypyridinyl, 3-halophenyl, 3 -hydroxyphenyl, 3- nitrophenyl, 3 -aminophenyl, halo-C l-C2-alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, bromophenyl-C1-C2-alkyl, 2-fluorophenyl-C1-C2-alkyl, nitrophenyl-C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C1-C2- alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, halo-C1-C4-alkylphenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl, 2-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl and 4-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl; still more particularly R2is selected from carboxy-C3-C4-alkyl, methoxy carbonyl-C2-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, chloroacetamido-C1-C4-alkyl, C1-C2-alkylsulfonamido-C 1 -C4- alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4-alkyloxy carbonyl, carboxyphenyl, carboxypyridinyl, 3-halophenyl, 3 -hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 3-halo- C1-C2-alkylphenyl, 2-(C2-C4-alkyloxycarbonyl)phenyl, methoxy carbonylphenyl, C1-C4- alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, bromophenyl-C1-C2-alkyl, 2- fluorophenyl-C1-C2-alkyl, nitrophenyl-C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4- alkylamidophenyl-C1-C2-alkyl, chloro-C1-C2-alkylamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, halo-C1-C2-alkylphenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl, 2-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl and 4-C1-C2-alkyloxycarbonylphenyl-C1-C2-alkyl; even more particularly R2is selected from 3 -carb oxy propyl, 4-carboxybutyl, 4-(m ethoxy carbonyl)butyl, acetamidoethyl, acetamidopropyl, acrylamidoethyl, aery 1 amidopropyl, chloroacetamidoethyl, chloroacetamidopropyl, methanesulfonamidoethyl, methanesulfonamidopropyl, vinylsulfonamidoethyl, vinylsulfonamidopropyl, tert-butyloxycarbonyl, 2-carboxyphenyl, 3 -carb oxy phenyl, 4-carboxyphenyl, 3-carboxypyridin-2-yl, 6-carboxypyri din-2 -yl, 3- fluorophenyl, 3 -chlorophenyl, 3 -bromophenyl, 3 -iodophenyl, 3 -hydroxyphenyl, 3- nitrophenyl, 3 -aminophenyl, 3 -trifluom ethylphenyl, 2-ethoxy carbonylphenyl, 3- methoxycarbonylphenyl, 4-methoxycarbonylphenyl; 3-vinylsulfonamidophenyl, 3- methoxycarbonylpyridin-2-yl, 5-methoxycarbonylpyridin-2-yl, 5-carboxypyridin-2-yl, 2- nitrobenzyl, 2-aminobenzyl, 2-(chloromethylacetamido)benzyl, 2-vinylsulfonamidobenzyl,

[0135] 3 -nitrobenzyl, 3 -aminobenzyl, 3-(chloromethylacetamido)benzyl, 3- vinylsulfonamidobenzyl, 4-nitrobenzyl, 4-aminobenzyl, 4-(chloromethylacetamido)benzyl,

[0136] 4-vinylsulfonamidobenzyl, 2-cyanobenzyl, 3 -cyanobenzyl, 4-cyanobenzyl, 2-bromobenzyl, 3 -bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 2-trifluoromethylbenzyl, 3- trifluoromethylbenzyl, 4-methoxycarbonylbenzyl, 4-carboxybenzyl, 3 -carboxybenzyl, 2- m ethoxy carbonylbenzyl, and 2-carboxybenzyl.

[0137] In one embodiment, the compounds of Formula I are those of Formula VIII:

[0138] VIII, or pharmaceutically acceptable salts or solvates thereof, wherein R1and R3are as defined above with respect to Formula I and any of its embodiments.

[0139] Preferred compounds of Formula VII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R3are defined as follows:

[0140] R1is benzyl; and

[0141] R3is selected from methylsulfonamido-C1-C6-alkyl, cyanovinyl, 3-amino-3- carboxypropyl, hydroxy-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4- alkyl oxy oxopropenyl and oxo-C1-C6-alkyl; in particular R3is selected from methylsulfonamido-C1-C4-alkyl, cyanovinyl, hydroxy-C1-C4-alkyl, vinylsulfonamido-C1- C4-alkyl, C1-C4-alkyloxy oxopropenyl and oxo-C1-C4-alkyl; more particularly R3is selected from methylsulfonamido-C1-C2-alkyl, cyanovinyl, hydroxy-C1-C4-alkyl, vinylsulfonamido-C1-C2-alkyl, C1-C4-alkyloxy oxopropenyl and oxo-C1-C4-alkyl; still more particularly R3is selected from methylsulfonamidoethyl, cyanovinyl, 3 -hydroxybutyl, vinylsulfonamidoethyl, tert-butyloxy-3-oxopro-l-pen-l-yl and 3-oxobutyl;

[0142] In one embodiment, the compounds of Formula I are those of Formula IX: or pharmaceutically acceptable salts or solvates thereof, wherein

[0143] R1is as defined above with respect to Formula I and any of its embodiments.

[0144] Preferred compounds of Formula IX, or pharmaceutically acceptable salts or solvates thereof, are those wherein R1is selected from (l,l’-biphenyl)-4-ylmethyl, (adamantan-1- yl)methyl and (halogenocyclohexyl)methyl; in particular R1is selected from (1,1’- biphenyl)-4-ylmethyl, (adamantan-l-yl)methyl and (4,4-difluorocyclohexyl)methyl.

[0145] In one embodiment, the compounds of Formula I are those of Formula X:

[0146] X, or pharmaceutically acceptable salts or solvates thereof, wherein

[0147] R1and R2are as defined above with respect to Formula I and any of its embodiments.

[0148] Preferred compounds of Formula X, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0149] R1is benzyl; and

[0150] R2is carboxyaryl or carb oxy heteroaryl; in particular R2is carboxyphenyl or carb oxy pyridyl; more particularly R2is selected from 2-carboxyphenyl, 3 -carboxyphenyl, 4-carboxyphenyl and 6-carboxypyridin-2-yl. In one embodiment, the compounds of Formula I are those of Formula XI:

[0151] XI, or pharmaceutically acceptable salts or solvates thereof, wherein

[0152] R1and R2are as defined above with respect to Formula I and any of its embodiments.

[0153] Preferred compounds of Formula XI, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0154] R1is benzyl; and R2is carboxyaryl or carb oxy heteroaryl; in particular R2is carboxyphenyl or carb oxy pyridyl; more particularly R2is selected from 2-carboxyphenyl, 3 -carboxyphenyl, 4-carboxyphenyl and 6-carboxypyridin-2-yl.

[0155] In one embodiment, the compounds of Formula I are those of Formula XII:

[0156] XII, or pharmaceutically acceptable salts or solvates thereof, wherein

[0157] R1, R2, R5, R6and R7are as defined above with respect to Formula I and any of its embodiments.

[0158] Preferred compounds of Formula XII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0159] R1is benzyl;

[0160] R2is H;

[0161] R5and R6are independently selected from H, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(O)Ome, NO2, NH2, CN and vinylsulfonamido; still more particularly R5is selected from H, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido, and R6is selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido;

[0162] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; particularly R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, C1-C2-alkyl and C1-C4-alkyloxy carbonyl; still more particularly R7is selected from H, methyl and tert-butyloxycarbonyl; with the proviso that:

[0163] R5is not NO2 or OH when R6and R7are H;

[0164] R6is not NO2 or methoxy when R5and R7are H; and

[0165] R7is not H when R5and R6are H.

[0166] In one embodiment, the compounds of Formula I are those of Formula XIII:

[0167]

[0168] XIII, or pharmaceutically acceptable salts or solvates thereof, wherein R1and R2are as defined above with respect to Formula I and any of its embodiments.

[0169] Preferred compounds of Formula XIII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0170] R1is benzyl; and

[0171] R2is H. In one embodiment, the compounds of Formula I are those of Formula XIV:

[0172] XIV, or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments. Preferred compounds of Formula XIV, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0173] R1is benzyl;

[0174] R2is nitroaryl-C1-C4-alkyl; in particular R2is nitrophenyl-C1-C4-alkyl; more particularly R2is nitrophenyl-C1-C2-alkyl; still more particularly R2is nitrobenzyl; even more particularly R2is 4 -nitrobenzyl;

[0175] R3is H; and

[0176] R4is H.

[0177] Particularly preferred compounds of the invention are those listed in Table 1 hereafter: Table 1

[0178] The compounds of the invention can be prepared by different ways with reactions known by the person skilled in the art, in particular as described by the examples.

[0179] The compounds of Formula I are indeed capable of modulating, in particular inhibiting, the YAP(TAZ)-TEAD interaction, in particular the YAP(TAZ)-TEAD interaction targeting the palmitate pocket. The invention thus also provides the use of the compounds of Formula I, or pharmaceutically acceptable salts or solvates thereof, as modulators, in particular as inhibitors, of the YAP(TAZ)-TEAD interaction, in particular the YAP(TAZ)-TEAD interaction targeting the palmitate pocket.

[0180] Accordingly, in a particularly preferred embodiment, the invention relates to the use of compounds of Formula I and subformulae, or pharmaceutically acceptable salts or solvates thereof, for the treatment of cancer, particularly cancers that are modulated by the YAP(TAZ)-TEAD interaction, in particular the YAP(TAZ)-TEAD interaction targeting the palmitate pocket.

[0181] APPLICATIONS

[0182] Unexpectedly, the inventors have discovered that the compounds of Formula I may be used as modulators, in particular as inhibitors, of the YAP(TAZ)-TEAD interaction, in particular the YAP(TAZ)-TEAD interaction targeting the palmitate pocket.

[0183] In fact, and without wanting to be tied to any theory whatsoever, the inventors think the specific structure of the compounds of the invention allow them to fit into the internal pocket of the YAP(TAZ)-TEAD complex.

[0184] The compounds of Formula I, or any of its subformulae as defined above, can thus be used for treating cancer, particularly cancers that are modulated by the YAP(TAZ)-TEAD interaction, in particular the YAP(TAZ)-TEAD interaction targeting the palmitate pocket.

[0185] The invention thus relates to a compound of Formula I: or a pharmaceutically acceptable salt or solvate thereof, wherein

[0186] R1is selected from C1-C6-alkyl, halo-C1-C6-alkyl, aryl-C1-C4-alkyl, haloaryl-C1-C6- alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl- C1-C4-alkyl;

[0187] R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido- C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C 1 -C6- alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6-alkyloxy carbonyl, aryl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl, C1-C4-alkyloxy carbonylaryl, C1-C4-alkyloxy carb oxy heteroaryl, vinylsulfonamidoaryl, aryl-C1-C4-alkyl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C 1 - C4-alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl;

[0188] R3is selected from H, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6- alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1-C4- alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy - C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, formyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3 -amino-3 -carboxypropyl, C1-C6-alkyl, carboxy- C1-C6-alkyl and C1-C4-alkyloxycarbonyl-C1-C6-alkyl;

[0189] A is N, C-R4or CH-R4wherein R4is H, or

[0190] R3and R4form together a group selected from

[0191] wherein

[0192] R5and R6are independently selected from H, OH, C(O)OH, C1-C4- alkyloxycarbonyl, NO2, NH2, CN and vinylsulfonamido; R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl;

[0193] I is a single bond or a double bond; with the proviso that:

[0194] R7is not H when R5and R6are H; and

[0195] ' is a double bond when A is N or C-R4; for use use in treating cancer.

[0196] Particular compounds for use of Formula I, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and A are defined as follows:

[0197] R1is selected from C1-C6-alkyl, halo-C1-C6-alkyl, aryl-C1-C4-alkyl, haloaryl-C1-C6- alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl-C1- C4-alkyl; in particular R1is selected from C1-C6-alkyl, aryl-C1-C4-alkyl, haloaryl-C1-C6- alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl-C1-C4-alkyl; more particularly R1is selected from C1-C4-alkyl, aryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl-C1-C4-alkyl; still more particularly R1is selected from C1-C4-alkyl, phenyl-C1-C4-alkyl, naphthalen-l-yl-C1-C4-alkyl, naphthal en- 2-yl-C1-C4-alkyl, biphenyl-C1-C4-alkyl, halo-C1-C4-alkylphenyl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl-C1-C4-alkyl; still more particularly R1is selected from C1-C4-alkyl, phenyl-C1-C4-alkyl, naphthalen-l-yl-C1-C4-alkyl, naphthal en- 2-yl-C1-C4-alkyl, biphenyl-C1-C4-alkyl, trifluoromethylphenyl-C1-C4-alkyl, cycloalkyl- C1-C4-alkyl and difluorocycloalkyl-C1-C4-alkyl; even more particularly R1is selected from iso-butyl, neopentyl, benzyl, phenylethyl, phenylpropyl, naphthalen-l-ylmethyl, naphthalen-2-ylmethyl, (1, l’-biphenyl)-4-ylmethyl, (3-trifluoromethylphenyl)methyl, cyclohexylmethyl, adamantan-l-ylmethyl and (4,4-difluorocycloalkyl)methyl; in a particular example R1is selected from phenyl-C1-C4-alkyl, naphthalen-l-yl-C1-C4-alkyl, naphthal en-2-yl-C1-C4-alkyl, biphenyl-C1-C4-alkyl, trifluoromethylphenyl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and difluorocycloalkyl-C1-C4-alkyl; in a more particular example R1is selected from phenyl-C1-C4-alkyl, naphthalen-l-yl-C1-C2-alkyl, naphthal en-2-yl-C1- C2-alkyl, biphenyl-C l-C2-alkyl, trifluoromethylphenyl-C l-C2-alkyl, cycloalkyl-C1-C2- alkyl and difluorocycloalkyl-C1-C2-alkyl; in a still particular example R1is benzyl;

[0198] R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino- C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6- alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6-alkyloxy carbonyl, aryl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxy aryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl, C1-C4-alkyloxy carbonylaryl, C1-C4-alkyloxy carbonylheteroaryl, vinylsulfonamidoaryl, aryl-C1-C4-alkyl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4-alkylamidoaryl- C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4- alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, carboxyaryl-C1-C4- alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino-C1-C6-alkyl, cyano- C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1-C4- alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6- alkyl, C1-C6-alkyloxycarbonyl, phenyl, carb oxy phenyl, carboxypyridinyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, halo-C1-C4-alkylphenyl, cyanophenyl, C1-C4- alkyloxy carbonylphenyl, C1-C4-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, phenyl-C1-C4-alkyl, halophenyl-C1-C4-alkyl, nitrophenyl-C1-C4-alkyl, aminophenyl-C1- C4-alkyl, C1-C4-alkyl amidophenyl -C1-C4-alkyl, halo-C1-C4-alkylamidophenyl-C 1 -C4- alkyl, C1-C4-alkylsulfonamidophenyl-C1-C4-alkyl, vinylsulfonamidophenyl-C1-C4-alkyl, cyanophenyl-C1-C4-alkyl, vinylsulfonamidophenyl-C1-C4-alkyl, carboxyphenyl-C 1 -C4- alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C4-alkyl; still more particularly R2is selected from H, carboxy-C1-C4-alkyl, C1-C4-alkyloxycarbonyl-C1-C4-alkyl, amino-C1-C4-alkyl, cyano-C1-C4-alkyl, C1-C2-alkylamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, halo-C 1- C2-alkylamido-C1-C4-alkyl, C1-C2-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C1- C4-alkyl, C1-C4-alkyloxy carbonyl, phenyl, carb oxy phenyl, carboxypyridinyl, 3- halophenyl, 3 -hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 3 -halo-C1-C4-alkylphenyl, 3- cyanophenyl, C1-C2-alkyloxy carbonylphenyl, C1-C2-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, phenyl-C1-C2-alkyl, halophenyl-C1-C2-alkyl, nitrophenyl-C1- C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C 1-C4- alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C l-C2-alkyl, cyanophenyl-C l-C2-alkyl, vinylsulfonamidophenyl- C1-C2-alkyl, carboxyphenyl-C l-C2-alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C2- alkyl; still more particularly R2is selected from H, carboxy-C1-C4-alkyl, amino-C1-C4- alkyl, cyano-C1-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, chloroacetamido-C1-C4-alkyl, methylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C 1 -C4- alkyl, C1-C4-alkyloxy carbonyl, phenyl, carboxyphenyl, carboxypyridinyl, 3-halophenyl, 3- hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 3-halo-C1-C4-alkylphenyl, 3 -cyanophenyl, C1-C2-alkyloxy carbonyl phenyl, C1-C2-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, phenyl-C1-C2-alkyl, halophenyl-C1-C2-alkyl, nitrophenyl-C1- C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C 1-C4- alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C l-C2-alkyl, cyanophenyl-C l-C2-alkyl, vinylsulfonamidophenyl- C1-C2-alkyl, carboxyphenyl-C l-C2-alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C2- alkyl; even more particularly R2is selected from H, carboxymethyl, 2-carboxyethyl, 3- carboxypropyl, 4-carboxybutyl, methoxycarbonylmethyl, 4-(methoxycarbonyl)butyl, 2- aminoethyl, 3 -aminopropyl, cyanomethyl, acetamidoethyl, acetamidopropyl, aery 1 amidoethyl, aery 1 amidopropyl, chloroacetamidoethyl, chloroacetamidopropyl, methylsulfonamidoethyl, methylsulfonamidopropyl, vinylsulfonamidoethyl, vinylsulfonamidopropyl, tert-butyloxycarbonyl, phenyl, 2-carboxyphenyl, 3- carb oxy phenyl, 4-carboxyphenyl, 3-carboxypyridin-2-yl, 6-carboxypyri din-2 -yl, 3- fluorophenyl, 3 -chlorophenyl, 3 -bromophenyl, 3 -iodophenyl, 3 -hydroxyphenyl, 3- nitrophenyl, 3 -aminophenyl, 3 -trifluom ethylphenyl, 3 -cyanophenyl, 2- ethoxycarbonylphenyl, 3 -ethoxy carbonylphenyl, 4-ethoxy carbonylphenyl, 2- methoxycarbonylphenyl, 3 -methoxy carbonylphenyl, 4-methoxy carbonylphenyl, 3- vinylsulfonamidophenyl, 3 -methoxy carbonylpyridin-2-yl, 5-methoxycarbonylpyri din-2 -yl, 5-carboxypyridin-2-yl, 2-nitrobenzyl, 2-aminobenzyl, 2-(chloromethylacetamido)benzyl, 2- vinylsulfonamidobenzyl, 3 -nitrobenzyl, 3 -aminobenzyl, 3-(chloromethylacetamido)benzyl,

[0199] 3-vinylsulfonamidobenzyl, 4-nitrobenzyl, 4-aminobenzyl, 4-

[0200] (chloromethylacetamido)benzyl, 4-vinylsulfonamidobenzyl, 2-cyanobenzyl, 3- cyanobenzyl, 4-cyanobenzyl, 2-bromobenzyl, 3 -bromobenzyl, 4-bromobenzyl, 2- fluorobenzyl, 2-trifluorom ethylbenzyl, 3 -trifluoromethylbenzyl, 4-methoxy carbonylbenzyl,

[0201] 4-carboxybenzyl, 3 -carboxybenzyl, 2-methoxy carbonylbenzyl, and 2-carboxybenzyl; in a particular example R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1- C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido- C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6-alkyloxy carbonyl, carboxyaryl, carb oxy heteroaryl, hydroxyaryl, nitroaryl, aminoaryl, C1-C4-alkyloxy carbonylaryl, C1-C4- alkyl oxy carbonylheteroaryl, vinylsulfonamidoaryl, nitroaryl-C1-C4-alkyl, aminoaryl-C1- C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4-alkylamidoaryl-C1-C4-alkyl, C1-C4-alkyl sulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in a more particular example R2is selected from carboxy-C1-C4-alkyl, C1-C2-alkyloxycarbonyl-C1- C4-alkyl, amino-C1-C4-alkyl, cyano-C1-C4-alkyl, C1-C2-alkylamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, halo-C1-C2-alkylamido-C1-C4-alkyl, C1-C2-alkylsulfonamido- C1-C4-alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4-alkyloxy carbonyl, carboxyphenyl, carboxypyridinyl, hydroxyphenyl, nitrophenyl, aminophenyl, C1-C2- alkyloxy carbonylphenyl, C1-C2-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, nitrophenyl-C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidoaryl-C1-C2-alkyl, halo-C1-C4-alkylamidoaryl-C1-C2-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C2-alkyl, vinylsulfonamidoaryl-C l-C2-alkyl, carboxyphenyl-C1-C2-alkyl and C1-C4- alkyloxycarbonylphenyl-C1-C2-alkyl; in a still more particular example R2is selected from carboxymethyl, 2-carboxy ethyl, 3 -carboxypropyl, 4-carboxybutyl, methoxy carbonylmethyl, 4-(methoxycarbonyl)butyl, 2-aminoethyl, 3 -aminopropyl, cyanomethyl, acetamidoethyl, acetamidopropyl, acrylamidoethyl, aery 1 amidopropyl, chloroacetamidoethyl, chloroacetamidopropyl, methylsulfonamidoethyl, methylsulfonamidopropyl, vinylsulfonamidoethyl, vinylsulfonamidopropyl, tert-butyloxycarbonyl, 2-carboxyphenyl, 3 -carb oxy phenyl, 4-carboxyphenyl, 3-carboxypyridin-2-yl, 6-carboxypyri din-2 -yl, 3- hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 2-ethoxy carbonylphenyl, 3- ethoxycarbonylphenyl, 4-ethoxy carbonylphenyl, 2-methoxy carbonylphenyl, 3- methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 3-vinylsulfonamidophenyl, 3- methoxycarbonylpyridin-2-yl, 5-methoxycarbonylpyridin-2-yl, 5-carboxypyridin-2-yl, 2- nitrobenzyl, 2-aminobenzyl, 2-(chloromethylacetamido)benzyl, 2-vinylsulfonamidobenzyl, 3-(chloromethylacetamido)benzyl, 3-vinylsulfonamidobenzyl, 4-

[0202] (chloromethylacetamido)benzyl, 4-vinylsulfonamidobenzyl, 4-methoxycarbonylbenzyl, 4- carboxybenzyl, 3 -carboxybenzyl, 2-methoxycarbonylbenzyl, and 2-carboxybenzyl;

[0203] R3is selected from H, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C 1-C6- alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido- C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonylcarbonyl, hydroxy-C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, formyl, C1-C4-alkyloxy oxopropenyl, carboxy vinyl, amino- C1-C6-alkyl, 3 -amino-3 -carb oxy propyl, C1-C6-alkyl, carboxy-C1-C6-alkyl and C1-C4- alkyloxycarbonyl-C1-C6-alkyl; in particular R3is selected from H, C1-C4- alkyl sulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4-alkylamido-C 1 -C6- alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy-C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, formyl, C1-C4-alkyl oxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3-amino-3- carboxypropyl and C1-C6-alkyl, more particularly R3is selected from H, C1-C2- alkyl sulfonamido-C1-C4-alkyl, vinylsulfonamido-C1-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, chloroacetamido-C1-C4-alkyl, carboxy carbonyl, C1-C2- alkyloxy carbonylcarbonyl, hydroxy-C1-C4-alkyl, oxo-C1-C4-alkyl, cyanovinyl, formyl, C1-C4-alkyl oxy oxopropenyl, carboxyvinyl, amino-C1-C4-alkyl, 3 -amino-3 -carboxypropyl and C1-C4-alkyl; still more particularly R3is selected from H, methanesulfonamidoethyl, vinylsulfonamidoethyl, acetamidoethyl, aery 1 amidoethyl, chloroacetamidoethyl, carboxycarbonyl, methyloxycarbonylcarbonyl, 2-hydroxethyl, 3 -hydroxybutyl, 3-oxobutyl, cyanovinyl, formyl, ethyloxyoxopropenyl, tert-butyloxyoxopropenyl, carboxyvinyl, 2- aminoethyl, 3 -amino-3 -carboxypropyl and methyl;

[0204] A is N, C-R4or CH-R4, in particular A is C-R4or CH-R4, more particularly A is C-R4wherein R4is H, or

[0205] R3and R4form together a group selected from wherein

[0206] R5and R6are independently selected from H, OH, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido;

[0207] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; in particular R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, methyl and C1-C4-alkyloxycarbonyl; still more particularly, R7is H or C1-C4-alkyloxy carbonyl, even more parti culary R7is H or tert-butyloxy carbonyl;

[0208] ! is a single bond or a double bond; in particular I is a double bond; with the proviso that: R7is not H when R5and R6are H; and

[0209] ' is a double bond when A is N or C-R4.

[0210] In the formula I as used herein, the atoms of the central core are numbered as follows: In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 4, 5 or 6 of the central core.

[0211] In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 4 or 5 of the central core.

[0212] In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 4 or 6 of the central core.

[0213] In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 5 or 6 of the central core.

[0214] In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 4 of the central core. In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 5 of the central core.

[0215] In one embodiment, the compounds for use of Formula I are those wherein the group -O- R1is located in position 6 of the central core.

[0216] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl. In one embodiment, the compounds for use of Formula I are those wherein R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1- C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1- C6-alkyl, C1-C6-alkyl oxy carbonyl, aryl, carboxyaryl, carboxyheteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl, C1-C4- alkyloxy carbonylaryl, C1-C4-alkyloxy carbonylheteroaryl, vinylsulfonamidoaryl, aryl-C1- C4-alkyl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4- alkylamidoaryl-C1-C4-alkyl, halo-C1-C4-alkylamidoaryl-C1-C4-alkyl, C1-C4- alkyl sulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C 1 -C4- alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, carboxyaryl-C1-C4-alkyl and C1-C4- alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from carboxy-C1-C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, aery 1 ami do-C 1- C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6-alkyloxy carbonyl, aryl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxy aryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl and C1-C4-alkyloxy carbonylaryl.

[0217] In one embodiment, the compounds for use of Formula I are those wherein R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1- C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1- C6-alkyl, C1-C6-alkyl oxy carbonyl, carboxyaryl, carb oxy heteroaryl, hydroxyaryl, nitroaryl, aminoaryl, C1-C4-alkyloxy carbonyl aryl, C1-C4-alkyloxycarbonylheteroaryl, vinylsulfonamidoaryl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4- alkylamidoaryl-C1-C4-alkyl, halo-C1-C4-alkylamidoaryl-C1-C4-alkyl, C1-C4- alkyl sulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, carboxyaryl-C 1 - C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from carboxy-C1-C4-alkyl, C1-C2-alkyloxycarbonyl-C1-C4-alkyl, amino-C1-C4-alkyl, cyano- C1-C4-alkyl, C1-C2-alkylamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, halo-C 1-C2- alkylamido-C1-C4-alkyl, C1-C2-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C1-C4- alkyl, C1-C4-alkyloxy carbonyl, carboxyphenyl, carboxypyridinyl, hydroxyphenyl, nitrophenyl, aminophenyl, C1-C2-alkyloxy carbonylphenyl, C1-C2- alkyl oxy carbonylpyndinyl, vinylsulfonamidophenyl, mtrophenyl-C1-C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidoaryl-C1-C2-alkyl, halo-C1-C4- alkylamidoaryl-C1-C2-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C2-alkyl, vinylsulfonamidoaryl-C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl and C1-C4- alkyloxycarbonylphenyl-C1-C2-alkyl; more particularly R2is selected from carboxymethyl, 2-carboxy ethyl, 3 -carboxypropyl, 4-carboxybutyl, methoxy carbonylmethyl, 4-

[0218] (m ethoxy carbonyl)butyl, 2-aminoethyl, 3 -aminopropyl, cyanomethyl, acetamidoethyl, acetamidopropyl, acrylamidoethyl, aery 1 amidopropyl, chloroacetamidoethyl, chloroacetamidopropyl, methylsulfonamidoethyl, methylsulfonamidopropyl, vinylsulfonamidoethyl, vinylsulfonamidopropyl, tert-butyloxycarbonyl, 2-carboxyphenyl, 3 -carb oxy phenyl, 4-carboxyphenyl, 3-carboxypyridin-2-yl, 6-carboxypyri din-2 -yl, 3- hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 2-ethoxy carbonylphenyl, 3- ethoxycarbonylphenyl, 4-ethoxy carbonylphenyl, 2-methoxy carbonylphenyl, 3- methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 3-vinylsulfonamidophenyl, 3- methoxycarbonylpyridin-2-yl, 5-methoxycarbonylpyridin-2-yl, 5-carboxypyridin-2-yl, 2- nitrobenzyl, 2-aminobenzyl, 2-(chloromethylacetamido)benzyl, 2-vinylsulfonamidobenzyl, 3-(chloromethylacetamido)benzyl, 3-vinylsulfonamidobenzyl, 4-

[0219] (chloromethylacetamido)benzyl, 4-vinylsulfonamidobenzyl, 4-methoxycarbonylbenzyl, 4- carboxybenzyl, 3 -carboxybenzyl, 2-methoxycarbonylbenzyl, and 2-carboxybenzyl

[0220] In one embodiment, the compounds for use of Formula I are those wherein R2is H.

[0221] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl and R2is H.

[0222] In one embodiment, the compounds for use of Formula I are those wherein R3is selected from C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4- alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy-C1-C6-alkyl, oxo-C1-C6- alkyl, cyanovinyl, formyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3 -amino-3 -carboxypropyl, C1-C6-alkyl, carboxy-C1-C6-alkyl and C1-C4- alkyloxycarbonyl-C1-C6-alkyl; in particular R3is selected from C1-C4-alkylsulfonamido- C1-C6-alkyl, vinyl sulfonamido-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido- C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4- alkyloxy carbonylcarbonyl, hydroxy-C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, formyl, C1-C4-alkyl oxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3 -amino-3 -carboxypropyl and C1-C6-alkyl.

[0223] In one embodiment, the compounds for use of Formula I are those wherein R3is H.

[0224] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl and R3is H.

[0225] In one embodiment, the compounds for use of Formula I are those wherein A is CH.

[0226] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl and A is CH.

[0227] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl, R2is H and A is CH.

[0228] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl, R3is H and A is CH.

[0229] In one embodiment, the compounds for use of Formula I are those wherein R2and R3are not H.

[0230] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl and R2and R3are not H.

[0231] In one embodiment, the compound for use of Formula I are those wherein A is C-R4and R3and R4form together the following group: In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl, A is C-R4and R3and R4form together the following group:

[0232] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl, R2is H, A is C-R4and R3and R4form together the following group:

[0233] In one embodiment, the compounds for use of Formula I are those wherein A is C-R4and R3and R4form together the following group: wherein

[0234] R5and R6are independently selected from H, OH, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; and R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; with the proviso that R7is not H when R5and R6are H.

[0235] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl, A is C-R4and R3and R4form together the following group: wherein

[0236] R5and R6are independently selected from H, OH, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; and

[0237] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; with the proviso that R7is not H when R5and R6are H.

[0238] In one embodiment, the compounds for use of Formula I are those wherein R1is benzyl, R2is H, A is C-R4and R3and R4form together the following group: wherein R5and R6are independently selected from H, OH, C(O)OH, C1-C4- alkyloxycarbonyl, NO2, NH2, CN and vinylsulfonamido; and

[0239] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; with the proviso that R7is not H when R5and R6are H. In one embodiment, the compounds for use of Formula I are those of Formula II:

[0240] II, or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments.

[0241] Preferred compounds for use of Formula II, or pharmaceutically acceptable salts or solvates thereof, are those wherein the group -O-R1is located in position 4, 5 or 6 of the central core.

[0242] In one embodiment, the compounds for use of Formula I are those of Formula III:

[0243] III, or pharmaceutically acceptable salts or solvates thereof, wherein

[0244] R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments.

[0245] In one embodiment, the compounds for use of Formula I are those of Formula IV: or pharmaceutically acceptable salts or solvates thereof, wherein

[0246] R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments. Preferred compounds for use of Formula IV, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0247] R1is benzyl;

[0248] R2is selected from H, carboxyaryl and carboxyheteroaryl; in particular R2is selected from

[0249] H, carboxyphenyl and carboxypyridinyl; more particularly R2is selected from H, 2- carb oxy phenyl, 3-carboxyphenyl, 4-carboxyphenyl and 6-carboxypyri din-2 -yl;

[0250] R3is H; and

[0251] R4is H.

[0252] In one embodiment, the compounds for use of Formula I are those of Formula V:

[0253] or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments.

[0254] Preferred compounds for use of Formula V, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0255] R1is benzyl;

[0256] R2is selected from H, carboxyaryl and carboxyheteroaryl; in particular R2is selected from H, carboxyphenyl and carboxypyridinyl; more particularly R2is selected from H, 2- carb oxy phenyl, 3-carboxyphenyl, 4-carboxyphenyl and 6-carboxypyri din-2 -yl;

[0257] R3is H; and

[0258] R4is H.

[0259] In one embodiment, the compounds for use of Formula I are those of Formula VI: or pharmaceutically acceptable salts or solvates thereof, wherein

[0260] R1, R2and R3are as defined above with respect to Formula I and any of its embodiments.

[0261] In one embodiment, the compounds for use of Formula I are those of Formula VII:

[0262] VII, or pharmaceutically acceptable salts or solvates thereof, wherein

[0263] R1and R2are as defined above with respect to Formula I and any of its embodiments.

[0264] Preferred compounds for use of Formula VII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0265] R1is benzyl; and

[0266] R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino- C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6- alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6-alkyloxy carbonyl, aryl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxy aryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl, C1-C4-alkyloxy carbonylaryl, C1-C4-alkyloxy carbonylheteroaryl, vinylsulfonamidoaryl, aryl-C1-C4-alkyl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C1-C4-alkylamidoaryl- C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4- alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, carboxyaryl-C1-C4- alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl; in particular R2is selected from carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl-C1-C6-alkyl, amino-C1-C6-alkyl, cyano- C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1-C4- alkylamido-C1-C6-alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C 1-C6- alkyl, C1-C6-alkyloxycarbonyl, phenyl, carb oxy phenyl, carboxypyridinyl, halophenyl, hydroxyphenyl, nitrophenyl, aminophenyl, halo-C1-C4-alkylphenyl, cyanophenyl, C1-C4- alkyloxy carbonylphenyl, C1-C4-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, phenyl-C1-C4-alkyl, halophenyl-C1-C4-alkyl, nitrophenyl-C1-C4-alkyl, aminophenyl-C1- C4-alkyl, C1-C4-alkyl amidophenyl -C1-C4-alkyl, halo-C1-C4-alkylamidophenyl-C 1 -C4- alkyl, C1-C4-alkylsulfonamidophenyl-C1-C4-alkyl, vinylsulfonamidophenyl-C1-C4-alkyl, cyanophenyl-C1-C4-alkyl, vinylsulfonamidophenyl-C1-C4-alkyl, carboxyphenyl-C 1 -C4- alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C4-alkyl; still more particularly R2is selected from carboxy-C1-C4-alkyl, C1-C4-alkyloxycarbonyl-C1-C4-alkyl, amino-C1-C4-alkyl, cyano-C1-C4-alkyl, C1-C2-alkylamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, halo-C 1- C2-alkylamido-C1-C4-alkyl, C1-C2-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C 1 - C4-alkyl, C1-C4-alkyloxy carbonyl, phenyl, carb oxy phenyl, carboxypyridinyl, 3- halophenyl, 3 -hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 3 -halo-C1-C4-alkylphenyl, 3- cyanophenyl, C1-C2-alkyloxy carbonylphenyl, C1-C2-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, phenyl-C1-C2-alkyl, halophenyl-C1-C2-alkyl, nitrophenyl-C1- C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C 1-C4- alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C l-C2-alkyl, cyanophenyl-C l-C2-alkyl, vinylsulfonamidophenyl- C1-C2-alkyl, carboxyphenyl-C l-C2-alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C2- alkyl; still more particularly R2is selected from carboxy-C1-C4-alkyl, amino-C1-C4-alkyl, cyano-C1-C4-alkyl, acetamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, chloroacetamido- C1-C4-alkyl, methylsulfonamido-C1-C4-alkyl, vinylsulfonamido-C1-C4-alkyl, C1-C4- alkyloxycarbonyl, phenyl, carb oxy phenyl, carboxypyridinyl, 3-halophenyl, 3- hydroxyphenyl, 3 -nitrophenyl, 3 -aminophenyl, 3-halo-C1-C4-alkylphenyl, 3 -cyanophenyl, C1-C2-alkyloxy carbonyl phenyl, C1-C2-alkyloxycarbonylpyridinyl, vinylsulfonamidophenyl, phenyl-C1-C2-alkyl, halophenyl-C1-C2-alkyl, nitrophenyl-C1- C2-alkyl, aminophenyl-C1-C2-alkyl, C1-C4-alkylamidophenyl-C1-C2-alkyl, halo-C 1-C4- alkylamidophenyl-C1-C2-alkyl, C1-C4-alkylsulfonamidophenyl-C1-C2-alkyl, vinylsulfonamidophenyl-C1-C2-alkyl, cyanophenyl-C1-C2-alkyl, vinylsulfonamidophenyl- C1-C2-alkyl, carboxyphenyl-C1-C2-alkyl and C1-C4-alkyloxycarbonylphenyl-C1-C2- alkyl; even more particularly R2is selected from carboxymethyl, 2-carboxyethyl, 3- carboxypropyl, 4-carboxybutyl, methoxycarbonylmethyl, 4-(methoxycarbonyl)butyl, 2- aminoethyl, 3 -aminopropyl, cyanomethyl, acetamidoethyl, acetamidopropyl, aery 1 amidoethyl, aery 1 amidopropyl, chloroacetamidoethyl, chloroacetamidopropyl, methylsulfonamidoethyl, methylsulfonamidopropyl, vinylsulfonamidoethyl, vinylsulfonamidopropyl, tert-butyloxycarbonyl, phenyl, 2-carboxyphenyl, 3- carb oxy phenyl, 4-carboxyphenyl, 3-carboxypyridin-2-yl, 6-carboxypyri din-2 -yl, 3- fluorophenyl, 3 -chlorophenyl, 3 -bromophenyl, 3 -iodophenyl, 3 -hydroxyphenyl, 3- nitrophenyl, 3 -aminophenyl, 3 -trifluom ethylphenyl, 3 -cyanophenyl, 2- ethoxycarbonylphenyl, 3 -ethoxy carbonylphenyl, 4-ethoxy carbonylphenyl, 2- m ethoxy carbonylphenyl, 3 -methoxy carbonylphenyl, 4-methoxy carbonylphenyl, 3- vinylsulfonamidophenyl, 3 -methoxy carbonylpyridin-2-yl, 5-methoxycarbonylpyri din-2 -yl, 5-carboxypyridin-2-yl, 2-nitrobenzyl, 2-aminobenzyl, 2-(chloromethylacetamido)benzyl, 2- vinylsulfonamidobenzyl, 3 -nitrobenzyl, 3 -aminobenzyl, 3-(chloromethylacetamido)benzyl,

[0267] 3-vinylsulfonamidobenzyl, 4-nitrobenzyl, 4-aminobenzyl, 4-

[0268] (chloromethylacetamido)benzyl, 4-vinylsulfonamidobenzyl, 2-cyanobenzyl, 3- cyanobenzyl, 4-cyanobenzyl, 2-bromobenzyl, 3 -bromobenzyl, 4-bromobenzyl, 2- fluorobenzyl, 2-trifluorom ethylbenzyl, 3 -trifluoromethylbenzyl, 4-methoxy carbonylbenzyl,

[0269] 4-carboxybenzyl, 3 -carboxybenzyl, 2-methoxy carbonylbenzyl, and 2-carboxybenzyl.

[0270] In one embodiment, the compounds for use of Formula I are those of Formula VIII:

[0271] VIII, or pharmaceutically acceptable salts or solvates thereof, wherein R1and R3are as defined above with respect to Formula I and any of its embodiments.

[0272] Preferred compounds for use of Formula VII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R3are defined as follows:

[0273] R1is benzyl; and

[0274] R3is selected from C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C 1 -C6- alkyl, carboxycarbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy-C1-C6-alkyl, oxo-C1- C6-alkyl, cyanovinyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3- amino-3 -carboxypropyl, C1-C6-alkyl, carboxy-C1-C6-alkyl and C1-C4-alkyloxycarbonyl- C1-C6-alkyl; in particular R3is selected from C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy-C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3 -amino-3 -carb oxy propyl, C1-C6-alkyl; more particularly R3is selected from C1-C2-alkylsulfonamido-C1-C4-alkyl, vinylsulfonamido- C1-C4-alkyl, C1-C2-alkylamido-C1-C4-alkyl, acrylamido-C1-C4-alkyl, halo-C 1-C2- alkylamido-C1-C4-alkyl, carboxycarbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy-C1- C4-alkyl, oxo-C1-C4-alkyl, cyanovinyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C4-alkyl, 3 -amino-3 -carboxypropyl, C1-C4-alkyl; still more particularly R3is selected from methylsulfonamidoethyl, vinylsulfonamidoethyl, acetamidoethyl, aery 1 amidoethyl, chloroacetamidoethyl, carboxycarbonyl, methyloxycarbonylcarbonyl, 2- hydroxethyl, 3 -hydroxybutyl, 3 -oxobutyl, cyanovinyl, ethyloxy oxopropenyl, carboxy vinyl, 2-aminoethyl, 3 -amino-3 -carboxypropyl and methyl;

[0275] In one embodiment, the compounds for use of Formula I are those of Formula IX: or pharmaceutically acceptable salts or solvates thereof, wherein

[0276] R1is as defined above with respect to Formula I and any of its embodiments.

[0277] Preferred compounds for use of Formula IX, or pharmaceutically acceptable salts or solvates, thereof are those wherein R1is selected from C1-C6-alkyl, phenyl-C1-C4-alkyl, (1 , 1’ -biphenyl)-C1-C4-alkyl, naphthal enyl-C1-C4-alkyl, trifluoromethylphenyl-C 1 -C4- alkyl, (adamantan-l-yl)-C1-C4-alkyl, cyclohexyl-C1-C4-alkyl and (halocyclohexyl)-C1- C4-alkyl; in particular R1is selected from iso-butyl, neopentyl, benzyl, phenylethyl, phenylpropyl, (l,l’-biphenyl)-4-ylmethyl, naphthalen-l-ylmethyl, naphthalen-2-ylmethyl, 3 -trifluorobenzyl, 3-(trifluoromethyl)benzyl, 4-(trifluoromethyl)benzyl, (adamantan-1- yl)m ethyl, cyclohexylmethyl and (4,4-difluorocyclohexyl)methyl.

[0278] In one embodiment, the compounds for use of Formula I are those of Formula X: or pharmaceutically acceptable salts or solvates thereof, wherein

[0279] R1and R2are as defined above with respect to Formula I and any of its embodiments.

[0280] Preferred compounds for use of Formula X, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0281] R1is benzyl; and R2is carboxyaryl or carb oxy heteroaryl; in particular R2is selected from H, carboxyphenyl and carboxypyridinyl; more particularly R2is selected from H, 2-carboxyphenyl, 3- carb oxy phenyl, 4-carboxyphenyl and 6-carboxypyridin-2-yl.

[0282] In one embodiment, the compounds for use of Formula I are those of Formula XI: or pharmaceutically acceptable salts or solvates thereof, wherein

[0283] R1and R2are as defined above with respect to Formula I and any of its embodiments. Preferred compounds for use of Formula XI, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1and R2are defined as follows:

[0284] R1is benzyl; and

[0285] R2is carboxyaryl or carb oxy heteroaryl; in particular R2is selected from H, carboxyphenyl and carboxypyridinyl; more particularly R2is selected from H, 2-carboxyphenyl, 3- carb oxy phenyl, 4-carboxyphenyl and 6-carboxypyridin-2-yl.

[0286] In one embodiment, the compounds for use of Formula I are those of Formula XII:

[0287]

[0288] XII, or pharmaceutically acceptable salts or solvates thereof, wherein

[0289] R1, R2, R5, R6and R7are as defined above with respect to Formula I and any of its embodiments.

[0290] Preferred compounds for use of Formula XII, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R5, R6and R7are defined as follows:

[0291] R1is benzyl;

[0292] R2is H;

[0293] R5and R6are independently selected from H, C(O)OH, C1-C4-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; in particular R5and R6are independently selected from H, OH, C(O)OH, C1-C2-alkyloxy carbonyl, NO2, NH2, CN and vinylsulfonamido; more particularly R5and R6are independently selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2, CN and vinylsulfonamido; still more particularly R5is selected from H, OH, C(O)OH, C(O)OMe, NO2, NH2 and vinylsulfonamido, and R6is selected from H, OH, C(O)OH, C(O)Ome, NO2, NH2, CN and vinylsulfonamido;

[0294] R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl; particularly R7is selected from H, C1-C4-alkyl and C1-C4-alkyloxy carbonyl; more particularly R7is selected from H, methyl and C1-C4-alkyloxy carbonyl; still more particularly R7is H or C1-C4- alkyloxycarbonyl; even more particularly R7is H or tert-butyloxycarbonyl; with the proviso that R7is not H when R5and R6are H.

[0295] In one embodiment, the compounds for use of Formula I are those of Formula XIII:

[0296] XIII, or pharmaceutically acceptable salts or solvates thereof, wherein

[0297] R1and R2are as defined above with respect to Formula I and any of its embodiments. In one embodiment, the compounds for use of Formula I are those of Formula XIV:

[0298] XIV, or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3and R4are as defined above with respect to Formula I and any of its embodiments. Preferred compounds for use of Formula XIV, or pharmaceutically acceptable salts or solvates thereof, are those wherein one or more of R1, R2, R3and R4are defined as follows:

[0299] R1is benzyl;

[0300] R2is H or nitroaryl-C1-C4-alkyl; in particular R2is H or nitrophenyl-C1-C4-alkyl; more particularly R2is H or nitrophenyl-C1-C2-alkyl; still more particularly R2is H or nitrobenzyl; even more particularly R2is H or 4-nitrobenzyl;

[0301] R3is H; and

[0302] R4is H.

[0303] The compounds for use according to the invention therefore include compounds of Formula I or any of its subformulae as defined above, in particular compounds of Table 2 below.

[0304] Table 2 In one embodiment, the compounds for use according to the invention are selected from compounds 1-42, 46-91 and 93-139 of Table 2 above, in particular from compounds 1-12, 15, 17-36, 38-42, 46-47, 49, 51-52, 54-68, 70-80, 82, 84-118 and 121-139 of Table 2 above, more particularly from compounds 20-23, 26, 27, 34-36, 42, 46, 49, 57, 58, 60, 61, 64, 70, 71, 73, 75-77, 80, 85, 87, 89, 91, 93, 95-97, 116-118, 122, 123, 125, 128-124 and 139 of Table 2 above, still more particularly from compounds 23, 26, 27, 34-36, and 49 of Table 2 above, even more particularly from compounds 23, 26, 27 and 36 of Table 2 above.

[0305] In one embodiment, the compounds for use according to the invention are selected from compounds 31-33, 36, 49, 116-118, 122, 123 and 133 of Table 2 above, in particular from compounds 31-33, 36, 116-118, 122 and 123 of Table 2 above.

[0306] The compounds of the invention are therefore useful in the treatment of cancers, and particularly cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket.

[0307] Cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket, within the meaning of the present invention include, but are not limited to, breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers, in particular breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer and pleural mesothelioma.

[0308] Thus, in one embodiment, there is provided a compound of the present invention, or a pharmaceutically acceptable salt or solvate thereof, for use in treating cancer.

[0309] The invention thus also relates to a compound of the present invention, in particular a compound of Formula I, or any of its subformulae as defined above, more particularly a compound of Table 2 above, or a pharmaceutically acceptable salt or solvate thereof, for use in treating cancer. Particularly, the cancer is selected from cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket. More particularly, the cancer is selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers. Still more particularly, the cancer is selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer and pleural mesothelioma.

[0310] In other terms, the invention also relates to a method of treating cancer, particularly a cancer selected from cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket, more particularly a cancer selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers, still more particularly a cancer selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer and pleural mesothelioma, comprising the administration of a therapeutically effective amount of a compound of the present invention, or a pharmaceutically acceptable salt or solvate thereof, to a patient in need of such treatment. Preferably the patient is a warm-blooded animal, more preferably a human. The cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD are preferably those defined above.

[0311] The invention further provides the use of a compound of the present invention, or a pharmaceutically acceptable salt or solvates thereof, for the manufacture of a medicament for use in treating cancer, in particular a cancer selected from cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket, more particularly a cancer selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers, still more particularly a cancer selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer and pleural mesothelioma. Preferably the patient is a warm-blooded animal, more preferably a human. The cancers that are modulated, in particular inhibited, by the interaction between YAP / TAZ and TEAD are preferably those defined above. According to a further feature of the present invention, there is provided the use of a compound of the present invention, preferably a compound of Formula I and any of its embodiments, or any of its subformulae as defined above, or a pharmaceutically acceptable salt or solvate thereof, for modulating, in particular for inhibiting, the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket, in a patient in need of such treatment, comprising administering to said patient an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt or solvate thereof. In other terms, the invention also provides a method for modulating, in particular for inhibiting, the interaction between YAP / TAZ and TEAD, in particular targeting the palmitate pocket, in a patient in need of such treatment, which comprises the step of administering to said patient an effective amount of a compound of the present invention, preferably a compound of Formula I and any of its embodiments, or any of its subformulae as defined above, or a pharmaceutically acceptable salt or solvate thereof. Preferably, the patient is a warm blooded animal, and even more preferably a human.

[0312] According to the present invention, the compound of the invention or the compound for use according to the invention may be administered as a pharmaceutical formulation in a therapeutically effective amount by any of the accepted modes of administration, preferably by intravenous or oral route.

[0313] Therapeutically effective amount ranges are typically from 0.1 to 50 000 pg / kg of body weight daily, preferably from 1 000 to 40 000 pg / kg of body weight daily, depending upon numerous factors such as the severity of the disease to be treated, the age and relative health of the subject, the potency of the compound, the route and the form of administration, the indication towards which the administration is directed, and the preferences and experience of the medical practitioner involved. One of ordinary skill in the art of treating such diseases will be able in reliance upon personal knowledge, to ascertain a therapeutically effective amount of the anti cancer agent of the present invention for a given cancer.

[0314] According to one embodiment, the compounds of the invention, their pharmaceutical acceptable salts or solvates may be administered as part of a combination therapy. Thus, are included within the scope of the present invention embodiments comprising coadministration of, and compositions and medicaments which contain, in addition to a compound of the present invention, a pharmaceutically acceptable salt or solvate thereof as active ingredient, additional therapeutic agents and / or active ingredients. Such multiple drug regimens, often referred to as combination therapy, may be used in the treatment of cancer, particularly those defined above.

[0315] Thus, the methods of treatment and pharmaceutical compositions of the present invention may employ the compounds of the invention or their pharmaceutical acceptable salts or solvates thereof in the form of monotherapy, but said methods and compositions may also be used in the form of multiple therapy in which one or more compounds of the invention or their pharmaceutically acceptable salts or solvates are co-administered in combination with one or more other therapeutic agents.

[0316] In one embodiment, the methods of treatment and pharmaceutical compositions of the present invention may employ the compounds of the present invention, or their pharmaceutical acceptable salts or solvates thereof, in combination with radiation therapy. According to this embodiment, the compounds of the invention, their pharmaceutical acceptable salts or solvates may be administered in combination with radiation therapy. Thus, there is provided a compound of Formula I and any of its embodiments, or any of its subformulae as defined above, for use in the treatment of cancers as defined above in combination with radiation therapy. Such radiation therapies include, but are not limited to, external beam radiation therapy, brachytherapy and systemic radioisotope therapy.

[0317] The invention also provides a pharmaceutical composition comprising a compound of the present invention, preferably a compound of Formula I and any of its embodiments, or any of its subformulae as defined above, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable carrier, diluent, excipient and / or adjuvant. As indicated above, the invention also covers pharmaceutical compositions which contain, in addition to a compound of the present invention, a pharmaceutically acceptable salt or solvate thereof as active ingredient, additional therapeutic agents and / or active ingredients.

[0318] The invention also provides a compound of the invention, or a pharmaceutically acceptable salt or solvate thereof, for use in a therapeutic treatment in humans or animals. Another object of this invention is a medicament comprising at least one compound of the invention, or a pharmaceutically acceptable salt or solvate thereof, as active ingredient.

[0319] Generally, for pharmaceutical use, the compounds of the invention may be formulated as a pharmaceutical preparation comprising at least one compound of the invention and at least one pharmaceutically acceptable carrier, diluent, excipient and / or adjuvant, and optionally one or more further pharmaceutically active compounds.

[0320] By means of non-limiting examples, such a formulation may be in a form suitable for oral administration, for parenteral administration (such as by intravenous, intramuscular or subcutaneous injection or intravenous infusion), for topical administration (including ocular), cerebral administration, for administration by inhalation, by a skin patch, by an implant, by a suppository, etc. Such suitable administration forms - which may be solid, semi-solid or liquid, depending on the manner of administration - as well as methods and carriers, diluents and excipients for use in the preparation thereof, will be clear to the skilled person; reference is made to the latest edition of Remington’s Pharmaceutical Sciences.

[0321] For example, the compound of the invention or a pharmaceutical composition comprising a compound of the invention can be administered orally in the form of tablets, coated tablets, pills, capsules, soft gelatin capsules, oral powders, granules, ovules, elixirs, solutions or suspensions, which may contain flavouring or colouring agents, for immediate-, delayed-, modified-, sustained-, pulsed- or controlled-release applications.

[0322] The tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, dibasic calcium phosphate and glycine, a disintegrant such as starch (preferably corn, potato or tapioca starch), sodium starch glycollate, croscarmellose sodium and certain complex silicates, a binder such as polyvinylpyrrolidone, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), sucrose, gelatin and acacia, a lubricant such as magnesium stearate, stearic acid, glyceryl behenate. Solid compositions of a similar type may also be employed as fillers in hard gelatin capsules. Preferred excipients in this regard include lactose, saccharose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives or gelatin. Hard gelatin capsules may contain granules of the compound of the invention. Soft gelatin capsules may be prepared with capsules containing the compound of the invention, vegetable oil, waxes, fat, or other suitable vehicle for soft gelatin capsules. As an example, the acceptable vehicle can be an oleaginous vehicle, such as a long chain triglyceride vegetable oil (e.g. corn oil).

[0323] Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water may contain the active ingredient in a mixture with dispersing agents, wetting agents, and suspending agents and one or more preservatives. Additional excipients, for example sweetening, flavouring and colouring agents, may also be present. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid.

[0324] Liquid dosage forms for oral administration may include pharmaceutically acceptable, solutions, emulsions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water or an oleaginous vehicle. Liquid dosage form may be presented as a dry product for constitution with water or other suitable vehicle before use. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, complexing agents such as 2-hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta-cylodextrin, and sweetening, flavouring, perfuming agents, colouring matter or dyes with diluents such as water, ethanol, propylene glycol and glycerin, and combinations thereof. These compositions may be preserved by the addition of an antioxidant such as butylated hydroxyanisol or alpha-tocopherol.

[0325] Finely divided powder of the compound of the invention may be prepared for example by micronisation or by processes known in the art. The compound of the invention may be milled using known milling procedures such as wet milling to obtain a particle size appropriate for tablet formation and for other formulation types.

[0326] If the compound of the present invention is administered parenterally, then examples of such administration include one or more of: intravenously, intraarterially, intraperitoneally, intrathecally, intraventricularly, intraurethrally, intrasternally, intracranially, intramuscularly or subcutaneously administering the agent; and / or by using infusion techniques. The compound of the invention can be administered via the parenteral route with a readily available or a depot-type formulation.

[0327] The pharmaceutical compositions for the parenteral administration of a readily available formulation may be in the form of a sterile injectable aqueous or oleagenous solution or suspension in a non-toxic parenterally-acceptable diluent or solvent and may contain formulatory agents such as suspending, stabilising dispersing, wetting and / or complexing agents such as cyclodextrin e.g. 2-hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta- cylodextrin.

[0328] The depot-type formulation for the parenteral administration may be prepared by conventional techniques with pharmaceutically acceptable excipient including without being limited to, biocompatible and biodegradable polymers (e.g. poly(P-caprolactone), polyethylene oxide), poly(gly colic acid), poly [(lactic acid)-co-(gly colic acid)...)], poly(lactic acid)...), non-biodegradable polymers (e.g. ethylene vinylacetate copolymer, polyurethane, polyester(amide), polyvinyl chloride...) aqueous and non-aqueous vehicles (e.g. water, sesame oil, cottonseed oil, soybean oil, castor oil, almond oil, oily esters, ethyl alcohol or fractionated vegetable oils, propylene glycol, DMSO, THF, 2-pyrrolidone, N- methylpyrrolidinone, N-vinylpyrrolidinone... ).

[0329] Alternatively, the active ingredient may be in dry form such as a powder, crystalline or freeze-dried solid for constitution with a suitable vehicle. The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well known to those skilled in the art.

[0330] As indicated, the compound of the present invention can be administered intranasally or by inhalation and is conveniently delivered in the form of a dry powder inhaler or an aerosol spray presentation from a pressurised container, pump, spray or nebuliser with the use of a suitable propellant, e.g. dichlorodifluoromethane, trichlorofluoromethane, di chlorotetrafluoroethane, (for example from Ineos Fluor), carbon dioxide or other suitable gas. In the case of a pressurised aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. The pressurised container, pump, spray or nebuliser may contain a solution or suspension of the active compound. Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator may be formulated to contain a powder mix of the compound and a suitable powder base such as lactose or starch. For compositions suitable and / or adapted for inhaled administration, it is preferred that the compound or salt of formula I is in a particle-size-reduced form, and more preferably the size-reduced form is obtained or obtainable by micronisation. The preferable particle size of the size-reduced (e.g. micronised) compound or salt or solvate is defined by a D50 value of about 0.5 to about 50 microns (for example as measured using laser diffraction).

[0331] Alternatively, the compound of the present invention can be administered in the form of a suppository or pessary, or it may be applied topically in the form of a gel, hydrogel, lotion, solution, cream, ointment or dusting powder. The compound of the present invention may also be dermally or transdermally administered, for example, by the use of a skin patch. They may also be administered by the pulmonary or rectal routes. It may also be administered by the ocular route. For ophthalmic use, the compound can be formulated as micronised suspensions in isotonic, pH adjusted, sterile saline, or, preferably, as solutions in isotonic, pH adjusted, sterile saline, optionally in combination with a preservative such as a benzylalkonium chloride. Alternatively, it may be formulated in an ointment such as petrolatum.

[0332] For topical application to the skin, the agent of the present invention can be formulated as a suitable ointment containing the active compound suspended or dissolved in, for example, a mixture with one or more of the following: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, it can be formulated as a suitable lotion or cream, suspended or dissolved in, for example, a mixture of one or more of the following: mineral oil, sorbitan monostearate, a polyethylene glycol, liquid paraffin, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water.

[0333] DEFINITIONS

[0334] The definitions and explanations below are for the terms as used throughout the entire application, including both the specification and the claims.

[0335] Unless otherwise stated, any reference to compounds of the invention herein, means the compounds as such as well as their pharmaceutically acceptable salts and solvates. When describing the compounds of the invention, the terms used are to be construed in accordance with the following definitions, unless indicated otherwise.

[0336] The term “unsubstituted” as used herein means that a radical, a group or a residue carries no substituents. The term “substituted” means that a radical, a group or a residue carries one or more substituents.

[0337] The term “halo” or “halogen” refers to the atoms of the group 17 of the periodic table (halogens) and includes in particular fluorine, chlorine, bromine and iodine atom. Preferred halo groups in the context of the invention are fluoro and iodo, fluoro being particularly preferred.

[0338] The term “alkyl” by itself or as part of another substituent refers to a hydrocarbyl group of Formula CnEEn+i wherein n is a number greater than or equal to 1. Alkyl groups may thus comprise 1 or more carbon atoms and generally, according to this invention comprise from 1 to 12, more preferably from 1 to 8 carbon atoms, and still more preferably from 1 to 6 carbon atoms. Alkyl groups within the meaning of the invention may be linear or branched. Examples of alkyl groups include but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopenyl, isopentyl, sec-pentyl, tert-pentyl, n-hexyl, neohexyl, isohexyl, sec-hexyl and tert-hexyl. Particular examples of alkyl groups in the context of the invention include methyl, ethyl, n-propyl, n-butyl and tert-butyl.

[0339] The term “haloalkyl” alone or in combination, refers to an alkyl group having the meaning as defined above wherein one or more hydrogens are replaced with a halogen as defined above. Non -limiting examples of such haloalkyl groups include chloromethyl, 1- bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1 -trifluoroethyl and the like. A particular example of haloalkyl groups according to the invention is trifluoromethyl.

[0340] The term “cycloalkyl” as used herein is a monovalent, saturated, or unsaturated monocyclic or bicyclic hydrocarbyl group. Cycloalkyl groups may comprise 3 or more carbon atoms in the ring and generally, according to this invention comprise from 3 to 10, more preferably from 3 to 8 carbon atoms, and still more preferably from 3 to 6 carbon atoms. Cycloalkyl groups may comprise 1 or more cycles, in particular 1 to 3 cycles. Examples of cycloalkyl groups include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and adamantanyl. Particular examples of cycloalkyl groups according to the invention include, cyclohexyl and adamantanyl.

[0341] The term “heteroatom” as used herein refers to any atom that is not carbon or hydrogen. Non-limiting examples of such heteroatoms include nitrogen, oxygen, sulfur, and phosphorus. Preferred heteroatoms according to the invention are nitrogen, oxygen and sulfur.

[0342] The terms “heterocyclyl”, “heterocycloalkyl” or “heterocyclo” as used herein by itself or as part of another group refer to non-aromatic, fully saturated or partially unsaturated cyclic groups (for example, 3- to 7-membered monocyclic, 7- to 11-membered bicyclic, or containing a total of 3 to 10 ring atoms) which have at least one heteroatom in at least one carbon atom-containing ring. Each ring of the heterocyclic group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from nitrogen, oxygen and / or sulfur atoms, where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system, where valence allows. Examples of heterocyclyl groups include but are not limited to aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, piperazinyl, morpholinyl.

[0343] The term “aryl” as used herein refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (e.g. phenyl) or multiple aromatic rings fused together (e.g. naphthyl), typically containing 5 to 12 atoms; preferably 6 to 10, wherein at least one ring is aromatic. Examples of aryl groups include but are not limited to phenyl, biphenyl, 1 -naphthyl (or naphthal ene-l-yl), 2-naphthyl (or naphthalene-2-yl), anthracenyl, indanyl, indenyl, 1, 2,3,4- tetrahydronaphthyl. Partticular examples of aryl groups according to the invention include phenyl, biphenyl, 1 -naphthyl (or naphthalene- 1-yl) and 2-naphthyl (or naphthal ene-2-yl).

[0344] The term “heteroaryl” as used herein by itself or as part of another group refers but is not limited to 5 to 12 carbon-atom aromatic rings or ring systems containing 1 to 2 rings which are fused together, each ring typically containing 5 to 6 atoms; at least one of which is aromatic, in which one or more carbon atoms in one or more of these rings is replaced by oxygen, nitrogen and / or sulfur atoms where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. Examples of heteroaryl groups include but are not limited to pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, quinolinyl, quinoxalinyl, quinazolinyl, furanyl, benzofuranyl, pyrrolyl, indolyl, thiophenyl, benzothiophenyl, imidazolyl, benzimidazolyl, pyrazolyl, indazolyl, oxazolyl, benzoxazolyl, isoxazolyl, benzisoxazolyl, thiazolyl, and benzothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dioxazolyl, dithiazolyl and tetrazolyl. A particular example of heteroaryl groups according to the invention is pyridinyl.

[0345] The term “vinyl sulfonamido” or “ethenesulfonamido” as used herein by itself or as part of another group refers to a group of the following formula: H2C=CH-SO2NH-

[0346] The compounds of the invention containing a basic functional group may be in the form of pharmaceutically acceptable salts. Pharmaceutically acceptable salts of the compounds of the invention containing one or more basic functional groups include in particular the acid addition salts thereof. Suitable acid addition salts are formed from acids which form nontoxic salts. Examples include the acetate, adipate, aspartate, benzoate, besylate, bicarbonate / carbonate, bi sulphate / sulphate, borate, camsylate, cinnamate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulphate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate and xinofoate salts.

[0347] Pharmaceutically acceptable salts of compounds of Formula I and subformulae may for example be prepared as follows:

[0348] (i) reacting the compound of Formula I or any of its subformulae with the desired acid; or

[0349] (ii) converting one salt of the compound of Formula I or any of its subformulae to another by reaction with an appropriate acid or by means of a suitable ion exchange column.

[0350] All these reactions are typically carried out in solution. The salt may precipitate from solution and be collected by filtration or may be recovered by evaporation of the solvent. The degree of ionization in the salt may vary from completely ionized to almost non-ionized. The term “solvate” is used herein to describe a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term “hydrate” is employed when said solvent is water.

[0351] The compounds of the invention include compounds of the invention as hereinbefore defined, including all polymorphs and crystal habits thereof, prodrugs and isomers thereof (including optical, geometric and tautomeric isomers) and isotopically-labeled compounds of the invention.

[0352] In addition, although generally, with respect to the salts of the compounds of the invention, pharmaceutically acceptable salts are preferred, it should be noted that the invention in its broadest sense also includes non-pharmaceutically acceptable salts, which may for example be used in the isolation and / or purification of the compounds of the invention. For example, salts formed with optically active acids or bases may be used to form diastereoisomeric salts that can facilitate the separation of optically active isomers of the compounds of the invention.

[0353] The term “patient” refers to a warm-blooded animal, more preferably a human, who / which is awaiting or receiving medical care or is or will be the object of a medical procedure.

[0354] The term “human” refers to subjects of both genders and at any stage of development (i.e. neonate, infant, juvenile, adolescent, adult). In one embodiment, the human is an adolescent or adult, preferably an adult.

[0355] The terms “treat”, “treating” and “treatment”, as used herein, are meant to include alleviating or abrogating a condition or disease and / or its attendant symptoms.

[0356] The term “therapeutically effective amount” (or more simply an “effective amount”) as used herein means the amount of active agent or active ingredient which is sufficient to achieve the desired therapeutic or prophylactic effect in the individual to which it is administered.

[0357] The term “administration”, or a variant thereof (e.g., “administering”), means providing the active agent or active ingredient, alone or as part of a pharmaceutically acceptable composition, to the patient in whom / which the condition, symptom, or disease is to be treated. By “pharmaceutically acceptable” is meant that the ingredients of a pharmaceutical composition are compatible with each other and not deleterious to the patient thereof.

[0358] The term “excipient” as used herein means a substance formulated alongside the active agent or active ingredient in a pharmaceutical composition or medicament. Acceptable excipients for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington’s Pharmaceutical Sciences, 21stEdition 2011. The choice of excipient can be selected with regard to the intended route of administration and standard pharmaceutical practice. The excipient must be acceptable in the sense of being not deleterious to the recipient thereof. The at least one pharmaceutically acceptable excipient may be for example, a binder, a diluent, a carrier, a lubricant, a disintegrator, a wetting agent, a dispersing agent, a suspending agent, and the like.

[0359] The term “pharmaceutical vehicle” as used herein means a carrier or inert medium used as solvent or diluent in which the pharmaceutically active agent is formulated and / or administered. Non-limiting examples of pharmaceutical vehicles include creams, gels, lotions, solutions, and liposomes.

[0360] The term “cancer” as used herein refers to the physiological condition in subjects that is characterized by unregulated or dysregulated cell growth with the potential to invade or spread to other parts of the body. The term “cancer” includes solid tumors and blood born tumors, whether malignant or benign.

[0361] Examples of cancer include, but are not limited to:

[0362] Acinar adenocarcinoma, acinar carcinoma, acral-lentiginous melanoma, actinic keratosis, adenocarcinoma, adenocystic carcinoma, adenosquamous carcinoma, adnexal carcinoma, adrenal rest tumor, adrenocortical carcinoma, aldosterone secreting carcinoma, alveolar soft part sarcoma, amelanotic melanoma, ameloblastic thyroid carcinoma, angiosarcoma, apocrine carcinoma, Askin’s tumor, astrocytoma, basal cell carcinoma, basaloid carcinoma, basosquamous cell carcinoma, biliary cancer, bone cancer, bone marrow cancer, botryoid sarcoma, brain cancer, breast cancer, bronchioalveolar carcinoma, bronchogenic adenocarcinoma, bronchogenic carcinoma, carcinoma ex pleomorphic adenoma, cervical cancer, chloroma, cholangiocellular carcinoma, chondrosarcoma, choriocarcinoma, choroid plexus carcinoma, clear cell adenocarcinoma, colon cancer, colorectal cancer, comedocarcinoma, corti sol -producing carcinoma, cylindrical cell carcinoma, dedifferentiated liposarcoma, ductal adenocarcinoma of the prostate, ductal carcinoma, ductal carcinoma in situ, duodenal cancer, eccrine carcinoma, embryonal carcinoma, endometrial carcinoma, endometrial stromal carcinoma, epithelioid sarcoma, esophageal cancer, Ewing’s sarcoma, exophytic carcinoma, fibroblastic sarcoma, fibrocarcinoma, fibrolamellar carcinoma, fibrosarcoma, follicular thyroid carcinoma, gallbladder cancer, gastric adenocarcinoma, giant cell carcinoma, giant cell sarcoma, giant cell tumor of bone, glioma, glioblastoma or glioblastoma multiforme, granulose cell carcinoma, head & neck cancer, hemangioma, hemangiosarcoma, hepatoblastoma, hepatocellular carcinoma, Hurthle cell carcinoma, ileal cancer, infiltrating lobular carcinoma, inflammatory carcinoma of the breast, intraductal carcinoma, intraepidermal carcinoma, jejuna cancer, Kaposi’s sarcoma, Krukenberg’s tumor, Kulchitsky cell carcinoma, Kupffer cell sarcoma, large cell carcinoma, larynx cancer, lentigo maligna melanoma, liposarcoma, liver cancer, lobular carcinoma, lobular carcinoma in situ, lung cancer, lymphoepithelioma, lymphoepithelioma, lymphosarcoma, malignant melanoma, medullary carcinoma, medullary thyroid carcinoma, medulloblastoma, meningeal carcinoma, Merkel cell carcinoma, micropapillary carcinoma, mixed cell sarcoma, mucinous carcinoma, mucoepidermoid carcinoma, mucosal melanoma, myxoid liposarcoma, myxosarcoma, nasopharyngeal carcinoma, nephroblastoma, neuroblastoma, nodular melanoma, non-clear cell renal cancer, non-small cell lung cancer, oat cell carcinoma, ocular melanoma, oral cancer, osteoid carcinoma, osteosarcoma, ovarian cancer, Paget’ s carcinoma, pancreatic cancer, pancreatoblastoma, papillary adenocarcinoma, papillary carcinoma, papillary thyroid carcinoma, pelvic cancer, periampullary carcinoma, phyllodes tumor, pituitary cancer, pleomorphic liposarcoma, pleuropulmonary blastoma, primary intraosseous carcinoma, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, round cell liposarcoma, scar cancer, schistosomal bladder cancer, Schneiderian carcinoma, sebaceous carcinoma, signet-ring cell carcinoma, skin cancer, small cell lung cancer, small cell osteosarcoma, soft tissue sarcoma, splindle cell carcinoma, spindle cell sarcoma, squamous cell carcinoma, stomach cancer, superficial spreading melanoma, synovial sarcoma, telangiectatic sarcoma, terminal duct carcinoma, testicular cancer, thyroid cancer, transitional cell carcinoma, tubular carcinoma, tumorigenic melanoma, undifferentiated carcinoma, urachal adenocarcinoma, urinary bladder cancer, uterine cancer, uterine corpus carcinoma, uveal melanoma, aginal cancer, cerrucous carcinoma, villous carcinoma, well-differentiated liposarcoma, Wilm’s tubor or yolk sac tumor. Particular examples of cancers according to the invention include breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers. Still more particular examples of cancers according to the invention include breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer and pleural mesothelioma.

[0363] The present invention will be better understood with reference to the following examples and figures. These examples are intended to be representative of specific embodiments of the invention, and are not intended as limiting the scope of the invention.

[0364] EXAMPLES

[0365] ABBREVIATIONS

[0366] DHP: 3,4-dihydro-2H-pyran;

[0367] DMAP: 4-dimethylaminopyridine;

[0368] DMEM: Dulbecco's Modified Eagle Medium;

[0369] DMF : N,N-dimethylformamide

[0370] DMSO: dimethyl suf oxide; eq.: equivalent;

[0371] ESI: electrospray ionization;

[0372] FBS: Fetal Bovine Serum;

[0373] HPLC: high-performance liquid chromatography;

[0374] LC-MS: liquid chromatography - mass spectrometry; Mp: melting point;

[0375] MS: mass spectrometry;

[0376] MW: molecular weight;

[0377] NMP: N-methyl-2-pyrrolidone;

[0378] NMR: nuclear magnetic resonance; ppm: parts per million;

[0379] PPTS: pyridinium p-toluenesulfonate;

[0380] THF : tetrahydrofurane;

[0381] TLC: thin-layer chromatography;

[0382] IR: retention time;

[0383] UV: ultraviolet.

[0384] SYNTHESIS

[0385] 1. Material and instrumentation

[0386] All reagents and solvents were purchased from various suppliers (Sigma-Aldrich, Alfa Aesar, Fisher, TCI, Fluorochem, VWR, Carlo Erba) and used without further purification. Reactions were monitored by TLC performed on Macher ey -Nagel Alugram® Sil 60 / UV254 sheets (thickness 0.2 mm). TLC were revealed by UV (X = 254 nm) and / or the appropriate stain.

[0387] All purifications were carried out by flash chromatography or preparative high pressure liquid chromatography (HPLC). Flash chromatography was performed on a Reveleris® Flash Chromatography System using Buchi FlashPure Silica gel (35-45 pm) and HPLC was performed on a Shimadzu LC-20AP using C18 Apollo (5 μM). NMR spectra were recorded on a Bruker Avance 300 spectrometer at 300 MHz (XH), 75 MHz (13C) and 282 MHz (19F) and / or on a Bruker Avance 500 spectrometer at 500 MHz (XH), 125 MHz (13C) and 471 MHz (19F). Chemical shifts are expressed in ppm relative to tetramethylsilane (TMS) using the residual proton peaks of deuterated solvent as internal reference. Chemical shifts are reported as position (5 in ppm), multiplicity (s = singulet, d = doublet, t = triplet, q = quartet, p = pentuplet, m = multiplet, br = broad), coupling constant (Jin Hz) and relative integral and assignment. The attributions of protons and carbons were achieved by analysis of ID and 2D experiments (XH,13C, COSY, HSQC and HMBC).

[0388] Mass spectra were recorded with an LC-MS (Waters Alliance Micromass ZQ 2000) using electrospray ionization (ESI) and a UV detector (diode array). LC-MS analysis was performed using a Waters XBridge Cl 8 column (5 pm particle size column, dimensions 50 mm x 4.6 mm). A gradient starting from 98% H2O / formate buffer 5 mM (pH 3.8) and reaching 100% CH3CN / formate buffer 5 mM (pH 3.8) within 4 min at a flow rate of 2 mL / min was used followed by a return to the starting conditions within 1 min. The MassLynx™ software was used to determine the nominal mass of main pics of the spectrum.

[0389] The melting points (Mp) were measured on Barnstead Electrothermel Melting Point Series IA9200 and were not corrected.

[0390] 2. Synthesis procedures

[0391] 2,1, Synthesis of 5-aryl / alkyl-oxy-7J / -indoles (Examples 1-10)

[0392] General procedure A for nucleophilic substitution: To a solution of 5-hydroxyindole (0.5 g, 1 eq., 1.88 mmol) and K2CO3 (1 eq.) in DMF (2.5 mL), alkyl or aryl bromide (1 eq.) was added. Reaction was stirred under reflux for 18 h. Solvent was removed under vacuum and residue was diluted in ethyl acetate and washed with water (three times). Organic phase was dried over MgSO4 and solvent was removed under vacuum. Product was purified by column chromatography with ethyl acetate: cyclohexane (5:95) as eluant.

[0393] General procedure B for Mitsunobu reaction: To a solution of 5-hydroxyindole (0.5 g, 1 eq., 1.88 mmol) in THF (8.5 mL), di- / c / 7-butyl azodi carb oxy late (2.1 eq.), triphenylphosphine (2.1 eq.) and alcohol derivative (1.5 eq.) were added. The reaction was stirred at 50 °C for 18 h. Solvent was removed under vacuum and residue was diluted in ethyl acetate and washed with water (three times). Organic phase was dried over MgSO4 and solvent was removed under vacuum. Product was purified by column chromatography with ethyl acetate / cyclohexane (10:90) as eluant. EXAMPLE 1: 5-(cvclohexylmethoxy)-7J / -indole (FT142) 229.32 g / mol; Mp = 63-65 °C.

[0394] Compound 1 was synthesized following general procedure B from cyclohexylmethanol (0.64 g) and was obtained as a brown solid in 72% yield.

[0395] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.07 (brs, 1 H, Hi), 7.28 (d, 1 H,3J = 8.8 Hz, H7), 7.20-7.17 (m, 2 H, H24), 6.94 (dd, 1 H,3J = 8.8 Hz,4J = 2.0 Hz, H6), 6.52 (ddd, 1 H,3J =

[0396] 3.2 Hz,4. / 2.2 Hz,5J = 1.0 Hz, H3), 4.11 (t, 2 H,3J = 6.7 Hz, Hr), 1.88-1.00 (m, 11 H, H2’,3’,4’,5’)

[0397] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.7 (5), 131.0 (7a), 128.3 (4a), 124.9 (2), 113.0 (6), 111.7 (7), 103.5 (4), 102.3 (3), 66.9 (!’), 36.9 (5’), 34.7 (2’), 33.4 (3’), 26.4 (4’). LC-MS (ESI): m / z Calculated: 229.2, Found: 230.1 [M+H]+, tR= 3.6 min.

[0398] EXAMPLE 2: 5-phenethoxy- / / / -indole (FT143)

[0399] CI6HI5NO; MW = 237.30 g / mol

[0400] Compound 2 was synthesized following general procedure A from (2-bromoethyl)benzene (0.51 mL) and was obtained as a white oil in 78% yield. 1H NMR (300 MHz, CDCI3): δ (ppm) 8.06 (brs, 1 H, Hi), 7.39-7.14 (m, 6 H, H74’,4’,5’), 7.20 (t, 1 H,3J = 2.9 Hz, H2), 7.15 (d, 1 H,4J = 2.4 Hz, H4), 6.90 (dd, 1 H,3J = 8.7 Hz,4J = 2.4 Hz, H6), 6.49 (1 H, ddd,3J = 2.9 Hz,4J = 2.0 Hz,5J = 0.9 Hz, H3), 4.26 (t, 1 H,3J = 7.3 Hz, Hr), 3.16 (t, 1 H,3J = 7.3 Hz, Hr).

[0401] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.2 (5), 138.6 (3’), 131.1 (7a), 129.0 (5’), 128.5 (4’), 128.3 (4a), 126.4 (6’), 124.8 (2), 113.0 (6), 111.6 (7), 103.7 (4), 102.4 (3), 69.6 (!’), 36.0 (2’).

[0402] LC-MS (ESI): m / z Calculated: 237.1, Found: 238.1 [M+H]+, tR= 3.1 min.

[0403] EXAMPLE 3: 5-isobutoxy-7#-indole (FT152) 189.26 g / mol; Mp = 65-67 °C.

[0404] Compound 3 was synthesized following general procedure B from isopropylmethanol (0.52 mL) and was obtained as a brown solid in 83% yield.

[0405] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.05 (brs, 1 H, Hi), 7.29 (d, 1 H,3J = 8.7 Hz, H7), 7.18-7.17 (m, 2 H, H24), 6.93 (dd, 1 H,3J = 8.7 Hz,4J = 2.4 Hz, H6), 6.52 (ddd, 1 H,3J = 3.0 Hz,4J = 2.0 Hz,5J = 0.9 Hz, H3), 3.83 (d, 2 H,3J = 6.7 Hz, Hr), 2.17 (non, 1 H,3J = 6.7 Hz, H2’), 1.10 (d, 6 H,3J = 6.7 Hz, Hr).

[0406] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.8 (5), 131.0 (7a), 128.3 (4a), 124.8 (2), 113.0 (6), 111.6 (7), 103.6 (4), 102.3 (3), 75.5 (!’), 28.4 (2’), 19.4 (3’).

[0407] LC-MS (ESI): m / z Calculated: 189.3, Found: 190.1 [M+H]+, tR= 3.1 min.

[0408] EXAMPLE 4: 5- -2-vlmethoxv)-777-indole (FT153) 273.34 g / mol; Mp = 123-125 °C.

[0409] Compound 4 was synthesized following general procedure A from 2-

[0410] (bromomethyl)naphthalene (0.83 g) and was obtained as an orange solid in 78% yield.

[0411] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.06 (brs, 1 H, Hi), 7.97 (m, 1 H, H6’), 7.93-7.88 (m, 3 H, H4’,9’,ii’), 7.63 (dd, 1 H,3J = 8.4 Hz,4J = 1.5 Hz, H3’), 7.54-7.50 (m, 2 H, H7’,8’), 7.32

[0412] (d, 1 H,3J = 9.0 Hz, H7), 7.28 (d, 1 H, V = 2.4 Hz, H4), 7.20 (t, 1 H,3J = 2.8 Hz, H2), 7.03 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.52 (ddd, 1 H,3J = 2.8 Hz,4J = 1.9 Hz,5J = 0.9 Hz, H3), 5.32 (S, 2 H, Hr).

[0413] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.5 (5), 135.3 (2’), 133.4 (10’), 133.1 (5’), 131.2 (7a), 128.3 (4a), 128.3 (3’), 128.0 (6’), 127.8 (9’), 126.3 (4’), 126.2 (11’), 125.9 (8’), 125.5

[0414] (7’), 124.9 (2), 113.1 (6), 111.7 (7), 104.2 (4), 102.5 (3), 71.1 (1’).

[0415] LC-MS (ESI): m / z Calculated: 273.1, Found: 274.1 [M+H]+, tR= 3.3 min.

[0416] EXAMPLE 5: 5-(naphthalen-l-ylmethoxy)-7J / -indole (FT155) 273.34 g / mol

[0417] Compound 5 was synthesized following general procedure A from 1-

[0418] (bromomethyl)naphthalene (0.83 g) and was obtained as a green oil in 75% yield.

[0419] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.18-8.14 (m, 1 H, Hur), 8.10 (brs, 1 H, Hi), 7.95- 7.92 (m, 1 H, H7’), 7.88 (d, 1 H,3J = 8.3 Hz, H5 ), 7.68 (dd, 1 H,3J = 7.0 Hz,4J = 1.2 Hz, H3’), 7.58 - 7.48 (m, 3 H, H4’,8’,9’), 7.34 (d, 1 H,3J = 8.8 Hz, H7), 7.34 (d, 1 H,4J = 2.4 Hz, I l l

[0420] H4), 7.23 (t, 1 H,3J = 2.8 Hz, H2), 7.01 (dd, 1 H,3J = 8.8 Hz, V = 2.4 Hz, H6), 6.53 (ddd, 1 H,3J = 2.8 Hz,4J = 2.0 Hz,5J = 0.9 Hz, H3), 5.57 (s, 2 H, Hr).

[0421] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.5 (5), 133.8 (2’), 133.0 (6’), 131.7 (11’), 131.2 (7a), 128.8 (7’), 128.6 (5’), 128.3 (4a), 126.5 (9’), 126.4 (8’), 125.8 (4’), 125.4 (3’), 124.9 (2), 123.9 (10’), 113.2 (6), 111.7 (7), 104.0 (4), 102.5 (3), 69.6 (1’).

[0422] LC-MS (ESI): m / z Calculated: 273.1, Found: 274.1 [M+H]+, tR= 3.3 min.

[0423] EXAMPLE 6: 5-(3-phenylpropoxy)-777-indole (FT161) 251.33 g / mol; Mp = 69-73 °C.

[0424] Compound 6 was synthesized following general procedure A from (3-bromopropyl)benzene (0.57 g) and was obtained as a brown solid in 81% yield.

[0425] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.03 (brs, 1 H, Hi), 7.47-7.28 (m, 6 H, H7,5’,6’,7’), 7.21-7.19 (m, 2 H, H24), 6.99 (dd, 1 H,3J = 8.7 Hz,4J = 2.3 Hz, H6), 6.56 (ddd, 1 H,3J = 3.0 Hz,4J = 2.0 Hz,5J = 0.9 Hz, H3), 4.11 (t, 2 H,3J = 6.3 Hz, Hr), 2.94 (t, 2 H,3J = 6.3 Hz, H3’), 2.27-2.18 (m, 2 H, Hr).13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 141.9 (4’), 131.1 (7a), 128.7 (6’), 128.5

[0426] (7’), 128.4 (4a), 126.0 (5’), 125.0 (2), 113.0 (6), 111.8 (7), 103.7 (4), 102.4 (3), 67.9 (!’), 32.4 (3’), 31.2 (2’).

[0427] LC-MS (ESI): m / z Calculated: 251.1, Found: 252.0 [M+H]+, tR= 3.3 min.

[0428] EXAMPLE 7: 5-([l J'-biphenyl]-4-ylmethoxy)-777-indole (FT162) 299.37 g / mol; Mp = 155-157 °C.

[0429] Compound 7 was synthesized following general procedure A from 4-(brom om ethyl)- 1,1'- biphenyl (0.93 g) and was obtained as a white solid in 74% yield.

[0430] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.09 (brs, 1 H, Hi), 7.66-7.62 (m, 4 H, H7’,8’), 7.59- 7.56 (m, 2 H, H3’), 7.50-7.45 (m, 2 H, H4’), 7.41-7.37 (m, 1 H, H9), 7.33 (d, 1 H,3J = 8.8

[0431] Hz, H7), 7.24 (d, 1 H, V = 2.4 Hz, H4), 7.22 (t, 1 H,3J = 3.0 Hz, H2), 7.00 (dd, 1 H,3J = 8.8 Hz, V = 2.4 Hz, H6), 6.53 (ddd, 1 H,3J = 3.0 Hz, V 1.9 Hz, V = 0.9 Hz, H3), 5.18 (s, 2 H, Hr).

[0432] 13C NMR (75 MHz, CDC13): δ (ppm) 153.4 (5), 140.9 (6’), 140.7 (5’), 136.8 (2’), 131.2 (7a), 128.8 (4’), 128.3 (4a), 128.0 (3’), 127.3 (8’), 127.2 (9’), 127.1 (7’), 124.9 (2), 113.1

[0433] (6), 111.7 (7), 104.0 (4), 102.5 (3), 70.7 (!’).

[0434] LC-MS (ESI): m / z Calculated: 299.1, Found: 300.0 [M+H]+, tR= 3.4 min.

[0435] EXAMPLE 8: 5-((4,4-difluorocvclohexyl)methoxy)-lH-indole (MD19) 265.30 g / mol; Mp = 117-119 °C. Compound 8 was synthesized following general procedure A from 4-(brom om ethyl)- 1,1- difluorocyclohexane (0.80 g) in distilled DMF under inert atmosphere and was obtained as a brown solid in 50 % yield. 1H NMR (300 MHz, CDCI3): δ (ppm) 8.09 (brs, 1 H, Hi), 7.30 (d, 1 H,3J = 8.8 Hz, H7), 7.19 (t, 1 H,3J = 2.8 Hz, H2), 7.14 (d, 1 H,4J = 2.3 Hz, H4), 6.90 (dd, 1 H,3J = 8.8 Hz,4J = 2.3 Hz, H6), 6.52 (ddd, 1 H,3J = 2.8 Hz,4J = 1.9 Hz,5J = 0.9 Hz, H3), 3.90 (d, 2 H,3J = 6.3 Hz, Hr), 2.21-1.47 (m, 9 H, H2’3’,4’).

[0436] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.5 (5), 131.1 (7a), 128.3 (4a), 125.0 (2), 123.8 (dd,1. / c-Feq = 241.6 Hz,1Jc-Fax = 239.8 Hz, 5’), 112.8 (6), 111.8 (7), 103.6 (4), 102.3 (3), 72.8 (d, Vc-Feq = 2.7 Hz, 1’), 36.0 (d, Vc-Feq = 1.2 Hz, 2’), 33.2 (dd, Vc-Feq = 25.2 Hz,Vc-Fax = 22.5 Hz, 4’), 26.0 (d, Vc-Feq = 9.6 Hz, 3’).

[0437] 19F NMR (282 MHz, CDCI3): δ (ppm) -91.8 (d,}J= 235.3 Hz), -102.3 (dtt,}J= 235.3 Hz, Vax-ax = 33.2 HZ, Vax-eq = 9.2 Hz).

[0438] LC-MS (ESI): m / z Calculated: 265.1, Found: 264.2 [M-H]", 266.1 [M+H]+, tR= 3.1 min.

[0439] EXAMPLE 9: 5-((3-(trifluoromethyl)benzyl)oxy)-lH-indole (FT322) 291.27 g / mol

[0440] Compound 9 was synthesized following general procedure A from l-(bromomethyl)-3- (trifluoromethyl)benzene (0.58 mL) in DMF and was obtained as a yellow oil in 74% yield.

[0441] 1H NMR (500 MHz, CDCI3): δ (ppm) 8.10 (brs, 1 H, Hi), 7.82 (m, 1 H, Hs ), 7.71-7.63 (m, 2 H, H3,5 ), 7.54 (t, 1 H,3J = 7.8 Hz, H4’), 7.32 (d, 1 H,3J = 8.8 Hz, H7), 7.25 (d, 1 H,4J = 2.3 Hz, H4), 7.20 (t, 1 H,4J = 2.8 Hz, H2), 7.02 (dd, 1 H,3J = 8.8 Hz,4J = 2.3 Hz, H6), 6.55 (ddd, 1H,3J = 2.8 Hz,4J = 1.9 Hz,5J = 0.8 Hz, H3), 5.19 (s, 2 H, Hr).

[0442] 13C NMR (125 MHz, CDCI3): δ (ppm) 153.1 (5), 138.8 (2’), 131.4 (7a), 130.8 (q,2J= 32.3

[0443] Hz, 6’), 130.7 (3’), 129.0 (4’), 128.3 (4a), 126.5 (q, V= 272.2 Hz, 7’), 125.2 (2), 124.6 (q,3J= 3.7 Hz, 8’), 124.1 (q,3J= 3.7 Hz, 5’), 113.0 (6), 111.8 (7), 104.1 (4), 102.5 (3), 70.2

[0444] 19F NMR (471 MHz, CDC13): δ (ppm) -63.1 (s).

[0445] LC-MS (ESI): m / z Calculated: 291.1, Found: 290.2 [M-H]", 292.1 [M+H]+, tR= 3.2 min. 123-125 °C.

[0446] Compound 10 was synthesized following general procedure A from l-(bromomethyl)-4- (trifluoromethyl)benzene (0.58 mL) in DMF and was obtained as a white solid in 82% yield.

[0447] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.11 (brs, 1H, Hi), 7.68-7.61 (m, 4 H, H3\4’), 7.33 (d, 1 H,3J = 8.7 Hz, H7), 7.22 (t, 1 H,3J = 2.9 Hz, H2), 7.18 (d, 1 H,4J = 2.4 Hz, H4), 6.97 (dd, 1 H,3J = 8.7 Hz,4J = 2.4 Hz, H6), 6.50 (ddd, 1H,3J = 2.9 Hz,4J = 2.0 Hz,5J = 0.9 Hz, H3), 5.20 (s, 2 H, Hr).

[0448] 13C NMR (75 MHz, CDC13): δ (ppm) 153.0 (5), 141.9 (2’), 131.3 (7a), 130.0 (q,2J= 32.1 Hz, 5’), 128.3 (4a), 127.4 (3’), 125.5 (q,3J= 3.7 Hz, 4’), 125.1 (2), 124.4 (q,lJ= 272.1 Hz, 6’), 112.9 (6), 111.8 (7), 104.0 (4), 102.5 (3), 70.0 (!’).

[0449] 19F NMR (471 MHz, CDC13): δ (ppm) -63.1 (s).

[0450] LC-MS (ESI): m / z Calculated: 291.1, Found: 290.2 [M-H]", 292.1 [M+H]+, tR= 3.2 min.

[0451] 2,2, Synthesis of 5-alkoxy-7J / -indoles (Examples 11-12)

[0452] General procedure C for the synthesis of compounds 11-12: To a solution of 5- hydroxyindole (0.2 g, 1 eq., 1.50 mmol) and CS2CO3 (3 eq.) in NMP (10 mL), alkyl bromide (3 eq.) was added. Reaction was stirred 45 min at room temperature and then under reflux for 18 h. Solution was diluted with a large amount of water and was extracted with ethyl acetate. Organic phase was dried over MgSO4and solvent was removed under vacuum. Product was purified by column chromatography with ethyl acetate / cyclohexane (5:95) as eluant.

[0453] EXAMPLE 11: 5-(neopentyloxy)-lH-indole (MDMPP2) 203.29 g / mol; Mp = 86-88 °C.

[0454] Compound 11 was synthesized following general procedure C from neopentyl bromide (0.20 g) and was obtained as a brown solid in 9% yield.

[0455] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.01 (brs, 1 H, Hi), 7.28 (d, 1 H,3J = 8.8 Hz, H7), 7.18 (t, 1 H,3J = 2.9 Hz, H2), 7.16 (d, 1 H,4J = 2.4 Hz, H4), 6.94 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 6.51 (ddd, 1 H,3J = 2.9 Hz,4J = 1.9 Hz,5J = 0.9 Hz, H3), 3.70 (s, 2 H, Hr), 1.12 (s, 9 H, H3’).

[0456] 13C NMR (75 MHz, CDC13): δ (ppm) 154.4 (5), 130.9 (7a), 128.3 (4a), 124.7 (2), 113.0 (6), 111.6 (7), 103.5 (4), 102.3 (3), 79.0 (1’), 32.0 (2’), 26.8 (3').

[0457] LC-MS (ESI): m / z Calculated: 203.3, Found: 204.1 [M+H]+, tR= 3.3 min.

[0458] EXAMPLE 12: 5-(adamantan-l-ylmethoxy)-lH-indole (MDMPP7) 281.40 g / mol; Mp = 117-119 °C.

[0459] Compound 12 was synthesized following general procedure C from 1- (bromomethyl)adamantane (0.41 g) and Nal (2.4 eq., 0.54 g) and was obtained as a brown solid in 17% yield. 1H NMR (300 MHz, CDCI3): δ (ppm) 8.04 (brs, 1 H, Hi), 7.28 (d, 1 H,3J = 8.8 Hz, H7), 7.18 (t, 1 H,3J = 3.0 Hz, H2), 7.13 (d, 1 H,4J = 2.3 Hz, H4), 6.90 (dd, 1 H,3J = 8.8 Hz,4J = 2.3 Hz, H6), 6.49 (ddd, 1 H,3J = 3.0 Hz,4J = 1.9 Hz,5J = 0.9 Hz, H3), 3.59 (s, 2 H, Hr), 2.08 - 1.72 (m, 13 H, HJ’,4’,5’)

[0460] 13C NMR (75 MHz, CDCI3): δ (ppm) 154.4 (5), 130.8 (7a), 128.3 (4a), 124.7 (2), 113.0 (6), 111.5 (7), 103.5 (4), 102.4 (3), 79.4 (!’), 39.6 (3’), 37.3 (4’), 34.0 (2’), 28.3 (5’).

[0461] LC-MS (ESI): m / z Calculated: 281.4, Found: 282.1 [M+H]+, tR= 3.9 min.

[0462] 2,3, Synthesis of (5-(benzyloxy)-lH-indol-l-yl)alkyl acids (Examples 13-16) and nitrile (Example 17)

[0463] General procedure D for the synthesis of compounds 13-16: To a solution of 5- benzyloxyindole (0.50 g, 1 eq., 2.2 mmol) in DMF (5 mL), NaH (1.5 eq.) was added. Reaction was stirred at room temperature, under argon for 1 h. Then, a solution of bromo ester or bromo nitrile (1.5 eq.) in DMF (3 mL) was added dropwise and the reaction mixture was stirred for 16 h.

[0464] Treatment for acids: Reaction was hydrolysed with HC1 (6 N, 5 mL) and stirred for another 3 h at 60 °C. Later, solvent was removed under vacuum and residue was dissolved in NaHCO3(I N) solution. Aqueous phase was extracted three times with diethyl ether and acidified with HC1 (1 N) to pH 1. Another extraction was completed with diethyl ether (three times). Combined organic phases was dried over MgSCh and solvent was removed under vacuum to afford the pure product.

[0465] Treatment for nitrile and phthalimide: Reaction was hydrolysed with water and solvent was removed under vacuum. Residue was dissolved ethyl acetate and was extracted three times with water (3 x 10 mL). Organic phase was dried over MgSO4and solvent was removed under vacuum. Product was purified by column chromatography with cyclohexane / ethyl acetate (50:50) as eluant and was obtained as a solid.

[0466] EXAMPLE 13: 2-(5-(benzyloxy)-7J / -indol-l-yl)acetic acid (FT55) 281.31 g / mol; Mp = 102-104 °C.

[0467] Compound 13 was synthesized according to the general procedure D from ethyl 2- bromoacetate (0.37 mL) and was obtained as a brown solid in 55% yield.

[0468] 1H NMR (300 MHz, CD2CI2): δ (ppm) 7.50-7.48 (m, 2 H, H3’), 7.44-7.32 (m, 3 H, H4,5 ), 7.19-7.16 (m, 2 H, H4,7), 7.09 (d, 1 H, V 3.2 Hz, H2), 6.97 (dd, 1 H,3J = 9.0 Hz,4J = 2.57

[0469] Hz, H6), 6.49 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.12 (2 H, s, Hr), 4.90 (s, 2 H, Hi”).

[0470] 13C NMR (75 MHz, CD2CI2): δ (ppm) 173.1 (COO), 153.5 (5), 137.8 (2’), 131.9 (7a), 129.1 (4a), 129.1 (2), 128.4 (4’), 127.7 (5’), 127.5 (3’), 112.9 (6), 109.6 (4), 104.4 (7), 102.1 (3), 70.7 (1’), 47.3 (1”). LC-MS (ESI): m / z Calculated: 281.1, Found: 280.2 [M-H]", 282.2 [M+H]+, tR= 2.6 min.

[0471] EXAMPLE 14: 3-(5-(benzyloxy)-7J / -indol-l-yl)propanoic acid (FT50) 295.34 g / mol; Mp = 118-120 °C.

[0472] Compound 14 was synthesized according to the general procedure D from ethyl 3- bromopropionate (0.38 mL) and was obtained as a pink solid in 44% yield.

[0473] 1H NMR (300 MHz, CD2CI2): δ (ppm) 7.51-7.48 (m, 2 H, Hr), 7.44-7.34 (m, 3 H, H4’,5’), 7.29 (d, 1 H,3J = 8.8 Hz, H7), 7.16-7.15 (m, 2 H, HM), 6.95 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 6.40 (dd, 1 H,3J = 3.0 Hz,5J = 0.9 Hz, H3), 5.11 (s, 2 H, Hr), 4.44 (t, 2 H,3J = 6.8 Hz, H2”), 2.89 (t, 2 H,3J = 6.8 Hz, Hi”).

[0474] 13C NMR (75 MHz, CD2C12): δ (ppm) 174.3 (COO), 153.2 (5), 137.9 (2’), 131.1 (7a), 129.1 (4a), 128.5 (2), 128.4 (4’), 127.7 (5’), 127.5 (3’), 112.4 (6), 109.8 (4), 104.2 (7), 101.1 (3), 70.7 (!’), 41.7 (2”), 34.3 (1”).

[0475] LC-MS (ESI): m / z Calculated: 295.1, Found: 294.3 [M-H]", 296.2 [M+H]+, tR= 2.8 min.

[0476] EXAMPLE 15: 4-(5-(benzyloxy)-777-indol-l-yl)butanoic acid (FT53) 309.37 g / mol; Mp = 126-128 °C.

[0477] Compound 15 was synthesized according to the general procedure D from ethyl 4- bromobutyrate (0.48 mL) and was obtained as a brown solid in 2% yield.

[0478] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.49 (m, 2 H, H3’), 7.44-7.34 (m, 3 H, H4,5), 7.27 (d, 1 H,3J = 8.9 Hz, H7), 7.19 (d, 1 H,4J = 2.42 Hz, H4), 7.08 (d, 1 H,3J = 3.0 Hz, H2), 6.98 (dd, 1 H, \J = 8.9 Hz, \J = 2.4 Hz, H6), 6.43 (dd, 1 H,3J = 3.0 Hz,5J = 0.6 Hz, H3), 5.13 (s, 2 H, Hr), 4.20 (t, 2 H,3J = 6.6 Hz, H3”), 2.36 (t, 2 H,3J = 6.6 Hz, Hi”), 2.18 (quin, 2 H,3J = 6.6 Hz, Hr).

[0479] 13C NMR (75 MHz, CDC13): δ (ppm) 177.3 (COO), 153.2 (5), 137.7 (2’), 131.4 (7a), 129.0 (4a), 128.5 (2), 128.3 (4’), 127.7 (5’), 127.5 (3’), 112.7 (6), 110.0 (4), 104.3 (7), 101.0 (3), 70.9 (1’), 45.4 (3”), 30.7 (1”), 25.2 (2”).

[0480] LC-MS (ESI): m / z Calculated: 309.1, Found: 308.3 [M-H]", 310.3 [M+H]+, tR= 2.9 min.

[0481] EXAMPLE 16: 5-(5-(benzyloxy)-777-indol-l-yl)Dentanoic acid (FT54)

[0482] 323.39 g / mol; Mp = 139-141 °C.

[0483] Compound 16 was synthesized according to the general procedure D from ethyl 5- bromopentanoate (0.53 mL) and was obtained as a brown solid in 20% yield.

[0484] 1H NMR (300 MHz, CD2CI2): d (ppm) 7.50-7.48 (m, 2 H, H3’), 7.43-7.34 (m, 3 H, H4,5 ), 7.27 (d, 1 H,3J = 8.9 Hz, H7), 7.17 - 7.11 (m, 2 H, H24), 6.96 (dd, 1 H,3J= 8.9 Hz,4J= 2.2

[0485] Hz, H6), 6.40 (dd, 1 H,3J = 3.0 Hz,5J = 0.9 Hz, H3), 5.12 (s, 2 H, Hr), 4.13 (t, 2 H,3J = 7.6 Hz, H4”), 2.37 (t, 2 H,3J = 7.6 Hz, Hi”), 1.89 (quin, 2 H,3J = 7.6 Hz, H3”), 1.64 (quin, 2 H,3J = 7.6 Hz, H2”).

[0486] 13C NMR (75 MHz, CD2CI2): δ (ppm) 177.8 (COO), 153.0 (5), 137.9 (2’), 131.5 (7a), 128.9 (4a), 128.4 (2), 128.3 (4’), 127.7 (5’), 127.5 (3’), 112.2 (6), 110.0 (4), 104.0 (7), 100.5

[0487] (3), 70.7 (!’), 46.1 (1”), 33.1 (4”), 29.6 (3”), 22.1 (2”).

[0488] LC-MS (ESI): m / z Calculated: 323.2, Found: 322.3 [M-H]~, 324.3 [M+H]+, tR= 3.0 min.

[0489] EXAMPLE 17: 2-(5-(benzyloxy)-lH-indol-l-yl)acetonitrile (MD16) 262.31 g / mol; Mp = 116-118 °C. Compound 17 was synthesized from ethyl 2-bromoacetonitrile (0.23 mL) and was obtained as a white solid in 32% yield. 1H NMR (300 MHz, CDCI3): δ (ppm) 7.45-7.38 (m, 5 H, H3’,4’,5’), 7.29 (d, 1 H,3J = 8.5 Hz, H7), 7.22 (d, 1H,3J = 2.3 Hz, H4), 7.10-7.06 (m, 2 H, H2,6), 6.54 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.15 (s, 2 H, Hr), 4.96 (s, 2 H, Hi”).

[0490] 13C NMR (75 MHz, CDC13): 154.1 (5), 137.4 (2’), 131.2 (7a), 129.5 (4a), 128.6 (4’), 127.9 (5’), 127.8 (2), 127.5 (3’), 114.4 (CN), 113.7 (6), 109.6 (4), 104.9 (7), 103.9 (3), 70.9 (!’), 34.4 (1”).

[0491] LC-MS (ESI): m / z Calculated: 262.1, Found: 263.2 [M+H]+, tR= 2.9 min.

[0492] 2.4. Synthesis of (5-(benzyloxy)-lH-indol-l-yl)alkyl methyl ester (Examples 18-19)

[0493] General procedure E for the synthesis of compounds 18-19: To a solution of 5- benzyloxyindole (0.40 g, 1 eq., 1.8 mmol) in dry acetone (10 mL), Cs2CO3(2 eq.) and bromo methyl ester (1.5 eq.) were added. Optionally, Nal (1 eq.) was added. Reaction was stirred and refluxed for 24-72h. Solvent was removed under vacuum. Residue was dissolved ethyl acetate and was extracted three times with water (3 x 10 mL). Organic phase was washed with brine then dried over MgSO4and solvent was removed under vacuum. Product was purified by column chromatography with cyclohexane / ethyl acetate (100:0 to 80:20) as eluant.

[0494] EXAMPLE 18: methyl 2-(5-(benzyloxy)-lH-indol-l-yl)acetate (BGZ0017) 295.34 g / mol

[0495] Compound 18 was synthesized following general procedure E from methyl bromoacetate

[0496] (0.26 mL) and was obtained as a pink solid in 70% yield.

[0497] 1H NMR (300 MHz, CDCI3): δ 7.50 - 7.32 (m, 5 H, H3’,4’,5’), 7.18 (d, 1 H,4. / = 2.4 Hz, H4),

[0498] 7.15 (d, 1 H,3J = 8.9 Hz, H7), 7.06 (d, 1 H,3J = 3.2 Hz, H2), 7.07 (d, 1 H,3J= 3.1 Hz, H6), 6.48 (dd, 1 H,3J = 3.2 Hz,5J= 0.7 Hz, H3), 5.11 (s, 2 H, Hr), 4.82 (s, 2 H, Hi”), 3.74 (s, 3 H, H2”).

[0499] 13C NMR (75 MHz, CDCk): δ 169.2 (COO), 153.7 (5), 137.8 (2’), 132.1 (7a), 129.2 (2), 129.1 (4a), 128.6 (4’), 127.9 (5’), 127.6 (3’), 113.2 (6), 109.8 (4), 104.6 (7), 102.3 (3), 71.0 (!’), 52.7 (1”), 48.0 (2”).

[0500] LC-MS (ESI): m / z Calculated: 295.3, Found: 296.1 [M+H]+, tR= 2.2 min.

[0501] (BGZ0020) / mol

[0502] Compound 19 was synthesized following general procedure E from methyl 5-bromovalerate (0.39 mL) and Nal (269 mg) and was obtained as a colourless oil which solidified as a white solid upon cold storage in 30% yield.

[0503] 1H NMR (300 MHz, CDCI3): δ 7.52 -7.29 (m, 5 H, Hr, 4’, 5’), 7.24 (d, 1 H,3. / = 8.9 Hz, H7), 7.18 (d, 1 H,4. / = 2.3 Hz, H4), 7.06 (d, 1 H,3. / = 3.2 Hz, H2), 6.97 (dd, 1 H,3. / = 8.9 Hz, V = 2.3 Hz, H6), 6.41 (dd, 1 H,3. / = 3.2 Hz,5J= 0.6 Hz, H3), 5.11 (s, 2 H, Hr), 4.10 (t, 2 H,

[0504] 3J = 7.0 Hz, Hi”), 3.66 (s, 3, Hs ), 2.32 (t, 2 H,3J = 7.3 Hz, H4”), 1.94-1.80 (m, 2 H, H2”), 1.72-1.56 (m, 2 H, H3”).

[0505] 13C NMR (75 MHz, CDCI3): δ 173.7 (COO), 153.3 (5), 137.9 (2’), 131.5 (7a), 129.0 (4a), 128.6 (4’), 128.4 (2), 127.8 (5’), 127.7 (3’), 112.7 (6), 110.1 (7), 104.3 (4), 100.8 (3), 71.0 (!’), 51.7 (5”), 46.3 (1”), 33.6 (4”), 29.8 (2”), 22.5 (3”).

[0506] LC-MS (ESI): m / z Calculated: 337.4, Found: 338.2 [M+H]+, tR= 2.4 min. 2.5. Synthesis of (5-(benzyloxy)-lH-indol-l-yl)alkyl amines 20-21)

[0507] General procedure F for the synthesis of compounds 20-21: To a solution of 5- benzyloxyindole (0.50 g, 1 eq., 2.2 mmol) in acetonitrile (8 mL), NaOH (5 eq.) and tetrabutylammonium hydrogen sulphate (0.2 eq.) were added. Reaction was stirred at room temperature during 1 h. Then, chloroalkylamine hydrochloride (1.2 eq.) was added and the reaction mixture was stirred at reflux for 16 h. Reaction was hydrolysed with water (15 mL) and extracted with di chloromethane (15 mL). Aqueous phase was washed with di chloromethane three times (3 ^ 15 mL). Combined organic phases was dried over MgSCL and solvent was removed under vacuum. Product was purified by column chromatography with dichloromethane / methanol (90: 10) as eluant and was obtained as a solid.

[0508] EXAMPLE 20: 2 (5- i-lH-indol-1- -1 -amine -127 °C; MW = 266.34 g / mol

[0509] Compound 20 was synthesized following the general procedure F from 2-chloroethylamine hydrochloride (0.31 g) and was obtained as a yellow solid in 88% yield.

[0510] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.34 (m, 5 H, Hs’,4’,5’), 7.29 (d, 1 H,3J = 9.0 Hz, H7), 7.21 (d, 1 H,3J = 2.4 Hz, H4), 7.14 (d, 1 H, V = 3.1 Hz, H2), 6.99 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.45 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.13 (s , 2 H, Hr), 4.18 (t, 1 H,3J = 5.9 Hz, H2”), 3.12 (t, 1 H,3J = 5.9 Hz, Hi”), 1.42 (s, 3 H, NH2).

[0511] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.3 (5), 137.7 (2’), 131.6 (7a), 129.1 (4a), 128.7 (2), 128.5 (4’), 127.8 (5’), 127.5 (3’), 112.7 (6), 110.1 (7), 104.3 (4), 101.0 (3), 70.9 (!’), 49.7 (1”), 42.1 (2”).

[0512] LC-MS (ESI): m / z Calculated: 266.1, Found: 267.1 [M+H]+, tR= 2.2 min. -1 -amine (FT260) C; MW = 280.37 g / mol

[0513] Compound 21 was synthesized following the general procedure F from 3 -chloropropylamine hydrochloride (0.35 g) and was obtained as a brown solid in 81% yield.

[0514] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.33 (m, 5 H, H3’,4’,5’), 7.28 (d, 1 H,3J = 8.9 Hz, H7), 7.19 (d, 1 H,4J = 2.4 Hz, H4), 7.09 (d, 1 H,3J = 3.1 Hz, H2), 6.97 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.42 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.12 (s, 2 H, Hr), 4.20 (t, 2 H,3J = 6.8 Hz, H3”), 2.72 (t, 2 H,3J = 6.8 Hz, Hi”), 1.98 (q, 2 H,3J = 6.8 Hz, H2”)

[0515] 13C NMR (75 MHz, CDC13): δ (ppm) 153.1 (5), 137.8 (2’), 131.5 (7a), 128.9 (4a), 128.5 (4’), 128.3 (2), 127.7 (5’), 127.5 (3’), 112.6 (6), 110.0 (7), 104.2 (4), 100.7 (3), 70.9 (!’), 44.0 (3”), 39.4 (1”), 33.8 (2”).

[0516] LC-MS (ESI): m / z Calculated: 280.2, Found: 281.1 [M+H]+, tR= 2.2 min.

[0517] 2.6. Synthesis of N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)alkylamides or sulfonamides es 22-:

[0518] General procedure G for the synthesis of compounds 22-36: To a solution of 5- benzyloxytryptamine (0.10 g, 1 eq., 0.38 mmol), 2-(5-(benzyloxy)-lH-indol-l- yl)ethanamine (0.10 g, 1 eq., 0.38 mmol) or 3-(5-(benzyloxy)-lH-indol-l-yl)propan-l- amine (0.10 g, 1 eq., 0.36 mmol) in dichloromethane (4 mL), triethylamine (2 eq.) was added, followed by the sulfonyl chloride or the acid chloride derivative (1 eq.). The reaction was stirred at room temperature for 2 h. Water (10 mL) was added and the solution was extracted. Organic layer was washed with brine (10 mL) two times and was dried over MgS04 and solvent was removed under vacuum. Product was purified by column chromatography with ethyl acetate / di chloromethane (50:50) as eluant.

[0519] EXAMPLE 22: N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)methanesulfonamide (FT238) 344.43 g / mol, Mp = 275-277 °C. Compound 22 was synthesized following the general procedure G from 5- benzyloxytryptamine and methanesulfonylchloride (0.03 mL) and was obtained as a yellow solid in 82% yield.

[0520] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.10 (brs, 1 H, Hi), 7.53-7.32 (m, 5 H, H3’,4’,5’), 7.28 (dd, 1 H,3J = 8.8 Hz,4J = 0.5 Hz, H7), 7.14 (d, 1 H,4J = 2.3 Hz, H4), 7.03 (m, 1 H, H2), 6.98 (dd, 1 H,3J = 8.8 Hz,4J = 2.3 Hz, H6), 5.14 (s, 2 H, Hr), 4.43 (brs, 1 H, NH), 3.42 (t,

[0521] 2 H,3J = 6.6 Hz, Hi”), 3.00 (t, 1H,3J = 6.6 Hz, Hr), 2.80 (s, 3 H, CH3).

[0522] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.3 (5), 137.6 (2’), 131.8 (7a), 128.6 (4’), 127.9 (5’), 127.6 (3’), 127.4 (4a), 123.5 (2), 113.2 (6), 112.2 (7), 111.4 (3), 102.2 (4), 71.0 (!’), 43.2 (1”), 40.2 (CH3), 26.1 (2”). LC-MS (ESI): m / z Calculated: 344.1, Found: 343.2 [M-H]", 345.1 [M+H]+, tR= 2.7 min.

[0523] EXAMPLE 23: N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)ethenesulfonamide (FT249) -261 °C; MW = 356.44 g / mol Compound 23 was synthesized following the general procedure G from 5- benzyloxytryptamine and ethenesulfonylchloride (0.05 g) and was obtained as a grey solid in 74% yield.

[0524] 1H NMR (300 MHz, CDC13): δ (ppm) 8.10 (brs, 1 H, Hi), 7.53-7.32 (m, 5 H, H3’,4’,5’), 7.28 (d, 1 H,3J = 8.8 Hz, H7), 7.12 (d, 1 H, V = 2.4 Hz, H4), 7.03 (d, 1 H,3J = 2.2 Hz, H2), 6.98 (dd, 1 H,3J = 8.8 Hz, V = 2.4 Hz, H6), 6.36 (dd, 1 H,3J = 16.6 Hz,3J = 9.8 Hz, HSO2CH=CH2), 6.18 (d, 1 H, V = 16.6 Hz, HSQ2CH=CH2), 5.83 (d, 1 H, V = 9.8 Hz, HSQ2CH=CH2), 5.14 (s, 2 H, Hr), 4.43 (s, 1 H, NH), 3.32 (q, 1 H, Hr), 2.99 (t, 1 H, Hi”).

[0525] 13C NMR (75 MHz, CDC13): δ (ppm) 153.3 (5), 137.5 (2’), 135.7 (SO2CH=CH2), 131.8 (7a), 128.6 (4’), 127.9 (5’), 127.6 (3’), 127.4 (4a), 126.5 (SO2CH=CH2), 123.5 (2), 113.2 (6), 112.1 (7), 111.4 (3), 102.2 (4), 71.0 (!’), 42.9 (2”), 25.9 (1”).

[0526] LC-MS (ESI): m / z Calculated: 356.1, Found: 355.2 [M-H]", 357.1 [M+H]+, tR= 2.9 min.

[0527] EXAMPLE 24: N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)methanesulfonamide (FT259) 344.43 g / mol; Mp = 241-243 °C.

[0528] Compound 24 was synthesized following the general procedure G from 2-(5-(benzyloxy)- lH-indol-l-yl)ethanamine and methanesulfonylchloride (0.03 mL) and was obtained as a pink solid in 38% yield.

[0529] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.34 (m, 5 H, H3’,4’,5’), 7.28 (d, 1 H,3J = 8.9 Hz, H7), 7.19 (d, 1 H, V = 2.4 Hz, H4), 7.12 (d, 1 H,3J = 3.1 Hz, H2), 7.00 (dd, 1 H,3J = 8.9 Hz, V = 2.4 Hz, H6), 6.45 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.12 (s, 2 H, Hr), 4.41 (t, 1 H,3J = 6.7 Hz, NH), 4.30 (t, 2 H,3J = 5.7 Hz, H2”), 3.52 (q, 2 H,3J = 6.7 Hz, Hi”), 2.71 (s, 3 H, CH3).13C NMR (75 MHz, CDCI3): δ (ppm) 153.5 (5), 137.6 (2’), 131.2 (7a), 129.2 (4a), 128.6 (2), 128.5 (4’), 127.8 (5’), 127.5 (3’), 113.1 (6), 109.9 (7), 104.5 (4), 101.8 (3), 70.9 (!’), 47.0 (2”), 43.2 (1”), 40.4 (CH3).

[0530] LC-MS (ESI): m / z Calculated: 344.1, Found: 343.2 [M-H]", 345.1 [M+H]+, tR= 2.9 min. EXAMPLE 25: N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)methanesulfonamide (FT261) 358.46 g / mol; Mp = 245-247 °C.

[0531] Compound 25 was synthesized following the general procedure G from 3-(5-(benzyloxy)- lH-indol-l-yl)propan-l-amine and methanesulfonylchloride (0.03 mL) and was obtained as a red solid in 39% yield.

[0532] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.35 (m, 5 H, H3’,4’,5’), 7.26 (d, 1 H,3J = 8.9 Hz, H7), 7.21 (d, 1 H, V = 2.4 Hz, H4), 7.12 (d, 1 H,3J = 3.1 Hz, H2), 6.99 (dd, 1 H,3J = 8.9 Hz, V = 2.4 Hz, H6), 6.44 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.12 (s, 2 H, Hr), 4.67 (t, 2 H,3J = 6.2 Hz, NH), 4.19 (t, 2 H,3J = 6.6 Hz, H3”), 3.04 (q, 2 H,3J = 6.5 Hz, Hi”), 2.83 (s, 3 H, CH3), 2.07 (quin, 2 H,3J = 6.6 Hz, H2”).13C NMR (75 MHz, CDC13): δ (ppm) 153.3 (5), 137.7 (2’), 131.3 (7a), 129.1 (4a), 128.6

[0533] (4’), 128.5 (2), 127.8 (5’), 127.6 (3’), 112.8 (6), 110.0 (7), 104.4 (4), 101.2 (3), 70.9 (!’), 43.4 (3”), 40.6 (1”), 39.8 (CH3), 30.4 (2”).

[0534] LC-MS (ESI): m / z Calculated: 358.1, Found: 357.2 [M-H]", 359.2 [M+H]+, tR= 2.9 min.

[0535] EXAMPLE 26: N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)ethenesulfonamide (FT263) 356.44 g / mol; Mp = 236-238 °C.

[0536] Compound 26 was synthesized following the general procedure G from 2-(5-(benzyloxy)- lH-indol-l-yl)ethanamine and ethenesulfonylchloride (0.05 g) and was obtained as a pink solid in 65% yield.

[0537] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.34 (m, 5 H, H3’,4’,5’), 7.26 (d, 1 H,3J = 8.9 Hz, H7), 7.19 (d, 1 H,4J = 2.3 Hz, H4), 7.11 (d, 1 H,3J = 3.1 Hz, H2), 6.99 (dd, 1 H,3J = 8.9 Hz,4J = 2.3 Hz, H6), 6.45 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 6.29 (dd,3J = 16.6 Hz,3J = 9.3 Hz, HSO2CH=CH2), 6.17 (d, 1 H,3J = 16.6 Hz, HSQ2CH=CH2), 5.81 (d, 1 H,3J = 9.3 Hz, HSO2CH=CH2), 5.13 (s, 2 H, Hr), 4.32 (t, 1 H,3J = 6.7 Hz, NH), 4.30 (t, 2 H,3J = 6.0 Hz, H2”), 3.42 (q, 2 H,3J = 6.3 Hz, Hi”).

[0538] 13C NMR (75 MHz, CDC13): δ (ppm) 153.5 (5), 137.6 (2’), 135.4 (SO2CH=CH2), 131.2 (7a), 129.2 (4a), 128.6 (2), 128.5 (4’), 127.8 (5’), 127.5 (3’), 127.0 (SO2CH=CH2), 113.1 (6), 109.9 (7), 104.5 (4), 101.8 (3), 70.9 (!’), 46.9 (2”), 42.8 (1”).

[0539] LC-MS (ESI): m / z Calculated: 356.1, Found: 355.1 [M-H]", 357.0 [M+H]+, tR= 3.0 min. EXAMPLE 27: N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)ethenesulfonamide (FT264)

[0540] 370.47 g / mol; Mp = 228-230 °C.

[0541] Compound 27 was synthesized according to the following the general procedure G from 3- (5-(benzyloxy)-lH-indol-l-yl)propan-l-amine and ethenesulfonylchloride (0.05 g) and was obtained as a yellow solid in 79% yield.

[0542] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.35 (m, 5 H, H3’,4’,5’), 7.25 (d, 1 H,3J = 8.9 Hz, H7), 7.20 (d, 1 H,4J = 2.4 Hz, H4), 7.11 (d, 1 H,3J = 3.1 Hz, H2), 6.99 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.44 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 6.38 (dd,3J = 16.6 Hz,3J = 9.8 Hz, HSO2CH=CH2), 6.18 (d, 1 H,3J = 16.6 Hz, HSQ2CH=CH2), 5.89 (d, 1 H,3J = 9.8 Hz, HSO2CH=CH2), 5.13 (S, 2 H, Hr), 4.53 (t, 1 H,3J = 6.1 Hz, NH), 4.20 (t, 2 H,3J = 6.6 Hz, H3”), 2.95 (q, 2 H,3J = 6.5 Hz, Hi”), 2.06 (q, 2 H,3J = 6.5 Hz, Hr).

[0543] 13C NMR (75 MHz, CDC13): δ (ppm) 153.3 (5), 137.7 (2’), 135.4 (SO2CH=CH2), 131.3 (7a), 129.1 (4a), 128.6 (2), 128.4 (4’), 127.8 (5’), 127.6 (3’), 127.2 (SO2CH=CH2), 112.8 (6), 110.0 (7), 104.4 (4), 101.2 (3), 70.9 (!’), 43.4 (3”), 40.4 (1”), 30.2 (2”).

[0544] LC-MS (ESI): m / z Calculated: 370.1, Found: 369.2 [M-H]", 371.1 [M+H]+, tR= 3.1 min. EXAMPLE 28: N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)acetamide (FT268) 308.38 g / mol; Mp = 271-273 °C. Compound 28 was synthesized following the general procedure G from 3-(5-(benzyloxy)- lH-indol-l-yl)propan-l-amine and acetyl chloride (0.03 mL) and was obtained as a yellow solid in 88% yield.

[0545] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.64 (brs, 1 H, Hi), 7.51 - 7.34 (m, 5 H, H3’,4\5’), 7.26 (d, 1 H,3J = 8.7 Hz, H7), 7.16 (d, 1 H,4J = 2.5 Hz, H4), 6.96 (d, 1 H,3J = 2.7 Hz, H2), 6.96 (dd, 1 H,3J = 8.7 Hz, \J = 2.5 Hz, H6), 5.86 (d, 1 H,3J = 5.6 Hz, NH), 5.11 (s, 2 H, Hr), 3.57 (q, 2 H,3J = 6.8 Hz, Hi”), 2.92 (t, 2 H,3J = 6.9 Hz, Hr), 1.92 (s, 3 H, CH3).

[0546] 13C NMR (75 MHz, CDCI3): δ (ppm) 170.5 (CO), 153.1 (5), 137.6 (2’), 131.9 (7a), 128.6 (4’), 127.9 (5’), 127.7 (4a), 127.7 (3’), 123.1 (2), 112.9 (6), 112.4 (3), 112.2 (7), 102.2 (4), 71.1 (!’), 39.8 (1”), 25.3 (2”), 23.3 (CH3).

[0547] LC-MS (ESI): m / z Calculated: 308.2, Found: 309.1 [M+H]+, tR= 2.5 min.

[0548] EXAMPLE 29: N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)acetamide (FT269) 308.38 g / mol; Mp = 232-234 °C.

[0549] Compound 29 was synthesized following the general procedure G from 2-(5-(benzyloxy)- lH-indol-l-yl)ethanamine and acetyl chloride (0.03 mL) and was obtained as a yellow solid in 85% yield.

[0550] 1H NMR (300 MHz, CDC13): δ (ppm) 7.50-7.34 (m, 5 H, H3’,4’,5’), 7.25 (d, 1 H,3J = 8.7 Hz, H7), 7.20 (d, 1 H, V = 2.4 Hz, H4), 7.04 (d, 1 H,3J = 3.1 Hz, H2), 6.98 (dd, 1 H,3J = 8.7 Hz, \J = 2.4 Hz, H6), 6.45 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.86 (t, 1 H,3J = 6.1 Hz, NH), 5.11 (s, 2 H, Hr), 4.20 (t, 2 H,3J = 5.8 Hz, Hr), 3.51 (q, 2 H,3J = 6.0 Hz, Hi”), 1.85 (s, 3 H, CH3).13C NMR (75 MHz, CDCI3): δ (ppm) 170.8 (CO), 153.3 (5), 137.6 (2’), 131.6 (7a), 129.0 (4a), 128.6 (4’), 128.5 (2), 127.9 (5’), 127.6 (3’), 112.8 (6), 110.0 (7), 104.4 (4), 101.3 (3), 70.9 (!’), 45.6 (2”), 40.0 (1”), 23.0 (CH3).

[0551] LC-MS (ESI): m / z Calculated: 308.2, Found: 309.1 [M+H]+, tR= 2.7 min. EXAMPLE 30: N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)acetamide (FT270) 322.41 g / mol; Mp = 234-236 °C.

[0552] Compound 30 was synthesized following the general procedure G from 3-(5-(benzyloxy)- lH-indol-l-yl)propan-l-amine and acetyl chloride (0.03 mL) and was obtained as a white solid in 79% yield.

[0553] 1H NMR (300 MHz, CDC13): d (ppm) 7.52-7.35 (m, 5 H, H3’,4’,5’), 7.23 (d, 1 H,3J = 8.9 Hz, H7), 7.21 (d, 1 H, V = 2.6 Hz, H4), 7.08 (d, 1 H,3J = 3.2 Hz, H2), 6.99 (dd, 1 H,3J = 8.9 Hz, V = 2.6 Hz, H6), 6.44 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.87 (t, 1 H,3J = 5.7 Hz, NH), 5.12 (s, 2 H, Hr), 4.09 (t, 2 H,3J = 6.8 Hz, H3”), 3.17 (q, 2 H,3J = 6.7 Hz, Hi”), 1.97 (quin, 2 H,3J = 6.7 Hz, Hr), 1.82 (s, 3 H, CH3).13C NMR (75 MHz, CDCI3): δ (ppm) 170.6 (CO), 153.2 (5), 137.7 (2’), 131.4 (7a), 129.1

[0554] (4a), 128.6 (4’), 128.5 (2), 127.9 (5’), 127.6 (3’), 112.7 (6), 110.1 (7), 104.4 (4), 101.0 (3), 70.9 (!’), 44.4 (3”), 37.4 (1”), 29.8 (2”), 23.0 (CH3).

[0555] LC-MS (ESI): m / z Calculated: 322.2, Found: 323.0 [M+H]+, tR= 2.8 min.

[0556] EXAMPLE 31: N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)acrylamide (FT271) 320.39 g / mol; Mp = 275-277 °C.

[0557] Compound 31 was synthesized following the general procedure G from 5- benzyloxytryptamine and acryloyl chloride (0.03 mg) and was obtained as a white solid in 69% yield.

[0558] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.57 (brs, 1 H, Hi), 7.51-7.34 (m, 5 H, H3’,4’,5’), 7.25 (d, 1 H,3J = 8.9 Hz, H7), 7.16 (d, 1 H,4J = 2.3 Hz, H4), 6.96 (dd, 1 H,3J = 8.9 Hz,4J = 2.3 Hz, H6), 6.94 (d, 1 H,3J = 3.2 Hz, H2), 6.29 (dd, 1 H, V= 16.9 Hz,5J= 1.6 Hz, HCQCH=CH2), 6.02 (dd, 1 H,3J = 16.9 Hz,3J = 10.3 Hz, HCOCH=CH2), 5.99 (m, 1 H, NH), 5.60 (dd, 1 H,3J = 10.3 Hz,5J = 1.6 Hz, HCoCH=CH2), 5.10 (s, 2 H, Hr), 3.65 (q, 2 H,3J = 6.9 Hz, Hi”), 2.96 (t, 2 H,3J = 6.9 Hz, H2”).

[0559] 13C NMR (75 MHz, CDCI3): δ (ppm) 165.8 (CO), 153.1 (5), 137.6 (2’), 131.9 (7a), 131.0 (COCH=CH2), 128.6 (4’), 127.9 (5’), 127.7 (3’), 127.7 (4a), 126.4 (COCH=CH2), 123.2 (2), 113.0 (6), 112.4 (3), 112.2 (7), 102.3 (4), 71.0 (!’), 39.9 (1”), 25.2 (2”).

[0560] LC-MS (ESI): m / z Calculated: 320.2, Found: 321.1 [M+H]+, tR= 2.7 min. EXAMPLE 32: N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)acrylamide (FT273) 320.39 g / mol; Mp = 266-268 °C. Compound 32 was synthesized following the general procedure G from 2-(5-(benzyloxy)- lH-indol-l-yl)ethanamine and acryloyl chloride (0.03 mg) and was obtained as a yellow solid in 71% yield.

[0561] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.34 (m, 5 H, H3’,4’,5’), 7.25 (d, 1 H,3J = 8.9 Hz, H7), 7.19 (d, 1 H, V = 2.4 Hz, H4), 7.03 (d, 1 H,3J = 3.2 Hz, H2), 6.97 (dd, 1 H,3J =

[0562] 8.9 Hz,4J = 2.4 Hz, H6), 6.43 (dd, 1 H,3J = 3.2 Hz,5J = 0.8 Hz, H3), 6.25 (dd, 1 H,3J = 17.0 Hz,5J = 1.4 Hz, HCOCH=CH2), 5.95 (dd, 1 H,3J = 17.0 Hz,3J = 10.4 Hz, HCOCH=CH2), 5.86 (m, 1 H, NH), 5.60 (dd, 1 H,3J = 10.4 Hz,5J = 1.4 Hz, HCQCH=CH2), 5.11 (s, 2 H, Hr), 4.25 (t, 2 H,3J = 5.7 Hz, Hr), 3.62 (q, 2 H,3J = 6.1 Hz, Hi”).

[0563] 13C NMR (75 MHz, CDC13): δ (ppm) 166.0 (CO), 153.3 (5), 137.6 (2’), 131.5 (7a), 130.4 (COCHCH2), 129.1 (4a), 128.6 (2), 128.6 (4’), 127.8 (5’), 127.6 (3’), 126.9 (COCHCH2),

[0564] 112.9 (6), 110.1 (7), 104.4 (4), 101.3 (3), 70.9 (!’), 45.6 (2”), 40.0 (1”).

[0565] LC-MS (ESI): m / z Calculated: 320.2, Found: 321.1 [M+H]+, tR= 2.8 min.

[0566] (FT274)

[0567] Compound 33 was synthesized following the general procedure G from 3-(5-(benzyloxy)- lH-indol-l-yl)propan-l-amine and acryloyl chloride (0.03 mg) and was obtained as a yellow oil in 74% yield.

[0568] 1H NMR (300 MHz, CDC13): δ (ppm) 7.51-7.34 (m, 5 H, H3’,4’,5’), 7.24 (d, 1 H,3J = 8.9 Hz, H7), 7.19 (d, 1 H, V = 2.3 Hz, H4), 7.10 (d, 1 H,3J = 3.1 Hz, H2), 6.98 (dd, 1 H,3J = 8.9 Hz,4J = 2.3 Hz, H6), 6.43 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 6.19 (dd, 1 H,3J = 17.0 Hz,5J = 1.5 Hz, HCoCH=CH2), 5.91 (dd, 1 H,3J = 17.0 Hz,3J = 10.3 Hz, HCOCH=CH2), 5.58 (dd, 1 H,3J = 10.3 Hz,5J = 1.5 Hz, HCQCH=CH2), 5.54 (m, 1 H, NH), 5.12 (s, 2 H, Hr), 4.16 (t, 2 H,3J = 6.7 Hz, H3”), 3.30 (q, 2 H,3J = 6.7 Hz, Hi”), 2.06 (quin, 2 H,3J = 6.7 Hz, Hi”).

[0569] 13C NMR (75 MHz, CDCI3): δ (ppm) 165.7 (CO), 153.3 (5), 137.7 (2’), 131.3 (7a), 130.6 (COCHCHi), 129.0 (4a), 128.5 (4’), 128.4 (2), 127.8 (5’), 127.5 (3’), 126.4 (COCHCH2), 112.8 (6), 110.0 (7), 104.4 (4), 101.1 (3), 70.9 (!’), 44.4 (3”), 37.4 (1”), 29.9 (2”).

[0570] LC-MS (ESI): m / z Calculated: 334.2, Found: 335.1 [M+H]+, tR= 2.9 min.

[0571] EXAMPLE 34: N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)-2-chloroacetamide (FT275)

[0572] Compound 34 was synthesized following the general procedure G from 5- benzyloxytryptamine and 2-chloroacetyl chloride (0.03 mL) and was obtained as a brown solid in 82% yield.

[0573] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.21 (brs, 1 H, Hi), 7.53-7.33 (m, 5 H, H3’,4\5’), 7.28 (d, 1 H,3J = 8.8 Hz, H7), 7.17 (d, 1 H, V = 2.4 Hz, H4), 7.03 (d, 1 H,3J = 2.3 Hz, H2), 6.98 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 6.72 (m, 1 H, NH), 5.14 (s, 2 H, Hr), 4.03 (s, 2 H, CH2CI), 3.64 (q, 2 H,3J = 6.7 Hz, Hi”), 2.99 (t, 2 H,3J = 6.7 Hz, Hr)

[0574] 13C NMR (75 MHz, CDCI3): δ (ppm) 165.9 (CO), 153.3 (5), 137.6 (2’), 131.8 (7a), 128.6 (4’), 127.9 (5’), 127.7 (3’), 127.6 (4a), 123.0 (2), 113.1 (6), 112.1 (3), 112.1 (7), 102.2 (4), 71.0 (!’), 42.7 (CH2CI), 40.0 (1”), 25.1 (2”).

[0575] LC-MS (ESI): m / z Calculated: 342.1, Found: 343.0 [M+H]+, tR= 2.8 min. EXAMPLE 35: N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)-2-chloroacetamide (FT276) 342.82 g / mol; Mp = 232-234 °C.

[0576] Compound 35 was synthesized following the general procedure G from 2-(5-(benzyloxy)- lH-indol-l-yl)ethanamine and 2-chloroacetyl chloride (0.03 mL) and was obtained as a brown solid in 89% yield.

[0577] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.53-7.33 (m, 5 H, H3’,4’,5’), 7.28 (d, 1 H,3J = 8.9 Hz, H7), 7.22 (d, 1 H,4J = 2.3 Hz, H4), 7.06 (d, 1 H,3J = 3.1 Hz, H2), 7.01 (dd, 1 H,3J =

[0578] 8.9 Hz,4J = 2.3 Hz, H6), 6.63 (m, 1 H, NH), 6.48 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.14 (s, 2 H, Hr), 4.27 (t, 2 H,3J = 5.8 Hz, Hr), 3.97 (s, 2 H, CH2CI), 3.66 (q, 2 H,3J = 5.8 Hz, Hi”).

[0579] 13C NMR (75 MHz, CDC13): δ (ppm) 166.5 (CO), 153.4 (5), 137.6 (2’), 131.4 (7a), 129.2 (4a), 128.6 (4’), 128.4 (2), 127.8 (5’), 127.6 (3’), 113.0 (6), 109.9 (7), 104.5 (4), 101.7 (3),

[0580] 70.9 (!’), 45.4 (2”), 42.4 (CH2CI), 40.2 (1”).

[0581] LC-MS (ESI): m / z Calculated: 342.1, Found: 343.0 [M+H]+, tR= 3.0 min. EXAMPLE 36: N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)-2-chloroacetamide (FT277)

[0582] 356.85 g / mol; Mp = 241-243 °C.

[0583] Compound 36 was synthesized following the general procedure G from 3-(5-(benzyloxy)- lH-indol-l-yl)propan-l-amine and 2-chloroacetyl chloride (0.03 mL) and was obtained as a brown solid in 75% yield.

[0584] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.53-7.32 (m, 5 H, H3’,4’,5’), 7.25 (d, 1 H,3J = 8.9 Hz, H7), 7.21 (d, 1 H,4J = 2.4 Hz, H4), 7.10 (d, 1 H,3J = 3.1 Hz, H2), 7.01 (dd, 1 H,3J =

[0585] 8.9 Hz,4J = 2.37 Hz, H6), 6.46 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 6.44 (m, 1 H, NH), 5.14 (s, 2 H, Hr), 4.18 (t, 2 H,3J = 6.6 Hz, H3”), 3.95 (s, 2 H, CH2CI), 3.29 (q, 2 H,3J = 6.7 Hz, Hi”), 2.10 (quin, 2 H,3J = 6.7 Hz, Hr).

[0586] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.2 (CO), 153.3 (5), 137.7 (2’), 131.3 (7a), 129.1 (4a), 128.5 (4’), 128.2 (2), 127.8 (5’), 127.6 (3’), 112.9 (6), 109.9 (7), 104.5 (4), 101.3 (3),

[0587] 70.9 (!’), 44.1 (1”), 42.5 (CH2CI), 37.6 (3”), 29.6 (2”).

[0588] LC-MS (ESI): m / z Calculated: 356.1, Found: 357.0 [M+H]+, tR= 3.0 min.

[0589] 2.7. Synthesis of (5-(benzyloxy)-lH-indol-3-yl)-2-oxoacetate (Examples 37-38)

[0590] General procedure H for the synthesis of compounds 35-36: To a solution of 5- benzyloxyindole (0.50 g, 1 eq., 2.2 mmol) in dry diethyl ether (8 mL), a solution of oxalyl chloride (1 eq.) in 2 mL of dry diethyl ether, was added dropwise at 0°C over 15 min. Reaction was allowed to warmup at room temperature and stirred for another 3 h. Then, a nucleophilic solution (2 mL) was added and the solution was stirred under reflux for 30 min. Mixture was cooled at room temperature and precipitate was filtrated and washed with water.

[0591] EXAMPLE 37: 2 (5- i-lH-indol-3-vl)-2-oxoacetic acid 295.29 g / mol; Mp = 202-204 °C.

[0592] Compound 37 was synthesized following the general procedure H by adding NaHCCh (I N) solution as nucleophilic solution and was obtained as an orange solid in 78% yield.

[0593] 1H NMR (300 MHz, CD6SO): δ (ppm) 12.33 (brs, 1 H, Hi), 8.33 (d, 1 H,3J = 3.4 Hz, H2), 7.76 (d, 1 H,4J = 2.5 Hz, H4), 7.49-7.32 (m, 6 H, H74’,4’,5’), 6.99 (dd, 1 H,3J = 8.8 Hz,4J =

[0594] 2.5 Hz, H6), 5.14 (S, 2 H, Hr).

[0595] 13C NMR (75 MHz, CD6SO): δ (ppm) 181.1 (CO), 165.7 (COO), 155.5 (5), 138.4 (2), 137.8 (13), 132.0 (7a), 128.9 (4a), 128.2 (4’), 128.1 (5’), 126.9 (3’), 114.3 (6), 114.0 (7), 112.6 (3), 105.1 (4), 70.1 (1’). LC-MS (ESI): m / z Calculated: 295.2, Found: 294.2 [M-H]", 296.1 [M+H]+, tR= 2.1 min.

[0596] EXAMPLE 38: Methyl 2-(5-(benzyloxy)-lH-indol-3-yl)-2-oxoacetate (FT88) 309.32 g / mol; Mp = 253-255 °C.

[0597] Compound 38 was synthesized following the general procedure H by adding methanol as nucleophilic solution and was obtained as a brown solid in 79% yield.

[0598] 1H NMR (300 MHz, CD6SO): δ (ppm) 12.35 (brs, 1 H, Hi), 8.36 (d, 1 H,3J = 3.4 Hz, H2), 7.75 (d, 1 H,3J = 2.4 Hz, H4), 7.50-7.32 (m, 6 H, H4,3’,4’,5’), 7.00 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 5.14 (s, 2 H, Hr), 3.88 (s, 3H, CH3).13C NMR (75 MHz, CD6SO): δ (ppm) 179.0 (CO), 164.5 (COO), 155.7 (5), 138.8 (2), 137.8 (2’), 132.0 (7a), 128.9 (4a), 128.2 (4’), 128.1 (5’), 126.8 (3’), 114.5 (6), 114.0 (7), 112.7 (3), 105.1 (4), 70.1 (1”), 53.0 (CH3).

[0599] LC-MS (ESI): m / z Calculated: 309.1, Found: 308.2 [M-H]", 310.0 [M+H]+, tR= 2.8 min.

[0600] 2.8. Synthesis 39-47

[0601] EXAMPLE 39: 2-(5-(benzyloxy)-lH-indol-3-yl)ethanol (FT112) 267.33 g / mol; Mp = 100-102 °C.

[0602] To a solution of compound 38 (0.25 g, 1 eq., 0.81 mmol) in dry THF (7.5 mL), LiAlELj (15 eq.) was added slowly. Reaction was stirred under reflux for 5 h. Then, NaOH (1 N) and water were added and formed precipitate was filtrated and washed with ethyl acetate. Both phases were separated and aqueous phase was washed three times with ethyl acetate. Aqueous phase was then acidified with HC1 (I N) and extracted with ethyl acetate (three times). Combined organic phases were dried over MgSCh and solvent was removed under vacuum. The residue was purified by column chromatography with ethyl acetate / cyclohexane (60:40) as eluant and compound 39 was obtained as a white solid in 69% yield.

[0603] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.99 (brs, 1 H, Hi), 7.52-7.50 (m, 2 H, H3’), 7.44- 7.28 (m, 4 H, H7,4’,5’), 7.18 (d, 1 H,4J = 2.4 Hz, H4), 7.08 (m, 1 H, H2), 6.98 (dd, 1 H,3J = 8.7 Hz,4J = 2.4 Hz, H6), 5.14 (s, 2 H, Hr), 3.91 (t, 2 H,3J = 6.0 Hz, Hr), 3.02 (t, 2 H,3J = 6.2 Hz, Hi”), 1.60 (brs, 1H, OH).

[0604] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.3 (5), 137.6 (2’), 131.8 (7a), 128.5 (4’), 127.8 (4a), 127.8 (5’), 127.6 (3’), 123.3 (2), 113.1 (6), 112.1 (3), 111.9 (7), 102.5 (4), 71.0 (!’), 62.6 (2”), 28.8 (1”). LC-MS (ESI): m / z Calculated: 267.1, Found: 266.2 [M-H]~, 268.1 [M+H]+, tR= 2.6 min.

[0605] EXAMPLE 40: 4-(5-(benzyloxy)-lH-indol-3-yl)butan-2-one (FT90) 293.37 g / mol; Mp = 83-85 °C.

[0606] To a solution of 5-benzyloxyindole (0.50 g, 1 eq., 2.2 mmol) in dichloromethane (5 mL), indium chloride (10 mol%) and methyl vinyl ketone (1 eq.) were added. Reaction was stirred at room temperature for 3 h. Then, water was added and solution was extracted with dichloromethane (three times). Combined organic phases were washed with water and dried over MgSO4. Solvent was removed under vacuum. Residue was purified by column chromatography with ethyl acetate / cyclohexane (50:50) as eluant and compound 40 was obtained as a pale yellow solid in 70% yield.

[0607] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.84 (brs, 1 H, Hi), 7.5-7.49 (m, 2 H, H3’), 7.43-7.33 (m, 3 H, H4’,5’), 7.26 (d, 1 H,3J = 8.7 Hz, H7), 7.12 (d, 1 H,4J = 2.4 Hz, H4), 6.98-6.97 (m, 1 H, H2), 6.95 (dd, 1 H,3J = 8.7 Hz,4J = 2.4 Hz, H6), 5.13 (s, 2 H, Hr), 3.04 - 2.99 (m, 2 H, H2”), 2.85 - 2.80 (m, 2 H, H3”), 2.15 (s, 3 H, Hi”).13C NMR (75 MHz, CDC13): δ (ppm) 208.7 (CO), 153.1 (5), 137.7 (2’), 131.6 (7a), 128.5

[0608] (4’), 127.8 (5’), 127.6 (4a), 127.6 (3’), 122.3 (2), 112.9 (2), 115.0 (3), 111.8 (7), 102.4 (4), 71.0 (!’), 43.9 (3”), 30.1 (2”), 19.3 (1”).

[0609] LC-MS (ESI): m / z Calculated: 293.1, Found: 294.1 [M+H]+, tR= 2.8 min.

[0610] EXAMPLE 41: 4-(5-(benzyloxy)-lH-indol-3-yl)butan-2-ol (FT99) 295.38 g / mol; Mp = 90-92 °C.

[0611] To a solution of compound 38 (0.05 g, 1 eq., 0.17 mmol) in dry THF (2.5 mL), NaBH4(5 eq.) and few drops of methanol were added slowly. Reaction was stirred at room temperature for 2 h. Solvent was removed under vacuum and residue was diluted in ethyl acetate and washed with NaHCCh (1 N). Aqueous phase was acidified and extracted with ethyl acetate (three times). Combined organic phases were dried over MgSO4. Solvent was removed under vacuum and compound 41 was obtained as a white solid in 93% yield.

[0612] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.86 (brs, 1 H, Hi), 7.52-7.50 (m, 2 H, H3’), 7.44- 7.35 (m, 3 H, H4,5), 7.27 (d, 1 H,3J = 8.8 Hz, H7), 7.16 (d, 1 H,4J = 2.4 Hz, H4), 7.01-7.00 (m, 1 H, H2), 6.96 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 5.15 (s, 1 H, Hr), 3.93-3.86 (m,

[0613] 1 H, H2”), 2.93-2.76 (m, 2 H, H3”), 1.90-1.82 (m, 2H, H4”), 1.36 (brd, 1 H,3J = 4.3 Hz, OH), 1.26 (d, 3 H,3J = 6.2 Hz, Hi”).

[0614] 13C NMR (75 MHz, CDC13): δ (ppm) 153.0 (5), 137.8 (2’), 131.7 (7a), 128.5 (4’), 127.9 (4a), 127.7 (5’), 127.6 (3’), 122.0 (2), 116.0 (3), 112.8 (6), 111.8 (7), 102.6 (4), 71.0 (!’), 67.8 (2”), 39.3 (3”), 23.7 (4”), 21.5 (1”).

[0615] LC-MS (ESI): m / z Calculated: 295.2, Found: 296.1 [M+H]+, tR= 2.8 min.

[0616] EXAMPLE 42: (E)-3-(5-(benzyloxy)-lH-indol-3-yl)acrylonitrile (FT95) 274.32 g / mol; Mp = 89-91 °C. To a solution of cyanoacetic acid (1.7 eq.) in dioxane (4 mL), trimethylamine (3.1 eq.) was added. Reaction was stirred at room temperature for 30 min. Then, 5-(benzyloxy)-lH- indole-3-carbaldehyde (0.50 g, 1 eq., 1.99 mmol) and piperidine (2.2 eq.) were added and reaction mixture was stirred under reflux for 18 h. Solvent was removed under vacuum and residue was diluted in ethyl acetate and washed with water (three times). Organic phase was dried over MgSO4 and solvent was removed under vacuum. The residue was purified by column chromatography with ethyl acetate / cyclohexane (5:95) as eluant and compound 42 was obtained as a pale yellow solid in 65% yield.

[0617] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.43 (brs, 1 H, Hi), 7.58-7.30 (m, 9 H, H2,4,7,3”3’,4’,5’), 7.05 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 5.70 (d, 1 H,3J = 16.5 Hz, H2”) 5.17 (s, 2 H, Hr)

[0618] 13C NMR (75 MHz, CDCI3): δ (ppm) 154.9 (5), 143.7 (2”), 137.1 (2’), 132.0 (7a), 128.9 (2), 128.6 (4’), 128.0 (5’), 127.5 (3’), 125.3 (4a), 119.9 (CN), 114.2 (6), 113.3 (3), 112.6 (7), 104.0 (4), 90.2 (1”), 71.0 (!’).

[0619] LC-MS (ESI): m / z Calculated: 274.1, Found: 275.1 [M+H]+, tR= 2.9 min.

[0620] EXAMPLE 43: Tert-butyl 5-(benzyloxy)-3-formyl-lH-indole-l-carboxylate (FT77) 351.40 g / mol; Mp = 172-174 °C.

[0621] To a solution of 5-(benzyloxy)-7TZ-indole-3-carbaldehyde (0.50 g, 1 eq., 1.99 mmol), trimethylamine (2 eq.) and DMAP (10 mol%) in dichloromethane (5 mL), Boc2O (1.1 eq.) was added slowly at 0 °C. Mixture was allowed to warmup at room temperature and was stirred for 16 h. Then, reaction was quenched with NaHCCh (I N) and extracted with dichloromethane (three times). Combined organic phases were dried over MgSCh and solvent was removed under vacuum. Compound 42 was purified by column chromatography ethyl acetate / cyclohexane (50:50) as eluant and was obtained as a brown solid in 90% yield. 1H NMR (300 MHz, CDCI3): δ (ppm) 10.08 (s, 1 H, CHO), 8.20 (s, 1 H, H2), 8.03 (d, 1 H,3J = 9.0 Hz, H7), 7.90 (d, 1 H,4J = 2.6 Hz, H4), 7.51-7.33 (m, 5 H, H3’,4’,5’), 7.10 (dd, 1 H,3J = 9.0 Hz, \J 2.6 Hz, H6), 5.16 (s, 2 H, Hr), 1.71 (s, 9 H, OtBu)

[0622] 13C NMR (75 MHz, CDCI3): δ (ppm) 185.9 (CHO), 156.5 (5), 148.8 (COO), 137.0 (2’), 136.8 (2), 130.7 (7a), 128.6 (4’), 128.0 (5’), 127.7 (3’), 127.0 (4a), 121.4 (3), 116.2 (6), 116.0 (7), 105.2 (4), 85.6 (OtBu), 70.1 (!’), 28.1 (OtBu)

[0623] LC-MS (ESI): m / z Calculated: 351.4, Found: 350.4 [M-H]", 352.4 [M+H]+, tR= 3.67 min.

[0624] General procedure I for the synthesis of compounds 44 and 45: To a solution of (2- alkoxy-2-oxoethyl)triphenylphosphonium (1 eq.) in dry toluene (10 mL), sodium hexamethyldi silazide (2 eq.) was added. Reaction was stirred at room temperature for 1 h. Then, compound 43 (0.50 g, 1 eq., 1.42 mmol) was added and mixture was stirred under reflux for 16 h. Solvent was removed under vacuum. Residue was diluted in ethyl acetate and washed three times with water. Organic phase was dried over MgSO4 and solvent was removed under vacuum. Residue was purified by column chromatography with 100% dichloromethane as eluant.

[0625] EXAMPLE 44: (£)-tert-butyl 5-(benzyloxy)-3-(3-ethoxy-3-' - 1 -en- 1 -yl)- IH-indole-

[0626] 1 -carboxylate (FT86) 421.49 g / mol

[0627] Compound 44 was synthesized following general procedure I from (2-ethoxy-2- oxoethyl)triphenylphosphonium bromide (0.60 g) and was obtained as a yellow oil in 58% yield.

[0628] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.10 (d, 1 H,3J = 9.0 Hz, H7), 7.86 (s, 1 H, H2), 7.83 (d, 1 H,3J = 16.0 Hz, H2”), 7.54-7.51 (m, 2 H, H3’), 7.46-7.34 (m, 4 H, H4,4’,5’), 7.10 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.49 (d, 1 H,3J = 16.5 Hz, Hi”), 5.17 (s, 1 H, Hr), 4.32 (q, 2 H,3J = 7.14 Hz, OCILCH3), 1.70 (s, 9 H, OtBu), 1.40 (t, 3 H,3J = 7.17 Hz, OCH2CH3)

[0629] 13C NMR (75 MHz, CDCI3): δ (ppm) 167.4 (COOCH2CH3), 155.7 (5), 149.1 (COOtBuY

[0630] 137.1 (2’), 136.4 (2”), 131.0 (7a), 129.1 (2), 128.8 (4a), 128.6 (4’), 128.0 (5’), 127.6 (3’),

[0631] 117.1 (1”), 116.5 (3), 116.2 (6), 114.3 (7), 104.8 (4), 84.5 (COOtBuY 70.8 (!’), 60.4 (OCH2CH3) 28 1 (COOtBuY 14.4 (OCH2CH3)

[0632] EXAMPLE 45: ( butyl 5-(benzyloxy)-3-(3-(tert-butoxy)-3-oxoprop-l-en-l-yl)-lH- indole-1 -carboxylate (FT262) 449.55 g / mol

[0633] Compound 45 was synthesized following general procedure I from (2-(tert-butoxy)-2- oxoethyl)triphenylphosphonium bromide (0.65 g) and was obtained as a yellow oil in 68% yield.

[0634] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.12 (d, 1 H,3J = 9.0 Hz, H7), 7.84 (s, 1 H, H2), 7.75 (d, 1 H,3J = 16.3 Hz, H2”), 7.54-7.37 (m, 6 H, H4,3’,4’,5’), 7.10 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.44 (d, 1 H,3J = 16.3 Hz, Hi”), 5.17 (s, 2 H, Hr), 1.71 (s, 9 H, OtBu), 1.61 (s, 9

[0635] H, OtBu)

[0636] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.8 (COOtBuY 155.6 (5), 149.1 (COOtBuY 137.1 (2’), 135.3 (2”), 131.0 (7a), 128.9 (4a), 128.8 (2), 128.7 (4’), 128.0 (5’), 127.6 (3’), 119.1 (1”), 116.6 (3), 116.2 (7), 114.2 (6), 104.9 (4), 84.4 (COOtBuY 80.4 (COOtBuY 70.8 (!’), 28 3 (COOtBuY 28.2 (COOtBu) EXAMPLE 46: (£)-ethyl 3-(5-(benzyloxy)-7J / -indol-3-yl)acrylate (FT196) 321.38 g / mol; Mp = 93-95 °C.

[0637] To a solution of compound 44 (0.30 g, 1 eq., 0.71 mmol) in dichloromethane (2 mL), trifluoroacetic acid (5 eq.) was added. Mixture was stirred for 6 h and then quenched with 1 M NaHCCh solution. Solution was extracted with di chloromethane (3 times) and the organic layer was dried over MgSCU and solvent was removed under vacuum. Compound 46 was obtained as a brown solid in 99% yield.

[0638] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.80 (brs, 1 H, Hi), 7.91 (d, 1 H,3J = 16.1 Hz, Hr), 7.54-7.51 (m, 2 H, H3’), 7.46-7.33 (m, 4 H, H7,4’,5’), 7.28-7.22 (m, 2 H, H24), 6.99 (dd, 1H,3J = 8.9 Hz,4J = 22 Hz, H6), 6.37 (d, 1 H,3J = 16.2 Hz, Hi”), 5.13 (s, 2 H, Hr), 4.32 (q, 2

[0639] H,3J = 7.0 Hz, OCH2CH3), 1.40 (t, 3 H,3J = 7.2 Hz, OCH2CH3)

[0640] 13C NMR (75 MHz, CDCI3): δ (ppm) 168.6 (CO), 154.6 (5), 138.5 (2’), 137.4 (2”), 132.3 (7a), 129.7 (4a), 128.9 (2), 128.6 (4’), 128.0 (5’), 127.7 (3’), 125.9 (1”), 113.7 (6), 113.2 (3), 112.6 (7), 104.3 (4), 71.0 (!’), 60.2 (OCH2CH3), 14.5 (OCH2CH3) LC-MS (ESI): m / z Calculated: 321.1, Found: 320.2 [M-H]", 322.1 [M+H]+, tR= 3.1 min.

[0641] EXAMPLE 47: (E)-3-(5-(benzyloxy)-lH-indol-3-yl)acrylic acid (FT265) 293.32 g / mol; Mp = 168-170 °C To a solution of compound 45 (0.30 g, 1 eq., 0.85 mmol) in dichloromethane (7.5 mL), trifluoroacetic acid (20 eq.) was added. Mixture was stirred for 6 h and then quenched with 1 N NaHCCf solution. Solution was extracted with dichloromethane (3 times). Aqueous solution was acidified with 1 N HC1 solution up to pH 3 and was extracted with dichloromethane (3 times). The organic layer was dried over MgSCh and solvent was removed under vacuum. Residue was purified by column chromatography with dichloromethane / methanol (90: 10) as eluant and compound 47 was obtained as a white solid in 88% yield.

[0642] 1H NMR (300 MHz, CD3OD): δ (ppm) 7.92 (d, 1 H,3J = 16.0 Hz, Hr), 7.63(s, 1 H, H2), 7.53-7.50 (m, 2 H, H3’), 7.43-7.30 (m, 5 H, H4,7,4’,5’), 6.98 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 6.29 (d, 1 H,3J = 16.0 Hz, Hi”), 5.16 (s, 2 H, Hr).

[0643] 13C NMR (75 MHz, CD3OD): δ (ppm) 170.9 (COO), 154.3 (5), 139.8 (2”), 137.8 (2’), 133.0 (7a), 130.8 (2), 128.1 (4’), 127.4 (5’), 127.3 (3’), 125.8 (4a), 113.0 (6), 112.4 (7), 112.2 (3), 110.6 (1”), 103.6 (4), 70.6 (!’).

[0644] LC-MS (ESI): m / z Calculated: 293.1, Found: 292.1 [M-H]", 294.0 [M+H]+, tR= 2.6 min.

[0645] 2,9, Synthesis of (x-(benzyloxy)-777-indol-l-yl)benzoic acids (Examples 48-58)

[0646] General procedure J for the synthesis of compounds 48-58: To a solution of x- benzyloxyindole derivative (1 eq.) in DMF (1 mL), K2CO3 (1 eq.), iodobenzoic acid (0.1 g, 0.9 eq., 0.40 mmol) and Cu (7 mol%) were added. Reaction was stirred under reflux for 18 h and was cooled at room temperature. Mixture was filtered through celite, quenched with NaHCCh (I N) and extracted three times with ethyl acetate. Aqueous phase was acidified with HC1 solution (1 N) and extracted with ethyl acetate (three times). Combined organic phases was dried over MgSCU and solvent was removed under vacuum. Residues were purified by HPLC (55 min, from 60% acetonitrile / 40% milli-Q water to 100% of acetonitrile).

[0647] EXAMPLE 48: 2-(5-(benzyloxy)-777-indol-l-yl)benzoic acid (FT117) 343.38 g / mol; Mp = 110-112 °C.

[0648] Compound 48 was synthesized following general procedure J from 2-iodobenzoic acid and 5-benzyloxyindole (0.10 g) and was obtained as a green solid in 55% yield.

[0649] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.07 (dd, 1 H,3J = 7.5 Hz,4J = 1.6 Hz, H6”), 7.70 (td, 1 H,3J = 7.6 Hz,4J = 1.6 Hz, H4”), 7.53-7.47 (m, 4 H, H3’,3”,5”), 7.44-7.32 (m, 3 H, H4’,5’), 7.23 (d, 1 H,4J = 2.4 Hz, H4), 7.17 (d, 1 H,3J= 3.2 Hz, H2), 7.09 (d, 1 H,3J = 8.8 Hz, H7), 6.93 (dd, 1 H,3J= 8.8 Hz,4J = 2.4 Hz, H6), 6.60 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.13 (S, 2 H, Hr).

[0650] 13C NMR (75 MHz, CDCI3): δ (ppm) 169.8 (COOH), 153.7 (5), 139.4 (2”), 137.7 (2’), 133.6 (4”), 132.6 (7a), 132.1 (6”), 129.6 (5”), 129.3 (4a), 128.7 (2), 128.5 (4’), 127.8 (5’),

[0651] 127.5 (3”), 127.5 (3’), 127.3 (1”), 113.1 (6), 110.7 (7), 104.3 (4), 103.3 (3), 70.9 (!’).

[0652] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.3 [M-H]", 344.2 [M+H]+, tR= 3.0 min.

[0653] EXAMPLE 49: 3-(5-(benzyloxy)-7J / -indol-l-yl)benzoic acid (FT118) 343.38 g / mol; Mp = 139-141 °C. Compound 49 was synthesized following general procedure J from 3-iodobenzoic acid and

[0654] 5-benzyloxyindole (0.10 g) and was obtained as a pink solid in 52% yield.1H NMR (300 MHz, CDCI3): δ (ppm) 8.26 (t, 1 H,4J = 1.8 Hz, Hr), 8.10 (dt, 1 H,3J = 7.9 Hz,4J = 1.7 Hz,4J = 1.1 Hz, H6”), 7.79 (ddd, 1 H,3J = 7.9 Hz,4J = 1.8 Hz,4J = 1.1 Hz, H4”), 7.65 (t, 1 H,3J = 7.9 Hz, Hs ), 7.53-7.50 (m, 3 H, H73 ), 7.45-7.35 (m, 4 H, H2,4’,5’), 7.25 (d, 1 H,4J = 2.5 Hz, H4), 7.02 (dd, 1 H,3J = 9.0 Hz,4J = 2.5 Hz, H6), 6.66 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.17 (s, 2 H, Hr).

[0655] 13C NMR (75 MHz, CDCI3): δ (ppm) 169.7 (COOH), 154.0 (5), 140.3 (3”), 137.5 (2’), 131.0 (7a), 130.8 (1”), 130.1 (4a), 129.9 (5”), 128.9 (4”), 128.6 (4’), 128.1 (2), 127.8 (5’), 127.7 (6”), 127.5 (3’), 125.3 (2”), 113.5 (6), 111.1 (7), 104.6 (4), 104.1 (3), 70.9 (!’).

[0656] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.3 [M-H]", 344.2 [M+H]+, tR= 3.1 min.

[0657] EXAMPLE 50: 4- i-777-indol-l - acid 343.38 g / mol; Mp = 162-164 °C.

[0658] Compound 50 was synthesized following general procedure J from 4-iodobenzoic acid and 5-benzyloxyindole (0.10 g) and was obtained as a brown solid in 18% yield.

[0659] 1H NMR (300 MHz, CO(CD3)2): δ (ppm) 8.23 (m, 2 H, Hr), 7.75 (m, 2 H, H3”), 7.65 (d, 1 H,3J = 9.0 Hz, H7), 7.62 (d, 1 H,3J = 3.3 Hz, H2), 7-54-7.33 (m, 5 H, H3’,4’,5’), 7.29 (d, 1 H,4J = 2.5 Hz, H4), 7.00 (dd, 1 H,3J = 9.0 Hz,4J = 2.5 Hz, H6), 6.67 (dd, 1 H,3J = 3.3 Hz,5J = 0.7 Hz, H3), 5.18 (S, 2 H, Hr).

[0660] 13C NMR (75 MHz, CO(CD3)2): δ (ppm) 169.3 (COOH), 154.1 (5), 143.7 (4”), 138.0 (2’), 131.3 (7a), 131.3 (2”), 130.8 (4a), 128.3 (2), 128.2 (4’), 127.6 (5’), 127.5 (1”), 127.5 (3’), 122.7 (3”), 113.2 (6), 111.4 (7), 104.6 (3), 104.5 (4), 70.1 (!’).

[0661] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.1 [M-H]", 344.1 [M+H]+, tR= 3.1 min. EXAMPLE 51: 3-(4-(benzyloxy)-lH-indol-l-yl)benzoic acid (FT214) 343.38 g / mol; Mp = 137-139 °C.

[0662] Compound 51 was synthesized following general procedure J from 3-iodobenzoic acid and 4-benzyloxyindole (0.10 g) and was obtained as a brown solid in 48% yield.1H NMR (300 MHz, CDCI3): δ (ppm) 8.29 (t, 1 H,4J = 2.0 Hz, Hr), 8.12 (dt, 1 H,3J = 7.9

[0663] Hz,4J = 2.0 Hz, H6”), 7.81 (ddd, 1 H,3J = 7.9 Hz,4J = 2.0 Hz,4J = 0.9 Hz, H4”), 7.66 (t, 1 H,3J = 7.9 Hz , H5”), 7.57-7.55 (m, 2 H, Hr), 7.47-7.37 (m, 3 H, H4,5), 7.32 (d, 1 H,3J = 3.3 Hz, H2), 7.24-7.15 (m, 2 H, H5,6), 6.93 (dd, 1 H,3J = 3.3 Hz,5J = 0.5 Hz, H3), 6.70 (dd, 1 H,3J = 7.4 Hz,4J = 1.1 Hz, H7), 5.30 (s, 2 H, Hr).13C NMR (75 MHz, CDCI3): δ (ppm) 170.8 (COOH), 152.7 (4), 140.4 (3”), 137.5 (7a),

[0664] 137.2 (2’), 130.8 (1”), 129.9 (5”), 129.4 (6”), 128.5 (4’), 128.0 (4”), 127.8 (5’), 127.3 (3’),

[0665] 126.2 (2), 125.7 (2”), 123.6 (6), 120.4 (4a), 103.9 (5), 102.6 (7), 101.9 (3), 70.1 (!’).

[0666] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.1 [M-H]", 344.0 [M+H]+, tR= 3.1 min.

[0667] EXAMPLE 52: 3-(6-(benzyloxy)-lH-indol-l-yl)benzoic acid (FT216) 343.38 g / mol; Mp = 134-136 °C.

[0668] Compound 52 was synthesized following general procedure J from 3-iodobenzoic acid and 6-benzyloxyindole (0.10 g) and was obtained as a brown solid in 52% yield.1H NMR (300 MHz, CDCI3): δ (ppm) 8.27 (t, 1 H,4J = 2.2 Hz, Hr), 8.14 (dt, 1 H,3J = 7.8 Hz,4J = 22 Hz, H6”), 7.74 (ddd, 1 H,3J = 8.0 Hz,4J = 2.2 Hz,4J = 1.1 Hz, H4”), 7.66 (t, 1 H,3J = 8.0 Hz, Hs ), 7.61 (d, 1 H,3J = 8.6 Hz, H4), 7.50 - 7.47 (m, 2 H, Hr), 7.44-7.35 (m, 3 H, H4’,5’), 7.29 (d, 1 H,3J = 3.4 Hz, H2), 7.16 (d, 1 H,4J = 2.2 Hz, H7), 6.99 (dd, 1 H,3J = 8.6 Hz,4J = 2.2 Hz, Hs), 6.69 (dd, 1 H,3J = 3.4 Hz,5J = 0.6 Hz, H3), 5.12 (s, 2 H, Hr).

[0669] 13C NMR (75 MHz, CDC13): δ (ppm) 171.3 (COOH), 156.1 (6), 140.3 (3”), 137.3 (7a), 136.4 (2’), 131.0 (1”), 130.0 (5”), 129.2 (6”), 128.6 (4’), 127.9 (5’), 127.9 (4”), 127.6 (3’), 126.8 (2), 125.6 (2”), 123.9 (4a), 121.8 (4), 111.1 (5), 104.3 (3), 95.7 (7), 70.7 (!’).

[0670] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.1 [M-H]", 344.0 [M+H]+, tR= 3.1 min. 5-117 °C.

[0671] Compound 53 was synthesized following general procedure J from 2-iodobenzoic acid and 4-benzyloxyindole (0.10 g) and was obtained as a brown solid in 41% yield.

[0672] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.08 (dd, 1 H,3J = 7.7 Hz,4J = 1.5 Hz, H6”), 7.70 (td, 1 H,3J = 7.8 Hz,4J = 1.5 Hz, H4”), 7.57-7.34 (m, 7 H, H3’,4’,5’,3”,5”), 7.12 (d, 1 H,3J = 3.3 Hz, H2), 7.08 (t, 1 H,3J = 8.2 Hz, H6), 6.86 (dd, 1 H,3J = 3.3 Hz,5J = 0.6 Hz, H3), 6.81 (d, 1 H,3J = 8.2 Hz, Hs), 6.65 (d, 1 H,3J = 7.8, H, H7), 5.27 (s, 2 H, Hr).

[0673] 13C NMR (75 MHz, CDCI3): δ (ppm) 170.2 (COOH), 152.5 (4), 139.4 (2”), 138.7 (7a), 137.6 (2’), 133.6 (4”), 132.1 (6”), 128.9 (1”), 128.5 (4’), 127.7 (5”), 127.7 (5’), 127.5 (2), 127.4 (3’), 127.4 (3”), 123.2 (6), 119.7 (4a), 103.6 (5), 101.8 (7), 101.1 (3), 70.0 (!’).

[0674] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.1 [M-H]", 344.0 [M+H]+, tR= 3.0 min. EXAMPLE 54: 2-(6-(benzyloxy)-lH-indol-l-yl)benzoic acid (FT220) 343.38 g / mol; Mp = 111-113 °C.

[0675] Compound 54 was synthesized following general procedure J from 2-iodobenzoic acid and 6-benzyloxyindole (0.10 g) and was obtained as a brown solid in 47% yield.1H NMR (300 MHz, CDCI3): δ (ppm) 8.08 (dd, 1 H,3J = 7.8 Hz,4J = 1 A Hz, H6”), 7.69

[0676] (td, 1 H,3J = 7.9 Hz,4J = 1.4 Hz, H4”), 7.57 (d, 1 H,3J = 8.6 Hz, H4), 7.51 (td, 1 H,3J = 7.8 Hz ,4J = 1.1 Hz, H5”), 7.46 (dd, 1 H,3J = 7.9 Hz,4J = 1.1 Hz, H3”), 7.41-7.28 (m, 5 H, H3’,4’,5’), 7.09 (d, 1 H,3J = 3.3 Hz, H2), 6.93 (dd, 1 H,3J = 8.6 Hz,4J = 2.0 Hz, Hs), 6.77 (d, 1 H,4J = 2.0 Hz, H7), 6.61 (dd, 1 H,3J = 3.3 Hz,5J = 0.8 Hz, H3), 5.01 (s, 2 H, Hr).13C NMR (75 MHz, CDC13): δ (ppm) 170.7 (COOH), 155.9 (6), 139.3 (2”), 137.8 (7a),

[0677] 137.3 (2’), 133.7 (4”), 132.1 (6”), 128.7 (3”), 128.5 (4’), 128.1 (2), 127.8 (5’), 127.7 (3’), 127.6 (5”), 127.6 (2), 127.3 (1”), 123.2 (4a), 121.6 (4), 110.8 (5), 103.5 (3), 95.1 (7), 70.6 (I’)-

[0678] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.1 [M-H]", 344.0 [M+H]+, tR= 3.0 min. EXAMPLE 55: 4-(4-(benzyloxy)-lH-indol-l-yl)benzoic acid (FT222) 343.38 g / mol; Mp = 162-164 °C.

[0679] Compound 55 was synthesized following general procedure J from 4-iodobenzoic acid and 4-benzyloxyindole (0.10 g) and was obtained as a brown solid in 25% yield. 1H NMR (300 MHz, CO(CD3)2): δ (ppm) 8.26-8.23 (m, 2 H, Hr), 7.77-7.74 (m, 2 H, Hr), 7.58 (d, 1 H,3J = 7.3 Hz, H7), 7.55 (d, 1 H,3J = 3.4 Hz, H2), 7.43-7.30 (m, 5 H, H3’,4’,5’), 7.17 (t, 1 H,3J = 7.8 Hz, H6), 6.86 (dd, 1 H,3J = 3.4 Hz,5J = 0.6 Hz, H3), 6.78 (d, 1 H,3J = 7.8 Hz, Hs), 5.31 (s, 2 H, Hr).

[0680] 13C NMR (75 MHz, CO(CD3)2): δ (ppm) 166.1 (COOH), 152.6 (4), 143.6 (4”), 137.8 (7a), 136.8 (2’), 131.3 (2”), 128.4 (4'), 128.1 (1”), 127.7 (5’), 127.4 (3’), 126.3 (2), 123.7 (6), 123.2 (3”), 120.7 (4a), 104.0 (7), 102.4 (3), 102.0 (5), 69.6 (!’).

[0681] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.2 [M-H]", 344.0 [M+H]+, tR= 3.1 min.

[0682] EXAMPLE 56: 4 (6- i-lH-indol-1- ic acid 343.38 g / mol; Mp = 161-163 °C.

[0683] Compound 56 was synthesized following general procedure J from 4-iodobenzoic acid and 6-benzyloxyindole (0.10 g) and was obtained as a brown solid in 38% yield.

[0684] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.30-8.27 (m, 2 H, Hr), 7.61-7.58 (m, 3 H, H4,r), 7.51 - 7.36 (m, 5 H, H3’,4’,5’), 7.31 (d, 1 H,3J = 3.3 Hz, H2), 7.23 (d, 1 H,4J = 2.2 Hz, H7), 6.99 (dd, 1 H,3J = 8.6 Hz,4J = 2.2 Hz, Hs), 6.69 (dd, 1 H,3J = 3.3 Hz,5J = 0.7 Hz, H3), 5.14 (s, 2 H, Hr).

[0685] 13C NMR (75 MHz, CDCI3): δ (ppm) 171.1 (COOH), 156.1 (6), 144.6 (4”), 137.2 (2’), 136.0 (7a), 132.0 (2”), 128.6 (4’), 128.0 (5’), 127.5 (3’), 126.5 (2), 126.3 (1”), 124.2 (4a), 123.1 (3”), 121.9 (4), 111.4 (5), 105.1 (3), 96.3 (7), 70.7 (!’).

[0686] LC-MS (ESI): m / z Calculated: 343.1, Found: 342.2 [M-H]", 344.1 [M+H]+, tR= 3.1 min.

[0687] EXAMPLE 57: 3-(5-(benzyloxy)-3-(3-oxobutyl)-lH-indol-l-yl)benzoic acid (FT231)

[0688] 413.47 g / mol; Mp = 132-134 °C.

[0689] Compound 57 was synthesized following general procedure J from 3 -iodobenzoic acid and 4-(5-(benzyloxy)-lH-indol-3-yl)butan-2-one (0.13 g) and was obtained as a grey solid in 44% yield.1H NMR (300 MHz, CDCh): <5 (ppm) 8.23 (dd, 1 H,4J = 2.19 Hz,4J = 1.75 Hz, Hr), 8.07 (ddd, 1 H,3J = 7.74 Hz,4J = 1.75 Hz,4J = 1.11 Hz, H6”), 7.74 (ddd, 1 H,3J = 7.85 Hz,4J = 2.19 Hz ,4J = 1.11 Hz, H4”), 7.61 (dd, 1 H,3J = 7.85 Hz,3J = 7.74 Hz, Hs ), 7.55-7.36 (m, 6H, H7,3’,4’,5’), 7.20-7.19 (m, 2H, HM), 7.02 (dd, 1 H,3J = 8.87 Hz,4J = 2.37 Hz, H6), 5.19 (s, 2 H, Hr), 3.09 (t, 2 H,3J = 7.24 Hz, H3’”), 2.91 (t, 2 H,3J = 7.24 Hz, H4’”), 2.23 (s, 3 H, Hi’”).

[0690] 13C NMR (75 MHz, CDCI3): δ (ppm) 209.1 (2”’), 170.9 (COOH), 153.7 (5), 140.2 (3”),

[0691] 137.5 (2’), 131.2 (7a), 131.0 (1”), 129.9 (5”), 129.5 (4a), 128.6 (4’), 128.5 (4”), 127.9 (5’),

[0692] 127.6 (3’), 127.4 (6”), 125.5 (2), 124.9 (2”), 116.7 (3), 113.4 (6), 111.3 (7), 102.9 (4), 71.0 (!’), 43.7 (3”’), 30.1 (!’”), 19.1 (4”’). LC-MS (ESI): m / z Calculated: 413.2, Found: 412.2 [M-H]", 414.1 [M+H]+, tR= 3.0 min.

[0693] EXAMPLE 58: (£)-3-(5-(benzyloxy)-3-(2-cvanovinyl)-lH-indol-l-yl)benzoic acid (FT232)

[0694] 394.43 g / mol; Mp = 151-153 °C.

[0695] Compound 58 was synthesized following general procedure J from 3 -iodobenzoic acid and (£)-3-(5-(benzyloxy)-lH-indol-3-yl)acrylonitrile (0.12 g) and was obtained as a green solid in 45% yield.

[0696] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.23 (dd, 1 H,4J = 1.75 Hz,4J = 1.59 Hz, Hr), 8.19 (ddd, 1 H,3J = 7.78 Hz,4J = 1.75 Hz,4J = 1.39 Hz, H6”), 7.77 (ddd, 1 H,3J = 8.01 Hz,4J = 1.59 Hz,4J = 1.39 Hz, H4”), 7.70 (dd, 1 H,3J = 8.01 Hz,3J = 7.78 Hz, Hs ), 7.60 (s, 1 H, H2), 7.58 (d, 1 H,3J = 16.71 Hz, Hi’”), 7.53-7.51 (m, 2 H, H3’), 7.47-7.37 (m, 4 H, H7,4’,5’), 7.34 (d, 1 H,4J = 2.42 Hz, H4), 7.09 (dd, 1 H,3J = 9.04 Hz,4J = 2.42 Hz, H6), 5.78 (d, 1 H,3J = 16. 71 Hz, Hr’), 5.20 (s, 2 H, Hr).

[0697] 13C NMR (75 MHz, CDCI3): δ (ppm) 168.9 (COOH), 155.4 (5), 142.9 (3”’), 138.8 (3”), 137.0 (2’), 132.3 (7a), 131.0 (1”), 130.3 (5”), 129.3 (4a), 129.2 (4”), 128.7 (4’), 128.6 (6”),

[0698] 128.1 (5’), 127.5 (3’), 126.9 (2”), 125.8 (2), 119.6 (!’”), 114.6 (6), 114.1 (3), 112.0 (7),

[0699] 104.2 (4), 91.3 (2”’), 71.0 (1’).

[0700] LC-MS (ESI): m / z Calculated: 394.1, Found: 393.1 [M-H]", 395.0 [M+H]+, tR= 3.0 min.

[0701] 2.10. Synthesis of 5-(benzyloxy)-l-phenyl-lH-indole (Examples 59-73)

[0702] General procedure K for the synthesis of compounds 59-73: To a solution of 5- benzyloxyindole (1 eq.) in DMF (1 mL), K2CO3 (1 eq.), iodobenzene derivative (0.9 eq., 0.40 mmol) and Cu (7 mol%) were added. Reaction was stirred under reflux for 18 h and was cooled at room temperature. Mixture was filtered through celite, diluted in more water (50 mL) and extracted three times with ethyl acetate. Combined organic phases was washed with brine (3 x 15 mL) and dried over MgSO4and solvent was removed under vacuum. Residue was purified by column chromatography with ethyl acetate / cyclohexane (2:98) as eluant.

[0703] EXAMPLE 59: 5-(benzyloxy)-l-phenyl-lH-indole (FT278) 299.37 g / mol; Mp = 99-101 °C. Compound 59 was synthesized following general procedure K from iodobenzene (0.05 mL) and was obtained as an orange solid in 80% yield.

[0704] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.57-7.39 (m, 10 H, H3 , 4\ 5\2”, 3”, 4”), 7.39 (d, 1 H,3J = 3.2 Hz, H2), 7.31 (d, 1 H, V = 2.4 Hz, H4), 7.06 (dd, 1 H,3J = 8.9 Hz, V = 2.4 Hz, H6), 6.68 (dd, 1 H,3J = 3.2 Hz,5J = 0.8 Hz, H3), 5.21 (s, 2 H, Hr).13C NMR (75 MHz, CDCI3): δ (ppm) 153.8 (5), 140.0 (1”), 137.7 (2’), 131.3 (7a), 129.9

[0705] (4a), 129.7 (3”), 128.6 (4’), 128.5 (2), 127.9 (5’), 127.6 (3’), 126.3 (4”), 124.1 (2”), 113.3 (6), 111.4 (7), 104.4 (4), 103.4 (3), 70.9 (!’).

[0706] LC-MS (ESI): m / z Calculated: 299.1, Found: 300.0 [M+H]+, tR= 3.7 min.

[0707] EXAMPLE 60: Ethyl 3-(5-(benzyloxy)-lH-indol-l-yl)benzoate (FT282) 371.44 g / mol Compound 60 was synthesized following general procedure K from ethyl 3 -iodobenzoate (0.07 mL) and was obtained as a green oil in 74% yield.

[0708] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.20 (t, 1 H,4J = 2.2 Hz, Hr ), 8.05 (dt, 1 H,3J = 7.6 Hz,4J = 22 Hz, H6”), 7.72 (ddd, 1 H,3J = 8.0 Hz,4J = 2.2 Hz,4J = 1.2 Hz, H4”), 7.61 (t, 1 H,3J = 8.0 Hz, H5”), 7.54-7.36 (m, 7 H, H2,7,3’,4’,5’), 7.26 (d, 1 H,4J = 2.4 Hz, H4), 7.02 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.66 (dd, 1 H,3J = 3.3 Hz,5J = 0.7 Hz, H3), 5.17 (s, 2 H, Hr), 4.45 (q, 2 H,3J = 7.1 Hz, OCH2CH3), 1.45 (t, 3 H,3J = 7.1 Hz, OCH2CH3)

[0709] 13C NMR (75 MHz, CDCI3): δ (ppm) 165.9 (COO), 153.9 (5), 140.1 (3”), 137.6 (2’), 132.2 (7a), 131.1 (1”), 130.0 (4a), 129.7 (5”), 128.6 (4’), 128.2 (5’), 128.1 (4”), 127.8 (2), 127.5 (3’), 127.2 (6”), 124.9 (2”), 113.5 (6), 111.1 (7), 104.5 (4), 103.9 (3), 70.8 (!’), 61.4 (OCH2CH3), 14 4 (OCH2CH3)

[0710] LC-MS (ESI): m / z Calculated: 371.2, Found: 372.0 [M+H]+, tR= 3.8 min

[0711] EXAMPLE 61 Ethyl 2-(5-i i-lH-indol-1-’ 371.44 g / mol

[0712] Compound 61was synthesized following general procedure K from ethyl 2-iodobenzoate (0.11 g) and was obtained as a yellow oil in 71% yield.

[0713] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.03 (dd, 1 H,3J = 7.6 Hz,4J = 1.4 Hz, H6”), 7.67 (td, 1 H,3J = 7.6 Hz,4J = 1.7 Hz, H4”), 7.56-7.34 (m, 7 H, H3’,4’,5’,3”,5”), 7.27 (d, 1 H,4J = 2.4 Hz, H4), 7.24 (d, 1 H,3J = 3.2 Hz, H2), 7.11 (d, 1 H,3J = 8.9 Hz, H7), 6.97 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.65 (dd, 1 H,3J = 3.2 Hz,5J = 0.8 Hz, H3), 5.18 (s, 2 H, Hr), 3.99 (q, 2 H,3J = 7.1 Hz, OCH2CH3), 0.83 (t, 3 H,3J = 7.1 Hz, OCH2CH3)13C NMR (75 MHz, CDCI3): δ (ppm) 166.6 (COO), 153.6 (5), 138.7 (2”), 137.7 (2’), 133.0 (7a), 132.7 (4”), 131.3 (6”), 129.6 (1”), 129.4 (5”), 129.1 (4a), 128.5 (2), 128.5 (4’), 127.8 (5’), 127.6 (3”), 127.6 (3’), 113.1 (6), 110.7 (7), 104.4 (4), 102.9 (3), 70.9 (!’), 61.4 (OCH2CH3). 13 5 (OCH2CH3)

[0714] LC-MS (ESI): m / z Calculated: 371.2, Found: 372.0 [M+H]+, tR= 3.6 min.

[0715] EXAMPLE 62 Ethyl 4-(5-(benzyloxy)-lH-indol-l-yl)benzoate (FT289)

[0716] Compound 62was synthesized following general procedure K from ethyl 4-iodobenzoate (0.07 mL) and was obtained as a green oil in 69% yield.

[0717] ’H NMR (300 MHz, CDCI3): δ (ppm) 8.24-8.21 (m, 2 H, Hr), 7.60-7.36 (m, 9 H, H2,7,3’,4’,5’,3”), 7.25 (d, 1 H,4J = 2.4 Hz, H4), 7.03 (dd, 1 H,3J = 9.0 Hz, \J = 2.4 Hz, H6), 6.67 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.17 (s, 2 H, Hr), 4.46 (q, 2 H,3J = 7.0 Hz, OCH2CH3), 0.83 (t, 3 H,3J = 7.0 Hz, OCH2CH3)

[0718] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.0 (COO), 154.1 (5), 143.7 (4”), 137.5 (2’), 131.3 (2”), 130.7 (7a), 130.4 (1”), 128.6 (4’), 127.9 (2), 127.9 (5’), 127.8 (4a), 127.5 (3’), 122.8 (3”), 113.5 (6), 111.5 (7), 104.7 (4), 104.6 (3), 70.8 (!’), 61.2 (OCH2CH3), 14.4 (OCH2CH3)

[0719] LC-MS (ESI): m / z Calculated: 371.2, Found: 372.0 [M+H]+, tR= 3.8 min.

[0720] EXAMPLE 63 5-(benzyloxy)-l-(3-(trifluoromethyl)phenyl)-lH-indole (FT300)

[0721]

[0722] Compound 63 was synthesized following general procedure K from l-iodo-3- (trifluoromethyl)benzene (0.06 mL) and was obtained as an orange solid in 65% yield.

[0723] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.85 (m, 1 H, Hr), 7.75-7.66 (m, 3 H, H4”,5”,6”), 7.60- 7.42 (m, 6 H, H73’,4’,5’), 7.38 (d, 1 H,3J = 3.3 Hz, H2), 7.33 (d, 1 H, V 2.4 Hz, H4), 7.11

[0724] (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.73 (dd, 1 H,3J = 3.3 Hz,5J = 0.7 Hz, H3), 5.23 (s, 2 H, Hr).

[0725] 13C NMR (75 MHz, CDCI3): δ (ppm) 154.1 (5), 140.5 (1”), 137.6 (2’), 132.3 (q,2J= 32.6 Hz, 3”), 131.0 (7a), 130.4 (5”), 130.3 (4a), 128.6 (4’), 128.1 (2), 127.9 (5’), 127.6 (3’), 127.0 (6”), 123.9 (q,}J= 272.8 Hz, CF3), 122.8 (q,3J= 3.6 Hz, 4”), 120.6 (q,3J= 3.5 Hz, 2”),

[0726] 113.7 (6), 111.1 (7), 104.7 (4), 104.5 (3), 70.8 (!’).

[0727] 19F NMR (282 Hz, CDCI3): δ (ppm) -63.2 (s).

[0728] LC-MS (ESI): m / z Calculated: 367.1, Found: 368.0 [M+H]+, tR= 3.8 min.

[0729] EXAMPLE 64: 3-(5-(benzyloxy)-lH-indol-l-yl)benzonitrile (FT301) 324.38 g / mol

[0730] Compound 64 was synthesized following general procedure K from 3 -iodo-benzonitrile (0.09 g) and was obtained as a yellow oil in 59% yield. 1H NMR (300 MHz, CDCI3): δ (ppm) 7.79-7.73 (m, 2 H, H4”,5”), 7.63-7.61 (m, 2 H, H2”,6”), 7.55-7.38 (m, 6 H, H73’,4’,5’), 7.30 (d, 1 H,3J = 3.3 Hz, H2), 7.27 (d, 1 H, V = 2.4 Hz, H4), 7.04 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.69 (dd, 1 H,3J = 3.3 Hz,5J = 0.7 Hz, H3), 5.17 (s, 2 H, Hr).

[0731] 13C NMR (75 MHz, CDCI3): δ (ppm) 154.2 (5), 140.7 (3”), 137.5 (2’), 130.7 (5”), 130.7 (7a), 130.4 (4a), 129.4 (4”), 128.6 (4’), 127.9 (2), 127.9 (6”), 127.8 (5’), 127.6 (3’), 126.8 (2”), 118.1 (CN), 113.9 (1”), 113.8 (6), 110.9 (7), 105.0 (4), 104.8 (3), 70.8 (!’).

[0732] LC-MS (ESI): m / z Calculated: 324.1, Found: 325.0 [M+H]+, tR= 3.5 min.

[0733] EXAMPLE 65: 5-(benzyloxy)-l-(3-fluorophenyl)-lH-indole (FT303)

[0734] Compound 65 was synthesized following general procedure K from l-iodo-3 -fluorobenzene (0.05 mL) and was obtained as a brown oil in 75% yield.

[0735] ’H NMR (500 MHz, CDCI3): δ (ppm) 7.54-7.47 (m, 4 H, H7,3’,5”), 7.45-7.35 (m, 3 H, H4’,H5’), 7.33 (d, 1 H,3J = 3.2 Hz, H2), 7.33-7.31 (m, 1 H, H6”), 7.27-7.25 (m, 1 H, Hr), 7.24 (d, 1 H, V = 2.3 Hz, H4), 7.07 (m, 1 H, H4”), 7.02 (dd, 1 H,3J = 9.0 Hz, V = 2.3 Hz, H6), 6.64 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.17 (s, 2 H, Hr).

[0736] 13C NMR (125 MHz, CDC13): δ (ppm) 163.3 (d, V= 247.5 Hz, 3”), 154.0 (5), 141.4 (d,3J= 10.0 Hz, 1”), 137.6 (2’), 130.9 (d,3J= 9.0 Hz, 5”), 130.9 (7a), 130.1 (4a), 128.6 (4’), 128.1 (2), 127.9 (5’), 127.6 (3’), 119.4 (d,4J= 3.0 Hz, 6”), 113.5 (6), 113.1 (d,2J= 20.9 Hz, 4”), 111.3 (7), 111.1 (d,2J= 24.0 Hz, 2”), 104.5 (4), 104.1 (3), 70.8 (!’).

[0737] 19F NMR (471 MHz, CDCI3): δ (ppm) -110.81 (ddd,3J = 9.8 Hz,3J = 8.3 Hz, V = 6.4 Hz). LC-MS (ESI): m / z Calculated: 317.1, Found: 318.1 [M+H]+, tR= 3.7 min.

[0738] EXAMPLE 66: 5-(benzyloxy)-l-(3-chlorophenyl)-lH-indole (FT304) 333.82 g / mol.

[0739] Compound 66 was synthesized following general procedure K from 1 -chi oro-3 -iodo- benzene (0.05 mL) and was obtained as a brown oil in 49% yield.

[0740] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.57-7.53 (m, 4 H, H2”,4”,5”,6”), 7.50-7.40 (m, 4 H, H7,4’,5’), 7.39-7.34 (m, 2 H, H3’), 7.33 (d, 1 H,3J = 3.3 Hz, H2), 7.30 (d, 1 H, V = 2.5 Hz, H4), 7.07 (dd, 1 H,3J = 9.0 Hz,4J = 2.5 Hz, H6), 6.68 (dd, 1 H,3J = 3.3 Hz,5J = 0.8 Hz, H3), 5.21 (s, 2 H, Hr).13C NMR (75 MHz, CDCI3): δ (ppm) 154.0 (5), 141.1 (1”), 137.6 (2’), 135.3 (3”), 131.0

[0741] (7a), 130.7 (5”), 130.2 (4a), 128.6 (4’), 128.1 (2), 127.9 (5’), 127.6 (3’), 126.3 (4”), 124.0 (6”), 122.0 (2”), 113.6 (6), 111.3 (7), 104.6 (4), 104.2 (3), 70.8 (!’).

[0742] LC-MS (ESI): m / z Calculated: 333.1; 335.1, Found: 334.0; 336.0 [M+H]+, tR= 4.2 min.

[0743] EXAMPLE 67: 5-(benzyloxy)-l-(3-bromoDhenyl)-lH-indole (FT306) 378.27 g / mol Compound 67 was synthesized according to the general procedure K from 3 -bromo- 1 -iodo- benzene (0.05 mL) and was obtained as a yellow oil in 71% yield.

[0744] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.70 (t, 1 H,4J = 2.0 Hz, Hr), 7.55-7.35 (m, 9 H, H7, 3’, 4’, s’, 4”, 5”, 6”), 7.31 (d, 1 H,3J = 3.3 Hz, H2), 7.26 (d, 1 H,4J = 2.5 Hz, H4), 7.03 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.65 (dd, 1 H,3J = 3.3 Hz,5J = 0.8 Hz, H3), 5.17 (s, 2 H, Hr).

[0745] 13C NMR (75 MHz, CDCI3): δ (ppm) 154.0 (5), 141.2 (1”), 137.6 (2’), 131.0 (7a), 130.9 (5”), 130.1 (4a), 129.2 (4”), 128.6 (4’), 128.1 (2), 127.9 (5’), 127.6 (3’), 126.9 (2”), 123.1 (3”), 122.4 (6”), 113.5 (6), 111.2 (7), 104.5 (4), 104.1 (3), 70.8 (!’).

[0746] LC-MS (ESI): m / z Calculated: 377.0; 379.0, Found: 377.9; 380.0 [M+H]+, tR= 3.9 min.

[0747] EXAMPLE 68: 5-(benzyloxy)-l-(3-iodophenyl)-lH-indole (FT309)

[0748] Compound 68 was synthesized following general procedure K from 1,3 -diiodobenzene (0.05 mL) and was obtained as an orange oil in 42% yield.

[0749] 1H NMR (300 MHz, CDC13): δ (ppm) 7.88 (t, 1 H,4J = 1.9 Hz, Hr ), 7.69 (ddd,3J = 7.8 Hz,4J = 1.7 Hz,4J = 1.0 Hz, H4”), 7.53-7.33 (m, 7 H, H7,3’,4’,5’,6”), 7.30 (d, 1 H,3J = 3.3 Hz, H2), 7.25-7.22 (m, 2 H, H4,s ), 7.01 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.63 (dd, 1 H,3J = 3.3 Hz,5J = 0.8 Hz, H3), 5.16 (s, 2 H, Hr).

[0750] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.9 (5), 141.0 (1”), 137.6 (2’), 135.2 (4”), 132.8 (2”), 131.0 (5”), 131.0 (7a), 130.0 (4a), 128.6 (4’), 128.1 (2), 127.8 (5’), 127.5 (3’), 123.2 (6”), 113.5 (6), 111.2 (7), 104.5 (4), 104.1 (3), 94.6 (3”), 70.8 (!’).

[0751] LC-MS (ESI): m / z Calculated: 425.0, Found: 425.9 [M+H]+, tR= 3.9 min. EXAMPLE 69: Methyl 4-(5-(benzyloxy)-lH-indol-l-yl)benzoate (FT319) 357.41 g / mol; Mp: 122-124 °C.

[0752] Compound 69 was synthesized following general procedure K from methyl 4-iodobenzoate (0.11 g) and was obtained as a white solid in 68% yield.

[0753] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.23-8.20 (m, 2 H, Hr), 7.61-7.58 (m, 2 H, H3”), 7.56 - 7.24 (m, 7 H, H2,7,3’,4’,5’), 7.25 (d, 1 H, V = 2.4 Hz, H4), 7.03 (dd, 1 H,3J = 9.0 Hz, V = 2.4 Hz, H6), 6.67 (dd , 1H,3J = 3.3 Hz,5J = 0.8 Hz, H3), 5.17 (s, 2 H, Hr), 3.99 (s, 3 H, OCH3)

[0754] 13C NMR (125 MHz, CDCI3): δ (ppm) 166.5 (COO), 154.1 (5), 143.8 (4”), 137.5 (2’), 131.3 (2”), 130.7 (1”), 130.5 (7a), 128.6 (4’), 127.9 (2), 127.9 (5’), 127.5 (3’), 127.4 (4a),

[0755] 122.8 (3”), 113.6 (6), 111.5 (7), 104.7 (4), 104.6 (3), 70.8 (1’), 52.3 (OCH3).

[0756] LC-MS (ESI): m / z Calculated: 357.1, Found: 358.1 [M+H]+, tR= 3.6 min.

[0757] EXAMPLE 70: Methyl 3-(5-(benzyloxy)-lH-indol-l-yl)benzoate (FT320) 357.41 g / mol Compound 70 was synthesized following general procedure K from methyl 3-iodo benzoate

[0758] (0.11 mg) and was obtained as a yellow oil in 60% yield.1H NMR (300 MHz, CDCI3): δ (ppm) 8.20 (t, 1 H,4J = 2.2 Hz, Hr), 8.04 (dt, 1H,3J = 7.8 Hz,4J = 22 Hz, H6”), 7.73 (ddd, 1 H,3J = 7.9 Hz,4J = 2.2 Hz,4J = 1.3 Hz, H4”), 7.61 (t, 1 H,3J = 7.9 Hz, H5”), 7.54-7.35 (m, 7 H, H2,7,3’,4’,5’), 7.25 (d, 1 H,4J = 2.5 Hz, H4), 7.01 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.65 (dd, 1 H,3J = 3.2 Hz,5J = 0.8 Hz, H3), 5.17 (s, 2 H, Hr), 3.99 (s, 3 H, OCH3).

[0759] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.4 (COO), 153.9 (5), 140.2 (3”), 137.6 (2’), 131.8 (7a), 131.1 (1”), 130.0 (4a), 129.7 (5”), 128.6 (4’), 128.2 (2), 128.1 (5’), 127.8 (4”), 127.5 (3’), 127.2 (6”), 124.8 (2”), 113.5 (6), 111.1 (7), 104.5 (4), 104.0 (3), 70.8 (1’), 52.4 (OCH3).

[0760] LC-MS (ESI): m / z Calculated: 357.1, Found: 358.1 [M+H]+, tR= 3.6 min.

[0761] Compound 71 was synthesized following general procedure K from methyl 2-iodobenzoate (0.06 mL) and was obtained as a yellow oil in 57% yield.

[0762] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.04 (dd, 1 H,3J = 8.3 Hz,4J = 1.6 Hz, H6”), 7.68 (td, 1 H,3J = 8.9 Hz,4J = 1.6 Hz, H4”), 7.57-7.39 (m, 7 H, H3-.-r.5-.5”, 3”), 7.30 (d , 1 H,4J = 2.4 Hz, H4), 7.25 (d, 1 H,3J = 3.2 Hz, H2), 7.14 (d, 1 H,3J = 8.9 Hz, H7), 7.00 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.68 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.19 (s, 2 H, Hr), 3.55 (s, 3 H, OCH3).

[0763] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.9 (COO), 153.7 (5), 138.9 (2”), 137.8 (2’), 132.8 (4”), 132.8 (7a), 131.3 (6”), 129.5 (2), 129.3 (4a), 128.9 (1”), 128.6 (4’), 128.4 (5”), 127.8 (5’), 127.6 (3’), 127.5 (3”), 113.2 (6), 110.6 (7), 104.4 (4), 103.1 (3), 70.9 (1’), 52.3 (OCH3).

[0764] LC-MS (ESI): m / z Calculated: 357.1, Found: 358.2 [M+H]+, tR= 3.5 min. indole (FT324) 344.36 g / mol; Mp = 122-124 °C.

[0765] Compound 72 was synthesized following general procedure K from l-iodo-3 -nitrobenzene (0.10 g) and was obtained as a yellow solid in 45% yield.

[0766] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.40 (t, 1 H, V = 2.2 Hz, Hr), 8.20 (ddd,3J = 8.2 Hz,4J = 2.2 Hz,4J = 1.2 Hz, H6”), 7.87 (ddd,3J = 8.1 Hz,4J = 2.2 Hz,4J = 1.2 Hz, H4”), 7.71 (t, 1 H,3J = 8.1 Hz, H5”), 7.53-7.36 (m, 7 H, H2,7,3’,4’,5’), 7.26 (d, 1 H,3J = 2.5 Hz, H4), 7.04 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.69 (dd, 1 H,3J = 3.3 Hz,5J = 0.7 Hz, H3), 5.17 (s, 2 H, Hr).

[0767] 13C NMR (75 MHz, CDCI3): δ (ppm) 154.2 (5), 149.2 (3”), 141.0 (1”), 137.4 (2’), 130.7 (7a), 130.6 (5”), 130.4 (4a), 129.2 (4”), 128.6 (4’), 127.9 (2), 127.7 (5’), 127.5 (3’), 120.6 (6”), 118.3 (2”), 113.9 (6), 110.9 (7), 105.2 (4), 104.8 (3), 70.8 (!’).

[0768] LC-MS (ESI): m / z Calculated: 344.1, Found: 345.1 [M+H]+, tR= 3.6 min.

[0769] (FT312) .37 g / mol; Mp = 123-125 °C

[0770] Synthesis of 2-(3-iodophenoxy)tetrahydro-2H- pyran: To a solution of 3 -iodophenol (2.0 g, 10.91 mmol, 1 eq.) in dichloromethane (27 mL), DHP (1.2 eq.) and PPTS (8 mol%) were added. Reaction was stirred for 8 h. Mixture was diluted in ethyl acetate and washed three times with K2CO3 solution (1 N). Combined organic phases was dried over MgSO4and solvent was removed under vacuum. Product was obtained as a yellow oil.

[0771] Synthesis of 3-(5-(benzyloxy)-lH-indol-l-yl)phenol: To a solution of 5-benzyloxyindole (1 eq.) in DMF (1 mL), K2CO3 (1 eq.), 2-(3-iodophenoxy)tetrahydro-2H-pyran (0.12 g, 0.9 eq., 0.40 mmol) and Cu (7 mol%) were added. Reaction was stirred under reflux for 18 h and was cooled at room temperature. Mixture was filtered through celite, diluted in more water (50 mL) and extracted three times with ethyl acetate. Combined organic phases was dried over MgSO4and solvent was removed under vacuum. Residue was diluted in THF and heated to 50 °C. Then, a HC1 solution (37%) (0.2 mL) was added and the reaction was stirred at 50 °C for Ih. Mixture was diluted in ethyl acetate and washed three times with K2CO3 solution (1 N). Combined organic phases was dried over MgSO4and solvent was removed under vacuum. Compound 73 was purified by column chromatography with ethyl acetate / cyclohexane (30:70) as eluant.

[0772] Compound 73 was synthesized from 2-(3-iodophenoxy)tetrahydro-2H-pyran (0.09 g) and was obtained as a brown solid in 71% yield.

[0773] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.54-7.49 (m, 3 H, H4’,7), 7.44-7.34 (m, 4 H, H3’,5’,5”), 7.32 (d, 1 H,3J = 3.2 Hz, H2), 7.23 (d, 1 H,4J = 2.4 Hz, H4), 7.09 (ddd, 1 H,3J = 8.0 Hz,4J = 2.0 Hz,4J = 0.9 Hz, H4”), 7.00 - 6.96 (m, 2 H, H6,2”), 6.81 (dd, 1 H,3J = 8.1 Hz,4J = 2.4 Hz, H6”), 6.60 (dd, 1 H,3J = 3.2 Hz,5J = 0.7 Hz, H3), 5.15 (s, 2 H, Hr), 5.14 (brs, 1 H, OH)

[0774] 13C NMR (75 MHz, CDCI3): δ (ppm) 156.5 (1”), 153.7 (5), 141.2 (3”), 137.6 (2’), 131.1 (7a), 130.6 (5”), 129.9 (4a), 128.6 (4’), 128.3 (2), 127.8 (5’), 127.5 (3’), 116.3 (4”), 113.2 (6”), 113.2 (2”), 111.5 (6), 111.0 (7), 104.4 (4), 103.4 (3), 70.9 (!’).

[0775] LC-MS (ESI): m / z Calculated: 315.1, Found: 314.2 [M-H]", 316.1 [M+H]+, tR= 3.3 min.

[0776] 2.11. Synthesis of Examples 74-75

[0777] EXAMPLE 74: 3-(5-(benzyloxy)-lH-indol-l-yl)aniline (FT325)

[0778]

[0779] To a solution of compound 72 (0.1 g, 0.29 mmol, 1 eq.) in methanol (35 mL), Ni (large excess) washed twice with methanol is added followed by hydrazine (30 eq.). Solution is stirred for 16 h. Solution is filtered through celite twice then the methanol is removed under vacuum. The residue diluted in dichloromethane (15 mL) and then washed 3 times with water (3 x 20 mL). The organic phase is dried over MgSO4and then evaporated. Compound 74 is obtained as a yellow oil without purification in 99% yield.

[0780] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.55-7.26 (m, 8 H, H2,7,3’,4’,5’,5”), 7.23 (d, 1 H,4J =

[0781] 2.4 Hz, H4), 6.98 (dd, 1 H,3J = 9.0 Hz,4J = 2.4 Hz, H6), 6.90 (dd, 1 H,3J = 7.9 Hz,4J = 2.2 Hz, H6”), 6.81 (t, 1 H,4J = 2.2 Hz, Hr), 6.67 (ddd, 1 H,3J = 8.0 Hz,4J = 2.2 Hz,4J =

[0782] 0.8 Hz, H4”), 6.59 (dd, 1 H,3J = 3.2 Hz,5J = 0.8 Hz, H3), 5.16 (s, 2 H, Hr), 3.84 (brs, 2 H, NH2)

[0783] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.7 (5), 147.6 (1”), 140.9 (3”), 137.7 (2’), 131.2 (7a), 130.4 (5”), 129.8 (4a), 128.5 (4’), 128.4 (2), 127.8 (5’), 127.5 (3’), 114.1 (6”), 113.1 (6), 112.9 (4”), 111.6 (7), 110.4 (2”), 104.3 (4), 103.0 (3), 70.9 (!’).

[0784] LC-MS (ESI): m / z Calculated: 314.1, Found: 315.1 [M+H]+, tR= 3.3 min.

[0785] EXAMPLE 75: N-(3-r5-(benzyloxy)-lH-indol-l-yl1phenvHethene-l -sulfonamide

[0786] (BGZ0080) 404.48 g / mol.

[0787] To a solution of compound 74 (100 mg, 0.32 mmol) in dry DCM (1 mL) and tri ethylamine (66 pL, 1.5 eq.) cooled to 0°C in an ice bath, ethenesulfonyl chloride (20 mg, 0.16 mmol, 0.5 eq.) in solution in dry DCM (1 mL) was added dropwise. The mixture was stirred at 0°C for 1 hour. The mixture was diluted with DCM and washed with saturated a NaHCCL aqueous solution (3 x 15 mL) and brine (1 x 15 mL). The organic phase was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The crude material was purified by column chromatography with toluene / ethyl acetate (9: 1) as the eluent. The desired compound was obtained as a dark red solid in 24% yield (m = 31 mg).

[0788] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.26 (m, 10 H, H3,4, s\ 2, 7, 2”, 5”, 6”), 7.21 (d, 1 H,4J = 2.4 Hz, H4), 7.07 (ddd, 1 H,3J = 8.0 Hz,4J = 2.1 Hz,5J = 0.9 Hz, H4”), 6.98 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.71-6.55 (m, 3 H, H3, NHSO2CHCH2, NHSO2CH=CH2), 6.36 (d, 1 H,3Jtrans= 16.6 Hz, NHSO2CH=CH2), 6.03 (d, 1 H,3JCIS= 9.9 Hz, NHSO2CHCH2), 5.13 (s, 2 H, Hr).

[0789] 13C NMR (75 MHz, CDC13): 3 (ppm) 154.0 (5), 141.1 (3”), 137.7 (1”), 135.3 (NHSO2CH=CH2), 131.0 (2’), 130.8 (6’), 130.2 (4a), 129.1 (NHSO2CH=CH2), 128.7 (4’), 128.2 (5’), 128.0 (7a), 127.7 (3’), 120.4 (2’), 118.0 (4”), 115.8 (CH), 113.6 (6), 111.4 (7), 104.6 (4), 104,1 (3), 71.0 (!’).

[0790] LC-MS (ESI): m / z Calculated: 404.1, Found: 405.2 [M+H]+, 403.2 [M-H]’, tR= 2.48 min.

[0791] 2,12, Synthesis of (5-(benzyloxy)-7J / -indol-l-yl)nicotinic and picolinic acids (Examples 76- 82) EXAMPLE 76: Methyl 6-r5-(benzyloxy)-lH-indol-l-yl]pyridine-2-carboxylate

[0792] (BGZ0078) 358.39 g / mol

[0793] Methyl 6-chloropyridine-2-carboxylate was obtained from 6-chloropyridine-2-carboxylic acid following the procedure from Tayama, E. et. al., Tetrahedron, 2022, 777, 132721.

[0794] In an oven-dried sealable tube 5 -benzyloxyindole (267 mg, 1.2 mmol, 1.2 eq.), K3PO4 (445 mg, 2.1 mmol, 2.1 eq.) and methyl 6-chloropyridine-2-carboxylate (172 mg, 1 mmol, 1 eq.) and BINAP (31 mg, 0.05 mmol, 5 mol%) were added and dissolved in 1,4-dioxane (2 mL). Nitrogen gas was bubbled in the mixture for 10 min then Pd(OAc)2 was added. The tube was sealed and the reaction was stirred with heating via oil bath at 110 °C for 18 h. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered through a celite plug. The crude mixture was purified by column chromatography with petroleum ether / ethyl acetate (9: 1) as the eluent. Compound 76 was obtained as a light yellow solid in 32% yield (m = 137 mg).

[0795] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.48 (d, 1 H,3J = 9.1 Hz, Hs ), 7.94-7.89 (m, 2 H, H3”,4”), 7.69 (d, 1 H,3J = 3.5 Hz, H2), 7.62-7.56 (m, 1 H, H7), 7.52-7.28 (m, 5 H, H3’,4’,5’), 7.18 (d, 1 H, V = 2.5 Hz, H4), 7.07 (dd, 1 H,3J = 9.0 Hz, V = 2.5 Hz, H6), 6.65 (dd, 1 H,3J = 3.5 Hz,5J = 0.6 Hz, H3), 5.15 (s, 2 H, Hr), 4.05 (s, 3 H, H7 )

[0796] 13C NMR (75 MHz, CDCI3): δ (ppm) 165.6 (COO), 154.6 (5), 152.5 (6”), 147.0 (2”), 139.5 (4”), 137.6 (2’), 131.4 (7a), 130.7 (4a), 128.7 (4’), 127.9 (5’), 127.6 (3’), 125.7 (2), 120.7 (3”), 116.6 (7), 115.2 (5”), 114.0 (6), 106.6 (3), 104.8 (4), 70.8 (!’), 53.1 (7”).

[0797] LC-MS (ESI): m / z Calculated: 358.1, Found: 359.2 [M+H]+, 381.2 [M+Na]+, tR= 2.47 min. EXAMPLE 77: methyl 2-r5-(benzyloxy)-lH-indol-l-yl]pyridine-4-carboxylate (BGZ077) 358.39 g / mol

[0798] In an oven-dried sealable tube, Cui (2.0 mg, 0.01 mmol, 1.0 mol%), 5-benzyloxyindole (267 mg, 1.2 mmol, 1.2 eq.) and K3PO4 (445 mg, 2.1 mmol, 2.1 eq.) were added. The tube was evacuated twice and back-filled with nitrogen gas. Methyl 2-iodopyridine-4-carboxylate (263 mg, 1 mmol, 1 eq.), traws-l,2-cyclohexanediamine (12 pL, 0.10 mmol, 10 mol%) and 1,4-di oxane (1 mL) were added under nitrogen gas. The tube was sealed and the reaction was stirred with heating via oil bath at 110 °C for 24 h. The mixture was cooled to room temperature, diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over Na2SO4 filtered and concentrated under reduced pressure. The crude mixture was purified by column chromatography with cy cl ohexane / di chloromethane (5:5) as the eluent. Compound 77 was obtained as a yellow solid in 28% yield (m = 101 mg).

[0799] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.66 (dd, 1 H,3J = 5.1 Hz,5J = 0.8 Hz, H6”), 8.27 (d, 1 H,3J = 9.1 Hz, H7), 8.01 (dd, 1 H, V = 1.1 Hz, H3”), 7.74 (d, 1 H,3J = 3.5 Hz, H2), 7.65 (dd, 1 H,3J = 5.1 Hz,4J = 1.3 Hz, Hs ), 7.53-7.28 (m, 5 H, H3’,4’,5’), 7.19 (d, 1 H, V =

[0800] 2.5, H4), 7.05 (dd, 1 H,3J = 9.1 Hz,4. / = 2.5 Hz, H6), 6.66 (dd, 1 H,3J = 3.5 Hz,5J = 0.6

[0801] Hz, H3), 5.14 (s, 2 H, Hr), 4.00 (s, 3 H, H7).

[0802] 13C NMR (75 MHz, CDCI3): δ (ppm) 165.4 (COO), 154.5 (2”), 153.5 (4”), 149.7 (6”),

[0803] 139.9 (5), 137.6 (2’), 131.4 (7a), 130.5 (4a), 128.7 (4’), 128.0 (5’), 127.7 (3’), 126.1 (2), 118.6 (5”), 114.7 (7), 113.8 (6), 113.0 (3”), 106.4 (3), 104.7 (4), 70.8 (!’), 53.1 (7”).

[0804] LC-MS (ESI): m / z Calculated: 358.1, Found: 359.2 [M+H]+, tR= 2.57 min.

[0805] EXAMPLE 78: 2-r5-(benzyloxy)-lH-indol-l-yl]pyridine-4-carboxylic acid (BGZ0079) 344.36 g / mol

[0806] To a solution of Compound 77 (63 mg, 0.18 mmol) in THF (0.75 mL) was added 2M aqueous LiOH (0.88 mL, 1.76 mmol, 10 eq.). The reaction was refluxed for 2 hours. The mixture was cooled to room temperature and acidified to pH 2-3 using IM aqueous HC1 then extracted with EtOAc (3 x 25 mL). The combined organic phases were washed with brine (1 x 30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Compound 78 was obtained as a yellow powder in 89% yield (m = 54 mg).

[0807] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 8.70 (dd, 1 H,3J = 5.1 Hz,5J = 0.6 Hz, H6”), 8.36 (d, 1 H,3J = 9.1 Hz, H7), 8.11 (d, 1 H,3J = 3.5 Hz, H2), 8.05 (dd, 1 H, V = l.l Hz,4J = 0.9 Hz, H3”), 7.66 (dd, 1 H,3J = 5.1 Hz,4J = 1.2 Hz, Hs ), 7.52-7.28 (m, 5 H, H3’,4’,5’), 7.25 (d, 1 H,4. / = 2.5, H4), 6.99 (dd, 1 H,3J = 9.1 Hz,4J = 2.5 Hz, H6), 6.70 (dd, 1 H,3J = 3.5 Hz,5J = 0.6 Hz, H3), 5.14 (s, 2 H, Hr).

[0808] 13C NMR (75 MHz, DMSO-d6): δ (ppm) 165.9 (COOH), 153.8 (2”), 152.9 (4”), 149.5 (6”), 141.6 (5), 137.5 (2’), 130.9 (7a), 129.8 (4a), 128.4 (4’), 127.7 (5’), 127.7 (3’), 126.8 (2), 118.7 (5”), 115.2 (7), 113.1 (6), 112.5 (3”), 106.0 (3), 104.2 (4), 69.6 (!’).

[0809] LC-MS (ESI): m / z Calculated: 344.1, Found: 343.1 [M-H]’, tR= 1.98 min.

[0810] General procedure L for the synthesis of compounds 79-82: To a solution of benzyloxyindole (1 eq.) in DMF (1 mL), K2CO3 (1 eq.), chloronicotinic or pinacolic acid (0.07 g, 0.40 mmol, 0.9 eq.) and Cu (7 mol%) was added. Reaction was stirred under reflux for 18 h and was cooled at room temperature. Mixture was quenched with NaHCO3(1 N) and extracted three times with ethyl acetate. Aqueous phase was acidified with acetic acid and extracted with ethyl acetate (three times). Combined organic phases was dried over MgSO4and solvent was removed under vacuum. Residues were purified by HPLC (55 min, from 60% acetonitrile / 40% mili-Q water to 100% of acetonitrile). EXAMPLE 79: 2 (5- i-777-indol-l - inic acid 344.36 g / mol; Mp = 86-88 °C.

[0811] Compound 79 was synthesized following general procedure L from 2-chloronicotinic acid and 5-benzyloxyindole (0.10 g) and was obtained as a pink solid in 38% yield.

[0812] 1H NMR (300 MHz, CO(CD3)2): δ (ppm) 8.73 (dd, 1 H,3J = 4.8 Hz,4J = 1.9 Hz, H6”), 8.39 (dd, 1 H,3J = 7.7 Hz,4J = 1.9 Hz, Hs ), 7.56-7.48 (m, 5 H, H2,7,4’,5”), 7.43-7.38 (m, 2 H, H3’), 7.35-7.30 (m, 1 H, Hs ), 7.24 (d, 1 H,4J = 2.5 Hz, H4), 6.93 (dd, 1 H,3J = 9.0 Hz,4J = 2.5 Hz, H6), 6.60 (dd, 1 H,3J = 3.4 Hz,5J = 0.7 Hz, H3), 5.16 (s, 2 H, Hr).

[0813] 13C NMR (75 MHz, CO(CD3)2): δ (ppm) 166.3 (COO), 154.1 (5), 151.4 (6”), 150.1 (2”), 140.4 (4”), 138.1 (2’), 131.3 (7a), 130.5 (4a), 128.7 (5”), 128.3 (4’), 127.5 (5’), 127.5 (3’), 122.1 (3”), 121.4 (2), 112.7 (6), 112.3 (7), 104.3 (3), 104.2 (4), 70.1 (!’).

[0814] LC-MS (ESI): m / z Calculated: 344.1, Found: 343.3 [M-H]~, 345.3 [M+H]+, tR= 2.3 min.

[0815] EXAMPLE 80: 6-(5-(benzyloxy)-777-indol-l-yl)Dicolinic acid (FT184) 344.36 g / mol; Mp = 178-180 °C.

[0816] Compound 80 was synthesized following general procedure L from 6-chloropicolinic acid and 5-benzyloxyindole (0.10 g) and was obtained as a white solid in 42% yield. 1H NMR (300 MHz, CDC13): δ (ppm) 8.10-8.09 (m, 2 H, Hr,4”), 7.97 (d, 1 H,3J = 9.0 Hz, H7), 7.77 (m, 1 H, Hs ), 7.68 (d, 1 H,3J = 3.6 Hz, H2), 7.53-7.33 (m, 5 H, H3’,4\5’), 7.24 (d, 1 H, \J = 2.5 Hz, H4), 7.08 (dd, 1 H,3J = 9.0 Hz, \J = 2.5 Hz, H6), 6.72 (dd, 1 H,3J = 3.6 Hz,5J = 0.6 Hz, H3), 5.17 (S, 2 H, Hr).

[0817] 13C NMR (75 MHz, CDC13): δ (ppm) 163.7 (COO), 154.7 (5), 151.3 (6”), 145.3 (2”), 141.0 (4”), 137.3 (2’), 131.5 (7a), 129.9 (4a), 128.6 (4’), 127.9 (5’), 127.5 (3’), 126.2 (2), 119.8 (3”), 118.7 (5”), 114.0 (6), 113.1 (7), 107.0 (3), 105.1 (4), 70.7 (!’).

[0818] LC-MS (ESI): m / z Calculated: 344.1, Found: 343.2 [M-H]", 345.1 [M+H]+, tR= 2.8 min.

[0819] EXAMPLE 81: 6-(4-(benzyloxy)-lH-indol-l-yl)picolinic acid (FT215) 344.36 g / mol; Mp = 173-175 °C.

[0820] Compound 81 was synthesized following general procedure L from 6-chloropicolinic acid and 4-benzyloxyindole (0.10 g) and was obtained as a white solid in 34% yield.

[0821] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.15-8.08 (m, 2 H, H3”,4”), 7.81 (dd, 1 H,3J = 6.6 Hz,4J = 2.6 Hz, H5”), 7.65 - 7.61 (m, 2 H, H2,7), 7.56-7.53 (m, 2 H, H3’), 7.47 - 7.37 (m, 3 H, H4’,5’), 7.27 (dd, 1 H,3J = 8.2 Hz,3J = 7.4 Hz, H6), 6.99 (dd, 1 H,3J = 3.6 Hz,5J = 0.7 Hz, H3), 6.77 (d, 1 H,3J = 7.4 Hz, Hs), 5.28 (s, 2 H, Hr).

[0822] 13C NMR (75 MHz, CDC13): δ (ppm) 163.6 (COO), 152.7 (4), 151.4 (6”), 145.3 (2”), 141.0 (4”), 137.2 (2’), 136.2 (7a), 128.6 (4’), 127.9 (5’), 127.4 (3’), 124.8 (6), 124.3 (2), 121.5 (4a), 120.1 (3”), 119.3 (5”), 105.5 (5), 104.4 (3), 103.7 (7), 70.1 (!’).

[0823] LC-MS (ESI): m / z Calculated: 344.1, Found: 343.2 [M-H]", 345.0 [M+H]+, tR= 2.9 min.

[0824] EXAMPLE 82: 6-(6-(benzyloxy)-lH-indol-l-yl)picolinic acid (FT217) 344.36 g / mol; Mp = 177-179 °C.

[0825] Compound 82 was synthesized following general procedure L from 6-chloropicolinic acid and 6-benzyloxyindole (0.10 g) and was obtained as a white solid in 39% yield.

[0826] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.13-8.06 (m, 2 H, Hr, 4”), 7.73-7.69 (m, 2 H, H7,5”), 7.60-7.57 (m, 2 H, HM), 7.51-7.48 (m, 2 H, Hr), 7.45-7.32 (m, 3 H, H4,s ), 7.03 (dd, 1 H,3J = 7.7 Hz,4J = 2.2 Hz, Hs), 6.73 (dd, 1 H,3J = 3.5 Hz,5J = 0.6 Hz, H3), 5.17 (s, 2 H, Hr).

[0827] 13C NMR (75 MHz, CDCI3): δ (ppm) 163.8 (COO), 156.6 (6), 151.4 (6”), 145.4 (2”), 140.9 (4”), 137.1 (2’), 135.6 (7a), 128.6 (4’), 128.0 (5’), 127.5 (3’), 124.8 (4a), 124.7 (2), 122.0 (4), 120.0 (3”), 118.9 (5”), 112.1 (5), 107.0 (3), 98.2 (7), 70.7 (!’).

[0828] LC-MS (ESI): m / z Calculated: 344.1, Found: 343.1 [M-H]", 345.0 [M+H]+, tR= 2.9 min.

[0829] 2,13, Synthesis of l-benzyl-5-(benzyloxy)-lH-indoles (Examples 83-115)

[0830] General procedure M for N-benzylation reactions of indoles: To a solution of 5- benzyloxyindole (300 mg-1.0 g, 1.34-4.48 mmol) in dry DMF (3-5 mL) cooled to 0 °C under N2 atmosphere, NaH (60 % suspension in mineral oil, 1.0-1.1 eq.) was added by portions. The mixture was stirred at room temperature for 20 minutes. The mixture was cooled to 0 °C and a solution of the appropriate benzyl bromide derivative (1.0-1.5 eq.) in dry DMF (3- 5 mL) was added dropwise. The mixture was stirred at room temperature for 15 minutes up to 2 hours. The mixture was poured in water (300 mL) and was extracted by EtOAc (3 / 50 mL). The combined organic phases were washed with brine and dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by by column chromatography with cyclohexane / ethyl acetate (9: 1) or alternatively petroleum ether / ethyl acetate (9: 1 or 8:2) as the eluent.

[0831] EXAMPLE 83: l-benzyl-5-(benzyloxy)-lH-indole (BGZ0014) 313.39 g / mol

[0832] Compound 83 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and benzyl bromide (253 mg) and was obtained as a white solid in 61% yield (m = 255 mg).

[0833] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.25 (m, 8 H, Haematics), 7.20 (d, 1 H4J = 2.4 Hz, H4), 7.17 (d, 1 H,3J = 8.9 Hz, H7), 7.14-7.07 (m, 3 H, Haromatics), 6.92 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.47 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.29 (s, 2H, Hi”), 5.17 (s, 2 H, Hr).

[0834] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.5 (5), 137.9 (2”), 137.7 (2’), 131.9 (4a), 129.2 (7a), 129.0 (CHaromatic), 128.9 (CHaromatic), 128.6 (CHaromatic), 127.9 (CHaromatic), 127.7

[0835] (CHaromatic), 127.7 (CHaromatic), 126.9 (CHaromatic), 112.8 (6), 110.6 (7), 104.3 (4), 101.4 (3), 71.1 (!’), 50.4 (1”).

[0836] LC-MS (ESI): m / z Calculated: 313.2, Found: 314.2 [M+H]+, tR= 2.5 min.

[0837] EXAMPLE 84: 5-(benzyloxy)-l-r(2-nitrobenzyl]-lH-indole (BGZ0034) 358.39 g / mol

[0838] Compound 84 was synthesized following general procedure M from 5-benzyloxyindole (500 mg) and 2-nitrobenzyl bromide (725 mg) and was obtained as a yellow solid in 45% yield (m = 358 mg). ’H NMR (300 MHz, CDCI3): δ (ppm) 8.20-8.12 (m, 1 H, H4”), 7.52-7.27 (m, 7 H H3’,4’,5’,5”,6”), 7.23 (d, 1 H, V = 2.4 Hz, H4), 7.12 (d, 1 H,3J = 3.1 Hz, H2), 7.05 (d, 1 H,3J = 8.9 Hz, H7), 6.92 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.55 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 6.52-6.44 (m, 1 H, H7), 5.73 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0839] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.8 (5), 147.2 (3’), 137.8 (2’), 134.5 (2”), 134.4 (6”), 131.8 (4a), 129.7 (7a), 129.2 (2), 128.7 (4’), 128.5 (5”), 128.3 (7”), 127.9 (5’), 127.7 (3’), 125.3 (4”), 113.3 (6) 110.4 (7), 104.5 (4), 102.4 (3), 71.0 (!’), 47.9 (1”).

[0840] LC-MS (ESI): m / z Calculated: 358.1, Found: 359.3 [M+H]+, tR= 2.54 min.

[0841] EXAMPLE 85: 2- (benzyloxy)-lH-indol-l-yl]methvHaniline (BGZ0061) 328.41 g / mol

[0842] To a stirred solution of compound 84 (284 mg, 0.79 mmol) in EtOH (50 mL) was added Raney Nickel and hydrazine monohydrate (0.50 mL, 15.85 mmol, 20 eq.). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through a pad of celite, washed with ethanol and the filtrate was evaporated under reduced pressure. The residue was dissolved in AcOEt, washed with water three times, dried over MgSO4, filtered and evaported under reduced pressure. The oily residue was dissolved in toluene and evaported under reduced pressure to give compound 85 as a light brown solid in 85% yield (m = 220 mg).

[0843] 1H NMR (300 MHz, CDC13): δ (ppm) 7.54-7.32 (m, 5 H H3’,4’,5’), 7.29 (d, 1 H,3J = 8.9 Hz, H7), 7.23-7.12 (m, 2 H, H4,7”), 7.05-6.99 (m, 2 H, H2,5), 6.97 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.79 (dt, 1 H,3J = 7.5 Hz,4J = 1.0 Hz, H6”), 6.70 (dd, 1 H,3J = 7.9 Hz,5J = 0.7 Hz, H4”), 6.46 (dd, 1 H,3J = 3.1 Hz,5J = 0.5 Hz, H3), 5.14 (s, 2 H, Hi”), 5.12 (s, 2 H, Hr), 3.50 (br, 2 H, NH2).13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 145.1 (3”), 137.9 (2’), 132.0 (4a), 129.9 (2), 129.4 (7”), 128.6 (4’), 128.1 (5”), 127.9 (5’), 127.7 (3’), 121.2 (2”) 119.1 (6”), 116.5 (4”), 112.9 (6), 110.4 (7), 104.5 (4), 101.7 (3), 71.0 (!’), 47.9 (1”).

[0844] LC-MS (ESI): m / z Calculated: 328.2, Found: 329.3 [M+H]+, tR= 2.42 min. ( / / / _- 106.2 (4- aminophenyl)methylium fragment) ; m / z 236.3 (-92; - PI1CH2)) thvnphenyl)-2-chloroacetamide 404.89 g / mol

[0845] To a solution of compound 85 (100 mg, 0.30 mmol) in dry DCM (2 mL) cooled to 0 °C, triethylamine (85 pL, 0.60 mmol, 2 eq.) was added. A solution of chloroacetyl chloride (36 pL, 0.46 mmol, 1.5 eq.) in dry DCM (2 mL) was added dropwise at 0 °C. The mixture was stirred at room temperature for 2 hours. The mixture was diluted with DCM and washed with a saturated NaHCO3solution (3 ^ 15mL) and brine (1 x 15mL). The organic phase was dried over MgSCU, filtered and concentrated under reduced pressure. The crude mixture was purified by flash chromatography with petroleum ether / ethyl acetate 8:2 as the eluent. Compound 86 was obtained as a white solid in 56% yield (m = 69 mg).

[0846] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.01 (br, 1 H, NH), 7.64 (d, 1 H,3J = 7.7 Hz, H4”), 7.51-7.28 (m, 6 H H3’,4’,5’,5”), 7.25-7.13 (m, 3 H, H4,7,6”), 7.06 (d, 1 H,3J = 7.7 Hz, H7 ), 6.98 (d, 1 H,3J = 3.2 Hz, H2), 6.93 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.48 (dd, 1 H,3J = 3.2 Hz,4J = 0.5 Hz, H3), 5.25 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr), 4.03 (s, 2 H, Hs )

[0847] 13C NMR (75 MHz, CDC13): δ (ppm) 164.7 (CONH), 153.6 (5), 137.7 (3”), 134.2 (2’), 132.0 (2”), 130.5 (4a), 129.4 (7a), 129.3 (7”), 129.1 (5”), 128.6 (4’), 128.2 (2), 127.9 (5’), 127.7 (3’), 127.1 (6”), 125.1 (4”), 113.1 (6), 110.5 (7), 104.5 (4), 102.3 (3), 70.9 (!’), 47.7 (1”), 42.8 (8”).

[0848] LC-MS (ESI):m / z Calculated: 404.1 Found: 405.2 [M+H]+, 403.2 [M-H]’ tR= 2.25 min.

[0849] EXAMPLE 87: N-(2-l r5-(benzyloxy)-lH-indol-l-yl]methvHDhenyl)ethene-l- sulfonamide (BGZ0098) 418.51 g / mol

[0850] To a solution of compound 85 (144 mg, 0.44 mmol) in dry DCM (1.5 mL) and triethylamine (91 pL, 0.66 mmol, 1.5 eq.) cooled to 0°C in an ice bath, ethenesulfonyl chloride (55 mg, 0.44 mmol, 1.0 eq.) in solution in dry DCM (1.5 mL) was added dropwise. The mixture was stirred at 0°C for 2 hours. The mixture was diluted with DCM (20 mL) and washed with a saturated NaHCCh aqueous solution (3 x 15 mL) and brine (1 x 15mL). The organic phase was dried over MgSCh, filtered and the solvent removed under reduced pressure. The crude material was purified by flash chromatography with toluene / ethyl acetate (9: 1) as the eluent. The residue was further purified by triturating it with diethyl ether, collecting the diethyl ether and evaporating it. Compound 87 was obtained as a brown sticky solid in 15% yield (m= 28 mg).

[0851] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.24 (m, 7 H Hr, 4’, 5’, 5”, 6”), 7.23-7.15 (m, 2 H, H4,4”), 7.12 (d, 1 H,3J = 8.9 Hz, H7), 7.07 (d, 1 H,3J = 3.1 Hz, H2), 6.97-6.86 (m, 2 H, H6,7”), 6.48 (dd, 1 H,3J = 3.1 Hz,5J = 0.6 Hz H3), 6.42 (dd, 1 H,3Jtrans= 16.5 Hz,3JC1S= 9.8 Hz, NHSO2CH=CH2), 6 22-6 10 (m, 2 H, NHSO2CH=CH2, NHSChCHCHi), 5 89 (d, 1 H,3JC1S= 9.8 Hz, NHSO2CH=CH2), 5.43 (s, 2 H, Hi”), 5.09 (s, 2 H, Hr).

[0852] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 137.8 (2’), 135.2 (NHSO2CH=CH2), 133.7 (3”), 133.6 (2”), 131.9 (4a), 129.3 (7a), 129.3 (7”), 128.9 (2), 128.8 (2), 128.7 (4’), 128.5 (NHSO2CH=CH2), 127.9 (4”), 127.9 (6”), 127.7 (3’), 126.3 (5”), 113.1 (6), 110.6 (7), 104.4 (4), 102.2 (3), 70.9 (!’), 47.7 (1”).

[0853] LC-MS (ESI): m / z Calculated: 418.1, Found: 417.2 [M-H]7419.3 [M+H]+, tR= 2.31 min.

[0854] EXAMPLE 88: 5-(benzyloxy)-l-r(3-nitrobenzyl]-lH-indole (BGZ0035) 358.39 g / mol

[0855] Compound 88 was synthesized following general procedure M from 5-benzyloxyindole (1.0 g) and 3-nitrobenzyl bromide (1.45 g) and was obtained as a yellow solid in 42% yield (m = 670 mg).

[0856] 1H NMR (300 MHz, CDCI3): 3 (ppm) 8.16-8.08 (m, 1 H, Hs ), 8.07-7.99 (m, 1 H H3”), 7.53-7.28 (m, 7 H, H3’,4’,5’,6”,7”), 7.21 (d, 1 H, V = 2.3 Hz, H4), 7.13 (d, 1 H,3J = 3.1 Hz,

[0857] H2), 7.10 (d, 1 H,3J = 8.9 Hz, H7), 6.93 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.52 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.37 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0858] 13C NMR (75 MHz, CDC13): δ (ppm) 153.7 (5), 148.7 (4”), 140.0 (2”), 137.7 (2’), 132.7 (7”), 131.6 (4a), 130.0 (6”), 129.4 (7a), 128.7 (2), 128.7 (4’), 127.9 (5’), 127.7 (3’), 122.8 (5”), 121.7 (3”), 113.3 (6) 110.2 (7), 104.6 (4), 102.4 (3), 71.0 (!’), 52.3 (8”), 49.7 (1”).

[0859] LC-MS (ESI): m / z Calculated: 358.1, Found: 359.2 [M+H]+, tR= 2.50 min.

[0860] EXAMPLE 89: 3-ir5-(benzyloxy)-lH-indol-l-yl1methyHaniline (BGZ0062) 328.41 g / mol

[0861] To a stirred solution of compound 88 (617 mg, 1.72 mmol) in EtOH (50 mL) was added Raney Nickel. Then hydrazine monohydrate (1.1 mL, 34.4 mmol, 20 eq.) was added to the solution. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered through a pad of celite, washed with ethanol and the filtrate was evaporated under reduced pressure. The residue was dissolved in AcOEt, washed with water three times, dried over MgSCh, filtered and evaported under reduced pressure. The oily residue was dissolved in toluene and evaported under reduced pressure to give compound 89 as a light brown solid in 86% yield (m = 485 mg).

[0862] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.53-7.28 (m, 5 H H3’,4’,5’), 7.22-7.15 (m, 2 H, H4,7), 7.11 (d, 1 H,3J = 3.1 Hz, H2), 7.08 (d, 1 H,3J = 7.8 Hz, H6”), 6.93 (dd, 1 H,3J = 8.8 Hz,4. / = 2.4 Hz, H6), 6.60-6.52 (m, 2H, H5”,7”) 6.47 (dd, 1 H,3J = 3.1 Hz,4J = 2.4 Hz, H3), 6.37- 6.31 (m, 1 H, H3”), 5.20 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr), 3.58 (br, 2 H, NH2).

[0863] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.4 (5), 147.0 (4”), 139.0 (2”), 137.9 (2’), 132.0 (4a), 129.8 (6”), 129.1 (2), 129.1 (7a) 128.6 (4’), 127.9 (5’), 127.7 (3’), 117.0 (7”), 114.4

[0864] (5”), 113.2 (3”), 112.8 (6), 110.7 (7), 104.2 (4), 101.2 (3), 71.0 (!’), 50.3 (1”).

[0865] LC-MS (ESI): m / z Calculated: 328.2, Found: 329.2 [M+H]+, tR= 2.35 min.

[0866] EXAMPLE 90: N-(3- (benzyloxy)-lH-indol-l-yl]methvHphenyl)-2-chloroacetamide

[0867] (BGZ0094)

[0868] 404.89 g / mol

[0869] To a solution of compound 89 (100 mg, 0.30 mmol) in dry DCM (2 mL) cooled to 0 °C, triethylamine (85 pL, 0.60 mmol, 2 eq.) was added. A solution of chloroacetyl chloride (36 pL, 0.46 mmol, 1.5 eq.) in dry DCM (2 mL) was added dropwise at 0 °C. The mixture was stirred at room temperature for 2 hours. The mixture was diluted with DCM and washed with a saturated NaHCCL solution (3 ^ 15mL) and brine (1 x 15mL). The organic phase was dried over MgSCU, filtered and concentrated under reduced pressure. The oily residue was precipitated in diethyl ether. Compound 90 was obtained by filtration and dried under vacuum as an off-white solid in 56% yield (m = 69 mg).

[0870] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.15 (br, 1 H, NH), 7.51-7.24 (m, 8 H H2,3\ 4\ 5’4”, 6”), 7.19 (d, 1 H, V = 2.3 Hz, H4), 7.17-7.09 (m, 2 H, H7,5”), 6.95-6.84 (m, 2 H, H6,7”), 6.48 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.28 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr), 4.15 (s, 2 H, Hs )

[0871] 13C NMR (75 MHz, CDCI3): δ (ppm) 164.0 (CONH), 153.5 (5), 139.1 (4”), 137.8 (2’), 137.3 (2”), 131.8 (4a), 129.8 (6”), 129.2 (7a), 129.0 (2), 128.6 (4’), 127.9 (5’), 127.7 (3’), 123.6 (7”), 119.5 (3”), 118.4 (5”), 112.9 (6), 110.5 (7), 104.4 (4), 101.7 (3), 71.0 (!’), 50.3 (1”), 42.9 (8”).

[0872] LC-MS (ESI): m / z Calculated: 404.1, Found: 405.2 [M+H]+403.2 [M-H]', tR= 2.29 min.

[0873] EXAMPLE _ 91: _ N-(3 - 1 [5 -(benzyl oxy)- IH-indol- 1 -yllmethyHnhenyDethene- 1 - sulfonamide (BGZ0095)

[0874] 418.51 g / mol

[0875] To a stirred solution of compound 88 (96 mg, 0.29 mmol) in dry DCM (1 mL) and triethylamine (61 pL, 0.44 mmol, 1.5 eq.) cooled to 0 °C in an ice bath, ethenesulfonyl chloride (39 mg, 0.29 mmol, 1.0 eq.) in solution in dry DCM (1 mL) was added dropwise. The mixture was stirred at 0 °C for 2 hours. The mixture was diluted with DCM (20 mL) and washed with a saturated NaHCCL aqueous solution (3 ^ 15 mL) and brine (1 x 15mL). The organic phase was dried over MgSCU, filtered and the solvent removed under reduced pressure. The crude material was purified by flash chromatography with toluene / ethyl acetate 9: 1 as the eluent. The residue was further purified by triturating it with diethyl ether, collecting the diethyl ether and evaporating it. After lyophylization, compound 91 was obtained as a yellow sticky solid in 44% yield (m= 54 mg).

[0876] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.51-7.27 (m, 5 H H3’,4’,5’), 7.23 (dd, 1 H,3J = 7.8 Hz, H6”), 7.19 (d, 1 H, V = 2.4 Hz, H4), 7.12-7.04 (m, 2 H, H2,7), 6.99 (dd, 1 H,3J = 8.0 Hz,4J = 1.7 Hz, H5”), 6.94-6.86 (m, 2 H, H6,7”), 6.77-6.73 (m, 1 H, H3”), 6.47 (dd, 1 H,3J = 3.1 Hz,5J = 0.5 Hz, H3), 6.43 (br, 1 H, NHSO2CH=CH2), 6.35 (dd, 1 H,3Jtrans= 16.5 Hz,3JC1S= 9.8 Hz, NHSO2CH=CH2), 6.01 (d, 1 H,3Jtrans= 16.5 Hz, NHSO2CH=CH2), 5.72 (d, 1 H,3JCIS= 9.8 Hz, NHSO2CH=CH2), 5.25 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr).

[0877] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.5 (5), 139.6 (4”), 137.8 (2’), 137.0 (2”), 134.8 (NHSO2CH=CH2), 131.7 (4a), 130.0 (6”), 129.3 (7a), 129.1 (2), 129.0 (NHSO2CH=CH2), 128.7 (4’), 127.9 (5’), 127.7 (3’), 123.4 (7”), 119.7 (5”), 118.3 (3”), 113.0 (6), 110.5 (7), 104.5 (4), 101.7 (3), 71.0 (!’), 50.1 (1”).

[0878] LC-MS (ESI): m / z Calculated: 418.1, Found: 417.2 [M-H]7419.2 [M+H]+, tR= 2.26 min.

[0879] EXAMPLE 92: 5-(benzyloxy)-2,3-dihydro-lH-indole (BGZ0064-2) 225.29 g / mol

[0880] To a solution of 5-benzyloxyindole (2.55 g, 11.4 mmol) in acetic acid (30 mL) cooled to 15 °C under nitrogen, NaBH3(CN) (2.2 g, 35 mmol, 5 eq.) was added in one portion. The solution was stirred at 15 °C for 1 hour. The reaction was quenched by the addition of water (150 mL) and the mixture was cooled in an ice bath and slowly made strongly basic with sodium hydroxyde pellets. The mixture was extracted with Et2O (4 x 75 mL). The combined organic extracts were washed with water (2 x 100 mL) and brine (2 x 100 mL), dried over anhydrous potassium carbonate and filtered before the solvent was removed under reduced pressure. Compound 92 was obtained as a light orange oil in 83% yield (m = 2.14 g).

[0881] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.48-7.28 (m, 5 H, H3’,4’,5’), 6.87-6.82 (m, 1 H H4), 6.68 (dd, 1 H,3J = 8.4 Hz,4J = 2.6 Hz, H6), 6.58 (d, 1 H,3J = 8.4 Hz, H7), 5.00 (s, 2 H, Hr), 5.10 (s, 2 H, Hr), 3.58 (t, 2 H, \J = 8.3 Hz, H2), 3.01 (t, 2 H, \J = 8.3 Hz, H3).

[0882] 13C NMR (75 MHz, CDCI3): δ (ppm) 152.8 (5), 145.7 (7a), 137.8 (2’), 131.2 (4a), 128.6 (4’), 127.9 (5’), 113.6 (6), 112.9 (4), 110.1 (7), 104.5 (4), 102.2 (3), 71.2 (!’), 47.9 (2), 30.6 (3).

[0883] LC-MS (ESI): m / z Calculated: 225.1, Found: 226.3 [M+H]+, tR= 1.84 min.

[0884] EXAMPLE 93: 5-(benzyloxy)-l-r(4-nitrobenzyl1-2,3-dihvdro-lH-indole (BGZ0065-2) 360.41 g / mol

[0885] To a solution of 92 (2.0 g, 8.88 mmol) in DCM (40 mL), triethylamine (2.0 mL, 14.4 mmol, 1.6 eq.) and 4-nitrobenzyl bromide (2.88 g, 13.32 mmol, 1.5 eq.) were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with saturated NaHCCh solution (3 x 15mL). The organic layer was dried over. Compound 93 was obtained as an orange solid in 96% yield (m = 3.07 g).

[0886] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.24-8.16 (m, 2 H, H4”), 7.60-7.52 (m, 2 H, H3” ), 7.46-7.28 (m, 5 H H3’,4’,5’), 6.88-6.83 (m, 1 H, H4), 6.68 (dd, 1 H,3J = 8.4 H6), 6.32 (d, 1 H,3J = 8.4 Hz, H7), 4.99 (s, 2 H, Hr), 4.26 (s, 2 H, Hi”), 3.30 (t, 1 H,3J = 8.1 Hz, H2), 2.98 (t, 1 H,3J = 8.1 Hz, H3).

[0887] 13C NMR (75 MHz, CDC13): δ (ppm) 152.6 (5), 147.3 (5”), 146.7 (2”), 146.6 (7a), 137.6 (2’), 131.7 (4a), 128.5 (4’), 128.5 (3”), 127.8 (5’), 127.5 (3’), 123.8 (4”), 113.3 (4), 113.1 (6), 107.6 (7), 71.1 (!’), 54.9 (2), 54.7 (1”), 29.0 (3).

[0888] LC-MS (ESI): m / z Calculated: 360.2, Found: 361.3 [M+H]+, tR= 2.61 min.

[0889] EXAMPLE 94: 5-(benzyloxy)-l-r(4-nitrobenzyl]-2,3-dihvdro-lH-indole (BGZ0083) 358.29 g / mol

[0890] To a solution of 93 (1.0 g, 2.77 mmol) in DCM (10 mL), DDQ was added (690 mg, 3.05 mmol, 1.1 eq.). The reaction mixture was stirred at room temperature for 15 minutes. The mixture was washed with a saturated sodium bicarbonate solution (3 x 10 mL). The organic phase was dried over MgSO4, filtered and the solvent evaporated under reduced pressure. The crude material was dissolved in hot EtOH and filtered. The filtrate was cooled to room temperature, treated with activated charcoal, filtered and evaporated under reduced pressure. Compound 94 was obtained as a yellow solid in 68% yield (m = 680 mg).

[0891] 1H NMR (300 MHz, CDC13): δ (ppm) 8.18-8.10 (m, 2 H, H4”), 7.52-7.28 (m, 5 H H3’,4’,5’),

[0892] 7.22 (d, 1 H,4J = 2.4 Hz, H4), 7.21-7.15 (m, 2 H, H3”), 7.12 (d, 1 H,3J = 3.2 Hz, H2), 7.06 (d, 1 H,3J = 8.8 Hz, H7), 6.92 (dd, 1 H,3J = 8.8 Hz, V = 2.4 Hz, H6), 6.53 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.39 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0893] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 147.6 (5”), 145.2 (2”), 137.7 (2’), 131.6 (4a), 129.4 (7a), 128.8 (2), 128.7 (4’), 127.9 (5’), 127.6 (3’), 127.3 (3”), 124.2 (4”), 113.3 (6), 110.2 (7), 104.5 (4), 102.3 (3), 70.9 (!’), 49.8 (1”).

[0894] LC-MS (ESI): m / z Calculated: 358.1, Found: 359.2 [M+H]+, tR= 2.43 min.

[0895] EXAMPLE 95: 4- (benzyloxy)-lH-indol-l-yl]methvHaniline (BGZ0090) 328.41 g / mol

[0896] To a suspension of compound 94 (358 mg, 1 mmol) in EtOH (5 mL), SnCh dihydrate (1.5 g, 5 mmol, 5 eq.) was added. The mixture was refluxed for 1 h. The mixture was cooled to room temperature and ice-cold water was added. The mixture was diluted with 20% NaOH and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (1 x 30 mL), dried over Na2SO4 and filtered before the solvent was removed under reduce pressure. The crude material was purified by flash chromatography with cyclohxane / ethyl acetate (8:2) as the eluent. Compound 95 was obtained as an off-white solid in 51% yield (m = 166 mg).

[0897] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.28 (m, 5 H Hs’,4’,5’), 7.24-7.15 (m, 2 H, H4,7), 7.08 (d, 1 H,3J = 3.1 Hz, H2), 6.99-6.87 (m, 3 H, H3”,6), 6.65-6.56 (m, 2 H, H4”), 6.43 (d, 1 H,3J = 3.1 Hz, H3), 5.16 (S, 2 H, Hi”), 5.10 (s, 2 H, Hr), 3.63 (br, 2 H, NH2).

[0898] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.3 (5), 146.0 (5”), 137.9 (2’), 131.9 (3”), 129.2 (4a), 128.8 (2), 128.6 (3”), 128.4 (4’), 127.8 (5’), 127.7 (3’), 127.4 (7a) 115.4 (4”), 112.7 (6), 110.6 (7), 104.2 (4), 101.0 (3), 71.0 (!’), 50.1 (1”). LC-MS (ESI): m / z Calculated: 328.2, Found: 329.2 [M+H]+, tR= 2.28 min. (m / z 106.1 (4- aminophenyl)methylium fragment)

[0899] EXAMPLE 96: N-(4- (benzyloxy)-lH-indol-l-yl]methvnphenyl)-2-chloroacetamide 404.89 g / mol

[0900] To a solution of compound 95 (100 mg, 0.30 mmol) in dry DCM (2 mL) cooled to 0 °C, triethylamine (85 pL, 0.60 mmol, 2 eq.) was added. A solution of chloroacetyl chloride (24 pL, 0.30 mmol, 1.0 eq.) in dry DCM (2 mL) was added dropwise at 0 °C. The mixture was stirred at room temperature for 1 hour. Another equivalent of chloroacetyl chloride 0.24 pL, 0.30 mmol, 1.0 eq.) in dry DCM (2 mL) was added dropwise at 0 °C ant the mixture was stirred at room temperature for 1 more hour. The mixture was diluted with DCM and washed with a saturated NaHCO3solution (3 ^ 15mL) and brine (1 x 15mL). The organic phase was dried over MgSCU, filtered and concentrated under reduced pressure. The crude mixture was purified by flash chromatography. (Cyclohexane / Ethyl acetate 8:2). Compound 96 was obtained as a white solid in 54% yield (m = 67 mg).

[0901] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.20 (br, 1 H, NH), 7.51-7.28 (m, 7 H H3’,4’,5’, 4”), 7.20 (d, 1 H,4J = 2.5 Hz, H4), 7.14 (d, 1 H,3J = 8.9 Hz, H7), 7.12-7.06 (m, 3 H, H2,3”), 6.92 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.47 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.25 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr), 4.16 (s, 2 H, H6”).

[0902] 13C NMR (75 MHz, CDCI3): δ (ppm) 163.9 (CONH), 153.5 (5), 137.8 (2’), 136.2 (5”),

[0903] 134.6 (2”), 131.8 (4a), 129.2 (7a), 128.9 (2), 128.6 (4’), 127.9 (5’), 127.7 (3’), 127.7 (3”),

[0904] 120.6 (4”), 112.9 (6), 110.5 (7), 104.3 (4), 101.5 (3), 70.9 (!’), 50.0 (1”).

[0905] LC-MS (ESI): m / z Calculated: 404.1, Found: 403.2 [M-H]7405.2 [M+H]+, tR= 2.27 min. EXAMPLE 97: N-(4-ir5-(benzvloxv)-lH-indol-l-- 418.51 g / mol

[0906] To a solution of compound 95 (96 mg, 0.29 mmol) in dry DCM (1 mL) and triethylamine (61 pL, 0.44 mmol, 1.5 eq.) cooled to 0 °C in an ice bath, ethenesulfonyl chloride (37 mg, 0.29 mmol, 1.0 eq.) in solution in dry DCM (1 mL) was added dropwise. The mixture was stirred at 0 °C for 1 hour. The mixture was diluted with DCM (20 mL) and washed with a saturated NaHCCh aqueous solution (3 x 15 mL) and brine (1 x 15mL). The organic phase was dried over MgSCh, filtered and the solvent removed under reduced pressure. The crude material was purified by flash chromatography with (Toluene / AE 9: 1) as the eluent. The residue was further purified by triturating it with diethyl ether, collecting the diethyl ether and evaporating it. Compound 97 was obtained as a yellow solid in 37% yield (m= 45 mg).

[0907] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.50-7.28 (m, 5 H H3’,4’,5’), 7.19 (d, 1 H,4J = 2.4 Hz, H4), 7.16-7.00 (m, 6 H, H2,7,3”,4”), 6.91 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.58-6.42 (m, 3 H, H3, NHSO2CH=CH2, NHSO2CH=CH2), 6.26 (d, 1 H,3Jfrara= 16.5 Hz, NHSO2CH=CH2), 5.93 (d, 1 H,3JCIS= 9.8 Hz, NHSO2CH=CH2), 5.24 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr).

[0908] 13C NMR (75 MHz, CDCh): 3 (ppm) 153.5 (5), 137.8 (2’), 135.7 (5”), 135.2 (NHSO2CH=CH2), 134.9 (4a), 131.8 (7a), 129.2 (2”), 128.9 (2), 128.7 (NHSO2CH=CH2), 128.7 (3”), 128.0 (4’), 127.9 (5’), 127.7 (3’), 121.4 (4”), 112.9 (6), 110.5 (7), 104.3 (4), 101.6 (3), 71.0 (!’), 49.8 (1”).

[0909] LC-MS (ESI): m / z Calculated: 418.1, Found: 417.2 [M-H]’, 419.2 [M+H]+, tR= 2.27 min.

[0910] EXAMPLE 98: 4-H5-(benzvloxv)-lH-indol-l-’ itrile (BGZ0093) 338.40 g / mol

[0911] Compound 98 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 4-cyanobenzyl bromide (316 mg) and was obtained as a light yellow solid in 44% yield (m = 199 mg).

[0912] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.62-7.54 (m, 2 H, H4”), 7.51-7.28 (m, 5 H H3’,4’,5’), 7.21 (d, 1 H,4J = 2.2 Hz, H4), 7.16-7.11 (m, 2 H, H3”), 7.10 (d, 1 H,3J = 3.1 Hz, H2), 7.06 (d, 1 H,3J = 8.9 Hz, H7), 6.92 (dd, 1 H,3J = 8.9 Hz,4J = 2.2 Hz, H6), 6.51 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.34 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr).

[0913] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.7 (5), 143.2 (2”), 137.7 (2’), 132.7 (4”), 131.6 (4a), 129.3 (7a), 128.8 (2), 128.7 (4’), 127.9 (5’), 127.6 (3’), 127.2 (3”), 118.7 (CN), 113.2

[0914] (6), 111.7 (5”), 110.3 (7), 104.5 (4), 102.2 (3), 70.9 (!’), 50.0 (1”).

[0915] LC-MS (ESI): m / z Calculated: 338.1, Found: 339.2 [M+H]+, tR= 2.41 min

[0916] EXAMPLE 99: 3-(r5-(benzyloxy)-lH-indol-l-yl1methyl)benzonitrile (BGZ0096) 338.40 g / mol Compound 99 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 3-cyanobenzyl bromide (316 mg) and was obtained as a light yellow solid in 46% yield (m = 211 mg). 1H NMR (300 MHz, CDCI3): δ (ppm) 7.58-7.52 (m, 1 H, H7), 7.51-7.25 (m, 8 H H3,4 ,5 , 3”, 5”, 6”), 7.21 (d, 1 H,4J = 2.3 Hz, H4), 7.11-7.04 (m, 2 H, H2,7), 6.93 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.51 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.32 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0917] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.7 (5), 139.5 (2”), 137.7 (2’), 131.6 (4a), 131.5 (7”), 131.0 (3”), 130.1 (6”), 129.8 (5”), 129.4 (7a), 128.7 (2), 128.7 (4’), 128.0 (5’), 127.7 (3’), 118.6 (CN), 113.3 (6), 113.1 (4”), 110.2 (7), 104.6 (4), 102.2 (3), 71.0 (!’), 49.6 (1”).

[0918] LC-MS (ESI): m / z Calculated: 338.2, Found: 339.2 [M+H]+, tR= 2.36 min.

[0919] EXAMPLE 100: 2-ir5-(benzyloxy)-lH-indol-l-yl]rnethvHbenzonitrile (BGZ0099) 338.40 g / mol

[0920] Compound 100 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 2-cyanobenzyl bromide (316 mg) and was obtained as a pale yellow solid in 38% yield (m = 171 mg).

[0921] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.71 (dd, 1 H,3J = 7.5 Hz,4J = 1.3 Hz, H6”), 7.52- 7.28 (m, 7 H H3’,4’,5’,4”,7”), 7.22 (d, 1 H,4J = 2.3 Hz, H4), 7.19-7.10 (m, 2 H, H2,7), 6.95 (dd, 1 H,3J = 8.9 Hz, V = 2.4 Hz, H6), 6.81 (dd, 1 H,3J = 7.7 Hz, V = 0.7 Hz, Hs ), 6.53 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.52 (s, 2 H, Hi”), 5.12 (s, 2 H, Hr).

[0922] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.7 (5), 141.5 (2”), 137.7 (2’), 133.5 (4”), 133.1 (6”), 131.7 (4a), 129.3 (7a), 129.1 (2), 128.6 (4’), 128.2 (5’), 127.9 (7”), 127.6 (3’), 127.5 (5”), 117.3 (CN), 113.2 (6), 110.7 (3”), 110.3 (7), 104.5 (4), 102.2 (3), 70.9 (!’), 48.4 (1”).

[0923] LC-MS (ESI): m / z Calculated: 338.2, Found: 339.2 [M+H]+, tR= 2.44 min.

[0924] EXAMPLE 101: 5-(benzyloxv)-l-F(4-1 -IH-indole (JUL1-4) 392.29 g / mol

[0925] Compound 101 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 4-bromobenzyl bromide (503 mg) and was obtained as a white solid after recrystallization from diethylether in 74% yield (m = 390 mg).

[0926] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.54-7.28 (m, 7 H H3’,4’,5’,4”), 7.20 (d, 1 H,4J = 2.3 Hz, H4), 7.15-7.05 (m, 2 H, H2, 7), 7.00-6.88 (m, 2 H, H6,3”), 6.48 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.23 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr).

[0927] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 137.8 (2’), 136.8 (2”), 132.0 (4”), 131.7 (4a), 129.3 (7a), 128.9 (2), 128.7 (3”), 128.5 (4’), 127.9 (5’), 127.7 (3’), 121.6 (5”), 113.0 (6), 110.5 (7), 104.4 (4), 101.7 (3), 71.0 (!’), 49.8 (1”).

[0928] LC-MS (ESI): m / z Calculated: 393.1, Found: 392.1 / 394.1 [M+H]+, tR= 2.62 min.

[0929] EXAMPLE 102: 5-(benzyloxy)-l-l(3-bromobenzyl1-lH-indole (JUL3) 392.29 g / mol

[0930] Compound 102 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 3-bromobenzyl bromide (503 mg) and was obtained as a white solid after recrystallization from di ethylether in 72% yield (m = 380 mg). 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.27 (m, 7 H H3’,4’,5’,4”,6”), 7.20 (d, 1 H,4J = 2.4 Hz, H4), 7.18-7.11 (m, 2 H, H7,7”), 7.10 (d, 1 H,3J = 3.1 Hz, H2), 7.01-6.95 (m, 1 H, H5”), 6.93 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.48 (dd,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.25 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0931] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 140.1 (2’), 137.8 (2’), 131.7 (4a), 130.9 (4”), 130.5 (7”), 129.8 (6”), 129.3 (7a), 128.9 (2), 128.7 (4’), 127.9 (5’), 127.7 (3’), 125.4 (5”), 123.0 (3”), 113.0 (6), 110.4 (7), 104.4 (4), 101.8 (3), 71.0 (!’), 49.8 (1”).

[0932] LC-MS (ESI): m / z Calculated: 393.1, Found: 392.1 / 394.1 [M+H]+, tR= 2.63 min.

[0933] EXAMPLE 103: 5-(benzyloxy)-l-r(2-bromobenzyl1-lH-indole (JUL2) 392.29 g / mol

[0934] Compound 104 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 2-bromobenzyl bromide (503 mg) and was obtained as a white solid after recrystallization from diethylether in 70% yield (m = 370 mg).

[0935] 1H NMR (300 MHz, CDC13): δ (ppm) 7.64-7.56 (m, 1 H, Hr), 7.53-7.29 (m, 5 H, Hr.4’,5’), 7.22 (d, 1 H,4J = 2.3 Hz, H4), 7.17-7.08 (m, 4 H, H2,7,5”,6”,), 6.93 (dd, 1 H,3J = 8.9 Hz,4J = 2.3 Hz, H6), 6.57-6.46 (m, 2 H, H3,7”), 5.35 (s, 2 H, Hi”), 5.12 (s, 2 H, Hr).

[0936] 13C NMR (75 MHz, CDC13): δ (ppm) 153.6 (5), 137.8 (2’), 136.9 (2”), 132.9 (3”), 131.9 (4a), 129.2 (5”), 129.1 (2) 128.6 (4’), 128.1 (6”), 128.0 (5’), 127.9 (7”), 127.7 (3’), 122.3 (4”), 113.0 (6), 110.5 (7), 104.3 (4), 101.8 (3), 71.0 (!’), 50.5 (1”).

[0937] LC-MS (ESI): m / z Calculated: 393.1, Found: 392.1 / 394.1 [M+H]+, tR= 2.62 min.

[0938] EXAMPLE 104: 5-(benzyloxy)-l-r(4-fluorobenzyl1-lH-indole (JUL004-2) 331.38 g / mol

[0939] Compound 104 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 4-fluorobenzyl bromide (253 mg) and was obtained as a white solid after recrystallization from petroleum ether in 84% yield (m = 375 mg).

[0940] 1H NMR (300 MHz, CDCh): 7.53-7.28 (m, 5 H, H3’,4’,5’), 7.20 (d,3J = 2.4 Hz, 1 H, H4), 7.14 (d, 1 H,3J = 8.9 Hz, H7), 7.11-7.03 (m, 3 H, H2,3”), 7.02-6.95 (m, 2 H, H4”), 6.92 (dd,3J = 8.9 Hz,4J = 2.4 Hz, 1H, H6), 6.47 (d,3J= 3.0 Hz, 1 H, H3), 5.25 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0941] 19F {’ H} NMR (282 MHz, CDCI3): δ (ppm) -115.4 (Cs-F)13C NMR (75 MHz, CDCI3): δ (ppm) 160.7 (d,1JC-F = 246.6 Hz, 5”), 153.5 (5), 137.8 (2’),

[0942] 133.4 (d,4JC-F = 3.3 Hz, 2”), 131.8 (4a), 129.3 (7a), 128.8 (2), 128.6 (4’), 128.5 (d,3JC-F = 8.1 Hz, 3”), 127.9 (5’), 127.7 (3’), 115.7 (d 21.7 Hz, 4”), 112.9 (6), 110.5 (7), 104.4 (4), 101.6 (3), 71.0 (!’), 49.8 (1”).

[0943] LC-MS (ESI): m / z Calculated: 331.1, Found: 332.2 [M+H]+, tR= 2.49 min. EXAMPLE 105: 5-(benzyloxy)-l-r(3-fluorobenzyl1-lH-indole (BGZ0100) 331.38 g / mol Compound 105 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 3 -fluorobenzyl bromide (253 mg) and was obtained as a pale orange solid after recrystallization from petroleum ether in 39% yield (m = 172 mg).

[0944] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.56-7.18 (m, 7 H, H4,3’,4’,5’,6”), 7.17-7.07 (m, 2 H, H2,7), 7.01-6.84 (m, 3 H, H6,3”,7”), 6.78 (d, 1 H,3J = 9.3 Hz, Hs ), 6.49 (d, 1 H,3J = 2.9 Hz, H3), 5.28 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0945] 19F {’ H } NMR (282 MHz, CDCI3): δ (ppm) -112.9 (C4”F).

[0946] 13C NMR (75 MHz, CDCI3): δ (ppm) 163.3 (d,1JC-F = 247.1 Hz, 4”), 153.6 (5), 140.4 (d,3JC-F = 7.0 Hz, 2”), 137.8 (2’), 131.8 (4a), 130.5 (d,3JC-F = 8.1 Hz, 6”), 129.3 (7a), 128.9 (2), 128.7 (4’), 127.9 (5’), 127.7 (3’), 122.3 (d,4JC-F = 2.9 Hz, 7”), 114.7 (d,2JC-F = 21.3 Hz, 3”), 113.8 (d,2JC-F = 22.1 Hz, 5”), 113.0 (6), 110.4 (7), 104.4 (4), 101.8 (3), 71.0 (!’), 49.9 (d,5JC-F = 1.6 Hz, 1”).

[0947] LC-MS (ESI): m / z Calculated: 331.1, Found: 332.2 [M+H]+, tR= 2.53 min. -indole (JUL0005) 331.38 g / mol

[0948] Compound 106 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 2 -fluorobenzyl bromide (380 mg) and was obtained as a white solid after recrystallization from petroleum ether in 78% yield (m = 348 mg).

[0949] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.52-7.27 (m, 5 H, H3’,4’,5’), 7.27-7.17 (m, 3 H, H4,7,7”), 7.15 (d, 1 H,3J = 3.1 Hz, H2), 7.08 (ddd, 1 H,3JH-F = 9.8 Hz,3J = 8.3 Hz,4J = 1.0 Hz, H4”), 7.01 (dt, 1 H,3J = 7.5 Hz,4J = 1.1 Hz, H6”), 6.94 (dd, 1 H,3J = 8.9 Hz,4J = 2.5 Hz, H6), 6.84 (dt, 1 H, V = 7.5 Hz,4J = 1.6 Hz, Hs ), 6.47 (dd, 1 H, V = 3.1 Hz,5J = 0.6 Hz, H3), 5.34 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0950] 19F {’ H } NMR (282 MHz, CDCI3): δ (ppm) -119.1 (C3”F).

[0951] 13C NMR (75 MHz, CDCI3): δ (ppm) 158.7 (d,1JC-F = 246.2 Hz, 3”), 153.5 (5), 137.9 (2’), 131.8 (4a), 129.5 (d,3JC-F = 8.0 Hz, 7”), 129.2 (7a), 129.1-128.9 (2+5”), 128.6 (4’), 127.9 (5’), 127.7 (3’), 124.7 (d,2JC-F = 14.7 Hz, 2”), 124.6 (d,4JC-F = 3.3 Hz, 6”), 115.4 (d,2JC-F = 21.1 Hz, 4”), 113.0 (6), 110.4 (7), 104.4 (4), 101.6 (3), 71.0 (!’), 44.1 (d,3JC-F = 4.9 Hz, 1”).

[0952] LC-MS (ESI): m / z Calculated: 331.1, Found: 332.2 [M+H]+, tR= 2.52 min.

[0953] EXAMPLE 107: 5-(benzyloxy)-l-14-(trifluoromethyl)benzvH-lH-indole (JUL0006) 381.39 g / mol

[0954] Compound 107 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 4-trifluorobenzyl bromide (380 mg) and was obtained as a light yellow solid after recrystallization from petroleum ether in 73% yield (m = 376 mg).

[0955] 1H NMR (300 MHz, CDC13): δ (ppm) 7.55 (d, 2 H,3J = 8.2 Hz, H4"), 7.51-7.29 (m, 5 H, H3’,4’,5’), 7.22 (d, 1 H,4J = 2.4 Hz, H4), 7.17 (d, 2 H,3J = 8.2 Hz, H3”), 7.13-7.06 (m, 2 H, H2,7), 6.93 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.51 (dd, 1 H,3J = 3.1 Hz,5J = 0.6 Hz H3), 5.35 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0956] 19F {’ H} NMR (282 MHz, CDC13): δ (ppm) -63.1 (CFs).

[0957] 13C NMR (75 MHz, CDC13): δ (ppm) 153.6 (5), 141.9 (2”), 137.8 (2’), 131.7 (4a), 129.8 (q,2JC-F = 32.8 Hz, 5”), 129.3 (7a), 128.9 (2), 128.7 (4’), 127.9 (5’), 127.7 (3'), 126.9 (3”), 125.9 (q,3JC-F = 3.8 Hz, 4”), 124.1 (q, \JC-F = 272.4 Hz, CF3), 113.1 (6), 110.4 (7), 104.4 (4), 102.0 (3), 71.0 (!’), 49.9 (1”).

[0958] LC-MS (ESI): m / z Calculated: 381.1, Found: 382.2 [M+H]+, tR= 2.59 min

[0959] EXAMPLE 108: 5-(benzyloxy)-l-f3-(trifluoromethyl)benzvH-lH-indole (BGZ0101) 381.39 g / mol

[0960] Compound 108 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 3 -trifluorobenzyl bromide (320 mg) and was obtained as a light orange solid after recrystallization from petroleum ether in 48% yield (m = 247 mg).

[0961] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.56-7.28 (m, 8 H, H3 .4\ 5’4”, 5”, 6”), 7.22 (d, 1 H,4J = 2.4 Hz, H4), 7.18 (d, 1 H,3J = 7.7 Hz, Hr ), 7.15-7.08 (m, 2 H, H2.7), 6.94 (dd, 1 H,3J = 8.9

[0962] Hz,4J = 2.4 Hz, H6), 6.51 (dd, 1 H,3J = 3.1 Hz,5J = 0.7 Hz, H3), 5.34 (s, 2 H, Hi”), 5.12 (s, 2 H, Hr).

[0963] 19F {’ H} NMR (282 MHz, CDCI3): δ (ppm) -63.1 (CF3).

[0964] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.6 (5), 138.8 (2”), 137.8 (2’), 131.8 (4a), 131.0 (q, VC F=32.8 Hz, 4”), 130.1 (d,4JC-F = 1.0 Hz, 7”), 129.5 (6”), 129.3 (7a), 128.8 (2), 128.7

[0965] (4’), 127.9 (5’), 127.6 (3’), 124.7 (q,3JC-F = 3.8 Hz, 3”), 124.1 (q, \JC-F = 272.4 Hz, CFJ), 123.6 (q,3JC-F = 3.8 HZ, 5”), 113.1 (6), 110.3 (7), 104.5 (4), 102.0 (3), 71.0 (!’), 50.0 (1”).

[0966] LC-MS (ESI): m / z Calculated: 381.1 Found: 382.2 [M+H]+, tR=2.63 min

[0967] EXAMPLE 109: 5-(benzyloxy)-l-(2-(trifluoromethyl)benzvn-lH-indole (BGZ0102) 381.39 g / mol

[0968] Compound 109 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and 2-trifluorobenzyl bromide (320 mg) and was obtained as a light orange solid after recrystallization from petroleum ether in 44% yield (m = 223 mg). ’H NMR (300 MHz, CDCI3): δ (ppm) 7.76-7.67 (m, 1 H, H4”), 7.54-7.28 (m, 7 H, H3’,4’,5’,6”,7”), 7.23 2.4 Hz, H4), 7.13 (d, 1 H,3J = 3.1 Hz, H2), 7.07 (d, 1 H,3J = 8.9 Hz, H7), 6.92 (dd, 1 H,3J = 8.9 Hz, V = 2.4 Hz, H6), 6.62-6.48 (m, 2 H, H3,5), 5.52 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0969] 19F {’ H} NMR (282 MHz, CDCI3): δ (ppm) -60.9 (CFs).13C NMR (75 MHz, CDCI3): δ (ppm) 153.7 (5), 137.8 (2’), 136.7 (d,4JC-F = 1.1 HZ, 2”),

[0970] 132.6 (6”), 131.8 (4a), 129.3 (2), 129.2 (7a), 128.7 (4’), 127.9 (5’), 127.7 (3’), 127.5 7”), 127.4 (5”), 126.2 (q,2JC-F = 30.9 Hz, 3”), 126.1 (q,3JC-F = 5.7 Hz, 4”), 124.6 (q,1JC-F = 274.0 Hz, CF3), 113.2 (6), 110.5 (7), 104.4 (4), 102.0 (3), 71.0 (1’), 46.7 (q,4JC-F = 3.4 Hz, 1”). LC-MS (ESI): m / z Calculated: 381.1 Found: 382.2 [M+H]+, tR=2.70 min

[0971] EXAMPLE 110: methyl 4-ir5-(benzyloxy)-lH-indol-l-yl]methyHbenzoate (BGZ0032-2) 371.43 g / mol Compound 110 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and methyl 4-(bromomethyl)benzoate (461 mg) and was obtained as a white solid in 55% yield (m = 274 mg).

[0972] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.96 (m, 2 H, H4”), 7.52-7.27 (m, 5 H H3’,4’,5’), 7.21 (d, 1 H, V = 2.4 Hz, H4), 7.17-7.06 (m, 4 H, H2, 7,3”), 6.91 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.48 (dd, 1 H,3. / 3.1 Hz,5J = 0.5 Hz, H3), 5.34 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr), 3.90 (s, 3 H, H6”).

[0973] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.8 (COOMe), 153.6 (5), 142.9 (2”), 137.8 (2’), 131.8 (5”), 130.2 (4”), 129.7 (4a), 129.3 (7a), 129.0 (2), 128.6 (4’), 127.9 (5’), 127.7 (3’), 126.6 (3”), 113.0 (6) 110.4 (7), 104.4 (4), 101.7 (3), 71.0 (!’), 52.3 (6”), 50.2 (1”).

[0974] LC-MS (ESI): m / z Calculated: 371.2, Found: 372.2 [M+H]+, tR= 2.51 min.

[0975] EXAMPLE 111: 4-ir5-(benzyloxy)-lH-indol-l-yl]methvHbenzoic acid (BGZ0087) 357.40 g / mol

[0976] To a solution of compound 110 (250 mg, 0.67 mmol) in THF (3 mL), 2M aqueous LiOH (3.4 mL, 1.76 mmol, 10 eq.) was added. The reaction was refluxed for 2.5 hours. The mixture was cooled to room temperature and diluted with a IM aqueous NaOH solution and extrated with ethyl acetate (3 x 20 mL). The aqueous phase was acidified to pH 2 using a IM aqueous HC1 then extracted with EtOAc (3 x 20 mL). The combined organic phases were washed with brine (1 x 20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Compound 111 was obtained as a pale yellow solid in 67% yield (m = 160 mg).

[0977] 1H NMR (300 MHz, CDC13): δ (ppm) 8.02 (d, 2 H,3J = 8.3 Hz, H4”), 7.52-7.28 (m, 5 H H3’,4’,5’), 7.20 (d, 1 H, V = 2.4 Hz, H4), 7.16 (d, 2 H,3J = 8.3 Hz, H3”), 7.13-7.06 (m, 2 H, H2,7), 6.91 (dd, I K3. / 8.9 Hz, V = 2.4 Hz, H6), 6.50 (dd, 1 H,3J = 3.1 Hz,5J = 0.6 Hz, H3), 5.36 (s, 2 H, Hi”), 5.10 (s, 2 H, Hr).

[0978] 13C NMR (75 MHz, CDCI3): δ (ppm) 170.9 (COOH), 153.6 (5), 143.9 (3”), 137.8 (2’), 131.8 (4a), 130.9 (4”), 129.3 (7a), 129.0 (2), 128.7 (5”), 128.7 (4’), 127.9 (5’), 127.7 (3’), 126.7 (3”), 113.1 (6), 110.4 (7), 104.4 (4), 101.9 (3), 71.0 (!’), 50.2 (1”).

[0979] LC-MS (ESI): m / z Calculated: 357.1, Found: 356.1 [M-H]7358.2 [M+H]+, tR= 2.29 min.

[0980] EXAMPLE 112: methyl 3-ir5-(benzyloxy)-lH-indol-l-yl]methyHbenzoate (BGZ0081) 371.43 g / mol

[0981] Compound 112 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and methyl 3-(bromomethyl)benzoate (461 mg) and was obtained as a light yellow oil which solidified upon storage in 72% yield (m = 359 mg).

[0982] 1H NMR (300 MHz, CDCI3): δ (ppm) 7.98-7.88 (m, 2 H, H3”, 5”), 7.52-7.24 (m, 6 H H2,3\ 4\ s’), 7.24-7.17 (m, 2 H, H4,7”), 7.17-7.10 (m, 2 H, H7,6”), 6.92 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.49 (dd, 1 H,3J = 3.1 Hz,5J = 0.8 Hz, H3), 5.75 (s, 2 H, Hi”), 5.12 (s, 2 H, Hr), 3.95 (s, 3 H, H8”).

[0983] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.9 (COOMe), 153.5 (5), 138.2 (2’), 137.8 (2”), 131.8 (4”), 131.3 (7”), 130.8 (4a), 129.3 (7a), 129.1 (3”), 129.0 (6”), 128.9 (2), 128.6 (4’), 128.1 (5”), 127.9 (5’), 127.7 (3’), 113.0 (6) 110.4 (7), 104.4 (4), 101.7 (3), 70.9 (!’), 52.3 (8”), 50.1 (1”).

[0984] LC-MS (ESI): m / z Calculated: 371.2, Found: 372.2 [M+H]+, tR= 2.51 min.

[0985] EXAMPLE 113: 3-1 T5-< i-lH-indol-1-

[0986] 357.40 g / mol

[0987] To a solution of compound 112 (314 mg, 0.85 mmol) in THF (3.8 mL), 2 M aqueous LiOH (4.2 mL, 8.45 mmol, 10 eq.) was added. The reaction was refluxed for 2.5 hours. The mixture was cooled to room temperature, diluted with water, acidified to pH 2 using a 1 M aqueous HC1 solution then extracted with EtOAc (3 x 40 mL). The combined organic phases were washed with brine (1 x 40 mL), dried over ISfeSCh, filtered and concentrated under reduced pressure. Compound 113 was obtained as a slightly yellow solid in 81% yield (m = 244 mg).

[0988] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.04-7.99 (m, 1 H, Hs ), 7.98-7.94 (m, 1 H, H3”), 7.51-7.28 (m, 6 H H3’,4’,5’,6”), 7.28-7.23 (m, 1 H, Hr ), 7.20 (d, 2 H,4J = 2.4 Hz, H4), 7.17- 7.10 (m, 2 H, H2,7), 6.92 (dd, 1 H,3J = 8.9 Hz,4J = 2.4 Hz, H6), 6.50 (dd, 1 H,3J = 3.1 Hz,

[0989] 5J = 0.7 Hz, H3), 5.35 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[0990] 13C NMR (75 MHz, CDCI3): δ (ppm) 171.6 (COOH), 153.6 (5), 138.4 (2”), 137.8 (2’), 132.2 (7”), 131.8 (4”), 129.9 (4a), 129.7 (6”), 129.3 (7a), 129.3 (5”), 128.9 (2), 128.6 (4’), 128.6 (3”), 127.9 (5’), 127.7 (3’), 113.0 (6), 110.4 (7), 104.4 (4), 101.9 (3), 71.0 (!’), 50.1 (1”).

[0991] LC-MS (ESI): m / z Calculated: 357.1, Found: 356.1 [M-H]7358.2 [M+H]+, tR= 2.28 min.

[0992] EXAMPLE 114: methyl 2-(r5-(benzyloxy)-lH-indol-l-yl1methyHbenzoate (BGZ0086)

[0993] 371.43 g / mol

[0994] Compound 114 was synthesized following general procedure M from 5-benzyloxyindole (300 mg) and methyl 2-(bromomethyl)benzoate (345 mg) and was obtained as a white solid in 41% yield (m = 203 mg). Methyl 2-(bromomethyl)benzoate was prepared in two steps following literature procedures from o-toluic acid (Yuan, C.; et al., Molecules, 2020, 25(1), 56 & Wang, H; et al., Tetrahedron Letters, 2021, 74, 153152).

[0995] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.10-8.00 (m, 1 H, H4”), 7.52-7.27 (m, 7 H H2,

[0996] 3\ 4\ 5\ 6”), 7.23 (d, 1 H,4J = 2.4 Hz, H4), 7.14-7.06 (m, 2 H, H7,7” ), 6.92 (dd, 1 H,3J = 8.8 Hz,4J = 2.4 Hz, H6), 6.55-6.43 (m, 2 H, H3, s ), 5.32 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr), 3.91 (s, 3 H, H8)

[0997] 13C NMR (75 MHz, CDCI3): δ (ppm) 167.6 (COOMe), 153.5 (5), 140.4 (2’), 137.9 (2”), 133.1 (6”), 132.0 (3”), 131.1 (4”), 129.4 (7”), 129.1 (4a), 128.6 (4’), 127.9 (5’), 127.8 (7a), 127.7 (3’), 127.3 (2), 127.1 (5”), 112.9 (6) 110.7 (7), 104.2 (4), 101.6 (3), 71.0 (1’), 52.3 (8”), 48.9 (1”). LC-MS (ESI): m / z Calculated: 371.2, Found: 372.2 [M+H]+, tR= 2.64 min.

[0998] EXAMPLE 115: 2- (benzyloxy)-lH-indol-l-yl]methvHbenzoic acid (BGZ0089) 357.40 g / mol To a solution of compound 114 (94 mg, 0.25 mmol) in THF (1.0 mL), 2 M aqueous LiOH (1.3 mL, 2.53 mmol, 10 eq.) was added. The reaction was refluxed for 2.5 hours. The mixture was cooled to room temperature, diluted with water, acidified to pH 2 using a 1 M aqueous HC1 solution then extracted with EtOAc (3 x 20 mL). The combined organic phases were washed with brine (1 x 20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Compound 115 was obtained as a light yellow solid in 82% yield (m = 74 mg).

[0999] 1H NMR (300 MHz, CDCI3): δ (ppm) 8.22-8.14 (m, 1 H, Hs ), 7.52-7.28 (m, 7 H H3’,4’,5\6”, 7”), 7.22 (d, 1 H,4J = 2.4 Hz, H4), 7.13 (d, 1 H,3J = 3.2 Hz, H2), 7.10 (d, 1 H,3J = 8.9 Hz, H7), 6.91 (dd, 1 H,3J = 8.9 Hz, \J = 2.4 Hz, H6), 6.52 (dd, 1 H,3J = 3.1 Hz,5J = 0.6 Hz, H3), 6.50-6.44 (m, 1 H, H4”), 5.80 (s, 2 H, Hi”), 5.11 (s, 2 H, Hr).

[1000] 13C NMR (75 MHz, CDC13): δ (ppm) 171.2 (COOH), 153.6 (5), 141.5 (2”), 137.9 (2’), 134.1 (6”), 132.1 (5”), 132.0 (3”), 129.4 (2), 129.1 (4a), 128.7 (4’), 127.9 (5’), 127.7 (3’), 127.5 (7”), 127.2 (4”), 126.3 (7a), 113.0 (6), 110.6 (7), 104.2 (4), 101.7 (3), 71.0 (!’), 49.1 (1”).

[1001] LC-MS (ESI): m / z Calculated: 357.1, Found: 356.1 [M-H]7358.2 [M+H]+, tR= 2.37 min.

[1002] 2.13. Synthesis of Examples 116-141

[1003] General procedures of Pictet-Spengler reactions for the synthesis of compounds 116- 128 and 138-141:

[1004] General N To a solution of 5-benzyloxytryptamine (1 eq and the appropriate aldehyde (0.9-1.5 eq.) in DCM (alternatively in a DCM / THF mixture), TFA (1.5-3.5 eq.) was added. The mixture was stirred at room temperature for 2 to 7 days. The work-up procedure was adaptated for each example.

[1005] General O: 5 ■benzyloxytryptamine (1 eq and the appropriate aldehyde (1 eq.) were placed in a sealed tube with a magnet stirrer. The sealed tube was filled with N2gas and anhydrous pyridine was added. The N2gas inlet was removed and chlorotrimethysilane was added dropwise. The mixture was stirred with heating to 120 °C in an oil bath for 24 hours. After cooling to room temperature, the tube was carefully opened and trimethylamine (5 eq.) was added dropwise. Water was added and the mixture was sonicated at room temperature for 1 hour. After one night at 4 °C, the precipitate was filtered, washed successively with water and diethyl ether and dried under vacuum. The solid as suspended in HC1 saturated Et20 to obtain the desired hydrochloride salts.

[1006] General P: 5 -benzyloxytryptamine (1 eq and the appropriate aldehyde (1 eq.) were dissolved in HFIP (0.8 mL) under nitrogen atmosphere. The resulting solution was refluxed for 24 hours. The reaction mixture was cooled and diethyl ether was added, then saturated HC1 diethyl ether and finally the solution was stirred for 30 min. Precipitate was filtered and washed with diethyl ether. The solid was treated with hot acetonitrile and filtered to give the final compound. (Wang LN, Shen SL, Qu J. Simple and efficient synthesis of tetrahydro-P-carbolines via the Pictet-Spengler reaction in 1,1, 1,3,3, 3-hexafluoro-2- propanol (HFIP). RSC Adv. 2014, 4(58), 30733-41).

[1007] EXAMPLE 116: 10-(benzyloxy)-7,8,13,13b-tetrahvdro-5H-benzorL21indolizinor8,7-

[1008] -5-one 380.44 g / mol

[1009] Compound 116 was synthesized according to the general procedure N from 5- benzyloxytryptamine (390 mg, 1.46 mmol, 1.0 eq.), methyl 2-formylbenzoate (264 mg, 1.61 mmol, 1.1 eq.) and TFA (0.16 mL, 2.2 mmol, 1.5 eq.) in DCM (10 mL). After 2 days, the mixture was diluted with DCM, washed with a 20% K2CO3 aqueous solution. The organic layer was dried overNa2SO4, filtered and concentrated under vacuum. After recrystallization from ACN, compound 116 was obtained in 38% yield.

[1010] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 11.22 (s, 1 H, NH), 8.29 (d, 1 H, J = 7.6 Hz, HAr”), 7.73 (m, 2 H, J= 7.3 Hz, HAF”), 7.55 (t, 1 H, J= 7.4 Hz, HAF ”), 7.46 (d, 1 H, J= 7.1 Hz, HAF ”), 7.40-7.29 (m, 5 H, HAF’), 7.04 (d, 1 H, J= 2.3 Hz, H4), 6.83 (dd, 1 H,3J = 8.8 Hz,4J= 2.4 Hz, H6), 6.04 (m, 1H, H7), 5.08 (s, 2 H, Hr), 4.60 (m, 1 H, Hi”), 3.35 (m, 4H, H8, H9)13C NMR (75 MHz, DMSO-d6): δ (ppm) 167.6, 152.8, 144.1, 138.2, 132.3, 132.1, 132.1, 132.1, 129.1, 128.8, 128.1, 127.0, 124.2, 123.6, 112.5, 112.4, 107.4, 102.3, 70.2, 57.1, 38.2, 22.0.

[1011] LC-MS (ESI): m / z Calculated: 380.2, Found: 381.0 [M+H]+, tR= 3.0 min.

[1012] EXAMPLE 117: methyl 3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyridor3,4-b]indol-l- yl)benzoate hydrochloride (RDB14)

[1013] Compound 117 was synthesized according to the general procedure N from 5- benzyloxytryptamine (473 mg, 1.78 mmol, 1.0 eq.), methyl 3 -formylbenzoate (260 mg, 1.58 mmol, 0.9 eq.) and TFA (0.33 mL, 4.43 mmol, 2.5 eq.) in DCM (10 mL). After 3 days, the mixture was diluted with DCM, washed with a 20% K2CO3 aqueous solution. The organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The residue was suspended in an oxalic acid solution in ethyl acetate. The precipitate was filtered and resuspended in HCI saturated diethyl ether. Compound 117 was obtained in 63% yield.

[1014] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.73 (s, 1 H, NHindoie), 8.09-8.03 (m, 2 H, HAr”), 7.71-7.62 (m, 2 H, HAr”), 7.51-7.34 (m, 5 H, HAr), 7.22-7.16 (m, 2 H, H4H7), 6.85 (dd, 1 H,3J= 8.7 Hz,4J= 2.3 Hz, H6), 6.01 (s, 1 H, Hi”,), 5.13 (s, 2 H, Hr), 3.91 (s, 3 H, Hs ), 3.86 (m, 4 H, Hs, H9).

[1015] 13C NMR (75 MHz, CDCh): <5 (ppm) 166.3, 164.5, 153.0, 138.2, 136.3, 135.3, 132.2, 131.0,

[1016] 130.8, 130.5, 129.8, 129.5, 128.8, 128.1, 126.5, 113.1, 112.7, 107.9, 102.3, 70.3, 55.7, 52.8,

[1017] 18.8.

[1018] LC-MS (ESI): m / z Calculated: 412.2, Found: 413.1 [M+H]+, tR= 2.6 min. EXAMPLE 118: methyl 4-(6-(benzyloxy)-2,3,4,9-tetrahvdro-lH-Dyridol3,4-b1indol-l- vDbenzoate hydrochloride (RDB23)

[1019] To a solution of compound 120 (100 mg, 0.23 mmol, 1 eq.) in MeOH (10 mL), HC1 was added. The mixture was stirred during one night at reflux. The mixture was filtered to recover a white precipitate. The material was suspended in HC1 saturated diethyl ether to give the compound 118 in 54% yield.

[1020] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.75 (s, 1 H, NHindoie), 8.06 (d, 2 H,3J = 8.4 Hz, H4”), 7.56 (d, 2 H,3J = 8.4 Hz, H3”), 7.49-7.30 (m, 5 H, H3’,4’,5’), 7.22-7.16 (m, 2 H, H4,7), 6.86 (dd, 1 H,3J= 8.8 Hz,4J= 2.4 Hz, H6), 6.01 (s, 1 H, Hi”), 5.13 (s, 2 H, Hr), 3.89 (s, 3

[1021] H, H6”), 3.43 (t, 2 H,3J= 6.2 Hz, H9), 3.17-2.93 (m, 2 H, H8).

[1022] 13C NMR (75 MHz, CDCI3): δ (ppm) 166.3, 153.0, 140.3, 138.2, 132.2, 131.2, 130.9, 130.0, 129.1, 128.8, 128.1, 128.0, 126.5, 113.2, 112.7, 107.8, 102.3, 70.3, 55.6, 52.9, 18.7.

[1023] LC-MS (ESI): m / z Calculated: 412.5, Found: 413.1 [M+H]+, tR= 2.6 min. EXAMPLE 119: 3-(6-(benzyloxy)-2,3 A9-tetrahvdro-lH-pyridol3,4-b1indol-l-yl)benzoic acid hydrochloride (RDB17) 434.91 g / mol An aqueous solution of NaOH was added to a solution of compound 117 (100 mg, 0.22 mmol, 1.0 eq.) in methanol and THF (5 mL). The mixture was stirred during one night at room temperature and then heated at 50 °C during 24 h. The obtained residue was diluted in water and the organic layer was extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated. The material was suspended in HC1 saturated diethylether and filtered. Compound 119 was isolated in 32% yield.

[1024] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.74 (s, 1 H, NHindoie), 8.07-8.04 (m, 1 H, HAF”), 8.00 (s, 1 H, H3”), 7.68-7.60 (m, 2 H, HAF”), 7.49-7.31 (m, 5 H, H3’,4’,5’), 7.22-7.17 (m, 2 H, H4,7), 6.86 (dd, 1 H,3J= 8.8 Hz,4J= 2.3 Hz, H6), 6.03 (s, 1 H, Hi”), 5.13 (s, 2 H, Hr), 3.15- 2.87 (m, 4 H, Hs, H9).

[1025] LC-MS (ESI): m / z Calculated: 398.2, Found: 397.1 [M-H]", tR= 2.3 min.

[1026] EXAMPLE 120: 4-(6-(benzyloxy)-2,3 A9-tetrahvdro-lH-pyridol3,4-b]indol-l-yl)benzoic 434.91 g / mol

[1027] Compound 120 was synthesized according to the general procedure O from 5- benzyloxytryptamine (266 mg, 1.0 mmol, 1.0 eq.), 4-formylbenzoic acid (150 mg, 1.0 mmol, 1.0 eq.) and chlorotrimethylsilane (0.64 mL, 5 mmol, 5 eq.) in anhydrous pyridine (2 mL). After 4 hours of heating, the solution was filtered, washed with diethyl ether and water. After drying under vacuum, the solid was boiled in ACN and filtered. The material was suspended in an HC1 saturated ether solution to form the hydrochloride salt. Compound 120 was isolated in 64% yield.

[1028] 1H NMR (300 MHz, DMSO-r / 6): δ (ppm) 10.74 (s, 1H, NHindoie), 8.03 (d, 2 H,3J = 8.2 Hz, H4”), 7.56 (d, 2 H, \J = 8.4 Hz, H3”), 7.49-7.31 (m, 5 H, H3’,4’,5’), 7.20 (d, 2 H, \J = 8.6 Hz, H7), 7.16 (d, 2 H, V = 3.0 Hz,H4), 6.85 (dd, 1 H,3J = 8.8 Hz,4J = 2.2 Hz, H6), 5.99 (s 1 H, Hi”), 5.13 (s, 2 H, HL), 3.21-2.92 (m, 4 H, H8,9).

[1029] 13C NMR (75 MHz, DMSO-d6): δ (ppm) 167.3, 153.0, 139.7, 138.2, 132.4, 132.3, 130.7, 130.1, 129.2, 128.8, 128.1, 128.1, 126.5, 113.1, 112.7, 107.8, 102.3, 70.3, 55.6, 18.7.

[1030] LC-MS (ESI): m / z Calculated: 398.2, Found: 397.1 [M-H]", tR= 2.3 min.

[1031] EXAMPLE 121: 4-(6-(benzyloxy)-2,3,4,9-tetrahvdro-lH-pyridol3,4-b1indol-l-yl)-2- nitrophenol hydrochloride (RDB24) 451.90 g / mol

[1032] Compound 121 was synthesized according to the general procedure N from 5- benzyloxytryptamine (350 mg, 1.31 mmol, 1.0 eq.), 4-hydroxy-3 -nitrobenzaldehyde (198 mg, 1.18 mmol, 0.9 eq.) and TFA (0.34 mL, 4.6 mmol, 3.5 eq.) in a DCM / THF mixture (2: 1, 30 mL). After 7 days, the mixture was washed with a 5% K2CO3 aqueous solution. The aqueous layer was extracted with DCM. The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. After recrystallization from ACN, the material was suspended in HCI saturated diethethyl ether to obtain compound 121 in 44% yield.

[1033] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 11.61 (s, 1 H, NHindoie), 10.76 (s, 1 H, OH); 7.97 (d, 1 H, J= 22 Hz, H3”), 7.55 (dd, 1 H,3J = 8.7 2.2 Hz, H7), 7.49-7.27 (m, 5 H, H3’,4’,5’), 7.21 (d, 1 H,3J = 8.8 Hz, H7), 7.16 (d, 1 H,4J= 2.3 Hz, H4), 6.86 (dd, 1 H,3J= 8.8 Hz,4J = 2.4 Hz, H6), 5.96 (s, 1 H, Hi”), 5.13 (s, 2 H, Hr), 3.40 (m, 4 H, Hs, H9).

[1034] 13C NMR (75 MHz, CDCI3): δ (ppm) 153.6, 153.0, 138.2, 137.1, 136.8, 132.2, 129.2, 128.8, 128.11, 128.06, 127.6, 126.5, 125.7, 119.8, 113.1, 112.7, 107.9, 102.3, 70.3, 54.9, 18.6.

[1035] LC-MS (ESI): m / z Calculated: 415.2, Found: 416.0 [M+H]+, tR= 2.6 min. EXAMPLE 122: 6-(benzyloxy)-l-(3-nitrophenyl)-2,3 A9-tetrahydro-lH-pyridor3,4- blindole hydrochloride (CCY06)

[1036] Compound 122 was synthesized according to the general procedure P from 5- benzyloxytryptamine (1.0 eq., 400 mg, 1.502 mmol), 3 -nitrobenzaldehyde (1,0 eq., 226.96 mg, 1.502 mmol) and HFIP (25 eq., 6384 mg, 4 mL, 37.99 mmol). Compound 122 was obtained in 92% yield as an orange solid.

[1037] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.78 (s, 1H, NH), 10.48 (s, 1H, NHindoie), 9.81 (s, 1H), 8.39-8.36 (m, 2H, HAF”), 7.90-7.77 (m, 2H, HAF”), 7.51-7.31 (m, 5H, HAr), 7.22-7.18 (m, 2H), 6.87 (dd, 1H, J=S.S Hz, 1=2.5 Hz, H6), 6.17 (s, 1H, Hi”), 5.13 (s, 2H, Hr), 3.19-

[1038] 2.98 (m, 4H, Hio).

[1039] 13C NMR (75 MHz, DMSO-d6): δ 155.89, 142.89, 135.57, 134.76, 132.36, 130.93, 129.24, 129.04, 128.76, 126.92, 126.34, 126.17, 123.78, 118.31, 116.76, 111.95, 109.76, 107.63, 55.09, 41.87, 18.54. LC-MS (ESI): m / z Calculated: 399.2, Found: 400.3 [M+H]+, [M-H]’= 398,1; tR= 1.96 min.

[1040] EXAMPLE 123: 6-(benzyloxy)- 1 -(4-ni trophenyl )-2i3 , 4.9-tetrahydro- lH-pyrido[3 ,4- blindole hydrochloride (CCY13) 335.90 g / mol Compound 123 was synthesized according to the general procedure P from 5- benzyloxytryptamine (1.0 eq., 400 mg, 1.502 mmol), 4-nitrobenzaldehyde (1.0 eq., 226.96 mg, 1.502 mmol) and HFIP (25 eq., 6384 mg, 4 mL, 37.99 mmol). Compound 123 was obtained in 92% yield as an orange solid.

[1041] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.78 (s, 1H, NH), 10.48 (s, 1H, NHindoie), 9.81 (s, 1H), 8.39-8.36 (m, 2H, HAF”), 7.90-7.77 (m, 2H, HAF”), 7.51-7.31 (m, 6H, HAr), 7.22-7.18 (m, 2H), 6.87 (dd, 1H, J=8.8 Hz, J=2.5 Hz, H6), 6.17 (s, 1H, Hi”), 5.13 (s, 2H, Hr), 3.19- 2.98 (m, 4H, H10).

[1042] 13C NMR (75 MHz, DMSO-d6): δ (ppm) 204.1, 188.4, 182.4, 152.8, 152.1, 132.5, 131.3, 129.8, 129.4, 128.4, 128.3, 127.7, 127, 111.7, 111.3, 108.4, 101.8, 101.6, 69.8, 69.7, 55.8, 48.7, 21.9, 18.9

[1043] LC-MS (ESI): m / z Calculated: 400.2, Found: 400.3 [M+H]+, m / z [M-H]‘ = 398,1; tR= 1.96

[1044] EXAMPLE 124: 3-(6-(Benzvloxv)-2.3.4.9-tetrahvdro-lH-pvridol3.4-b1indol-l-vl)aniline dihydrochl pride (CCY08) 442.38 g / mol

[1045] Hydrazine hydrate was added to a mixture of compound 122 (140 mg, 0.32 mmol, 1.0 eq.) and Raney Ni in MeOH (50 mL). The reaction mixture was stirred at room temperature until the starting material was consumed according to LC-MS monitoring. The reaction mixture was filtered over a pad of celite, washed with methanol and the filtrate was evaporated under reduced pressure. The residue was treated with HC1 saturated ether for 30 min, filtered and dried to yield to compound 124 as a dihydrochloride salt (0.12 g; 0.27 mmol; 84%). 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.81 (s, 1H, NH), 10.50 (s, 1H, NHindoie), 9.60 (s, 1H), 7.50-7.15 (m, 13H, HAr”), 6.85 (dd, 1H, J=8.7 Hz, J=2.2 Hz, H6), 5.90 (s, 1H), 5.13 (s, 2H), 3.61 (s, 3H), 3.30 (m, 2H), 3.04 (m, 2H).

[1046] 13C NMR (75 MHz, DMSO-d6): δ (ppm) =152.9, 138.2, 136.6, 132.2, 130.4, 129.3, 128.8, 128.1, 128.0, 126.5, 123.2, 113.1, 112.7, 107.8, 102.3, 70.3, 55.4, 18.6.

[1047] LC-MS (ESI): m / z Calculated: 369.2, Found: 370.2 [M+1H]+; tR= 1.85 min.

[1048] EXAMPLE 125: 4-(6-(Benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)aniline dihydrochl pride (CCY14) 442.38 g / mol

[1049] Hydrazine hydrate was added to a mixture of compound 123 (140 mg, 0.32 mmol, 1.0 eq.) and Raney Ni in MeOH (50 mL). The reaction mixture was stirred at room temperature until the starting material was consumed according to LC-MS monitoring. The reaction mixture was filtered over a pad of celite, washed with methanol and the filtrate was evaporated under reduced pressure. The residue was treated with HC1 saturated ether for 30 min, filtered and dried to yield to compound 125 as a dihydrochloride salt (0.08 g; 0.19 mmol; 59%).

[1050] 1H NMR (300 MHz, DMSO-d6): δ (ppm) = 10,74 (s, 1H), 10,09 (s, 1H), 9,32 (s, 1H), 7,50- 7,01 (m, 12H), 6,84 (dd, 1H, J=9,l Hz, J=2,0 Hz), 5,80 (s, 1H), 5,12 (s, 2H), 3.61-3.00 (m, 7H).

[1051] LC-MS (ESI): m / z Calculated: 369.2, Found: 370.4 [M+H]+; tR= 2.46 min.

[1052] EXEMPLE 126: 6-(benzyloxy)-2-methyl-l-(3-nitrophenyl)-2,3,4,9-tetrahydro-lH- pyrido[3,4-b]indole hydrochloride (YNM07)

[1053] Compound 122 (1 eq., 300 mg, 0.69 mmol) was dissolved in ethyl acetate, then traited with K2CO3 5% solution and the organic layer was dried over Na2SO4 and evaporated. To a solution of the basic form of compound 123 in ethanol (11.4 mL), formic acid (17 eq., 538.48 mg, 0.44 mL, 11.7 mmol) and paraformaldehyde (5 eq., 103.32 mg, 0.095 mL, 3.44 mmol) were added. The mixture was refluxed over night. Ethanol was evaporated and ethyl acetate was added and washed with K2CO3 5% solution. The organic layed is dried over Na2SO4 and evaporated to obtain a dark yellow oil which was dissolved in diethyl ether and HC1 saturated diethyl ether was added. The resulting solution was stirred for 30 minutes until completed precipitation. The precipitate was filtered and dried to give the compound 126 in 35% yield.

[1054] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 12.00 (s, 1H, NH), 10.48 (s, 1H, NHindoie), 8.26 (d, 2H, J=8.8 Hz, HAr”), 7.77 (d, 2H, J=8.8 Hz, HAr), 7.50-7.30 (m, 5H, HAr), 7.16 (m, 2H), 6.87 (dd, 1H, J=8.8 Hz, J=2.5 Hz, H6), 5.85 (s, 1H, Hi”), 5.13 (s, 2H, Hr), 3.53-3.37 (m, 2 H, H9), 3.20-3.03 (m, 2 H, Hs), 2.78 (bs, 3 H, NCH3),

[1055] LC-MS (ESI): m / z Calculated: 413.4, Found: m / z [M+H]+= 414.3; tR= 2.30 min.

[1056] EXEMPLE 127: 6-(benzyloxy)-2-methyl-l-(4-nitrophenyl)-2,3,4,9-tetrahydro-lH- pyrido[3,4-b]indole hydrochloride (YNM11) 449.93 g / mol; Mp = 220 °C Compound 123 (1 eq., 300 mg, 0.69 mmol) was dissolved in ethyl acetate, then traited with K2CO3 5% solution and the organic layer was dried over Na2SO4 and evaporated. To a solution of the basic form of compound 123 in ethanol (11.4 mL), formic acid (17 eq., 538.48 mg, 0.44 mL, 11.7 mmol) and paraformaldehyde (5 eq., 103.32 mg, 0.095 mL, 3.44 mmol) were added. The mixture was refluxed over night. Ethanol was evaporated and ethyl acetate was added and washed with K2CO3 5% solution. The organic layed is dried over Na2SO4 and evaporated to obtain a dark yellow oil which was dissolved in diethyl ether and HCI saturated diethyl ether was added. The resulting solution was stirred for 30 minutes until completed precipitation. The precipitate was filtered and dried to give the compound 127 in 26% yield.

[1057] 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.78 (s, 1H, NH), 10.48 (s, 1H, NHindoie), 8.34 (s, 1H, HAr”), 8.29 (dd, 1H, J=8.8 Hz, J=2.1 Hz, HAF”), 7.91 (d, 1H, J=8.8 Hz, HAr), 7.76 (t, 1H, J=8.8 Hz, HAF), 7.50-7.30 (m, 5H, HAr), 7.16 (m, 2H), 6.87 (dd, 1H, J=8.8 Hz, J=2.5 Hz, H6), 5.97 (s, 1H, Hr), 5.13 (s, 2H, Hr), 3.70-3.40 (m, 2 H, H9), 3.20-3.00 (m, 2 H, Hs), 2.81 (bs, 3 H, NCH3).

[1058] LC-MS (ESI): m / z Calculated: 413.4, Found: m / z [M-H]+= 412.2 m / z [M+H]+= 414.3; tR= 2.26 min.

[1059] EXEMPLE 128: 6-(benzyloxv)-2-methyl- 1 -phenyl-2,3 ,4,9-tetrahydro- lH-pyrido[3 ,4- b]indole hydrochloride (YNM08) 390.90 g / mol; Mp = 243 °C

[1060] Compound 128 was synthesized according to the general procedure P from 5- benzyloxytryptamine (1.0 eq., 250 mg, 0.94 mmol), benzaldehyde (1.0 eq., 99.61 mg, 0.94 mmol) and HFIP (25.3 eq., 3990 mg, 2.5 mL, 23.74 mmol). Compound 128 was obtained in 71% yield as a grey powder. 1H NMR (300 MHz, DMSO-d6): 10.77 (s, 1H, NH), 10.25 (s, 1H, NHindoie), 9.45 (s, 1H), 7.55-7.35 (m, 10H, HArHAr), 7.22 (d, 1H, J=8.8 Hz, H7), 7.16 (d, 1H, J=2.5 Hz, H4), 6.85 (dd, 1H, J=8.8 Hz, J=2.5 Hz, H6), 5.91 (s, 1H, Hi”), 5.12 (s, 2H, Hr), 3.53-3.37 (m, 2 H, H9), 3.20-3.03 (m, 2 H, Hs)

[1061] LC-MS (ESI): m / z Calculated: 354.4, Found: 455.2 [M+H]+, tR= 1.86 min.

[1062] EXAMPLE 129: 3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzo nitrile hydrochloride (FOP32) 415.91 g / mol

[1063] Compound 129 was synthesized according to the general procedure O from 5- benzyloxytryptamine (300 mg, 1.13 mmol, 1.0 eq.), 3 -cyanobenzaldehyde (148 mg, 1.13 mmol, 1.0 eq.) and chlorotrimethylsilane (0.72 mL, 5.63 mmol, 5 eq.) in anhydrous pyridine (1.69 mL). The crude material was purified by flash chromatography using DCM / MeOHNH3sat 96:4 as the eluent. The purified compound was suspended in HC1 saturated Et2O to give compound 129 in 20% yield.

[1064] 1H NMR (300 MHz, DMSO-d6): (ppm) 10.75 (s, 1 H, NHindoie), 7.98 (d, 1 H,3J= 1A Hz, H5”), 7.92 (s, 1 H, Hi”), 7.79-7.65 (m, 2 H, H6”,7”), 7.53-7.27 (m, 5 H, H3\4’,5’), 7.20 (d, 1 H,3J = 8.7 Hz, H7), 7.16 (d, 1 H,4J = 2.1 Hz, H4), 6.86 (dd, 1 H,3J= 8.8 Hz,4J = 2.1 Hz, H6), 6.01 (s, 1 H, Hi”), 5.12 (s, 2 H, Hr), 3.79-3.62 (m, 2 H, NH2), 3.53-3.37 (m, 2 H, H9), 3.25- 2.87 (m, 2 H, Hs).

[1065] 13C NMR (75 MHz, CDCh): <5 (ppm) 152.5, 137.7, 136.2, 134.9, 133.8, 133.4, 131.8, 130.0, 128.4, 128.3, 127.6, 127.6, 126.0, 118.4, 112.8, 112.3, 111.6, 107.6, 101.9, 70.5, 69.8, 66.3, 54.7, 43.6, 18.1.

[1066] LC-MS (ESI): m / z Calculated: 379.2, Found: 380.3 [M+H]+, 378.3 [M-H]’, tR= 1.86 min. EXAMPLE 130: 4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l- yl)benzonitrile hydrochloride (FOP12) 415.91 g / mol

[1067] Compound 130 was synthesized according to the general procedure N from 5- benzyloxytryptamine (253 mg, 0.95 mmol, 1.0 eq.), 4-cyanobenzaldehyde (186 mg, 1.42 mmol, 1.5 eq.) and TFA (0.25 mL, 3.32 mmol, 3.5 eq.) in DCM (15 mL). The combined organic extraxts were washed with 1 M NaOH, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The material was further purified by flash chromatography using (DCM / MeOH(NH3)sat 96:4) as the eluent. Conversion to the hydrochloride salt by suspension in HCI saturated diethylether and filtration provided 130 in 40% yield.

[1068] ’H-NMR (300 MHz, DMSO-r / 6): δ (ppm) 10.31 (s, 1H, NHindoie), 7.80 (d,3J = 8.3 Hz, 2 H, H4”), 7.50-7.44 (m, 4 H, H3\3”), 7.42-7.28 (m, 3 H, H4,5 ), 7.12 (d,3J = 8.7 Hz, 1 H, H7), 7.04 (d,4J= 2.3 Hz, 1 H, H4), 6.74 (dd,3J= 8.7,4J= 2.4 Hz, 1 H, H6), 5.14 (s, 1 H, Hi”), 5.09 (s, 2 H, Hr), 3.75-3.60 (m, 2 H, NH2), 3.02-2.89 (m, 2 H, H9), 2.70-2.59 (m, 2 H, H10).

[1069] 13C-NMR (75 MHz, DMSO-J6): δ (ppm) 152.1, 148.9, 137.9, 135.1, 132.1, 131.2, 129.4, 128.4, 128.3, 128.3, 127.6, 127.6, 127.5, 127.5, 127.1, 119, 111.7, 111.2, 109.8, 108.5, 69.8, 56.1, 22.1

[1070] LC-MS (ESI): m / z Calculated: 379.2, Found: 380.2 [M+H]+, 378.2 [M-H]’, tR= 1.90 min.

[1071] EXAMPLE 131: 3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)phenol hydrochloride (FOP25) 406.90 g / mol

[1072] Compound 131 was synthesized according to the general procedure from 5- benzyloxytryptamine (335 mg, 1.26 mmol, 1.0 eq.), 3-hydroxybenzaldehyde (154 mg, 1.26 mmol, 1.0 eq.) and chlorotrimethylsilane (1.67 mL, 13.08 mmol, 10.4 eq.) in anhydrous pyridine (1.89 mL). Compound 131 was obtained in 80% yield.

[1073] ’H-NMR (300 MHz, (CD3OD): δ (ppm) 7.49-7.44 (m, 2 H, H3’), 7.42-7.27 (m, 4 H, H4’,5’6”), 7.21 (d,3. / = 8.9 Hz, 1 H, H7), 7.12 (d, V = 2.3 Hz, 1 H, H4), 6.94-6.86 (m, 3 H, H6,5”,7”), 6.79 (m, 1 H, H3”), 5.75 (s, 1 H,Hi”), 5.12 (s, 2 H, Hr), 3.65-3.43 (m, 2 H,H9), 3.23-3.02 (m, 2 H, Hs)13C-NMR (75 MHz, (CD3OD): δ (ppm) 159.5, 154.6, 139.3, 137.3, 133.8, 131.5, 129.7, 129.5, 128.8, 128.6, 127.6, 121.5, 118.2, 117.4, 114.5, 113.2, 108.7, 103, 72, 58.4, 42.2, 19.8.

[1074] LC-MS (ESI): m / z Calculated: 370.2, Found: 371.2 [M+H]+, 369.2 [M-H]’, tR= 1.75 min

[1075] EXAMPLE 132: 4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)phenol hydrochloride (FOP23) 406.90 g / mol

[1076] Compound 132 was synthesized according to the general procedure O from 5- benzyloxytryptamine (261 mg, 0.98 mmol, 1.0 eq.), p-hydroxybenzaldehyde (120 mg, 0.98 mmol, 1.0 eq.) and chlorotrimethylsilane (1.3 mL, 10.19 mmol, 5 eq.) in anhydrous pyridine (1.47 mL). Compound 132 was obtained in 63% yield.

[1077] ’H-NMR (300 MHz, (CD3OD): δ (ppm) 7.49-7.42 (m, 2 H, H3’), 7.41-7.26 (m, 3 H, H4,5 ), 7.21 (m, 3 H, H7,3”), 7.10 (d, 1 H,4J= 2.2 Hz, H4), 6.93-6.84 (m, 3 H, H6 / 4”), 5.73 (s, 1 H, Hr), 5.09 (s, 2 H, Hr), 3.63-3.40 (m, 2 H, H9), 3.23-2.98 (m, 2 H, Hs).

[1078] 13C-NMR (75 MHz, (CD3OD): δ (ppm) 160.5, 154.6, 139.2, 133.8, 132.2, 130.0, 129.4, 128.7, 128.6, 128.6, 127.7, 126.1, 117.0, 114.4, 113.2, 108.7, 103.1, 72.0, 58.2, 42.1, 19.7.

[1079] LC-MS (ESI): m / z Calculated: 370.2, Found: 371.3 [M+H]+, 369.2 [M-H]’, tR= 1.81 min.

[1080] BIOLOGICAL EVALUATION

[1081] 1. Materials and methods

[1082] Cell cultures

[1083] HEK293T cell line was purchased from the American Type Culture Collection and cultivated in DMEM media containing 10% of heat inactivated FBS, L-glutamine and penicillin / streptomycin.

[1084] MDA-MB-231 cell line was purchased from the American Type Culture Collection and cultivated in DMEM media containing 10% of heat inactivated FBS, L-glutamine and penicillin / streptomycin.

[1085] Cells were passaged every 3 days upon reaching confluence, and the absence of mycoplasma contamination was verified (MycoAlertTM Detection Kit, Lonza, Basel, Switzerland). Cell lines were cultured at 37 °C in a 5% CO2 atmosphere.

[1086] Luciferase Reporter Assay

[1087] HEK293T cells were seeded at a density of 1 x 105cells in 24 well plates coated with polyethylenimine (10 pg / mL). Cells were transfected with the TEAD luciferase reporter plasmid 8XGTIIC -Luciferase (Addgene reference 34615) and a control P-galactosidase plasmid CMV-PGal using the lipofectamine 2000 Reagent (Life Technologies, Inc.) according to the manufacturer’s instructions. Compounds were tested at different concentrations ranging from 0.25 to 20 μM in DMEM media containing 0.2% of heat inactivated FBS. After 24 h post transfection, cells were lysed in Reporter Lysis Buffer (Promega, Charbonnieres-les-Bains, France) and luciferase activity was measured on the Varioskan LUX Multimode Microplate Reader and normalized to P-galactosidase. We use beta-galactosidase protein as an unbiased standard for transfection efficiency. A significant decrease in this is linked to the cytotoxicity of the molecules.

[1088] Protein expression

[1089] MDA-MB-231 cells were seeded at a density of 2 x 105cells in 6 well plates. Compounds were tested at 10 μM in DMEM media containing 0.2% of heat inactivated FBS for 48 h. Total extracts of cells were obtained with a RIPA based buffer containing protease inhibitors (Roche). Western blots were carried out using 10 pg of protein lysates.

[1090] The primary antibodies used included AXL (C44G1), CYR61 (D4H5D), CTGF (E2W5M) and Survivin (71G4B7) from Cell Signaling according to the manufacturer's instructions. Histone H3 07-690 (Millipore) was used as loading control for total extracts.

[1091] Proliferation of MDA-MB-231 cells

[1092] MDA-MB-231 cells were seeded at a density of 0.25 x io4cells in 96 well plates. Compounds were tested at different concentrations in DMEM media containing 0.2% of heat inactivated FBS for 72 h. Cell proliferation is monitored in real time with Incucyte® Live- Cell Analysis, Cell-by-Cell Analysis software module.

[1093] 2. Results

[1094] Luciferase Reporter Assay

[1095] The results of the Luciferase Reporter Assay are shown in the Table 3 hereafter, wherein:

[1096] A: IC5o < O.Ol μM

[1097] B: 0.01 μM < IC50 < 1 μM

[1098] C: 1 μM < IC50 < 10 μM D: 10 μM < IC50 < 100 μM

[1099] E: 100 μM < IC50 < 1000 μM

[1100] Table 3 N^y a H 8

[1101] SIZ Proliferation of MDA-MB-231 cells

[1102] The results of the MDA-MB-231 cell number evolution assay are shown in Table 4 hereafter:

[1103] Table 4

Claims

CLAIMS1. A compound of Formula I:a pharmaceutically acceptable salt or a solvate thereof, whereinR1is selected from benzyl, (l,r-biphenyl)-4-ylmethyl, (adamantan-l-yl)methyl and (halogenocyclohexyl)methyl;R2is selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarboxy-C1-C6-alkyl, C1- C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C 1 -C6- alkyl, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxycarbonyl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, C1-C4-alkyloxy carbonylaryl, C1-C4- alkyloxy carb oxy heteroaryl, vinylsulfonamidoaryl, haloaryl-C1-C4-alkyl, nitroaryl-C1- C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4-alkyl, halo-C 1-C4- alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C1-C4-alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C1-C4-alkylaryl-C 1 - C4-alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1-C4-alkyl;R3is selected from H, cyanovinyl, 3 -amino-3 -carboxypropyl, hydroxy-C1-C6-alkyl, C1- C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C4- alkyloxy oxopropenyl and oxo-C1-C6-alkyl;A is C-R4or CH-R4wherein R4is H, orR3and R4form together a group selected fromwherein R5and R6are independently selected from H, OH, C(O)OH, C1-C4- alkyloxycarbonyl, NO2, NH2, CN and vinylsulfonamido;R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl;I is a single bond or a double bond; with the proviso that: R2and R3are not both H when R1is benzyl,R2is not t-butyloxycarbonyl, carboxyethyl, methoxycarbonylmethyl, 2- (m ethoxy carbonyl)phenyl, 3-(ethoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 3- cyanophenyl, benzyl, 4-chlorobenzyl, 4-fluorobenzyl, 3 -fluorobenzyl 4- trifluoromethylbenzyl or 3-methoxycarbonylbenzyl when R1is benzyl and R3is H, R3is not hydroxy ethyl when R1is benzyl and R2is H,R5is not NO2 or OH when R6and R7are H and R1is benzyl,R6is not NO2 or methoxy when R5and R7are H and R1is benzyl;R7is not H when R5and R6are H; and> is a double bond when A is C-R4.

2. The compound according to claim 1, wherein the group -O-R1is located in position 4,5 or 6 of Formula I.

3. The compound according to claim 1 or 2, wherein R1is benzyl.

4. The compound according to claim 1, having the formula II:or a pharmaceutically acceptable salt or solvate thereof, whereinR1, R2, R3and R4are as defined in claim 1.

5. The compound according to claim 1, having the formula III:or a pharmaceutically acceptable salt or solvate thereof, whereinR1, R2, R3and R4are as defined in claim 1.

6. The compound according to claim 1, having the formula XII:XII, or pharmaceutically acceptable salts or solvates thereof, whereinR1, R2, R5, R6and R7are as defined in claim 1.

7. The compound according to claim 1, selected from the group consisting of:5-([l,l'-biphenyl]-4-ylmethoxy)-lH-indole;5-((4,4-difluorocyclohexyl)methoxy)-lH-indole;5-(adamantan- 1 -ylmethoxy)- IH-indole;3-(5-(benzyloxy)-lH-indol-l-yl)butanoic acid;4-(5-(benzyloxy)-lH-indol-l-yl)pentanoic acid; methyl 5-(5-(benzyloxy)-7J / -indol-l-yl)pentanoate;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)methanesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)ethenesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)methanesulfonamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)methanesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)ethenesulfonamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)ethenesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)acetamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)acetamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)acrylamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)acrylamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)-2-chloroacetamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)-2-chloroacetamide;4-(5-(benzyloxy)-lH-indol-3-yl)butan-2-ol;(E)-3-(5-(benzyloxy)-lH-indol-3-yl)acrylonitrile;(E)-tert-butyl 5 -(benzyloxy)-3 -(3 -(tert-butoxy)-3 -oxoprop- 1 -en- 1 -yl)- 1 H-indole- 1 - carboxylate;2-(5-(benzyloxy)-lH-indol-l-yl)benzoic acid;3-(5-(benzyloxy)-lH-indol-l-yl)benzoic acid;4-(5-(benzyloxy)-lH-indol-l-yl)benzoic acid;3-(4-(benzyloxy)-lH-indol-l-yl)benzoic acid;3-(6-(benzyloxy)-lH-indol-l-yl)benzoic acid;2-(4-(benzyloxy)-lH-indol-l-yl)benzoic acid;2-(6-(benzyloxy)-lH-indol-l-yl)benzoic acid;4-(4-(benzyloxy)-lH-indol-l-yl)benzoic acid;4-(6-(benzyloxy)-lH-indol-l-yl)benzoic acid;3 -(5-(benzyloxy)-3 -(3 -oxobutyl)- IH-indol- 1 -yl)benzoic acid;(E)-3-(5-(benzyloxy)-3-(2-cyanovinyl)-lH-indol-l-yl)benzoic acid; ethyl 2-(5-(benzyloxy)-lH-indol-l-yl)benzoate;5-(benzyloxy)-l-(3-(trifluoromethyl)phenyl)-lH-indole;5 -(benzyloxy)- 1 -(3 -fluorophenyl)- IH-indole;5-(benzyloxy)-l-(3-chlorophenyl)-lH-indole;5-(benzyloxy)-l-(3-bromophenyl)-lH-indole;5 -(benzyloxy)- 1 -(3 -iodophenyl)- IH-indole; methyl 4-(5-(benzyloxy)-lH-indol-l-yl)benzoate; methyl 3-(5-(benzyloxy)-lH-indol-l-yl)benzoate;5-(benzyloxy)-l-(3-nitrophenyl)-lH-indole;3 -(5 -(benzyloxy)- 1 H-indol- 1 -yl)phenol ;3 -(5 -(benzyloxy)- 1 H-indol- 1 -yl)aniline;N-{ 3 -[5-(benzyloxy)- IH-indol- 1 -yl]phenyl } ethene- 1 -sulfonamide;Methyl 6-[5-(benzyloxy)- IH-indol- l-yl]pyridine-2-carboxylate;Methyl 2-[5-(benzyloxy)- IH-indol- l-yl]pyridine-4-carboxylate;2-[5-(benzyloxy)-lH-indol-l-yl]pyridine-4-carboxylic acid;2-(5-(benzyloxy)-lH-indol-l-yl)nicotinic acid;6-(5-(benzyloxy)-lH-indol-l-yl)picolinic acid;3-(4-(benzyloxy)-lH-indol-l-yl)picolinic acid;6-(6-(benzyloxy)-lH-indol-l-yl)picolinic acid;1-benzyl-5-(benzyloxy)-lH-indole;5-(benzyloxy)-l-[(2-nitrobenzyl]-lH-indole;2-{[5-(benzyloxy)-lH-indol-l-yl]methyl}aniline;N-(2-{[5-(benzyloxy)-lH-indol-l-yl]methyl}phenyl)-2-chloroacetamide;N-(2-{[5-(benzyloxy)-lH-indol-l-yl]methyl}phenyl)ethene-l-sulfonamide;5 -(b enzy loxy ) - 1 - [(3 -nitrob enzy 1 ] - 1 H-indol e;3-{[5-(benzyloxy)-lH-indol-l-yl]methyl}aniline;N-(3-{[5-(benzyloxy)-lH-indol-l-yl]methyl}phenyl)-2-chloroacetamide;N-(3-{[5-(benzyloxy)-lH-indol-l-yl]methyl}phenyl)ethene-l-sulfonamide;5-(benzyloxy)-2,3-dihydro-lH-indole;5-(benzyloxy)-2,3-dihydro-l-[(4-nitrobenzyl]-lH-indole;5-(benzyloxy)-l-[(4-nitrobenzyl]-lH-indole;4-{[5-(benzyloxy)-lH-indol-l-yl]methyl}aniline;N-(4-{[5-(benzyloxy)-lH-indol-l-yl]methyl}phenyl)-2-chloroacetamide;N-(4-{[5-(benzyloxy)-lH-indol-l-yl]methyl}phenyl)ethene-l -sulfonamide;4-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzonitrile;3-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzonitrile;2-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzonitrile;5-(benzyloxy)-l-[(4-bromobenzyl]-lH-indole;5-(benzyloxy)-l-[(3-bromobenzyl]-lH-indole;5-(benzyloxy)-l -[(2 -bromobenzyl]- IH-indole;5-(benzyloxy)-l-[(4-fluorobenzyl]-lH-indole;5 -(b enzy loxy ) - 1 - [(3 -fluorob enzy 1 ] - 1 H-indol e;5-(benzyloxy)-l-[(2-fluorobenzyl]-lH-indole;5-(benzyloxy)-l-[(4-(trifluoromethyl)benzyl]-lH-indole;5-(benzyloxy)-l-[(3-(trifluoromethyl)benzyl]-lH-indole;5-(benzyloxy)-l-[(2-(trifloromethyl)benzyl]-lH-indole; methyl 4-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzoate;4-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzoic acid; methyl 3-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzoate;3-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzoic acid; methyl 2-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzoate;2-{[5-(benzyloxy)-lH-indol-l-yl]methyl}benzoic acid;10-(benzyloxy)-7,8,13,13b-tetrahydro-5H-benzo[l,2]indolizino[8,7-b]indol-5-one; methyl 3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoate hydrochloride; methyl 4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoate hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoic acid hydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoic acid hydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)-2-nitrophenol hydrochloride;6-(benzyloxy)-l-(3-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;6-(benzyloxy)-l-(4-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)aniline dihydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)aniline dihydrochloride;6-(benzyloxy)-2-methyl-l-(3-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;6-(benzyloxy)-2-methyl-l-(4-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;6-(benzyloxy)-2-methyl-l-phenyl-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzonitrile hydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzonitrile hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)phenol hydrochloride; and4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)phenol hydrochloride.

8. A pharmaceutical composition comprising the compound according to any one of claims1 to 7, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable carrier, diluent, excipient and / or adjuvant.

9. A compound of Formula I:a pharmaceutically acceptable salt or a solvate thereof, whereinR1is selected from C1-C6-alkyl, halo-C1-C6-alkyl, aryl-C1-C4-alkyl, haloaryl-C1-C4- alkyl, halo-C1-C4-alkylaryl-C1-C4-alkyl, cycloalkyl-C1-C4-alkyl and halocycloalkyl- C1-C4-alkyl;R2is selected from selected from H, carboxy-C1-C6-alkyl, C1-C4-alkyloxycarbonyl- C1-C6-alkyl, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C1-C4-alkylamido-C1-C6-alkyl, C1-C4- alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6-alkyl, C1-C6- alkyloxy carbonyl, aryl, carboxyaryl, carb oxy heteroaryl, haloaryl, hydroxyaryl, nitroaryl, aminoaryl, halo-C1-C4-alkylaryl, cyanoaryl, C1-C4-alkyloxy carbonylaryl, C1-C4- alkyloxy carb oxy heteroaryl, vinylsulfonamidoaryl, aryl-C1-C4-alkyl, haloaryl-C1-C4-alkyl, nitroaryl-C1-C4-alkyl, aminoaryl-C1-C4-alkyl, C1-C4-alkylamidoaryl-C1-C4- alkyl, halo-C1-C4-alkylamidoaryl-C1-C4-alkyl, C1-C4-alkylsulfonamidoaryl-C 1 -C4- alkyl, vinylsulfonamidoaryl-C1-C4-alkyl, cyanoaryl-C1-C4-alkyl, halo-C 1-C4- alkylaryl-C1-C4-alkyl, carboxyaryl-C1-C4-alkyl and C1-C4-alkyloxycarbonylaryl-C1- C4-alkyl;R3is selected from H, C1-C4-alkylsulfonamido-C1-C6-alkyl, vinylsulfonamido-C1-C6- alkyl, C1-C4-alkylamido-C1-C6-alkyl, acrylamido-C1-C6-alkyl, halo-C 1-C4- alkylamido-C1-C6-alkyl, carboxy carbonyl, C1-C4-alkyloxy carbonyl carbonyl, hydroxy - C1-C6-alkyl, oxo-C1-C6-alkyl, cyanovinyl, formyl, C1-C4-alkyloxy oxopropenyl, carboxyvinyl, amino-C1-C6-alkyl, 3 -amino-3 -carboxypropyl, C1-C6-alkyl, carboxy- C1-C6-alkyl and C1-C4-alkyloxycarbonyl-C1-C6-alkyl;A is N, C-R4or CH-R4wherein R4is H, orR3and R4form together a group selected fromwhereinR5and R6are independently selected from H, OH, C(O)OH, C1-C4- alkyloxycarbonyl, NO2, NH2, CN and vinylsulfonamido;R7is selected from H, C1-C6-alkyl and C1-C4-alkyloxy carbonyl;I is a single bond or a double bond; with the proviso that:R7is not H when R5and R6are H; and! is a double bond when A is N or C-R4; for use in treating cancer.

10. The compound for use according to claim 9, wherein the group -O-R1is located in position 4, 5 or 6 of Formula I.

11. The compound for use according to claim 9 or 10, wherein R1is benzyl.

12. The compound for use according to claim 9, having the formula III:or a pharmaceutically acceptable salt or solvate thereof, whereinR1, R2, R3and R4are as defined in claim 9.

13. The compound for use according to claim 9, having the formula XII:XII, or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R5, R6and R7are as defined in claim 9.

14. The compound for use according to claim 9, wherein the compound is selected from the group consisting of:5-(cyclohexylmethoxy)-777-indole;5-phenethoxy-777-indole;5-isobutoxy-777-indole;5-(naphthalen-2-ylmethoxy)-777-indole;5-(naphthalen-l-ylmethoxy)-777-indole;5-(3-phenylpropoxy)-777-indole;5-([ 1 , 1 '-biphenyl]-4-ylmethoxy)-777-indole;5-((4,4-difluorocyclohexyl)methoxy)-lH-indole;5-((3-(trifluoromethyl)benzyl)oxy)-lH-indole;5-((4-(trifluoromethyl)benzyl)oxy)-lH-indole;5-(neopentyloxy)-lH-indole;5-(adamantan-l-ylmethoxy)-lH-indole;2-(5-(benzyloxy)-777-indol-l-yl)acetic acid;3-(5-(benzyloxy)-777-indol-l-yl)propanoic acid;4-(5-(benzyloxy)-777-indol-l-yl)butanoic acid;5-(5-(benzyloxy)-777-indol-l-yl)pentanoic acid;2-(5-(benzyloxy)-lH-indol-l-yl)acetonitrile;Methyl 2-(5-(benzyloxy)-777-indol-l-yl)acetate;Methyl 5-(5-(benzyloxy)-777-indol-l-yl)pentanoate;2-(5-(benzyloxy)-lH-indol-l-yl)ethan-l -amine;3 -(5 -(benzyloxy)- IH-indol- 1 -yl)propan- 1 -amine;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)methanesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)ethenesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)methanesulfonamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)methanesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)ethenesulfonamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)ethenesulfonamide;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)acetamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)acetamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)acetamide;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)acrylamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)acrylamide;N-(3 -(5 -(benzyloxy)- IH-indol- 1 -yl)propyl)acrylamide;N-(2-(5-(benzyloxy)-lH-indol-3-yl)ethyl)-2-chloroacetamide;N-(2-(5-(benzyloxy)-lH-indol-l-yl)ethyl)-2-chloroacetamide;N-(3-(5-(benzyloxy)-lH-indol-l-yl)propyl)-2-chloroacetamide;2-(5-(benzyloxy)-lH-indol-3-yl)-2-oxoacetic acid; methyl 2-(5-(benzyloxy)-lH-indol-3-yl)-2-oxoacetate;2-(5-(benzyloxy)-lH-indol-3-yl)ethanol;4-(5-(benzyloxy)-lH-indol-3-yl)butan-2-one;4-(5-(benzyloxy)-lH-indol-3-yl)butan-2-ol;(7y)-3-(5-(benzyloxy)-lH-indol-3-yl)acrylonitrile; tert-butyl 5-(benzyloxy)-3-formyl-lH-indole-l -carboxylate;(7y)-terZ-butyl 5-(benzyloxy)-3 -(3 -ethoxy-3 -oxoprop- 1 -en- 1 -yl)- IH-indole- 1 - carboxylate;(7y)-terZ-butyl 5 -(benzyloxy)-3 -(3 -(tert-butoxy )-3 -oxoprop- 1 -en- 1 -yl)- 1 H-indole- 1 - carboxylate;( / s)-ethyl 3-(5-(benzyloxy)-777-indol-3-yl)acrylate;(E)-3 -(5-(benzyloxy)- 1 H-indol-3 -yl)acrylic acid;2-(5-(benzyloxy)- / / / -indol- l-yl (benzoic acid;3-(5-(benzyloxy)-777-indol-l-yl)benzoic acid;4-(5-(benzyloxy)-777-indol-l-yl)benzoic acid;3 -(4-(benzyloxy)- IH-indol- 1 -yl)benzoic acid;3 -(6-(benzyloxy)- IH-indol- 1 -yl)benzoic acid;2-(4-(benzyloxy)- IH-indol- 1 -yl)benzoic acid;2-(6-(benzyloxy)- IH-indol- 1 -yl)benzoic acid;4-(4-(benzyloxy)- IH-indol- 1 -yl)benzoic acid;4-(6-(benzyloxy)- IH-indol- 1 -yl)benzoic acid;3 -(5 -(b enzyloxy)-3 -(3 -oxobutyl)- 1 H-indol- 1 -yl)benzoic acid;(E)-3 -(5-(benzyloxy)-3 -(2-cy anovinyl)- IH-indol- 1 -yl)benzoic acid;5-(benzyloxy)- 1 -phenyl- IH-indole; ethyl 3-(5-(benzyloxy)-lH-indol-l-yl)benzoate; ethyl 2-(5-(benzyloxy)-lH-indol-l-yl)benzoate; ethyl 4-(5-(benzyloxy)-lH-indol-l-yl)benzoate;5-(benzyloxy)-l-(3-(trifluoromethyl)phenyl)-lH-indole;3 -(5 -(benzyloxy)- IH-indol- l-yl)benzonitrile;5-(benzyloxy)- 1 -(3 -fluorophenyl)- IH-indole;5-(benzyloxy)- 1 -(3 -chlorophenyl)- IH-indole;5-(benzyloxy)- 1 -(3 -bromophenyl)- IH-indole;5-(benzyloxy)-l-(3-iodophenyl)-lH-indole; methyl 4-(5-(benzyloxy)- IH-indol- 1 -yl)benzoate; methyl 3 -(5-(benzyloxy)- IH-indol- 1 -yl)benzoate; methyl 2-(5-(benzyloxy)- IH-indol- 1 -yl)benzoate;5-(benzyloxy)- 1 -(3 -nitrophenyl)- IH-indole;3 -(5 -(b enzyloxy)- 1 H-indol- 1 -yl)phenol ;3 -(5 -(benzyloxy)- IH-indol- l-yl)aniline;N-{3-[5-(benzyloxy)-lH-indol-l-yl]phenyl}ethene-l-sulfonamide;Methyl 6-[5-(benzyloxy)-lH-indol-l-yl]pyridine-2-carboxylate;Methyl 2-[5-(benzyloxy)-lH-indol-l-yl]pyridine-4-carboxylate;2- [5 -(benzyloxy)- IH-indol- l-yl]pyridine-4-carboxylic acid;2-(5 -(benzyloxy)- IH-indol- l-yl)nicotinic acid;6-(5-(benzyloxy)- / / / -indol- l-yl (picolinic acid;6-(4-(benzyloxy)- IH-indol- 1 -yl)picolinic acid;6-(6-(benzyloxy)- IH-indol- 1 -yl)picolinic acid;1-benzyl-5-(benzyloxy)-lH-indole ;5-(benzyloxy)-l-[(2-nitrobenzyl]-lH-indole ;2- { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl ( aniline;N-(2-{[5-(benzyloxy)-lH-indol-l-yl]methyl(phenyl)-2-chloroacetamide;N-(2-{[5-(benzyloxy)-lH-indol-l-yl]methyl(phenyl)ethene-l -sulfonamide;5-(benzyloxy)-l-[(3-nitrobenzyl]-lH-indole;3 - { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl ( aniline;N-(3-{[5-(benzyloxy)-lH-indol-l-yl]methyl(phenyl)-2-chloroacetamide;N-(3-{[5-(benzyloxy)-lH-indol-l-yl]methyl(phenyl)ethene-l -sulfonamide;5-(benzyloxy)-2,3-dihydro-lH-indole;5-(benzyloxy)-2,3-dihydro-l-[(4-nitrobenzyl]-lH-indole;5-(benzyloxy)-l-[(4-nitrobenzyl]-lH-indole;4- { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl ( aniline;N-(4-{[5-(benzyloxy)-lH-indol-l-yl]methyl(phenyl)-2-chloroacetamide;N-(4-{[5-(benzyloxy)-lH-indol-l-yl]methyl(phenyl)ethene-l -sulfonamide;4- { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl (benzonitrile;3 - { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl (benzonitrile;2- { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl (benzonitrile;5-(benzyloxy)-l-[(4-bromobenzyl]-lH-indole;5-(benzyloxy)-l-[(3-bromobenzyl]-lH-indole;5-(benzyloxy)-l-[(2-bromobenzyl]-lH-indole;5-(benzyloxy)- 1 -[(4-fluorobenzyl]- IH-indole;5-(benzyloxy)- 1 -[(3 -fluorobenzyl]- IH-indole;5-(benzyloxy)- 1 -[(2 -fluorobenzyl]- IH-indole;5-(benzyloxy)-l-[(4-(trifluoromethyl)benzyl]- IH-indole;5-(benzyloxy)-l-[(3-(trifluoromethyl)benzyl]- IH-indole;5-(benzyloxy)- 1 -[(2-(tri fl oromethyl)benzyl]- IH-indole; methyl 4-{ [5-(benzyloxy)- IH-indol- 1 -yl]methyl (benzoate;4- { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl (benzoic acid;methyl 3 -{ [5-(benzyloxy)- IH-indol- 1 -yl]methyl (benzoate;3 - { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl (benzoic acid; methyl 2-{ [5-(benzyloxy)- IH-indol- 1 -yl]methyl (benzoate;2- { [5 -(benzyloxy)- IH-indol- 1 -yl]methyl (benzoic acid;10-(benzyloxy)-7,8,13,13b-tetrahydro-5H-benzo[l,2]indolizino[8,7-b]indol-5-one; methyl 3 -(6-(benzyloxy)-2,3 ,4,9-tetrahydro- lH-pyrido[3 ,4-b]indol- 1 -yl)benzoate hydrochloride; methyl 4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoate hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoic acid hydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzoic acid hydrochloride;4-(6-(benzyloxy)-2, 3, 4, 9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)-2 -nitrophenol hydrochloride;6-(benzyloxy)-l-(3-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;6-(benzyloxy)-l-(4-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)aniline dihydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)aniline dihydrochloride;6-(benzyloxy)-2-methyl-l-(3-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;6-(benzyloxy)-2-methyl-l-(4-nitrophenyl)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;6-(benzyloxy)-2-methyl-l-phenyl-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indole hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzonitrile hydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)benzonitrile hydrochloride;3-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)phenol hydrochloride;4-(6-(benzyloxy)-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-yl)phenol hydrochloride;5-(benzyloxy)-lH-indole;4-(benzyloxy)-lH-indole;6-(benzyloxy)-lH-indole;5-(benzyloxy)-lH-indazole;2-(5-(benzyloxy)-lH-indol-3-yl)ethan-l -amine;(S)-2-amino-4-(5-(benzyloxy)-lH-indol-3-yl)butanoic acid; and 5-(benzyloxy)-3-methyl-lH-indole.

15. The compound for use according to any one of claims 9 to 14, wherein the cancer is selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer, pleural mesothelioma, blood cancers, neural cancers and neuroendocrine cancers, preferably the cancer is selected from breast cancer, cervical cancer, prostate cancer, pancreatic cancer, colorectal cancer, lung cancer, liver cancer, brain cancer and pleural mesothelioma.

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