TRPM3-modulating benzofuran derivatives

Abstract

The invention relates to compounds that are useful for the prevention or treatment of TRPM3 mediated disorders, more in particular disorders including pain, inflammatory pain or inflammatory hypersensitivity, and epilepsy. The invention also relates to a method for the prevention or treatment of said TRPM3 mediated disorders.

Description

TRPM3-MODULATING BENZOFURAN DERIVATIVESCROSS-REFERENCE TO RELATED APPLICATION

[0001] This International Patent Application claims priority to United States Provisional Patent Application No. 63 / 601,262, filed November 21, 2023, which is incorporated by reference herein in its entirety.FIELD OF THE INVENTION

[0002] The invention relates to compounds and pharmaceutical compositions that are useful for the prevention or treatment of TRPM3 mediated disorders, more in particular disorders selected from pain, such as migraine pain, inflammatory hypersensitivity, and epilepsy. The invention also relates to a methods for the prevention or treatment of said TRPM3 mediated disorders.BACKGROUND OF THE INVENTION

[0003] The TRP superfamily consists of proteins with six transmembrane domains (6TM) that assemble as homo- or heterotetramers to form cation-permeable ion channels. The name TRP originates from the Drosophila trp (transient receptor potential) mutant, which is characterized by a transient receptor potential in the fly photoreceptors in the response to sustained light. In the last 15 years, trp-related channels have been identified in yeast, worms, insects, fish and mammals, including 27 TRPs in humans. Based on sequence homology, TRP channels can be divided into seven subfamilies: TRPC, TRPV, TRPM, TRP A, TRPP, TRPML and TRPN.

[0004] Members of the TRP superfamily are expressed in probably all mammalian organs and cell types, and in recent years great progress has been made in the understanding of their physiological role. The tailored selectivity of certain TRP channels enables them to play key roles in the cellular uptake and / or transepithelial transport of Ca2+, Mg2+and trace metal ions. Moreover, the sensitivity of TRP channels to a broad array of chemical and physical stimuli, allows them to function as dedicated biological sensors involved in processes ranging from vision to taste, and tactile sensation. In particular, several members of the TRP superfamily exhibit a very high sensitivity to temperature. These so-called thermoTRPs are highly expressed in sensory neurons and / or skin keratinocytes, where they act as primary thermosensors for the detection of innocuous and noxious (painful) temperatures.

[0005] It is becoming increasingly clear that TRP channel dysfunction is directly involved in the etiology of various inherited and acquired diseases. Indeed, both loss-of-function and gain-of-function mutations in the TRP channel genes have been identified as the direct cause of inherited diseases, including brachyolmia, hypomagnesemia with secondary hypocalcemia, polycystic kidney disease, mucolipidosis type IV and familial focal segmental glomerulosclerosis. Moreover, TRP channel function / dysfunction has been directly linked to a wide range of pathological conditions, including chronic pain, hypertension, cancer and neurodegenerative disorders.

[0006] TRPM3 (Transient receptor potential melastatin 3) represents a promising pharmacological target. TRPM3 is expressed in a large subset of small-diameter sensory neurons from dorsal root and trigeminal ganglia, and is involved in heat sensing. The neurosteroid pregnenolone sulfate is a potent known activator of TRPM3 (Wagner et al., 2008). The neurosteroid pregnenolone sulfate evoked pain in wild type mice but not in knock-out TRPM3 mice. It was also recently shown that CFA induced inflammation and inflammatory pain are eliminated in TRPM3 knock-out mice. Therefore, TRPM3 antagonists could be used as analgesic drugs to counteract pain, such as inflammatory pain (Vriens J. et al. Neuron, May 2011).

[0007] A few TRPM3 antagonists are known, but none of them points towards the compounds disclosed herein(Straub I et al. Mol Pharmacol, November 2013). For instance, Liquiritigenin, a postulated TRPM3 blocker has been described to decrease mechanical and cold hyperalgesia in a rat pain model (Chen L et al. Scientific reports, July 2014). There is still a great medical need for novel, alternative and / or better therapeutics for the prevention or treatment of TRPM3 mediated disorders, more in particular for pain such as inflammatory pain, or for epilepsy. Therapeutics with good potency on a certain type of pain, low level or no side-effects (such as no possibilities for addiction as with opioates, no toxicity) and / or good or better pharmacokinetic or -dynamic properties are highly needed.

[0008] The invention provides a class of novel compounds which are antagonists of TRPM3 and can be used as modulators of TRPM3 mediated disorders.SUMMARY OF THE INVENTION

[0009] The invention provides benzofuran derivatives and pharmaceutical compositions comprising such benzofuran derivatives. The invention also provides benzofuran derivatives for use as a medicament, more in particular for use in the prevention and / or treatment of TRPM3 mediated disorders, especially for use in the prevention and / or treatment of pain and / or inflammatory pain or hypersensitivity; and / or for treating or preventing epilepsy; and / or for counteracting pain and / or inflammatory pain or hypersensitivity.

[0010] The invention also provides the use of benzofuran derivatives for the manufacture of pharmaceutical compositions or medicaments for the prevention and / or treatment of TRPM3 mediated disorders, especially for the prevention and / or treatment of pain and / or inflammatory pain or hypersensitivity; and / or for treating or preventing epilepsy; and / or for counteracting pain and / or inflammatory pain or hypersensitivity.

[0011] The invention also provides a method for the prevention or treatment of a TRPM3 mediated disorder by administering the benzofuran derivatives according to the invention to a subject in need thereof. More in particular, the invention relates to such method for the prevention and / or treatment of pain and / or inflammatory pain or hypersensitivity; and / or for treating or preventing epilepsy; and / or for counteracting pain and / or inflammatory pain or hypersensitivity.

[0012] The invention further provides a method for the preparation of the benzofuran derivatives of the invention, comprising the synthetic procedures described herein.DETAILED DESCRIPTION OF THE INVENTION

[0013] The invention will be further described and in some instances with respect to particular embodiments, but the invention is not limited thereto.

[0014] A first aspect of the invention is the provision of a compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereofpreferably for use in the treatment of pain or epilepsy;whereinR1represents -F, -Cl, -Br, -I, -CN, -Rw, -ORW, -OC(=O)RW, -NRWRX, -NRWC(=O)RX, -SRW, -S(=O)RW, -S(=O)2RW, -C(=O)RW, -C(=O)ORW, or -C(=O)NRWRX;R3represents -OH or -RY;X represents a single bond between Cy and the carbon atom to which it is attached, or X represents -O-, -CR5R5'- , -S-, -S(O)n-, -S-CR5R5-, -CR5R5-S-, -CR5R5-CR4R4-, -NR5-CR4R4-, -C=, -C=C-, or -CR5R5-NR5-, in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -0RY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ;R4and R4' independently of one another represent -RY; n is an integer ranging from 1 to 2;R5and R5' independently of one another represent -RY, or R5and R5' together form a carbonyl, a 3-6-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted, or a 3 -6-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted, on the atom to which they are attached;R6and R7independently of one another represent -F, -Cl, -Br, -I, -CN, -N02, -SF5, -Rw, -ORW, -OC(=O)RW, -NRWRX, -NRWC(=O)RX, -SRW, -S(=O)RW, -S(=O)2RW, -C(=O)RW, -C(=O)ORW, or -C(=O)NRWRX;Cy represents 3-14-membered cycloalkyl, saturated or unsaturated, 3-14-membered heterocycloalkyl, saturated or unsaturated; 5-14-membered aryl, or 5-14-membered heteroaryl; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -N02, =0, =S, -SF5, -RY, -0RY, -OC(=O)RY, -NRYRZ, -NRYC(=0)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ; whereinRwand Rxindependently of one another in each case independently represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;RYand Rzindependently of one another in each case independently represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-Cc-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through -C1-C6-alkylene- or -C1-Cc-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through -C1-C6-alkylene- or -C1-Cc-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or RYand Rztogether form a 4, 5, 6, 7 or 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, saturated or unsaturated, unsubstituted or mono- or polysubstituted; and wherein "mono- or polysubstituted" in each case independently means substituted with one or more, e.g. 1, 2, 3, 4, or more substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -C1-6-alkyl, -CF3, -CF2H, -CFH2, -CF2CI, -CFCI2, -C1-6-alkylcnc-CF,. -C1-6-alkylene-CF2H, -C1-6-alkylene-CFH2, -C1-6-alkylene-O-CF3, -C1-6-alkylene-O-CF2H, -C1-6-alkylene-O-CFFF, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C1-6-alkylene-N(C1-6-alkyl)-C1-6-alkylene-CF3, -C(=O)-C1-6-alkyl, -C1-6-alkylene-C(=O)-C1-6-alkyl, -C(=O)OH, -C1-6-alkylene-C(=O)-OH, -C(=O)-OC1-6-alkyl, -C1-6-alkylene-C(=O)-OC1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)-NH2, -C1-6-alkylene-C(=O)-NH2, -C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-C(=O)-NH(C1-6-alkyl), -C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-C(=O)-N(C1-6-alkyl)2, -C(=O)-NH(OH), -C1-6-alkylene-C(=O)-NH(OH), -OH, -C1-6-alkylene-OH, =0, -OCF3, -OCF2H, -OCFH2, -OCF2CI, -OCFCI2, -O-C1-6-alkyl, -C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene-NH2, -O-C1-6-alkylene-NH-C1-6a- alkyl, -O-C1-6-alkylene-N(C1-6-alkyl)2, -0-C(=0)-C1-6-alkyl, -C1-6-alkylene-O-C(=O)-C1-6-alkyl, -O-C(=O)-O-C1-6-alkyl, -Ci -6-alkylene-0-C(=0)-0-C1-6-alkyl, -O-C(=O)-NH(C1-6-alkyl), -Ci -6-alkylene-0-C(=0)-NH(C1-6-alkyl), -O-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-O-C(=O)-N(C1-6-alkyl)2, -O-S(=O)2-NH2, -C1-6-alkylene-O-S(=O)2-NH2, -O-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-O-S(=O)2-NH(C1-6-alkyl), -O-S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-O- S(=O)2-N(C1-6-alkyl)2, -NH2, -NO, -NO2, -C1-6-alkylene-NH2, -NH(C1-6-alkyl), -N(3-14-membered cycloalkyl)(C1-6-alkyl), -N(C1-6-alkyl)-C1-6-alkylene-0H, -N(H)-C1-6-alkylene-OH, -C1-6-alkylene-NH(C1-6-alkyl), -N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)2, -NH-C(=O)-C1-6-alkyl, -C1-6-alkylene-NH-C(=O)-C1-6-alkyl, -NH- C(=O)-O-C1-6-alkyl, -C1-6-alkylene-NH-C(=O)-O-C1-6-alkyl, -NH-C(=0)-NH2, -C1-6-alkylene-NH-C(=O)-NH2, - NH-C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-NH-C(=O)-NH(C1-6-alkyl), -NH-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene- NH-C(=O)-N(C1-6-alkyl)2, -N(C1-6-alkyl)-C(=O)-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-C1-6-alkyl, -N(Ci -6-alkyl)-C(=O)-O-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-O-C1-6-alkyl, -N(C1-6-alkyl)-C(=O)-NH2, -C1-6a- alkylene-N(C1-6-alkyl)-C(=O)-NH2, -N(C1-6-alkyl)-C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6-alkyl)-C(=O)- NH(C1-6-alkyl), -N(C1-6-alkyl)-C(=0)-N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)-C(=0)-N(C1-6-alkyl)2, -NH- S(=O)2OH, -C1-6-alkylene-NH-S(=O)2OH, -NH-S(=O)2-C1-6-alkyl, -C1-6-alkylene-NH-S(=O)2-C1-6-alkyl, -NH- S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-NH-S(=O)2-O-C1-6-alkyl, -NH-S(=O)2-NH2, -C1-6-alkylene-NH-S(=O)2-NH2, -NH-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-NH-S(=O)2-NH(C1-6-alkyl), -NH-S(=O)2N(C1-6-alkyl)2, -C1-e- alkylene-NH-S(=O)2N(C1-6-alkyl)2, -N(C1-6-alkyl)-S(=O)2-OH, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-OH, -N(C1-e- alkyl)-S(=0)2-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-S(=0)2-C1-6-alkyl, -N(C1-6-alkyl)-S(=0)2-0-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-O-C1-6-alkyl, -N(C1-6-alkyl)-S(=O)2-NH2, -C1-6-alkylene-N(C1-6-alkyl)-S(=0)2- NH2, -N(C1-6-alkyl)-S(=0)2-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-NH(C1-6-alkyl), -N(C1-6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -SH, =S, -SFs, -SCF3, -SCF2H, - SCFH2, -S-C1-6-alkyl, -C1-6-alkylene-S-C1-6-alkyl, -S(=O)-C1-6-alkyl, -C1-6-alkylene-S(=O)-C1-6-alkyl, -S(=O)2-C1-6-alkyl, -C1-6-alkylene-S(=O)2-C1-6-alkyl, -S(=0)2-0H, -C1-6-alkylene-S(=O)2-OH, -S(=O)2-O-C1-6-alkyl, -C1-6- alkylene-S(=O)2-O-C1-6-alkyl, -S(=O)2-NH2, -C1-6-alkylene-S(=O)2-NH2, -S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene- S(=O)2-NH(C1-6-alkyl), -S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-S(=O)2-N(C1-6-alkyl)2, 3-14-membered cycloalkyl, -C1-6-alkylene-(3-14-membered cycloalkyl), 3 to 14-membered heterocycloalkyl, -C1-6-alkylene-(3 to 14- membered heterocycloalkyl), -phenyl, -C1-6-alkylene-phenyl, 5 to 14-membered heteroaryl, -C1-6-alkylene-(5 to 14-membered heteroaryl), -O-(3-14-membered cycloalkyl), -O-(3 to 14-membered heterocycloalkyl), -O-phenyl, -O-(5 to 14-membered heteroaryl), -C(=O)-(3-14-membered cycloalkyl), -C(=O)-(3 to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5 to 14-membered heteroaryl), -S(=O)2-(3-14-membered cycloalkyl), -S(=O)2-(3 to 14-membered heterocycloalkyl), -S(=O)2-phenyl, -S(=O)2-(5 to 14-membered heteroaryl).

[0015] Generally, X is described such that the first atom listed in the notation is bonded to the benzofuran ring system, i.e., the first atom in the notations -S-CR5R5-, -CR5R5-S-, -CR5R5-CR4R4-, -NR5-CR4R4-, or -CR5R5- NR5- is bonded to the benzofuran ring system and the second atom in the notation is bonded to Cy.

[0016] In an embodiment of the benzofuran derivative according to the invention, R1is selected from -C1-C6- alkyl. In an embodiment, R1is selected from methyl, ethyl, and propyl. In an embodiment, R1is methyl.

[0017] In an embodiment of the benzofuran derivative according to the invention, R3represents -CR9R9'R9", wherein R9, R9', and R9" are independently RY, or C1-6alkyl or C1-eheteroalkyl optionally substituted with one or more RY, optionally wherein two of R9, R9', and R9" together form a 3-14-membered cycloalkyl, 3-14-membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl, said 3-14-membered cycloalkyl, 3-14- membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl optionally monosubstituted or polysubstituted with one or more RY.

[0018] In an embodiment, R5and R5' together form a 3-4-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted, or a 3-4-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted. In an embodiment, R5and R5' together form cyclopropyl, cyclobutyl, or oxetane.

[0019] In an embodiment of the benzofuran derivative according to the invention, R7and R8are independently selected from H, C1-C6-alkyl, and C1-C6-heteroalkyl. In an embodiment, R7and R8are preferably each -H.

[0020] In an embodiment of the benzofuran derivative according to the invention, R6is selected from H, halogen, and C1-ehaloalkyl. In an embodiment, R6is selected from H and F.

[0021] In an embodiment of the benzofuran derivative according to the invention, R6is selected from cyano, carbonyl, carboxylic acid, carboxylic esters, nitro, ammonium, aldehyde, and sulfonyl.

[0022] In an embodiment of the benzofuran derivative according to the invention, Cy includes one or more cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings, wherein, for Cy having more than one cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring, said rings may share one or more atoms in a spiro or fused system, or may be optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0023] In an embodiment of the benzofuran derivative according to the invention Cy represents 5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SFs, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ.

[0024] In some embodiments, the 5-14-membered heteroaryl within the definition of Cy is not benzofuran, unsubstituted, mono- or polysubstituted.

[0025] In some embodiments, the 5-14-membered heteroaryl or aryl within the definition of Cy is selected from azulene, benzimidazole, benzisoxazole, benzoazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furane, furazane, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [l,2,4]triazolo[4,3- a]pyrimidine; in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, - SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ

[0026] In some embodiments, the 5-14-membered heteroaryl within the definition of Cy is selected from the group consisting of furane, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, triazole, pyridine, isoquinoline, benzothiazole, pyridazine, pyrimidine, imidazopyridine; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, - C(=O)ORY, or -C(=O)NRYRZ.

[0027] In an embodiment, the 5-14-membered heteroaryl within the definition of Cy is selected from the group consisting of furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, pyrazol-5-yl, oxazol-5-yl, isoxazol-4-yl, thiazol- 2-yl, thiazol-5-yl, l,2,4-triazol-3-yl, l,2,3-triazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, isoquinolin- 1-yl, isoquinolin-5-yl, benzo [d]thiazol-2-yl, pyridazin-3-yl, pyrimidin-5-yl, and imidazo[l,2-a]pyridin-6-yl; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, - S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ

[0028] In an embodiment of the benzofuran derivative according to the invention Cy represents 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ

[0029] In an embodiment, the 3-14-membered heterocycloalkyl within the definition of Cy is selected from azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxalidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofurane, tetrahydropyrane, tetrahydrothiopyrane, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1 -dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8- azabicyclo[3.2. l]octane, 9-azabicyclo[3.3. l]nonane, hexahydro- IH-pyrrolizine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[l,2-a]pyrazin; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, - C(=O)ORY, or -C(=O)NRYRZ.

[0030] In an embodiment, the 3-14-membered heterocycloalkyl within the definition of Cy is tetrahydropyrane or pyrrolidine; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, - SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ

[0031] In an embodiment, the 3-14-membered heterocycloalkyl within the definition of Cy is tetrahydropyran- 4-yl or pyrrolidin-3-yl; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, - NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ

[0032] In an embodiment of the benzofuran derivative according to the invention Cy is unsubstituted, mono- or poly substituted with substituents independently of one another selected from-F, -Cl, -Br, -I, -CN, -C(=O)OH, -NH2, -NO2, -OH, =0, -SF5;-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C(=0)0-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-NHC1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-N(C1-6-alkyl)2, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-O-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-S(=O)2-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0033] In an embodiment, Cy is unsubstituted, mono- or polysubstituted with substituents independently of one another selected from-OH, -F, -Cl, -Br, -I, -SH, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -CN, -NO2, -C(=O)OH, -NH2, or -N(CH3)2;-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted with substituents independently of one another , selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, C(=O)CHF2, and -C(=O)NH2;-C1-6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted with substituents independently of one another , selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, C(=O)CHF2, and -C(=O)NH2;-OC1-6-alkyl, unsubstituted, mono- or polysubstituted with substituents independently of one another, selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, C(=O)CHF2, and -C(=O)NH2;-0(C=0)C1-6-alkyl, unsubstituted, mono- or polysubstituted with substituents independently of one another , selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -0CF3, -OCHF2, -OCH2F, SF5, -N02, -C(=O)OH, -NH2, C(=O)CHF2, and -C(=O)NH2; -C(=0)0C1-6-alkyl, unsubstituted, mono- or polysubstituted with substituents independently of one another , selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, -SH, =S, - CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -N02, -C(=O)OH, -NH2, C(=O)CHF2, and -C(=O)NH2; 3-14-membered cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl; in each case unsubstituted, mono- or polysubstituted with substituents independently of one another , selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, - SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -N02, -C(=O)OH, -NH2, C(=O)CHF2, and - C(=0)NH2;3-14-membered heterocycloalkyl selected from the group consisting of azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxalidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro- [3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo- [3.3.1]nonane, hexahydro- IH-pyrrolizine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[l,2-a]pyrazin, in each case unsubstituted, mono- or poly substituted with substituents independently of one another , selected from the group consisting of -F, -Cl, -Br, -I, -C1-6-alkyl, C2-6-alkenyl, -C2-6-alkynyl, -OH, =0, -SH, =S, -CN, -CF3, -CHF2, -CH2F. -OCF3, -OCHF2, -OCH2F, SF5, -N02, -C(=O)OH, -NH2, C(=O)CHF2, and -C(=O)NH2.

[0034] In an embodiment, Cy is unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -CN, -OH, =0, -C1-6-alkyl, -CHF2, -CF3, -C1-6-alkylene-NH2, -C1-6-alkylene- NHC(=0)0-C1-6-alkyl, -C1-6-alkylene-OH, -C1-6-alkylene-NHC(=O)-O-C1-6-alkyl, -C(=O)O-C1-6-alkyl, -N(C1-6- alkyl)2, -OC1-6-alkyl, -OCF3, -O-C1-6-alkylene-N(C1-6-alkyl)2, -S(=O)2-C1-6-alkyl, -azetidine, -C1-6-alkylene-O- tetrahydropyran, or -piperazine substituted with -C1-6-alkyl.

[0035] In some embodiments of the benzofuran derivative according to the invention Cy is(i) unsubstituted;(ii) monosubstituted;(iii) disubstituted;(iv) trisubstituted; or(v) tetrasubstituted; wherein the particular substituents of (iii)-(v) may be independently different from one another or where one or more of the particular substituents of (iii)-(v) may be the same.

[0036] In some embodiments of the benzofuran derivative according to the invention Cy is(i) unsubstituted;(ii) monosubstituted; or(iii) disubstituted.

[0037] In some embodiments, Cy represents C3-C8cycloalkyl, phenyl, Cs-C8heterocycloalkyl, or Cs-C8heteroaryl, optionally substituted with one or more of halogen, C1-C3-haloalkyl, hydroxy, acyl, carboxamide, methyl, methoxy, ethyl, ethoxy, propyl, cyclopropyl, butyl, cyclobutyl, oxetane, pyrrole, or diazole, said carboxamide, acyl, cyclopropyl, cyclobutyl, oxetane, pyrrole and diazole optionally being further substituted with halogen, C1-Cs-haloalkyl, hydroxy, phenyl, methyl, methoxy, ethyl, ethoxy, or propyl, optionally connected through C1-C6- alkylene- or -C1-C6-heteroalkylene-.

[0038] A further aspect of the invention is the provision of a compound of Formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate, and / or polymorph thereof:wherein:R3is selected from -CR9R9'R9", wherein R9, R9', and R9" are independently RY, or C1-6alkyl or C1-eheteroalkyl optionally substituted with one or more RY, optionally wherein two of R9, R9', and R9" together form a 3-14- membered cycloalkyl, 3-14-membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl, said 3-14-membered cycloalkyl, 3-14-membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl optionally monosubstituted or polysubstituted with one or more RY;R6is selected from H, halogen, and Ci -ehaloalky 1;X represents a single bond between Cy and the carbon atom to which it is attached, or X represents -O-, -CR5R5'- , -S-, -S(O)n-, -S-CR5R5-, -CR5R5-S-, -CR5R5-CR4R4-, -NR5-CR4R4-, -C=, -C=C-, -CR5R5-NR5-, in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -ORY, -OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, - S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ; n is an integer ranging from 1 to 2;R4and R4' independently of one another represent -RY;R5and R5' independently of one another represent -RY, or R5and R5' together form a carbonyl, a 3-6-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted, or a 3 -6-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted, on the atom to which they are attached;Cy represents 3-14-membered cycloalkyl, saturated or unsaturated, 3-14-membered heterocycloalkyl, saturated or unsaturated; 5-14-membered aryl, or 5-14-membered heteroaryl; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -0RY, -OC(=O)RY, -NRYRZ, -NRYC(=0)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, - C(=O)ORY, or -C(=O)NRYRZ; whereinRYand Rzindependently of one another in each case independently represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or RYand Rztogether form a 4, 5, 6, 7 or 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, saturated or unsaturated, unsubstituted or mono- or polysubstituted; and wherein "mono- or polysubstituted" in each case independently means substituted with one or more, e.g. 1, 2, 3, 4, or more substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -C1-6-alkyl, -CF3, - CF2H, -CFH2, -CF2CI, -CFCI2, -C1-6-alkylene-CFs, -C1-6-alkylene-CF2H, -C1-6-alkylene-CFFF, -C1-6-alkylene-O- CF3, -C1-6-alkylene-O-CF2H, -C1-6-alkylene-O-CFFF, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C1-6-alkylene-N(C1-6-alkyl)-C1-6-alkylene-CF3, -C(=O)-C1-6-alkyl, -C1-6-alkylene-C(=O)-C1-6-alkyl, -C(=O)OH, -C1-6-alkylene- C(=O)-OH, -C(=O)-OC1-6-alkyl, -C1-6-alkylene-C(=O)-OC1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)-NH2, - C1-6-alkylene-C(=O)-NH2, -C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-C(=O)-NH(C1-6-alkyl), -C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-C(=O)-N(C1-6-alkyl)2, -C(=O)-NH(OH), -C1-6-alkylene-C(=O)-NH(OH), -OH, -C1-6-alkylene-OH, =0, -OCF3, -OCF2H, -OCFH2, -OCF2CI, -OCFCb, -O-C1-6-alkyl, -C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene- O-C1-6-alkyl, -O-C1-6-alkylene-NH2, -O-C1-6-alkylene-NH-C1-6-alkyl, -O-C1-6-alkylene-N(C1-6-alkyl)2, -0-C(=0)- C1-6-alkyl, -C1-6-alkylene-O-C(=O)-C1-6-alkyl, -0-C(=0)-0-C1-6-alkyl, -C1-6-alkylene-O-C(=O)-O-C1-6-alkyl, -O- C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-O-C(=O)-NH(C1-6-alkyl), -O-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-O- C(=O)-N(C1-6-alkyl)2, -O-S(=O)2-NH2, -C1-6-alkylene-O-S(=O)2-NH2, -O-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene- O-S(=O)2-NH(C1-6-alkyl), -O-S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-O-S(=O)2-N(C1-6-alkyl)2, -NH2, -NO, -NO2, - C1-6-alkylene-NH2, -NH(C1-6-alkyl), -N(3-14-membered cycloalkyl)(C1-6-alkyl), -N(C1-6-alkyl)-C1-6-alkylene-OH, -N(H)-C1-6-alkylene-0H, -C1-6-alkylene-NH(C1-6-alkyl), -N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)2, -NH- C(=O)-C1-6-alkyl, -C1-6-alkylene-NH-C(=O)-C1-6-alkyl, -NH-C(=O)-O-C1-6-alkyl, -C1-6-alkylene-NH-C(=O)-O- C1-6-alkyl, -NH-C(=0)-NH2, -C1-6-alkylene-NH-C(=O)-NH2, -NH-C(=0)-NH(C1-6-alkyl), -C1-6-alkylene-NH- C(=O)-NH(C1-6-alkyl), -NH-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C(=O)-N(C1-6-alkyl)2, -N(C1-6-alkyl)- C(=0)-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-C1-6-alkyl, -N(C1-6-alkyl)-C(=O)-O-C1-6-alkyl, -C1-6- alkylene-N(C1-6-alkyl)-C(=O)-O-C1-6-alkyl, -N(C1-6-alkyl)-C(=O)-NH2, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-NH2, -N(C1-6-alkyl)-C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-NH(C1-6-alkyl), -N(C1-6-alkyl)-C(=O)- N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-N(C1-6-alkyl)2, -NH-S(=O)2OH, -C1-6-alkylene-NH- S(=O)2OH, -NH-S(=O)2-C1-6-alkyl, -C1-6-alkylene-NH-S(=O)2-C1-6-alkyl, -NH-S(=O)2-O-C1-6-alkyl, -C1-6- alkylene-NH-S(=O)2-O-C1-6-alkyl, -NH-S(=O)2-NH2, -C1-6-alkylene-NH-S(=O)2-NH2, -NH-S(=O)2-NH(CI-6-alkyl), -C1-6-alkylene-NH-S(=O)2-NH(C1-6-alkyl), -NH-S(=O)2N(C1-6-alkyl)2, -C1-6-alkylene-NH-S(=O)2N(C1-6- alkyl)2, -N(C1-6-alkyl)-S(=O)2-OH, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-OH, -N(C1-6-alkyl)-S(=O)2-C1-6-alkyl, - C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-C1-6-alkyl, -N(C1-6-alkyl)-S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)- S(=O)2-O-C1-6-alkyl, -N(C1-6-alkyl)-S(=O)2-NH2, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-NH2, -N(C1-6-alkyl)- S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-NH(C1-6-alkyl), -N(C1-6-alkyl)-S(=O)2-N(C1-6- alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -SH, =S, -SFs, -SCF3, -SCF2H, -SCFH2, -S-C1-6-alkyl, -C1-6-alkylene-S-C1-6-alkyl, -S(=0)-C1-6-alkyl, -C1-6-alkylene-S(=O)-C1-6-alkyl, -S(=O)2-C1-6-alkyl, -C1-6- alkylene-S(=O)2-C1-6-alkyl, -S(=O)2-OH, -C1-6-alkylene-S(=O)2-OH, -S(=O)2-O-C1-6-alkyl, -C1-6-alkylene- S(=O)2-O-C1-6-alkyl, -S(=O)2-NH2, -C1-6-alkylene-S(=O)2-NH2, -S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-S(=O)2- NH(C1-6-alkyl), -S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-S(=O)2-N(C1-6-alkyl)2, 3-14-membered cycloalkyl, -C1-6- alkylene-(3- 14-membered cycloalkyl), 3 to 14-membered heterocycloalkyl, -C1-6-alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C1-6-alkylene-phenyl, 5 to 14-membered heteroaryl, -C1-6-alkylene-(5 to 14-membered heteroaryl), -O-(3- 14-membered cycloalkyl), -O-(3 to 14-membered heterocycloalkyl), -O-phenyl, -O-(5 to 14- membered heteroaryl), -C(=O)-(3-14-membered cycloalkyl), -C(=O)-(3 to 14-membered heterocycloalkyl), - C(=O)-phenyl, -C(=O)-(5 to 14-membered heteroaryl), -S(=O)2-(3- 14-membered cycloalkyl), -S(=O)2-(3 to 14- membered heterocycloalkyl), -S(=O)2-phenyl, -S(=O)2-(5 to 14-membered heteroaryl).

[0039] In an embodiment of the benzofuran derivative according to the invention, R6is selected from -H, halogen, and Ci -ehaloalky 1. In an embodiment, R6is selected from -H and -F.

[0040] In an embodiment of the benzofuran derivative according to the invention, R6is selected from cyano, carbonyl, carboxylic acid, carboxylic esters, nitro, ammonium, aldehyde, and sulfonyl.

[0041] In an embodiment of the benzofuran derivative according to the invention, Cy includes one or more cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings, wherein, for Cy having more than one cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring, said rings may share one or more atoms in a spiro or fused system, or may be optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0042] In some embodiments of Formulas (I) and (II), Cy represents a 3-14-membered cycloalkyl (preferably 3, 4, 5 or 6-membered cycloalkyl), saturated or unsaturated, in each case unsubstituted, mono- or polysubstituted; optionally a residue selected from the group consisting of:

[0043] In some embodiments of Formulas (I) and (II), Cy represents a 3-14-membered aryl, in each case unsubstituted, mono- or polysubstituted; optionally a residue selected from the group consisting of:

[0044] In some embodiments of Formulas (I) and (II), Cy represents a 3-14-membered heterocycloalkyl (optionally 4, 5 or 6-membered heterocycloalkyl), saturated or unsaturated; or 5-14-membered heteroaryl (optionally 5 or 6-membered heteroaryl); in each case unsubstituted, mono- or poly substituted; optionally a residue selected from the group consisting of:

[0045] In an embodiment of Formulas (I) and (II), Cy represents -oxetanyl, unsubstituted, mono- or polysubstituted; preferably

[0046] In some embodiments of Formulas (I) and (II), Cy represents a residue according to general formula (E)whereinYE1represents -N=, -NRE2-, S, O, or -CRE3=; YE2represents -N=, -NRE3-, S, O, or -CRE4=; and YE3represent - N=, -NRE4-, S, O, or -CRE5=; with the proviso that at least one of YE1, YE2, and YE3is not -CRE3=, -CRE4=, and - CRE5=, respectively. In another embodiment, Cy represents a residue according to general formula (E) wherein YE1 represents -N=, -NRE2-, S, or -CRE3=; YE2 represents -N=, -NRE3-, S, or -CRE4=; and YE3 represent -N=, -NRE4-, S, or -CRE5=; with the proviso that at least one of YE1, YE2, and YE3 is not -CRE3=, - CRE4=, and -CRE5=, respectively.RE1, RE2, RE3, and RE4independently of one another represent -H, -CH3,-CH2-cyclopropyl, -CH2CF3, -CH2CHF2 or -CF3; more in particular RE1, RE2, RE3, and RE4independently of one another represent -H, -CH3, or -CF3; preferably with the proviso that only one of RE1, RE2, RE3, and RE4represents a residue that is not -H.

[0047] In some embodiments of Formulas (I) and (II), Cy represents 2-pyridine, unsubstituted, mono- orpolysubstituted. In preferred embodiments, Cy represents a residue selected from the group consisting of:

[0048] In some embodiments of Formulas (I) and (II), Cy represents 3-pyridine, unsubstituted, mono- or polysubstituted. In some embodiments, Cy represents a residue selected from the group consisting of:

[0049] In some embodiments of Formulas (I) and (II), Cy represents 4-pyridine, unsubstituted, mono- or polysubstituted. In some embodiments, Cy represents a residue selected from the group consisting of:

[0050] In some embodiments of Formulas (I) and (II), Cy represents a residue selected from the group consisting of:

[0051] In some embodiments of Formulas (I) and (II), Cy represents a bicyclic heteroaryl, unsubstituted, mono-

[0052] In some embodiments of Formulas (I) and (II), Cy represents a residue according to general formula (F’)whereinYF1represents -N= or -CRF4=; and Y12represents -N= or -CRF5=; and YF3represents -N= or -CRF3=; with the proviso that at least one of YF1and Y12is not -CRF4= and -CRF5=, respectively;RF1, RF2, RF3, RF4, and RFSindependently of one another represent -H, -CH3, -CF3,-OH, -OCH3, -OCH2CH3, -Cl, or -azetidinyl; preferably with the proviso that only one of RF1, RF2, RF3, RF4, and RFSrepresents a residue that is not -H.In another embodiment, Cy represents a residue according to general formula (F)whereinYF1represents -N= or -CRF4=; and YF2represents -N= or -CRF5=; with the proviso that at least one of YF1and YF2is not -CRF4= and -CRF5=, respectively;RF1, RF2RF3RF 4and RF5independently of one another represent -H, -CH3, -CF3,-OH, -OCH3, -OCH2CH3, -Cl, or -azetidinyl; preferably with the proviso that only one of RF1, RF2, RF3, RF4, and RF5represents a residue that isnot -H.

[0053] In some embodiments, Cy represents a residue according to general formula (G) or (H)(G) (H) wherein RG1and RH1are selected from the group consisting of -H, -CH3, -CF3, -OH, -OCH3, -OCH2CH3, -Cl, azetidinyl, -cyclopropyl, -O-cyclopropyl, and -CHF2; or wherein RG1and RH1are selected from the group consisting of -H, -CH3, -CF3, -OH, -OCH3, -OCH2CH3, -Cl, and azetidinyl.In other preferred embodiments, Cy represents a residue according to general formula (G’) or (H’)wherein RG1and RH1are selected from the group consisting of -H, -CH3, -CF3, -OH, -OCH3, -OCH2CH3, -Cl, azetidinyl, -cyclopropyl, -O-cyclopropyl, and -CHF2; or wherein RG1and RH1are selected from the group consisting of -H, -CH3, -CF3, -OH, -OCH3, -OCH2CH3, -Cl, and azetidinyl;

[0054] In an embodiment of the benzofuran derivative according to the invention R1represents-H, -F, -Cl, -Br, -I, -CN;-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted; -O-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C(=O)C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C(=O)OC1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C(=O)NHC1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C(=O)N(C1-6-alkyl)2, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-S(=O)C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-S(=O)2-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted; or3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0055] In an embodiment, R1represents -H, -F, -Cl, -Br, -I, -C1-6-alkyl, -O-C1-6-alkyl, -C1-6-alkylene-O-C1-6- alkyl, -C1-6-alkylene-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6-alkyl)2, -CF3, -CF2H, -CFH2, -CF2CI, -CFCI2, -C1-6- alkylene-CFs, -C1-6-alkylene-CF2H, -C1-6-alkylene-CFH2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C1-6-alkylene- N(C1-6-alkyl)-C1-6-alkylene-CF3, -C(=O)C1-6-alkyl, -C(=O)OC1-6-alkyl, -C(=O)NH2, -C(=O)NHC1-6-alkyl, -C(=O)N(C1-6-alkyl)2, -S(=0)-C1-6-alkyl, -S(=O)2-C1-6-alkyl, -O-C1-6-alkyl, -cyclopropyl unsubstituted, cyclobutyl unsubstituted, cyclopentyl unsubstituted or cyclohexyl unsubstituted.

[0056] In an embodiment, R1represents -H, -C1-6-alkyl, -C1-6-alkylene-O-C1-6-alkyl, -CH2F, -CHF2, -CF3, - cyclopentyl, unsubstituted, or -cyclopropyl. In an embodiment, R1represents -H, -C1-6-alkyl, -C1-6-alkylene-O-C1-6-alkyl, -CH2F, -CHF2, -CF3, -cyclopentyl, or unsubstituted. In an embodiment, R1represents -CH3.

[0057] In an embodiment, R1represents -CH2F, -CHF2, -CH3, or -cyclopropyl. In an embodiment, R1represents -CH2F, -CHF2, or -CH3. In an embodiment, R1represents -C(=O)NH2, or -CHF2.

[0058] In an embodiment, R1represents -H, -C1-3-alkyl, -CF3, -CF2H, -CFH2, -CF2CI, -CFCI2, -C1-3-alkylene- CF3, -C1-3-alkylene-CF2H, -C1-3-alkylene-CFH2, or -cyclopropyl; in an embodiment, R1represents -H, -C1-3-alkyl, -CF3, -CF2H, -CFH2, -CF2CI, -CFCI2, -C1-3-alkylene-CF3, -C1-3-alkylene-CF2H, or -C1 -3-alkylene-CFH2; more preferably -CH3.

[0059] In an embodiment, R1represents methyl, ethyl, or propyl.

[0060] In an embodiment, R1represents methyl.

[0061] In an embodiment of Formulas (I) and (II), R3optionally represents -H, -OH, -C1-6-alkyl, -C1-6-alkylene- OH, -C1-6-alkylene-O-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6- alkyl)2, -CF3, -CF2H, -CFH2, -CF2CI, -CFCI2, -C1-6-alkylene-CF3, -C1-6-alkylene-CF2H, -C1-6-alkylene-CFH2, -C1- 6-alkylene-NH-C1-6-alkylene-CF3, or -C1-6-alkylene-N(C1-6-alkyl)-C1-6-alkylene-CF3, optionally unsubstituted, monosubstituted, or polysubstituted.

[0062] In some embodiments, R3represents -H, -OH, or -C1-6-alkyl, saturated, unsubstituted or monosubstituted with -OH. In an embodiment, R3represents -H.

[0063] In some embodiments of the benzofuran derivative of Formula (I) or Formula (II), R3is connected to the N to which it is attached through a -C1-C1-alkylene-. saturated or unsaturated, unsubstituted, monosubstituted, or poly substituted, or through a -C1-C4-heteroalkylene-, saturated or unsaturated, unsubstituted, monosubstituted, or polysubstituted. In some embodiments of the benzofuran derivative of Formula (I) or Formula (II), R3instead represents -CR10R10’R10’’ (i.e., in embodiments of Formula I or Formula II where R10is specified, R3may represent -C-R10R10’R10”). In various embodiments, when R10, R10’, and / or R10’’ independently represent one or more substituents herein, one or more of R10, R10’ , and R10’’ may be -H or any other substituent disclosed for R10, R10’ , and R10”.

[0064] In an embodiment, R10, R10’ , and / or R10’’ independently represent:-H;-S(=O)C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-S(=O)2-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0065] In an embodiment, R10, R10’ , and / or R10’’ independently represent-S(=O)2C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -Cl, -C1-6-alkyl, -C1-6-alkylcnc-CF ,. -OH, =0, -OC1-6-alkyl, -C1-6-alkylene-OH, -C1-6-alkylene-O-C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, - NHC(=O)O-C1-6-alkyl, -N(C1-6-alkyl)C(=O)O-C1-6-alkyl, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -C1-6-alkylene- NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=O)- C1-6-alkyl, -C(=O)OH, -C(=O)O-C1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)NH2, -C(=O)NH(C1-6-alkyl), - C(=O)N(C1-6-alkyl)2, -S(=O)2C1-6-alkyl, -phenyl, -C1-6-alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5-14-membered heteroaryl, unsubstituted;-S(=O)2(3- 14-membered cycloalkyl), wherein said 3-14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, in each case saturated or unsaturated, unsubstituted, mono- or poly substituted with substituents independently of one another selected from the group consisting of -F, -Cl, -C1-6-alkyl, -C1-6-alkylcnc-CF,. -OH, =0, -OC1-6-alkyl, -C1-6-alkylene-OH, -C1-6- alkylene-O-C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, -NHC(=O)O-C1-6-alkyl, -N(C1-6-alkyl)C(=0)0-C1-6- alkyl, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C1-6-alkylene- N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=0)-C1-6-alkyl, -C(=O)OH, -C(=0)0-C1-6-alkyl, - C(=O)O-C1-6-alkylene-CF3, -C(=O)NH2, -C(=O)NH(C1-6-alkyl), -C(=O)N(C1-6-alkyl)2, -S(=O)2C1-6-alkyl, - phenyl, -C1-6-alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5- 14-membered heteroaryl, unsubstituted;-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -Cl, -C1-6-alkyl, -C1-6-alkylcnc-CF,. -OH, =0, -OC1-6-alkyl, -C1-6-alkylene-OH, -C1-6-alkylene-O-C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, -NHC(=O)O-C1-6-alkyl, - N(C1-6-alkyl)C(=O)O-C1-6-alkyl, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH- C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=0)-C1-6-alkyl, -C(=O)OH, - C(=0)0-C1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)NH2, -C(=O)NH(C1-6-alkyl), -C(=O)N(C1-6-alkyl)2, - S(=O)2C1-6-alkyl, -phenyl, -C1-6-alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5-14-membered heteroaryl, unsubstituted;3-14-membered cycloalkyl or -C1-6-alkylene-(3-14-membered cycloalkyl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 3-14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, in each case saturated or unsaturated, in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -Cl, -C1-6-alkyl, -C1-6-alkylcnc-CF,. -OH, =0, -OC1-6-alkyl, -C1-6- alkylene-OH, -C1-6-alkylene-O-C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, -NHC(=0)0-C1-6-alkyl, -N(C1-6- alkyl)C(=0)0-C1-6-alkyl, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=0)-C1-6-alkyl, -C(=O)OH, - C(=O)O-C1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)NH2, -C(=O)NH(C1-6-alkyl), -C(=O)N(C1-6-alkyl)2, - S(=O)2C1-6-alkyl, -phenyl, -C1-6-alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5-14-membered heteroaryl, unsubstituted;3-14-membered heterocycloalkyl or -C1-6-alkylene-(3-14-membered heterocycloalkyl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 3-14-membered heterocycloalkyl in each case is selected from the group consisting of azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxalidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7- azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-lH-pyrrolizine, hexa- hydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[l,2-a]pyrazin; in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -Cl, -C1-6-alkyl, -C1-6-alkylcnc-CF,. -OH, =0, -OC1-6-alkyl, -C1-6-alkylene-OH, -C1-6-alkylene-O- C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, -NHC(=0)0-C1-6-alkyl, -N(C1-6-alkyl)C(=O)O-C1-6-alkyl, -C1-6- alkylene-NHC(=0)0-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=O)-C1-6-alkyl, -C(=O)OH, -C(=O)O-C1-6-alkyl, -C(=O)O-C1-6- alkylene-CF3, -C(=0)NH2, -C(=O)NH(C1-6-alkyl), -C(=O)N(C1-6-alkyl)2, -S(=O)2C1-6-alkyl, -phenyl, -C1-6- alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5-14-membered heteroaryl, unsubstituted;-phenyl unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -Cl, -CN, -C1-6-alkyl, -C1-6-alkylene-CF3, -OH, =0, -OC1-6-alkyl, -C1-6-alkylene-OH, -C1- 6-alkylene-O-C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, -NHC(=O)O-C1-6-alkyl, -N(C1-6-alkyl)C(=0)0-C1-6-alkyl, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C1-6-alkylene- N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=0)-C1-6-alkyl, -C(=O)OH, -C(=0)0-C1-6-alkyl, - C(=O)O-C1-6-alkylene-CF3, -C(=0)NH2, -C(=O)NH(C1-6-alkyl), -C(=O)N(C1-6-alkyl)2, -S(=O)2C1-6-alkyl, - phenyl, -C1-6-alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5- 14-membered heteroaryl, unsubstituted;5-14-membered heteroaryl or -C1-6-alkylene-(5-14-membered heteroaryl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 5-14-membered heteroaryl in each case is selected from the group consisting of benzimidazole, benzisoxazole, benzoazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furane, furazane, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [l,2,4]triazolo[4,3-a]pyrimidine; in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -Cl, -CN, -C1-6-alkyl, -C1-6-alkylene-CF3, - OH, =0, -OC1-6-alkyl, -C1-6-alkylene-OH, -C1-6-alkylene-O-C1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, - NHC(=0)0-C1-6-alkyl, -N(C1-6-alkyl)C(=O)O-C1-6-alkyl, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C(=0)- C1-6-alkyl, -C(=O)OH, -C(=O)O-C1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)NH2, -C(=O)NH(C1-6-alkyl), - C(=O)N(C1-6-alkyl)2, -S(=O)2C1-6-alkyl, -phenyl, -C1-6-alkylene-phenyl, 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted; and 5-14-membered heteroaryl, unsubstituted.

[0066] In an embodiment, R10, R10’ , and / or R10’’ independently represent-H;-S(=O)2C1-6-alkyl, saturated, unsubstituted, monosubstituted or polysubstituted with -F;-S(=O)2(3- 14-membered cycloalkyl), saturated, unsubstituted;-C1-6-alkyl, saturated, unsubstituted, monosubstituted or disubstituted with substituents independently of one another selected from the group consisting of -OH, =0, -NH2, -NHC1-6-alkyl, -N(C1-6-alkyl)2, -OC1-6-alkyl, -C1-6- alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C(=O)NH2, -C(=O)-NH-C1-3-alkyl, -C(=O)-N(C1-3-alkyl)2, -phenyl unsubstituted;3-14-membered cycloalkyl or -C1-6-alkylene-(3-14-membered cycloalkyl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 3-14-membered cycloalkyl is saturated, unsubstituted, monosubstituted or disubstituted with substituents independently of one another selected from the group consisting of -C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C1-6-alkylene-OH, -C1-6-alkylene- NHC(=O)O-C1-6-alkyl, -OH, -OC1-6-alkyl, -NH2, -N(C1-6-alkyl)2, -NHC(=O)O-C1-6-alkyl;3-14-membered heterocycloalkyl or -C1-6-alkylene-(3-14-membered heterocycloalkyl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 3-14-membered heterocycloalkyl in each case is selected from azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydro- pyrrolo[l,2-a]pyrazin, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-lH- pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1 -dioxothiacyclohexane, in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -OH, =0, -C1-6-alkyl, -C1-6-alkylcnc-CF,. -C1-6-alkylene-OH, -C1-6-alkylene-O-C1-6- alkyl, -NH2, -N(C1-6-alkyl)2, -C1-6-alkylene-NH2, -C1-6-alkylene-N(C1-6-alkyl)2, -C(=0)-C1-6-alkyl, -C(=O)OH, - C(=0)0-C1-6-alkyl, -C(=O)O-C1-6-alkylene-CF3, -C(=O)NH2, -C(=O)NH(C1-6-alkyl), -S(=O)2C1-6-alkyl, oxetanyl, pyrimidinyl, -C1-6-alkylene-phenyl;-phenyl unsubstituted;5-14-membered heteroaryl or -C1-6-alkylene-(5-14-membered heteroaryl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 5-14-membered heteroaryl in each case is selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [l,2,4]triazolo[4,3-a]pyrimidine, in each case unsubstituted, monosubstituted or disubstituted with substituents independently of one another selected from the group consisting of -C1-6-alkyl, -OH.

[0067] In some embodiments, R3represents -H.

[0068] In some embodiments, , R3represents a residue selected from the group consisting of:

[0069] In some embodiments, R3represents a residue -CR'R"-(CH2)m-OH, wherein m is an integer of from 1 to6, preferably from 1 to 3; and wherein R' and R" independently of one another represent -H, -C1-3-alkyl, -CF3, - CF2H, -CFH2, -C1-3-alkylene-CF3, -C1-3-alkylene-CF2H, -C1-3-alkylene-CFH2, -C1-3-alkylene-O-C1-3-alkyl, -C1-3- alkylene-OH, -C(=O)-NH2, or C(=O)-NH-C1-3-alkyl; preferably -H, -CH3, -C1-3-alkylene-OH, -C(=O)-NH2, or C(=O)-NH-C1-3-alkyl. In a preferred embodiment, at least R' or R" does not represent -H. In an embodiment, neither R' nor R" represents -H.

[0070] In other embodiments, R10, R10’, and / or R10’’ independently represent a 3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0071] In some embodiments, R10, R10’, and / or R10” independently represent a 3-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted; or a 3 -membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted. In some embodiments, R3represents, or R10, R10’, and / or R10” represent, a residue selected from the group consisting of:

[0072] In some embodiments, R3, R10, R10’, and / or R10’’ independently represent a 3-14-membered cycloalkyl (in some cases a 4-membered cycloalkyl), saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 3-14-membered heterocycloalkyl (in some cases a 4-membered heterocycloalkyl), saturated or unsaturated, unsubstituted, mono- or polysubstituted. In preferred embodiments, R3, R10, R10’, and / or R10” independently represent a residue selected from the group consisting of:

[0073] In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue according to general formula (A),wherein mAis 0 or 1;YAis selected from -O-, -NRA6- and -CRA7RA8-; andRA1, RAIRA3R \4 RAS R \6 RA? RAS independently of one another represent -H, F, -C1-3-alkyl, -C1-3- alkylene-OH, -C1-3-alkylene-NH2, -C1-3-alkylene-NH(C1-3-alkyl), -C1-3-alkylene-N(C1-3-alkyl)2, -C1-3-alkylene- NH(C1-3-alkylene-CF3), -C1-3-alkylene-C(=O)NH2, -C1-3-alkylene-NH-C(=O)OC1-4-alkyl, -C(=O)NH2, -C(=O)- NH-C1-3-alkyl, -C(=O)-N(C1-3-alkyl)2, -3-oxetanyl, or -CHF2; preferably, RA1, RA2. RAJ. RA4, RAS, RA6, RA7, and RA8independently of one another represent -H, F, -C1-3-alkyl, -C1-3-alkylene-OH, -C1-3-alkylene-NH2, -C1-3- alkylene-NH(C1-3-alkyl), -C1-3-alkylene-N(C1-3-alkyl)2, -C1-3-alkylene-NH(C1-3-alkylene-CF3), -C1-3-alkylene- C(=O)NH2, -C1-3-alkylene-NH-C(=O)OC1-4-alkyl, -C(=O)NH2, -C(=O)-NH-C1-3-alkyl, -C(=O)-N(C1-3-alkyl)2, or -3-oxetanyl; or RA7and RA8together with the carbon atom to which they are attached form a ring and represent - CH2OCH2-, -CH2OCH2CH2- or -CH2CH2OCH2CH2-, -CH2NHCH2-, -CH2NHCH2CH2- or -CH2CH2NHCH2CH2-.

[0074] In some embodiments, R3or R10, R10’, and / or R10” independently represent a residue according to general formula (A) as defined above, wherein mAis 0 or 1;YAis selected from -O- and -CRA7RA8-; andRA1, RA2. RA3, RA4, RAS, RA7, and RA8independently of one another represent -H, -C1-3-alkylene-OH, -C1-3- alkylene-N(C1-3-alkyl)2, -C(=O)NH2, or -CHF2; preferably RA1, RA2, RA3, RA4, RAS, RA7, and RA8independently of one another represent -H, -C1-3-alkylene-OH, -C1-3-alkylene-N(C1-3-alkyl)2, or -C(=O)NH2; preferably with the proviso that only one of RA1, RA2. RAJ. RA4, RAS, RA7, and RA8represents a residue that is not -H.

[0075] In some embodiments, R3or R4represent a residue according to general formula (A) as defined above,wherein mAis 0 or 1;YAis selected from -O- and -CRA7RA8-; and

[0076] In some embodiments, R3, R10, R10’, and / or R10’’ independently represent a 3-14-membered cycloalkyl (in some cases, a 5-membered cycloalkyl), saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 3-14-membered heterocycloalkyl (in some cases, a 5-membered heterocycloalkyl), saturated or unsaturated, unsubstituted, mono- or poly substituted; or a 5-14-membered heteroaryl (in some cases, a 5-membered heteroaryl), unsubstituted, mono- or polysubstituted. In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue selected from the group consisting of:

[0077] In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue according to general formula (B),whereinYBis selected from -O-, -NRB8- and -CRB9RB10-; andRB1, RB2, RB3, RB4, RBS, RB6, RB7, RB8, RB9and RB1° independently of one another represent -H, -F, -OH, -C1-3- alkyl, -C1-3-alkylene-OH, -C1-3-alkylene-O-C1-3-alkyl, -C1-3-alkylene-CF3, -C1-s-alkylene-COzH, -C1-3-alkylene- C(=O)O-C1-3-alkyl, -C(=O)NH2, -C(=O)NH-C1-3-alkyl, or -C(=O)N(C1-3-alkyl)2; orRB2and RB3together represent =0; or RB4and RBStogether represent =0.

[0078] In some embodiments, R3or R10, R10’, and / or R10” independently represent a residue according to general formula (B) as defined above, whereinYBis selected from -O- and -NRB8-; andRB1, RB2, RB3, RB4, RBS, RB6, RB7, RB8independently of one another represent -H, -F, -C1-3-alkyl, -C1-3-alkylene- OH, -C1-3-alkylene-CF3 or -C(=O)NH2; or RB2and RB3together represent =0; or RB4and RBStogether represent =0; preferably with the proviso that only 1, 2 or 3 of RA1, RA2, RA3, RA4, RAS, RA7, and RA8represent a residue that is not -H; preferably with the proviso that at least one of RA1, RA2, RA3, RA4, RAS, RA7, and RA8represent a residue that is not -H.

[0079] In some embodiments, R3, R10, R10’, and / or R10’’ independently represent a 3-14-membered cycloalkyl (in some cases, a 6-membered cycloalkyl), saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 3-14-membered heterocycloalkyl (in some cases, a 6-membered heterocycloalkyl), saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 6-14-membered aryl (in some cases, a 6-membered aryl), unsubstituted, mono- or poly substituted; or a 5-14-membered heteroaryl (in some cases, a 6-membered heteroaryl), unsubstituted, mono- or poly substituted. In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue selected from the group consisting of:

[0080] In some embodiments, R3, R10, R10’ , and / or R10” independently represent a residue according to general formula (C),-H, -F, -OH, -C(=O)OC1-3-alkyl, -NH2, -NH(C1-3-alkyl), -N(C1-3-alkyl)2, -C1-3-alkyl, -C1-3-alkylene-OH, -C1-3- alkylene-, -C(=O)NH2, -C(=O)NH-C1-3-alkyl, or -C(=O)N(C1-3-alkyl)2: or RC2and RC3together represent =0; orRC4and Rcstogether represent =0; or RC9and RC10together represent =0; or RC11and RC12together represent=0.

[0081] In some embodiments, R3or R10, R10’, and / or R10” independently represent a residue according to general formula (C) as defined above, wherein YC1is selected from -O- or -NRC8- and YC2represents -CRcllRcl2-; or YC1represents -CRC9RC10- and YC2is selected from -0-, and -NRC8-;RC1, RC2, RC3, RC4, RC5, RC6, RC7, RC8,RC9, RC10, RC11and RC12independently of one another represent -H, -F ,-C1-3-alkyl, -C1-3-alkylene-OH, or -C(=0)NH2; preferably with the proviso that only 1, 2 or 3 of RC1, RC2, RC3, RC4, RC5, RC6, RC7, RC8,RC9, RC10, Rcl1and RC12represent a residue that is not -H; preferably with the proviso that at least one of RC1, RC2, RC3, RC4, Rcs, RC6, RC7, RC8,RC9, RC10, RC11and RC12represent a residue that is not -H.

[0082] In some embodiments, R3, R10, R10’, and / or R10” independently represent a 7-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 7-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted. In some embodiments, R3, R10, R10’, and / or R10” independently represent the residue:

[0083] In some embodiments, R3, R10, R10’, and / or R10’’ independently represent a 3-14-membered cycloalkyl (in some cases, a 4, 5 or 6-membered cycloalkyl), saturated or unsaturated, unsubstituted, mono- or poly substituted; wherein said 3-14-membered cycloalkyl is connected through -C1-C6-alkylene-, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 3-14-membered heterocycloalkyl (in some cases, a 4, 5 or 6-membered heterocycloalkyl), saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is connected through -C1-C6-alkylene-, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 6-14-membered aryl (in some cases, a 6-membered aryl), unsubstituted, mono- or polysubstituted; wherein said 36-14-membered aryl is connected through -C1-C6-alkylene-, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5-14-membered heteroaryl (in some cases, a 5 or 6- membered heteroaryl), unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is connected through -C1-C6-alkylene-, saturated or unsaturated, unsubstituted, mono- or poly substituted. In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue selected from the group consisting of:

[0084] In some embodiments, R3, R10, R10’, and / or R10’’ independently represent a 5-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 5-membered heterocycloalkyl is connected through -C1-C6-alkylene-, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-membered heteroaryl is connected through -C1-C6-alkylene-, saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0085] In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue selected from the group consisting of:

[0086] In some embodiments, R3, R10, R10’, and / or R10’’ independently represent(i) a residue -CR'R"-(CH2)m-OH, wherein m is an integer of from 1 to 6, preferably from 1 to 3; and wherein R' and R" independently of one another represent -H, -C1-3-alkyl, -CF3, -CF2H, -CFH2, -C1-3-alkylene-CF3, -C1-3-alkylene-CF2H, -C1-3-alkylene-CFH2, -C1-3-alkylene-O-C1-3-alkyl, or -C1-3-alkylene-OH; preferably -H, -CH3, or -C1-3-alkylene-OH. In an embodiment, at least R' or R" does not represent -H. In a preferred embodiment, neither R' nor R" represents -H; or(ii) a residue according to general formula (D),wherein mDand nDindependently of one another are 0, 1, 2, or 3; preferably with the proviso that mD+ nD< 3;YD1is selected from -O-, -S(=O)2-, -S(=O)(=NH)-, -NRD8- and -CRD9RD10- and YD2represents -CRD11RD12- ; or YD1is selected from -O-, -S(=O)2-, -NRD8- and -CRD9RD1°- and YD2represents -CRD11RD12-; or YD1represents -CRD9RD1°- and YD2is selected from -O-, -S(=O)2-, and -NRD8-;RD1, RD2, RD3, RD4, RDS, RD6, RD7, RD8,RD9, RD1°, RD11and RD12independently of one another represent -H, -F , -OH, -C1-3-alkylene-OH, -C(=O)NH2, -C1-3-alkylene-C(O)NH2, -C(=O)O-C1-3-alkyl, -NH2, -C1-3- alkylene-NH2, -NH(C1-3-alkyl), -N(C1-3-alkyl)2, -NH(C1-3-alkylene-CF3), -C1-3-alkylene-OCH3, -C1-3-alkyl, - C1-s-alkylene-CFs: or RD2and RD3together represent =0; or RD4and RDStogether represent =0; or RD9and RD10together represent =0; or RD11and RD12together represent =0; preferably wherein mDand nDindependently of one another are 0, 1, 2 or 3; preferably with the proviso that mD+ nD< 3;YD1is selected from -0-, -NRD8- and -CRD9RD1°- and YD2represents -CRD11RD12-; or YD1represents - CRD9RD1°- and YD2is selected from -O- and -NRD8-;RD1, RD2, RD3, RD4, RDS, RD6, RD7, RD8,RD9, RD1°, RD11and RD12independently of one another represent -H, -F , -OH, -C1-3-alkylene-OH, -C(=O)NH2, -CH2NH2, -CH2N(CH3)2, -NHCH2CF3, -CH3, or -CH2CF3: or RD2and RD3together represent =0; or RD4and RDStogether represent =0; or RD9and RD10together represent =0; or RD11and RD12together represent =0; preferably with the proviso that only 1, 2 or 3 of RD1, RD2, RD3, RD4, RD5, RD6, RD7, RD8,RD9, RD10, RD11and RD12represent a residue that is not -H; preferably with the proviso that at least one of RD1, RD2, RD3, RD4, RDS, RD6, RD7, RD8,RD9, RD1°, RD11and RD12represent aresidue that is not -H.

[0087] In some embodiments, R3, R10, R10’, and / or R10” independently represent a residue selected from the group consisting of:

[0088] In an embodiment of the benzofuran derivative according to the invention R5and R5' independently of one another represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14- membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

[0089] In an embodiment, R5and R5' independently of one another represent -H, -C1-C6-alkyl, or -C1-C6- alkylene-N(Ci -C6-alkyl)2.

[0090] In an embodiment of the benzofuran derivative according to the invention, at least one of R5and R5' is not -H.

[0091] In an embodiment of the benzofuran derivative according to the invention, R5and R5' are both -H.

[0092] In some embodiments, R5represents -H and R5' represents a residue selected from the group consisting of -H, -C1-3-alkyl, -CF3, -CF2H, -CFH2, -C1-3-alkylene-CF3, -C1-3-alkylene-CF2H, -C1-3-alkylene-CFH2, and -C1-3- alkylene-OH; in some cases, -H or C1-3-alkyl.

[0093] In an embodiment of the benzofuran derivative according to the invention R6and R7independently of one another represent-H;-F, -Cl, -Br, -I, -OH, -SH, -SF5, -CN, -NO2, -C(=O)OH, -NH2;-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-O-C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-NHC1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-N(C1-6-alkyl)2, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C(=O)OC1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-OC(=O)C1-6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;-C1-6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted.

[0094] In an embodiment, R6and R7independently of one another represent-H, -F, -Cl, -Br, -I, -OH, -SH, -SF5, -CN, -NO2, -C(=O)OH, -NH2,-C1-6-alkyl, -CF3, -CHF2, -CH2F,-O-C1-6-alkyl, -OCF3, -OCHF2, -OCH2F,-NHC1-6-alkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, - C(=O)OH, -NH2, and -C(=O)NH2;-N(C1-6-alkyl)2 unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, - C(=O)OH, -NH2, and -C(=O)NH2;-C(=0)0C1-6-alkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2;-0C(=0)C1-6-alkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2; or-C1-6-heteroalkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, - C(=O)OH, -NH2, and -C(=O)NH2.

[0095] In some embodiments, R6and R7independently of one another represents a residue selected from the group consisting of -H, -F, -Cl, -Br, -I, -CN, C1-3-alkyl, -CF3, -CF2H, and -CFH2; preferably -H or -F.

[0096] In some embodiments of the benzofuran derivative according to the invention R7represents -H, -F, -Cl, - CN, or -C1-C6-alkyl.

[0097] In an embodiment of the benzofuran derivative according to the invention, R7does not represent -H.

[0098] In some embodiments, R7represents a residue selected from the group consisting of -H, -F, -Cl, -CN or -CH3; preferably -H, -F, -CN or -CH3

[0099] In some embodiments of the benzofuran derivative according to the invention R6represents -H, -F, -Cl, - CN, or -C1-C6-alkyl.

[0100] In an embodiment of the benzofuran derivative according to the invention R6does not represent -H.

[0101] In some embodiments, R6represents a residue selected from the group consisting of -H, -F, -Cl, -CN or CH3; preferably -H, or -F

[0102] In some embodiments, R6represents a residue selected from the group consisting of -H or(i) R6and R7each represent -H; or(ii) one of R6and R7represents -H and the other of R6and R7independently of one another represent -F, -Cl, - CN, or -CH3.

[0104] In some embodiments of the invention, the benzofuran derivative is selected from the group consisting of:Cpd 1 - N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran- 3 -carboxamide;Cpd 2 - N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(cis-2-phenylcyclopropyl)benzofuran-3 - carboxamide;Cpd 3 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 4 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyridin-3- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 5 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-2-(pyridin-3- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 6 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyridin-4- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 7 - 5-(trans-[ 1 , 1 ’-bi(cyclopropan)] -2-yl)-N-((S)- l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 8 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-cyclopentylcyclopropyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 9 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-2-(l-methyl-lH-pyrazol-5- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 10 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(l-methyl-lH-pyrazol-5- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 11 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran- 3 -carboxamide;Cpd 12 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2,2-difluoro-3-phenylcyclopropyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 13 - N-(4,4-difluoro- 1 -hydroxy-2-methylbutan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3 - carboxamide;Cpd 14 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 15 - 2-methyl-5-(trans-2-phenylcyclopropyl)-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3-carboxamide;Cpd 16 - N-(l,3-dimethoxy-2-methylpropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 17 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 18 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(trans-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 19 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(cis-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 20 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-6-fluoro-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 21 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 22 - N-(3-hydroxy-2-methyl-l-(methylamino)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 23 - N-(3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 24 - N-(l-(dimethylamino)-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 25 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 26 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2,2-dimethyl-3-(pyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 27 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(3-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 28 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(4-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 29 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(5-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 30 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(6-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 31 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyrazin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 32 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3- carboxamide;Cpd 33 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3- carboxamide;Cpd 34 - N-(l-amino-3-methoxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 35 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(l-methyl-lH-pyrazol-4- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 36 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 37 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(trans-2-methyl-2-(pyridin-2-yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 38 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-6-fluoro-2-methyl-5-(trans-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 39 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-l-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 40 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-l-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 41 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(dimethylcarbamoyl)cyclopropyl)- 2-methy lbenzofuran-3 -carboxamide ;Cpd 42 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(trifluoromethyl)cyclopropyl)benzofuran-3-carboxamide;Cpd 43 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(3- (trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 44 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(4-(trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 45 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(5-(trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 46 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(6- (trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 47 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyrimidin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 48 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(4-methylpyrimidin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 49 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(l,3,5-trimethyl-lH- pyrazol-4-yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 50 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(3-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 51 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(4-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 52 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(5-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 53 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(6-methoxypyridin-2-yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 54 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenylcyclopropyl)benzofuran- 3 -carboxamide;Cpd 55 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cis-2-cyclopentylcyclopropyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 56 - N-(l-amino-3-butoxy-l-oxopropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 57 - N-(l-amino-3-hydroxy-2-(hydroxymethyl)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 58 - N-( 1 -amino-2-(hydroxymethyl)- 1 -oxobutan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran- 3 -carboxamide;Cpd 59 - N-(l-amino-3-(3-hydroxypropoxy)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 60 - N-(l-amino-4,4-difluoro-2-(hydroxymethyl)-l-oxobutan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 61 - N-(l-amino-3-(azetidin-3-ylmethoxy)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 62 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((trans(cis)-bicyclo[3.1.0]hexan-3-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 63 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cis(cis)-bicyclo[3.1.0]hexan-3-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 64 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-3-(trifluoromethyl)cyclobutoxy)benzofuran-3-carboxamide;Cpd 65 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-3-(trifluoromethyl)cyclobutoxy)benzofuran-3-carboxamide;Cpd 66 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclopentyloxy)-2-methylbenzofuran-3- carboxamide;Cpd 67 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((2,3-dihydro-lH-inden-2-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 68 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclohexyloxy)-2-methylbenzofuran-3- carboxamide;Cpd 69 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((octahydropentalen-2- y l)oxy )benzofuran-3 -carboxamide ;Cpd 70 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(((ls,4R)-4-(trifluoromethyl)cyclohexyl)oxy)benzofuran-3 -carboxamide ;Cpd 71 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(((lr,4S)-4-(trifluoromethyl)cyclohexyl)oxy)benzofuran-3 -carboxamide ;Cpd 72 - 5-((6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)oxy)-2-methyl-N-(4,4,4-trifluoro-l-hydroxybutan-2- yl)benzofuran-3-carboxamide;Cpd 73 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((6,7-dihydro-5H-cyclopenta[b]pyridin-7- yl)oxy)-2-methylbenzofuran-3-carboxamide;Cpd 74 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-5-((6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 75 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((6,7-dihydro-5H-cyclopenta[b]pyridin-5- yl)oxy)-2-methylbenzofuran-3-carboxamide;Cpd 76 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((5,6,7,8-tetrahydroquinolin-8- y l)oxy )benzofuran-3 -carboxamide ;Cpd 77 - 2-methyl-5-((5,6,7,8-tetrahydroquinolin-8-yl)oxy)-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran- 3 -carboxamide;Cpd 78 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((2,3-dihydrobenzofuran-7-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 79 - 5-((2,3-dihydrobenzofuran-7-yl)oxy)-N-(3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 80 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-phenoxybenzofuran-3- carboxamide;Cpd 81 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3- carboxamide;Cpd 82 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(m-tolyloxy)benzofuran-3- carboxamide;Cpd 83 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(p-tolyloxy)benzofuran-3- carboxamide;Cpd 84 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(2-methoxyphenoxy)-2-methylbenzofuran- 3 -carboxamide;Cpd 85 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-methoxyphenoxy)-2-methylbenzofuran- 3 -carboxamide;Cpd 86 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-methoxyphenoxy)-2-methylbenzofuran- 3 -carboxamide;Cpd 87 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-(trifluoromethy l)phenoxy )benzofuran-3 -carboxamide ;Cpd 88 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-(trifluoromethy l)phenoxy )benzofuran-3 -carboxamide ;Cpd 89 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-(trifluoromethy l)phenoxy )benzofuran-3 -carboxamide ;Cpd 90 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((l-isopropyl-lH-pyrazol-4-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 91 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(pyridin-3-yloxy)benzofuran-3- carboxamide;Cpd 92 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((2-methylpyridin-3- y l)oxy )benzofuran-3 -carboxamide ;Cpd 93 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((6-methylpyridin-3- y l)oxy )benzofuran-3 -carboxamide ;Cpd 94 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(m-tolyloxy)benzofuran-3-carboxamide;Cpd 95 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3-carboxamide;Cpd 96 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(m-tolyloxy)benzofuran-3-carboxamide;Cpd 97 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3-carboxamide;Cpd 98 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(o-tolyloxy)benzofuran- 3 -carboxamide;Cpd 99 - 6-fluoro-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3- carboxamide;Cpd 100 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-6-fluoro-2-methyl-5-(o-tolyloxy)benzofuran-3- carboxamide;Cpd 101 - (S)-N-(l-amino-3 -hydroxy -2 -methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-phenoxybenzofuran-3- carboxamide;Cpd 102 - N-( 1,3 -dihydroxy -2 -methylpropan-2-yl)-6-fluoro-2-methyl-5-phenoxybenzofuran-3 -carboxamide;Cpd 103 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-phenoxybenzofuran-3-carboxamide;Cpd 104 - N-(3-hydroxy-2-methyl-l-(methylamino)-l-oxopropan-2-yl)-2-methyl-5-phenoxybenzofuran-3- carboxamide;Cpd 105 - N-(3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)-2-methyl-5-phenoxybenzofuran-3-carboxamide;Cpd 106 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3,3-difluorocyclohexyl)-2 -methylbenzofuran- 3 -carboxamide;Cpd 107 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-cyclopropylphenyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 108 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-cyclopropylphenyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 109 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-phenylazetidin-l- yl)benzofuran-3-carboxamide;Cpd 110 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-cyclopropyl-lH-pyrazol-4-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 111 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenyl-lH-l,2,3-triazol-4- yl)benzofuran-3-carboxamide;Cpd 112 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(5-cyclopropylpyridin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 113 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 114 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(5-cyclopropylpyrazin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 115 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-cyclopropylpyridin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 116 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(5-cyclopropylpyridin-3-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 117 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 118 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-phenylpiperazin-l- yl)benzofuran-3-carboxamide;Cpd 119 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(quinolin-3-yl)benzofuran-3- carboxamide;Cpd 120 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(lH-benzo[d]imidazol-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 121 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2 -methy l-5-( 1 -methyl- IH-benzo [d]imidazol-2-yl)benzofuran-3 -carboxamide;Cpd 122 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-(4-cyclobutylphenyl)-2 -methy Ibenzofuran-3 -carboxamide;Cpd 123 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-(oxetan-3- y l)pheny l)benzofuran-3 -carboxamide ;Cpd 124 - 5-(4-cyclopropylphenyl)-N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 125 - 5-(4-cyclopropylphenyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 126 - 5-(4-cyclopropylphenyl)-2-methyl-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 127 - 5-(4-cyclopropylphenyl)-2-methyl-N-(l,l,l-trifhioro-3-hydroxypropan-2-yl)benzofuran-3- carboxamide;Cpd 128 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenyl-lH-pyrazol-4- yl)benzofuran-3-carboxamide;Cpd 129 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-cyclopropyl-2-fluorophenyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 130 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-(l-methyl-lH-pyrazol-4- y l)pheny l)benzofuran-3 -carboxamide ;Cpd 131 - 2-methyl-5-(l-phenyl-lH-pyrazol-4-yl)-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 132 - 5-(4-cyclopropyl-2-fluorophenyl)-2-methyl-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 133 - 2-methyl-5-(4-(l-methyl-lH-pyrazol-4-yl)phenyl)-N-(4,4,4-trifluoro-l-hydroxybutan-2- yl)benzofuran-3-carboxamide;Cpd 134 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-phenyloxetan-3- yl)benzofuran-3-carboxamide;Cpd 135 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-(o-tolyl)oxetan-3- yl)benzofuran-3-carboxamide;Cpd 136 - N-( 1 ,3 -dihydroxy -2 -methylpropan-2-yl)-6-fluoro-2-methyl-5-( 1 -phenyl- lH-pyrazol-5-yl)benzofuran- 3 -carboxamide;Cpd 137 - 5-(3,4-dihydroquinolin-l(2H)-yl)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 138 - 5-(2-cyclopropylphenyl)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-6-fluoro-2-methylbenzofuran-3- carboxamide;Cpd 139 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3,4-dihydroquinolin-l(2H)-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 140 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(l-phenyl-lH-pyrazol-5- yl)benzofuran-3-carboxamide;Cpd 141 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-(3 ,4-dihydroquinolin- 1 (2H)-yl)-6-fluoro-2- methy lbenzofuran-3 -carboxamide ;Cpd 142 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(2-cyclopropylphenyl)-6-fluoro-2- methy lbenzofuran-3 -carboxamide ;Cpd 143 - 5-(3,4-dihydroquinolin-l(2H)-yl)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-6-fluoro-2- methy lbenzofuran-3 -carboxamide ;Cpd 144 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-phenylpyrrolidin-l- yl)benzofuran-3-carboxamide;Cpd 145 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(piperidin-l- ylmethyl)benzofuran-3 -carboxamide;Cpd 146 - 5 -((3 -azabicyclo [3.1.0]hexan-3-yl)methyl)-N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 147 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 148 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(piperidine-l- carbony l)benzofuran-3 -carboxamide ;Cpd 149 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclopentylidenemethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 150 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-benzyl-2-methylbenzofuran-3- carboxamide;Cpd 151 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclohexylmethyl)-2-methylbenzofuran-3- carboxamide;Cpd 152 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenylethyl)benzofuran-3- carboxamide;Cpd 153 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((tetrahydro-2H-pyran-4-yl)methyl)benzofuran-3-carboxamide;Cpd 154 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-methylbenzyl)benzofuran-3- carboxamide;Cpd 155 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-methylbenzyl)benzofuran-3- carboxamide;Cpd 156 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-methylbenzyl)benzofuran-3- carboxamide;Cpd 157 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(2-fluorobenzyl)-2-methylbenzofuran-3- carboxamide;Cpd 158 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-fluorobenzyl)-2-methylbenzofuran-3- carboxamide;Cpd 159 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-fluorobenzyl)-2-methylbenzofuran-3- carboxamide;Cpd 160 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(fluoro(phenyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 161 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2,2,2-trifluoro-l- pheny lethy l)benzofuran-3 -carboxamide ;Cpd 162 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-(cyclopropylmethyl)-2-methylbenzofuran- 3 -carboxamide;Cpd 163 - N-((S)- 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-((2,2-difluorocyclopropyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 164 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-2-ylmethyl)benzofuran- 3 -carboxamide;Cpd 165 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-3 -ylmethyl)benzofuran- 3 -carboxamide;Cpd 166 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-4-ylmethyl)benzofuran- 3 -carboxamide;Cpd 167 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((4,4-difluorocyclohexyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 168 - 5-((4,4-difluorocyclohexyl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 169 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((3-hydroxycyclobutyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 170 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(((lR,3s,5S)-bicyclo[3.1.0]hexan-3- yl)methyl)-2-methylbenzofuran-3-carboxamide;Cpd 171 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(((lR,3r,5S)-bicyclo[3.1.0]hexan-3- yl)methyl)-2-methylbenzofuran-3-carboxamide;Cpd 172 - 5-(((lR,3s,5S)-bicyclo[3.1.0]hexan-3-yl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 173 - 5-(((lR,3r,5S)-bicyclo[3.1.0]hexan-3-yl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 174 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((cis-3- (trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 175 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((trans-3-(trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 176 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-((cis-3-(trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 177 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-((trans-3- (trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 178 - (S)-5-((2-oxaspiro[3.3]heptan-6-yl)methyl)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 179 - 5-((2-oxaspiro[3.3]heptan-6-yl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 180 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(phenylthio)benzofuran-3- carboxamide;Cpd 181 - N-((S)- 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2 -methy l-5-(phenylsulfinyl)benzofuran-3- carboxamide;Cpd 182 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2 -methy l-5-(phenylsulfonyl)benzofuran-3 - carboxamide;Cpd 183 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-(phenylthio)benzofuran-3-carboxamide;Cpd 184 - N-(4,4-difluoro-l -hydroxy -2 -methy lbutan-2-yl)-2-methyl-5-(phenylthio)benzofuran-3 -carboxamide;Cpd 185 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-(pyridin-2-ylthio)benzofuran-3-carboxamide;Cpd 186 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2 -methy l-5-(pyridin-2-ylthio)benzofuran-3 - carboxamide;Cpd 187 - N-( 1 ,3 -dihydroxy -2 -methy lpropan-2-yl)-6-fluoro-2-methyl-5-(phenylthio)benzofuran-3-carboxamide;Cpd 188 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-6-fluoro-2-methyl-5-(phenylthio)benzofuran- 3 -carboxamide;Cpd 189 - 5-(benzylthio)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3-carboxamide;Cpd 190 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(benzylthio)-2-methylbenzofuran-3- carboxamide;Cpd 191 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-((pyridin-2-ylmethyl)thio)benzofuran-3- carboxamide;Cpd 192 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((pyridin-2- y Imethy l)thio)benzofuran-3 -carboxamide ;Cpd 193 - 5-((cyclopropylmethyl)thio)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 194 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-phenethylbenzofuran-3-carboxamide;Cpd 195 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l,l-difluoro-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 196 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-phenylacetyl)benzofuran-3- carboxamide;Cpd 197 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(phenylethynyl)benzofuran-3- carboxamide;Cpd 198 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-(piperidin-l- yl)ethyl)benzofuran-3 -carboxamide ;Cpd 199 - 5-(2-(3-azabicyclo[3.1.0]hexan-3-yl)ethyl)-N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 200 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-(dimethylamino)-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 201 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-hydroxy-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 202 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-methoxy-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 203 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cyclopentyl(methyl)amino)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 204 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cyclopentylamino)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 205 - (S)-N3 -( l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2 -methy l-N5-(pyridin-2-yl)benzofuran-3 ,5- dicarboxamide;Cpd 206 - (S)-N3-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-N5-phenylbenzofuran-3,5- dicarboxamide;Cpd 207 - (S)-N3 -( l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-N5,2-dimethyl-N5-phenylbenzofuran-3 ,5- dicarboxamide;Cpd 208 - (S)-N3 -( l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-N5-cyclopropyl-2 -methy lbenzofuran-3 ,5- dicarboxamide;Cpd 209 - (S)-N3-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-N5-cyclopropyl-N5,2-dimethylbenzofuran- 3,5-dicarboxamide,Cpd 210 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-((cyclopropylmethyl)(methyl)amino)-2- methy lbenzofuran-3 -carboxamide ;Cpd 211 - 5-(benzyl(methyl)amino)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 212 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(benzyl(methyl)amino)-2- methy lbenzofuran-3 -carboxamide ;Cpd 213 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-((cyclopropylmethyl)(isopropyl)amino)-2- methy lbenzofuran-3 -carboxamide; andCpd 214 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cyclopropylmethyl)thio)-2- methy lbenzofuran-3 -carboxamide ; and physiologically acceptable salts of any of these benzofuran derivatives.

[0105] The benzofuran derivative according to the invention is for use in the treatment of pain which is preferably selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is postoperative pain or migraine pain.

[0106] All definitions, embodiments and meanings of X, Cy, RY,RZ, R1, R3, R4, R4' R5, R5, R6, R7, R9(including R9’ and R9”), and R10(including R10’ and R10”) including the disclosed substituents also analogously apply to all benzofuran derivatives according to the invention, which are not necessarily restricted for use in the treatment of pain. Moreover, the meanings of X, Cy, RY,RZ, R1, R3, R4, R4' R5, R5, R6, R7, R9, and R10are also expressly considered to incorporate any exemplified groups in the exemplified compounds at these positions according to Formula I, Formula II, and / or Formula III. Thus, this aspect of the invention relates to the benzofuran derivatives as such, compositions comprising the benzofuran derivatives, medicaments comprising the benzofuran derivatives, and the benzofuran derivatives for use in the prevention and / or treatment of TRPM3 mediated disorders such as pain and / or inflammatory hypersensitivity; and / or for treating or preventing epilepsy or epileptic seizures; and / or for counteracting pain and / or inflammatory hypersensitivity. Preferably, the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is post-operative pain.

[0107] In preferred embodiments of the invention, the benzofuran derivative is selected from the group consisting of cpd 1 to cpd 214as mentioned above and the physiologically acceptable salts thereof.

[0108] Another aspect of the invention relates to a pharmaceutical composition or a medicament comprising a compound according to the invention as described above.

[0109] Reference throughout this specification to "one embodiment" or "an embodiment" or “some embodiments” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may refer to various embodiments compatible with the elements following the phrase(s). Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments. Also, embodiments described for an aspect of the invention may be used for another aspect of the invention and can be combined. Where an indefinite or definite article is used when referring to a singular noun e.g., "a" or "an", "the", this includes a plural of that noun unless something else is specifically stated.

[0110] Similarly, it should be appreciated that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects.

[0111] In each of the following definitions, the number of carbon atoms represents the maximum number of carbon atoms generally optimally present in the substituent or linker; it is understood that where otherwise indicated in the present application, the number of carbon atoms represents the optimal maximum number of carbon atoms for that particular substituent or linker.

[0112] The term “leaving group” or “LG” as used herein means a chemical group which is susceptible to be displaced by a nucleophile or cleaved off or hydrolyzed in basic or acidic conditions. In a particular embodiment, a leaving group is selected from a halogen atom (e.g., Cl, Br, I) or a sulfonate (e.g., mesylate, tosylate, triflate).

[0113] The term "protecting group" refers to a moiety of a compound that masks or alters the properties of afunctional group or the properties of the compound as a whole. The chemical substructure of a protecting group varies widely. One function of a protecting group is to serve as intermediates in the synthesis of the parental drug substance. Chemical protecting groups and strategies for protection / deprotection are well known in the art. See: "Protective Groups in Organic Chemistry", Theodora W. Greene (John Wiley & Sons, Inc., New York, 1991. Protecting groups are often utilized to mask the reactivity of certain functional groups, to assist in the efficiency of desired chemical reactions, e.g., making and breaking chemical bonds in an ordered and planned fashion. Protection of functional groups of a compound alters other physical properties besides the reactivity of the protected functional group, such as the polarity, lipophilicity (hydrophobicity), and other properties which can be measured by common analytical tools. Chemically protected intermediates may themselves be biologically active or inactive.

[0114] Protected compounds may also exhibit altered, and in some cases, optimized properties in vitro and in vivo, such as passage through cellular membranes and resistance to enzymatic degradation or sequestration. In this role, protected compounds with intended therapeutic effects may be referred to as prodrugs. Another function of a protecting group is to convert the parental drug into a prodrug, whereby the parental dmg is released upon conversion of the prodrug in vivo. Because active prodrugs may be absorbed more effectively than the parental drug, prodmgs may possess greater potency in vivo than the parental dmg. Protecting groups are removed either in vitro, in the instance of chemical intermediates, or in vivo, in the case of prodmgs. With chemical intermediates, it is not particularly important that the resulting products after deprotection, e.g., alcohols, be physiologically acceptable, although in general it is more desirable if the products are pharmacologically innocuous.

[0115] The term “heteroatom(s)” as used herein means an atom selected from nitrogen, which can be quatemized; oxygen; sulfur, including sulfoxide and sulfone; and phosphorous, including phosphorates.

[0116] The term “alkyl, saturated or unsaturated” as used herein encompasses saturated alkyl as well as unsaturated alkyl such as alkenyl, alkynyl, and the like, which may be linear or branched. The term “alkyl” as used herein means normal, secondary, or tertiary, linear or branched hydrocarbon with no site of unsaturation. However, it is generally contemplated that in various embodiments reciting “alkyl,” further corresponding embodiments with “alkyl, saturated or unsaturated” are contemplated, and vice versa. Examples are methyl, ethyl, 1 -propyl (n- propyl), 2-propyl (iPr), 1 -butyl, 2-methyl-l-propyl(i-Bu), 2-butyl (s-Bu), 2-dimethyl-2 -propyl (t-Bu), 1 -pentyl (n- pentyl), 2-pentyl, 3 -pentyl, 2-methyl-2 -butyl, 3-methyl-2-butyl, 3 -methyl- 1 -butyl, 2-methyl-l -butyl, 1 -hexyl, 2- hexyl, 3 -hexyl, 2-methy 1-2 -pentyl, 3 -methy 1-2 -pentyl, 4-methy 1-2 -pentyl, 3 -methy 1-3 -pentyl, 2-methy 1-3 -pentyl, 2,3 -dimethy 1-2 -butyl, and 3,3-dimethyl-2-butyl. The term “alkenyl” as used herein means normal, secondary or tertiary, linear or branched hydrocarbon with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond. Examples include, but are not limited to: ethylene or vinyl (-CH=CH2), allyl (- CH2CH=CH2), and 5-hexenyl (-CH2CH2CH2CH2CH=CH2). The double bond may be in the cis or trans configuration. The term “alkynyl” as used herein means normal, secondary, tertiary, linear or branched hydrocarbon with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond. Examples include, but are not limited to: ethynyl (-C=CH). and 1-propynyl (propargyl, -CH2CACH).

[0117] The term “alkylene, saturated or unsaturated” as used herein encompasses saturated alkylene as well as unsaturated alkylene such as alkenylene, alkynylene, alkenynylene and the like. The term "alkylene" as used herein means saturated, linear or branched chain hydrocarbon radical having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkane. Typicalalkylene radicals include, but are not limited to: methylene (-CH2-), 1,2-ethyl (-CH2CH2-), 1,3-propyl (- CH2CH2CH2-), 1,4-butyl (-CH2CH2CH2CH2-), and the like. The term "alkenylene" as used herein means linear or branched chain hydrocarbon radical with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond, and having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkene. The term "alkynylene" as used herein means linear or branched chain hydrocarbon radical with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond, and having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkyne.

[0118] The term “heteroalkyl, saturated or unsaturated” as used herein encompasses saturated heteroalkyl as well as unsaturated heteroalkyl such as heteroalkenyl, heteroalky nyl, heteroalkenynyl and the like. The term “heteroalkyl” as used herein means linear or branched chain alkyl wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by a heteroatom, i.e., an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. This means that one or more -CH3 of said alkyl can be replaced by -NH2and / or that one or more -CH2- of said alkyl can be replaced by -NH-, -O- or -S-. The S atoms in said chains may be optionally oxidized with one or two oxygen atoms, to afford sulfoxides and sulfones, respectively. Furthermore, the heteroalkyl groups in the benzofuran derivatives of the invention can contain an oxo or thio group at any carbon or heteroatom that will result in a stable compound. Exemplary heteroalkyl groups include, but are not limited to, alcohols, alkyl ethers (such as for example -methoxy, -ethoxy, -butoxy ... ), primary, secondary, and tertiary alkyl amines, amides, ketones, esters, alkyl sulfides, and alkyl sulfones. The term “heteroalkenyl” means linear or branched chain alkenyl wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. The term heteroalkenyl thus comprises imines, -O-alkenyl, -NH-alkenyl, - N(alkenyl)2, -N(alkyl)(alkenyl), and -S-alkenyl. The term “heteroalkynyl” as used herein means linear or branched chain alkynyl wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. The term heteroalkynyl thus comprises -cyano, -O-alkynyl, -NH-alkynyl, -N(alkynyl)2, -N(alkyl)(alkynyl), - N(alkenyl)(alkynyl), and -S-alkynyl.

[0119] The term “heteroalkylene, saturated or unsaturated” as used herein encompasses saturated heteroalkylene as well as unsaturated heteroalkylene such as heteroalkenylene, heteroalkynylene, heteroalkenynylene and the like. The term “heteroalkylene” as used herein means linear or branched chain alkylene wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by a heteroatom, i.e., an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. The term “heteroalkenylene” as used herein means linear or branched chain alkenylene wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. The term “heteroalkynylene” as used herein means linear or branched chain alkynylene wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms.

[0120] The term “cycloalkyl, saturated or unsaturated” as used herein encompasses saturated cycloalkyl as well as unsaturated cycloalkyl such as cycloalkenyl, cycloalkynyl and the like. The term “cycloalkyl” as used herein and unless otherwise stated means a saturated cyclic hydrocarbon radical, such as for instance cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbomyl, fenchyl, decalinyl, adamantyl and the like. The term “cycloalkenyl” as used herein means a non-aromatic cyclic hydrocarbon radical with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond. Examples include, but are not limited to cyclopentenyl and cyclohexenyl. The double bond may be in the cis or trans configuration. The term “cycloalkynyl” as used herein means a non-aromatic cyclic hydrocarbon radical with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple. An example is cyclohept- 1-yne. Fused (two shared ring atoms) and spiro (one shared ring atom) systems of two cycloalkyl rings are contemplated under the term “cycloalkyl.” Fused systems of a cycloalkyl ring with a heterocycloalkyl ring are considered as heterocycloalkyl irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkyl ring with an aryl ring are considered as aryl irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkyl ring with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure.

[0121] The term “heterocycloalkyl, saturated or unsaturated” as used herein encompasses saturated heterocycloalkyl as well as unsaturated non-aromatic heterocycloalkyl including at least one heteroatom, i.e., an N, O, or S as ring member. The term “heterocycloalkyl” as used herein and unless otherwise stated means "cycloalkyl" wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. The term “heterocycloalkenyl” as used herein and unless otherwise stated means "cycloalkenyl" wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. The term “heterocycloalkynyl” as used herein and unless otherwise stated means "cycloalkynyl" wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by an oxygen, nitrogen or sulfur atom, with the proviso that said chain may not contain two adjacent O atoms or two adjacent S atoms. Examples of saturated and unsaturated heterocycloalkyl include but are not limited to azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxalidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1 -dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8- azabicyclo[3.2. l]octane, 9-azabicyclo[3.3. l]nonane, hexahydro- IH-pyrrolizine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[l,2-a]pyrazin. Further heterocycloalkyls in the meaning of the invention are described in Paquette, Leo A. "Principles of Modem Heterocyclic Chemistry" (W.A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; "The Chemistry of Heterocyclic Compounds, A series of Monographs" (John Wiley & Sons, New York, 1950 to present), in particular Volumes 13, 14, 16, 19, and 28; Katritzky, AlanR., Rees, C.W. and Scriven, E. "Comprehensive Heterocyclic Chemistry" (Pergamon Press, 1996); and J. Am. Chem. Soc. (1960) 82:5566. When the heterocycloalkyl contains no nitrogen as ring member, it is typically bonded through carbon. When the heterocycloalkyl contains nitrogen as ring member, it may be bonded through nitrogen or carbon. Fused systems of heterocycloalkyl ring with a cycloalkyl ring are considered as heterocycloalkyl irrespective of the ring that is bound to the core structure. Fused systems of a heterocycloalkyl ring with an aryl ring are considered as heterocycloalkyl irrespective of the ring that is bound to the core structure. Fused systems of a heterocycloalkyl ring with a heteroaryl ring are considered as heteroaryl irrespective of thering that is bound to the core structure.

[0122] The term "aryl" as used herein means an aromatic hydrocarbon. Typical aryl groups include, but are not limited to 1 ring (such as phenyl or others), or 2 or 3 rings fused together, radicals derived from benzene, naphthalene, anthracene, biphenyl, and the like. Fused systems of an aryl ring with a cycloalkyl ring are considered as aryl irrespective of the ring that is bound to the core structure. Fused systems of an aryl ring with a heterocycloalkyl ring are considered as heterocycloalkyl irrespective of the ring that is bound to the core structure. Thus, indoline, dihydrobenzofuran, dihydrobenzothiophene and the like are considered as heterocycloalkyl according to the invention. Fused systems of an aryl ring with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure.

[0123] The term “heteroaryl” as used herein means an aromatic ring system including at least one heteroatom, i.e., N, O, or S as ring member of the aromatic ring system. Examples of heteroaryl include but are not limited to benzimidazole, benzisoxazole, benzoazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furane, furazane, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [l,2,4]triazolo[4,3- a]pyrimidine.

[0124] By further way of example, carbon bonded heterocyclic rings are bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline.

[0125] Preferred carbon bonded heterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3- pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6- pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl. By way of example, nitrogen bonded heterocyclic rings are bonded at position 1 of an aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3 -pyrroline, imidazole, imidazolidine, 2-imidazoline, 3 -imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, IH-indazole, position 2 of an isoindole, or isoindoline, position 4 of a morpholine, and position 9 of a carbazole, or B-carboline. Preferred nitrogen bonded heterocycles include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1- piperidinyl. Further heteroaryls in the meaning of the invention are described in Paquette, Leo A. "Principles of Modem Heterocyclic Chemistry" (W.A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; "The Chemistry of Heterocyclic Compounds, A series of Monographs" (John Wiley & Sons, New York, 1950 to present), in particular Volumes 13, 14, 16, 19, and 28; Katritzky, Alan R., Rees, C.W. and Scriven, E. "Comprehensive Heterocyclic Chemistry" (Pergamon Press, 1996); and J. Am. Chem. Soc. (1960) 82:5566.

[0126] As used herein with respect to a substituting group, and unless otherwise stated, the terms “monosubstituted”, "disubstituted", "trisubstituted", "polysubstituted" and the like means chemical structures defined herein, wherein the respective moiety is substituted with one or more substituents, meaning that one or more hydrogen atoms of said moiety are each independently replaced with a substituent. For example, -C1-6-alkylthat may be polysubstituted with -F covers -CH2F, -CHF2, -CF3, -CH2CF3, CF2CF3, and the like. Likewise, -C1-6- alkyl that may be polysubstituted with substituents independently of one another selected from -F and -Cl covers -CH2F, -CHF2, -CF3, -CH2CF3, CF2CF3, -CH2CI, -CHCI2, -CCI3, -CH2CCI3, CCI2CCI3, -CHC1F, -CCIF2, -CCI2CF3, -CF2CCI3, -CCIFCCI2F, and the like. Any substituent designation that is found in more than one site in a compound of this invention shall be independently selected.

[0127] In some embodiments, compounds are shown with wedge stereochemical bonds. For example, the wedge stereochemical bonds in cpd 1 (with one wedge pointing out of the plane and the other pointing into the plane) represent a trans configuration, and the wedge stereochemical bonds in cpd 2 (both wedges pointing out of the plane) represent a cis configuration. Neither trans nor cis configuration depicts absolute stereochemistry at the ring junction stereogenic centers, but are inclusive of all possible absolute stereochemistries at the bonded chiral center(s). For example, cpd 1 as depicted in Table 1 includes both the (R,R) and (S,S) absolute configurations of the chiral centers on the cyclopropyl group of the trans stereoisomer. Likewise, cpd 2 as depicted in Table 1 includes both the (S,R) and (R,S) absolute configurations of the chiral centers on the cyclopropyl group of the cis stereoisomer.

[0128] In these or some other embodiments, compounds are shown with bar, rather than wedge, stereochemical bonds. For example, the bar stereochemical bonds at the stereogenic centers of the amide side chain in cpd 1 and cpd 2 do not depict absolute stereochemistry at those centers, but are inclusive of both possible absolute stereochemistries at the bonded stereogenic center(s). For example, cpd 1 and cpd 2 as depicted in Table 1 include both the (R) and (S) absolute configurations of the stereogenic centers at the amide side chain.

[0129] As used herein and unless otherwise stated, the term “solvate” includes any combination which may be formed by a derivative of this invention with a suitable inorganic solvent (e.g., hydrates) or organic solvent, such as but not limited to alcohols, ketones, esters, ethers, nitriles and the like.

[0130] The term “subject” as used herein, refers to an animal including humans, preferably a mammal, most preferably a human, who has been the object of treatment, observation or experiment.

[0131] The term “therapeutically effective amount” as used herein, means that amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation or partial alleviation of the symptoms of the disease or disorder being treated.

[0132] The term “composition” as used herein is intended to encompass a product comprising the specified ingredients in the therapeutically effective amounts, as well as any product which results, directly or indirectly, from combinations of the specified ingredients in the specified amounts.

[0133] The term “antagonist” or “inhibitor” as used herein refers to a compound capable of producing, depending on the circumstance, a functional antagonism of the TRPM3 ion channel, including competitive antagonists, noncompetitive antagonists, desensitizing agonists, and partial agonists.

[0134] For purposes of the invention, the term “TRPM3 -modulated” is used to refer to the condition of being affected by the modulation of the TRPM3 ion channel, including the state of being mediated by the TRPM3 ion channel.

[0135] The term “TRPM3 mediated disorder” as used herein refers to disorders or diseases for which the use of an antagonist of TRPM3 would prevent, treat, (partially) alleviate or improve the symptoms and consist of pain and inflammatory hypersensitivity condition. According to the International Association for the Study of Pain andfor the purpose of the invention, pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Preferably, the TRPM3 mediated disorder is pain which is preferably selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is post-operative pain or migraine pain. For the purpose of the invention, the term "inflammatory hypersensitivity" is used to refer to a condition that is characterized by one or more hallmarks of inflammation, including edema, erythema, hyperthermia, and pain, and / or by an exaggerated physiologic or pathophysiologic response to one or more than one type of stimulation, including thermal, mechanical and / or chemical stimulation.

[0136] The benzofuran derivatives of the invention have been shown to be antagonists of TRPM3 and the invention therefore provides the compounds as such, the compounds for use as a medicine, more specifically for use as a medicine in the prevention or treatment of TRPM3 mediated disorders in a subject with a therapeutically effective amount of a benzofuran derivative of the invention.

[0137] In a preferred embodiment of the invention, the benzofuran derivative of the invention is the sole pharmacologically active compound to be administered for therapy. In another preferred embodiment of the invention, the benzofuran derivative of the invention may be employed in combination with other therapeutic agents for the treatment or prophylaxis of TRPM3 mediated disorders. The invention therefore also relates to the use of a composition comprising:- one or more compounds of the formulae and embodiments herein, and- one or more further therapeutic or preventive agents that are used for the prevention or treatment of TRPM3 mediated disorders as biologically active agents in the form of a combined preparation for simultaneous, separate or sequential use.

[0138] The pharmaceutical composition or combined preparation according to this invention may contain benzofuran derivatives of the invention over a broad content range depending on the contemplated use and the expected effect of the preparation. Generally, the content of the benzofuran derivatives of the invention of the combined preparation is within the range of 0.1 to 99.9% by weight, preferably from 1 to 99% by weight, more preferably from 5 to 95% by weight.

[0139] In view of the fact that, when several active ingredients are used in combination, they do not necessarily bring out their joint therapeutic effect directly at the same time in the mammal to be treated, the corresponding composition may also be in the form of a medical kit or package containing the two ingredients in separate but adjacent repositories or compartments. In the latter context, each active ingredient may therefore be formulated in a way suitable for an administration route different from that of the other ingredient, e.g., one of them may be in the form of an oral or parenteral formulation whereas the other is in the form of an ampoule for intravenous injection or an aerosol.

[0140] Those of skill in the art will also recognize that the benzofuran derivatives of the invention may exist in many different protonation states, depending on, among other things, the pH of their environment. While the structural formulae provided herein depict the compounds in only one of several possible protonation states, it will be understood that these structures are illustrative only, and that the invention is not limited to any particular protonation state - any and all protonated forms of the compounds are intended to fall within the scope of the invention.

[0141] The term "pharmaceutically acceptable salts" as used herein means the therapeutically active non-toxic salt forms which the compounds of formulae herein are able to form. Therefore, the compounds of this inventionoptionally comprise salts of the compounds herein, especially pharmaceutically acceptable non-toxic salts containing, for example, Na+, Li+, K+, Ca2+and Mg2+. Such salts may include those derived by combination of appropriate cations such as alkali and alkaline earth metal ions or ammonium and quaternary amino ions with an acid anion moiety, typically a carboxylic acid. The benzofuran derivatives of the invention may bear multiple positive or negative charges. The net charge of the benzofuran derivatives of the invention may be either positive or negative. Any associated counter ions are typically dictated by the synthesis and / or isolation methods by which the compounds are obtained. Typical counter ions include, but are not limited to ammonium, sodium, potassium, lithium, halides, acetate, trifluoroacetate, etc., and mixtures thereof. It will be understood that the identity of any associated counter ion is not a critical feature of the invention, and that the invention encompasses the compounds in association with any type of counter ion. Moreover, as the compounds can exist in a variety of different forms, the invention is intended to encompass not only forms of the compounds that are in association with counter ions (e.g., dry salts), but also forms that are not in association with counter ions (e.g., aqueous or organic solutions). Metal salts typically are prepared by reacting the metal hydroxide with a compound of this invention. Examples of metal salts which are prepared in this way are salts containing Li+, Na+, and K+. A less soluble metal salt can be precipitated from the solution of a more soluble salt by addition of the suitable metal compound. In addition, salts may be formed from acid addition of certain organic and inorganic acids to basic centers, typically amines, or to acidic groups. Examples of such appropriate acids include, for instance, inorganic acids such as hydrohalogen acids, e.g. hydrochloric or hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, 2-hydroxypropanoic, 2-oxopropanoic, lactic, pyruvic, oxalic (i.e. ethanedioic), malonic, succinic (i.e. butanedioic acid), maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic (i.e. 2- hydroxybenzoic), p-aminosalicylic and the like. Furthermore, this term also includes the solvates which the compounds of formulae herein as well as their salts are able to form, such as for example hydrates, alcoholates and the like. Finally, it is to be understood that the compositions herein comprise benzofuran derivatives of the invention in their unionized, as well as zwitterionic form, and combinations with stoichiometric amounts of water as in hydrates.

[0142] Also included within the scope of this invention are the salts of the parental compounds with one or more amino acids, especially the naturally -occurring amino acids found as protein components. The amino acid typically is one bearing a side chain with a basic or acidic group, e.g., lysine, arginine or glutamic acid, or a neutral group such as glycine, serine, threonine, alanine, isoleucine, or leucine.

[0143] The benzofuran derivatives of the invention also include physiologically acceptable salts thereof. Examples of physiologically acceptable salts of the benzofuran derivatives of the invention include salts derived from an appropriate base, such as an alkali metal (for example, sodium), an alkaline earth (for example, magnesium), ammonium and NX4+(wherein X is -C1-6-alkyl). Physiologically acceptable salts of a hydrogen atom or an amino group include salts of organic carboxylic acids such as acetic, benzoic, lactic, fumaric, tartaric, maleic, malonic, malic, isethionic, lactobionic and succinic acids; organic sulfonic acids, such as methanesulfonic, ethanesulfonic, benzenesulfonic and p-toluenesulfonic acids; and inorganic acids, such as hydrochloric, sulfuric, phosphoric and sulfamic acids. Physiologically acceptable salts of a compound containing a hydroxy group include the anion of said compound in combination with a suitable cation such as Na+and NX4+(wherein X typically is independently selected from -H or a -C1-4-alkyl group). However, salts of acids or bases which are notphysiologically acceptable may also find use, for example, in the preparation or purification of a physiologically acceptable compound. All salts, whether or not derived form a physiologically acceptable acid or base, are within the scope of the invention.

[0144] As used herein and unless otherwise stated, the term "enantiomer" means each individual optically active form of a benzofuran derivative of the invention, having an optical purity or enantiomeric excess (as determined by methods standard in the art) of at least 80% (i.e., at least 90% of one enantiomer and at most 10% of the other enantiomer), preferably at least 90% and more preferably at least 98%.

[0145] The term "isomers" as used herein means all possible isomeric forms, including tautomeric and stereochemical forms, which the compounds of formulae herein may possess, but not including position isomers. Typically, the structures shown herein exemplify only one tautomeric or resonance form of the compounds, but the corresponding alternative configurations are contemplated as well. Unless otherwise stated, the chemical designation of compounds denotes the mixture of all possible stereochemically isomeric forms, said mixtures containing all diastereomers and enantiomers (since the compounds of formulae herein may have at least one chiral center) of the basic molecular structure, as well as the stereochemically pure or enriched compounds. More particularly, stereogenic centers may have either the R- or S -configuration, and multiple bonds may have either cis- or trans-configuration.

[0146] Pure isomeric forms of the said compounds are defined as isomers substantially free of other enantiomeric or diastereomeric forms of the same basic molecular structure. In particular, the term "stereoisomerically pure" or “chirally pure" relates to compounds having a stereoisomeric excess of at least about 80% (i.e., at least 90% of one isomer and at most 10% of the other possible isomers), preferably at least 90%, more preferably at least 94% and most preferably at least 97%. The terms "enantiomerically pure" and "diastereomerically pure" should be understood in a similar way, having regard to the enantiomeric excess, respectively the diastereomeric excess, of the mixture in question.

[0147] Separation of stereoisomers is accomplished by standard methods known to those in the art. One enantiomer of a benzofuran derivative of the invention can be separated substantially free of its opposing enantiomer by a method such as formation of diastereomers using optically active resolving agents ("Stereochemistry of Carbon Compounds," (1962) by E. L. Eliel, McGraw Hill; Lochmuller, C. H., (1975) J. Chromatogr., 113 :(3) 283-302). Separation of isomers in a mixture can be accomplished by any suitable method, including: (1) formation of ionic, diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers, and conversion to the pure enantiomers, or (3) enantiomers can be separated directly under chiral conditions. Under method (1), diastereomeric salts can be formed by reaction of enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine (amphetamine), and the like with asymmetric compounds bearing acidic functionality, such as carboxylic acid and sulfonic acid. The diastereomeric salts may be induced to separate by fractional crystallization or ionic chromatography. For separation of the optical isomers of amino compounds, addition of chiral carboxylic or sulfonic acids, such as camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid can result in formation of the diastereomeric salts. Alternatively, by method (2), the substrate to be resolved may be reacted with one enantiomer of a chiral compound to form a diastereomeric pair (Eliel, E. and Wilen, S. (1994) Stereochemistry of Organic Compounds, John Wiley & Sons, Inc., p. 322). Diastereomeric compounds can be formed by reactingasymmetric compounds with enantiomerically pure chiral derivatizing reagents, such as menthyl derivatives, followed by separation of the diastereomers and hydrolysis to yield the free, enantiomerically enriched compound. A method of determining optical purity involves making chiral esters, such as a menthyl ester or Mosher ester, a- methoxy-a-(trifluoromethyl)phenyl acetate (Jacob III. (1982) J. Org. Chem. 47:4165), of the racemic mixture, and analyzing the NMR spectrum for the presence of the two atropisomeric diastereomers. Stable diastereomers can be separated and isolated by normal- and reverse-phase chromatography following methods for separation of atropisomeric naphthyl-isoquinolines (Hoye, T., WO 96 / 15 l ll).Under method (3), a racemic mixture of two asymmetric enantiomers is separated by chromatography using a chiral stationary phase. Suitable chiral stationary phases are, for example, polysaccharides, in particular cellulose or amylose derivatives. Commercially available polysaccharide based chiral stationary phases are ChiralCel® CA, OA, OB5, OC5, OD, OF, OG, OJ and OK, and Chiralpak® AD, AS, OP(+) and OT(+). Appropriate eluents or mobile phases for use in combination with said polysaccharide chiral stationary phases are hexane and the like, modified with an alcohol such as ethanol, isopropanol and the like. ("Chiral Liquid Chromatography" (1989) W. J. Lough, Ed. Chapman and Hall, New York; Okamoto, (1990) "Optical resolution of dihydropyridine enantiomers by High-performance liquid chromatography using phenylcarbamates of polysaccharides as a chiral stationary phase", J. of Chromatogr. 513:375-378).

[0148] The terms cis and trans are used herein in accordance with Chemical Abstracts nomenclature and include reference to the position of the substituents on a ring moiety. The absolute stereochemical configuration of the compounds of the formulae described herein may easily be determined by those skilled in the art while using well- known methods such as, for example, X-ray diffraction.

[0149] When a compound is crystallized from a solution or slurry, it canbe crystallized in a different arrangement lattice of spaces (this property is called "polymorphism") to form crystals with different crystalline forms, each of which is known as "polymorphs". The term “Polymorph” as used herein, therefore, refers to a crystal form of a compound of Formula (I) or Formula (II), where the molecules are localized in the three-dimensional lattice sites. Different polymorphs of the compound of Formula (I) or Formula (II) may be different from each other in one or more physical properties, such as solubility and dissolution rate, true specific gravity, crystal form, accumulation mode, flowability and / or solid state stability. Etc.

[0150] Benzofuran derivatives of the invention and their physiologically acceptable salts (hereafter collectively referred to as the active ingredients) may be administered by any route appropriate to the condition to be treated, suitable routes including oral, rectal, nasal, topical (including ocular, buccal and sublingual), vaginal and parenteral (including subcutaneous, intramuscular, intranasal, intravenous, intraarterial, intradermal, intrathecal and epidural). The preferred route of administration may vary with for example the condition of the recipient.

[0151] The therapeutically effective amount of the preparation of the compound(s), especially for the treatment of TRPM3 mediated disorders in humans and other mammals or in animals, preferably is a TRPM3 ion channel inhibiting amount of the compounds as defined herein and corresponds to an amount which ensures a plasma level of between Ipg / ml and 100 mg / ml, optionally of 10 mg / ml.

[0152] Suitable dosages of the compounds or compositions of the invention should be used to treat or prevent the TRPM3 mediated disorders in a subject. Depending upon the pathologic condition to be treated and the patient’s condition, the said effective amount may be divided into several sub-units per day or may be administered at more than one day intervals.

[0153] The invention further provides (pharmaceutical) compositions comprising one or more benzofuran derivatives of the invention, more in particular of all the Formula (I) and Formula (II) and other formulas and embodiments described herein and the more particular aspects or embodiments thereof. Furthermore, the invention provides the compounds or (pharmaceutical) compositions of the invention, more in particular of all the Formula (I) and other formulas and embodiments described herein and the more particular aspects or embodiments thereof, for use as a medicine, more in particular for use in the treatment of pain. The TRPM3 mediated disorders are selected from pain and an inflammatory hypersensitivity condition.

[0154] The benzofuran derivatives of the invention may be formulated with conventional carriers and excipients, which will be selected in accord with ordinary practice. Tablets will contain excipients, glidants, fillers, binders and the like. Aqueous formulations are prepared in sterile form, and when intended for delivery by other than oral administration generally will be isotonic. Formulations optionally contain excipients such as those set forth in the "Handbook of Pharmaceutical Excipients" (1986).

[0155] Subsequently, the term "pharmaceutically acceptable carrier" as used herein means any material or substance with which the active ingredient is formulated in order to facilitate its application or dissemination to the locus to be treated, for instance by dissolving, dispersing or diffusing the said composition, and / or to facilitate its storage, transport or handling without impairing its effectiveness. The pharmaceutically acceptable carrier may be a solid or a liquid or a gas which has been compressed to form a liquid, i.e., the compositions of this invention can suitably be used as concentrates, emulsions, solutions, granulates, dusts, sprays, aerosols, suspensions, ointments, creams, tablets, pellets or powders.

[0156] Suitable pharmaceutical carriers for use in the said pharmaceutical compositions and their formulation are well known to those skilled in the art, and there is no particular restriction to their selection within the invention. They may also include additives such as wetting agents, dispersing agents, stickers, adhesives, emulsifying agents, surfac6-active agents, solvents, coatings, antibacterial and antifungal agents, isotonic agents and the like, provided the same are consistent with pharmaceutical practice, i.e., carriers and additives which do not create permanent damage to mammals. The pharmaceutical compositions of the invention may be prepared in any known manner, for instance by homogeneously mixing, coating and / or grinding the active ingredients, in a one-step or multi-steps procedure, with the selected carrier material and, where appropriate, the other additives such as surfac6-active agents, may also be prepared by micronisation, for instance in view to obtain them in the form of microspheres usually having a diameter of about 1 to 10 gm, namely for the manufacture of microcapsules for controlled or sustained release of the active ingredients.

[0157] While it is possible for the benzofuran derivatives to be administered alone it is preferable to present them as pharmaceutical formulations. The formulations, both for veterinary and for human use, of the invention comprise at least one active ingredient, as above described, together with one or more pharmaceutically acceptable carriers therefore and optionally other therapeutic ingredients. The carrier(s) optimally are "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The formulations include those suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients. In general, the formulationsare prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.

[0158] Formulations of the invention suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary or paste.

[0159] A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein. For infections of the eye or other external tissues e.g., mouth and skin, the formulations are optionally applied as a topical ointment or cream containing the active ingredient(s) in an amount of, for example, 0.075 to 20% w / w (including active ingredient(s) in a range between 0.1% and 20% in increments of 0.1% w / w such as 0.6% w / w, 0.7% w / w, etc.), preferably 0.2 to 15% w / w and most preferably 0.5 to 10% w / w. When formulated in an ointment, the active ingredients may be employed with either a paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may include, for example, at least 30% w / w of a polyhydric alcohol, i.e., an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3 -diol, mannitol, sorbitol, glycerol and polyethylene glycol (including PEG400) and mixtures thereof. The topical formulations may desirably include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethyl sulfoxide and related analogs.

[0160] The oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner. While the phase may comprise merely an emulsifier (otherwise known as an emulgent), it desirably comprises a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Optionally, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer. It is also preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations.

[0161] The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Thus, the cream should optionally be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters known as Crodamol CAP may be used, the last three being preferred esters. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and / or liquid paraffin or other mineral oils can be used.

[0162] Formulations suitable for topical administration to the eye also include eye drops wherein the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient. The active ingredient is optionally present in such formulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10% particularly about 1.5% w / w. Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavored basis, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.

[0163] Formulations for rectal administration may be presented as a suppository with a suitable base comprising for example cocoa butter or a salicylate. Formulations suitable for nasal administration wherein the carrier is a solid include a coarse powder having a particle size for example in the range 20 to 500 microns (including particle sizes in a range between 20 and 500 microns in increments of 5 microns such as 30 microns, 35 microns, etc.), which is administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close up to the nose. Suitable formulations wherein the carrier is a liquid, for administration as for example a nasal spray or as nasal drops, include aqueous or oily solutions of the active ingredient. Formulations suitable for aerosol administration may be prepared according to conventional methods and may be delivered with other therapeutic agents.

[0164] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

[0165] Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.

[0166] Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as herein above recited, or an appropriate fraction thereof, of an active ingredient.

[0167] It should be understood that in addition to the ingredients particularly mentioned above the formulations of this invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents.

[0168] Benzofuran derivatives of the invention can be used to provide controlled release pharmaceutical formulations containing as active ingredient one or more benzofuran derivatives of the invention ("controlled release formulations") in which the release of the active ingredient can be controlled and regulated to allow less frequency dosing or to improve the pharmacokinetic or toxicity profile of a given invention compound. Controlled release formulations adapted for oral administration in which discrete units comprising one or more benzofuran derivatives of the invention can be prepared according to conventional methods.

[0169] Another embodiment of this invention relates to various precursor or “prodrug” forms of the benzofuran derivatives of the invention. It may be desirable to formulate the benzofuran derivatives of the invention in theform of a chemical species which itself is not significantly biologically -active, but which when delivered to the animal, mammal or human will undergo a chemical reaction catalyzed by the normal function of the body, inter alia, enzymes present in the stomach or in blood serum, said chemical reaction having the effect of releasing a compound as defined herein. The term “prodrug” thus relates to these species which are converted in vivo into the active pharmaceutical ingredient.

[0170] The prodrugs of the benzofuran derivatives of the invention can have any form suitable to the formulator, for example, esters are non-limiting common pro-dmg forms. In the present case, however, the pro-drug may necessarily exist in a form wherein a covalent bond is cleaved by the action of an enzyme present at the target locus. For example, a C-C covalent bond may be selectively cleaved by one or more enzymes at said target locus and, therefore, a pro-drug in a form other than an easily hydrolysable precursor, inter alia an ester, an amide, and the like, may be used. The counterpart of the active pharmaceutical ingredient in the pro-dmg can have different structures such as an amino acid or peptide structure, alkyl chains, sugar moieties and others as known in the art.

[0171] For the purpose of the invention the term “therapeutically suitable pro-drug” is defined herein as “a compound modified in such a way as to be transformed in vivo to the therapeutically active form, whether by way of a single or by multiple biological transformations, when in contact with the tissues of the animal, mammal or human to which the pro-drug has been administered, and without undue toxicity, irritation, or allergic response, and achieving the intended therapeutic outcome ”.

[0172] More specifically the term “prodrug”, as used herein, relates to a derivative of a compound such as represented by the structural formulae herein described, which undergoes spontaneous or enzymatic transformation within the body in order to release the pharmacologically active form of the compound. For a comprehensive review, reference is made to Rautio J. et al. (“Prodrugs: design and clinical applications” Nature Reviews Drug Discovery, 2008, doi: 10.1038 / nrd2468).

[0173] Representative benzofuran derivatives of the invention can be synthesized in accordance with the general synthetic methods described below and illustrated in the schemes that follow. Since the schemes are an illustration, the invention should not be construed as being limited by the specific chemical reaction and specific conditions described in the schemes and examples. The various starting material used in the schemes are commercially available or may be prepared by methods well within the skill persons versed in the art. The variables are as defined herein and within the skill of persons verses in the art.EXAMPLES

[0174] The following examples are provided for the purpose of illustrating the invention and by no means should be interpreted to limit the scope of the invention.

[0175] Representative compounds of the present invention can be synthesized in accordance with the general synthetic methods described below and illustrated in the schemes that follow. Since the schemes are an illustration, the invention should not be construed as being limited by the specific chemical reaction and specific conditions described in the schemes and examples. The various starting material used in the schemes are commercially available or may be prepared by methods well within the skill of persons versed in the art. The variables are as defined herein an within the skill of persons versed in the art.

[0176] Abbreviations used in the instant specification, particularly in the schemes and examples, are as follows: ABC - Aqueous solution of Ammonium Bicarbonate, ACN - acetonitrile, AcOH - Acetic acid, ADDP - 1,1'-(Azodicarbonyl)dipiperidide, aq. - Aqueous, AIBN - Azobisisobutyronitrile, BrettPhos - 2- (Dicyclohexylphosphino)3,6-dimethoxy-2',4',6'-triisopropyl-l, 1'-biphenyl, CAN - Ceric ammonium nitrate, COMU - (l-Cyano-2 -ethoxy -2 -oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate, DABCO - l,4-diazabicyclo[2.2.2]octane, DAST - Diethylaminosulfur trifluoride, DBU - l,8-Diazabicyclo[5.4.0]undec-7-ene, DCC - N,N'-dicyclohexylcarbodiimide, DCM - Dichloromethane, DEAD - Diethyl azodicarboxylate, DIA - Diastereomer, DIAD - Diisopropyl azodicarboxylate, DEA - Diethylamine, DIPEA - Diisopropyl-ethyl amine, DMAP -4-Dimethylaminopyridine, DME - 1,2-Dimethoxy ethane, DMEDA - 1,2-Dimethylethylenediamine, DMF - N,N-Dimethylformamide, DMSO - Dimethylsulfoxide, DPP A - Diphenylphosphoryl azide, 2,4-DNPH - 2,4-Dinitrophenylhydrazine, DTBAD - tert-Butylazodicarboxylate, EDCI or EDC - l-Ethyl-3-(3-dimethylaminopropyl)_,carbodiimide, En - Enantiomer, Et2O - Diethyl ether, EtOH - Ethanol, EtOAc - Ethyl acetate, Eq. - Equivalent, FA - Formic acid, FCC - Flash column chromatography, h - Hour, HATU - O-(7-Azabenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, HPLC - High performance liquid chromatography, IPA - isopropyl alcohol, LAH - Lithiumaluminiumhydrid, LG - Leaving group, mCPBA - meta-Chloroperoxybenzoic acid, MeOH - methanol, min. - Minute, Ms - Methanesulfonyl, NBS - N-Bromosuccinimide, nBuLi - n-Butyl lithium, NMP - l-Methyl-2-pyrrolidinone, Pd(PPh3)4 - Tetrakis- (triphenylphosphine)-palladium(O), PdC12(dppf).DCM - [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Pd2(dba)3 - Tris(dibenzylideneacetone)dipalladium, Pet ether - Petroleum ether, PPh3 - Triphenylphospine, PS-DIEA - Diisoprpropyl-ethyl amine supported on PolyStyrene, PS-PPh3 - Triphenylphospine supported on PolyStyrene, PyBop - Benzotriazol-l-yl- oxytripyrrolidinophosphonium hexafluorophosphate, Pyr. - Pyridine, PTSA - p-Toluenesulfonic acid, RF : ratio of frontiers, RM - Reaction mixture, RP - Reverse phase, RT - Room temperature, sat. - Saturated, SEM - [2- (Trimethylsilyl)ethoxy]methyl acetal, SFC - Supercritical fluid chromatography, SPE - Solid Phase Extraction, TBDMS - Tert-Butyldimethylsilyl ether, TBAF - Tetrabutylammonium fluoride hydrate, TBAI - Tetrabutylammonium iodide, TEA - Triethylamine, Tf - Trifluoromethanesulfonate, THF - Tetrahydrofurane , TFA - Trifluoroacetic acid, TLC - thin layer chromatography, TPP - triphenyl phosphine, IPA - isopropyl alcohol, TMS - trimethyl silyl, T3P - Propylphosphonic anhydride, XPhos Pd G3 - (2-Dicyclohexylphosphino-2',4',6'- triisopropyl-1, l'-biphenyl)[2-(2'-amino-l, r-biphenyl)]palladium(II) methanesulfonate.

[0177] The compounds of interest having a structure according to the general formula (A) and all other formulas described herein and embodiments thereof can be prepared as outlined in the general chemical scheme 1.Scheme 1 : all R1, R2, R3, R4, R5, R6, and R7are as described for the compounds of the present invention.

[0178] 5-Hydroxy-benzofuran-3-carboxylic acid derivatives 1, wherein R’ is an ester protecting group (e.g. methyl, ethyl, t-Bu and the like), (commercially available or synthesized by procedures known in the art) may be reacted with a triflating reagent (e.g. N,N-bis(trifluoromethanesulfonyl)aniline, OTf2 and the like) in the presence of a base (e.g., DIPEA, DBU, TEA, and the like) with or without a nucleophilic catalyst (e.g., DMAP , Pyr. and the like) in a polar aprotic solvent (e.g. DCM, DMF and the like) to provide intermediates of formula 2. Derivatives of formula 2 may be reacted with appropriate boronic derivatives 3 (commercially available or synthesized by procedures known to people skilled in the art or as set forth in the examples below), wherein R” is an hydrogen or an alkyl group (e.g. methyl, butyl and the like), in combination with Pd catalyst (e.g. Pd(PPh3)4, PdC12(dppf) and the like) and a salt (e.g., KF, K3PO4, Na2COs and the like) in a solvent (e.g., DMF, toluene, dioxane, water, and the like) to provide intermediates of formula 4. Cyclopropanation of olefin derivatives 4 with hydrazone derivatives 5 (commercially available or synthesized by procedures known in the art or as set forth in the examples below), in the presence of a base (e.g. NaH, K2CO3 and the like) in a polar aprotic solvent (e.g. DCM, Dioxane and the like) may supply intermediates of formula 6. Ester derivatives 6 may then be converted into the desired compounds of formula 7 via standard saponification reactions. The desired compounds of formula 9 may be obtained from acid derivatives of formula 7 by reaction with amine derivatives of formula 8 (commercially available or synthesized by procedures known in the art or as set forth in the examples below) under standard peptide coupling conditions (e.g. DCC, EDCI, HATU, PyBop and the like) in a polar aprotic solvent (e.g. DCM, DMF and the like). Alternatively, a Lemieux-Johnson oxidation of olefin derivatives 4 may provide aldehyde intermediates 10. More detailed information can be found in the following reference : Hua, Z.; Yu, W.; Jin, Z. (2004). "An Improved Procedure for the Oxidative Cleavage of Olefins by OsO i-NalO4". Org. Lett. 6 (19): 3217- 3219. Aldehyde intermediates 10 may be reacted with tosylhydrazine in a polar protic solvent (e.g. MeOH, EtOH and the like) to afford intermediates 11. Cyclopropanation of hydrazone derivatives 11 with olefin derivatives 12 (commercially available or synthesized by procedures known in the art or as set forth in the examples below), in the presence of a base (e.g. NaH, K2CO3 and the like) in a polar aprotic solvent (e.g. DCM, Dioxane and the like) may supply intermediates of formula 6..

[0179] In a more particular embodiment, the compounds of the present invention may be synthesized as depicted in scheme 2.Scheme 2: all R1, R2, R3, R4, R5and R6are as described for the compounds of the present invention.

[0180] Derivatives of formula 2 may be reacted with appropriate boronic derivatives 13 (commercially available or synthesized by procedures known to people skilled in the art or as set forth in the examples below), wherein R’ ’is an hydrogen or an alkyl group (e.g. methyl, butyl and the like), in combination with Pd catalyst (e.g. Pd(PPh3)4, PdCP dppf) and the like) and a salt (e.g., KF, K3PO4, Na2COs and the like) in a solvent (e.g., DMF, toluene, dioxane, water, and the like) to provide intermediates of formula 14. Cyclopropanation of the olefin derivatives 14 with derivatives 15 (commercially available or synthesized by procedures known in the art or as set forth in the examples below), wherein X is a halogen (e.g. Cl, I and the like), mediated by a metal (e.g. NiCL and the like) and Diethyl zinc in a polar aprotic solvent (e.g. DCM, Dioxane and the like) may supply intermediates of formula 16. Ester derivatives 16 may then be converted into the desired compounds of formula 17 via standard saponification reactions. The desired compounds of formula 18 may be obtained from acid derivatives of formula 17 by reaction with amine derivatives of formula 8 (commercially available or synthesized by procedures known in the art or as set forth in the examples below) under standard peptide coupling conditions (e.g. DCC, EDCI, HATU, PyBop and the like) in a polar aprotic solvent (e.g. DCM, DMF and the like).

[0181] In a more particular embodiment, compounds of the present invention, wherein Cy represents 3-14- membered cycloalkyl or heterocycloalkyl, may be synthesized as depicted in scheme 3Scheme 3 : all R1, R2, R3, R4, R5, R6, and R7are as described for the compounds of the present invention.

[0182] 5-Hydroxy-benzofuran-3 -carboxylic acid derivatives 1 may then be converted into the desired compounds of formula 22 via nucleophilic substitution using intermediates of formula 21 (commercially available or synthesized), wherein LG is a leaving group, in the presence of a base (e.g., DIPEA, DBU, triethylamine, Cs2CO3, and the like) in a polar solvent (e.g., acetonitrile, DMF, NMP, and the like), with or without a chelating agent (e.g., 18-crown-6, cis-anti-cis-dicyclohexano-18-crown-6, and the like) at a temperature ranging from 0 to 100°C. Alternatively, 5-Hydroxy-benzofuran-3-carboxylic acid derivatives 1 may also be reacted with intermediates of formula 20 (commercially available or synthesized) in the presence of an azodicarboxylate reagent (e.g., DEAD, DIAD, ADDP, and the like) and a phosphine (e.g., tributylphosphine, triphenylphosphine and the like) in a solvent (e.g., THF, toluene, and the like) at a temperature ranging from 0 to 100°C, to provide the desired compounds of formula 22. Ester derivatives 22 may then be converted into the desired compounds of formula 23 via standard saponification reactions. The desired compounds of formula 24 may be obtained from acid derivatives of formula 23 by reaction with amine derivatives of formula 8(commercially available or synthesized by procedures known in the art or as set forth in the examples below) under standard peptide coupling conditions (e.g. DCC, EDCI, HATU, PyBop and the like) in a polar aprotic solvent (e.g. DCM, DMF and the like). Alternatively, carboxylic acid derivatives of formula 23, may be converted into acid chloride derivatives by procedures known to those skilled in the art or as set forth in the examples below, and then reacted with amines of formula 8 to obtain the desired compounds of formula 24 by procedures known to those skilled in the art or as set forth in the examples below.

[0183] In a more particular embodiment, intermediates 22 of the present invention, wherein Cy represents aryl or heteroaryl, may be synthesized as depicted in scheme 4Scheme 4: all R1, R2, R3, R4, R5, R6, and R7are as described for the compounds of the present invention.

[0184] 5-Hydroxy-benzofuran-3 -carboxylic acid derivatives 1 may then be converted into the desired compounds of formula 22 via Ullmann coupling mediated by copper catalyst (e.g., Cui) using intermediates of formula 25 (commercially available or synthesized), wherein Y is a Halogen, in the presence of a base (e.g.,DIPEA, DBU, triethylamine, Cs2CO3, and the like) in apolar solvent (e.g., 1,4-dioxane and the like), with a ligand(e.g., Tetramethyl-3,5-heptanedione and the like) at a temperature ranging from 0 to 100°C.

[0185] In a more particular embodiment, the compounds of the present invention may be synthesized as depicted in scheme 5.Scheme 5: all R1, R2, R3, R4, R5, R6, R7, X and Cy are as described for the compounds of the present invention.

[0186] Derivatives of formula 2 (commercially available or synthesized by procedures known to people skilled in the art or as set forth in the examples below), may be reacted with appropriate boronic derivatives 30 (commercially available or synthesized by procedures known to people skilled in the art or as set forth in the examples below), wherein R” is an hydrogen or an alkyl group (e.g. methyl, butyl and the like), in combination with Pd catalyst (e.g. Pd(PPh3)4, PdC12(dppf) and the like) and a salt (e.g., KF, K3PO4, Na2CO3 and the like) in a solvent (e.g., DMF, toluene, dioxane, water, and the like) to provide intermediates of formula 31. Alternatively, derivatives 2 may be converted in a boronic ester of general formula 32, via a Miyaura Borylation Reaction (For an article of such methods, see e.g., T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem., 1995, 60, 7508-7510). The desired compound of general formula 31 may be obtained via a Suzuki coupling between the boronic ester of general formula 32 and intermediates of formula 33 (commercially available or synthesized), wherein Y is a Halogen (commercially available or synthesized by procedures known to the person skilled in the art). Ester derivatives 31 may then be converted into the desired compounds of formula 32, via standard saponification reactions, followed by a reaction with amine derivatives of formula 8 (commercially available or synthesized by procedures known in the art or as set forth in the examples below) under standard peptide coupling conditions (e.g. DCC, EDCI, HATU, PyBop and the like) in a polar aprotic solvent (e.g. DCM, DMF and the like).Table 1: Exemplary Compounds

[0187] The following examples are provided for the purpose of illustrating the present invention and by no means should be interpreted to limit the scope of the present invention.

[0188] Part A represent the preparation of the compounds whereas Part B represents the pharmacological examples.Part A

[0189] All starting materials which are not explicitly described were either commercially available (the details of suppliers such as for example ABCR, Apollo Scientific Combi-Blocks, Enamine, FluoroChem, MatrixScientific, Maybridge, Merck, TCI etc. can be found in the SciFinder® Database for example) or the synthesis thereof has already been described precisely in the specialist literature (experimental guidelines can be found in the Reaxys® Database or the SciFinder® Database respectively, for example) or can be prepared using the conventional methods known to the person skilled in the art.

[0190] The reactions were, if necessary, carried out under an inert amosphere (mostly argon and N2). The number of equivalents of reagents and the amounts of solvents employed as well as the reaction temperatures and times can vary slightly between different reactions carried out by analogous methods. The work-up and purification methods were adapted according to the characteristic properties of each compound and can vary slightly for analogous methods. The yields of the compounds prepared are not optimized.

[0191] The indication „equivalents“ ("eq." or “eq” or “equiv.”) means molar equivalents, “RT” or “rt” means room temperature T (23 ± 7 °C), “M” are indications of concentration in mol / 1, “sol.” means solution, "cone." means concentrated. The mixing ratios of solvents are usually stated in the volume / volume ratio.

[0192] Key analytical characterization was carried out by means of1H-NMR spectroscopy and / or mass spectrometry (MS, m / z for [M+H]+and / or [M-H | ) for all the exemplary compounds and selected intermediate products. In certain cases, where e.g. regioisomers and / or diastereomers could be / were formed during the reaction, additional analytics, such as, e.g.13C NMR and NOE (nuclear Overhauser effect) NMR experiments were in some cases performed.

[0193] Analytical instruments employed were e.g. for NMR analysis a BRUKER 400MHz or a BRUKER 500MHz machine (Software Topspin), alternatively a BRUKER AVANCE 300MHz and 400Mhz was employed. For LC / MS analysis e.g. an Agilent 1290 infinity ,Mass:6150 SQD(ESI / APCI) or an Agilent 1200 SERIES, Mass:6130 SQD(ESI / APCI) (Software Chemistation) was employed. Analytical HPLCs were measured e.g. on Waters (Software Empower), an Agilent-1200-ELSD (Software Chemistation) or an Agilent-1260 (Software OpenLAB). Analytical SFC were performed e.g. on a PIC solution (Software: SFC PICLAB ONLINE), a WATERS-X5 (Software MASSLYNX) or a WATERS-UPC2 (Empower).

[0194] Preparative HPLC were performed e.g. on a Waters 2998 (Software Empower) or a YMC (Software K- Prep). Preparative SFC were performed e.g. on a Waters, SFC- 200 (Software Chromscope or Super chrome), a Waters, SFC-80 (Super chrome) or a PIC, PIC-175 (Software S10-100).

[0195] Structures of example compounds that contain stereocenters are drawn and named with absolute stereochemistry, if known. In case of unknown absolute stereochemistry the compounds can be either racemic, a mixture of diastereomers, a pure diastereomer of unknown stereochemistry, or a pure enantiomer of unknown stereochemistry. Dia 1 and Dia 2 means that diastereoisomers were separated but the stereochemistry is unknown. En 1 and En 2 means that both enantiomers were separated but the absolute configuration is unknown. No suffix given after the compound code means that a compound containing stereocenters was obtained as a racemic mixture or a mixture of diastereomers, respectively, unless the chemical name of the compound specifies the exact stereochemistry.Synthesis of (S -2-amino-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanamide (Int-AOOl - Enl),and (R)-2- amino-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanamide (Int-AOOl - En2),lnt-A001 lnt-A001 - En1 lnt-A001 - En2

[0196] Step 1 : A solution of l-((tert-butyldimethylsilyl)oxy)propan-2-one (20 g, 106.19 mmol) in EtOH (100 mL) was treated with (4-methoxyphenyl)methanamine (15.3 mL, 116.81 mmol), TMSCN (15.94 mL, 127.42 mmol) and NH iCI (1.7 g, 31.8 mmol) at RT. The RM was stirred at 80 °C for 16 h. After completion of the reaction, volatiles were removed under reduced pressure. The residue was diluted with EtOAc (200 mL), washed with saturated NaHCO3(100 ml), brine solution (100 mL), dried over MgSO i. filtered and evaporated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in pet ether as an eluent to afford 3 -((tert-butyldimethylsilyl)oxy)-2-((4-methoxybenzyl)amino)-2 -methylpropanenitrile as a pale yellow liquid (20 g, 56.30%).1H NMR (400 MHz, DMSO-D6) δH ppm: 7.25 (d, 2 H), 6.88 (d, 2 H), 3.72 (s, 5 H), 3.65 - 3.75 (m, 1 H), 3.45 - 3.51 (m, 1 H), 2.74 - 2.77 (m, 1 H), 1.36 (s, 3 H), 0.87 (s, 9 H), 0.77 (m, 6 H).

[0197] Step 2 : A solution of 3-((tert-butyldimethylsilyl)oxy)-2-((4-methoxybenzyl)amino)-2- methylpropanenitrile (10 g, 29.940 mmol) in DMSO (70 mL) was treated withK2CO3 (28.966 g, 209.581 mmol) and H2O2 (14.041 mL, 598.802 mmol) at 0° C. The RM was stirred at RT for 16 h. After completion, the RM was cooled to RT and quenched with ice-cold water (100 mL). The aqueous layer was extracted with Et20 (3 x 100 mL). Combined organic phases was washed with brine (50 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by FCC on silica gel using 40-50% EtOAc in pet ether as an eluent to afford 3-((tert-butyldimethylsilyl)oxy)-2-((4-methoxybenzyl)amino)-2-methylpropanamide as a pale yellow liquid (3.8 g, 36%).1H NMR (400 MHz, DMSO-D6) 5H ppm: 7.25 (d, 2 H), 7.24 (br s, 1 H), 7.07 (brs, 1 H), 6.86 (d, 2 H), 3.72 (s, 3 H), 3.68 - 3.71 (m, 1 H), 3.56 - 3.59 (m, 1 H), 3.51 (d, 2 H), 2.05 (br s, 1 H), 1.15 (s, 3 H), 0.85 (s, 9 H), 0.03 (s, 6 H). LCMS: Rt= 1.85 min (97.01%), m / z: 353.39 [M+H]+.

[0198] Step 3 : A solution of 3-((tert-butyldimethylsilyl)oxy)-2-((4-methoxybenzyl)amino)-2- methylpropanamide (10 g, 28.365 mmol) in MeOH (200 mL) was treated with 10% palladium hydroxide (5.178 g, 36.874 mmol) at RT. The RM stirred at RT for 48 h under H2pressure (70 psi). After completion, the reaction mixture was filtered through a celite pad, washed with 10% MeOH in DCM (200 mL), filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 80% EtOAc in Pet. ether as an eluent to afford 2-amino-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanamide as an off white solid (, 5.5 g).1H NMR (400 MHz, DMSO) 5H ppm: 7.25 (s, 1 H), 6.95 (s, 1 H), 3.76 (d, 1 H), 3.25 (d, 1 H), 1.77 (s, 2 H), 1.04 (s, 3 H), 0.85 (s, 9 H), 0.02 (s, 6 H).

[0199] Step 4 : 5.5 g of Int-001 was separated by Prep. SFC. Column [Dimensions]: Lux. Cellulose-4 [250 x 30 x 5pm], % CO2: 75%, % solvent: 25% (0.5% Diethyl Amine in ACN), Total Flow: 90 g / min, Back Pressure: 120.0 bar, Temperature: 30°C, Wavelength: 215 nm, stack: 18.0 min, Loadability: 44.0 mg / injection, Solubility: 70 mL of ACN, No of Injection: 93, Instrument details: Make / Model: SFC-MASS. The collected fractions were concentrated and lyophilized to afford two isomers: First eluting (Int-AOOl - Enl) , as a pale yellow gummy (1.7 g). 1H NMR (400 MHz, DMSO-D6) 5 ppm: 7.24 (s, 1 H), 6.93 (s, 1 H), 3.76 (d, 1 H), 3.26 (d, 1 H), 1.77 (s, 2 H), 1.04 (s, 3 H), 0.85 (s, 9 H), 0.02 (s, 6H). SOR: -28.62 (1.0% in CHCl3) and second eluting (Int-AOOl - En2), as a pale yellow gummy (1.5 g,).1H NMR (400 MHz, DMSO-D6) 5 ppm: 7.24 (s, 1 H), 6.93 (s,l H), 3.76 (d, 1 H), 3.26 (t, 1 H), 1.77 (s, 2 H), 1.04 (s, 3 H), 0.85 (s, 9 H), 0.02 (t, 6 H). SOR: +47.54 (1.0% in CHCh).Synthesis of 2-amino-4,4-difluoro-2-methylbutan-l-ol (Int-A003),

[0200] Step 1 : To a solution of t-BuOK (13.2 g, 117.83 mmol) in DMF (150 mL) was added ethyl 2- ((diphenylmethylene)amino)acetate (30 g, 112.22 mmol) at 0 °C. After 30 min, l,l-difluoro-2 -iodoethane (24.9 g,130.18 mmol) was added over 10 min at 0 °C. The RM was stirred at 0°C for 1 h. After completion of the reaction, the RM was diluted with 5% aq NH4C1 (100.0 mL), extracted with EtOAc (3 x 50.0 mL). Combined organic layer was washed with brine (100.0 mL), dried over Na2SC>4, fdtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 5% EtOAc in pet ether as an eluent to afford ethyl 2- ((diphenylmethylene)amino)-4,4-difluorobutanoate as a pale yellow liquid (30 g, 80.67%). 1H NMR (400 MHz, CDCl3) 5 ppm: 7.63 - 7.65 (m, 2 H), 7.39 - 7.48 (m, 4 H), 7.31 - 7.36 (m, 2 H), 7.18 - 7.20 (m, 2 H), 5.75 - 5.91 (m, 1 H), 4.27 - 4.30 (m, 1 H), 4.14 - 4.19 (m, 2 H), 2.45 - 2.53 (m, 2 H), 1.25 (t, 3 H).

[0201] Step 2: To a solution of t-BuOK (7.450 g, 112.21 mmol) in DMF (30 mL) was added Ethyl N- (diphenylmethylene)glycinate (20 g, 331.36 mmol) at 0 °C. After 30 min, iodomethane (42.83 g, 141.93 mmol) was added over 10 min at 0 °C. The RM was stirred at 0°C for 1 h. After completion of the reaction, the RM was diluted with 5% aq NH4CI (100 mL), extracted with EtOAc (3 x 50 mL). Combined organic layer was washed with brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in pet ether as an eluent to afford ethyl 2- ((diphenylmethylene)amino)-4,4-difluoro-2-methylbutanoateas a pale yellow liquid (16 g, 76.75%). 1H NMR (400 MHz, CDCl3) 5 ppm: 7.50 - 7.59 (m, 2 H), 7.36 - 7.41 (m, 4 H), 7.28 - 7.32 (m, 2 H), 7.13 - 7.15 (m, 2 H), 6.16 - 6.49 (m, 1 H), 3.69 - 3.77 (m, 2 H), 2.31 - 2.57 (m, 2 H), 1.44 (s, 3 H), 1.11 (t, 3 H).

[0202] Step 3 : To a solution of ethyl 2-((diphenylmethylene)amino)-4,4-difluoro-2-methylbutanoate (16 g, 46.32 mmol) in Pet. ether (75 mL) was added IN HO (150 mL) at RT. The RM was stirred at RT for 16 h. The RM was washed with EtOAc (2 x 50 mL). The aqueous solution was basified with NaHCO3(pH ~8), extracted with EtOAc (3 x 50 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford ethyl 2-amino-4,4-difluoro-2-methylbutanoate as a pale yellow liquid (5.910 g, 70.42%). 1H NMR (400 MHz, CDCl3) 5 ppm: 5.87 - 6.15 (m, 1 H), 4.17 - 4.12 (m, 2 H), 2.04 - 2.33 (m, 2 H), 1.39 (s, 3 H), 1.27 (t, 3 H).

[0203] Step 4 : To a solution of ethyl 2-amino-4,4-difluoro-2-methylbutanoate (5.6 g, 30.90 mmol) in EtOH (50 mL) was added sodium borohydride (3.508 mg, 92.72 mmol) at 0 °C. The RM was stirred at RT for 7 h. The RM was quenched with water (10 mL), extracted with EtOAc (3 x 30 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford 2-amino-4,4-difluoro-2-methylbutan-l-ol (Int-A003) as a colorless gum (2.3 g, 53%). 1H NMR (400 MHz, DMSO-De) δ ppm: 6.02 -6.33 (m, 1 H), 4.76 (t, 1 H), 3.09 - 3.19 (m, 2 H), 1.75 - 1.87 (m, 2 H), 1.48 (br, s, 2 H), 0.95 (s, 3 H).Synthesis of 2-amino-3 -hydro xy-N,2-dimethylpropanamide hydrochloride (Int-A004),int-A004

[0204] Step 1 : A stirred solution of 2-((tert-butoxycarbonyl) amino)-3-hydroxy-2-methylpropanoic acid (1 g, 4.56 mmol) in MeCN (50 mL) was treated with DIPEA (3.983 mL, 22.806 mmol) and methylamine hydrochloride (0.615 g, 9.123 mmol) followed by TBTU (1.904 mg, 5.930 mmol) at RT. The RM was stirred at RT for 6 h. The RM was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 4% MeOH inDCM as a gradient to afford tert-butyl (3-hydroxy-2-methyl-l-(methylamino)-l-oxopropan-2-yl)carbamate (1 g, 94.38%) as a pale yellow gummy.!H NMR (400 MHz, DMSO-d6) 5 ppm: 7.95 (d, 1 H), 7.53-7.51 (m, 1 H), 4.87 (t, 1 H), 3.17 - 3.12 (m, 2 H), 2.56 (d, 3 H), 1.36 (s, 9 H), 1.26-1.23 (m, 3 H).

[0205] Step 2 : A solution of tert-butyl (3-hydroxy-2-methyl-l-(methylamino)-l-oxopropan-2-yl)carbamate (1 g, 4.3 mmol) in 4M Dioxane. HO (10 mL) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure to afford 2-amino-3 -hydroxy -N,2-dimethylpropanamide hydrochloride (Int-A004) (725 mg, 99.87%) as a pale brown gummy. This crude compound was proceeded to next step without further purification.1H NMR (400 MHz, DMSO-de) δ ppm: 8.98 (br s, 2 H), 8.19 (br s, 1 H), 3.60 - 3.56 (m, 1 H), 3.15 - 3.09 (m, 1 H), 2.69 (s, 3 H), 1.34 (s, 3 H).Synthesis of 3-Amino-3-(hvdroxymethyl)pyrrolidin-2-one (Int-A005 - Enl) and (Int-A005 - En2),int-A005 - En2

[0206] Step 1 : To a stirred solution of diethyl 2-(2-(l,3-dioxoisoindolin-2-yl)ethyl)malonate (60 g, 179.99 mmol) in 1,4-Dioxane (600 mL) was added TEA (49.90 mL, 359.99 mmol) at 0 °C. After 15 minutes, formaldehyde (29.18 g, 359.99 mmol) was added at 0 °C. The RM was warmed to RT and stirred at 80 °C for 16 h. The RM was diluted with ice-cold water (200 mL) and extracted with EtOAc (2 x 300 mL). The combined organic layers were washed with brine (150 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0 to 40% EtOAc in pet ether to afford diethyl 2-(2-(l,3-dioxoisoindolin-2-yl)ethyl)-2-(hydroxymethyl)malonate (59 g, 90%) as pale yellow gummy.1H NMR (400 MHz, CDCl3) 5 ppm: 7.86-7.82 (m, 2 H), 7.74-7.69 (m, 2 H), 4.25-4.18 (m, 4 H), 4.07 (d, 2 H), 3.83- 3.79 (m, 2 H), 2.79 (t, 1 H), 2.33-2.30 (m, 2 H), 1.28 (t, 6 H).

[0207] Step 2: To a stirred solution of diethyl 2-(2-(l,3-dioxoisoindolin-2-yl)ethyl)-2-(hydroxymethyl)malonate (68 g, 187.13 mmol) in DCM (700 mL) was added Imidazole (25.48 g, 374.27 mmol) at 0 °C . After 15 min., tert- Butyldimethylsilyl chloride (33.84 g, 224.56 mmol) at 0 °C was added. The RM was stirred for 16 h at RT. The RM was diluted with ice cold water (300 mL) and extracted with DCM (2 x 500 mL). The combined organic layers were washed with brine (200 mL), dried over Na2SC>4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 10% EtOAc in pet ether to afford diethyl 2-(((tert- butyldimethylsilyl)oxy)methyl)-2-(2-(l,3-dioxoisoindolin-2-yl)ethyl)malonate (68 g, 77%) as an off-white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.84-7.82 (m, 2 H), 7.71-7.69 (m, 2 H), 4.18-4.11 (m, 6 H), 3.76-3.72 (m, 2 H), 2.41-2.37 (m, 2 H), 1.26 (t, 6 H), 0.89 (s, 9 H), 0.08 (s, 6 H).

[0208] Step 3 : To a stirred solution of diethyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-2-(2-(l,3- dioxoisoindolin-2-yl)ethyl)malonate (68 g, 142.37 mmol) in Ethanol (700 mL) was added Hydrazine hydrate (10.69 g, 213.55 mmol) at 0 °C. The RM was stirred for 16 h at RT. The RM was diluted with ice cold water (300 mL) and extracted with EtOAc (2 x 500 mL). The combined organic layers were washed with brine solution (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-30% EtOAc in Pet. ether to afford ethyl 3-(((tert-butyldimethylsilyl)oxy)methyl)- 2 -oxopyrrolidine-3 -carboxylate (30.7 g, 71%) as an off white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 5.76 (s, 1 H), 4.22-4.17 (m, 2 H), 4.06 (d, 1 H), 3.94 (d, 1 H), 3.46-3.42 (m, 1 H), 3.36-3.35 (m, 1 H), 2.59-2.55 (m, 1 H), 2.49-2.43 (m, 1 H), 1.27 (t, 3 H), 0.87 (d, 9 H), 0.06 (d, 6 H).

[0209] Step 4 : To a solution of ethyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-2-oxopyrrolidine-3-carboxylate (29 g, 96.19 mmol) in EtOH (120 mL), THF (60 mL) and H2O (30 mL) was added LiOH.H2O (20.18 g, 480.99 mmol) at 0 °C. The RM was stirred for 16 h at RT. The volatiles were removed under reduced pressure. The residue was diluted with cold water (20 mL) and then acidified with saturated aqueous Citric acid solution (pH~4). The solid was filtered, washed with water (10 mL) followed by water (10 mL), dried under vacuum to afford 3- (((tert-butyldimethylsilyl)oxy)methyl)-2-oxopyrrolidine-3-carboxylic acid (16.7 g, 63%) as a white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 7.82 (s, 1 H), 3.88 (d, 1 H), 3.70 (d, 1 H), 3.27-3.21 (m, 1 H), 3.17-3.12 (m, 1 H), 2.34-2.32 (m, 1 H), 2.24-2.22 (m, 1 H), 0.84 (s, 9 H), 0.01 (d, 6 H).

[0210] Step 5 : To a stirred solution of 3 -(((tert-butyldimethylsilyl)oxy)methyl)-2 -oxopyrrolidine-3 -carboxy lie acid (9.5 g, 34.74 mmol) in THF (40 mL) and benzene (120 mL) were added TEA (14.65 mL, 104.24 mmol) followed by DPPA (19.12 g, 69.49 mmol) at RT. The RM was stirred at RT for 2 h. The RM was quenched with ice cold water (100 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate (2 x 50 mL), brine solution (50 mL), then dried over Na2SO4, filtered, and concentrated under reduced . The residue was dissolved in THF (40 mL) and benzene (120 mL). Then, Benzyl alcohol (7.51 g, 69.49 mmol) was added at RT. The RM was stirred at 55 °C for 16 h. The RM was diluted with ice-cold water (100 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with brine solution (100 mL), dried over Na2SO4, fdtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-40% EtOAc in Pet. ether to afford benzyl (3-(((tert- butyldimethylsilyl)oxy)methyl)-2-oxopyrrolidin-3-yl)carbamate (9 g, 68%).1NMR (400 MHz, CDCl3) δ ppm: 7.37-7.29 (m, 5 H), 5.84 (brs, 1 H), 5.42 (bis, 1 H), 5.07 (s, 2 H), 3.85 (d, 1 H), 3.67 (d, 1 H), 3.39-3.33 (m, 2 H), 2.63-2.62 (m, 1 H), 2.53-2.51 (m, 1 H), 0.88 (s, 9 H), 0.05 (d, 6 H).

[0211] Step 6 : To a stirred solution of benzyl (3-(((tert-butyldimethylsilyl)oxy)methyl)-2-oxopyrrolidin-3- yl)carbamate (11 g, 29.05 mmol) in MeOH (150 mL) was added PTSA monohydrate (2.21 g, 11.62 mmol) in MeOH (50 mL) over 2 h at 0 °C. The RM was stirred for 16 h at RT. The RM was concentrated under reduced pressure. The residue was quenched with ice-cold water (50 mL) and extracted with 10% MeOH in DCM (3 x 50 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was triturated with n-pentane (3 x 15 mL) followed by diethyl ether (15 mL), filtered and dried undervacuum to afford benzyl (3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)carbamate (7 g, 91%) as an off white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 7.66 (s, 1 H), 7.38-7.29 (m, 5 H), 7.08 (s, 1 H), 4.98-4.95 (m, 3 H), 3.46- 3.38 (m, 2 H), 3.18-3.15 (m, 1 H), 3.13-3.07 (m, 1 H), 2.28-2.25 (m, 2 H). 3.5 g of benzyl (3-(hydroxymethyl)- 2-oxopyrrolidin-3-yl)carbamate was purified by chiral SFC prep.[ Preparative SFC Conditions: Column: Chiral peak IF (250 * 30 x 5pm), %CO2: 65%, %Co-solvent: 35% (100% Methanol), Total Flow: 90 g / min, Back Pressure: 100.0 bar, Temperature: 30 °C, Wavelength: 215 nm, Stack time: 7.2 min, Solubility: 100 ml of MeOH.] The collected pure fractions were concentrated under reduced pressure to afford two isomers Enl (the first eluting) and En2 (the second eluting).

[0212] Step 7 : To a stirred solution of benzyl (3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)carbamate Enl (1.4 g, 5.297 mmol) in Ethanol (30 mL) was added Pd / C (450 mg) at RT. The RM was stirred under H2(70 psi) at RT for 16 h. The RM was fdtered through a pad of Celite, and washed with MeOH (50 mL). The filtrate concentrated under reduced pressure. The residue was triturated with diethyl ether (2 x 5 mL) and dried under high vacuum to afford 3-amino-3-(hydroxymethyl)pyrrolidin-2-one (Int-A005 - Enl) (610 mg, 88%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) 5 ppm: 7.54 (s, 1 H), 4.73 (t, 1 H), 3.36-3.34 (m, 1 H), 3.18-3.12 (m, 2 H), 3.10- 3.04 (m, 1 H), 2.22-2.15 (m, 1 H), 1.76-1.72 (m, 1 H), 1.56 (s, 2 H). UPLC: Rt = 2.29 min (98%).

[0213] Step 8 : To a stirred solution of benzyl (3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)carbamate En2 (1.2 g, 4.54 mmol) in Ethanol (30 mL) was added Pd / C (350 mg) at RT. The RM was stirred under H2(70 psi) at RT for 16 h. The RM was filtered through a pad of Celite, and washed with MeOH (50 mL). The filtrate was concentrated under reduced pressure. The residue was triturated with diethyl ether (2 x 5 L) and dried under high vacuum to afford 3-amino-3-(hydroxymethyl)pyrrolidin-2-one (Int-A005 - En2) (550 mg, 93%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) 5 ppm: 7.54 (s, 1 H), 4.73 (brs, 1 H), 3.36-3.32 (m, 1 H), 3.18-3.12 (m, 2 H), 3.10- 3.04 (m, 1 H), 2.22-2.15 (m, 1 H), 1.76-1.71 (m, 1 H), 1.57 (s, 2 H).Synthesis of methyl O-butyl-L-serinate (Int-A006),

[0214] Step 1 : A stirred solution of methyl N-((benzyloxy)carbonyl)-O-butyl-L-serinate (400 mg, 1.293 mmol) in MeOH (4 mL), was treated with Pd / C (70.081 mg, 0.582 mmol). The RM was stirred under H2balloon pressure at RT for 2.5 h. The RM was filtered through Celite pab, washed with MeOH (10 mL). The filtrate was concentrated under reduced pressure to afford methyl O-butyl-L-serinate (200 mg, Yield: 88%).1H NMR (400 MHz, DMSO-de) δ ppm: 3.61 (s, 3 H), 3.52 - 3.43 (m, 3 H), 3.37 - 3.31 (m, 2 H), 1.86 (s, 2 H), 1.46 - 1.39 (m, 2 H), 1.32 - 1.24 (m, 2 H), 0.85 (t, 3 H).Synthesis of 5-amino-2,2-dimethyl-l,3-dioxane-5-carboxamide (Int-A007),

[0215] Step 1 : A stirred solution of 2,2-dimethyl-l,3-dioxan-5-one (5 g, 38.420 mmol) in EtOH (50 mL) were treated with (4-methoxyphenyl)methanamine (5.522 mL, 42.262 mmol,), TMSCN (5.8 mL, 46.104 mmol) and NH4CI (616.5 mg, 11.526 mmol) at RT. The RM was stirred at 80 °C for 16 h. The RM was concentrated under reduced pressure. The residue was diluted with EtOAc (250 mL), washed with saturated NaHC’O? (100 mL) and brine solution (100 mL). The combined organic layer was dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-10% EtOAc in pet ether to afford 5-((4-methoxybenzyl)amino)-2,2-dimethyl-l,3-dioxane-5-carbonitrile (280 g, Yield: 65%) as an off white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.27 (d, 2 H), 6.87 (d, 2 H), 4.03 (d, 2 H), 3.85 (d, 4 H), 3.80 (s, 3 H), 1.48 (s, 3 H), 1.43 (s, 3 H).

[0216] Step 2 : A stirred solution of 5-((4-methoxybenzyl)amino)-2,2-dimethyl-l,3-dioxane-5-carbonitrile (5.7 g, 20.627 mmol) in DMSO (80 mL) were treated with K2CO3 (20 g, 144.389 mmol) and H2O2 (9.7 mL, 412.541 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was quenched with ice cold water (250 mL) and extracted with EtOAc (2 x 250 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure The residue was purified by FCC on silica gel using a gradient of 0-100% EtOAc in pet ether to afford 5-((4-methoxybenzyl)amino)-2,2-dimethyl-l,3-dioxane-5-carboxamide ( 4.5 g, Yield: 74%) as an off-white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 7.35 (d, 2 H), 7.30 (d, 2 H), 6.87 (d, 2 H), 4.07 (d, 2 H), 3.73-3.71 (m, 5 H), 3.49 (d, 2 H), 2.33-2.30 (m, 1 H), 1.37 (s, 3 H), 1.31 (s, 3 H).

[0217] Step 3 : A stirred solution of 5-((4-methoxybenzyl)amino)-2,2-dimethyl-l,3-dioxane-5-carboxamide (4.50 g, 15.288 mmol) in MeOH (100 mL) was added palladium hydroxide on carbon (2.25 g) at RT. The RM was stirred under H2balloon pressure at RT for 16 h. The RM was filtered through a celite pad, washed with DCM (150 mL) and the filtrate was concentrated under reduced pressure. The residue was triturated with n-pentane (20 mL) and dried under reduced pressure to afford 5-amino-2,2-dimethyl-l,3-dioxane-5-carboxamide (Int-A007) ( 1.60 g, Yield: 60%) as an off white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 7.31 - 7.24 (m, 2 H), 4.04 (d, 2 H), 3.42 (d, 2 H), 2.05 (bs, 2 H), 1.35 (d, 6 H).Synthesis of 3 -(tert-butyl) 4-methyl 2-(tert-butyl)oxazolidine-3,4-dicarboxylate (Int-A008) and 2-amino-2- (hydroxymethyDbutanamide hydrochloride (Int-A009),

[0218] Step 1 : A stirred solution of methyl serinate hydrochloride (40 g, 257.10 mmol) in 2 -methylpentane (400 mL) were treated with TEA (39.47 mL, 282.8 mmol) and pivalaldehyde (34.06 mL, 308.52 mmol) at RT. The RM was stirred at 100 °C for 4 h. The RM was filtered through a celite pad and washed with 2-methylpentane (100 mL). The filtrate was concentrated under vacuum to afford methyl 2-(tert-butyl)oxazolidine-4-carboxylate (50 g, Yield: Crude) as a pale yellow oil.

[0219] Step 2 : A stirred solution of methyl 2-(tert-butyl)oxazolidine-4-carboxylate (50 g, 267.03 mmol) in THF(300 mL) was treated with di-tert-butyl dicarbonate (67.48 mL, 293.7 mmol) and stirred at RT for 6 h. Then, the RM was treated with a solution of K2CO3 (147.6 g, 1068 mmol) in water (300 mL) at RT. The RM was stirred at RT for 12 h. The RM was diluted with water (200 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layer was dried over Na2SO4, fdtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 5% EtOAc in pet ether to afford 3 -(tert-butyl) 4-methyl 2-(tert- butyl)oxazolidine-3,4-dicarboxylate (Int-A008) as a colorless oil (60 g, Yield: 78.1%).1H NMR (400 MHz, CDCL) 5 ppm: 5.03 (s, 1 H), 4.70 (bs, 1 H), 4.29 - 4.26 (m, 1 H), 4.14 (t, 1 H), 3.75 (s, 3 H), 1.47 (s, 9 H), 0.93 (s, 9 H).

[0220] Step 3 : A stirred solution of 3 -(tert-butyl) 4-methyl 2-(tert-butyl)oxazolidine-3,4-dicarboxylate (25 g, 87 mmol) in THF (200 mL) was treated with LDA (2 M in THF, 87 mL, 174 mmol) at -78 °C and stirred for 30 min. Then, the RM was treated with a solution of iodoethane (27.9 mL, 348 mmol) in THF (50 mL) and stirred at -78 °C for 3 h. The RM was stirred for 12 h at RT. The RM was quenched with ice cooled aq. NH4CI solution (200 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 3% EtOAc in pet ether to afford 3 -(tert-butyl) 4-methyl 2-(tert-butyl)-4-ethyloxazolidine-3,4-dicarboxylate (5.0 g, Yield: 18.22%) as a colorless oil.1H NMR (400 MHz, CDCL) 5 ppm: 5.16 (s, 1 H), 4.25 (q, 1 H), 3.98 (d, 1 H), 3.74 (s, 3 H), 2.44 (bs, 1 H), 2.04 - 1.92 (m, 1 H), 1.44 (s, 9 H), 0.99 (s, 9 H), 0.90 (t, 3 H).

[0221] Step 4 : To a stirred solution of 3 -(tert-butyl) 4-methyl 2-(tert-butyl)-4-ethyloxazolidine-3,4- dicarboxylate (5.0 g, 15.85 mmol) in THF (50 mL) and H2O (50 mL) was treated with LiOH.H2O (6.65 g, 158.5 mmol) at RT. The RM was stirred at 50 °C for 36 h. The RM was concentrated under reduced pressure. The residue was acidified with saturated citric acid solution (pH~6) and extracted with EtOAc (2 x 100 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to 3-(tert-butoxycarbonyl)- 2-(tert-butyl)-4-ethyloxazolidine-4-carboxylic acid (3.5 g, Yield: 73%) as a yellow gummy.1H NMR (400 MHz, DMSO-de) δ ppm: 12.75 (bs, 1 H), 5.01 (s, 1 H), 4.15 - 4.13 (m, 1 H), 4.01 (d, 1 H), 2.35 (bs, 1 H), 1.88 - 1.80 (m, 1 H), 1.38 (s, 9 H), 0.93 (s, 9 H), 0.77 (t, 3 H).

[0222] Step 5 : A solution of 3-(tert-butoxycarbonyl)-2-(tert-butyl)-4-ethyloxazolidine-4-carboxylic acid (3.5 g, 11.61 mmol) inDMF (35 mL) were treated with HATU (6.62 g, 17.42 mmol) and DIPEA (10.12 mL, 58.06 mmol) at RT and stirred for 10 min. Then, the RM was treated with ammonium chloride (1.86 g, 34.83 mmol) at RT and stirred for 16 h. The RM was diluted with cold sat. NaHCO3solution (200 mL) and precipitated solid was filtered, washed with water (20 mL) and dried under vacuum to afford tert-butyl 2-(tert-butyl)-4-carbamoyl-4- ethyloxazolidine-3-carboxylate (2.0 g, Yield: 57.3%) as a pale brown solid. 1H NMR (400 MHz, DMSO-d6) 5 ppm: 7.34 (s, 2 H), 5.09 (s, 1 H), 4.30 (bs, 1 H), 3.92 (d, 1 H), 2.31 (bs, 1 H), 1.83 (bs, 1 H), 1.43 (s, 9 H), 0.88 (s, 9 H), 0.76 (t, 3 H).

[0223] Step 6 : A solution of tert-butyl 2-(tert-butyl)-4-carbamoyl-4-ethyloxazolidine-3-carboxylate (2.0 g, 6.65 mmol) in MeOH (20 mL) was treated with 6 M HO (20 mL) at RT and stirred for 6 h. The RM was concentrated under reduced pressure. The residue was triturated with diethyl ether (2 x 20 mL) and dried under vacuum to afford 2-amino-2-(hydroxymethyl)butanamide hydrochloride (Int-A009) ( 700 mg, Yield: 62%) as pale yellow gummy.1H NMR (400 MHz, DMSO-de) δ ppm: 7.94 (s, 3 H), 7.69 (s, 1 H), 7.59 (s, 1 H), 5.62 (bs, 1 H), 3.78 (d, 1 H),3.58 (d, 1 H), 1.86 - 1.67 (m, 2 H), 0.85 (t, 3 H).Synthesis of (S)-2-amino-3-(3-hvdroxypropoxy)propanamide (Int-AOlO.)

[0224] Step 1 : A solution of 1-benzyl 2-methyl (S)-aziridine-l,2-dicarboxylate (2 g, 8.502 mmol) in DCM (20 mL), were added 3-(benzyloxy)propan-l-ol (2.019 mL, 12.753 mmol) and Boron trifluoride diethyl etherate, 45- 49% (0.160 mL, 1.275 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was diluted with chilled water (20 mL) and extracted with DCM (30 mL) followed by washing with brine (10 mL). The organic layer was dried over Na2SC>4 and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-10% EtOAc in Pet-ether to afford methyl N-((benzyloxy)carbonyl)-O-(3-(benzyloxy)propyl)-L- serinate (1.5 g, yield: 43.95%) .

[0225] Step 2 : A solution of methyl N-((benzyloxy)carbonyl)-O-(3-(benzyloxy)propyl)-L-serinate (1.0 g, 3.48 mmol) in MeOH (5.0 mL), was treated with NFL in MeOH (7 M)(20 mL) at 0 °C. The RM was stirred at 75 °C for 16 h. The RM was cooled to RT and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 50% EtOAc in pet ether to afford benzyl (S)-(l-amino-3-(3-(benzyloxy)propoxy)- l-oxopropan-2-yl)carbamate as a color less gummy (1.0 g, 74.25%),

[0226] Step 3 : A solution of benzyl (S)-(l-amino-3-(3-(benzyloxy)propoxy)-l-oxopropan-2-yl)carbamate (1 g, 2.588 mmol) in MeOH:THF (20 mL) was treated with Pd / C (1.0 g) at RT. The RM was stirred at RT for 24 h under FL atmosphere (balloon pressure). The RM was filtered through Celite pad washed with MeOH (100 mL) and filtrate was concentrated to afford (S)-2-amino-3-(3-hydroxypropoxy)propenamide (Int-AOlO) (250 mg, 59.57%) as a color less gummy mass,1H NMR (400 MHz, DMSO-de) δ ppm: 7.36 - 7.30 (m, 1 H), 7.07 (br s, 1 H), 4.44 - 4.30 (m, 1 H), 3.51 - 3.37 (m, 7 H), 1.66 - 1.60 (m, 2 H).Synthesis of 2-amino-4,4-difluoro-2-(hvdroxymethyl)butanamide hydrochloride (Int-AOll),

[0227] Step 1 : A solution of LDA (2M in THF) (40 mL, 80 mmol) in THF (80 mL) was treated with a solution of 3 -(tert-butyl) 4-methyl 2-(tert-butyl)oxazolidine-3,4-dicarboxylate (10 g, 34.8 mmol) in THF (20 mL) dropwise at -78 “over 10 min and stirred at same temp for 30 min. Then, the RM was treated with a solution of 1,1-difluoro- 2 -iodoethane (12.7 mL, 139.2 mmol) in Hexamethylphosphoramide (30.3 mL, 174 mmol) dropwise at -78 ° and stirred at -78 °C for 4 h. Then, the RM was slowly allowed to come back at RT. The RM was stirred for 16 h atRT. The RM was quenched with Aq. NH4CI solution (100 mL) at 0 °C and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-99% EtOAc in hexane to afford 3 -(tert-butyl) 4-methyl 2-(tert-butyl)-4-(2,2-difluoroethyl)oxazolidine-3,4- dicarboxylate (9.2 g, Yield: 58%) as a pale-brown Oil. 1H NMR (400 MHz, CDCL) 5 ppm: 6.07 (tt, 1 H), 5.08 (s, 1 H), 4.31 - 4.27 (m, 1 H), 4.17 - 4.07 (m, 1 H), 3.79 (s, 3 H), 2.92 (brs, 1 H), 2.56 - 2.43 (m, 1 H), 1.53 (s, 9 H), 0.95 (s, 9 H).

[0228] Step 2 : To a stirred solution of 3 -(tert-butyl) 4-methyl 2-(tert-butyl)-4-(2,2-difluoroethyl)oxazolidine- 3,4-dicarboxylate (9 g, 25.612 mmol) in THF (80 mL), MeOH (20 mL), and H2O (30 mL) was treated with LiOH.H2O (10.7 g, 256.125 mmol) at RT and stirred for 16 h. The RM was concentrated under reduced pressure and the residue was acidified with saturated Citric acid solution (pH~6) and extracted with EtOAc (2 x 100 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-99% EtOAc in hexane to afford 3-(tert-butoxycarbonyl)- 2-(tert-butyl)-4-(2,2-difluoroethyl)oxazolidine-4-carboxylic acid (1.5 g, Yield: 17%) as an off-white solid.1H NMR (400 MHz, CDCL) 5 ppm: 6.01 (tt, 1 H), 5.13 (s, 1 H), 4.69 - 4.59 (m, 1 H), 4.18 (d, 1 H), 3.09 - 3.01 (m, 1 H), 2.33 - 2.27 (m, 1 H), 1.53 (s, 9 H), 0.95 (s, 9 H).

[0229] Step 3 : A solution of 3-(tert-butoxycarbonyl)-2-(tert-butyl)-4-(2,2-difluoroethyl)oxazolidine-4- carboxylic acid (2.4 g, 7.114 mmol) in DMF (30 mL) was treated with DIPEA (8.3 mL, 47.810 mmol) followed by HATU (3.9 g, 10.245 mmol) at RT and stirred for 10 min. Then, the RM was treated with Ammonium Chloride (1.09 g, 20.490 mmol) and stirred at RT for 16 h. The RM was poured into ice-cold water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layer was washed with water (2 x 100 mL), brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure The residue was purified by FCC on silica gel using a gradient of 0-30% EtOAc in hexane to afford tert-butyl 2-(tert-butyl)-4-carbamoyl-4-(2,2- difluoroethyl)oxazolidine-3 -carboxylate (600 mg, Yield: 26%) as an off-white solid.1H NMR (400 MHz, CDCL) 5 ppm: 7.82 (brs, 1 H), 5.87 (tt, 1 H), 5.53 (s, 1 H), 5.18 (s, 1 H), 4.54 (s, 1 H), 4.13 (d, 1 H), 3.09 - 2.99 (m, 1 H), 2.56 - 2.46 (m, 1 H), 1.51 (s, 9 H), 0.97 (s, 9 H).19F NMR (376 MHz, CDCL) 5 ppm: -111.32 - -112.20 (m), - 114.50 - -114.87 (m).

[0230] Step 4 : A stirred solution of tert-butyl 2-(tert-butyl)-4-carbamoyl-4-(2,2-difluoroethyl)oxazolidine-3- carboxylate (0.6 g, 1.784 mmol) in MeOH (10 mL) was treated with 6N aq. HO (4.5 mL) at 0 °C. The RM was stirred for 16 h at RT. The RM was concentrated under reduced pressure and the resultant residue was co-distilled with MeOH (2 x 30 mL) and dried under high vacuum to afford 2-amino-4,4-difluoro-2- (hydroxymethyl)butanamide hydrochloride (Int-AOl l) (380 mg, Yield: Quantitative) as a brown gummy solid.1H NMR (400 MHz, DMSO-de) δ ppm: 8.34 (s, 3 H), 7.88 (s, 1 H), 7.74 (s, 1 H), 6.23 (tt, 1 H), 5.88 (bs, 1 H), 3.79 - 3.68 (m, 2 H), 2.59 - 2.54 (m, 2 H).19F NMR (376 MHz, DMSO-de) δ ppm: -112.46 - -112.93 (m).Synthesis of tert-butyl (S)-3-((2,3-diamino-3-oxopropoxy)methyl)azetidine-l-carboxylate (Int-A012.)

[0231] Step 1 : To a stirred solution of tert-butyl 3 -(hydroxymethyl)azetidine-l -carboxylate (1.592 g, 8.502 mmol, 1 equiv.) in CHCT, (20 mL) was treated with Boron trifluoride diethyl etherate (0.210 mL, 1.7 mmol) dropwise at -30 °C and stirred for 5 min. Then, the RM was treated with 1-benzyl 2-methyl (S)-aziridine-l,2- dicarboxylate (2 g, 8.502 mmol) in CHCT, (20 mL) dropwise over 3 h via syringe pump at -30 °C. The RM was stirred for 16 h at RT. The RM was quenched with saturated NaHCCh solution (pH ~8) and extracted with DCM (2 x 20 mL). The combined organic layer was washed with brine solution (40 mL), dried over Na2SC>4, filtered and the filterate was concentrated under reduced pressure The residue was purified by FCC on silica gel using a gradient of 0-25% EtOAc / Pet-ether to afford tert-butyl (S)-3-((2-(((benzyloxy)carbonyl)amino)-3-methoxy-3- oxopropoxy)methyl)azetidine-l -carboxylate (1 g, Yield: 28%) as a colorless gummy.1H NMR (400 MHz, CDCL) 5 ppm: 7.39 - 7.32 (m, 5 H), 5.13 (s, 2 H), 5.55 (brs, 1 H), 4.51 - 4.48 (m, 1 H), 3.96 - 3.81 (m, 2 H), 3.77 - 3.62 (m, 5 H), 3.59 - 3.48 (m, 4 H), 2.72 - 2.65 (m, 1 H), 1.43 (s, 9 H).

[0232] Step 2 : A stirred solution of tert-butyl (S)-3-((2-(((benzyloxy)carbonyl)amino)-3-methoxy-3- oxopropoxy)methyl)azetidine-l -carboxylate (2 g, 4.734 mmol, 1 equiv.) in MeOH (10 mL), was cooled to 0 °C and treated with 7M NH3 in MeOH (80 mL). The RM was stirred in sealed tube at 60 °C for 16 h. The RM was concentrated under reduced pressure and co-distilled with MeOH (50 mL) under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-1% MeOH in DCM to afford tert-butyl (S)-3-((3-amino- 2-(((benzyloxy)carbonyl)amino)-3-oxopropoxy)methyl)azetidine-l -carboxylate (1.2 g, Yield: 62%) as a colorless gummy.1H NMR (400 MHz, DMSO-de) δ ppm: 7.39 - 7.29 (m, 7 H), 7.12 (s, 1 H), 5.03 (d, 2 H), 4.18 (d, 1 H), 3.82 (d, 2 H), 3.60 - 3.49 (m, 6 H), 2.72 - 2.69 (m, 1 H), 1.36 (s, 9 H).

[0233] Step 3 : To a solution of tert-butyl (S)-3-((3-amino-2-(((benzyloxy)carbonyl)amino)-3- oxopropoxy)methyl)azetidine-l -carboxylate (600 mg, 1.473 mmol.) in Ethanol (10 mL) was treated with Palladium on carbon (400 mg, 14.725 mmol) and the RM was stirred under H2gas (balloon pressure) at RT for 2 h. The RM was filtered through a Celite pad and washed with 10% MeOH / DCM (3 x 30 mL). The filtrate was concentrated under reduced pressure to afford tert-butyl (S)-3-((2,3-diamino-3-oxopropoxy)methyl)azetidine-l- carboxylate (Int-A012) (400 mg, Yield: 99%) as a colorless gummy. 1H NMR (400 MHz, DMSO-d6) 5 ppm: 7.31 (s, 1 H), 7.02 (s, 1 H), 3.84 (s, 2 H), 3.59 - 3.50 (m, 5 H), 3.40 - 3.38 (m, 1 H), 3.29 - 3.24 (m, 1 H), 2.73 - 2.68 (m, 1 H), 1.91 (brs, 2 H), 1.36 (s, 9 H)Synthesis of Synthesis of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int-BOOl)

[0234] A solution of ethyl 5-hydroxy-2-methylbenzofuran-3-carboxylate (10 g, 45.44 mmol) in DCM (100 mL) was treated with DIPEA (9.49 mL, 54.52 mmol), DMAP (555 mg, 4.54 mmol) and Tf20 (9.92 mL, 59.07 mmol) at 0 °C. The RM was stirred at RT for 4 h. After completion, the RM was diluted with DCM (100 mL), washed with ice water (100 mL), brine solution (50 mL), dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 20% EtOAc in pet ether as a gradient to afford ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int-BOOl) as an off-white solid (12 g, 75%).1H NMR (400 MHz, CDCl3) 5 ppm: 7.87 (d, 1H), 7.46 (d, 1 H), 7.18 (dd, 1 H), 4.42 (q, 2 H), 2.79 (s, 3 H), 1.45 (t, 3 H).

[0235] The following intermediate was prepared in a manner similar to Int-BOOl (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 2: Exemplary intermediate.Synthesis of ethyl 2-methyl-5-vinylbenzofuran-3-carboxylate (Int-B002)

[0236] A stirred solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int - B001) (5 g, 14.189 mmol) in 1,4-dioxane (30 mL) and water (10 mL) was degassed with nitrogen for 20 min. and then treated with potassium trifluoro(vinyl)borate (1.9 g, 14.2 mmol), sodium carbonate (4.5 g, 42.46 mmol) and PdCL(dppf).DCM (0.576 g, 0.709 mmol), and degassed with nitrogen for another 10 min. The RM was stirred to 90 °C for 16 h. After completion, the RM was diluted with EtOAc (200 mL), washed with water (100 mL), brine (100 mL), dried over Na2SO4 and filtered and distilled under reduced pressure. The residue was purified by FCC on silica gel using 20% EtOAc in Pet. ether as a gradient to afford ethyl 2-methyl-5-vinylbenzofuran-3-carboxylate (Int-B002) as a pale yellow liquid (1.6 g).1H NMR (400 MHz, CDCl3) 5 ppm: 7.98 (s, 1 H), 7.37 (d, 2 H), 6.83 (dd, 1 H), 5.78 (dd, 1 H), 5.48 (dd, 1 H), 4.43 (q, 2 H), 2.77 (s, 3 H), 1.44 (t, 3 H).

[0237] The following intermediates were prepared in a manner similar to Int-B002 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 3 : Exemplary intermediates.Synthesis of ethyl 2-methyl-5-(2-phenylcvclopropyl)benzofuran-3-carboxylate (Int-B003) and 2-methyl-5-(2- phenylcvclopropyl)benzofuran-3 -carboxylic acid (Int-B004)

[0238] Step 1 : A solution of N-benzylidene-4-methylbenzenesulfonohydrazide (1.9 g, 6.95 mmol) in 1,4 dioxane (30 mL) was treated with K2CO3 (1.44 g, 10.43 mmol) and ethyl 2-methyl-5-vinylbenzofuran-3-carboxylate (1.6 g, 6.95 mmol) at RT. The RM was stirred at 110 °C for 6 h. After cooling to RT, the RM was diluted with water (50 mL), extracted with EtOAc (2 x 50 mL). Combined organic layer was dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 5% EtOAc in Pet. ether as a gradient to afford ethyl 2-methyl-5-(2-phenylcyclopropyl)benzofuran-3-carboxylate (Int-B003) (mixture of cis & trans isomers) as an off white solid (1.8 g, 80%).

[0239] Step 2 : A solution of ethyl 2-methyl-5-(2-phenylcyclopropyl)benzofuran-3-carboxylate (Int-B003) (1.6 g, 4.99 mmol) in THF (25 mL) and MeOH (10 mL) was treated with LiOH.FLO (1.25 g, 30 mmol) in water (10 mL) at 0 °C. The RM was stirred at RT for 24 h. After completion, the RM was concentrated under reduced pressure. The residue was diluted with water (10 mL), acidified with 10% citric acid (pH~4), extracted with 10% MeOH in DCM (2 x 50 mL), dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 50% EtOAc in Pet. ether as a gradient to afford a crude residue. The residue was dissolved in THF (25 mL) and treated with OsO4 (125 mg, 0.495 mmol) and sodium periodate (3.17 g, 14.84 mmol) in water (5 mL ) at RT. The RM was stirred at RT for 3 h. After 3 h, the reaction mixture was diluted with DCM (50 mL), washed with water (30 mL), dried over Na2SO4 and filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 30% EtOAc in pet ether as a gradient, to afford 2-methyl-5-(2-phenylcyclopropyl)benzofuran-3-carboxylic acid (Int-B004) (600 mg) as a brown solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.80 (d, 1H), 7.36-6.95 (m, 10 H), 2.80 (s, 3 H), 2.34-2.18 (m, 2 H), 1.55-1.46 (m, 3 H).Synthesis of 2-methyl-5-(trans-2-(pyridin-2-yl) cyclopropyl) benzofuran-3 -carboxylic acid (Int-B005)

[0240] Step 1 : To a stirred solution of 4-methylbenzenesulfonohydrazide (5 g, 26.849 mmol) in EtOH (100 mL) was added picolinaldehyde (2.809 ml, 29.534 mmol) at RT. The RM was stirred at RT for 3 h. The RM wasconcentrated under reduced pressure. The residue was purified by FCC on silica gel using 50% EtO Ac in pet. ether as a gradient to afford 4-Methyl-N'-(pyridin-2-ylmethylene) benzenesulfonohydrazide (6 g, 81.17%) as a yellowish solid.!H NMR (400 MHz, DMSO-de) δ ppm: 11.77 (s, 1 H), 8.55 - 8.54 (m, 1 H), 7.91 (s, 1 H), 7.82 - 7.72 (m, 4 H), 7.42 - 7.39 (m, 2 H), 7.39 - 7.36 (m, 1 H), 2.36 (s, 3 H).

[0241] Step 2 : To a stirred solution of 4-Methyl-N'-(pyridin-2-ylmethylene) benzenesulfonohydrazide (4 g, 14.528 mmol) in Toluene (50 mL) were added CS2CO3 (4.734 g, 14.528 mmol), Cobalt (II) Tetraphenylporphyrin (0.195 g, 0.291 mmol) and ethyl 2-methyl-5-vinylbenzofuran-3 -carboxylate (2.0 g, 8.717 mmol) at RT. The RM was stirred at 110°C for 16 h. The RM was cooled to RT, diluted with water (100 mL) and extracted with EtO Ac (2 x 150 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 30% to 50% of EtO Ac in pet. ether as a gradient to afford ethyl 2-methyl-5-(trans-2-(pyridin-2-yl) cyclopropyl) benzofuran-3 -carboxylate (2.0 g, 42.84%) brown gummy.1H NMR (400 MHz, CDCl3) 5 ppm: 8.51 - 8.49 (m, 1 H), 7.75 (d, 1 H), 7.57 - 7.52 (m, 1 H), 7.32 (d, 1 H), 7.22 - 7.19 (m, 1 H), 7.10 - 7.05 (m, 2 H), 4.43 - 4.38 (m, 2 H), 2.75 (s, 3 H), 2.66 - 2.63 (m, 1 H), 2.33 - 2.28 (m, 1 H), 1.81 - 1.76 (m, 1 H), 1.53 - 1.49 (m, 1 H), 1.44 (t, 3 H).

[0242] Step 3 : To a stirred solution of ethyl 2-methyl-5-(2-(pyridin-2-yl) cyclopropyl) benzofuran-3 -carboxylate (2.0 g, 6.223 mmol) in MeOH: THF: H2O (1: 1: 1) (21 mL) was treated with NaOH (2.489 g, 62.232 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure. The residue was neutralized (pH~7) with sat. Citric acid solution in water (10 mL), precipitated solid was filtered, washed with water (50 mL), and dried under high vacuum to afford 2-methyl-5-(2-(pyridin-2-yl) cyclopropyl) benzofuran-3 -carboxylic acid (1.5 g, 82.17%) as a pale brown solid.1H NMR (400 MHz, DMSO-de) δ ppm: 12.99 (s, 1 H), 8.46-8.45 (m, 1 H), 7.68 - 7.63 (m, 2 H), 7.48 (d, 1 H), 7.39 (d, 1 H), 7.17 - 7.14 (m, 2 H), 2.71 (s, 3 H), 2.57 - 2.50 (m, 1 H), 2.38 - 2.35 (m, 1 H), 1.69 - 1.64 (m, 1 H), 1.49 - 1.45 (m, 1 H).

[0243] The following cyclopropyl derivatives were prepared in a manner similar to Int-B005 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 4: Exemplary intermediates.Synthesis of 5-(trans-[l,T-bi(cyclopropan)]-2-yl)-2-methylbenzofuran-3-carboxylic acid (Int-B009)

[0244] Step 1 : Ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int-BOOl) (3.0 g, 8.51 mmol) in 1,4-dioxane (20 mL), H2O (5.0 mL) was treated with (E)-2-(2-cyclopropylvinyl)-4, 4,5,5- tetramethyl-l,3,2-dioxaborolane (1.98 g, 10.21 mmol) andNa2CO3 (1.80 g, 17.03 mmol) was degassed with argon for 5 min and followed by addition of PdCl2dppf.DCM (694.98 mg, 0.85 mmol), The RM was stirred at 110°C for 16 h in sealed tube, The RM was filtered through Celite pad, washed with EtOAc (20 mL). The filtrate was concentrated under reduced pressure The residue was purified by FCC on silica gel using 2% EtOAc in pet etherto afford ethyl (E)-5-(2-cyclopropylvinyl)-2-methylbenzofuran-3-carboxylate (3) as a colorless liquid (1.50 g, 84%),1H NMR (400 MHz, CDCl3) 5 ppm: 7.87 (s, 1 H), 7.32 - 7.29 (m, 1 H), 7.25 - 7.22 (m, 1 H), 7.57 (d, 1 H), 5.76 - 5.70 (m, 1 H), 4.40 (q, 2 H), 2.75 (s, 3 H), 1.59 - 1.55 (m, 1 H), 144 (t, 3 H), 0.84 - 0.79 (m, 2 H), 0.53- 0.52 (m, 2 H).

[0245] Step 2 : To a solution of ethyl (E)-5-(2-cyclopropylvinyl)-2-methylbenzofuran-3-carboxylate (1.50 g, 5.54 mmol) in DCE (40 mL) was added NiCL (143.82 mg, 1.11 mmol), DCM (3.62 mL, 44.39 mmol) at 0°C and stirred at 65°C for 10 min and then Et2Zn (1.0 M in Hexane) was added (22.22 mL, 22.19 mmol). The RM was stirred at 65°C for 16 h. After completion of the reaction mixture was quenched with ice water (30 mL), extracted with DCM (2 x 15 mL). Combined organic phases were washed with sat. brine solution (40 mL), dried over anhydrous Na2SC>4 and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 2% EtOAc in pet. ether as a gradient to afford ethyl 5-([l,l'-bi(cyclopropan)]-2-yl)-2-methylbenzofuran-3- carboxylate (450 mg, 28.52%). 1H NMR (400 MHz, CDCl3) 5 ppm: 7.62 (s, 1 H), 7.26 (s, 1 H), 6.96 (dd, 1 H), 4.40 (q, 2 H), 2.75 (s, 3 H), 1.54 (s, 1 H), 1.44 (t, 3 H), 0.97 - 0.84 (m, 1 H), 0.82 - 0.80 (m, 1 H), 0.79 - 0.75 (m, 2 H), 044 - 0.40 (m, 2 H), 0.18 - 0.15 (m, 2 H).

[0246] Step 3 : A solution of ethyl 5-([l,l'-bi(cyclopropan)]-2-yl)-2-methylbenzofuran-3-carboxylate (450 mg, 1.58 mmol) in MeOH: THF: Water (1: 1: 1, 15.0 mL), was treated with NaOH (316.50 mg, 7.91 mmol) at 0 °C. The RM was stirred at RT for 16 h. After completion of the reaction, the RM was concentrated under reduced pressure. The residue was acidified with sat. citric acid solution (pH~5). extracted with DCM (2 x 15 mL). Combined organic phases were washed with sat. brine solution (40 mL), dried over anhydrous Na2SC>4 and concentrated under reduced pressure, to afford cmde compound as brown gummy mass (550 mg). The residue was purified by RP and a gradient of 100% ACN in Water to afford 5-(trans-[l,l'-bi(cyclopropan)]-2-yl)-2- methylbenzofuran-3 -carboxylic acid (Int-B009) as an off-white solid (250 mg, 61.64%),1H NMR (400 MHz, CDCl3) 5 ppm: 12.92 (brs, 1 H), 7.56 (s, 1 H), 7.40 (d, 1 H), 6.98 (d, 1 H), 2.68 (s, 3 H), 1.80 - 1.77 (m, 1 H), 1.10- 1.06 (m, 1 H), 0.96 - 0.92 (m, 1 H), 0.79 - 0.75 (m, 2 H), 042 - 0.40 (m, 2 H), 0.16 - 0.14 (m, 2 H).Synthesis of ethyl (E)-2-methyl-5-styrylbenzofuran-3-carboxylate (Int-B114) and 5-((trans)-2,2-difluoro-3- phenylcvclopropyD-2-methylbenzofuran-3-carboxylic acid (Int-B012)

[0247] Step 1 : A solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int- B001) (1 g, 2.84 mmol) in 1,4-dioxane (8 mL) and water (2 mL) were treated with (E)-styrylboronic acid (0.504 g, 3.406 mmol), sodium carbonate (0.903 g, 8.516 mmol), degassed with nitrogen gas for 15 min. Then, it was treated with PdC12(dppf).DCM (115.9 mg, 0.142 mmol) at RT. The RM was stirred at 90 °C for 16 h. Another reaction with same scale was performed and both RM were combined, filtrated through small pad of Celite, washed with EtOAc (50 mL). The filtrate was concentrated under reduced pressure and the residue was diluted with water (30 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 2% EtOAc in Pet. ether as to afford ethyl (E)-2-methyl-5-styrylbenzofuran-3-carboxylate (1 g, Yield: 57%) as off white solid.1HNMR (400 MHz, CDCl3) 5 ppm: 8.09 (d, 1 H), 7.54-7.42 (m, 2 H), 7.49-7.46 (m, 1 H), 7.41-7.33 (m, 3 H), 7.27- 7.24 (m, 1 H), 7.21 (s, 1 H), 7.14 (s, 1 H), 4.44 (q, 2 H), 2.80 (s, 3 H), 1.47 (t, 3 H).

[0248] Step 2 : A stirred solution of ethyl (E)-2-methyl-5-styrylbenzofuran-3-carboxylate (1 g, 3.26 mmol) in 1,4-dioxane (1.1 mL) and toluene (1 mL) were treated with dry KI at 60 °C under nitrogen. Then, the RM was heated to 120 °C and treated with trimethylsilyl chloride (0.835 mL, 6.53 mmol) followed by methyl 2,2-difluoro- 2-(fluorosulfonyl)acetate (1.25 g, 6.53 mmol). The RM was stirred at 120 °C for 48 h. The RM was allowed cool to RT, and diluted with water (30 mL), extracted with EtOAc (2 x 30 mL). The combined organic layers were dried over Na2SC>4, fdtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in Pet. Ether as a gradient. The residue was purified by Prep. HPLC [Prep. HPLC conditions: Mobile phase: lOmM ABC in Water, Mobile phase B: ACN, Column: X-SELECT C18 (19 x 150) x 5 pm, FLOW: 20 ml / min, Method: (T in min. / % of B): 0 / 60, 2 / 60, 10 / 80, 16.2 / 80, 16.2 / 98, 20.2 / 98, 20.3 / 60, 24 / 60, Temperature: RT.] The desired fractions were evaporated and lyophilized to afford ethyl 5-((trans)-2,2-difluoro-3- phenylcyclopropyl)-2-methylbenzofuran-3-carboxylate (400 mg, 34%) as a brown gummy.1H NMR (400 MHz, CDCl3) 5 ppm: 7.95 (d, 1 H), 7.42-7.39 (d, 1 H), 7.38-7.29 (m, 5 H), 7.26-7.23 (m, 1 H), 4.42 (q, 2 H), 3.16-3.12 (m, 1 H), 3.10-3.05 (m, 1 H), 2.77 (s, 3 H), 1.43 (t, 3 H).

[0249] Step 3 : A stirred solution of ethyl 5-(2,2-difluoro-3-phenylcyclopropyl)-2-methylbenzofuran-3- carboxylate (400 mg, 1.123 mmol) in THF (10 mL), MeOH (3 mL) was treated with LiOH.H2O (282 mg, 6.73 mmol) in water (3 mL) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the residue was diluted with water (4 mL), and acidified with IN HO (pH~4). The solid was fdtered, washed with water (5 mL) and dried under vacuum to afford 5-((trans)-2,2-difluoro-3-phenylcyclopropyl)-2- methylbenzofuran-3 -carboxylic acid (350 mg, 89%) as an off white solid.1H NMR (400 MHz, DMSO-de) 5 ppm: 8.09 (d, 1 H), 7.45-7.37 (m, 5 H), 7.33-7.31 (m, 1 H), 7.21-7.19 (m, 1 H), 3.62-3.56 (m, 1 H), 3.42-3.36 (m, 1 H), 2.68 (s, 3 H).19F NMR (376 MHz, CDCl3) 5 ppm: -133.42 - -134.69 (m).Synthesis of 2-methyl-5-(cis-2-phenylcvclopropyl)benzofuran-3-carboxylic acid (Int-B013) and 2-methyl-5- (trans-2-phenylcvclopropyl)benzofuran-3 -carboxylic acid (Int-B014)

[0250] 2.5g of CIS / TRANS mixture of Int-B004 were separated by Prep. HPLC [Prep. HPLC conditions: Mobile phase: 10%FA in Water, Mobile phase B: ACN, Column: UniHybride C18 (25 x 150 mm) x 8 pm, FLOW: 20 ml / min, Method: (T in min. / % ofB): 0 / 5, 2 / 55, 10 / 80, 12 / 80, 12.1 / 100, 15 / 100, 15.1 / 55, 20 / 55, Temperature: RT.] The desired fractions were evaporated and lyophilized to afford 2-methyl-5-(cis-2-phenylcyclopropyl)benzofuran- 3-carboxylic acid (Int-B013) (200 mg, the first eluting) and 2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran- 3-carboxylic acid (Int-B014) (1.3 g, the second eluting). Int-B014 :1H NMR (400 MHz, DMSO-de) 5 ppm: 12.96 (brs, 1 H), 7.68 (d, 1 H), 7.48 (d, 1 H), 7.30 - 7.26 (m, 2 H), 7.20 - 7.11 (m, 4 H), 2.71 (s, 3 H), 2.38 - 2.33 (m, 1 H), 2.19 - 2.15 (m, 1 H), 1.46 (t, 2 H).

[0251] A preparative chiral SFC was performed on the racemic mixture of Int-B014 to afford Int-B014 - Enl and Int-B014 - En2.Synthesis of ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (Int-B015) and 2-methyl-5-((2- tosylhydrazineylidene) methyl)benzofuran-3 -carboxylate (Int-B016)

[0252] Step 1 : A solution of ethyl 2-methyl-5-vinylbenzofuran-3-carboxylate (Int-B002) (6.0 g, 26.057 mmol) inTHF (120 mL) was treated with OsO i (4%wt aqueous) (1.65 mL) followed by the addition of Sodium periodate (16.720 g, 78.171 mmol) and water (24 mL) at RT. The RM was stirred at RT for 16 h. After completion of the reaction, RM was diluted with water (100 mL) and extracted with EtOAc (2 x 50 mL). Combined organic layer was washed with water (2 x 50 mL), brine (50 mL) dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 9% EtOAc in pet ether as gradient to afford ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (Int-B015) (3.5 g, 57.84%) as off-white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 10.09 (s, 1 H), 8.48 (d, 1 H), 7.89 - 7.86 (d, 1 H), 7.54 (d, 1 H), 4.48 - 4.43 (m, 2 H), 2.81 (s, 3 H), 1.47 (t, 3 H).

[0253] Step 2 : A solution of 4-methylbenzenesulfonohydrazide (2.8 g, 15.035 mmol) in EtOH (30.0 mL) was treated with ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (Int-B015) (3.492 g, 15.035 mmol). The RM was stirred at RT for 16 h. After completion of reaction, RM was filtered and washed with ethanol (5.0 mL). Solid was dried under vacuum to afford 2-methyl-5-((2-tosylhydrazineylidene) methyl)benzofuran-3 -carboxylate (Int- B016) (5.1 g, 84.71%) as an off-white solid.!H NMR (400 MHz, CDCl3) 5 ppm: 8.05 (s, 1 H), 7.88 (t, 3 H), 7.69- 7.65 (m, 2 H), 7.40 (d, 1 H), 7.31 (d, 2 H), 4.44-4.39 (m, 2 H), 2.76 (s, 3 H), 2.40 (s, 3 H), 1.45 (t, 3 H).

[0254] The following intermediate was prepared in a manner similar to Int-B016 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 5: Exemplary intermediate.Synthesis of 2-methyl-5-(trans-2-methyl-2-(pyridin-2-yl)cvclopropyl)benzofuran-3-carboxylic acid (Int-B017) and 2-methyl-5-(cis-2-methyl-2-(pyridin-2-yl)cvclopropyl)benzofuran-3-carboxylic acid (Int-B018)

[0255] Step 1 : To a stirred solution of 2-(prop-l-en-2-yl)pyridine (700 mg, 5.874 mmol, 1.0 equiv.) in toluene (20.0 mL) was treated with ethyl 2-methyl-5-((2-tosylhydrazineylidene)methyl)benzofuran-3-carboxylate (Int- B016) (2.352 g, 5.874 mmol), CS2CO3 (2.871 g, 8.811 mmol.) and degassed with N2 for 10 min. Then treated withcobalt(II) meso-tetraphenylporphyrin (394.546 mg, 0.587 mmol) and stirred at 120 °C for 16 h. The RM was diluted with water (15 mL) and extracted with EtOAc (2 x 50 mL). Combined organic layer was washed with brine (15 mL), dried over ySO i. filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in pet ether gradient to afford ethyl 2-methyl-5-(2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxylate (600 mg, 30.45%) as black gum.1H NMR (400 MHz, CDCL) 5 ppm: 8.55 (d, 1 H), 7.82 (s, 1 H), 7.63-7.60 (m, 1 H), 7.37-7.32 (m, 2 H), 7.18-7.15 (m, 1 H), 7.10-7.06 (m, 1 H), 4.47- 4.38 (m, 2 H), 2.93 (t, 1 H), 2.75 (s, 3 H), 1.90-1.87 (m, 1 H), 1.45 (t, 3 H), 1.45 (t, 1 H), 1.2 (s, 3 H).

[0256] Step 2 : To a stirred solution of ethyl 2-methyl-5-(2-methyl-2-(pyridin-2-yl)cyclopropyl)benzofuran-3- carboxylate (500 mg, 1.491 mmol) in THF: MeOH: H2O (1:1: 1) (6 mL) was cooled to 0 °C and treated with LiOH. H2O (312.773 mg, 7.454 mmol) at RT. The RM was stirred at RT for 24 h. The RM was concentrated under reduced pressure and the residue was acidified with saturated citric acid (pH~4). The solid was filtered and washed with water (2.0 mL). The residue was purified by FCC on silica gel using 30% EtOAc in pet ether as a gradient to afford 2-methyl-5-(trans-2-methyl-2-(pyridin-2-yl)cyclopropyl)benzofuran-3-carboxylic acid (Int-B017) (350 mg, 76.39%) as pale brown solid and 2-methyl-5-(cis-2-methyl-2-(pyridin-2-yl)cyclopropyl)benzofuran-3- carboxylic acid (Int-B018) (6 mg, 1.31%) as pale brown solid.1H NMR of Int-B017 (400 MHz, DMSO-de) 5 ppm: 12.94 (s, 1 H), 8.52 (s, 1 H), 7.74 (d, 2 H), 7.50 - 7.42 (m, 2 H), 7.18 (t, 2 H), 3.25 (s, 1 H), 2.83-2.73 (m, 3 H), 1.99 (s, 1 H), 1.79 (s, 1 H), 1.40 (s, 3 H).

[0257] The following intermediates were prepared in a manner similar to Int-B017 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 6: Exemplary intermediates.Synthesis of 5-(2-cyclopentylcyclopropyl)-2-methylbenzofuran-3-carboxylic acid (Int-B038)

[0258] Step 1 : A solution of ethyl 2-methyl-5-((2-tosylhydrazineylidene) methyl) benzofuran-3 -carboxylate (Int-B016) (3.0 g, 7.49 mmol), in DCM (40 mL) was cooled to 0°C, treated with NaH (60%) (0.468 g, 11.23 mmol,) and stirred at RT for 1 h. After Ih, Vinylcyclopentane (1.80 g, 18.72 mmol) in DCM (10 mL) and Silver carbonate (0.413 g, 1.49 mmol) were added at RT. The RM was stirred for 16 h at 40°C in sealed tube. The RM was filterd through the celite bed was washed with DCM (50 mL) and concentrated under reduced pressure, to afford crude product as a brown gummy mass (4.0 g). The residue was purified by FCC on silica gel using 2% EtOAc in Pet ether as a gradient to afford ethyl 5-(2-cyclopentylcyclopropyl)-2-methylbenzofuran-3-carboxylate (1.0 g, 42.73%).

[0259] Step 2 : A solution of ethyl 5-(2-cyclopentylcyclopropyl)-2-methylbenzofuran-3-carboxylate (900 mg, 2.88 mmol) in MeOH: THF : Water (10.0 mL), was treated with NaOH (576.16 mg, 14.40 mmol) at 0 °C. The RM was stirred for 16 h at RT. The RM was concentrated under reduced pressure and the obtained residue was acidified with sat. citric acid solution (pH~5, 15 mL). extracted with EtOAc (3 x 10 mL). Combined organic phases were washed with brine (15.0 mL), dried over anhydrous Na2SO i and concentrated under reduced pressure. The residue was purified by FCC on silica gel 20% EtOAc in pet-ether as a gradient to afford 5-(2-cyclopentylcyclopropyl)-2- methylbenzofuran-3 -carboxylic acid (Int-B038) (150 mg, 32.96%) as a pale yellow gummy mass.Synthesis of 5-(trans-2,2-dimethyl-3-(pyridin-2-yl)cvclopropyl)-2-methylbenzofuran-3-carboxylic acid (Int-

[0260] Step 1 : To a stirred solution of (E)-2-(2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)vinyl)pyridine (3.0 g, 12.98 mmol), ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int-BOOl) (5.03 g, 14.27 mmol) in 1,4-dioxane (30 mL) and water (10 mL) was added Na2COs (3.44 g, 32.45 mmol) and degassed with argon for 15 min. PdCL(dppf).DCM (529.63 mg, 0.649 mmol) was added to the RM at RT. The RM was stirred at 110 °C for 16 h. The RM was filtered through celite bed, rinsed with EtOAc (50 mL), filtrate was extracted with EtOAc (2 x 50 mL), the combined organic layer was washed with brine solution (50 mL). Organic layer was dried over Na2SO i. filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in pet ether as a gradient to afford ethyl (E)-2-methyl-5-(2-(pyridin-2- yl)vinyl)benzofuran-3 -carboxylate as a pale yellow gummy (1.4 g, 35.09%).

[0261] Step 2 : A solution of NiCL (177.10 mg, 1.367 mmol), 2,2-diiodopropane (3.37 g, 11.38 mmol) and ethyl (E)-2-methyl-5-(2-(pyridin-2-yl)vinyl)benzofuran-3-carboxylate (1.4 g, 4.555 mmol) inDCE (30 mL) was treated with Diethyl zinc (1 M in hexane) (22.77 mL, 22.77 mmol) at 70 °C over 30 min. The RM was stirred for 1 h at 70 °C. The RM was quenched with water (100 mL) and extracted with DCM (2 x 100 mL). Organic layer was dried over Na2SO i. filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in pet ether as a gradient to afford ethyl 5-(2,2-dimethyl-3-(pyridin-2-yl)cyclopropyl)-2-methylbenzofuran-3 -carboxylate as a pale yellow gummy (800 mg, 50.26%).1H NMR (400 MHz, CDCh) 5 ppm: 8.55 - 8.54 (m, 1 H), 7.85 (bs, 1 H), 7.62 - 7.57 (m, 1 H), 7.32 (d, 1 H), 7.30 (d, 1 H), 7.20 (dd, 1 H), 7.11 - 7.08 (m, 1 H), 4.43 - 4.38 (m, 2 H), 2.99 (d, 1 H), 2.75 (s, 3 H), 2.54 (d, 1 H), 1.43 (m, 3 H), 1.15 (s, 3 H), 1.01 (s, 3 H).

[0262] Step 3 : To a stirred solution of ethyl 5-(2,2-dimethyl-3-(pyridin-2-yl)cyclopropyl)-2-methylbenzofuran- 3-carboxylate (800 mg, 2.289 mmol) in THF (5.0 mL), MeOH (2.5 mL) and water (2.5 mL) was added NaOH (457.85 mg, 11.44 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the obtained residue was acidified with citric acid solution (pH~0.6). The white precipitate was filtered and washed with water (20 mL). The solid was dried using high vacuum to afford 5-(trans-2,2-dimethyl- 3 -(pyridin-2-yl)cyclopropyl)-2-methylbenzofuran-3 -carboxylic acid (Int-B021) as a pale yellow solid (400 mg, 54.36%).1H NMR (400 MHz, DMSO-de) δ ppm: 12.97 (bs, 1 H), 8.50 (d, 1 H), 7.79 (bs, 1 H), 7.71 - 7.67 (m, 1 H), 7.47 (d, 2 H), 7.23 - 7.17 (m, 2 H), 3.02 (d, 1 H), 2.71 (s, 3 H), 2.57 (d, 1 H), 1.09 (s, 3 H), 0.94 (s, 3 H).Synthesis of 2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3-carboxylic acid (Int-B027) and 5- (cyclopentylidenemethyl)-2-methylbenzofuran-3-carboxylic acid (Int-B093)

[0263] Step 1 : A stirred solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int-BOOl) (7.5 g, 21.290 mmol) and 2-(cyclopentylidenemethyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (6.646 g, 31.935 mmol) in 1,4-dioxane and water (4: 1, 25 mL) was treated with Na2COs (6.770 g, 63.870 mmol) and degassed with nitrogen for 20 min. Then, the RM was treated with PdChdppf.DCM (1.737 mg, 2.129 mmol) at RT and stirred at 90 °C for 16 h. The RM was filtered through small pad of Celite and washed with DCM (4 x 50 mL). the filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0- 5% EtOAc in Pet. ether as a gradient to afford ethyl 5-(cyclopentylidenemethyl)-2-methylbenzofuran-3- carboxylate (5.5 g, 90%) as a yellow solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.93 (s, 1 H), 7.35 (m, 1 H), 7.22 - 7.19 (m, 1 H), 6.47 - 6.46 (m, 1 H), 4.43 - 4.38 (m, 2 H), 2.75 (m, 3 H), 2.60 - 2.50 (m, 4 H), 1.81 - 1.78 (m, 2 H), 1.70 - 1.66 (m, 2 H), 1.47 - 1.43 (m, 3 H), 1.25 (d, 1H).

[0264] Step 2 : A stirred solution of NiCh (1.003 g, 4.220 mmol), DCM (4.5 mL, 56.268 mmol) and ethyl 5- (cyclopentylidenemethyl)-2-methylbenzofuran-3-carboxylate (4 g, 14.067mmol) in DCE (100 mL) was treated with Diethyl zinc (IM in hexane, 56 mL, 56.268 mmol) at 60 °C in 30 min. The RM was stirred at 60 °C for 16 h. The RM was quenched with water (100 mL) and extracted with DCM (2 x 100 mL). The combined organic layers were dried over Na2SC>4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0-40% EtOH in Pet. ether as a gradient to afford the mixture of desired product and starting material (3.9 g, 1 / 1) as yellow gummy.

[0265] Step 3 : A stirred solution of ethyl 2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3-carboxylate (2.7 g,9.049 mmol) in MeOH:THF:H2O (2:2:1, 10 mL) was treated with LiOH.H2O (1.519 g, 36.195 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated and the residue was diluted with water (10 mL), acidified with AcOH (pH ~2) and stirred for 30 min. The precipitated solid was filtered, washed with water (100 mL) and dried under vacuum suction to afford 2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3-carboxylic acid (Int-B027) and 5-(cyclopentylidenemethyl)-2-methylbenzofuran-3-carboxylic acid (Int-B093) (1.4 g. 57%) as an off-white solid.Synthesis of Trans-5-(-2-(dimethylcarbamoyl) cvclopropyl)-2-methylbenzofuran-3-carboxylic acid (Int-B035)

[0266] Step 1 : A solution of diethyl (2-(dimethylamino)-2 -oxoethyl) phosphonate (3.17 g, 14.21 mmol) in THF (60 mL) was treated with NaH (60 %) (620.06 mg, 25.83 mmol) at 0 °C and stirred for 10 min. After 10 min, ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (3.0 g, 12.91 mmol) in THF (15 mL) was added at 0 °C. The RM was stirred at RT for 3 h. The RM was diluted with cold water (50 mL), extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO i. filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 70% EtOAc in pet ether as a gradient afford ethyl (E)-5-(3-(dimethylamino)-3-oxoprop-l-en-l-yl)-2-methylbenzofuran-3-carboxylate as a pale yellow solid (1.8 g, 46.24%).1H NMR (400 MHz, CDCl3) 5 ppm: 8.14 (d, 1 H), 7.80 (d, 1 H), 7.47 (dd, 1 H), 7.40 (d, 1 H), 6.91 (d, 1 H), 4.42 (q, 2 H), 3.15 (d, 6 H), 2.77 (s, 3 H), 1.46 (t, 3 H).

[0267] Step 2 : A solution of NiCl2(180.63 mg, 1.394 mmol), DCM (2.99 mL, 37.16 mmol) and ethyl (E)-5-(3- (dimethylamino)-3 -oxoprop- l-en-l-yl)-2-methylbenzofuran-3 -carboxy late (1.4 g, 4.646 mmol) in DCE (60 mL) was treated with Diethyl zinc (1 M in hexane) (18.5 mL, 18.58 mmol) at 70 °C over 30 min. The RM was stirred for 16 h at 70 °C. The RM was quenched with water (500 mL) and extracted with DCM (2 x 50 mL). Organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 40% EtOAc in pet ether as a gradient to afford Trans-ethyl 5-(2-(dimethylcarbamoyl) cyclopropyl)-2-methylbenzofuran-3 -carboxylate as a pale yellow gummy (450 mg, 30.71% ). 1H NMR (400 MHz, CDC13) 5 ppm: 7.71 (d, 1 H), 7.32 (d, 1 H), 7.06 (dd, 1 H), 4.40 (q, 2 H), 3.14 (s, 3 H), 3.00 (s, 3 H), 2.75 (s, 3 H), 2.62 - 2.57 (m, 1 H), 2.03 - 1.99 (m, 1 H), 1.69 - 1.64 (m, 1 H), 1.44 (t, 3 H), 1.34 - 1.30 (m, 1 H).

[0268] Step 3 : To a stirred solution of Trans-ethyl 5-(-2-(dimethylcarbamoyl)cyclopropyl)-2-methylbenzofuran- 3-carboxylate (550 mg, 1.744 mmol) in THF (5.0 mL), MeOH (2.5 mL) and H2O (2.5 mL) was added NaOH (348.77 mg, 8.72 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the obtained residue was acidified with IN HO solution (pH~0.4). The white precipitate was fdtered, washed with water (10 mL) and dried using high vacuum to afford Trans-5-(-2-(dimethylcarbamoyl) cyclopropyl)- 2 -methylbenzofuran-3 -carboxylic acid as an off white solid (Int-B035) (400 mg, 79.83%). 1H NMR (400 MHz, DMSO-D6) 5 ppm: 12.90 (bs, 1 H), 7.66 (d, 1 H), 7.47 (d, 1 H), 7.13 (dd, 1 H), 3.08 (s, 3 H), 2.86 (s, 3 H), 2.71 (s, 3 H), 2.41 - 2.36 (m, 1 H), 2.19 - 2.14 (m, 1 H), 1.42 - 1.38 (m, 1 H), 1.27 - 1.22 (m, 2 H).Synthesis of 2-methyl-5-(l-phenylcvclopropyl)benzofuran-3 -carboxylic acid (Int-B037)

[0269] Step 1 : To a stirred solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3- carboxylate (5.0 g, 14.19 mmol), 4,4,5,5-tetramethyl-2-(l-phenylvinyl)-l,3,2-dioxaborolane (4.24 g, 18.45 mmol) in 1,4-dioxane (30 mL) and water (10 mL) was added K3PO4 (4.51 g, 21.29 mmol) and degassed with argon for 15 min. Then treated with PdC12(dppf).DCM (579.08 mg, 0.710 mmol) at RT. The RM was stirred at 80 °C for 16 h. The RM was filtered through celite bed, rinsed with EtOAc (50 mL), filtrate was extracted with EtOAc (2 x 50 mL), the combined organic layer was washed with brine solution (100 mL). Organic layer was dried overNa2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 4% EtOAc in pet ether as a gradient to afford ethyl 2-methyl-5-(l-phenylvinyl)benzofuran-3-carboxylate as a pale yellow gummy (2.3 g, 52.89%).!H NMR (400 MHz, CDCl3) 5 ppm: 7.95 (d, 1 H), 7.37 - 7.30 (m, 6 H), 7.23 (dd, 1 H), 5.48 (d, 2 H), 4.36 (q, 2 H), 2.77 (s, 3 H), 1.34 (t, 3 H).

[0270] Step 2 : A solution of Et2Zn (IM in hexane) (8.48 mL, 8.48 mmol) in DCM (10 mL) was cooled in an ice bath. A solution of TFA (0.649 mL, 8.487 mmol) in DCM (3.0 mL) was then added dropwise. Upon stirring for 20 min, a solution of DCM (0.685 mL, 8.487 mmol) in DCM (3.0 mL) was added to the RM. After an additional 20 min of stirring, a solution of the ethyl 2-methyl-5-(l-phenylvinyl)benzofuran-3-carboxylate (1.3 g, 4.24 mmol) in DCM (4.0 mL) was added and the ice bath was removed. The RM was stirred for 48 h at RT. The RM was quenched with water (50 mL) and extracted with DCM (2 x 50 mL). Organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 3% EtOAc in pet ether as a gradient to afford ethyl 2-methyl-5 -( 1 -pheny Icy clopropyl)benzofuran-3 -carboxylate as a pale yellow gummy (380 mg, 27.95%).1H NMR (400 MHz, DMSO-de) δ ppm: 7.74 (d, 1 H), 7.50 (d, 1 H), 7.29 - 7.16 (m, 6 H), 4.30 (q, 2 H), 2.71 (s, 3 H), 1.31 - 1.27 (m, 7 H).

[0271] Step 3: To a stirred solution of ethyl 2-methyl-5-(l-phenylcyclopropyl)benzofuran-3-carboxylate (380 mg, 1.186 mmol) inTHF (4.0 mL), MeOH (2.0 mL) and water (2.0 mL) was added NaOH (237.19 mg, 5.93 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the obtained residue was acidified with citric acid solution (pH~0.6). The white precipitate was filtered and washed with water (20 mL). The collected precipitate fraction was dried using high vacuum to afford 2-methyl-5-(l- phenylcyclopropyl)benzofuran-3-carboxylic acid (Int-B037) as an off white solid (330 mg, 95%). 1H NMR (400 MHz, DMSO-d6) 5 ppm: 12.91 (bs, 1 H), 7.80 (d, 1 H), 7.48 (d, 1 H), 7.28 - 7.23 (m, 3 H), 7.18 - 7.12 (m, 2 H), 2.70 (s, 3 H), 1.28 - 1.25 (m, 4 H).Synthesis of 2-methyl-5-(l-phenylethyl)benzofuran-3 -carboxylic acid (Int-B096)

[0272] Step 1 : To a stirred solution of ethyl 2-methyl-5-(l-phenylvinyl) benzofuran-3 -carboxylate (800 mg,2.611 mmol) in EtOH (10 mL) was added 10% Pd / C (416 mg, 3.917 mmol) at RT. The RM was stirred for 16 h under H2balloon pressure at RT. The RM was filtered through celite bed, rinsed with EtOAc (100 mL) and the filtrate was concentrated under reduced pressure to afford ethyl 2-methyl-5-(l-phenylethyl)benzofuran-3- carboxylate (650 mg, 80.72%).1H NMR (400 MHz, CDCl3) 5 ppm: 7.84 (d, 1 H), 7.31 - 7.23 (m, 5 H), 7.19 - 7.17 (m, 1 H), 7.10 (dd, 1 H), 4.38 (q, 2 H), 4.27 (q, 1 H), 2.74 (s, 3 H), 1.67 (d, 3 H), 1.40 (t, 3 H).

[0273] Step 2 : To a stirred solution of ethyl 2-methyl-5-(l-phenylethyl)benzofuran-3-carboxylate (600 mg, 1.94 mmol) in THF (5. mL), MeOH (2.5 mL) and water (2.5 mL) was added NaOH (389.1 mg, 9.72 mmol) at RT. The RM was stirred at RT for 6 h. The RM was concentrated under reduced pressure. The residue was acidified with citric acid solution (pH~0.6). The precipitate was filtered and washed with water (5 mL). The collected precipitate fraction was dried using high vacuum to afford 2-methyl-5-(l-phenylethyl)benzofuran-3 -carboxylic acid (Int- B096) (400 mg, 73.34%).1H NMR (400 MHz, DMSO-de) δ ppm: 7.78 (bs, 1 H), 7.46 (d, 1 H), 7.29 - 7.24 (m, 4 H), 7.21 - 7.18 (m, 1 H), 7.17 - 7.14 (m, 1 H), 4.29 (q, 1 H), 2.07 (s, 3 H), 1.61 (d, 3 H).Synthesis of 2-methyl-5-(cis-3-(trifluoromethyl)cvclobutoxy)benzofuran-3-carboxylic acid (Int-B039),

[0274] Step 1 : A solution of ethyl 5-hydroxy-2-methylbenzofuran-3-carboxylate (1.5 g, 6.811 mmol), trans-3- (trifluoromethyl)cyclobutyl 4-methylbenzenesulfonate (2.20 g, 7.492 mmol) in ACN (20 mL) was treated with CS2CO3 (8.87 g, 27.24 mmol) at RT. The RM was stirred at 80 °C for 16 h. The RM was diluted with ice-cold water (30 mL), extracted with EtOAc (2 x 30 mL). Combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 5% EtOAc in Pet. ether as a gradient to afford ethyl 2-methyl-5-(trans-3- (trifluoromethyl)cyclobutoxy)benzofuran-3-carboxylate as a pale yellow solid (1.0 g, 42.89%).1H NMR (400 MHz, DMSO-de) δ ppm: 7.51 (d, 1 H), 7.26 (d, 1 H), 6.86 - 6.89 (dd, 1 H), 4.71 - 4.75 (m, 1 H), 4.31 - 4.36 (q, 2 H), 2.97 - 3.04 (m, 1 H), 2.71 - 2.75 (m, 5 H), 2.11 - 2.18 (m, 2 H), 1.37 (t, 3 H).

[0275] Step 2 : A solution of ethyl 2-methyl-5-(cis-3-(trifluoromethyl)cyclobutoxy)benzofuran-3-carboxylate (1.0 g, 2.921 mmol) in THF (10 mL), MeOH (5.0 mL) and water (5.0 mL) was added NaOH (1.16 g, 29.21 mmol) at 0 °C. The RM was stirred at RT for 24 h. The RM was concentrated under reduced pressure and the resulting residue was acidified with IN HO (pH~3). The white precipitate was filtered and washed with water (20 mL) and dried using high vacuum to afford 2-methyl-5-(cis-3-(trifluoromethyl)cyclobutoxy)benzofuran-3-carboxylic acid (Int-B039) as an off white solid (750 mg, 81.70%).

[0276] The following acidic intermediates were prepared in a manner similar to Int-B039 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 7: Exemplary intermediates.Synthesis of 2-methyl-5-((octahydropentalen-2-yl)oxy)benzofuran-3-carboxylic acid (Int-B044),

[0277] Step 1 : A solution of ethyl 5-hydroxy-2-methylbenzofuran-3-carboxylate (600 mg, 2.72 mmol) in THF (20.0 mL) was treated with PPln (1.07 mg, 4.08 mmol) and DEAD (40% in toluene) (948.33 mg, 2.72 mmol) followed by addition of octahydropentalen-2-ol (412.27 mg, 3.26 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was diluted with cold water (30 mL) and extracted with EtOAc (2 x 20 mL), dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 15% EtOAc in Pet. ether as a gradient to afford ethyl 2-methyl-5-((octahydropentalen-2-yl) oxy) benzofuran-3 -carboxylate as a pale yellow gummy (200 mg, 33.56%).!H NMR (400 MHz, CDCl3) 5 ppm: 7.43 - 7.44 (d, 1 H), 7.26 (s, 1 H), 6.81 - 6.84 (d, 1 H), 4.83 (s, 1 H), 4.37 - 4.42 (m, 2 H), 2.68 - 2.73 (m, 5 H), 2.12 - 2.14 (m, 2 H), 1.67 - 1.74 (m, 3 H), 1.50 - 1.57 (m, 2 H), 1.40 - 1.46 (m, 4 H), 1.53 (s, 3 H).

[0278] Step 2 : A solution of ethyl 2-methyl-5-((octahydropentalen-2-yl) oxy) benzofuran-3 -carboxylate (250 mg, 0.76 mmol) in MeOH: THF: Water (1: 1:1, 6 mL), was treated with NaOH (91.35 mg, 2.28 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure. The residue was acidifiedwith IN HO (pH~0.3) and extracted with EtOAc (2 x 20 mL), dried over Na2SC>4, fdtered and concentrated under reduced pressure to afford 2-methyl-5-((octahydropentalen-2-yl)oxy)benzofuran-3-carboxylic acid (Int-B044) as a pale brown gummy (200 mg, 87.47%).

[0279] The following acidic intermediates were prepared in a manner similar to Int-B044 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 8: Exemplary intermediates.Synthesis of 5-((2,3-dihvdrobenzofuran-7-yl)oxy)-2-methylbenzofuran-3-carboxylic acid (Int-B050),

[0280] Step 1 : A stirred solution of CS2CO3 (5.907 g, 18.163 mmol), ethyl 5-hydroxy-2-methylbenzofuran-3- carboxylate (2 g, 9.082 mmol) in 1,4-Dioxane (10 mL) was purged with N2 gas for 10 min. Then, 7-bromo-2,3-dihydrobenzofuran (4.519 mg, 22.704 mmol), 2,2,6,6-Tetramethyl-3,5-heptanedione (0.334 mg, 1.816 mmol), and Copper(I) iodide (0.173 g, 0.908 mmol) were added at RT. The RM was purged with N2 gas for 10 min. The RM was stirred at 120 °C for 16 h. The RM was diluted with ice cold water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with ice cold water (100 mL), brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0-5% EtOAc in Pet. ether as a gradient to afford ethyl 5-((2,3-dihydrobenzofuran-7-yl)oxy)-2-methylbenzofuran- 3-carboxylate (700 mg, 22%).1H NMR (400 MHz, CDCl3) 5 ppm: 7.55 (d, 1 H), 7.34 (d, 1 H), 6.99-6.96 (m, 2 H), 6.96-6.75 (m, 2 H), 4.63 (m, 2 H), 4.363 (q, 2 H), 3.28 (t, 2 H), 2.75 (s, 3 H), 1.34 (t, 3 H).

[0281] Step 2 : A solution of ethyl 5-((2,3-dihydrobenzofuran-7-yl)oxy)-2-methylbenzofuran-3-carboxylate (700 mg, 2.069 mmol) in MeOH:THF:H2O (2:2: 1, 7.5 mL) was treated with LiOH.H2O (0.347 g, 8.275 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure. The residue was diluted with water (100 mL), acidified with AcOH (pH ~7) and stirred for 30 minutes. The solid was fdtered, washed with water (100 mL) and dried under vacuum to afford 5-((2,3-dihydrobenzofuran-7-yl)oxy)-2-methylbenzofuran-3- carboxylic acid (Int-B050) (450 mg, 70%).1H NMR (400 MHz, DMSO-de) δ ppm: 12.89 (brs, 1 H), 7.54 (d, 1 H), 7.32 (d, 1 H), 7.09-7.07 (m, 1 H), 6.95 (dd, 1 H), 6.86-6.82 (m, 2 H), 4.52 (t, 2 H), 3.24 (t, 2 H), 2.71 (s, 3 H).

[0282] The following acidic intermediates were prepared in a manner similar to Int-B050 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 9: Exemplary intermediates.Synthesis of 2-methyl-5-(o-tolyloxy)benzofuran-3 -carboxylic acid (Int-B052),

[0283] Step 1 : To a stirred solution of ethyl 5-hydroxy-2-methylbenuran-3-carboxylate (1.5 g, 6.811 mmol) inDioxane (15 mL) was treated with l-iodo-2-methylbenzene (2.184 mL, 17.028 mmol), Cui (129.720 mg, 0.681 mmol), CS2CO3 (6.645 g, 20.434 mmol) in a sealed tube, degassed with N2 for 10 min. After 10 min 2, 2,6,6- Tetramethyl-3,5-Heptanedione (0.285 mL, 1.362 mmol) was added. The RM was stirred for 16 h at 110 °C. The RM was diluted with water (20 mL), extracted with EtOAc (2 x 50 mL). Combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 1% EtOAc in pet. ether as a gradient to afford ethyl 2-methyl-5-(o-tolyloxy) benzofuran- 3-carboxylate (800 mg, 37.85%) as a brown gummy.1H NMR (400 MHz, CDCL) 5 ppm: 7.45 (d, 1 H), 7.34 (d,1 H), 7.25-7.24 (m, 1 H), 7.16-7.12 (m, 1 H), 7.05-7.01 (m, 1 H), 6.91-6.89 (m, 1 H), 6.86-6.84 (m, 1 H), 4.33 (q,2 H), 2.75 (s, 3 H), 2.29 (s, 3 H), 1.33 (t, 3 H).

[0284] Step 2 : To a stirred solution of ethyl 2-methyl-5-(o-tolyloxy) benzofuran-3 -carboxylate (800 mg, 2.578 mmol) in THF (10 mL), MeOH (5 mL) and water (5 mL) was added NaOH (515.51 mg, 12.889 mmol) at 0 °C. The RM was stirred at RT for 6 h. The RM was concentrated under reduced pressure. The residue was acidified with saturated citric acid solution (pH~3). The solid was filtered and washed with water (20 mL), dried under high vacuum. The residue was purified by FCC on silica gel using 25% EtOAc in pet. ether as a gradient to 2-methyl- 5 -(o-tolyloxy)benzofuran-3 -carboxylic acid (Int-B052) (570 mg, 78.33%) as an off white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 7.57 (d, 1 H), 7.33-7.29 (m, 2 H), 7.21-7.18 (m, 1 H), 7.10-7.06 (m, 1 H), 6.99-6.96 (m,1 H), 6.85-6.83 (m, 1 H), 2.71 (s, 3 H), 2.21 (s, 3 H).

[0285] The following acidic intermediates were prepared in a manner similar to Int-B052 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 10: Exemplary intermediates.Synthesis of 5-(3,3-difluorocvclohexyl)-2-methylbenzofuran-3-carboxylic acid (Int-B066),

[0286] Step 1 : A stirred solution of ethyl 2-methyl-5-(tosyloxy)benzofuran-3-carboxylate (5 g, 13.354 mmol) and 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclohex-2-en-l-one (3.707 g, 16.693 mmol) in 1,4-Dioxane (30 mL) and water (10 mL) was treated with sodium carbonate (4.25 g, 40.063 mmol) and degassed with Ar for 15 min. Then, bis(triphenylphosphine)palladium(II) dichloride (1.0 g, 1.335 mmol) was added. The RM was stirred at 90 °C for 16 h. After cooling to RT, the RM diluted with EtOAc (100 mL), washed with water (100 mL), brine (100 mL), dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0-30% EtOAc in hexane to afford ethyl 2-methyl-5-(3-oxocyclohex-l-en-l-yl) benzofuran-3 -carboxylate compound as an off white solid (2.6 g, 66.2%).1H NMR (400 MHz, CDCL) 5 ppm: 8.16 (s, 1 H), 7.47-7.42 (q, 2 H), 6.46 (t, 1 H), 4.46-4.41 (q, 2 H), 2.87 (t, 2 H), 2.78 (s, 3 H), 2.52-2.49 (m, 2 H), 2.20-2.17 (m, 2 H), 1.45 (t, 1 H).

[0287] A stirred solution of ethyl 2-methyl-5 -(3 -oxocyclohex- 1-en-l-yl) benzofuran-3 -carboxylate (2.6 g, 8.715mmol) in EtOAc (30 mL) and IPA (10 mL) was treated with 20% Pd(OH)2 (250 mg) and stirred at RT for 5 h under H2Balloon pressure. The RM was filtered through a celite bed, washed with EtOAc (50 mL) and the filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0-30% EtOAc in hexane to afford ethyl 2-methyl-5-(3-oxocyclohexyl) benzofuran-3 -carboxylate as an off white solid (650 mg, 25%). 1H NMR (400 MHz, CDCL) 5 ppm: 7.83 (s, 1 H), 7.37 (d, 1H), 7.13 (dd, 1 H), 4.42 (q, 2 H), 3.18 - 3.07 (m, 1 H), 2.74 (s, 3 H), 2.68 - 2.52 (m, 2 H), 2.49 - 2.32 (m, 2 H), 2.18 - 2.10 (m, 2 H), 1.94 - 1.78 (m, 2 H), 1.44 (t, 3 H).

[0288] Step 3 : A solution of ethyl 2-methyl-5-(3-oxocyclohexyl) benzofuran-3 -carboxylate (550 mg, 1.831 mmol) in DCM (15 mL) was treated with DAST (0.6 mL, 4.578 mmol) dropwise at 0 °C. The RM was stirred at RT for 16 h. The RM was quenched with saturated aq. NaHCOs solution (20 mL), extracted with DCM (2 x 30 mL). Combined organic layer was washed with water (2 x 25 mL), brine (25 mL), dried over Na2SOs, filtered and concentrated under reduced pressure to afford ethyl 5-(3,3-difluorocyclohexyl)-2-methylbenzofuran-3- carboxylate as an off white solid (480 mg, 81%).1H NMR (400 MHz, CDCL) 5 ppm: 7.80 (s, 1 H), 7.34 (d, 1H), 7.14 - 7.10 (m, 1 H), 4.45 - 4.39 (q, 2 H), 2.98 (t, 1 H), 2.75 (s, 3 H), 2.34 - 2.25 (m, 1 H), 2.23 - 2.12 (m, 1 H), 1.95 - 1.82 (m, 3 H), 1.78 - 1.61 (m, 2 H), 1.49 - 1.41 (m, 4 H).

[0289] Step 4 : A solution of ethyl 5-(3,3-difluorocyclohexyl)-2-methylbenzofuran-3-carboxylate (500 mg, 1.551mmol) in THF (10 mL), MeOH (2 mL) and water (2 mL) was treated with LiOH.H2O (650 mg, 15.511 mmol) at RT and stirred at 50 °C for 16 h. The RM was concentrated under reduced pressure and the residue was acidified with IN HO (pH~3). The precipitate was filtered and washed with water (20 mL) and dried using high vacuum to afford 5-(3,3-difluorocyclohexyl)-2-methylbenzofuran-3-carboxylic acid (Int-B066) as an off white solid (400 mg, 88%).1H NMR (400 MHz, DMSO-D6) 5 ppm: 7.77 (s, 1 H), 7.50 (d, 1 H), 7.27 - 7.24 (dd, 1 H), 2.90 (t, 1 H), 2.71 (s, 3 H), 2.19 - 2.02 (m, 2 H), 1.99 - 1.82 (m, 3 H), 1.60 - 1.51 (m, 2 H).Synthesis of 5-(4-cvclopropylphenyl)-2-methylbenzofuran-3-carboxylic acid (Int-B067),

[0290] Step 1 : A solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (2.0 g, 5.67 mmol) in 1,4-Dioxane (20 mL) and H2O (5.0 mL) was treated with (4-cyclopropylphenyl)boronic acid (0.920 g, 5.67 mmol) and Na2CC>3 (1.80 g, 17.03 mmol). The RM was degassed with Ar for 15 min and then treated with PdC12dppf-DCM (0.463 g, 0.56 mmol). The RM was stirred at 90 °C for 16 h in a sealed tube. The RM was filtered through a celite pad, washed with EtOAc (50 mL) and the filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 2% EtOAc in pet. ether to afford ethyl 5-(4-cyclopropylphenyl)- 2-methylbenzofuran-3-carboxylate as an off-white gummy solid (1.50 g, 65.97%).

[0291] Step 2 : A solution of ethyl 5-(4-cyclopropylphenyl)-2-methylbenzofuran-3-carboxylate (1.20 g, 3.74 mmol) in MeOH (20 mL), THF (20 mL) and H2O (20 mL) was treated with NaOH (0.749 g, 18.72 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the residue was acidified with sat. citric acid solution (pH~5). The solid was collected by filtration, washed with water (30 mL) and dried using high vacuum. The residue was purified by FCC on silica gel using 30% EtOAc in pet ether to afford 5-(4-cyclopropylphenyl)-2-methylbenzofuran-3-carboxylic acid (Int-B067) as a pale brown solid (450 mg, 46%).1H NMR (400 MHz, CDCl3) 5 ppm: 7.43 - 7.55 (m, 5 H), 7.12 - 7.16 (m, 2 H), 2.78 - 2.81 (s, 3 H), 1.91 - 1.96 (m,1 H), 0.97 - 1.02 (m, 2 H), 0.88 - 0.90 (m, 2 H).

[0292] The following acidic intermediates were prepared in a manner similar to Int-B067 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 11 : Exemplary intermediates.Synthesis of 2-methyl-5-(3-phenylazetidin-l-yl)benzofuran-3-carboxylic acid (Int-B069),

[0293] Step 1 : A stirred solution of ethyl 5-bromo-2-methylbenzofuran-3-carboxylate (1.80 g, 6.358 mmol) and3 -phenylazetidine hydrochloride (1.61 mg, 9.537 mmol) in toluene (20 mL) was treated with Potassium tert- butoxide (2.14 g, 19.073 mmol) and the RM was degassed with argon gas for 15 minutes and treated with BrettPhos (341.26 mg, 0.636 mmol), and with XPhos Pd G3 (269.07 mg, 0.318 mmol) at RT. The RM was stirred in Microwave at 100 °C for 1 h. The RM was filtered through a small pad of Celite and washed with EtOAc (40 mL). The filtrate was washed with H2O (2 ^ 15 mL) and the organic layer was dried over Na2SC>4 and evaporated under reduced pressure. The residue was purified by FCC on silica gel using 3% EtOAc in Pet. ether as gradient to afford ethyl 2-methyl-5-(3-phenylazetidin-l-yl)benzofuran-3-carboxylate (300 mg, 25%).1H NMR (400 MHz, CDCL) 5 ppm: 7.43-7.32 (m, 6 H), 7.06 (d, 1 H), 6.49 (dd, 1 H), 4.41-4.33 (m, 4 H), 3.96-3.90 (m, 3 H), 2.72 (s, 3 H), 1.42 (t, 3 H).

[0294] Step 2 : A stirred solution of ethyl 2-methyl-5-(3-phenylazetidin-l-yl)benzofuran-3-carboxylate (300 mg, 0.894 mmol) in MeOH (2 mL), THF (2 mL) and H2O (1 mL) was treated with NaOH (178.88 mg, 4.472 mmol) at 0 °C. Then, the RM was warmed to RT and stirred at 70 °C for 16 h. The RM was concentrated under reduced pressure to remove volatiles. The residue was diluted with ice-cold water (3 mL), neutralized with aqueous citric acid solution (pH~4-5). The solid was filtered, washed with n-pentane (10 mL) and dried under vacuum to afford 2-methyl-5-(3-phenylazetidin-l-yl)benzofuran-3-carboxylic acid (Int-B069). (200 mg, 73%) as an off white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 12.72 (brs, 1 H), 7.42-7.33 (m, 5 H), 7.24 (t, 1 H), 6.93 (d, 1 H), 6.49 (dd, 1 H), 4.27 (t, 2 H), 3.97-3.94 (m, 1 H), 3.79 (t, 2 H), 2.68 (s, 3 H).

[0295] The following acidic intermediates were prepared in a manner similar to Int-B069 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 12: Exemplary intermediates.Synthesis of 2-methyl-5-(l -phenyl- 1H- 1,2,3 -triazol-4-yl)benzofuran-3 -carboxy lie acid (Int-B071),

[0296] Step 1 : A solution of ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (Int-B015) (1.0 g, 4.30 mmol) in EtOH (20 mL) treated with Potassium carbonate (1.78 g, 12.91 mmol) and dimethyl (l-diazo-2 -oxopropyl) phosphonate (0.993 g, 5.16 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and diluted with H2O (20 mL) and extracted with EtOAc (3 x 10 mL). Organic layer was separated and dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 2% EtOAc in pet. ether as a gradient to afford ethyl 5-ethynyl-2-methylbenzofuran-3-carboxylate (450 mg, 46%) as an off-white solid,!H NMR (400 MHz, CDCl3) 5 ppm: 8.10 (s, 1 H), 7.42 (d, 1 H), 7.36 (d, 1 H), 4.41 (t, 2 H), 3.05 (s, 1 H), 2.75 (s, 3 H), 1.44 (t, 3 H).

[0297] Step 2 : A solution of ethyl 5-ethynyl-2-methylbenzofuran-3-carboxylate (300 mg, 1.31 mmol) in EtOH (14 mL), water (6 mL) was cooled to 0°C, treated with NaN3(179.01 mg, 2.62 mmol) and DMEDA (11.58 mg, 0.13 mmol), followed by Cui (49.97 mg, 0.26 mmol), Sodium ascorbate (26.03 mg, 0.13 mmol) at 0 °C. The RM was stirred at 50°C for 16 h in sealed tube. The RM was diluted with ice cold water (20 mL). The solid was filtered and washed with water, dried under vacuum to afford ethyl 2-methyl-5-(l-phenyl-lH-l,2,3-triazol-4-yl) benzofuran-3 -carboxylate as an off-white solid (400 mg, 87.61%),1H NMR (400 MHz, CDCh) 5 ppm: 8.43 (s, 1 H), 8.24 (s, 1 H), 7.93 (d, 1 H), 7.81 (d, 2 H), 7.58 - 7.46 (m, 4 H), 4.45 (t, 2 H), 2.80 (s, 3 H), 1.47 (t, 3 H).

[0298] Step 3 : A solution of 2-methyl-5-(l-phenyl-lH-l,2,3-triazol-4-yl) benzofuran-3 -carboxylate (400 mg, 1.15 mmol) inMeOH (5 mL), THF (5 mL) and H2O (5 mL) was treated with NaOH (230.3 mg, 5.75 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure. The residue was acidified with sat. citric acid solution (pH~5). The solid was collected by filtration, washed with H2O (30 mL) and dried using high vacuum to afford 2-methyl-5-(l-phenyl-lH-l,2,3-triazol-4-yl)benzofuran-3-carboxylic acid (Int- B071) as an off-white solid (300 mg, 81.59%),1H NMR (400 MHz, CDCl3) 5 ppm: 9.30 (bis, 1 H), 8.61 (bis, 1 H), 8.00 - 8.01 (m, 2 H), 7.84 - 7.82 (m, 1 H), 7.63 - 7.61 (m, 3 H), 7.52 - 7.51 (m, 1 H), 2.74 (s, 3 H).Synthesis of ethyl 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzofuran-3-carboxylate (Int-B072)

[0299] A stirred solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (Int- B001) (10 g, 28.387 mmol) in 1,4-dioxane (100 mL) was treated with Bis(pinacolato)diboron (14.417 g, 56.773 mmol), AcOK (5.572 g, 56.773 mmol) at RT and degassed with N2 for 10 min. Then, the RM was treated with Pd(dppf)C12. DCM (2.316 g, 2.839 mmol) and stirred at 80 °C for 16 h. The RM was diluted with water (100 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layers were dried over Na2SC>4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0-15% EtOAc in Pet. ether as a gradient to afford ethyl 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzofuran-3-carboxylate (Int-B072) (9.3 g, 99%) as an off-white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.80 (s, 1 H), 7.74- 7.72 (m, 1 H), 7.42 - 7.39 (m, 1 H), 4.43 (q, 2 H), 2.76 (s, 3 H), 1.45 (t, 3 H), 1.37 (d, 12 H).Synthesis of 5-(5-cvclopropylpyridin-2-yl)-2-methylbenzofuran-3-carboxylic acid (Int-B073)

[0300] Step 1 : A solution of ethyl 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzofuran-3- carboxylate (Int-B072) (800 mg, 2.423 mmol) in 1,4-dioxane (10 mL) and water (10 mL) was degassed with N2 for 5 min in a sealed tube. 2-chloro-5-cyclopropylpyridine (372.174 mg, 2.423 mmol), Sodium carbonate (770.400 mg, 7.269 mmol) and PdC12(dppf).DCM (19.786 mg, 0.024 mmol) were added to the RM. The RM was heated to 90°C for 16 h. The RM was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SC>4 and concentrated under reduced pressure The residue was purified by FCC on silica gel using 25% EtOAc in pet. ether as a gradient to afford ethyl 5-(5-cyclopropylpyridin-2-yl)-2-methylbenzofuran-3-carboxylate (230 mg, 29.54 %).1H NMR (400 MHz, DMSO-de) δ ppm: 8.50 (d, 1 H), 8.46 (d, 1 H), 7.94 (dd, 1 H), 7.66 (d, 1 H), 7.49 (d, 1 H), 7.38 (dd, 1 H), 4.44 (q, 2 H), 2.79 (s, 3 H), 1.97-1.93 (m, 1 H), 1.46 (q, 3 H), 1.08-1.03 (m, 2 H), 0.80-0.70 (m, 2 H).

[0301] Step 2 : A solution of ethyl 5-(5-cyclopropylpyridin-2-yl)-2-methylbenzofuran-3-carboxylate (230 mg, 0.716 mmol) in THF (5 mL), MeOH (2 mL) and H2O (2 mL) was treated with NaOH (143.124 mg, 3.578 mmol) at 0°C. The RM was stirred at RT for 16 h. Th RM was concentrated under reduced pressure. The residue was acidified with IN HO (pH~3). The white precipitate was filtered, washed with water (20 mL) and dried using high vacuum to afford 5-(5-cyclopropylpyridin-2-yl)-2-methylbenzofuran-3-carboxylic acid (Int-B073) as an off white solid (150 mg, 71.45 %).1H NMR (400 MHz, DMSO-de) δ ppm: 13.10 (s, 1 H), 8.56-8.54 (m, 2 H), 7.98-7.91 (m, 2 H), 7.70-7.64 (m, 2 H), 2.76 (s, 3 H), 2.05-2.01 (m, 1 H), 1.09-1.04 (m, 2 H), 0.84-0.82 (m, 2 H).

[0302] The following acidic intermediates were prepared in a manner similar to Int-B073 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 13: Exemplary intermediates.Synthesis of 5-(5-cyclopropylpyrazin-2-yl)-2-methylbenzofuran-3-carboxylic acid (Int-B075)

[0303] Step 1 : To a solution of 2-bromo-5-chloropyrazine (2.0 g, 10.340 mmol) in 1,4-Dioxane (30 mL) and water (3 mL) in a sealed tube were added ethyl 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl) benzofuran-3 -carboxylate (Int-B072) (2.048 g, 6.204 mmol) and Sodium carbonate (3.288 g, 31.019 mmol). The RM was degassed with argon for 10 min. PdC12(dppf)-DCM (422.191mg, 0.517 mmol) was added at RT. The RM was stirred at 50 °C for 16 h. The RM was cooled to RT and filtered through a celite bed and washed with EtOAc (30 mL), diluted with water (70 mL), and extracted with EtOAc (2 x 20 mL). The total organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 4-5% of EtOAc in pet ether gradient to afford ethyl 5-(5-chloropyrazin-2-yl)-2- methylbenzofuran-3 -carboxylate (800 mg, 24.43%) as an off-white solid.1H NMR (400 MHz, CDCL) 5 ppm: 8.84 (d, 1 H), 8.64 (d, 1 H), 8.56 (d, 1 H), 7.97-7.94 (m, 1 H), 7.56-7.54 (m, 1 H), 4.48-4.42 (m, 2 H), 2.81 (s, 3 H), 1.47 (t, 3 H).

[0304] Step 2 : To a solution of ethyl 5-(5-chloropyrazin-2-yl)-2-methylbenzofuran-3-carboxylate (800 mg, 2.526 mmol) in 1,4-Dioxane (15 mL) were added cyclopropylboronic acid (759.3 mg, 8.840 mmol) and Potassium carbonate (698.1 mg, 5.051 mmol). The RM was degassed with argon for 10 min. Then, Pd(dppf)CL (103.13 mg, 0.126 mmol) was added at RT. The RM was stirred at 80 °C for 16 h. The RM was cooled to RT then filtered through a celite bed and washed with EtOAc (20 mL), diluted with water (60 mL), and extracted with EtOAc (2 x 30 mL). Combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure The residue was purified by FCC on silica gel using 4-5% of EtOAc in pet ether gradient to afford ethyl 5-(5-cyclopropylpyrazin-2-yl)-2-methylbenzofuran-3-carboxylate (400 mg, 49%) as a pale yellow solid.1H NMR (400 MHz, CDCL) 5 ppm: 8.87 (d, 1 H), 8.53 (d, 1 H), 8.50 (d, 1 H), 7.94-7.92 (m, 1 H), 7.53-7.51(m, 1 H), 4.47-4.41 (m, 2 H), 2.80 (s, 3 H), 2.14-2.10 (m, 1 H), 1.47 (t, 3 H), 1.12-1.10 (m, 4 H).

[0305] Step 3 : A solution of ethyl 5-(5-cyclopropylpyrazin-2-yl)-2-methylbenzofuran-3-carboxylate (400 mg, 1.241 mmol) in THF (3 mL), MeOH (3 mL) and water (1.5 mL) was added NaOH (496.3 mg, 12.408 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the resulting residue was acidified with a saturated citric acid solution (10 mL, pH~3). The precipitate was filtered and washed with water (15 mL) and dried using a high vacuum to afford 5 5-(5-cyclopropylpyrazin-2-yl)-2-methylbenzofuran-3- carboxylic acid (Int-B075) (300 mg, 82 %) as a pale yellow solid.1H NMR (400 MHz, DMSO-de) 5 ppm: 13.13 (s, 1 H), 9.04 (d, 1 H), 8.68 (d, 1 H), 8.61 (d, 1 H), 8.03-8.00 (m, 1 H), 7.70 (d, 1 H), 2.76 (s, 3 H), 2.27-2.22 (m, 1 H), 1.10-1.05 (m, 2 H), 1.04-1.01 (m, 2 H).Synthesis of 2-methyl-5-(4-phenylpiperazin-l-yl)benzofuran-3 -carboxylic acid (Int-B078)

[0306] Step 1 : To a solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl) oxy) benzofuran-3 -carboxylate (Int-BOOl) (1.5 g, 4.258 mmol) in Toluene (12 mL) was added 1 -phenylpiperazine (0.671 mL, 4.258 mmol) and CS2CO3 (2.775 g, 8.516 mmol) at RT and degassed with argon for 10 min. Then, BINAP (132.6 mg, 0.213 mmol) and Pd(OAc)2 (19.119 mg, 0.085 mmol) were added at RT. The RM was stirred at 100°C for 16 h. The RM was cooled to RT then filtered through a celite bed and washed with EtOAc (50 mL). The filtrate was diluted with water (80 mL) and extracted with EtOAc (2 x 80 mL). The total organic layer was washed with brine (80 mL), dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 2-5% of EtOAc in pet ether gradient to afford ethyl 2-methyl-5-(4-phenylpiperazin-l- yl) benzofuran-3 -carboxylate (400 mg, 25.78%) as a pale yellow solid.1H NMR (400 MHz, CDCL) 5 ppm: 7.57 (d, 1 H), 7.35-7.28 (m, 3 H), 7.02-6.99 (m, 3 H), 6.89 (t, 1 H), 4.44-4.38 (m, 2 H), 3.39-3.34 (m, 8 H), 2.74 (s, 3 H), 1.45 (t, 3 H).

[0307] Step 2 : A solution of ethyl 2-methyl-5-(4-phenylpiperazin-l-yl) benzofuran-3 -carboxylate (300 mg, 0.823 mmol) in THF (2 mL), MeOH (2 mL) and water (1 mL) was added NaOH (493.9 mg, 12.3 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the residue was neutralized with a saturated citric acid solution (pH~6). The precipitate was fdtered and washed with water (5 mL) and dried using a high vacuum to afford 2-methyl-5-(4-phenylpiperazin-l-yl)benzofuran-3-carboxylic acid (Int- B078) (180 mg, 65%) as a pale yellow solid.1H NMR (400 MHz, CDCL) 5 ppm: 7.59-7.55 (m, 1 H), 7.37-7.28 (m, 3 H), 7.04-6.99 (m, 3 H), 6.91-6.87 (m, 1 H), 3.40-3.34 (m, 8 H), 2.78-2.74 (m, 3 H).Synthesis of 5-(lH-benzo[d]imidazol-2-yl)-2-methylbenzofuran-3-carboxylic acid (Int-B080),

[0308] To a stirred solution of ethyl 5 -formyl-2-methylbenzofuran-3 -carboxylate (1.0 g, 4.306 mmol) and benzene- 1,2-diamine (0.512 g, 4.737 mmol) in DMF (10 mL) were added with KI (0.786 g, 4.7 mmol) and molecular sieves 4 A (1 g) at RT. The RM was stirred at 80 °C for 16 h. The RM was diluted with ice-cold water (20 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 30% EtOAc in Pet. ether, as gradient to afford ethyl 5-(lH-benzo[d]imidazol-2-yl)-2-methylbenzofuran- 3 -carboxylate (800 mg, 58%).

[0309] Step 2 : A stirred solution of ethyl 5-(lH-benzo[d]imidazol-2-yl)-2-methylbenzofuran-3-carboxylate (800 mg, 2.497 mmol) in THF (10 mL) and MeOH (2 mL) was treated with NaOH (599.3 mg, 14.984 mmol) in FEO (2 mL) at 0 °C. The RM was warmed to RT and stirred for 48 h. The RM was concentrated under reduced pressure. The residue was diluted ice-cold water (20 mL) and acidified with IN HO (pH~2-3). The obtained solid was filtered, washed with n-pentane (10 mL) and dried under vacuum to afford 5-(lH-benzo[d]imidazol-2-yl)-2- methylbenzofuran-3 -carboxylic acid (Int-B080) (600 mg, 82%) as brown solid.1H NMR (400 MHz, DMSO-de) 5 ppm: 13.30 (brs, 1 H), 8.83 (d, 1 H), 8.31-8.29 (dd, 1 H), 7.95 (d, 1 H), 7.81-7.78 (m, 2 H), 7.52-7.49 (m, 2 H), 2.81 (s, 3 H).

[0310] The following acidic intermediate was prepared in a manner similar to Int-B080 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 14: Exemplary intermediate.Synthesis of 2-methyl-5-(3-phenyloxetan-3-yl)benzofuran-3-carboxylic acid (Int-B087),

[0311] Step 1 : A solution of 3-phenyloxetan-3-ol (1.5 g, 9.99 mmol), 2-iodophenol (2.637 g, 11.986 mmol) in DCM (50 mL) was cooled to 0 °C and treated with A1CL (1.598 g, 11.986 mmol). Then, the RM was stirred at RT for 3 h. The RM was diluted with DCM (50 mL), washed with water (2 x 20 mL), brine (20 mL), dried over Na2SC>4, fdtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0- 25% of EtOAc in Pet. ether as a gradient to afford 2-iodo-4-(3-phenyloxetan-3-yl)phenol (550 mg, 16%) as an off white solid. 1H NMR (400 MHz, CDCl3) 5 ppm: 7.52 (d, 1 H), 7.40 - 7.34 (m, 2 H), 7.32 - 7.27 (m, 1 H), 7.21 - 7.15 (m, 2 H), 7.08 (dd, 1 H), 6.95 (d, 1 H), 5.29 (s, 1 H), 5.23 (d, 2 H), 5.15 (d, 2 H).

[0312] Step 2 : A solution of 2-iodo-4-(3-phenyloxetan-3-yl)phenol (1 g, 2.840 mmol) in ACN (10 mL) wastreated with DABCO (318.510 mg, 2.84 mmol), and stirred at 70 °C for 15 mins. Then, the RM was treated with solution of ethyl but-2-ynoate (0.332 mL, 2.840 mmol) in ACN (5 mL). The RM was stirred at 70 °C for 16 h. The RM was concentrated under reduced pressure and the residue was diluted with water (25 mL), and extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried over Na2SC>4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0-10% EtOAc in Pet ether as a gradient to afford ethyl (E)-3-(2-iodo-4-(3-phenyloxetan-3-yl)phenoxy)but- 2 -enoate (950 mg, 72%) as an off-white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.74 (d, 1 H), 7.44 - 7.37 (m, 2 H), 7.34 - 7.28 (m, 1 H), 7.21 (dd, 1 H), 7.20 - 7.15 (m, 2 H), 7.00 (d, 1 H), 5.29 (d, 2 H), 5.16 (d, 2 H), 4.76 (s, 1 H), 4.10 (q, 2 H), 2.53 (s, 3 H), 1.23 (t, 3 H).

[0313] Step 3 : A solution of ethyl (E)-3 -(2 -iodo-4-(3-phenyloxetan-3-yl)phenoxy)but-2 -enoate (950 mg, 2.046 mmol) in ACN (10 mL) was treated with TEA (0.560 mL, 4.092 mmol) . The RM was degassed with N2 for 5 min, then treated with PdC12(dppf).DCM (167.094 mg, 0.205 mmol). The RM was stirred at 85 °C for 16 h. The RM was concentrated under reduced pressure and the residue was diluted with water (25 mL), extracted with EtOAc (2 x 25 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 0- 12% of EtOAc in Pet ether as a gradient to afford ethyl 2-methyl-5-(3-phenyloxetan-3-yl)benzofuran-3- carboxylate (650 mg, 94%) as an off-white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.72 (d, 1 H), 7.41 (d, 1 H), 7.39 - 7.32 (m, 2 H), 7.29 - 7.26 (m, 2 H), 7.25 - 7.24 (m, 1 H), 7.21 (dd, 1 H), 5.31 (q, 4 H), 4.34 (q, 2 H), 2.76 (s, 3 H), 1.33 (t, 3 H).

[0314] Step 4 : A solution of ethyl 2-methyl-5-(3-phenyloxetan-3-yl)benzofuran-3-carboxylate (650 mg, 1.932 mmol) in THF (4 mL), H2O (4 mL), MeOH (4 mL) was cooled to 0 °C and treated with LiOH.H2O (405.4 mg, 9.661 mmol). Then, the RM was stirred at 45 °C for 16 h. The RM was diluted with water (10 mL) and acidified with Aq. Citric acid solution (pH ~ 3-4). The precipitated was filtered and dried under vacuum. The isolated solid was triturated with n-pentane and dried under reduced pressure to afford 2-methyl-5-(3-phenyloxetan-3- yl)benzofuran-3 -carboxylic acid (Int-B087) (540 mg, 90%) as an off-white solid.1H NMR (400 MHz, DMSO-de) 5 ppm: 7.84 (d, 1 H), 7.49 (d, 1 H), 7.37 - 7.30 (m, 4 H), 7.27 - 7.20 (m, 1 H), 7.17 (dd, 1 H), 5.20 (q, 4 H), 2.70 (3 H).

[0315] The following acidic intermediate was prepared in a manner similar to Int-B087 (use of appropriate reagent (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 15: Exemplary intermediates.

[0316] Synthesis of 2-methyl-5-(piperidin-l-ylmethyl)benzofuran-3-carboxylic acid (Int-B088),

[0317] Step 1: A solution of ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (800 mg, 3.445 mmol) in a MeOH (50 mL) was treated with piperidine (0.682 mL, 6.889 mmol), molecular sieves (2.0 g), acetic acid (0.394 mL, 6.889 mmol) and sodium cyanoborohydride (432.92 mg, 6.889 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was filtered through a celite bed, washed with MeOH (30 mL), concentrated and the residue was diluted with EtOAc (100 mL), washed with sat. sodium bicarbonate (50 mL), brine (100 mL) and dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel to afford ethyl 5-formyl-2-methylbenzofuran-3-carboxylate as a colorless liquid (400 mg, 39%).

[0318] Step 2 : A stirred solution of ethyl 2-methyl-5-(piperidin-l-ylmethyl)benzofuran-3-carboxylate (400 mg, 1.327 mmol) in THF (15 mL), water (15 mL) and MeOH (15 mL) was treated with NaOH (530 mg, 13.272 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the resulting residue was diluted with water (10 mL), acidified with sat. citric acid solution (Ph~6). The solid was filtered, washed with water (10 mL) and dried to afford 2-methyl-5-(piperidin-l-ylmethyl)benzofuran-3-carboxylic acid (Int-B088) as an off-white solid (300 mg, 82.70%).

[0319] The following acidic intermediates were prepared in a manner similar to Int-B088 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 16: Exemplary intermediates.Synthesis of 3-(ethoxycarbonyl)-2-methylbenzofuran-5-carboxylic acid (Int-B090)

[0320] A solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl) oxy) benzofuran-3 -carboxylate (Int-BOOl) (1.0 g, 2.83 mmol) in 1,4-dioxane (7.0 mL) and H2O (3.0 mL) was treated with TEA (1.10 mL, 8.51 mmol) and degassed with argon for 15 min. Then, the RM was treated with Pd(OAc)2 (63.61 mg, 2.84 mmol) and Xanthphos (328.20 mg, 5.68) at RT . The RM was stirred at 90 °C for 16 h in a steal bomb under CO gas atmosphere (50 psi). The RM was filtered through a celite pad, washed with EtOAc (20 mL) and the filtrate was concentrated under reduced pressure and the resulting residue was diluted with water (20 mL), acidified with IN HC1 (pH~5), extracted with EtOAc (2 x 15 mL). The combined organic layer was washed with brine solution (25 mL), dried over Na2SOr and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 25% EtOAc in pet ether to afford 3-(ethoxycarbonyl)-2-methylbenzofuran-5-carboxylic acid (Int- B090) as an off-white solid (650 mg, 92 %),!H NMR (400 MHz, DMSO-de) δ ppm: 13.00 (s, 1 H), 8.51 (s, 1 H), 7.93 - 7.96 (d, 1 H), 7.69 - 7.71 (d, 1 H), 4.35 - 4.40 (t, 2 H), 2.77 (s, 3 H), 1.36 - 1.39 (t, 3 H).Synthesis of 5-(3-azabicvclo[3.1.01hexane-3-carbonyl)-2-methylbenzofuran-3-carboxylic acid (Int-B091)

[0321] Step 1 : A solution of 3-(ethoxycarbonyl)-2-methylbenzofuran-5-carboxylic acid (0.500 g, 2.014 mmol) in DMF (10 mL) was treated with HATU (1.148 g, 3.021 mmol), DIPEA (0.520 mL, 3.021 mmol) and 3- azabicyclo [3.1.0] hexane (0.251 g, 3.021 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was diluted with ice-cold water (30 mL), extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with saturated NaHCOs solution (15 mL), brine (15 mL), dried over ySO i. filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-50% EtOAc in pet. ether to afford ethyl 5-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-2-methylbenzofuran-3-carboxylate (450 mg, 71%) as a pale yellow gummy.

[0322] Step 2 : A solution of ethyl 5-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-2-methylbenzofuran-3-carboxylate (420 mg, 1.340 mmol) in THF (20 mL) and MeOH (2.5 mL) was treated with LiOH.H2O (152 mg, 4.021 mmol) in water (2.5 mL) at RT and the RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the residue was acidified with 2N HC1 (pH~3). The precipitate was filtered and washed with water (20 mL), n-pentane (20 mL) and dried under high vacuum to afford 5-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-2- methylbenzofuran-3 -carboxylic acid (Int-B091) (250 mg, 65%) as a white solid.1H NMR (400 MHz, DMSO-de) 5 ppm: 13.07 (brs, 1H), 7.94 (s, 1H), 7.60 (d, 1H), 7.40-7.38 (m, 1H), 3.98-3.95 (m, 1H), 3.64-3.62 (m, 1H), 3.40-3.36 (m, 2H), 2.74 (s, 3H), 1.56-1.52 (m, 2H), 0.66-0.61 (m, 1H), 0.11-0.08 (m, 1H).

[0323] The following acidic intermediates were prepared in a manner similar to Int-B091 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 17: Exemplary intermediates.Synthesis of 5-(cvclohexylmethyl)-2-methylbenzofuran-3-carboxylic acid (Int-B095)

[0324] Step 1 : To a stirred solution of ethyl 2-methyl-5-(((trifluoromethyl)sulfonyl)oxy)benzofuran-3- carboxylate (2.0 g, 5.677 mmol) and 2-(cyclohexylidenemethyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (1.892 g, 8.516 mmol) in 1,4-dioxane (16 mL) and water (4 mL) was treated with sodium carbonate (1.805 g, 17.032 mmol) at RT and degassed with N2 gas for 15 min. Then, the RM was treated with PdC12(dppf)-DCM (144.169 mg, 0.568 mmol) under an N2 atmosphere. The RM was stirred at 90 °C for 16 h. The RM was cooled to RT, filtered through a small pad of celite, and washed with EtOAc (40 mL). The filtrate was diluted with water (30 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with water (30 mL), and brine (30 mL), dried over sodium sulphate, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-2% EtOAc in Pet. ether to afford ethyl 5- (cyclohexylidenemethyl)-2-methylbenzofuran-3 -carboxylate (1.1 g, 65%) as an off-white solid.1H NMR (400 MHz, CDCL) 5 ppm: 7.78 (s, 1 H), 7.34 (d, 1 H), 7.10 (dd, 1 H), 6.33 (s, 1 H), 4.40 (q, 2 H), 2.76 (s, 3 H), 2.49 - 2.29 (m, 2 H), 2.28 - 2.21 (m, 2 H), 1.69 - 1.56 (m, 6 H), 1.44 (t, 3 H).

[0325] Step 2 : To a stirred solution of ethyl 5-(cyclohexylidenemethyl)-2-methylbenzofuran-3-carboxylate (1.1 g, 3.687 mmol) in in ethanol (20 mL) was treated with Palladium on activated carbon (784.6 mg, 7.373 mmol) atRT. The RM was stirred under Hydrogen gas balloon atmosphere at RT for 16 h. The RM was filtered through a small pad of celite and washed with EtOAc (100 mL). The filtrate was concentrated under reduced pressure to afford ethyl 5-(cyclohexylmethyl)-2-methylbenzofuran-3-carboxylate (1.0 g, 90) as a colorless liquid.1H NMR (400 MHz, CDCl3) 5 ppm: 7.71 (d, 1 H), 7.30 (d, 1 H), 7.04 (dd, 1 H), 4.41 (q, 2 H), 2.74 (s, 3 H) 2.58 (d, 2 H), 1.65 - 1.63 (m, 6 H), 1.44 (t, 3 H), 1.20 - 1.15 (m, 2 H), 0.97 - 0.70 (m, 3 H).

[0326] Step 3 : To a stirred solution of ethyl 5-(cyclohexylmethyl)-2-methylbenzofuran-3-carboxylate (1.0 g, 3.329 mmol) in in THF (10 mL), MeOH (10 mL) and Water (10 mL) was treated with NaOH (1.332 g, 33.289 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure, and the residue was acidified with saturated aqueous citric acid (pH ~4). The solid was filtered, washed with water (25 mL), and dried under high vacuum suction to afford 5-(cyclohexylmethyl)-2-methylbenzofuran-3-carboxylic acid (Int-B095) (700 mg, 77%) as an off-white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 7.66 (d, 1 H), 7.43 (d, 1 H), 7.07 (dd, 1 H), 2.70 (s, 3 H), 2.53 (d, 2 H), 1.61 - 1.46 (m, 6 H), 1.16 - 1.12 (m, 4 H), 0.96 - 0.91 (m, 2 H).

[0327] The following acidic intermediate was prepared in a manner similar to Int-B095 (use of appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to the person skilled in the art):Table 18: Exemplary intermediates.Synthesis of 2-methyl-5-(2, 2, 2-trifluoro-l-phenylethyl)benzofuran-3 -carboxylic acid (Int-B105)

[0328] Step 1 : To a stirred solution of 2,2,2-trifluoro-l -phenylethyl 4-methylbenzenesulfonate (1 g, 3.027 mmol), ethyl 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl) benzofuran-3 -carboxylate (1.499 g, 4.541mmol) and Potassium phosphate, monobasic, 99+%, extra pure (1.230 g, 4.844 mmol) in 1,4-Dioxane (20 mL) and Water (10 mL) at RT was added X-PhosPdG2 (0.048 g, 0.061 mmol). Then the RM was degassed with Argon for 10 minutes. The RM was stirred for 16 hours at 90 °C. The RM was diluted with water (10 mL) and extracted with EtOAc (2 x 50 mL). Combined organic layers were washed with brine (20 mL), dried over Na2SC>4, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 8% EtOAc in Pet. ether to afford ethyl 2-methyl-5-(2,2,2-trifluoro-l-phenylethyl)benzofuran-3-carboxylate (500 mg, 45.58%) as a pale yellow gummy.!H NMR (400 MHz, CDCl3) 5 ppm: 7.42 - 7.25 (m, 8 H), 4.84 - 4.76 (m, 1 H), 4.42 - 4.36 (m, 2 H), 2.75 (s, 3 H), 1.42 (t, 3 H).

[0329] Step 2 : To a stirred solution of ethyl 2-methyl-5-(2,2,2-trifluoro-l-phenylethyl) benzofuran-3- carboxylate (400 mg, 1.104 mmol) in THF (5 mL), MeOH (5 mL) and Water (2 mL) was added NaOH (220.782 mg, 5.520 mmol) at RT. The RM was stirred for 16 h at RT. The RM was concentrated under reduced pressure. The residue was acidified with saturated citric acid solution (10 mL) up to pH~4-5 then extracted with EtOAc (2 x 50 mL). The total organic layer was dried over Na2SO4, fdtered and concentrated under reduced pressure to afford 2-methyl-5-(2,2,2-trifluoro-l-phenylethyl)benzofuran-3-carboxylic acid (Int-105) (230 mg, 62.33%).1H NMR (400 MHz, CDCl3) 5 ppm: 8.04 (s, 1 H), 7.60-7.58 (m, 1 H), 7.49 - 7.41 (m, 2 H), 7.40 - 7.37 (m, 3 H), 7.35 - 7.30 (m, 1 H), 5.49 - 5.41 (m, 1 H), 2.77 - 2.72 (m, 3 H).Synthesis of ethyl 5-allyl-2-methylbenzofuran-3-carboxylate (Int-B120) and 5-(cyclopropylmethyl)-2- methylbenzofuran-3 -carboxylic acid (Int-B106)

[0330] Step 1 : To a stirred solution of ethyl 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)benzofuran-3 -carboxylate (3.0 g, 9.086 mmol) in 1,4 Dioxane (30 mL), Water (10 mL) was treated with 3- bromoprop-l-ene (1.649 g, 13.629 mmol), Potassium phosphate, tribasic, 97%, pure, anhydrous (5.786 g, 27.257 mmol) in a sealed tube, degassed with N2 for 10 min, followed by addition of PdCh(dppf).DCM (0.371 g, 0.454 mmol). The RM was stirred for 16 h at 90°C. The RM was diluted with EtOAc (20 mL), washed with water (2 x 10 mL). The organic layer was dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 2% EtOAc in pet ether to afford ethyl 5 -ally l-2-methylbenzofuran-3 -carboxylate (Int-B120) (1.0 g, 45 %) as brown liquid. 1H NMR (400 MHz, CDCh) 5 ppm: 7.77 (d, 1 H), 7.33 (d, 1 H), 7.11-7.09 (m, 1 H), 6.06-5.96 (m, 1 H), 5.12-5.07 (m, 2 H), 4.41 (q, 2 H), 3.49 (d, 2 H), 2.79-2.75 (m, 3 H), 1.45 (t, 3 H).

[0331] Step 2 : To a stirred solution of KOH (75% in water) (30 mL) in Et20 (30 mL) was added 1-methyl-l- nitrosourea (6.329 g, 61.402 mmol) at 0°C and stirred for 15 min. After 15 min, water and Et20 layers were separated, Et20 layer was dried over Na2SO4 and added to suspension of ethyl 5-allyl-2-methylbenzofuran-3- carboxylate (1.5 g, 6.140 mmol) and Palladium acetylacetonate (0.094 g, 0.307 mmol) in Et20 (30 mL) at 0°C. The RM was stirred for 2 h. The RM was concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 1% EtOAc in pet. ether to afford ethyl 5 -(cyclopropylmethyl)-2 -methylbenzofuran-3-carboxylate (500 mg, 31.52%) as colorless oil.1H NMR (400 MHz, CDCL) 5 ppm: 7.85 (d, 1 H), 7.34-7.32 (m, 1 H), 7.18-7.15 (m, 1 H), 4.42 (q, 2 H), 2.77-2.73 (m, 3 H), 2.65 (d, 2 H), 1.45 (t, 3 H), 1.05-1.00 (m, 1 H), 0.56- 0.55 (m, 2 H), 0.30-0.20 (m, 2 H).

[0332] Step 3 : To a stirred solution of ethyl 5-(cyclopropylmethyl)-2-methylbenzofuran-3-carboxylate (500 mg, 1.936 mmol) in THF (10 mL), MeOH (5 mL) and water (5 mL) was added Lithium hydroxide monohydrate, 98% (406.090 mg, 9.678 mmol) at RT. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure and the residue was acidified with saturated citric acid solution (pH~3). The white precipitate was filtered, washed with water (20 mL) and dried using high vacuum to afford -(cyclopropylmethyl)-2-methylbenzofuran-3- carboxylic acid (Int-B106) (350 mg, 78.53%) as white solid. iH NMR (400 MHz, CDCL) 5 ppm: 7.88 (d, 1 H), 7.37-7.35 (m, 1 H), 7.20-7.19 (m, 1 H), 2.80 (s, 3 H), 2.66 (d, 2 H), 1.07-1.03 (m, 1 H), 0.56-0.51 (m, 2 H), 0.26- 0.22 (m, 2 H).Synthesis of 5-((2,2-difluorocvclopropyl)methyl)-2-methylbenzofuran-3-carboxylic acid (Int-B107)

[0333] Step 1 : A stirred solution of ethyl 5 -ally l-2-methylbenzofuran-3 -carboxylate (500 mg, 2.047 mmol) in THF (3 mL) was treated with Nal (152.38 mg, 1.023 mmol) and CF3TMS (6.277 mL, 40.935 mmol) at RT. The RM was irradiated under Micro wave at 100 °C for 4 h. The RM was dilute with water (20 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were dried over NaiSO i. filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-1% EtOAc in Pet. ether to afford ethyl 5-((2,2-difluorocyclopropyl)methyl)-2-methylbenzofuran-3-carboxylate (300 mg, 50%) as an off- white solid.1H NMR (400 MHz, CDCL) 5 ppm: 7.84 (s, 1 H), 7.35 (d, 1 H), 7.15 (d, 1 H), 4.43 (q, 2 H), 2.97 - 2.86 (m, 2 H), 2.76 (s, 3 H), 1.85 - 1.79 (m, 1 H), 1.53 - 1.44 (m, 4 H), 1.35 - 1.25 (m, 1 H).19F NMR (376 MHz, CDCL) 5 ppm: -127.91 (t), -128.33 (t), -142.73 (t), -143.18 (t).

[0334] Step 2 : A stirred solution of ethyl 5-((2,2-difluorocyclopropyl)methyl)-2-methylbenzofuran-3- carboxylate (500 mg, 1.699 mmol) in THF (20 mL), MeOH (10 mL) and Water (10 mL) was treated with lithium hydroxide monohydrate (712.9 mg, 16.99 mmol) at RT. The RM was stirred at 50 °C for 16 h. The RM was concentrated under reduced pressured. The residue was diluted with water (5 mL) and acidified (pH ~4) with saturated aq. Citric acid solution. The solid was filtered and dried under vacuum to afford 5-((2,2- difluorocyclopropyl)methyl)-2-methylbenzofuran-3 -carboxylic acid (Int-B107) (400 mg, 88%) as an off-white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 12.93 (brs, 1 H), 7.79 (s, 1 H), 7.51 (d, 1 H), 7.22 (d, 1 H), 2.85 (d, 2 H), 2.71 (s, 3 H), 2.01 - 1.93 (m, 1 H), 1.60 - 1.57 (m, 1 H), 1.30 - 1.28 (m, 1 H).19F NMR (376 MHz, DMSO- de) δ ppm: -126.25 (t), -126.66 (t), -141.14 (d), -141.54 (d).Synthesis of 2-methyl-5-(phenylthio)benzofuran-3-carboxylic acid (Int-Blll),

[0335] Step 1 : At 0°C, a solution of sulfinothioyldibenzene (462.69 mg, 2.11 mmol) in THF (30 mL) was treated with Zinc (173.22 mg, 2.64 mmol). The RM was degassed with nitrogen for 10 min. Ethyl 2-methyl-5- (((trifluoromethyl)sulfonyl)oxy)benzofuran-3-carboxylate (500 mg 1.76 mmol) and Pd(dppf)C12 (64.55 mg, 0.08 mmol) were added. The RM was stirred at 80°C for 16 h. The RM was filtered through Celite pad, washed with EtOAc (40 mL) and filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 2% EtOAc in pet. ether to afford ethyl 2-methyl-5-(phenylthio)benzofuran-3-carboxylate (300 mg, 54.38%) as a pale yellow solid.

[0336] Step 2 : A solution of ethyl 2-methyl-5-(phenylthio)benzofuran-3-carboxylate (300 mg, 0.960 mmol) in MeOH: THF: Water (15.0 mL), was treated with NaOH (192.07 mg, 4.80 mmol) at 0 °C and the RM was stirred for 16 h at RT. The RM was concentrated under reduced pressure and the residue was acidified with sat. citric acid solution (pH~5). Precipitate solid was collected by filtration, washed with H2O (30 mL) and dried using vacuum to afford 2-methyl-5-(phenylthio)benzofuran-3-carboxylic acid (Int-Blll) as an off-white solid (250 mg, 91.56%), 1H NMR (400 MHz, CDCl3) 5 ppm: 1H NMR (400 MHz, CDCl3) 5 ppm: 8.38 (s, 1 H), 7.42 - 7.36 (m, 2 H), 7.27 - 7.22 (m, 4 H), 7.19 - 7.15 (m, 1 H), 2.81 (s, 3 H).Synthesis of 2-methyl-5-(phenylsulfinyl)benzofuran-3 -carboxylic acid (Int-B112),

[0337] Step 1 : A stirred solution of ethyl 2-methyl-5-(phenylthio)benzofuran-3-carboxylate (500 mg, 1.601 mmol) in DCM (10 mL) was treated with m-CPBA (219.986 mg, 1.28 mmol) portion wise at 0 °C. The RM was stirred at RT for 3 h. The RM was quenched with saturated sodium bicarbonate solution (20 mL) and extracted with DCM (2 x 30 mL). The combined organic layers were dried over ySO i. filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0-15% EtOAc in Pet. ether to afford ethyl 2-methyl-5-(phenylsulfinyl)benzofuran-3-carboxylate (400 mg, 76%) as an off-white solid.1H NMR (400 MHz, CDCl3) 5 ppm: 8.26 (d, 1 H), 7.67 - 7.65 (m, 2 H), 7.60 (d, 1 H), 7.50 - 7.42 (m, 4 H), 4.41 (q, 2 H), 2.77 (s, 3 H), 1.43 (t, 3 H).

[0338] Step 2 : A stirred solution of ethyl 2-methyl-5-(phenylsulfinyl)benzofuran-3 -carboxylate (400 mg, 1.218 mmol) in THF (5 mL), MeOH (5 mL), and Water (5 mL) was treated with NaOH (194.880 mg, 4.872 mmol) at 0 °C. The RM was stirred at RT for 16 h. The RM was concentrated under reduced pressure. The residue was acidified with saturated aq. Citric acid solution (pH~4). The obtained solid was filtered, washed with water (50 ml) and dried under vacuum to afford 2-methyl-5-(phenylsulfinyl)benzofuran-3 -carboxylic acid (Int-B112). (350 mg, 96%) as an off-white solid.1H NMR (400 MHz, DMSO-de) δ ppm: 13.2 (br s, 1 H), 8.28 (d, 1 H), 7.72 - 7.69 (m, 3 H), 7.61 - 7.59 (m, 1 H), 7.55 - 7.46 (m, 3 H), 2.72 (s, 3 H).Synthesis of 2-methyl-5-(phenylsulfonyl)benzofuran-3 -carboxylic acid (Int-B113),

[0339] Step 1 : A stirred solution of ethyl 2-methyl-5-(phenylthio) benzofuran-3 -carboxylate (800 mg, 2.56 mmol) in DCM (20 mL) was added mCPBA (879.94 mg, 5.122 mmol) portion wise at 0 °C. The RM stirred at RT for 3 h. The RM was quenched with sat. Aq NaHCOi, solution (25 mL) and extracted with DCM (2 x 30 mL), the separated layers were dried over Na?SO i and evaporated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 15% EtOAc in pet-ether to afford ethyl 2-methyl-5-(phenylsulfonyl) benzofuran- 3-carboxylate (550 mg, 62 %).1H NMR (400 MHz, CDCl3) 5 ppm: 8.57 (s, 1 H), 7.97 (d, 2 H), 7.88 (dd, 1 H), 7.55 - 7.47 (m, 4 H), 4.43 (q, 2 H), 2.77 (s, 3 H), 1.45 (t, 3 H).

[0340] Step 2 : A solution of ethyl 2-methyl-5 -(phenylsulfonyl) benzofuran-3 -carboxylate (550 mg, 1.59 mmol) in MeOH: THF: Water (1: 1:1, 15 mL), was treated with NaOH (319.41 mg, 7.98 mmol) at 0 °C and the RM was stirred for 16 h at RT. The RM was concentrated under reduced pressure. The residue was acidified with sat. citric acid solution (pH~5). Precipitate solid was collected by filtration, washed with H2O (30 mL) and dried using vacuum to afford 2-methyl-5-(phenylsulfonyl)benzofuran-3 -carboxylic acid (Int-B113) as an off-white solid (350 mg, 69.28%),1H NMR (400 MHz, CDCl3) 5 ppm: 8.69 (s, 1 H), 8.00 (d, 2 H), 7.92 (dd, 1 H), 7.56 - 7.49 (m, 4 H), 2.85 (s, 3 H).Synthesis of 2-methyl-5-phenethylbenzofuran-3 -carboxylic acid (Int-B115)

[0341] Step 1 : A solution of ethyl (E)-2-methyl-5-styrylbenzofuran-3-carboxylate (Int-B114) (1 g, 3.264 mmol) in EtOH (20 mL) was treated with 10% Pd / C (0.3 g) under nitrogen atmosphere. The RM was stirred at RT for 16 h under a balloon of hydrogen. The RM was filtered through a celite pad, washed with EtOH (20 mL) and the filtrate was evaporated under vacuum to afford ethyl 2-methyl-5-phenethylbenzofuran-3-carboxylate as a pale yellowish gummy (650 mg, 64.58%).1H NMR (400 MHz, CDCl3) 5 ppm: 7.77 (s, 1 H), 7.32 - 7.25 (m, 3 H), 7.21 - 7.17 (m, 3 H), 7.07 (dd, 1 H), 7.41 (q, 2 H), 3.03 - 2.93 (m, 4 H), 2.75 (s, 3 H), 1.43 (t, 3 H).

[0342] Step 2 : A solution of ethyl 2-methyl-5-phenethylbenzofuran-3-carboxylate (0.95 g, 3.081 mmol) in THF (20 mL), MeOH (5 mL) and water (5 mL) was treated with LiOH.H2O (0.646 g, 15.403 mmol) at RT. The RM was stirred at 60 °C for 16 h. The RM was concentrated under reduced pressure. The residue was diluted with water (50 mL), acidified with 6N HO (pH~4), precipitated solid was collected by filtration, washed with water (20 ml) and dried to afford 2-methyl-5-phenethylbenzofuran-3-carboxylic acid (Int-B115) (0.750g, 86.85%).1H NMR (400 MHz, DMSO-de) δ ppm: 7.84 (s. 1 H), 2.32 (d, 1 H), 7.27 - 7.22 (m, 4 H), 7.18 - 7.09 (m, 2 H), 2.95 - 2.89 (m, 4 H), 2.68 (s, 3 H).Synthesis of ethyl 5-(l-hvdroxy-2-phenylethyl)-2-methylbenzofuran-3-carboxylate (Int-B124) , ethyl 2-methyl-5- (2-phenylacetvDbenzofuran-3-carboxylate (Int-B116) and 2-methyl-5-(2-phenylacetyl)benzofuran-3-carboxylic acid (Int-B117),

[0343] Step 1 : A solution of ethyl 5-formyl-2-methylbenzofuran-3-carboxylate (1 g, 4.30 mmol) in THF (30 mL) was treated with benzyl magnesium chloride (3.89 mL, 12.91 mmol) at 0 °C. The RM was stirred at 0 °C for 3 h. The RM was quenched with aqueous ammonium chloride solution (50 mL), extracted with EtOAc (100 mL), dried over ySO i. filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 20% EtOAc in Pet. ether to afford ethyl 5-(l-hydroxy-2-phenylethyl)-2-methylbenzofuran- 3-carboxylate (Int-B124) as a pale yellow liquid (0.7 g, 45%).1H NMR (400 MHz, CDCL) 5 ppm: 7.34 - 7.40 (m, 2 H), 7.29 - 7.32 (m, 3 H), 7.16- 7.27 (m, 3 H), 5.00 - 5.04 (m, 1 H), 4.70 (d, 1 H), 4.39 - 4.44 (q, 2 H), 3.02 - 3.10 (m, 2 H), 2.77 (s, 3 H), 1.44 (t, 3 H).

[0344] Step 2 : A solution of ethyl 5-(l-hydroxy-2-phenylethyl)-2-methylbenzofuran-3-carboxylate (2.4 g, 7.39 mmol) in DCM (30 mL) was treated with Dess-Martin periodinane (15.69 g, 36.99 mmol) at 0 °C. The RM was stirred at RT for 3 h. The RM was quenched with sat. sodium bicarbonate solution (30 mL), extracted with DCM (2 x 100 mL). The combined organic layers were dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 20% EtOAc in Pet. ether to afford ethyl 2-methyl-5-(2-phenylacetyl)benzofuran-3-carboxylate (Int-B116) as a pale yellow solid. (1.8 g, 75%).1H NMR (400 MHz, CDCL) 5 ppm: 8.67 (d, 1 H), 8.00 (dd, 1 H), 7.46 (d, 1 H), 7.29 - 7.35 (m, 1 H), 7.23 - 7.26 (m, 1 H), 4.45 (q, 2 H), 4.36 (s, 2 H), 2.79 (s, 3 H), 1.47 (t, 3 H).

[0345] Step 3 : A solution of ethyl 2-methyl-5-(2-phenylacetyl)benzofuran-3-carboxylate (800 mg, 2.48 mmol) in THF (4 mL), water (4 mL) and MeOH (4 mL) was treated with LiOH.H2O (416 mg, 17.37 mmol) at RT. The RM was stirred at RT for 3 h. The RM was concentrated under reduced pressure and the residue was acidified with 1 N HO solution (pH~4), extracted with EtOAc (2 x 50 mL). Combined organic layers were washed with saturated NaHCCL solution (15 mL), brine (15 mL), dried over Na2SO4, fdtered and concentrated under reduced pressure to afford 2-methyl-5-(2-phenylacetyl)benzofuran-3-carboxylic acid (Int-B117) (600 mg, 82%).1H NMR (400 MHz, CDCL) 5 ppm: 8.72 (d, 1 H), 8.02 (dd, 1 H), 7.49 (d, 1 H), 7.31 - 7.33 (m, 4 H), 7.24 - 7.26 (m, 1 H), 4.39 (s, 2 H), 2.84 (s, 3 H).Synthesis of 5-(l,l-difluoro-2-phenylethyl)-2-methylbenzofuran-3-carboxylic acid (Int-B118),[0346...

Claims

CLAIMS1. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereofwhereinR1represents -F, -Cl, -Br, -I, -CN, -Rw, -ORW, -OC(=O)RW, -NRWRX, -NRWC(=O)RX, -SRW, -S(=O)RW, -S(=O)2RW, -C(=O)RW, -C(=O)ORW, or -C(=O)NRWRX;R3represents -RY;X represents a single bond between Cy and the carbon atom to which it is attached, or X represents -O-, - CR5R5'-, -S-, -S(O)n-, -S-CR5R5, -CR5R5-S-, -CR5R5-CR4R4-, -NR5-CR4R4-, -C=,-C=C-, -CR5R5'-NR5-, in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -0RY, - OC(=O)RY, -NRYRZ, -NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or - C(=O)NRYRZ;R4and R4' independently of one another represents -RY; n is an integer ranging from 1 to 2;R5and R5' independently of one another represent -RY, or R5and R5' together form a carbonyl, a 3-6- membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted, or a 3-6- membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted, on the atom to which they are attached;R6and R7independently of one another represent -F, -Cl, -Br, -I, -CN, -N02, -SF5, -Rw, -ORW, - OC(=O)RW, -NRWRX, -NRWC(=O)RX, -SRW, -S(=O)RW, -S(=O)2RW, -C(=O)RW, -C(=O)ORW, or - C(=O)NRWRX;Cy represents 3-14-membered cycloalkyl, saturated or unsaturated, 3-14-membered heterocycloalkyl, saturated or unsaturated; 5-14-membered aryl, or 5-14-membered heteroaryl; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -N02, =0, =S, -SF5, -RY, -0RY, -OC(=O)RY, -NRYRZ, -NRYC(=0)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ; whereinRwand Rxindependently of one another in each case independently represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6- heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1- Ce-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;RYand Rzindependently of one another in each case independently represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6- heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1- Ce-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or RYand Rztogether form a 4, 5, 6, 7 or 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, saturated or unsaturated, unsubstituted or mono- or polysubstituted; and wherein "mono- or polysubstituted" in each case independently means substituted with one or more substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -C1-6-alkyl, -CF3, -CF2H, - CFH2, -CF2CI, -CFCI2, -C1-6-alkylene-CFs, -C1-6-alkylene-CF2H, -C1-6-alkylene-CFFF, -C1-6-alkylene-O- CF3, -C1-6-alkylene-O-CF2H, -C1-6-alkylene-O-CFFF, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C1-6- alkylene-N(C1-6-alkyl)-C1-6-alkylene-CF3, -C(=O)-C1-6-alkyl, -C1-6-alkylene-C(=O)-C1-6-alkyl, -C(=O)OH, -C1-6-alkylene-C(=O)-OH, -C(=O)-OC1-6-alkyl, -C1-6-alkylene-C(=O)-OC1-6-alkyl, -C(=O)O-C1-6- alkylene-CF3, -C(=O)-NH2, -C1-6-alkylene-C(=O)-NH2, -C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-C(=O)- NH(C1-6-alkyl), -C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-C(=O)-N(C1-6-alkyl)2, -C(=O)-NH(OH), -C1-6- alkylene-C(=O)-NH(OH), -OH, -C1-6-alkylene-OH, =0, -OCF3, -OCF2H, -OCFH2, -OCF2CI, -OCFCI2, - O-C1-6-alkyl, -C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene-NH2, -O-C1-6- alkylene-NH-C1-6-alkyl, -O-C1-6-alkylene-N(C1-6-alkyl)2, -0-C(=0)-C1-6-alkyl, -C1-6-alkylene-0-C(=0)- C1-6-alkyl, -O-C(=O)-O-C1-6-alkyl, -C1-6-alkylene-O-C(=O)-O-C1-6-alkyl, -O-C(=O)-NH(C1-6-alkyl), -C1-6- alkylene-0-C(=0)-NH(C1-6-alkyl), -O-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-O-C(=O)-N(C1-6-alkyl)2, -O-S(=O)2-NH2, -C1-6-alkylene-O-S(=O)2-NH2, -O-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-O-S(=O)2-NH(C1-6- alkyl), -O-S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-O-S(=O)2-N(C1-6-alkyl)2, -NH2, -NO, -NO2, -C1-6- alkylene-NH2, -NH(C1-6-alkyl), -N(3- 14-membered cycloalkyl)(C1-6-alkyl), -N(C1-6-alkyl)-C1-6-alkylene- OH, -N(H)-C1-6-alkylene-OH, -C1-6-alkylene-NH(C1-6-alkyl), -N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6- alkyl)2, -NH-C(=O)-C1-6-alkyl, -C1-6-alkylene-NH-C(=O)-C1-6-alkyl, -NH-C(=O)-O-C1-6-alkyl, -C1-6- alkylene-NH-C(=O)-O-C1-6-alkyl, -NH-C(=O)-NH2, -C1-6-alkylene-NH-C(=O)-NH2, -NH-C(=O)-NH(C1- 6-alkyl), -C1-6-alkylene-NH-C(=O)-NH(C1-6-alkyl), -NH-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-NH-C(=O)- N(C1-6-alkyl)2, -N(C1-6-alkyl)-C(=O)-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-C1-6-alkyl, -N(C1-6- alkyl)-C(=O)-O-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-O-C1-6-alkyl, -N(C1-6-alkyl)-C(=O)-NH2, - C1-6-alkylene-N(C1-6-alkyl)-C(=O)-NH2, -N(C1-6-alkyl)-C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6- alkyl)-C(=O)-NH(C1-6-alkyl), -N(C1-6-alkyl)-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)- N(C1-6-alkyl)2, -NH-S(=O)2OH, -C1-6-alkylene-NH-S(=O)2OH, -NH-S(=O)2-C1-6-alkyl, -C1-6-alkylene- NH-S(=O)2-C1-6-alkyl, -NH-S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-NH-S(=O)2-O-C1-6-alkyl, -NH-S(=O)2- NH2, -C1-6-alkylene-NH-S(=O)2-NH2, -NH-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-NH-S(=O)2-NH(C1-6- alkyl), -NH-S(=O)2N(C1-6-alkyl)2, -C1-6-alkylene-NH-S(=O)2N(C1-6-alkyl)2, -N(C1-6-alkyl)-S(=O)2-OH, - C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-OH, -N(C1-6-alkyl)-S(=O)2-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)- S(=O)2-C1-6-alkyl, -N(C1-6-alkyl)-S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-O-C1-6-alkyl, - N(C1-6-alkyl)-S(=O)2-NH2, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-NH2, -N(C1-6-alkyl)-S(=O)2-NH(C1-6- alkyl), -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-NH(C1-6-alkyl), -N(C1-6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -C1-6- alkylene-N(C1-6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -SH, =S, -SFs, -SCF3, -SCF2H, -SCFH2, -S-C1-6-alkyl, -C1-6- alkylene-S-C1-6-alkyl, -S(=O)-C1-6-alkyl, -C1-6-alkylene-S(=O)-C1-6-alkyl, -S(=O)2-C1-6-alkyl, -C1-6- alkylene-S(=O)2-C1-6-alkyl, -S(=O)2-OH, -C1-6-alkylene-S(=O)2-OH, -S(=O)2-O-C1-6-alkyl, -C1-6-alkylene- S(=O)2-O-C1-6-alkyl, -S(=O)2-NH2, -C1-6-alkylene-S(=O)2-NH2, -S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene- S(=O)2-NH(C1-6-alkyl), -S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-S(=O)2-N(C1-6-alkyl)2, 3-14-membered cycloalkyl, -C1-6-alkylene-(3- 14-membered cycloalkyl), 3 to 14-membered heterocycloalkyl, -C1-6- alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C1-6-alkylene-phenyl, 5 to 14-membered heteroaryl, -C1-6-alkylene-(5 to 14-membered heteroaryl), -O-(3- 14-membered cycloalkyl), -O-(3 to 14- membered heterocycloalkyl), -O-phenyl, -O-(5 to 14-membered heteroaryl), -C(=O)-(3-14-membered cycloalkyl), -C(=O)-(3 to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5 to 14-membered heteroaryl), -S(=O)2-(3- 14-membered cycloalkyl), -S(=O)2-(3 to 14-membered heterocycloalkyl), -S(=O)2- phenyl, -S(=O)2-(5 to 14-membered heteroaryl).

2. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in claim 1, wherein R1represents C1-3 alkyl.

3. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in claim 2, wherein R1represents methyl.

4. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 3, wherein R3represents C-R9R9'R9', where R9,R9', and R9" are independently RY, or C1-6alkyl or C1-eheteroalkyl optionally substituted with one or moreRY5. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 3, wherein R3represents C-R9R9'R9", where one of R9, R9, and R9" is RY, or C1-6alkyl or C1-eheteroalkyl optionally substituted with one or more RY, and where two of R9, R9', and R9" together form a 3-14-membered cycloalkyl, 3-14-membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl, said 3-14-membered cycloalkyl, 3- 14-membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl optionally monosubstituted or polysubstituted with one or more RY.

6. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 3, wherein R3represents C-R9R9'R9', where R9, R9', and R9" are independently -H, -C1-6alkyl, -C1-6alky 1-OH, -C1-6alkyl-O-CH3,. -(C=0)-NH2, -(C=O)-NH- CH3, -(C=O)-N(CH3)2, -C1-6alkyl-CF2H, and -C1-6alkyl-CF3.

7. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 6, wherein Cy represents Ce-Cx cycloalkyl, phenyl, C1-C8heterocycloalkyl, or C5-C8heteroaryl, optionally substituted with one or more of halogen, C1-C3- haloalkyl, hydroxy, acyl, carboxamide, methyl, methoxy, ethyl, ethoxy, propyl, cyclopropyl, butyl, cyclobutyl, oxetane, pyrrole, or diazole, said carboxamide, acyl, cyclopropyl, cyclobutyl, oxetane, pyrrole and diazole optionally being further substituted with halogen, C1-C3-haloalky I. hydroxy, phenyl, methyl, methoxy, ethyl, ethoxy, or propyl optionally connected through -C1-C6-alkylene- or -Ci -Ce-heteroalkylene-.

8. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 7, wherein Cy represents a residue selected from:

9. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 8, wherein R3represents -C-R10R10’R10”, and wherein R10, R10’, and R10’’ independently represent -H;-S(=O)2C1-6-alkyl, saturated, unsubstituted, monosubstituted or polysubstituted with -F;-S(=O)2(3- 14-membered cycloalkyl), saturated, unsubstituted;-C1-6-alkyl, saturated, unsubstituted, monosubstituted or disubstituted with substituents independently of one another selected from the group consisting of -OH, , =0, -OC1-6-alkyl, -NH2, -NHC1-6-alkyl, -N(C1-6- alkyl)2, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkyl, -C(=0)NH2, -C(=0)-NH-C1-3-alkyl, - C(=O)N(C1-3-alkyl)2, -phenyl unsubstituted;3-14-membered cycloalkyl or -C1-6-alkylene-(3-14-membered cycloalkyl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 3-14-membered cycloalkyl is saturated, unsubstituted, monosubstituted or disubstituted with substituents independently of one another selected from the group consisting of -C1-6-alkyl, -C1-6-alkylene-NH2, -C1-6-alkylene-NH-C1-6-alkylene-CF3, -C1-6- alkylene-OH, -C1-6-alkylene-NHC(=O)O-C1-6-alkyl, -OH, -OC1-6-alkyl, -NH2, -N(C1-6-alkyl)2, - NHC(=0)0-C1-6-alkyl;3-14-membered heterocycloalkyl or -C1-6-alkylene-(3-14-membered heterocycloalkyl), wherein -C1-6- alkylene- is unsubstituted or monosubstituted with -OH, wherein said 3-14-membered heterocycloalkyl in each case is selected from azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[l,2-a]pyrazin, 8-azabicyclo[3.2.1]octane, 9-azabicyclo- [3.3.1]nonane, quinuclidine, hexahydro- IH-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1 -dioxothiacyclohexane, in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from the group consisting of -F, -OH, =0, -C1-6- alkyl, -C1-6-alkylene-CFs, -C1-6-alkylene-OH, -C1-6-alkylene-O-C1-6-alkyl, -NH2, -N(C1-6-alkyl)2, -C1-6- alkylene-NH2, -C1-6-alkylene-N(C1-6-alkyl)2, -C(=0)-C1-6-alkyl, -C(=O)OH, -C(=0)0-C1-6-alkyl, - C(=O)O-C1-6-alkylene-CF3, -C(=0)NH2, -C(=0)NH(C1-6-alkyl), -S(=O)2C1-6-alkyl, oxetanyl, pyrimidinyl, -C1-6-alkylene-phenyl;-phenyl unsubstituted;5-14-membered heteroaryl or -C1-6-alkylene-(5-14-membered heteroaryl), wherein -C1-6-alkylene- is unsubstituted or monosubstituted with -OH, wherein said 5-14-membered heteroaryl in each case is selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [l,2,4]triazolo[4,3-a]pyrimidine, in each case unsubstituted, monosubstituted or disubstituted with substituents independently of one another selected from the group consisting of -C1-6-alkyl, -OH.

10. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 9, wherein R5and R5' independently of one another represent -H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

11. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 9, wherein R5and R5' together form a 3-4- membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted, or a 3-4- membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted.

12. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 11 , wherein R6and R7independently of one another represent-H, -F, -Cl, -Br, -I, -OH, -SH, -SF5, -CN, -NO2, -C(=O)OH, -NH2,-C1-6-alkyl, -CF3, -CHF2, -CH2F,-O-C1-6-alkyl, -OCF3, -OCHF2, -OCH2F,-NHC1-6-alkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2;-N(C1-6-alkyl)2 unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2;-C(=0)0C1-6-alkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2;-0C(=0)C1-6-alkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2; or-C1-6-heteroalkyl unsubstituted or substituted with one or more substituents independently of one another selected from -OH, =0, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2, and -C(=O)NH2.

13. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 12 wherein R6and R7represent -H.

14. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 12 wherein R6represents -H, -Cl, or -F.

15. A compound a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof selected from the group consisting ofCpd 1 - N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzoftiran- 3 -carboxamide;Cpd 2 - N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(cis-2-phenylcyclopropyl)benzofuran-3 - carboxamide;Cpd 3 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyridin-2-yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 4 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyridin-3- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 5 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-2-(pyridin-3- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 6 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyridin-4- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 7 - 5-(trans-[ 1 , 1 ’-bi(cyclopropan)] -2-yl)-N-((S)- l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 8 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-cyclopentylcyclopropyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 9 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-2-(l-methyl-lH-pyrazol-5- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 10 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(l-methyl-lH-pyrazol-5- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 11 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran- 3 -carboxamide;Cpd 12 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2,2-difluoro-3-phenylcyclopropyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 13 - N-(4,4-difluoro- 1 -hydroxy-2-methylbutan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3 - carboxamide;Cpd 14 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 15 - 2-methyl-5-(trans-2-phenylcyclopropyl)-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 16 - N-(l,3-dimethoxy-2-methylpropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 17 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 18 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(trans-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 19 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(cis-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 20 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-6-fluoro-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 21 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(trans-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 22 - N-(3-hydroxy-2-methyl-l-(methylamino)-l-oxopropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 23 - N-(3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 24 - N-(l-(dimethylamino)-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 25 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 26 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2,2-dimethyl-3-(pyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 27 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(3-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 28 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(4-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 29 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(5-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 30 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(6-methylpyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 31 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyrazin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 32 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3- carboxamide;Cpd 33 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(spiro[2.4]heptan-l-yl)benzofuran-3- carboxamide;Cpd 34 - N-(l-amino-3-methoxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 35 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(l-methyl-lH-pyrazol-4- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 36 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 37 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(trans-2-methyl-2-(pyridin-2-yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 38 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-6-fluoro-2-methyl-5-(trans-2-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 39 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-l-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 40 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-l-methyl-2-(pyridin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 41 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(dimethylcarbamoyl)cyclopropyl)-2-methy lbenzofuran-3 -carboxamide ;Cpd 42 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(trifluoromethyl)cyclopropyl)benzofuran-3-carboxamide;Cpd 43 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(3- (trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 44 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(4- (trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 45 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(5- (trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 46 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(6- (trifluoromethy l)py ridin-2-y l)cy clopropy l)benzofuran-3 -carboxamide ;Cpd 47 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(pyrimidin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 48 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(4-methylpyrimidin-2- yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 49 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-2-(l,3,5-trimethyl-lH- pyrazol-4-yl)cyclopropyl)benzofuran-3-carboxamide;Cpd 50 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(3-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 51 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(4-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 52 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(5-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 53 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(trans-2-(6-methoxypyridin-2- yl)cyclopropyl)-2-methylbenzofuran-3-carboxamide;Cpd 54 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenylcyclopropyl)benzofuran-3 -carboxamide;Cpd 55 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cis-2-cyclopentylcyclopropyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 56 - N-(l-amino-3-butoxy-l-oxopropan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran-3- carboxamide;Cpd 57 - N-(l-amino-3-hydroxy-2-(hydroxymethyl)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 58 - N-( 1 -amino-2-(hydroxymethyl)- 1 -oxobutan-2-yl)-2-methyl-5-(trans-2-phenylcyclopropyl)benzofuran- 3 -carboxamide;Cpd 59 - N-(l-amino-3-(3-hydroxypropoxy)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 60 - N-(l-amino-4,4-difluoro-2-(hydroxymethyl)-l-oxobutan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 61 - N-(l-amino-3-(azetidin-3-ylmethoxy)-l-oxopropan-2-yl)-2-methyl-5-(trans-2- phenylcyclopropyl)benzofuran-3-carboxamide;Cpd 62 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((trans(cis)-bicyclo[3.1.0]hexan-3-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 63 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cis(cis)-bicyclo[3.1.0]hexan-3-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 64 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(cis-3-(trifluoromethyl)cyclobutoxy)benzofuran-3-carboxamide;Cpd 65 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(trans-3-(trifluoromethyl)cyclobutoxy)benzofuran-3-carboxamide;Cpd 66 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclopentyloxy)-2-methylbenzofuran-3- carboxamide;Cpd 67 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((2,3-dihydro-lH-inden-2-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 68 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclohexyloxy)-2-methylbenzofuran-3- carboxamide;Cpd 69 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((octahydropentalen-2- y l)oxy )benzofuran-3 -carboxamide ;Cpd 70 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(((ls,4R)-4-(trifluoromethyl)cyclohexyl)oxy)benzofuran-3 -carboxamide ;Cpd 71 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(((lr,4S)-4-(trifluoromethyl)cyclohexyl)oxy)benzofuran-3 -carboxamide ;Cpd 72 - 5-((6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)oxy)-2-methyl-N-(4,4,4-trifluoro-l-hydroxybutan-2- yl)benzofuran-3-carboxamide;Cpd 73 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((6,7-dihydro-5H-cyclopenta[b]pyridin-7- yl)oxy)-2-methylbenzofuran-3-carboxamide;Cpd 74 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-5-((6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 75 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((6,7-dihydro-5H-cyclopenta[b]pyridin-5- yl)oxy)-2-methylbenzofuran-3-carboxamide;Cpd 76 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((5,6,7,8-tetrahydroquinolin-8- y l)oxy )benzofuran-3 -carboxamide ;Cpd 77 - 2-methyl-5-((5,6,7,8-tetrahydroquinolin-8-yl)oxy)-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran- 3 -carboxamide;Cpd 78 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((2,3-dihydrobenzofuran-7-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 79 - 5-((2,3-dihydrobenzofuran-7-yl)oxy)-N-(3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 80 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-phenoxybenzofuran-3- carboxamide;Cpd 81 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3- carboxamide;Cpd 82 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(m-tolyloxy)benzofuran-3- carboxamide;Cpd 83 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(p-tolyloxy)benzofuran-3- carboxamide;Cpd 84 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(2-methoxyphenoxy)-2-methylbenzofuran- 3 -carboxamide;Cpd 85 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-methoxyphenoxy)-2-methylbenzofuran- 3 -carboxamide;Cpd 86 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-methoxyphenoxy)-2-methylbenzofuran- 3 -carboxamide;Cpd 87 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2- (trifluoromethy l)phenoxy )benzofuran-3 -carboxamide ;Cpd 88 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-(trifluoromethy l)phenoxy )benzofuran-3 -carboxamide ;Cpd 89 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-(trifluoromethy l)phenoxy )benzofuran-3 -carboxamide ;Cpd 90 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((l-isopropyl-lH-pyrazol-4-yl)oxy)-2- methy lbenzofuran-3 -carboxamide ;Cpd 91 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(pyridin-3-yloxy)benzofuran-3- carboxamide;Cpd 92 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((2-methylpyridin-3- y l)oxy )benzofuran-3 -carboxamide ;Cpd 93 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((6-methylpyridin-3- y l)oxy )benzofuran-3 -carboxamide ;Cpd 94 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(m-tolyloxy)benzofuran-3-carboxamide;Cpd 95 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3-carboxamide;Cpd 96 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(m-tolyloxy)benzofuran-3-carboxamide;Cpd 97 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3-carboxamide;Cpd 98 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(o-tolyloxy)benzofuran- 3 -carboxamide;Cpd 99 - 6-fluoro-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-(o-tolyloxy)benzofuran-3- carboxamide;Cpd 100 - N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-6-fluoro-2-methyl-5-(o-tolyloxy)benzofuran-3- carboxamide;Cpd 101 - (S)-N-(l-amino-3 -hydroxy -2 -methy l-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-phenoxybenzofuran-3-carboxamide;Cpd 102 - N-( 1,3 -dihydroxy -2 -methylpropan-2-yl)-6-fluoro-2-methyl-5-phenoxybenzofuran-3 -carboxamide;Cpd 103 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-phenoxybenzofuran-3-carboxamide;Cpd 104 - N-(3-hydroxy-2-methyl-l-(methylamino)-l-oxopropan-2-yl)-2-methyl-5-phenoxybenzofuran-3- carboxamide;Cpd 105 - N-(3-(hydroxymethyl)-2-oxopyrrolidin-3-yl)-2-methyl-5-phenoxybenzofuran-3-carboxamide;Cpd 106 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3,3-difluorocyclohexyl)-2 -methylbenzofuran- 3 -carboxamide;Cpd 107 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-cyclopropylphenyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 108 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-cyclopropylphenyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 109 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-phenylazetidin-l- yl)benzofuran-3-carboxamide;Cpd 110 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-cyclopropyl-lH-pyrazol-4-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 111 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenyl-lH-l,2,3-triazol-4- yl)benzofuran-3-carboxamide;Cpd 112 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(5-cyclopropylpyridin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 113 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 114 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(5-cyclopropylpyrazin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 115 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-cyclopropylpyridin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 116 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(5-cyclopropylpyridin-3-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 117 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 118 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-phenylpiperazin-l- yl)benzofuran-3-carboxamide;Cpd 119 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(quinolin-3-yl)benzofuran-3- carboxamide;Cpd 120 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(lH-benzo[d]imidazol-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 121 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-( 1 -methyl- IH-benzo [d]imidazol- 2-yl)benzofuran-3 -carboxamide;Cpd 122 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-(4-cyclobutylphenyl)-2-methylbenzofuran-3 -carboxamide;Cpd 123 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-(oxetan-3- y l)pheny l)benzofuran-3 -carboxamide ;Cpd 124 - 5-(4-cyclopropylphenyl)-N-(4,4-difluoro-l-hydroxy-2-methylbutan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 125 - 5-(4-cyclopropylphenyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 126 - 5-(4-cyclopropylphenyl)-2-methyl-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 127 - 5-(4-cyclopropylphenyl)-2-methyl-N-(l,l,l-trifluoro-3-hydroxypropan-2-yl)benzofuran-3- carboxamide;Cpd 128 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenyl-lH-pyrazol-4- yl)benzofuran-3-carboxamide;Cpd 129 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-cyclopropyl-2-fluorophenyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 130 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-(l-methyl-lH-pyrazol-4- y l)pheny l)benzofuran-3 -carboxamide ;Cpd 131 - 2-methyl-5-(l-phenyl-lH-pyrazol-4-yl)-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 132 - 5-(4-cyclopropyl-2-fluorophenyl)-2-methyl-N-(4,4,4-trifluoro-l-hydroxybutan-2-yl)benzofuran-3- carboxamide;Cpd 133 - 2-methyl-5-(4-(l-methyl-lH-pyrazol-4-yl)phenyl)-N-(4,4,4-trifluoro-l-hydroxybutan-2- yl)benzofuran-3-carboxamide;Cpd 134 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-phenyloxetan-3- yl)benzofuran-3-carboxamide;Cpd 135 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-(o-tolyl)oxetan-3- yl)benzofuran-3-carboxamide;Cpd 136 - N-( 1 ,3 -dihydroxy -2 -methylpropan-2-yl)-6-fluoro-2-methyl-5-( 1 -phenyl- lH-pyrazol-5-yl)benzofuran- 3 -carboxamide;Cpd 137 - 5-(3,4-dihydroquinolin-l(2H)-yl)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 138 - 5-(2-cyclopropylphenyl)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-6-fluoro-2-methylbenzofuran-3- carboxamide;Cpd 139 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3,4-dihydroquinolin-l(2H)-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 140 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-6-fluoro-2-methyl-5-(l-phenyl-lH-pyrazol-5- yl)benzofuran-3-carboxamide;Cpd 141 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-(3 ,4-dihydroquinolin- 1 (2H)-yl)-6-fluoro-2- methy lbenzofuran-3 -carboxamide ;Cpd 142 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(2-cyclopropylphenyl)-6-fluoro-2- methy lbenzofuran-3 -carboxamide ;Cpd 143 - 5-(3,4-dihydroquinolin-l(2H)-yl)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-6-fluoro-2- methy lbenzofuran-3 -carboxamide ;Cpd 144 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-phenylpyrrolidin-l- yl)benzofuran-3-carboxamide;Cpd 145 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(piperidin-l- ylmethyl)benzofuran-3 -carboxamide;Cpd 146 - 5 -((3 -azabicyclo [3.1.0]hexan-3-yl)methyl)-N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 147 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 148 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(piperidine-l- carbony l)benzofuran-3 -carboxamide ;Cpd 149 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclopentylidenemethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 150 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-benzyl-2-methylbenzofuran-3- carboxamide;Cpd 151 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(cyclohexylmethyl)-2-methylbenzofuran-3- carboxamide;Cpd 152 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(l-phenylethyl)benzofuran-3- carboxamide;Cpd 153 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((tetrahydro-2H-pyran-4- yl)methyl)benzofuran-3-carboxamide;Cpd 154 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-methylbenzyl)benzofuran-3- carboxamide;Cpd 155 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(3-methylbenzyl)benzofuran-3- carboxamide;Cpd 156 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(4-methylbenzyl)benzofuran-3- carboxamide;Cpd 157 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(2-fluorobenzyl)-2-methylbenzofuran-3- carboxamide;Cpd 158 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(3-fluorobenzyl)-2-methylbenzofuran-3- carboxamide;Cpd 159 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(4-fluorobenzyl)-2-methylbenzofuran-3- carboxamide;Cpd 160 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(fluoro(phenyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 161 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2,2,2-trifluoro-l-pheny lethy l)benzofuran-3 -carboxamide ;Cpd 162 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-(cyclopropylmethyl)-2-methylbenzofuran- 3 -carboxamide;Cpd 163 - N-((S)- 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-((2,2-difluorocyclopropyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 164 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-2-ylmethyl)benzofuran- 3 -carboxamide;Cpd 165 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-3 -ylmethyl)benzofuran- 3 -carboxamide;Cpd 166 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-4-ylmethyl)benzofuran- 3 -carboxamide;Cpd 167 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((4,4-difluorocyclohexyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 168 - 5-((4,4-difluorocyclohexyl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 169 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((3-hydroxycyclobutyl)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 170 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(((lR,3s,5S)-bicyclo[3.1.0]hexan-3- yl)methyl)-2-methylbenzofuran-3-carboxamide;Cpd 171 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(((lR,3r,5S)-bicyclo[3.1.0]hexan-3- yl)methyl)-2-methylbenzofuran-3-carboxamide;Cpd 172 - 5-(((lR,3s,5S)-bicyclo[3.1.0]hexan-3-yl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 173 - 5-(((lR,3r,5S)-bicyclo[3.1.0]hexan-3-yl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 174 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((cis-3- (trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 175 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((trans-3-(trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 176 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-((cis-3-(trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 177 - N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-((trans-3- (trifluoromethy l)cy clobuty l)methy l)benzofuran-3 -carboxamide ;Cpd 178 - (S)-5-((2-oxaspiro[3.3]heptan-6-yl)methyl)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 179 - 5-((2-oxaspiro[3.3]heptan-6-yl)methyl)-N-(l-hydroxy-3-methoxy-2-methylpropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 180 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(phenylthio)benzofuran-3- carboxamide;Cpd 181 - N-((S)- 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(phenylsulfinyl)benzofuran-3- carboxamide;Cpd 182 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(phenylsulfonyl)benzofuran-3 - carboxamide;Cpd 183 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-(phenylthio)benzofuran-3-carboxamide;Cpd 184 - N-(4,4-difluoro-l -hydroxy -2 -methylbutan-2-yl)-2-methyl-5-(phenylthio)benzofuran-3 -carboxamide;Cpd 185 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-(pyridin-2-ylthio)benzofuran-3-carboxamide;Cpd 186 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2-methyl-5-(pyridin-2-ylthio)benzofuran-3 - carboxamide;Cpd 187 - N-( 1 ,3 -dihydroxy -2 -methylpropan-2-yl)-6-fluoro-2-methyl-5-(phenylthio)benzofuran-3-carboxamide;Cpd 188 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-6-fluoro-2-methyl-5-(phenylthio)benzofuran- 3 -carboxamide;Cpd 189 - 5-(benzylthio)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3-carboxamide;Cpd 190 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(benzylthio)-2-methylbenzofuran-3- carboxamide;Cpd 191 - N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-5-((pyridin-2-ylmethyl)thio)benzofuran-3- carboxamide;Cpd 192 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-((pyridin-2- y Imethy l)thio)benzofuran-3 -carboxamide ;Cpd 193 - 5-((cyclopropylmethyl)thio)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 194 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-phenethylbenzofuran-3-carboxamide;Cpd 195 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l,l-difluoro-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 196 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-phenylacetyl)benzofuran-3- carboxamide;Cpd 197 - N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(phenylethynyl)benzofuran-3- carboxamide;Cpd 198 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-5-(2-(piperidin-l- yl)ethyl)benzofuran-3 -carboxamide ;Cpd 199 - 5-(2-(3-azabicyclo[3.1.0]hexan-3-yl)ethyl)-N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 200 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-(dimethylamino)-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 201 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-hydroxy-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 202 - N-((S)-l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(l-methoxy-2-phenylethyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 203 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cyclopentyl(methyl)amino)methyl)-2-methy lbenzofuran-3 -carboxamide ;Cpd 204 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cyclopentylamino)methyl)-2- methy lbenzofuran-3 -carboxamide ;Cpd 205 - (S)-N3 -( l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-2 -methy l-N5-(pyridin-2-yl)benzofuran-3 ,5- dicarboxamide;Cpd 206 - (S)-N3-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-2-methyl-N5-phenylbenzofuran-3,5- dicarboxamide;Cpd 207 - (S)-N3 -( l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-N5,2-dimethyl-N5-phenylbenzofuran-3 ,5- dicarboxamide;Cpd 208 - (S)-N3 -( l-amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-N5-cyclopropyl-2 -methy lbenzofuran-3 ,5- dicarboxamide;Cpd 209 - (S)-N3-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-N5-cyclopropyl-N5,2-dimethylbenzofuran-3 ,5 -dicarboxamide,Cpd 210 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-((cyclopropylmethyl)(methyl)amino)-2- methy lbenzofuran-3 -carboxamide ;Cpd 211 - 5-(benzyl(methyl)amino)-N-(l,3-dihydroxy-2-methylpropan-2-yl)-2-methylbenzofuran-3- carboxamide;Cpd 212 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-(benzyl(methyl)amino)-2- methy lbenzofuran-3 -carboxamide ;Cpd 213 - (S)-N-( 1 -amino-3 -hydroxy -2 -methyl- 1 -oxopropan-2-yl)-5-((cyclopropylmethyl)(isopropyl)amino)-2- methy lbenzofuran-3 -carboxamide; andCpd 214 - (S)-N-(l-amino-3-hydroxy-2-methyl-l-oxopropan-2-yl)-5-((cyclopropylmethyl)thio)-2- methy lbenzofuran-3 -carboxamide ;16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 15, and a pharmaceutically-acceptable carrier.

17. A compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 1 to 15 or the pharmaceutical composition according to claim 16, for use in the treatment of pain or epilepsy.

18. The compound or the pharmaceutical composition for use in the treatment of pain according to claim 17, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain; preferably postoperative pain or migraine pain.

19. A method of treating pain or epilepsy, comprising administering to a patient in need thereof a therapeutically effective amount of a compound as defined in any one of claims 1 to 15, or the pharmaceutical composition according to claim 16.

20. The method of claim 19, wherein the pain is selected from nociceptive pain, inflammatory pain, andneuropathic pain; preferably post-operative pain or migraine pain.

21. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereofwhereinR3represents C-R9R9'R9", where R9, R9', and R9" are independently RY, or C1-6alkyl or C1-eheteroalkyl optionally substituted with one or more RY; or wherein one of R9, R9', and R9" is RY, or C1-6alkyl or C1- eheteroalkyl optionally substituted with one or more RY, and where two of R9, R9', and R9" together form a 3-14-membered cycloalkyl, 3-14-membered heterocycloalkyl, 5-14-membered aryl, or 5-14-membered heteroaryl, said 3-14-membered cycloalkyl, 3-14-membered heterocycloalkyl, 5-14-membered aryl, or 5- 14-membered heteroaryl optionally monosubstituted or polysubstituted with one or more RY;R6is selected from H, halogen, and C1-ehaloalkyl;X represents a single bond between Cy and the carbon atom to which it is attached, or X represents -O-, - CR5R5'-, -S-, -S(O)n-, -S-CR5R5, -CR5R5-S-, -CR5R5-CR4R4-, -NR5-CR4R4-, -O-CR5R5-, -C=, -C=C-, -CR5R5'-NR5-, in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -0RY, -OC(=O)RY, -NRYRZ, - NRYC(=O)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ; n is an integer ranging from 1 to 2;R4and R4' independently of one another represents -RY;R5and R5' independently of one another represent -RY, or R5and R5' together form a carbonyl, a 3-6- membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted, or a 3-6-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted, on the atom to which they are attached;Cy represents 3-14-membered cycloalkyl, saturated or unsaturated, 3-14-membered heterocycloalkyl, saturated or unsaturated; 5-14-membered aryl, or 5-14-membered heteroaryl; in each case unsubstituted, mono- or poly substituted with substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -NO, -NO2, =0, =S, -SF5, -RY, -0RY, -OC(=O)RY, -NRYRZ, -NRYC(=0)RZ, -SRY, -S(=O)RY, -S(=O)2RY, -C(=O)RY, -C(=O)ORY, or -C(=O)NRYRZ; whereinRYand Rzindependently of one another in each case independently represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-Cc-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered heterocycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6- heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through -C1-C6-alkylene- or -C1-Cc-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through -C1-C6-alkylene- or -C1-Cc-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted; or RYand Rztogether form a 4, 5, 6, 7 or 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, saturated or unsaturated, unsubstituted or mono- or polysubstituted; and wherein "mono- or polysubstituted" in each case independently means substituted with one or more, e.g. 1, 2, 3, 4, or more substituents independently of one another selected from -F, -Cl, -Br, -I, -CN, -C1-6- alkyl, -CF3, -CF2H, -CFH2, -CF2CI, -CFCI2, -C1-6-alkylene-CF3, -C1-6-alkylene-CF2H, -C1-6-alkylene-CFH2, -C1-6-alkylene-O-CF3, -C1-6-alkylene-O-CF2H, -C1-6-alkylene-O-CFFF, -C1-6-alkylene-NH-C1-6-alkylene- CF3, -C1-6-alkylene-N(C1-6-alkyl)-C1-6-alkylene-CF3, -C(=O)-C1-6-alkyl, -C1-6-alkylene-C(=O)-C1-6-alkyl, - C(=O)OH, -C1-6-alkylene-C(=O)-OH, -C(=O)-OC1-6-alkyl, -C1-6-alkylene-C(=O)-OC1-6-alkyl, -C(=O)O- C1-6-alkylene-CF3, -C(=O)-NH2, -C1-6-alkylene-C(=O)-NH2, -C(=O)-NH(C1-6-alkyl), -C1-6-alkylene- C(=O)-NH(C1-6-alkyl), -C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-C(=O)-N(C1-6-alkyl)2, -C(=O)-NH(OH), -C1-6-alkylene-C(=O)-NH(OH), -OH, -C1-6-alkylene-OH, =0, -OCF3, -OCF2H, -OCFH2, -OCF2CI, -OCFCk, - O-C1-6-alkyl, -C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene-O-C1-6-alkyl, -O-C1-6-alkylene-NH2, -O-C1-6- alkylene-NH-C1-6-alkyl, -O-C1-6-alkylene-N(C1-6-alkyl)2, -0-C(=0)-C1-6-alkyl, -C1-6-alkylene-0-C(=0)-C1-6-alkyl, -O-C(=O)-O-C1-6-alkyl, -C1-6-alkylene-O-C(=O)-O-C1-6-alkyl, -O-C(=O)-NH(C1-6-alkyl), -C1-6- alkylene-0-C(=0)-NH(C1-6-alkyl), -O-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-O-C(=O)-N(C1-6-alkyl)2, -O- S(=O)2-NH2, -C1-6-alkylene-O-S(=O)2-NH2, -O-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-O-S(=O)2-NH(C1-6- alkyl), -O-S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-O-S(=O)2-N(C1-6-alkyl)2, -NH2, -NO, -NO2, -C1-6- alkylene-NH2, -NH(C1-6-alkyl), -N(3-14-membered cycloalkyl)(C1-6-alkyl), -N(C1-6-alkyl)-C1-6-alkylene- OH, -N(H)-C1-6-alkylene-0H, -C1-6-alkylene-NH(C1-6-alkyl), -N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)2, -NH-C(=O)-C1-6-alkyl, -C1-6-alkylene-NH-C(=O)-C1-6-alkyl, -NH-C(=O)-O-C1-6-alkyl, -C1-6-alkylene-NH- C(=O)-O-C1-6-alkyl, -NH-C(=0)-NH2, -C1-6-alkylene-NH-C(=O)-NH2, -NH-C(=0)-NH(C1-6-alkyl), -C1-6- alkylene-NH-C(=O)-NH(C1-6-alkyl), -NH-C(=O)-N(Ci -6-alkyl)2, -C1-6-alkylene-NH-C(=O)-N(C1-6-alkyl)2, -N(Ci -6-alkyl)-C(=0)-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-C1-6-alkyl, -N(C1-6-alkyl)-C(=O)-O- C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-O-C1-6-alkyl, -N(C1-6-alkyl)-C(=0)-NH2, -C1-6-alkylene- N(C1-6-alkyl)-C(=O)-NH2, -N(C1-6-alkyl)-C(=O)-NH(C1-6-alkyl), -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-NH(C1-6-alkyl), -N(C1-6-alkyl)-C(=O)-N(C1-6-alkyl)2, -C1-6-alkylene-N(C1-6-alkyl)-C(=O)-N(C1-6-alkyl)2, - NH-S(=O)2OH, -C1-6-alkylene-NH-S(=O)2OH, -NH-S(=O)2-C1-6-alkyl, -C1-6-alkylene-NH-S(=O)2-C1-6- alkyl, -NH-S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-NH-S(=O)2-O-C1-6-alkyl, -NH-S(=O)2-NH2, -C1-6- alkylene-NH-S(=O)2-NH2, -NH-S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-NH-S(=O)2-NH(C1-6-alkyl), -NH- S(=O)2N(C1-6-alkyl)2, -C1-6-alkylene-NH-S(=O)2N(C1-6-alkyl)2, -N(C1-6-alkyl)-S(=O)2-OH, -C1-6-alkylene- N(C1-6-alkyl)-S(=O)2-OH, -N(C1-6-alkyl)-S(=O)2-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-C1-6- alkyl, -N(C1-6-alkyl)-S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-O-C1-6-alkyl, -N(C1-6- alkyl)-S(=O)2-NH2, -C1-6-alkylene-N(C1-6-alkyl)-S(=O)2-NH2, -N(C1-6-alkyl)-S(=O)2-NH(C1-6-alkyl), -C1-6- alkylene-N(Ci -6-alkyl)-S(=O)2-NH(C1-6-alkyl), -N(Ci -6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-N(C1- 6-alkyl)-S(=O)2-N(C1-6-alkyl)2, -SH, =S, -SF5, -SCF3, -SCF2H, -SCFH2, -S-C1-6-alkyl, -C1-6-alkylene-S-C1- 6-alkyl, -S(=O)-C1-6-alkyl, -C1-6-alkylene-S(=O)-C1-6-alkyl, -S(=O)2-C1-6-alkyl, -C1-6-alkylene-S(=O)2-C1-6- alkyl, -S(=O)2-OH, -C1-6-alkylene-S(=O)2-OH, -S(=O)2-O-C1-6-alkyl, -C1-6-alkylene-S(=O)2-O-C1-6-alkyl, - S(=O)2-NH2, -C1-6-alkylene-S(=O)2-NH2, -S(=O)2-NH(C1-6-alkyl), -C1-6-alkylene-S(=O)2-NH(C1-6-alkyl), - S(=O)2-N(C1-6-alkyl)2, -C1-6-alkylene-S(=O)2-N(C1-6-alkyl)2, 3-14-membered cycloalkyl, -C1-6-alkylene-(3- 14-membered cycloalkyl), 3 to 14-membered heterocycloalkyl, -C1-6-alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C1-6-alkylene-phenyl, 5 to 14-membered heteroaryl, -C1-6-alkylene-(5 to 14- membered heteroaryl), -O-(3-14-membered cycloalkyl), -O-(3 to 14-membered heterocycloalkyl), -O- phenyl, -O-(5 to 14-membered heteroaryl), -C(=O)-(3- 14-membered cycloalkyl), -C(=O)-(3 to 14- membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5 to 14-membered heteroaryl), -S(=O)2-(3-14- membered cycloalkyl), -S(=O)2-(3 to 14-membered heterocycloalkyl), -S(=O)2-phenyl, -S(=O)2-(5 to 14- membered heteroaryl).

22. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in claim 21, wherein R3represents C-R’R’R9', where R9, R9', and R9" are independently RY, or C1-6alkyl or C1-eheteroalkyl optionally substituted with one or more RY.

23. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 21 to 22, wherein R3represents C-R’R’R9', where R9, R9', and R9" are independently -H, -C1-6alkyl, -C1-6alky 1-OH, -C1-6alkyl-O-CH,. -(C=O)-NH2, -(C=O)-NH- CH3, -(C=O)-N(CH3)2, -C1-6alkyl-CF^, and -C1-6alkyl-CF3.

24. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 21 to 23, wherein Cy represents C3-C8cycloalkyl, phenyl, Cs-C8heterocycloalkyl, or Cs-C8heteroaryl, optionally substituted with one or more of halogen, C1-C3-haloalkyl, hydroxy, acyl, carboxamide, methyl, methoxy, ethyl, ethoxy, propyl, cyclopropyl, butyl, cyclobutyl, oxetane, pyrrole, or diazole, said carboxamide, acyl, cyclopropyl, cyclobutyl, oxetane, pyrrole and diazole optionally being further substituted with halogen, C1-C3-haloalkyl, hydroxy, phenyl, methyl, methoxy, ethyl, ethoxy, or propyl optionally connected through -C1-C6-alkylene- or -Ci -Cc-heteroalkylene-.

5. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 21 to 23, wherein Cy represents a residue selected from:

26. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 21 to 25, wherein R5and R5' independently of one another represent-H;-C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;-C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-14-membered cycloalkyl is optionally connected through -C1-C6-alkylene- or -C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted.

27. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 21 to 25, wherein R5and R5' together form a 3-4- membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted, or a 3-4- membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted.

28. A compound of formula (II), a stereo-isomeric form, a physiologically acceptable salt, solvate and / or polymorph thereof, as defined in any one of claims 21 to 27 wherein R6represents -H, -Cl, or -F.

29. A pharmaceutical composition comprising a compound according to any one of claims 21 to 28.

30. The compound according to any one of claims 21 to 28 or the pharmaceutical composition according to claim 29, for use in the treatment of pain or epilepsy.

31. The compound or the pharmaceutical composition for use in the treatment of pain according to claim 30, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain; preferably post-operative pain or migraine pain.

32. A method of treating pain or epilepsy, comprising administering to a patient in need thereof a therapeutically effective amound of a compound as defined in any one of claims 21 to 28, or the pharmaceutical composition according to claim 29.

33. The method of claim 32, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain; preferably post-operative pain or migraine pain.

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