Substituted indole compounds and uses thereof

Abstract

The present disclosure relates to compounds having the following formula (I): or a pharma- ceutically acceptable salt, hydrate, derivative, or solvate thereof: The compounds of formula (I) disrupt the activity of tropomyosin isoform Tpm4.2. [Formula 1] TIFF2024533748000022.tif32158

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to AU2021903130, the entire disclosure of which is incorporated herein by cross-reference.

[0002] FIELD OF THE DISCLOSURE This disclosure relates generally to a class of substituted indole compounds and uses of the compounds. [Background technology]

[0003] Tropomyosin is a coiled-coil protein that copolymerizes with actin filaments in the cytoplasm and muscle sarcomeres. Through alternative splicing, four mammalian tropomyosin genes can give rise to 40 distinct tropomyosin isoforms, each with a uniquely defined function in the actin filament assembly to which it is associated. These actin-tropomyosin structures are involved in a diverse array of cellular processes, including cell division, morphogenesis, and migration.

[0004] The present inventors have developed a class of substituted indole compounds that disrupt the activity of the tropomyosin isoform Tpm4.2. Summary of the Invention

[0005] In a first embodiment, the compound of formula (I):

[0006] [ka]

[0007] (In the formula: R1 is -(CH2) v -X-R3; X is absent, NH, O or S; R3 is morpholinyl or -C(Y)(Y1)(Y2); Y, Y1 and Y2 are H, C 1-6 Alkyl and -(CH2)j independently selected from OR4; R4 is H or C 1-6 is alkyl; R2 is

[0008] [ka]

[0009] is Z is O, NH, -C(O)NH- or -C(O)O-; Z1 is -(CH2) t - is; R5 is OH, -COOH, -C(O)OR6, halogen, C 1-6 Alkyl, C 1-6 alkoxy, -NR6R7 or -CF3; R6 and R7 are H and C 1-6 independently selected from alkyl; v is 1, 2 or 3; t is 1, 2 or 3; u is 0 to 4; and j is 1, 2 or 3. or a pharma- ceutically acceptable salt, hydrate, derivative or solvate thereof.

[0010] In a second aspect, there is provided a method for disrupting Tpm4.2-containing actin filaments, the method comprising contacting Tpm4.2-containing actin filaments with a compound of formula (I) as defined in the first aspect.

[0011] In a third aspect, there is provided the use of a compound of formula (I) as defined in the first aspect for disrupting Tpm4.2-containing actin filaments.

[0012] Tpm4.2-containing actin filaments can be present intracellularly.

[0013] In a fourth aspect, there is provided the use of a compound of formula (I) as defined in the first aspect as a tool compound. [Brief description of the drawings]

[0014] [Figure 1] Representative images showing the disruption of the Tpm4.2 filament network by compound 13 under treatment conditions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] definition Below are some definitions that may be helpful in understanding the description of this disclosure. These are intended as general definitions and should in no way limit the scope of the disclosure to only those terms, but are presented for a better understanding of the following description.

[0016] Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0017] The terms "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0018] In the context of this specification, the term "alkyl" is understood to mean a linear or branched monovalent saturated hydrocarbon group having the stated number of carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, 1-propyl, isopropyl, 1-butyl, 2-butyl, isobutyl, tert-butyl, amyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, pentyl, isopentyl, hexyl, 4-methylpentyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, etc.

[0019] In the present context, the term "alkoxy" is taken to mean an O-alkyl group, where alkyl is as defined herein. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, sec-butoxy and tert-butoxy.

[0020] In the context of this specification, the terms "halo" and "halogen" are used interchangeably and refer to fluorine, chlorine, bromine and iodine.

[0021] Detailed Description In a first embodiment, the compound of formula (I):

[0022] [ka]

[0023] (In the formula: R1 is -(CH2) v -X-R3; X is absent, NH, O or S; R3 is morpholinyl or -C(Y)(Y1)(Y2); Y, Y1 and Y2 are H, C 1-6 Alkyl and -(CH2) j independently selected from OR4; R4 is H or C 1-6is alkyl; R2 is

[0024] [ka]

[0025] is Z is O, NH, -C(O)NH- or -C(O)O-; Z1 is -(CH2) t - is; R5 is OH, -COOH, -C(O)OR6, halogen, C 1-6 Alkyl, C 1-6 alkoxy, -NR6R7 or -CF3; R6 and R7 are H and C 1-6 independently selected from alkyl; v is 1, 2 or 3; t is 1, 2 or 3; u is 0 to 4; and j is 1, 2 or 3. or a pharma- ceutically acceptable salt, hydrate, derivative or solvate thereof.

[0026] In one embodiment, X can be NH or absent.

[0027] In another embodiment, Z can be O, NH, -C(O)NH- or -C(O)O-.

[0028] In another embodiment, Z can be O or NH.

[0029] In further embodiments, t can be 1 or 2.

[0030] In yet other embodiments, v can be 2 or 3.

[0031] In another embodiment, u can be 0, 1, 2 or 3.

[0032] In still further embodiments, u can be 0, 1 or 2.

[0033] In yet another embodiment, R4 is H or C 1-3 It may be alkyl.

[0034] In another embodiment, R4 can be H or methyl.

[0035] In a further embodiment, R 6 and R 7 may be independently selected from H and methyl.

[0036] In yet another embodiment, R5 is -COOH, -C(O)OR6, halogen, C 1-3 Alkyl, C 1-3 It can be alkoxy, -NR6R7 or -CF3.

[0037] In a further embodiment, R5 is halogen, C 1-3 Alkyl, C 1-3 It can be alkoxy, -NR6R7 or -CF3.

[0038] In yet another embodiment, R5 is halogen, C 1-3 Alkyl, C 1-3 It can be alkoxy or -CF3.

[0039] In still further embodiments, R5 can be halogen, methyl, methoxy, or -CF3.

[0040] In another embodiment, R5 can be fluoro, methyl, methoxy, or -CF3.

[0041] In further embodiments, R3 can be -C(Y)(Y1)(Y2).

[0042] In another embodiment, Y is H or C 1-3alkyl and Y1 is -(CH2) j OR4, H or C 1-3 alkyl and Y2 is -(CH2) j OR4 or C 1-3 It is an alkyl.

[0043] In a further embodiment, Y is H or methyl and Y is -(CH) j OR4, H or methyl; Y2 is -(CH2) j OR4 or methyl, where j is 1 or 2.

[0044] In yet another embodiment, Y is H or methyl and Y is -(CH) j OR4, H or methyl; Y2 is -(CH2) j OR4 or methyl, where j is 1.

[0045] In one embodiment, R2 is located at the 6 position.

[0046] In one embodiment, R1 is:

[0047] [ka]

[0048] Selected from

[0049] In another embodiment, R2 is:

[0050] [ka]

[0051] is selected from.

[0052] Representative compounds according to formula (I) include:

[0053] [ka] TIFF2024533748000009.tif253150TIFF2024533748000010.tif176158

[0054] Includes:

[0055] In one embodiment, the compound of formula (I) is selected from any one or more of the above compounds 1-25, in any combination.

[0056] The selected compound of formula (I) may contain one or more chiral centers. The present disclosure covers all enantiomers and diastereoisomers and their mixtures in any ratio. The present disclosure also covers isolated enantiomers or pairs of enantiomers. Methods for separating enantiomers and diastereoisomers are well known to those skilled in the art. In some embodiments, the compound of formula (I) is a racemic mixture. In other embodiments, the compound of formula (I) exists in optically pure form.

[0057] The compounds of formula (I) are also intended to include hydrates and solvates. A solvate is a complex formed by the association of molecules of a solvent with a compound of formula (I). In the case of compounds of formula (I) that are solids, those skilled in the art will understand that such compounds may exist in various crystalline forms or polymorphs, all of which are intended to be within the scope of this disclosure.

[0058] The compound of formula (I) may be in the form of a pharmaceutically acceptable salt. Such salts are well known to those skilled in the art. SM Berge et al. describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66:1-19. The pharmaceutically acceptable salts can be prepared in situ during the final isolation and purification of the compound of formula (I) or separately by reacting the free base compound with a suitable organic acid. The suitable pharmaceutically acceptable acid addition salts of the compounds of the present disclosure may be prepared from inorganic acids or from organic acids. Examples of such inorganic acids are hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid, and phosphoric acid. Suitable organic acids may be selected from aliphatic, alicyclic, aromatic, heterocyclic carboxylic and sulfonic classes of organic acids, examples of which are formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucoronic acid, fumaric acid, maleic acid, pyruvic acid, alkylsulfonic acid, arylsulfonic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, mesylic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, pamoic acid, pantothenic acid, sulfanilic acid, cyclohexylaminosulfonic acid, stearic acid, algenic acid, β-hydroxybutyric acid and galacturonic acid. Suitable pharma- ceutically acceptable base addition salts of the compounds of the present disclosure include metallic salts made from lithium, sodium, potassium, magnesium, calcium, aluminum and zinc, and organic salts made from organic bases such as choline, diethanolamine and morpholine.Alternatively, organic salts made from N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine), procaine, ammonium salts, quaternary salts such as tetramethylammonium salts, amino acid addition salts such as salts with glycine and arginine.

[0059] The compounds of formula (I) also extend to include all derivatives which have a physiologically cleavable leaving group which can be cleaved in vivo to provide the compounds of formula (I).

[0060] Compounds of formula (I) may be synthesized as illustrated in the Examples section below. Armed with these synthetic procedures and common general knowledge, one skilled in the art will be able to readily prepare all compounds encompassed by formula (I).

[0061] After purification, the compound of formula (I) may be substantially pure. For example, the compound of formula (I) may be isolated in a form that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% pure.

[0062] The compound of formula (I) may be obtained as a racemic mixture. The enantiomers may be isolated using techniques known to those skilled in the art, including chiral resolution, supercritical fluid chromatography, and enantioselective synthesis. The individual enantiomers may be isolated in substantially pure form or in enantiomeric excess (ee). For example, in a preferred embodiment, the enantiomers may be isolated in about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater than 99% enantiomeric excess.

[0063] Small molecules that disrupt biological targets in a dose-dependent manner resulting in a detectable effect can be used to "probe" the role of the target in a biological process. Such molecules may be referred to as "tool" compounds. The compounds of the present disclosure provide a means to selectively manipulate the activity of the tropomyosin isoform Tpm4.2. As such, the compounds of the present disclosure can be used to test hypotheses about the biological role of this isoform. This allows researchers to compare biological readouts from cells treated with the compounds of the present disclosure to those of untreated cells to assess the impact of disrupting Tpm4.2-containing filaments on a biological process of interest. As such, the compounds of the present disclosure are useful as tool compounds.

[0064] Working Example The present disclosure is further described below with reference to the following non-limiting examples. Example 1 - Synthesis of Compounds of Formula (I)

[0065] [ka] Reagents and conditions: a) RPhCH2CH2OH, K2CO3, KI, 2-butanone, 80°C, 16 h; b) BrCH2CH2OTs, NaH, DMF, 0°C to rt, 2 h; c) 2-amino-2-methylpropane-1,3-diol, DIPEA, MeCN, 100°C, 1 h.

[0066] Preparation of 6-phenethoxy-1H-indole To a stirred solution of 1H-indol-6-ol (1.00 g, 7.51 mmol) in 2-butanone (20 mL) was added K2CO3 (3.10 g, 22.53 mmol) and KI (125 mg, 0.75 mmol), followed by 2-phenylethan-1-ol (4.17 g, 22.53 mmol). The resulting reaction mixture was stirred at 80 °C for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was diluted with water and extracted with EtOAc (100 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as an off-white solid (600 mg, 34%). LCMS: m / z 238.18 [M+H] + .

[0067] Other analogues prepared by this method: 6-(2-fluorophenethoxy)-1H-indole (19%). LCMS: m / z 256.24 [M+H] + . 6-(3-fluorophenethoxy)-1H-indole (29%). LCMS: m / z 256.25 [M+H] + . 6-(4-fluorophenethoxy)-1H-indole (17%). LCMS: m / z 256.03 [M+H] + .

[0068] Preparation of 2-(6-phenethoxy-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate To a stirred solution of 6-phenethoxy-1H-indole (1.00 g, 4.21 mmol) in DMF (20 mL) was added NaH (60% dispersion in mineral oil) (202 mg, 5.06 mmol) at 0° C. The mixture was stirred at this temperature for 20 min. Then, 2-bromoethyl 4-methylbenzenesulfonate (1.76 g, 6.32 mmol) dissolved in DMF was slowly added dropwise to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice and extracted with EtOAc (100 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 25% EtOAc in petroleum ether to give the title compound as an off-white solid (150 mg, 8%). LCMS: m / z 436.55 [M+H] + .

[0069] Other analogues prepared by this method: 2-(6-(2-fluorophenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (22%). LCMS: m / z 454.21 [M+H] + . 2-(6-(3-fluorophenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (22%). LCMS: m / z 454.35 [M+H] + . 2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (14%). LCMS: m / z 454.0 [M+H] + .

[0070] Compound 1 Preparation of 2-((2-(6-phenethoxy-1H-indol-1-yl)ethyl)amino)-2-methylpropane-1,3-diol To a stirred solution of 2-(6-phenethoxy-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (150 mg, 0.34 mmol) and 2-amino-2-methylpropane-1,3-diol (179 mg, 1.70 mmol) in CH3CN (3 mL) was added DIPEA (0.6 mL, 3.40 mmol). The resulting reaction mixture was stirred at 100° C. for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was diluted with water and extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4 and concentrated under vacuum to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluting with 4% MeOH in DCM to give the title compound as an off-white solid (35 mg, 28%). 1 H NMR(400MHz,DMSO-d6)δ7.38-7.30(m,5H),7.25-7.20(m,2H),7.03(d,J=2. 0Hz,1H),6.64(dd,J=8.4,2.0Hz,1H),6.30(dd,J=2.8,0.4Hz,1H),4.26(t,J =5.4Hz,2H),4.21(t,J=7.0Hz,2H),4.10(t,J=6.7Hz,2H),3.17(d,J=5.4Hz, 4H), 3.06 (t, J=6.9Hz, 2H), 2.82 (t, J=5.7Hz, 2H), 1.59 (s, 1H), 0.82 (s, 3H). LCMS: m / z 369.32 [M+H] + .

[0071] Other analogues prepared by this method: Compound 2 2-((2-(6-(2-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)-2-methylpropane-1,3-diol (17%). 1H NMR(400MHz,DMSO-d6)δ7.45-7.42(m,1H),7.37(d,J=8.6Hz,1H),7.32-7.27(m,1H), 7.21-7.03(m,3H),7.03(d,J=2.0Hz,1H),6.63(dd,J=8.4,2.0Hz,1H),6.30(d,J=3.1 Hz,1H),4.26(t,J=5.4Hz,2H),4.21(t,J=6.9Hz,2H),4.10(t,J=6.7Hz,2H),3.17(d, J=5.3Hz,4H),3.10(t,J=6.8Hz,2H),2.82(t,J=6.7Hz,2H),1.61(s,1H),0.82(s,3H). LCMS:m / z387.66[M+H] + .

[0072] Compound 3 2-((2-(6-(3-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)-2-methylpropane-1,3-diol (62%). 1 H NMR(400MHz,DMSO-d6)δ7.39-7.33(m,2H),7.21-7.18(m,3H),7.08-7.03(m,2H),6.64(dd,J=8.4,2.0Hz,1H),6.30-6.29(m,1H),4.2 5-4.21(m,4H),4.10(t,J=6.6Hz,2H),3.17(d,J=5.4Hz,4H),3.09(t,J=6.8Hz,2H),2.82(t,J=6.6Hz,2H),1.62(s,1H),0.82(s,3H). LCMS:m / z387.36[M+H] + .

[0073] Compound 4 2-((2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)-2-methylpropane-1,3-diol (25%). 1H NMR(400MHz,DMSO-d6)δ7.41-7.35(m,3H),7.21(d,J=3.1Hz,1H),7.17-7.12(m, 2H),7.03(d,J=1.9Hz,1H),6.64(dd,J=8.4,2.0Hz,1H),6.30(d,J=3.0Hz,1H),4 .27(t,J=5.3Hz,2H),4.19(t,J=6.9Hz,2H),4.10(t,J=6.6Hz,2H),3.17(d,J=5. 2Hz, 4H), 3.05 (t, J=6.8Hz, 2H), 2.82 (t, J=6.3Hz, 2H), 1.60 (s, 1H), 0.82 (s, 3H). LCMS: m / z 387.28 [M+H] + .

[0074] [ka] Reagents and conditions: a) BrCH2CH2OTHP, NaH, DMF, 0°C to rt, 3 h; b) p-TSA, MeOH, rt, 2 h; c) TsCl, Et3N, DMAP, DCM, rt, 3 h; d) RH, DIPEA, MeCN, 100°C, 1 h.

[0075] Preparation of 6-(4-fluorophenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole To a stirred solution of 6-(4-fluorophenethoxy)-1H-indole (600 mg, 2.35 mmol) in DMF (5 mL) was added NaH (60% dispersion in mineral oil) (141 mg, 3.53 mmol) at 0° C. The mixture was stirred for 20 min. Then, 2-(2-bromoethoxy)tetrahydro-2H-pyran (737 mg, 3.53 mmol) dissolved in DMF was slowly added dropwise to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (30 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was diluted with anhydrous Na2SO 4でDrying, filtration and concentration under reduced pressure gave the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 25% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (440 mg, 49%). LCMS: m / z 384.42 [M+H] + .

[0076] Other analogues prepared by this method: 6-(4-Fluorophenethoxy)-1-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1H-indole (71%). LCMS: m / z 398.33 [M+H] + .

[0077] Preparation of 2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethan-1-ol To a stirred solution of 6-(4-fluorophenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (440 mg, 1.15 mmol) in MeOH (10 mL) was added p-TSA (100 mg, 0.58 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was concentrated under reduced pressure to give the crude compound. The crude was quenched with ice water (10 mL) and extracted with EtOAc (2×50 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 25% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (320 mg, 93%). LCMS: m / z 300.38 [M+H] + .

[0078] Other analogues prepared by this method: 3-(6-(4-fluorophenethoxy)-1H-indol-1-yl)propan-1-ol (92%). LCMS: m / z 314.22 [M+H] + .

[0079] Preparation of 2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate To a stirred solution of 2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethan-1-ol (320 mg, 1.07 mmol) in DCM (20 mL) was added Et3N (0.45 mL, 3.21 mmol) and TsCl (307 mg, 1.61 mmol), followed by DMAP (66 mg, 0.54 mmol). The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (10 mL) and extracted with DCM (2 x 50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (350 mg, 72%). LCMS: m / z 454.22 [M+H] + .

[0080] Other analogues prepared by this method: 3-(6-(4-fluorophenethoxy)-1H-indol-1-yl)propyl 4-methylbenzenesulfonate (48%). LCMS: m / z 468.49 [M+H] + .

[0081] Compound 5 Preparation of 2-((2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)-2-methylpropan-1-ol To a stirred solution of 2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (150 mg, 0.33 mmol) and 2-amino-2-methylpropan-1-ol (294 mg, 3.3 mmol) in MeCN (5 mL) was added DIPEA (0.58 mL, 3.3 mmol). The resulting reaction mixture was heated at 110° C. for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (2×30 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by reverse phase preparative HPLC to give the title compound as an off-white solid (65 mg, 53%). 1 H NMR(400MHz,DMSO-d6)δ7.40-7.36(m,3H),7.21(d,J=3.1Hz,1H),7.14(t,J=8. 9Hz,2H),7.02(d,J=1.6Hz,1H),6.64(dd,J=8.8,2.4Hz,1H),6.30(d,J=3.1Hz,1 H),4.43(br.s,1H),4.19(t,J=6.9Hz,2H),4.10(t,J=6.7Hz,2H),3.11(s,2H),3 .05(t,J=6.8Hz,2H),2.79(q,J=7.0Hz,2H),1.51(t,J=7.8Hz,1H),0.87(s,6H). LCMS: m / z 371.46 [M+H] + .

[0082] Other analogues prepared by this method: Compound 6 2-((2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (37%). 1H NMR(400MHz,DMSO-d6)δ7.41-7.36(m,3H),7.21(d,J=3.1Hz,1H),7.14(t,J=8.8Hz,2H),7.03(s,1H),6.64(dd,J=8.4,1.6Hz,1H),6.30(d,J=3 .0Hz,1H),4.34(t,J=5.2Hz,2H),4.21-4.13(m,4H),3.38-3.24(m,4H), 3.05(t,J=6.8Hz,2H),2.91(t,J=6.3Hz,2H),2.53(s,1H),1.66(s,1H). LCMS:m / z373.33[M+H] + .

[0083] Compound 7 (S)-2-((2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)propan-1-ol (38%). 1 H NMR(400MHz,DMSO-d6)δ7.41-7.36(m,3H),7.21(d,J=3.1Hz,1H),7.14(t,J=8 .9Hz,2H),7.02(s,1H),6.64(dd,J=8.4,2.0Hz,1H),6.30(d,J=3.0Hz,1H),4.4 4(t,J=5.2Hz,1H),4.21-4.13(m,4H),3.25-3.14(m,2H),3.05(t,J=6.8Hz,2H) ,2.89-2.81(m,2H),2.58(t,J=5.9Hz,1H),1.62(s,1H),0.87(d,J=6.3Hz,3H). LCMS: m / z 357.34 [M+H] + .

[0084] Compound 8 (R)-2-((2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)propan-1-ol (34%). 1H NMR(400MHz,DMSO-d6)δ7.41-7.36(m,3H),7.21(d,J=3.1Hz,1H),7.14(t,J =8.8Hz,2H),7.02(s,1H),6.64(dd,J=8.4,2.0Hz,1H),6.30(d,J=3.0Hz,1H) ,4.44(t,J=4.9Hz,1H),4.21-4.13(m,4H),3.25-3.15(m,2H),3.05(t,J=6.8 Hz,2H),2.89-2.83(m,2H),2.51(s,1H),1.62(s,1H),0.87(d,J=6.3Hz,3H). LCMS: m / z 357.34 [M+H] + .

[0085] Compound 9 2-((2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)amino)ethan-1-ol (36%). 1 H NMR(400MHz,DMSO-d6)δ7.40-7.35(m,3H),7.20-7.11(m,3H),7.01(s,1H),6.64(dd,J=8.4,6.4Hz,1H),6.30(d,J=2.8Hz,1H),4.43(t,J =5.2Hz,1H),4.21-4.13(m,4H),3.40(q,J=5.2Hz,2H),3.05(t,J=6.8Hz,2H),2.85(t,J=6.4Hz,2H),2.57(t,J=5.6Hz,2H),1.71(s,1H). LCMS:m / z343.37[M+H] + .

[0086] Compound 10 N-(2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)-2-methylpropan-2-amine (32%). 1H NMR(400MHz,DMSO-d6)δ7.38(t,J=7.7Hz,3H),7.22(d,J=3.1Hz,1H),7.14(t,J=8.8Hz,2H),7.01(s,1H),6.64(dd,J=8.4,2.0Hz,1H),6. 30(d,J=3.0Hz,1H),4.19(t,J=6.9Hz,2H),4.09(t,J=6.8Hz,2H),3.05(t,J=6.8Hz,2H),2.80(t,J=6.7Hz,2H),1.40(s,1H),0.97(s,9H). LCMS:m / z355.36[M+H] + .

[0087] Compound 11 4-(3-(6-(4-fluorophenethoxy)-1H-indol-1-yl)propyl)morpholine (58%). 1 H NMR(400MHz,DMSO-d6)δ7.40-7.37(m,3H),7.19-7.12(m,3H),6.97(s,1H),6.66-6.63(m,1H),6.31(d,J=2.9Hz,1H),4.19(t,J=6.8H) z,2H),4.13(t,J=6.8Hz,2H),3.54(t,J=4.4Hz,4H),3.05(t,J=6.8Hz,2H),2.28(br.s,4H),2.17(t,J=6.9Hz,2H),1.88-1.84(m,2H). LCMS:m / z383.28[M+H] + .

[0088] Compound 12 N-(2-(6-(4-fluorophenethoxy)-1H-indol-1-yl)ethyl)-1,3-dimethoxy-2-methylpropan-2-amine (98%). 1H NMR(400MHz,DMSO-d6)δ8.75(br.s,2H),7.45-7.37(m,3H),7.26(d,J=3.0Hz,1H),7.15(t,J=8.8Hz,2H),6.99(s,1H),6.74(s,1H),6.39(d,J=2. 7Hz,1H),4.38(t,J=7.2Hz,2H),4.19(t,J=6.9Hz,2H),3.47(q,J=10.5Hz,4H),3.30(s,6H),3.20(br.s,2H),3.08(t,J=6.8Hz,2H),1.22(s,3H). LCMS:m / z415.46[M+H] + .

[0089] [ka] Reagents and conditions: a) (4-F-Ph)CH2CH2Br, K2CO3, KI, MeCN, 110°C, 1 h; b) (Boc)2O, Et3N, THF, rt, 2 h; c) BrCH2CH2OTHP, NaH, DMF, 0°C to rt, 3 h; d) p-TSA, MeOH, rt, 2 h; e) TsCl, Et3N, DMAP, DCM, rt, 3 h; f) 2-amino-2-methylpropane-1,3-diol, DIPEA, MeCN, 110°C, 1 h; g) TFA, DCM, rt, 3 h.

[0090] Preparation of N-(4-fluorophenethyl)-1H-indol-6-amine To a stirred solution of 1H-indole-6-amine (0.5 g, 3.78 mmol) in MeCN (5 mL) was added K2CO3 (1.57 g, 11.34 mmol) and KI (63 mg, 0.38 mmol), followed by 2-(4-fluorophenyl)ethan-1-amine (1.54 g, 7.56 mmol). The resulting reaction mixture was heated at 110 °C for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (2 x 50 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 20% EtOAc in petroleum ether to give the title compound as an off-white solid (380 mg, 40%). LCMS: m / z 255.30 [M+H] + .

[0091] Preparation of tert-butyl (4-fluorophenethyl)(1H-indol-6-yl)carbamate To a stirred solution of N-(4-fluorophenethyl)-1H-indol-6-amine (0.38 g, 1.49 mmol) in THF (5 mL) was added Et3N (0.6 mL, 4.47 mmol) at 0° C., followed by Boc anhydride (0.35 mL, 1.49). The mixture was then stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (15 mL) and extracted with EtOAc (2×50 mL). The organic phases were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography by using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as an off-white solid (420 mg, 79%). LCMS: m / z 353.37 [MH] - .

[0092] Preparation of tert-butyl (4-fluorophenethyl)(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indol-6-yl)carbamate To a stirred solution of tert-butyl (4-fluorophenethyl)(1H-indol-6-yl)carbamate (420 mg, 1.19 mmol) in DMF (5 mL) was added NaH (60% dispersion in mineral oil) (95 mg, 2.38 mmol) at 0° C., and the mixture was stirred for 30 min. Then, 2-(2-bromoethoxy)tetrahydro-2H-pyran (374 mg, 1.79 mmol) dissolved in DMF was slowly added dropwise to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (30 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 5% EtOAc in petroleum ether to give the title compound as a colorless liquid (500 mg, 87%). LCMS: m / z 483.37 [M+H] + .

[0093] Preparation of tert-butyl (4-fluorophenethyl)(1-(2-hydroxyethyl)-1H-indol-6-yl)carbamate To a stirred solution of tert-butyl (4-fluorophenethyl)(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indol-6-yl)carbamate (500 mg, 1.04 mmol) in MeOH (10 mL) was added p-TSA (59 mg, 0.31 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was concentrated under reduced pressure to give the crude compound. The crude was quenched with ice water (10 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude compound. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 25% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (380 mg, 92%). LCMS: m / z 399.49 [M+H] + .

[0094] Preparation of 2-(6-((tert-butoxycarbonyl)(4-fluorophenethyl)amino)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate To a stirred solution of tert-butyl (4-fluorophenethyl)(1-(2-hydroxyethyl)-1H-indol-6-yl)carbamate (380 mg, 0.95 mmol) in DCM (20 mL) was added Et3N (0.6 mL, 4.29 mmol) and TsCl (273 mg, 1.43 mmol), followed by DMAP (59 mg, 0.48 mmol). The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (10 mL) and extracted with DCM (2 x 50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (420 mg, 80%). LCMS: m / z 553.36 [M+H] + .

[0095] Preparation of tert-butyl (1-(2-((1,3-dihydroxy-2-methylpropan-2-yl)amino)ethyl)-1H-indol-6-yl)(4-fluorophenethyl)carbamate To a stirred solution of 2-(6-((tert-butoxycarbonyl)(4-fluorophenethyl)amino)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (420 mg, 0.76 mmol) and 2-amino-2-methylpropane-1,3-diol (799 mg, 7.60 mmol) in MeCN (5 mL) was added DIPEA (1.32 mL, 7.60 mmol). The resulting reaction mixture was heated at 110° C. for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (2×50 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by reverse phase preparative HPLC to give the title compound as a yellow liquid (190 mg, 51%). LCMS: m / z 486.56 [M+H] + .

[0096] Preparation of compound 13 2-((2-(6-((4-fluorophenethyl)amino)-1H-indol-1-yl)ethyl)amino)-2-methylpropane-1,3-diol To a stirred solution of tert-butyl (1-(2-((1,3-dihydroxy-2-methylpropan-2-yl)amino)ethyl)-1H-indol-6-yl)(4-fluorophenethyl)carbamate (190 mg, 0.39 mmol) in DCM (2 mL) was added TFA (0.3 mL) at 0° C. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (2×25 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by reverse-phase preparative HPLC to give the title compound as a pale yellow semi-solid (65 mg, 42%). 1 H NMR(400MHz,DMSO-d6)δ8.51(brs,2H),7.35-7.32(m,3H),7.14(t,J=8.9Hz,3H),6.62(brs,2H),6.32(s,1H),5 .51(brs,2H),4.37(t,J=7.3Hz,2H),3.62-3.45(m,4H),3.32-3.23(m,4H),2.91(t,J=7.5Hz,2H),1.15(s,3H). LCMS:m / z386.38[M+H] + .

[0097] [ka] Reagents and conditions: a) (4-F-Ph)CH2NH2, HATU, DIPEA, DMF, rt, 16 h; b) BrCH2CH2OTs, NaH, DMF, 0°C to rt, 3 h; c) 2-amino-2-methylpropane-1,3-diol, DIPEA, MeCN, 110°C, 1 h.

[0098] Preparation of N-(4-fluorobenzyl)-1H-indole-6-carboxamide To a stirred solution of 1H-indole-6-carboxylic acid (1.0 g, 6.21 mmol) in DMF (10 mL) was added DIPEA (3.2 mL, 18.63 mmol) and HATU (4.7 g, 12.42 mmol), followed by (4-fluorophenyl)methanamine (1.16 g, 9.31 mmol). The resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (20 mL) and extracted with EtOAc (2×200 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as an off-white solid (600 mg, 36%). LCMS: m / z 269.16 [M+H] + .

[0099] Preparation of 2-(6-((4-fluorobenzyl)carbamoyl)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate To a stirred solution of N-(4-fluorobenzyl)-1H-indole-6-carboxamide (300 mg, 1.12 mmol) in DMF (5 mL) was added NaH (60% dispersion in mineral oil) (44 mg, 1.12 mmol) at 0° C. The mixture was stirred for 20 min. Then, 2-bromoethyl 4-methylbenzenesulfonate (624 mg, 2.24 mmol) dissolved in DMF was slowly added dropwise to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (20 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 4% MeOH in DCM to give the title compound as an off-white solid (150 mg, 29%). LCMS: m / z 467.37 [M+H] + .

[0100] Preparation of compound 14 1-(2-((1,3-dihydroxy-2-methylpropan-2-yl)amino)ethyl)-N-(4-fluorobenzyl)-1H-indole-6-carboxamide To a stirred solution of 2-(6-((4-fluorobenzyl)carbamoyl)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (100 mg, 0.21 mmol) and 2-amino-2-methylpropane-1,3-diol (225 mg, 2.14 mmol) in MeCN (5 mL) was added DIPEA (0.37 mL, 2.14 mmol). The resulting reaction mixture was heated at 110° C. for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (10 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by reverse phase preparative HPLC to give the title compound as an off-white solid (30 mg, 35%). 1 H NMR(400MHz,DMSO-d6)δ8.94(t,J=5.9Hz,1H),8.11(s,1H),7.57(t,J=6.8Hz,3H),7.39(q,J=4.7Hz,2H),7.16(t,J=8.8Hz,2H),6.47(d, J=2.9Hz,1H),4.50(d,J=5.8Hz,2H),4.30-4.21(m,4H),3.18(d,J=5.0Hz,4H),2.89(t,J=6.4Hz,2H),1.65(d,J=8.4Hz,1H),0.82(s,3H). LCMS:m / z398.54[MH] - .

[0101] [ka] Reagents and conditions: a) (4-F-Ph)CH2OH, DCC, DMAP, DCM, rt, 3 h; b) BrCH2CH2OTHP, NaH, DMF, 0°C to rt, 3 h; c) p-TSA, MeOH, rt, 1 h; d) TsCl, Et3N, DMAP, DCM, rt, 1 h; e) 2-amino-2-methylpropane-1,3-diol, DIPEA, MeCN, 110°C, 1 h.

[0102] Preparation of 4-fluorobenzyl 1H-indole-6-carboxylate To a stirred solution of 1H-indole-6-carboxylic acid (1.0 g, 6.21 mmol) and (4-fluorophenyl)methanol (861 mg, 6.83 mmol) in DCM (20 mL) was added DCC (1.4 g, 6.83 mmol) followed by DMAP (83 mg, 0.68 mmol). The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2×100 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 20% EtOAc in petroleum ether to give the title compound as an off-white solid (600 mg, 35%). LCMS: m / z 270.22 [M+H] + .

[0103] Preparation of 4-fluorobenzyl 1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole-6-carboxylate To a stirred solution of 4-fluorobenzyl 1H-indole-6-carboxylate (600 mg, 2.23 mmol) in DMF (5 mL) was added NaH (60% dispersion in mineral oil) (134 mg, 3.35 mmol) at 0° C. The mixture was stirred for 20 min. Then, 2-(2-bromoethoxy)tetrahydro-2H-pyran (513 mg, 2.45 mmol) dissolved in DMF was slowly added dropwise to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (30 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (420 mg, 47%). LCMS: m / z 398.40 [M+H] + .

[0104] Preparation of 4-fluorobenzyl 1-(2-hydroxyethyl)-1H-indole-6-carboxylate To a stirred solution of 4-fluorobenzyl 1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole-6-carboxylate (420 mg, 1.06 mmol) in MeOH (10 mL) was added p-TSA (61 mg, 0.32 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was concentrated under reduced pressure, quenched with ice water (10 mL), and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 25% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (310 mg, 94%). LCMS: m / z 314.22 [M+H] + .

[0105] Preparation of 4-fluorobenzyl 1-(2-(tosyloxy)ethyl)-1H-indole-6-carboxylate To a stirred solution of 4-fluorobenzyl 1-(2-hydroxyethyl)-1H-indole-6-carboxylate (310 mg, 0.99 mmol) in DCM (20 mL) was added Et3N (0.45 mL, 2.97 mmol) and TsCl (284 mg, 1.49 mmol), followed by DMAP (12 mg, 0.099 mmol). The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (10 mL) and extracted with DCM (2 x 50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (350 mg, 48%). LCMS: m / z 468.37 [M+H] + .

[0106] Preparation of Compound 15 1-(2-((1,3-dihydroxy-2-methylpropan-2-yl)amino)ethyl)-1H-indole-6-carboxylate 4-fluorobenzyl To a stirred solution of 4-fluorobenzyl 1-(2-(tosyloxy)ethyl)-1H-indole-6-carboxylate (220 mg, 0.47 mmol) and 2-amino-2-methylpropane-1,3-diol (495 mg, 4.71 mmol) in MeCN (5 mL) was added DIPEA (0.82 mL, 4.71 mmol). The resulting reaction mixture was heated at 110° C. for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (2×30 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by reverse-phase preparative HPLC to give the title compound as a colorless semi-solid (40 mg, 21%). 1 H NMR(400MHz,DMSO-d6)δ8.19(s,1H),7.64(t,J=2.9Hz,3H),7.55(q,J=4.7Hz,2H),7.24(t,J=8.9Hz,2H),6.52(d,J=2 .9Hz,1H),5.36(s,2H),4.26(q,J=5.4Hz,4H),3.16(d,J=5.3Hz,4H),2.87(t,J=6.2Hz,2H),1.65(s,1H),0.80(s,3H). LCMS:m / z401.73[M+H] + .

[0107] [ka] Reagents and conditions: a) RPhCH2CH2OH, PPh3, DIAD, THF, 0°C to rt, 16 h; b) BrCH2CH2OTHP, NaH, DMF, 0°C to rt, 3 h; c) TsCl, Et3N, DMAP, DCM, rt, 1 h; d) TsCl, Et3N, DMAP, DCM, rt, 1 h; e) 2-amino-2-methylpropane-1,3-diol, DIPEA, MeCN, 110°C, 1 h.

[0108] Preparation of 6-(2-methylphenethoxy)-1H-indole To a stirred solution of 1H-indol-6-ol (300 mg, 2.25 mmol) and 2-(o-tolyl)ethan-1-ol (368 mg, 2.70 mmol) in THF (10 mL) was added PPh3 (1.2 g, 4.50 mmol) followed by DIAD (909 mg, 4.50 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was diluted with water (25 mL) and extracted with EtOAc (2×50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 15% EtOAc in petroleum ether to give the title compound as a yellow liquid (220 mg, 39%). LCMS: m / z 252.25 [M+H] + .

[0109] Other analogues prepared by this method: 6-(3-Methylphenethoxy)-1H-indole (24%). LCMS: m / z 252.25 [M+H] + . 6-(4-Methylphenethoxy)-1H-indole (21%). LCMS: m / z 252.10 [M+H] + . 6-(2-Methoxyphenethoxy)-1H-indole (22%). LCMS: m / z 268.24 [M+H] + . 6-(3-Methoxyphenethoxy)-1H-indole (30%). LCMS: m / z 268.29 [M+H] + . 6-(4-Methoxyphenethoxy)-1H-indole (31%). LCMS: m / z 268.29 [M+H] + . 6-(2-(trifluoromethyl)phenethoxy)-1H-indole (54%). 1 H NMR(400MHz,DMSO-d6)δ10.81(s,1H),7.72(d,J=7.6Hz,1H),7.69-7.59(m,2H),7.57-7.55(m,1H),7.38(d,J=8.4Hz,1H),7.17(t, J=2.8Hz,1H),6.90(d,J=1.6Hz,1H),6.65(dd,J=8.4,2.0Hz,1H),6.31-6.30(m,1H),4.21(t,J=6.8Hz,2H),3.24(t,J=6.4Hz,2H). 6-(4-(trifluoromethyl)phenethoxy)-1H-indole (18%). LCMS: m / z 306.33 [M+H] + . 6-(3,4-difluorophenethoxy)-1H-indole (58%). LCMS: m / z 274.10 [M+H] + . 6-(3,4-Dimethylphenethoxy)-1H-indole (35%). 1 H NMR(400MHz,DMSO-d6)δ10.81(s,1H),7.37(d,J=8.4Hz,1H),7.17-7.16(m,1H),7.10-7.02(m,3H),6.88(d,J=2.0Hz, 1H),6.62(dd,J=8.4,2.4Hz,1H),6.31-6.30(m,1H),4.13(t,J=6.8Hz,2H),2.96(t,J=7.2Hz,2H),2.20-2.16(m,6H).

[0110] Preparation of 6-(2-methylphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole To a stirred solution of 6-(2-methylphenethoxy)-1H-indole (200 mg, 0.80 mmol) in DMF (5 mL), NaH (60% dispersion in mineral oil) (48 mg, 1.20 mmol) was added at 0° C. and stirred for 20 min. Then, 2-(2-bromoethoxy)tetrahydro-2H-pyran (250 mg, 1.19 mmol) dissolved in DMF was slowly added dropwise to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with ice water (30 mL) and extracted with EtOAc (2×25 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product as a colorless semi-solid (280 mg, 93%), which was used in the next step without further purification. LCMS: m / z 380.32 [M+H] + .

[0111] Other analogues prepared by this method: 6-(3-Methylphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (80%). LCMS: m / z 380.40 [M+H] + . 6-(4-Methylphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (55%). LCMS: m / z 380.32 [M+H] + . 6-(2-Methoxyphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (99%). LCMS: m / z 396.41 [M+H] + . 6-(3-Methoxyphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (90%). LCMS: m / z 396.32 [M+H] + . 6-(4-Methoxyphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (56%). LCMS: m / z 396.53 [M+H]+ . 6-(2-(trifluoromethyl)phenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (99%). LCMS: m / z 434.42 [M+H] + . 6-(4-(trifluoromethyl)phenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (77%). LCMS: m / z 434.42 [M+H] + . 6-(3,4-Difluorophenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (56%). LCMS: m / z 402.38 [M+H] + . 6-(3,4-Dimethylphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (61%). LCMS: m / z 394.49 [M+H] + .

[0112] Preparation of 2-(6-(2-methylphenethoxy)-1H-indol-1-yl)ethan-1-ol To a stirred solution of 6-(2-methylphenethoxy)-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-indole (280 mg, 0.74 mmol) in MeOH (6 mL) was added p-TSA (71 mg, 0.37 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 1 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was concentrated under reduced pressure, quenched with water (10 mL), and extracted with EtOAc (2×25 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 25% EtOAc in petroleum ether to give the title compound as a colorless semi-solid (150 mg, 69%). LCMS: m / z 296.20 [M+H] + .

[0113] Other analogues prepared by this method: 2-(6-(3-methylphenethoxy)-1H-indol-1-yl)ethan-1-ol (71%). LCMS: m / z 296.48 [M+H] + . 2-(6-(4-methylphenethoxy)-1H-indol-1-yl)ethan-1-ol (98%). LCMS: m / z 296.39 [M+H] + . 2-(6-(2-methoxyphenethoxy)-1H-indol-1-yl)ethan-1-ol (35%). LCMS: m / z 312.34 [M+H] + . 2-(6-(3-methoxyphenethoxy)-1H-indol-1-yl)ethan-1-ol (70%). LCMS: m / z 312.24 [M+H] + . 2-(6-(4-Methoxyphenethoxy)-1H-indol-1-yl)ethan-1-ol (89%). LCMS: m / z 312.45 [M+H] + . 2-(6-(2-(trifluoromethyl)phenethoxy)-1H-indol-1-yl)ethan-1-ol (40%). LCMS: m / z 350.23 [M+H] + . 2-(6-(4-(trifluoromethyl)phenethoxy)-1H-indol-1-yl)ethan-1-ol (69%). LCMS: m / z 350.23 [M+H] + . 2-(6-(3,4-difluorophenethoxy)-1H-indol-1-yl)ethan-1-ol (89%). LCMS: m / z 318.41 [M+H] + . 2-(6-(3,4-dimethylphenethoxy)-1H-indol-1-yl)ethan-1-ol (81%). LCMS: m / z 310.42 [M+H] + .

[0114] Preparation of 2-(6-(2-methylphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate To a stirred solution of 2-(6-(2-methylphenethoxy)-1H-indol-1-yl)ethan-1-ol (150 mg, 0.51 mmol) in DCM (5 mL) was added Et3N (0.2 mL, 1.53 mmol) and TsCl (147 mg, 0.77 mmol), followed by DMAP (6 mg, 0.05 mmol). The resulting reaction mixture was stirred at room temperature for 1 h. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (10 mL) and extracted with DCM (2 x 20 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by column chromatography using 100-200 silica gel eluted with 10% EtOAc in petroleum ether to give the title compound as a yellow semi-solid (200 mg, 87%). LCMS: m / z 450.42 [M+H] + .

[0115] Other analogues prepared by this method: 2-(6-(3-methylphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (33%). LCMS: m / z 450.38 [M+H] + . 2-(6-(4-methylphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (33%). LCMS: m / z 450.38 [M+H] + . 2-(6-(2-methoxyphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (81%). LCMS: m / z 466.42 [M+H] + . 2-(6-(3-methoxyphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (76%). LCMS: m / z 466.27 [M+H] + . 2-(6-(4-methoxyphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (42%). LCMS: m / z 466.23 [M+H] + . 2-(6-(2-(trifluoromethyl)phenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (30%). LCMS: m / z 504.27 [M+H] + . 2-(6-(4-(trifluoromethyl)phenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (88%). LCMS: m / z 504.27 [M+H] + . 2-(6-(3,4-difluorophenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (64%). LCMS: m / z 472.38 [M+H] + . 2-(6-(3,4-dimethylphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (44%). LCMS: m / z 464.38 [M+H] + .

[0116] Preparation of compound 16 2-methyl-2-((2-(6-(2-methylphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol To a stirred solution of 2-(6-(2-methylphenethoxy)-1H-indol-1-yl)ethyl 4-methylbenzenesulfonate (150 mg, 0.33 mmol) and 2-amino-2-methylpropane-1,3-diol (347 mg, 3.30 mmol) in CH3CN (5 mL) was added DIPEA (0.57 mL, 3.30 mmol). The resulting reaction mixture was heated at 110° C. for 1 h under microwave conditions. The progress of the reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (2×30 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude compound was purified by reverse-phase preparative HPLC to give the title compound as a colorless semi-solid (16 mg, 13%). 1H NMR(400MHz,DMSO-d6)δ7.37(d,J=8.6Hz,1H),7.28(t,J=4.2Hz,1H),7.21-7.13( m,4H),7.03(s,1H),6.64(dd,J=8.4,2.0Hz,1H),6.30(d,J=3.0Hz,1H),4.26(t,J= 5.2Hz,2H),4.18(t,J=7.1Hz,2H),4.10(t,J=6.6Hz,2H),3.17(d,J=5.1Hz,4H),3. 06(t,J=7.1Hz,2H),2.81(t,J=6.5Hz,2H),2.35(s,3H),1.62(s,1H),0.81(s,3H). LCMS: m / z 383.40 [M+H] + .

[0117] Other analogues prepared by this method: Compound 17 2-Methyl-2-((2-(6-(3-methylphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (15%). 1 H NMR(400MHz,DMSO-d6)δ7.37(d,J=8.6Hz,1H),7.22-7.12(m,4H),7.04(d,J=8.3Hz,2H),6.65(d,J=8.4Hz,1H),6.30(d,J= 2.8Hz,1H),4.34-4.11(m,6H),3.19(s,4H),3.02(t,J=6.9Hz,2H),2.83(br.s,2H),2.30(s,3H),1.63(s,1H),0.83(s,3H). LCMS:m / z383.48[M+H] + .

[0118] Compound 18 2-Methyl-2-((2-(6-(4-methylphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (31%). 1H NMR(400MHz,DMSO-d6)δ7.36(d,J=8.6Hz,1H),7.24-7.20(m,3H),7.12(d,J=7.8H z,2H),7.02(s,1H),6.63(dd,J=8.4,1.6Hz,1H),6.30(d,J=3.0Hz,1H),4.27(t,J= 5.0Hz,2H),4.17(t,J=7.0Hz,2H),4.10(t,J=6.6Hz,2H),3.17(d,J=5.2Hz,4H),3. 01(t,J=6.9Hz,2H),2.82(t,J=6.6Hz,2H),2.28(s,3H),1.62(s,1H),0.82(s,3H). LCMS: m / z 383.48 [M+H] + .

[0119] Compound 19 2-Methyl-2-((2-(6-(2-methoxyphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (33%). 1 H NMR(400MHz,DMSO-d6)δ7.36(d,J=8.4Hz,1H),7.28-7.19(m,3H),7.01-6. 98(s,2H),6.91(t,J=8.4,1H),6.63(t,J=8.4,1H),6.29(d,J=2.4Hz,1H), 4.26(t,J=4.8Hz,2H),4.15-4.08(m,4H),3.82(s,3H),3.16(d,J=4.8Hz,4 H),3.05(t,J=7.2Hz,2H),2.82(t,J=6.0Hz,2H),1.60(s,1H),0.81(s,3H). LCMS:m / z399.40[M+H] + .

[0120] Compound 20 2-Methyl-2-((2-(6-(3-methoxyphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (60%). 1H NMR(400MHz,DMSO-d6)δ7.37(d,J=8.4Hz,1H),7.25-7.20(m,2H),7.03(s,1H),6.93-6 .90(m,2H),6.81-6.78(m,1H),6.65(dd,J=8.4,6.4Hz,1H),6.30(d,J=3.2Hz,1H),4.2 6(t,J=5.2Hz,2H),4.21(t,J=6.8Hz,2H),4.10(t,J=6.8Hz,2H),3.74(s,3H),3.17(d, J=5.2Hz,4H),3.04(t,J=6.8Hz,2H),2.82(t,J=6.4Hz,2H),1.61(s,1H),0.81(s,3H). LCMS:m / z399.44[M+H] + .

[0121] Compound 21 2-Methyl-2-((2-(6-(4-methoxyphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (42%). 1 H NMR(400MHz,DMSO-d6)δ7.36(d,J=8.6Hz,1H),7.26(d,J=8.4Hz,2H),7.20(d,J=3.0Hz, 1H),7.02(br.s,1H),6.88(d,J=8.4Hz,2H),6.65-6.63(m,1H),6.30(d,J=3.0Hz,1H),4. 27(t,J=5.0Hz,2H),4.16(t,J=6.8Hz,2H),4.10(t,J=6.8Hz,2H),3.73(s,3H),3.17(d,J =4.8Hz,4H),2.99(t,J=6.9Hz,2H),2.82(t,J=6.1Hz,2H),1.59(br.s,1H),0.82(s,3H). LCMS:m / z399.44[M+H] + .

[0122] Compound 22 2-Methyl-2-((2-(6-(2-(trifluoromethyl)phenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (18%). 1H NMR(400MHz,DMSO-d6)δ7.73(d,J=7.6Hz,1H),7.66-7.65(m,2H),7.48-7.46( m,1H),7.37(d,J=8.8Hz,1H),7.21(d,J=2.8Hz,1H),7.04(s,1H),6.65(d,J=7 .6Hz,1H),6.30(d,J=2.8Hz,1H),4.25-4.22(m,4H),4.10(t,J=6.4Hz,2H),3. 26-3.23(m,2H),3.16(d,J=4.8Hz,4H),2.81(s,2H),1.64(s,1H),0.81(s,3H). LCMS: m / z 437.44 [M+H] + .

[0123] Compound 23 2-Methyl-2-((2-(6-(2-(trifluoromethyl)phenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (46%). 1 H NMR(400MHz,DMSO-d6)δ7.68(d,J=8.0Hz,2H),7.59(d,J=8.0Hz,2H),7.36(d,J=8.8Hz,1H),7.21(d,J=2.8Hz,1H),7.03(s,1H),6.64(d,J=8. 4Hz,1H),6.29(d,J=2.8Hz,1H),4.27-4.24(m,4H),4.10(t,J=6.4Hz,2H),3.18-3.14(m,6H),2.82(t,J=6.4Hz,2H),1.62(s,1H),0.81(s,3H). LCMS:m / z437.44[M+H] + .

[0124] Compound 24 2-Methyl-2-((2-(6-(3,4-difluorophenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (16%). 1H NMR(400MHz,DMSO-d6)δ7.47-7.31(m,3H),7.22(d,J=2.9Hz,2H),7.03(s,1H),6.65-6.63(m,1H),6.30(d,J=2.9Hz,1H),4.27(t,J=5.1Hz,2H) ),4.21(t,J=6.8Hz,2H),4.10(t,J=6.5Hz,2H),3.17(d,J=5.2Hz,4H),3.06(t,J=6.7Hz,2H),2.88-2.82(m,2H),1.62(br.s,1H),0.82(s,3H). LCMS:m / z405.48[M+H] + .

[0125] Compound 25 2-Methyl-2-((2-(6-(3,4-dimethylphenethoxy)-1H-indol-1-yl)ethyl)amino)propane-1,3-diol (27%). 1 H NMR(400MHz,DMSO-d6)δ7.36(d,J=8.6Hz,1H),7.20(d,J=3.1Hz,1H),7.11-7.01(m,4H),6.64(dd,J=8.4,2.0Hz,1H),6.29(d,J=3.1Hz,1H),4.27 (t,J=5.0Hz,2H),4.18-4.08(m,4H),3.17(d,J=4.7Hz,4H),2.97(t,J=7 .0Hz,2H),2.81(s,2H),2.19(d,J=7.9Hz,6H),1.59(s,1H),0.82(s,3H). LCMS:m / z397.41[M+H] + .

[0126] Example 2 - Anti-tropomyosin activity of compounds of formula (I) The ability of compounds of the present disclosure to disrupt Tpm4.2-containing actin microfilaments was examined in primary mouse embryonic fibroblast (PMEF) cells. 3×10 cells were cultured per well in a volume of 1000 μL of complete medium. 4For the cells, cells were seeded in 12-well plates containing 13 mm coverslips and the plates were left for 24 h before treatment. The cells were then treated with DMSO and two concentrations of the test compound. 24 h after treatment, the cells were fixed with 16% paraformaldehyde (PBS) and stained with rabbit polyclonal anti-tropomyosin delta / 9d antibody to visualize Tpm4.2. Single-plane images were acquired using an Olympus IX83 epifluorescence microscope. For each treatment condition, 10 fields were collected for both Tpm4.2 fluorochrome and 488-Atto-phalloidin. Images were visually assessed to determine whether the Tpm4.2 filament network was disrupted under this treatment condition (Table 1). A representative example of an image is given for compound 13 (Figure 1), where the parallel filament bundles observed in the control condition are lost and after exposure to compound 13, punctate aggregates of Tpm4.2 are observed near its nucleus.

[0127] [Table 1]

[0128] The citation of any reference herein should not be construed as an admission that such reference is available as prior art to the present application. Further, reference herein to any prior publication (or information derived therefrom) or to any known matter is not, and should not be construed as, an acknowledgement or admission or in any way suggestion that the prior publication (or information derived therefrom) or known matter forms part of the common general knowledge in the field of endeavor to which this specification pertains.

[0129] Those skilled in the art will recognize that the present disclosure described herein may have variations and modifications other than those specifically described.It should be understood that the present disclosure includes all such variations and modifications.The present disclosure also includes all steps, features, compositions and compounds individually or collectively mentioned or suggested herein, and any and all combinations of two or more of said steps, features, compositions and compounds.

Claims

1. Formula (I): 【Chemical 1】 (In the formula: R １ is -(CH ２ ) ｖ -X-R ３ is; X is absent, NH, O or S; R ３ is morpholinyl or -C(Y)(Y １ ) (Y ２ ) is; Y, Y １ and Y ２ is H, C １－６ Alkyl and -(CH ２ ) ｊ OR ４ are independently selected from R ４ is H or C １－６ is alkyl; R ２ teeth, 【Chemistry 2】 is Z is O, NH, —C(O)NH—, or —C(O)O—; Z １ is -(CH ２ ) ｔ - is; R ５ is OH, —COOH, —C(O)OR ６ , halogen, C １－６ Alkyl, C １－６ Alkoxy, —NR ６ R ７ or -CF ３ is; R ６ and R ７ is H and C １－６ independently selected from alkyl; v is 1, 2 or 3; t is 1, 2 or 3; u is 0 to 4; and j is 1, 2 or 3. or a pharmaceutically acceptable salt, hydrate, derivative, solvate or prodrug thereof.

2. 2. The compound of claim 1, wherein X is NH or absent.

3. 3. The compound of claim 2, wherein X is NH.

4. The compound of claim 1, wherein Z is O, NH, —C(O)NH, or —C(O)O—.

5. R ５ -COOH, -C(O)OR ６ , halogen, C １－３ Alkyl, C １－３ Alkoxy, —NR ６ R ７ or -CF ３ 2. The compound of claim 1, wherein:

6. R ５ But halogen, C １－３ Alkyl, C １－３ Alkoxy, —NR ６ R ７ or -CF ３ 6. The compound of claim 5, wherein:

7. R ６ and R ７ is independently selected from H and methyl.

8. R ５ But halogen, C １－３ Alkyl, C １－３ Alkoxy or -CF ３ 2. The compound of claim 1, wherein:

9. R ５ is halogen, methyl, methoxy or —CF ３ 9. The compound of claim 8, wherein:

10. R ５ is fluoro, methyl, methoxy or —CF ３ 10. The compound of claim 9, wherein:

11. The compound of claim 1 , wherein t is 1 or 2.

12. 2. The compound of claim 1, wherein v is 2 or 3.

13. 2. The compound of claim 1, wherein u is 0, 1, 2, or 3.

14. 14. The compound of claim 13, wherein u is 0, 1 or 2.

15. Y is H or C １－３ is alkyl, and Y １ But -(CH ２ ) ｊ OR ４ , H or C １－３ is alkyl, and Y ２ But -(CH ２ ) ｊ OR ４ or C １－３ The compound of claim 1 , wherein the aryl group is alkyl.

16. Y is H or methyl, and Y １ But -(CH ２ ) ｊ OR ４ , H or methyl, and Y ２ But -(CH ２ ) ｊ OR ４ or methyl, wherein j is 1 or 2.

17. Y is H or methyl, and Y １ But -(CH ２ ) ｊ OR ４ , H or methyl, and Y ２ But -(CH ２ ) ｊ OR ４ or methyl, wherein j is 1.

18. R ４ is H or C １－３ The compound of claim 1 , wherein the aryl group is alkyl.

19. R ４ 19. The compound of claim 18, wherein is H or methyl.

20. R ３ But -C(Y)(Y １ ) (Y ２ 2. The compound of claim 1, wherein

21. R ２ The compound of claim 1 , wherein is located at the 6-position.

22. R １ but: 【Chemistry 3】 2. The compound of claim 1 selected from:

23. R ２ but: 【Chemistry 4】 2. The compound of claim 1 selected from:

24. A compound of formula (I) selected from any one of compounds 1-25.

25. A method for disrupting Tpm4.2-containing actin filaments, comprising contacting the Tpm4.2-containing actin filaments with a compound of formula (I) as defined in any one of claims 1 to 24.

26. 25. Use of a compound of formula (I) as defined in any one of claims 1 to 24 for disrupting Tpm4.2-containing actin filaments.

27. The method of claim 25, wherein the Tpm4.2-containing actin filaments are present intracellularly.

28. The use of claim 26, wherein the Tpm4.2-containing actin filaments are present intracellularly.

29. Use of a compound of formula (I) as defined in claim 1 as a tool compound.

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