MXPA97005843A - Derivatives of propen - Google Patents

Abstract

The present invention relates to propenone derivatives represented by the following general formula (I) or pharmacologically acceptable salts thereof: wherein R 1 represents a substituted lower alkyl or YR 5 (wherein Y represents S or O, and R 5 represents optionally substituted lower alkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic group or optionally substituted cyclic ether residue), R 2 and R 3 may be the same or different and each represents hydrogen, optionally substituted lower alkyl or aralkyl, or R 2 and R3 may be linked together to form optionally substituted methylene or ethylene, R4 represents hydrogen, hydroxy, lower alkyl, optionally substituted aralkyl, lower alkoxy, optionally substituted aralkyloxy or halogen and X represents substituted indolyl optionally

Description

PROPENONE DERIVATIVES DESCRIPTION OF THE INVENTION The present invention relates to propenone derivatives having an antitumor activity, an immunosuppressive activity and a therapeutic effect for an autoimmune disease. Typical examples of compounds having antitumor activity include mitomycin C, adriamycin, vincristine and the like, all of which are clinically useful as anticancer agents. However, since each of the compounds also have adverse effects such as myelotoxicity, cardiotoxicity, nerve damage, etc., a novel anticancer agent having less adverse effects is required. In addition, an excellent immunosuppressive agent and a therapeutic agent for an autoimmune disease that have reduced adverse effects are always required. Propeneone derivatives are known to have an anti-cancer activity (WO 95/14003). Chalcone derivatives are known to have activity to inhibit the polymerization of tubilin [Journal of the Medicinal Chemistry (J. Med. Chem.), 3_3, 1948 (1990) and Journal of Natural Products (J. Nat. Prod.), 5_6, 1718 (1993)]. Chalcone derivatives are also known to have an anti-cancer activity, being useful as a therapeutic agent for gout, and being useful as a therapeutic agent for multiple sclerosis (U.S. Patent Nos. 4904697, 4863968 and 4753965, respectively). The 3-indolyl-1-phenyl-2-propen-1-one derivatives are known to inhibit tyrosine phosphorylation of the receptor of a cell proliferation factor [Cancer Research (Cancer Res.), 54., 6106 (1994) and WO 91/16305], to be useful as organic nonlinear optical materials (Japanese Published Patent Application Unexamined No. 255426/91), and to have antiallergic activity [Khim.-Farm. Zh. , 25, 18 (1991)]. In addition, the 3 - (indol-3-yl) -1-phenyl-2-propen-1-one derivatives are described in French Patent No. 2230349, Khim. Geterotsikl. Soedin, 1066 (1970), Khim. Geterotsikl. Soedin, 268 (1969), Khim. Geterotsikl. Soedin, 399 (1970), Drug Ed. Sci., 26, 591 (1971), etc. The present invention relates to propenone derivatives represented by the following formula (I): wherein R1 represents a substituted lower alkyl or YR5 (wherein Y represents S or O, and R5 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl replace, substituted or unsubstituted heteroaryl or a substituted or unsubstituted cyclic ether residue), R2 and R3 independently represents hydrogen, substituted or unsubstituted lower alkyl or aralkyl, or R2 and R3 are combined to represent substituted or unsubstituted methylene or ethylene , R 4 represents hydrogen, hydroxy, lower alkyl, substituted or unsubstituted aralkyl, lower alkoxy, substituted or unsubstituted aralkyloxy or halogen, and X represents substituted or unsubstituted indolyl or its pharmaceutically acceptable salts. The compounds represented by Formula (I) are hereinafter referred to as Compounds (I). Compounds (la) and the like are included in Compounds (I). In the definitions of the groups of the formula (I), the lower alkyl and the lower alkyl portion of the lower alkoxy mean a straight or branched chain alkyl group having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, 2-butyl, isobutyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, isoamyl and hexyl. Aryl means phenyl, naphthyl and the like, and heteroaryl means pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thienyl, furyl, thiazolyl, oxazolyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, purinyl and the like. The cyclic ether residue means a cyclic ether residue having 2 to 6 carbon atoms, such as oxiranyl, oxetanyl, tetrahydrofuranyl and tetrahydropyranyl. The aralkyl and aralkyl portion of the aralkyloxy means an aralkyl group having 7 to 15 carbon atoms, such as benzyl, phenethyl, naphthylmethyl and benzhydryl. Halogen includes fluorine, chlorine, bromine and iodine. The substituted alkyl has from 1 to 4 equal or different substituents such as vinyl, hydroxy, lower alkoxy, aryloxy, amino, lower alkylamino, di (lower alkyl) amino, lower alkanoylamino, lower alkoxycarbonylamino, halogen, nitro, carboxy, lower alkanoyl, lower alkoxycarbonyl, tri (lower alkyl) silyl and a cyclic ether residue. The substituted aryl, substituted heteroaryl, substituted cyclic ether, substituted aralkyl and substituted aralkyloxy residue each have 1 to 4 same or different substituents such as lower alkyl, vinyl, hydroxy, hydroxymethyl, lower alkoxy, aryloxy, amino, lower alkylamino, di (lower alkyl) -amino, lower alkanoylamino, lower alkoxycarbonylamino, halogen, nitro, carboxy, lower alkanoyl, lower alkoxycarbonyl, tri (lower alkyl) silyl, aralkyl and a cyclic ether residue. In the definitions of substituents, the lower alkyl portion of lower alkylamino, di (lower alkyl) amino, lower alkanoylamino, lower alkoxycarbonylamino and tri (lower alkyl) silyl have the same meaning as the lower alkyl defined in the above and the aryl portion of aryloxy has the same meaning as the Aryloxy defined in the foregoing and the lower alkyl, lower alkoxy, halogen, cyclic ether and aralkyl residue each have the same meaning as defined above. The substituted methylene and substituted ethylene each has 1 to 3 same or different substituents such as lower alkyl, and the lower alkyl has the same meaning as defined above. Examples of the substituent on the nitrogen atom at the 1-position of the substituted indolyl are lower alkyl, lower alkanoyl, lower alkoxycarbonyl and aralkyl, and examples of the substituents on the carbon atoms at positions 2 to 7 of the substituted indolyl are lower alkyl , lower alkoxy, amino, lower alkylamino, di (lower alkyl) amino, lower alkanoylamino, lower alkoxycarbonylamino, halogen, nitro, carboxy, lower alkanoyl, lower alkoxycarbonyl and aralkyl. In the definitions of substituents, lower alkyl, lower alkoxy, lower alkylamino, di (lower alkyl) amino, lower alkanoylamino, lower alkoxycarbonylamino, halogen, lower alkanoyl, lower alkoxycarbonyl and aralkyl each have the same meaning as defined above. The pharmaceutically acceptable salts of the Compounds (I) include inorganic acid addition salts such as hydrochloride, sulfate and phosphate, organic acid addition salts such as acetate, maleate, fumarate, succinate, tartrate, citrate, oxalate and methanesulfonate, alkali metal salts such as salt sodium and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, metal salts such as aluminum salt and zinc salt and ammonium salts such as ammonium and tetramethylammonium. The present invention is described in detail as follows. In the processes shown in the following, if the defined groups are converted into undesirable groups under the conditions of the processes or are not suitable for carrying out the processes, the processes can be easily carried out by applying to them means conventionally used in the processes. Organic synthesis chemistry, for example, a means such as protection or deprotection of functional groups, or a method such as oxidation, reduction or hydrolysis.

Compound (IV) is commercially available, is reported in the literature, or can be prepared according to the following reaction stages. Process for Producing Compound (IV) - 1 Compound (IV) can be prepared according to the following reaction steps of the carboxylic acid or ester, which is commercially available or known in the literature.

Stage 2 (IV) (In the formulas, R6 represents hydrogen, lower alkyl, or aralkyo, and R2, R3 and R4 have the same meaning as defined above).

In the definition of R6, lower alkyl and aralkyl have the same meanings as defined above. Step 1 Compound (III) can be obtained by treating the Compound (II) with a hydride reagent in an inert solvent. As the hydride reagent, 1 to 100 equivalents of sodium borohydride, lithium aluminum hydride, alane, borane, aluminum hydride diisopropyl and the like can be used. As the solvent, the aprotic solvents (e.g., diethyl ether and tetrahydrofuran), aromatic hydrocarbons (e.g., toluene), alcohols (e.g., methanol and ethanol) and the like, may be used alone or in combination. The reaction is carried out at a temperature between -78 ° C and the boiling point of the solvent used in the reaction, and is completed in 0.1 hour to 3 days. Step 2 Compound (IV) can be obtained by treating Compound (III) with an oxidation agent in an inert solvent. As the oxidizing agent, from 1 to 50 equivalents of chromium trioxide, a pyridine complex or a hydrochloric acid complex thereof, potassium dichromate, manganese dioxide, 2,3-dichloro-5,6-dicyanobenzoate, can be used. quinone and similar. As the solvent, aprotic solvents can be used alone or in combination (eg example, acetone and N, N-dimethylformamide), halogenated hydrocarbons = (for example, dichloromethane and chloroform), acetic acid, sulfuric acid, water and the like. The reaction is carried out at the temperature between -10 ° C and the boiling point of the solvent used in the reaction, and is completed in 0.1 to 150 hours. Process for Producing Compound (IV) - 2 Compound (IVb) which is Compound (IV), in which R2 is lower alkyl or substituted or unsubstituted aralkyl can be prepared alternatively according to the next reaction step of the aldehyde (IVa), which is Compound (IV), in which R2 is hydrogen, and commercially available or known in the literature.

(In the formulas, R 2a represents a substituted or unsubstituted lower alkyl or aralkyl, Z represents halogen, and R 3 and R 4 have the same meaning as defined above). In the definition of R2a, the lower alkyl and the substituted or unsubstituted aralkyl have the same meanings as defined in the above. In the definition of Z, halogen has the same meaning as defined above. Step 3 Compound (IVb) can be obtained by reacting Compound (IVa) with Compound (V) in the presence of a base in an inert solvent. As the base, the inorganic bases such as sodium hydroxide, potassium carbonate, sodium carbonate and cesium fluoride, quaternary ammonium fluorides such as tetra-n-butylammonium fluoride, secondary amines such as piperidine, pyrrolidine and morpholine, alkoxides metal such as sodium methoxide and sodium tert-butoxide, metal amides such as lithium diisopropylamide, metal hydrides such as sodium hydride and the like can be used in an amount of 1 to 100 equivalents. As the solvent, the aprotic solvents (eg, ethyl acetate, tetrahydrofuran, acetone and N, N-dimethylformamide), aromatic hydrocarbons (eg, toluene), halogenated hydrocarbons (eg, chloroform), alcohols (eg methanol) and ethanol) and the like can be used alone or in combination. The reaction is carried out at the temperature between -7 ° C and the boiling point of the solvent used in the reaction and is completed in 0.1 hour to 3 days.

Process for Producing Compound (IV) - 3 Compound (IVd) which is Compound (IV), wherein R3 is substituted lower or substituted or unsubstituted aralkyl can be prepared alternatively according to the following reaction step of the aldehyde (IVc), which is commercially available or known in the literature. (ivc) avd) (In the formulas, R 3a represent substituted or unsubstituted lower alkyl or aralkyl, and R 2, R 4 and Z have the same meanings as defined above). Step 4 Compound (IVd) can be obtained by reacting Compound (IVc) with Compound (VI) according to the same method as that in Step 3. Compound (IX) is commercially available, reported in the literature , or it can be prepared according to the following reaction stages. Process for Producing Compound (IX) - 1 Compound (IX) can be prepared according to the following reaction steps.

(IX) (In the formulas, M represents alkali metal, alkaline earth metal halide or cerium dichloride, and R1, R2, R3 and R4 have the same meanings as defined above). In the definition of M, the alkali metal means lithium, sodium, potassium, cesium or the like and the alkaline earth metal halide means magnesium chloride, magnesium bromide, magnesium iodide or the like. Step 5: Compound (VIII) can be obtained by reacting Compound (IV) with 1 or 2 equivalents of Compound (VII) in an aqueous solvent. As the solvent, aprotic solvents (eg, diethyl ether and tetrahydrofuran), aromatic hydrocarbons (e.g., toluene) and the like may be used alone or in combination. The reaction is carried out at the temperature between -100 ° C and the boiling point of the solvent used in the reaction, and it is completed in 0.1 to 24 hours. Step 6 Compound (IX) can be obtained by reacting Compound (VIII) according to the same method as that in Step 2. Process for Producing Compound (IX) -2 Compound (IXa) which is Compound (IX), in which R1 and YR5 can be prepared alternatively according to the following reaction steps.

(In the formulas, R2, R3, R4, R5, Y and Z have the same meanings as defined in the above). Step 7 Compound (XI) can be obtained by treating Compound (X) with a halogenating agent in an inert solvent. As the halogenating agent, 1 to 5 equivalents of pyrrolidone hydrothromide, tetra-n-butylammonium tribromide, bromine and the like can be used. As the solvent, the aprotic solvents (e.g., ethyl acetate and tetrahydrofuran), acetic acid, water and the like can be used alone or in combination. The reaction is carried out at the temperature between 0 ° C and the boiling point of the solvent used in the reaction, and is completed in 0.1 to 24 hours. Step 8 Compound (IXa) can be obtained by reacting Compound (XI) with a compound represented by the formula H-Y-R ^ in the presence of a base in an inert solvent. As the base, the inorganic bases such as potassium carbonate, sodium carbonate, cesium fluoride and sodium hydroxide, quaternary ammonium fluorides such as tetra-n-butylammonium fluoride, secondary amines such as piperidine, pyrrolidine and morpholine, alkoxy of metal such as sodium methoxide and potassium tert-butoxide, metal such as lithium diisopropylamide, metal hydrides such as sodium hydride and the like, can be used in an amount of 1 to 10 equivalents. As the solvent, the aprotic solvents (for example, ethyl acetate, tetrahydrofuran and dimethyl sulfoxide), aromatic hydrocarbons (for example, toluene), halogenated hydrocarbons (for example, chloroform) and the like can be used alone or in combination. The reaction is carried out at a temperature between -78 ° C and the boiling point of the solvent used in the reaction, and is completed in 0.1 hour to a day. Process for Producing Compound (IX) -3 Compound (IX) can be prepared alternatively according to the next reaction step.

(XH) (IX) (In the formulas, R1, R, R3, R4 and M have the same meanings as they were defined in the previous one). Step 9 Compound (IX) can be obtained by reacting Compound (XII) with 1 to 2 equivalents of the Compound (VII) in an inert solvent. As the solvent, the aprotic solvents (e.g., diethyl ether and tetrahydrofuran), aromatic hydrocarbons (e.g., toluene), and the like can be used alone or in combination. The reaction is carried out at the temperature between 0 ° C and the boiling point of the solvent used in the reaction, and is complete in 0.1 to 24 hours. Process for Producing Compound (IX) - 4 Compound (IXc) which is Compound (IX), wherein R2 is substituted or unsubstituted lower alkyl or aralkyl can be prepared alternatively according to the following reaction step of Compound (IXb), which is Compound (IX), in which R2 is hydrogen.

(In the formulas, R1, R2a, R3, R4 and Z have the same meanings as defined in the above). Step 10 Compound (IXc) can be obtained by reacting Compound (IXb) with Compound (V) according to the same method as that in Step 3.

Process for Producing Compound (IX) - 5 Compound (IXe) which is Compound (IX), in which R3 is substituted or unsubstituted lower alkyl or aralkyl can be prepared alternatively according to the following reaction step of Compound (IXd), which is Compound (IX), in which R3 is hydrogen.

(IXd) (IXe) (In the formulas, R1, R2, R3a, R4 and Z have the same meanings as defined in the above). Step 11 Compound (IXe) can be obtained by reacting Compound (IXd) with Compound (VI) according to the same method as that in Step 3. Process for Producing Compound (IX) -6 Compound (IXh) ) which Compound (IX) having a 1,2-dihydroxyethyl group as a substituent of R 1 can be prepared alternatively according to the following reaction steps of Compound (IXf) having a vinyl group as a substituent of R ^.

Stage 13 (IXh) [In the formulas, Rla represent a substituted lower alkyl or YR ^ a (in which R ^ a represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or a substituted or unsubstituted cyclic ether residue) replace; and Y has the same meaning as defined in the above); and R2, R3 and R4 have the same meanings as defined in the above]. In the definition of R ^ -a, the lower alkyl c + ~~~~~~~ e_t-? the above. In the definition of R5a, substituted or unsubstituted lower alkyl, unsubstituted substituted aryl c, substituted or unsubstituted heteroaryl and the substituted or unsubstituted cyclic ether residue, each having the same meaning as defined above. Step 12 Compound (IXg) which is Compound (IX) having an oxiranyl group as an R 1 substituent can be obtained by treating Compound (IXf) with an oxidizing agent, if necessary, in the presence of a catalyst or a base, in an inert solvent. As the oxidizing agent, 1 to 10 equivalents of m-chloroperbenzoic acid, tert-butyl hydroperoxide, hydrogen peroxide and the like can be used. As the catalyst, 0.01 to 10 equivalents of vanadium acetylacetonate, titanium tetraisopropoxide and the like can be used. As the base, 1 to 10 equivalents of sodium bicarbonate, potassium carbonate, sodium acetate and the like can be used. As the solvent, the aprotic solvents (e.g., ethyl acetate and tetrahydrofuran), protic solvents (e.g., methanol), halogenated hydrocarbons (e.g., chloroform), acetic acid, water and the like, may be used alone or in combination. The reaction is carried out at the temperature between -30 ° C and the boiling point r »1 or 72 hours Step 13 Compound (IXh) can be obtained by treating Compound (IXg) with a salt of a carboxylic acid or a base in an inert solvent. As the salt of a carboxylic acid, 1 to 100 equivalents of sodium acetate, potassium benzoate and the like can be used. As the base, 1 to 100 equivalents of sodium bicarbonate, potassium carbonate, sodium acetate and the like can be used. As the solvent, the aprotic solvents (for example, N, N-dimethylformamide, pyridine and tetrahydrofuran), protic solvents (for example, methanol), water and the like can be used alone or in combination. The reaction is carried out at the temperature between 0 ° C and the boiling point of the solvent used in the reaction, and is complete in 0.1 to 72 hours. Process for Producing Compound (IX) -7 Compound (IXa) can be prepared alternatively according to the following reaction steps of Compound (IV) c Compound (XI).

(In the formulas, R2, R, R4, R-, Y and Z have the same meanings as defined in the above). Step 14 Compound 'XIII) can be obtained by reacting Compound (IV) with trimethylsulfoxcn iodide c according to the same method as that in Step 8.

Step 15 Compound (XIII) can be obtained by treating Compound (XI) according to the same method as that in Step 1 or by adding a base therein and reacting the resulting mixture in an inert solvent at the temperature between 0 ° C and the boiling point of the solvent used in the reaction for 1 to 24 hours. As the base, 1 to 10 equivalents of sodium bicarbonate, potassium carbonate, sodium acetate and the like can be used. As the solvent, the aprotic solvents (for example, diethyl ether and tetrahydrofuran), aromatic hydrocarbons (for example toluene), alcohols (for example, methanol and ethanol), water, and the like can be used alone or in combination. Step 16 Compound (VIII) can be obtained by reacting Compound (XIII) with Compound HY-R5 according to the same method as that in Step 8. Step 17: Compound (IXa) can be obtained by treating Compound (VIII) according to the same method as that in Step 2. Process for Producing Compound (I) - 1? L 7: - u S o (I) can be prepared according to the next reaction step of the Compound (IX) and the (In the formulas, R1, R2, R3, R4 and X have the same meanings as defined in the above). Step 18: Compound (I) can be obtained by reacting Compound (IX) with Compound (XIV) according to the same method as that in Step 3. Process for Producing Compound (I) - 2 Compound (I ) can be prepared alternatively according to the following reaction stages.

(I) (In the formulas, R7 represents lower alkyl, and P,? .2, K-3, R4, X and Z have the same meanings as defined above). In the definition of R7, lower alkyl has the same meaning as defined above.

Step 19 Compound (XV) can be obtained by treating Compound (IX) according to the same method as that in Step 7. Step 20 Compound (XVII) can be obtained by reacting Compound (XV) with 1 to 10 equivalents of Compound (XVI) in an inert solvent or without a solvent. As the solvent, aprotic solvents (e.g., ethyl acetate, tetrahydrofuran, toluene, benzene and N, N-dimethylfor amide), protic solvents (e.g., methanol) and the like can be used alone or in combination. The reaction is carried out at the temperature between 0 ° C and 200 ° C and is completed in 0.5 to 100 hours. Step 21 Compound 'I' can be obtained by reacting Compound (XVII) with Compound (XIV) according to the same method as that in Step 3. Some Compounds [1] thus obtained can also be used with .z intermediates for preparing novel derivatives (I) by subjecting them to oxidation, reduction, alkylation, acylation or the like. The question "I" is commercially available, reported in the literature (WO95 / 14003), or it can be easily prepared according to the reaction stages reported in the literature. HS-R5 which is the initial compound H-Y-R ^ in which Y is S is commercially available, is reported in the literature, or can be prepared according to the reaction steps c ° R5 Stage 23, te% "5 Stage 22 (XVIII) (XIX) (XX) (In the formulas, A represents halogen, trifluoromethane-eulphonyloxy, methane-sulphonyloxy, benzenesulfonyl-cxy-toluene-eulphonyloxy, and R5 has the same meaning as defined above). In the definition of A, halogen has the same meaning as defined in the above. Step 22: Compound (XIX) can be obtained by reacting Compound (XVIII) with 1 to 5C equivalents of potassium thioacetate in an inert solvent. As the solvent, the aprotic solvents (for example, N, N-dimethylforma ida, N-methylpyrrolidone, dimethyl sulfoxide, pyridine and tetrahydrofuran), rftips solvents, for example, methanol), water and the like can be used alone or in combination. The reaction is carried out at the temperature between 0 ° C and the boiling point of the solvent used in the reaction and is completed in 0.1 to 72 hours. Step 23 Compound (XX) can be obtained by treating the Compound (XIX) with a base in an inert solvent or without a solvent. As the base, inorganic bases such as sodium bicarbonate, potassium carbonate, sodium acetate and sodium hydroxide, amines such as piperidine, pyrrolidine and morpholine, and the like can be used in an amount of 1 to 100 equivalents. As the solvent, the aprotic solvents (for example, N, N-dimethylformamide, pyridine and tetrahydrofuran), protic solvents (for example, methanol), water and the like can be used alone or in combination. The reaction is carried out at the temperature between 0 ° C and the boiling point of the solvent used in the reaction and is completed in 0.1 to 72 hours. The intermediates and compounds desired in the processes described above can be isolated and purified by purification methods conventionally used in organic synthetic chemistry, for example, filtration, extraction, washing, drying, concentration, recrystallization and various types of chromatography. . Intermediaries can also be eti ied to the subsequent reaction sir. aiel rr.ier.tc.

In the case where a salt of Compound (I) is desired and is produced in the form of the desired salt, it may be subjected to purification as such. In the case where Compound (I) is produced in the free form and its salt is desired, Compound (I) is dissolved or suspended in a suitable organic solvent, followed by the addition of an acid or a base to form a salt by a conventional method. Compounds (I) may exist in the form of geometric E / Z isomers, and the present invention covers all isomers including these geometric isomers and mixtures of the mers. In the case where Compound (I) is obtained in an E / Z mixture, and the separation of E / Z isomers is desired, they can be isolated and purified by fractionation methods, for example, fractional crystallization, fractional precipitation, fractional solution. or similar. The compounds (I) and pharmaceutically acceptable salts can be in the form of adducts with water or different solvents, which are also included in the Examples of the Compounds (I) obtained in the process described in the above are shown in FIG. Table 1.

Table 1-1 Compound No. R1 RB 1 OCH 3 H 2 OCH 2 CH 3 H 3 0 (CH 2) 2 CH 3 H 4 OCH (CH 3) 2 H 5 0 (CH 2) 2 Si (CH 3) 3 H 6 0 (CH 2) 3 Si (CH 3) 3 H 8 H 9 SCH 3 H 10 S (CH 2) 2 Si (CH 3) 3 H 11 s FH 12 S (CH 2) 2 OH H 13 S (CH 2) 2 OH CH 3"... ^ -0- ^ - OH 14 CH 3 HO 15 SCH 2 C02H H 16 SCH2COzCH3 H17S (CH2) 2N (CH2CH3) 2 H18S (CH2) 4OC6H5 H19 (CH2) 2CH (OH) CH2OH H20 (CH2) 2CH (OH) CH2? H CH3 Table 1-2 Compound No. R- R 10 R 11 R 12 21 H H H H 22 CH 3 H H H 23 H CH 3 H H 24 H Cl H H 25 H H CH 3 H 26 H H Cl H 27 H H F H 28 H H H CH 3 29 H H H CH 2 CH 3 30 H H H CH (CH 3) 2 31 H H H Cl 32 H H H F 33 H H H NHCOCH 3 34 CH3 H H NHCOCH3 Table 1-3 Compound 35 Compound 36 Compound 37 Compound 3Sa Compound 33b The pharmacological activities of the Compounds are shown in detail in the following by the examples tested, Test Example 1: HeLa S Cell Growth Inhibition Test Each 0.1 ml of HeLa S cells which have been prepared at 3 x 10 4 cells / ml using a medium consisting of MEM medium, 10% bovine serum fetal, and 2 mM glutamine are distributed in each well of 96 well microtitre plate. HeLa S3 is grown at 37 ° C overnight in a C02 incubator, each 0.05 ml of test compounds which have been properly diluted with The culture solution is added to them, and the mixture is grown at 37 ° C for 72 hours in a C02 incubator. The supernatant is removed, each 0.1 ml of the culture solution containing 0.02% neutral red are added to the residue, the mixture is incubated at 37 ° C for one hour in a C02 incubator and the cells are stained. The supernatant is removed and the residue washed once with physiological saline. Then, the pigment is extracted with 0.001 N hydrochloric acid / 30% ethanol and the absorbance is measured at 550 nm by an icroDiaca reader. A concentration of the control substance (CICO in which the cell growth is inhibited by 50%) is calculated by comparing the absorbance of untreated cells and that of the cells treated with a predetermined concentration of the test compound.

Results are shown in table 2 Table 2 Compound No. Cl 50 (72 h, nM) 1 2.4 2 2.5 3 13 4 3.7 7 68 8 62 9 2.2 13 2.5 16 4.7 19 2.1 20 5.6 21 4.8 22 20 23 19 24 15 27 6.3 28 6.3 29 18 31 7.2 32 5.9 35 4.4 36 5.3 37 7.1 Test Example 2: Effect on Ascites Tumor P388 The experiment is carried out using groups of 6-week-old male CDF mice, each group consisting of five mice. 106 P388 mouse leukemia cells were implanted into the abdominal cavities of the mice. A test compound is sufficiently wetted by adding 10 μl of Tween 80 relative to 1 mg of a sample, and a 0.3% CMC solution (sodium carboxymethylcellulose) is then added to the test compound to form a suspension. The resulting suspension is administered once 24 hours after tumor implantation, or repeatedly for 5 consecutive days for 24 hours after tumor implantation. It is calculated two days of average survival (T) in a group, from the days of survival of the respective mice in the group administered with the test compound in each dose. Otherwise, the days of average survival (C) of a group which is not administered are measured, and the increased life duration [ILS (%)] ee is calculated according to the following equation: [(T - C) / C] x 100 (%) The results are shown in Table 3.

Table 3 US { %) [Dosage (mg / kg.].] Five Compound No. consecutive administrations one administration 1 50 (5.0) (25) 2 35 (10) 34 (50) 3 41 (13) 25 (50) 8 31 (50) 49 (200) 9 33 (5.0) 18 (13) 10 73 (100) 16 (100) 11 47 (25) 38 (50) 12 52 (20) 20 (50) 13 67 (5.0) 40 (25) 21 74 (10) 48 (50) 27 99 (20) 65 (50) 28 54 (10) 24 (13) 31 70 (20) 52 (50) E "Test Template 3: Effect focuses the Reaction of Air.cha of Type of Delayed Hypersensitivity? Í p? M? N Í 7 a r v = r p.i" -? or P Zi TC / m chOS 'Cc 8 SS ™. SS age, Charles River Japan Inc.) by intradermal injection in the doreal coefficient of 100 μl of 2, 4, 6-trinitrobenzene sulfonic acid 10 mM ( TNBS) in saline solution Five mice are used in each group, ie the control group [the group administered with 0.5% methylcellulose containing 10% of dimethyl sulfoxide (DMSO)], The group administered with cyclosporin A (Sandoz) and the group administered with the test compound, in which a determined concentration of the test composition euspended in 0.5% methylcellulose containing 10% is administered. of DMSO. Each cyclosporin A test compound is administered intraperitoneally 30 minutes before and once a day for 4 days after immunization. 50 μl of 10 mM TNBS is injected intradermally as an antigen challenged 5 days after immunization when antigen sensitization has been developed. The thickness of both paddles of each animal in each dose of the group administered with the test compound is measured with a calibrator of thickness graduated 18 hours after putting the antigen to test, and the value of the difference in thickness of the left pad and right (T) is determined. Otherwise, the thickness of both pads in the control group is measured, and the value of the difference in thickness ~ -Zt to 1"! 3 -j" m i -i -r 3 \ t r- \ a - * - ¿r ~ \ - a (C or + - -v-m i to T, a Calculate how [(C-T) / C] x 100. The results are shown in Table 4.

Table 4 Suppression index (%) Compound No. [Dosage (mg / kg x 5)] 2 1 8. 5 (3. 0) 6 9 (1 0) Cyclosporine A 8 9 (3 0) Test Example 4: Effect against the Production of Anti-Trinitrophenyl (TNP) Antibody Blood samples are taken from the mouse which were used for the effect against the pad reaction? E type of delayed hypersepability, is separated in serum by centrifugation at 3000 rpm at 4 ° C for 10 minutes, and then the concentration of the anti-TKP antibody is measured. Enzyme coupled immunoabenence (ELISA) is used to measure the anti-TNP antibody. The well 96 well plates for ELISA (NUNC Inc.) are coated with TNP-BSA which is prepared according to the method of Sch itt-Verh let, et al.

[Journal of Experimental Medicine, 147, 352 (1978)) and after coating, the culture supernatant is added and the mixture is reacted. The labeled peroxidase is added as an anti-mouse IgG + IgA + IgM (American Qualex International, Inc.) and binds to the anti-TNP antibody in the supernatant of culture, which is attached to the plate. The solution of orthophenylenea ina (Wako Pure Chemical Industries, Ltd) containing hydrogen peroxide (Wako Pure Chemical Industries, Ltd) is added and the reaction of the enzyme is initiated. After sufficient color has been generated, the color reaction is stopped by the addition of 10% sulfonic acid (Wako Puré Chemical, Industriee, Ltd) and the abeorbance is measured at 490 nm by means of the immunity reader (Intermed. Japan, NJ-2000). The results are shown in Table 5. The supreesion ratio of the production of the anti-TNP antibody by the test compound is calculated according to the following equation. Suppression Index (%) = (Absorbance in the Control Group) - (Absorbance in the Test Group) x 1 0 0 Absorbance in the Control Group Table 5 Suppression index (%) Compound No. [Dosage (mg / kg x 5)] 2 1 1 5 (3. 0) 5 7 (1 0) Cyclosporin A 3 9 (3 0) Test Example 5: T Cell Proliferation Inhibition Test Using the Mouse Mixed Lymphocyte Reaction (MLR) The removed spleen of C3H / He mouse is sterilized and the suspension of individual cells is prepared. This suspension is irradiated with 2000R of X-rays and adjusted to 8 x106 cells / ml. 50 μl of BALB / c mouse lymph node cells (containing 2 x 10 5 cells), 50 μl of spleen cell suspension irradiated with mouse X-ray C3H / He (containing 4 x 10 5 cells) and 50 μl of the The determined concentration of the test compound solution is added to each well of the well 96 microtitre plate and cultured at 37 ° C for 72 hours in the C02 incubator. Eight hours before the incubation is finished, [3H] -Timidine (1.85 KBq) is added. At the end of the culture, the cells are trapped in the filter paper by cell harvesting and dried. The toluene-type scintillator is added and the radioactivity of the [3 H] -Thymidine incorporated into the cells is measured by the liquid scintillation counter. The results are shown in Table 6. The suppression ratio of T cell proliferation is calculated according to the following equation.

Suppression index (%) = « (Radioactivity in the Control Group) - (Radioactivity in the Test Group ^ X 1 0 0 (Radioactivity in the Control Group) - (Radioactivity in C3H / He + Radioactivity in Balb / c) Table 6 Suppression Index (%) Compound No. [Concentration (M)] 1 0 7 (1 O - 7) 1 0 6 (1 O - 8) 7. 8 (1 O "9) The compounds obtained in accordance with the present invention are useful as anti-tumor agents, immuno-suppressive agents and therapeutic agents for an autoimmune disease, and can be used as they are or in various forms of administration. For example, when Compounds (I) are used as injections, Compounds (I) can be dissolved in a diluent agent conventionally used in this field such as a physiological saline solution, glucose injections, lactose injections, mannitol injections or similar, lyophilized at the base of the Japanese Pharmacopoeia or mixed with sodium chloride to form powder injections. These Injections may contain an adjuvant such as polyethylene glycol, HCO-60 (surfactant produced by Nikko Chemical Co., Ltd.), or the like; and a carrier such as ethanol and / or liposome, cyclodextrin, or the like. Since the injections are generally subjected to intravenous administration, they may also be subject to arterial administration, intra-abdominal administration or intrathoracic administration. When Compounds (I) are mixed with excipients, disintegrants, binders, suitable lubricants and the like and formed into tablets, granules, powders, lozenges or the like by a conventional method, the compounds can also be used as oral agents. Compounds (I) can be mixed with carriers conventionally used and formed, by a conventional method, to suppositories, which can be administered to the rectum. The different doses depend on the mode of administration, the type of the Compuate (I), the age and condition of a patient, etc., and the administration schedule may be changed according to the condition of the patient or the patient. For example, administration can be done in a dosie of 0.01 to 100 mg / kg once a week or once every three weeks. Reference Examples and Examples are described in the following.

The physiochemical data of each compound are measured by the following devices: NMR-1 !!: Nihon Denshi JNM-GX270 (270 MHz) Hitachi R-90H (90 MHz) MS: Nihon Denshi JSM-D300 Elemental Analysis: Perkin Elmer 2400 CHN Analyzer Reference Example 1 2 -Bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla) The 3', 4 ', 5' -Trimethoxyacetophenone (15.0 g) and the pyrrolidone hydrothribromide (35.39 g) were dissolved in tetrahydrofuran (225 ml), followed by stirring at 40 ° C for one hour. The reaction is cooled to room temperature, the precipitated crystals are removed by filtration, and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel, and the obtained purify crystals were washed with hexane (100 ml) to give 2-bromo-3 ', 4'-5'-trimethoxyacetophenone (Compound Xla, 12.20 g. ). NMR-1-H (90 MHz, CDCl 3) d 3.92 (s, 6H), 3.94 (s, 3H), 4.41 (s, 2H), 7.24 (s, 2H) EI-MS m / z = 288, 290 (M +) Elemental Analysis: C11H13Br04 Calculated (%): C, 45.70; H, 4.53 Found (%): C, 45.61; H, 4.30 Reference Example 2 Oxide 3 ', 4', 5 '-Trimethoxystyrene (Comet XHIa) The 2-bromo-3', 4 '-5' -trimethoxyacetophenone (Compound Xla, 10.0 g) obtained in Reference Example 1 was dissolved in methanol (350 ml), and sodium borohydride (1.31 g) is added thereto, followed by stirring at room temperature for 1.5 hours. The sodium borohydride (1.38 g) is added to the reaction solution and the mixture is stirred at room temperature for 0.5 hour. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give the 3 ', 4', 5'-trimethoxystyrene oxide (Compound XlIIa, 4.95 g). NMR-XH (90 MHz, CDCl 3) d 2.74 (dd, J = 5.5, 2.4 Hz, 1H), 3.14 (dd, J = 5.5, 4.3 Hz, 1H), 3.83 (m, 1H), 3.86 (s, 9H), 6.51 (s, 2H) EI-MS m / z = 210 (M +) Example of Reference 3 Oxide 3 ', 4', 5 '-trimethoxystyrene (Compound XHIa) 3, 4, 5-Trimethoxybenzaldehyde (1.84 g) and trimethylsulfoxonium iodide (2.28) are dissolved in dimethyl sulfoxide (18 ml), and sodium hydride (414.4 mg) is added thereto, followed by stirring at room temperature. ambient for an hour. The reaction solution is subjected to division between ethyl acetate and water and the organic layer is washed successively with water and a saturated saline solution and dried over anhydrous sodium sulfate. The organic solvent is evaporated under reduced pressure to give the 3 ', 4', 5'-trimethoxystyrene oxide (Compound XlIIa, 1.30 g). Reference Example 4 2-Methoxy-3 ', 4', 5 '-trimethoxyacetophenone (Compound IX-1) The 3', 4 ', 5'-trimethoxystyrene oxide (Compound XlIIa, 700.0 mg) obtained in Reference Example 2 is dissolved in methanol (100 ml), and sodium methoxide (0.90 g) is added thereto, followed by heating under reflux for 6 hours. The reaction solution is subjected to splitting between chloroform and water, and the organic layer is washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is dissolved in acetone (29 ml), and Jones reagent (1.5 ml) is added thereto cooling with ice, followed by stirring for 30 minutes. 2-Propanol (1.5 ml) is added to the reaction solution, and the solution is concentrated under reduced pressure, followed by the division between ethyl acetate and water. The organic layer is washed successively with water and a saturated saline solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 2-methoxy-3 ', 4', 5 -trimethoxyacetophenone (Compound IX-1, 363.2 mg). NMR-iH (90 MHz, CDC13) d 3.51 (s, 3H), 3.92 (s, 9H), 4.65 (e, 2H), 7.21 (e, 2H) EI-MS m / z = 240 (M +) Example of Reference 5 2-Ethoxy-3 ', 4', 5 '-trimethoxyacetophenone (Compound IX-2) 3', 4 ', 5'-trimethoxystyrene oxide (Compound XlIIa, 1.0 g) obtained in Reference Example 2, is dissolved in ethanol (14 ml) and potassium tert-butoxide (1.07 g) is added thereto, followed by heating under reflux for one hour. The reaction solution is subjected to partition between ethyl acetate and water, and the organic layer is washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is dissolved in acetone (33 ml), and Jones reagent (1.7 ml) is added thereto under cooling with ice, followed by stirring for 30 minutes. 2-Propanol (1.7 ml) is added to the reaction solution and the solution is concentrated under reduced pressure, followed by division between ethyl acetate and water. The organic layer is washed successively with water and a saturated saline solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 2-ethoxy-3 ', 4 ', 5'-trimethoxyacetophenone (Compound-IX-2, 615.0 mg). NMR-iH (90 MHz, CDC13) d 1.27 (t, J = 7.0 Hz, 3H), 3.68 (c, J = 7.0 Hz, 2H), 3.91 (s, 9H), 4.64 (s, 2H), 7.28 ( s, 2H) EI-MS m / z = 254 (M +) Reference Example 6 3 ', 4', 5 '-Trimethoxy-2-propyloxyacetophenone (Compound IX-3) Substantially the same procedure is repeated as in Example Reference 5 using the oxide 3 ', 4', 5 '-trimethoxystyrene (Compound XlIIa, 1.0 g) obtained in Reference Example 2 and 1-propanol (17.8 ml) to give the 3', 4 ', 5' -trimethoxy -2-propyloxyacetophenone (Compound IX-3, 6.15 mg). R -! H (90 MHz, CDCI3) d 0.95 (t, J = 6.9 Hz, 3H), 1.64 (m, 2H), 3.53 (c, J = 6.9 Hz, 2H), 3.91 (s, 9H), 4.65 (e, 2H), 7.26 (e, 2H) FAB-MS m / z = 269 (M ++ 1) Reference Example 7 2-Ieopropyloxy-3 ', 4', 5'-trimethoxyacetophenone (Compound IX-4) The same procedure is repeated substantially as in Reference Example 5 using the oxide 3 ', 4', 5 '-trimethoxystyrene (Compound XlIIa, 1.0 g)' obtained in Reference Example 2 and 1-propanol (18.2 ml) to give 2-isopropyl loxy-3 ',', 5 '-trimethoxyacetophenone (Compound IX-4, 548.9 mg). NMR - ^ - H (90 MHz, CDCl 3) d 1.24 (d, J = 7.0 Hz, 6H), 3. 68 (m, 1H), 3.91 (s, 9H), 4.67 (s, 2H), 7.25 '(s, 2H) EI-MS m / z = 268 (M +) Reference Example 8 3', 4 ', 5 '-Trimethoxy-2- (2-trimethylsilylethoxy) -acetophenone (Compound IX-5) The same procedure is repeated substantially as in Reference Example 5 using the 3', 4 ', 5'-trimethoxystyrene oxide (Compound XlIIa, 1.05 g) obtained in Reference Example 2 and 2-trimethylsilylethanol (35.8 ml) to give the 3 ', 4', 5'-trimethoxy-2- (2-trimethylsilylethoxy) acetophenone (Compound IX-5, 825.0 mg). I-NMR (270 MHz, CDCl 3) d 0.02 (s, 9H), 1.04 (t, J = 8.5 Hz, 2H), 3.66 (t, J = 8.5 Hz, 2H), 3.91 (s, 6H), 3.92 ( e, 3H), 4.67 (e, 2H), 7.24 (s, 2H) EI-MS m / z = 326 (M +) Reference Example 9 3 ', 4', 5 '-Trimethoxy-2- (3-trimethylsilylpropyloxy) ) -acetophenone (Compound IX-6) The same procedure is repeated substantially as in Reference Example 5 using the oxide 3 ',', 5 '-trimethoxystyrene (Compound XlIIa, 1.0 g) obtained in Example -Reference 2 and 3 -trimethylsilylpropanol (18.9 ml) to give the 3', 4 ', 5'-trimethoxy -2- (3 -tri ethylerylpropyloxy) acetophenone (Compoteto IX-6, 948.4 mg). NMR-! H (90 MHz, CDC13) d 0.00 (e, 9H), 0.53 (m, 2H), 1.68 (m, 2H), 3.53 (t, J = 6.9 Hz, 2H), 3.92 (e, 9H) , 4.67 (s, 2H), 7.27 (s, 2H) FAB-MS m / z = 341 (M ++ 1) Reference Example 10 3 ', 4', 5 '-Trimethoxy-2- (2-methylphenoxy) acetophenone (Compound IX-7) The 2-bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 1.45 g) obtained in Reference Example 1 and 2-methylphenol (648.0 mg) were dissolved in tetrahydrofuran (50 mg). mi) and a 2N aqueous solution of sodium hydroxide (3.0 ml) is added thereto, followed by stirring at room temperature for one hour. The reaction solution is partitioned between ethyl acetate and water, and the organic layer is washed successively with water and a saturated saline solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give the 3 ', 4', 5'-trimethoxy-2- (2-methylphenoxy) acetophenone (Compound IX-7, 0.69 g).

NMR-XH (90 MHz, CDCl 3) d 2.30 (s, 3H), 3.90 (s, 6H), 3.93 (s, 3H), 5.20 (s, 2H), 6.76 (dd, J = _ 6.9, 2.0 Hz, 1H), 6.93 (dd, J = 6.9, 1.6 Hz, 1H), 7.13 (broad t, J = 6.9 Hz, 2H), 7.30 (s, 2H) EI-MS m / z = 316 (M +) Reference Example 2- (4-Bromophenoxy) -3 ', 4', 5 '-Trimethoxyacetophenone (Compoteto IX-8) The same procedure is repeated substantially as in Reference Example 10 using 2-bromo-3', 4 ', 5'-trimethoxyacetophenone (Compound Xla, 1.45 g) obtained in Reference Example 1 and 4-bromophenol (1.04 g) to give 2- (4-bromophenoxy) -3 ', 4', 5'-trimethoxy-acetophenone ( Compound IX-8, 1.14 g). NMR-! H (90 MHz, CDCl 3) d 3.91 (s, 6H), 3.93 (s, 3H), 5.20 (s, 2H), 6.81 (d, J = 9.0 Hz, 2H), 7.25 (s, 2H), 7.38 (d, J = 9.0 Hz, 2H) EI-MS m / z = 380 (M + Reference Example 12 2-Methylthio-3 ', 4', 5'-trimethoxyacetophenone (Compound IX-9) 2-Bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 0.87 g) obtained in Reference Example 1, was dissolved in tetrahydrofuran (60 ml), and a 10% aqueous solution of sodium ethantiolate (3.0 ml) was added thereto. followed by stirring at room temperature for one hour. The reaction solution is subjected to partition between ethyl acetate and water, and the organic layer is washed successively with a 5% aqueous solution of sodium bicarbonate and a saturated saline solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 3 ', 4', 5'-trimethoxy-2-methylthioacetophenone (Compound IX-9, 1.02 g). NMR-! H (90 MHz, CDCl 3) d 2.16 (e, 3 H), 3.73 (s, 2H), 3.92 (s, 9H), 7.26 (e, 2H) EI-MS m / z = 256 (M +) Reference Example 13 3 ', 4', 5 '-Trimethoxy-2- (2-trimethylsilylethylthio) - acetophenone (Compound IX-10) 2-Trimethylsilylethyletol (1.00 g) is dissolved in tetrahydrofuran (75 ml) and an aqueous IN solution of sodium hydroxide (7.5 ml) and then 2-bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 1.79 g) obtained in Reference Example 1 are added thereto, followed by stirring at room temperature for one hour, The reaction solution is subjected to dividing between ethyl acetate and water, and the organic is washed successively with a 5% aqueous solution of sodium bicarbonate and a saturated saline solution over anhydrous magnesium sulfate, and it is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give the 3 ', 4', 5'-trimethoxy-2- (2-trimethylsilylethylthio) acetophenone (Compound IX-10, 2.07 g). RM -iH (90 MHz, CDCl 3) d 0.00 (s, 9H), 0.86 (m, 2H), 2.62 (, 2H), 3.74 (e, 2H), 3.89 (s, 9H), 7.22 (s, 2H) EI-MS m / z = 342 (M +) Reference Example 14 2- (4-Fluorophenylthio) ) -3 ', 4', 5'-trimethoxyacetophenone (Compound IX-11) The same procedure is repeated substantially as in Reference Example 13 using 2-bromo-3 ', 4', 5'-trimethoxyacetophenone (Compound Xla) , 1.54 g) obtained in Reference Example 1 to give 2- (4-fluorophenylthio) -3 ', 4', 5'-trimethoxyacetophenone (Compound IX-11, 2.24 g). NMR-iH (90 MHz, CDCl 3) d 3.87 (s, 6H), 3.92 (s, 3H), 4.15 (s, 2H), 6.97 (t, J = 8.9 Hz, 2H), 7.16 (e, 2H), 7.40 (dd, J = 8.9, 5.3 Hz, 2H) EI-MS m / z = 336 (M +) Reference Example 15 2- (4-Hydroxyethylthio) -3 ', 4', 5'-trimethoxyacetophenone (Compound IX- 12) Substantially repeat the same procedure as in Reference Example 13 using 2- mercaptoethanol (0.82 g) and 2-bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 2.60 g) _ obtained in Reference Example 1 to give hydroxyethylthio) -3', 4 ', 5' -trimetoxyacetophenone (Compoteto IX-12, 1.98 g). NMR-H (90 MHz, CDCl 3) d 2.41 (t, J = 6.0 Hz, 1H), 2. 86 (t; J = 6.0 Hz, 2H), 3.82 (c, J = 6.0 Hz, 2H), 3.85 (8, 2H), 3.92 (8, 9H), 7.23 (s, 2H) EI-MS m / z = 286 (M +) Reference Example 16 2- (2,3-Dihydroxypropylthio) -3 ', 4 *, 5'-trimethoxyacetophenone (Compoteto IX-13) The same procedure is repeated substantially as in Reference Example 13 using 1 -mercapto-2, 3-propanediol (12.25 g) and 2-bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 16.39 g) obtained in Reference Example 1 to give 2- (2, 3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (Compound IX-13, 17.0 g). NMR-1H (270 MHz, CDCl 3) d 2.18 (t, J = 4.0 Hz, 1H), 2.68 (dd, J = 14.1, 7.9 Hz, 1H), 2.79 (dd, J = 14.1, 4.5 Hz, 1H), 3.20 (d, J = 3.5 Hz, 1H), 3.58 (m, 1H), 3.73 (m, 1H), 3.85 (, 1H), 3.89 (s, 1H), 3.90 (s, 1H), 3.92 (s, 6H), 3.93 (s, 3H), 7.23 (e, 2H) FAB-MS m / z = 317 (M ++ 1) Reference Example 17 2- (β-D-Glucoethylthio) -3 ', 4', 5'-trimethoxyacetafenone (Compound IX-14) 2-Bromo-3 ', 4', 5'-trimethoxyacetophenone (Compound Xla, 289.0 mg) obtained in Reference Example 1 and the sodium salt l-thio-β-D-glucose (290.0 mg) were dissolved in a mixed solvent of tetrahydrofuran (25 ml) and methanol (10 ml), followed by stirring at room temperature for one hour. The reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give 2- (β-D-glucosylthio) -3 ', 4', 5'-trimethoxyacetophenone (Compoteto IX-14 390.4 mg). I-NMR (270 MHz, DMSO-dg) d 3.01-3.21 (m, 4H), 3.46 (m, 1H), 3.66 (m, 1H), 3.77 (e, 3H), 3.86 (e, 6H), 4.15 (d, J = 14.8 Hz, 1H), 4.23 (d, J = 14.8 Hz, 1H), 4.33 (d, J = 9.6 Hz, 1H), 4.40 (t, J = 5.9 Hz, 1H), 4.91 (d , J = 4.0 Hz, 1H), 5.03 (d, J = 4.5 Hz, 1H), 5.15 (d, J = 5.5 Hz, 1H), 7.27 (s, 2H) FAB-MS m / z = 405 (M + +1) Reference Example 18 2-Carboxymethylthio-3 ', 4', 5'-trimethoxyacetophenone (Compound IX-15) 2-Bromo-3 ', 4', 5'-trimethoxyacetophenone (Compound Xla, 1.16 mg) obtained in Reference Example 1 and thioglycolic acid (460.0 mg) were dissolved in tetrahydrofuran (30 mL), and a 2N aqueous solution of sodium hydroxide (5.0 mL) is added thereto, followed by stirring at room temperature for 16 hours. The reaction solution is subjected to partition between chloroform and IN hydrochloric acid, and the organic layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 2-carboxymethylthio-3 ', 4', 5'-trimethoxyacetophenone (Compound IX-15, 0.92 g). NMR-XH (90 MHz, CDCl 3) d (s, 2H), 3.92 (s, 9H), 4. 02 (s, 2H), 6.04 (s broad, 1H), 7.22 (s, 2H) FAB-MS m / z = 301 (M ++ 1) Reference Example 19 2- (2-Diethylaminoethylthio) -3 ', 4 ', 5' -trimethoxyacetophenone (Compound IX-16) 2-Bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 1.16 mg) obtained in Reference Example 1 and N, N-diethylaminoethiol hydrochloride (1.16 g) were dissolved in tetrahydrofuran (30 ml), and a 2N aqueous solution of sodium hydroxide (5.0 ml) was added thereto, followed by stirring at room temperature for 16 hours. The reaction solution is subjected to splitting between chloroform and water, and the organic layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by gel column chromatography of silica to give 2- (2-diethylaminoethylthio) -3 ', 4', 5'-trimethoxyacetophenone (Compound IX-16, 1.37 g). R N-! H (90 MHz, CDCI3) d 1.02 (t, J = 7.1 Hz, 6H), 2.54 (c, J = 7.1 Hz, 4H), 2.69 (s, 4H), 3.80 (s, 2H), 3.91 (s, 9H), 7.24 (s, 2H) EI-MS m / z = 341 MM +) Reference Example 20 3 ', 4', 5 '-Trimethoxy-2- (4-phenoxybutylthio) acetophenone (Compound IX- 17) Process 1 4-Phenoxybutyl bromide (5.73 g) is dissolved in dimethyl sulfoxide and potassium thioacetate (10.71 g) is added thereto followed by stirring at room temperature for 18 hours. The reaction solution is subjected to partition between ethyl acetate and water, and the organic layer is successively washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 1-acetylthio-4-phenoxybutane (Compound XIX-1, 5.53 g). I-NMR (270 MHz, CDCl 3) d 1.70-1.92 (m, 4H), 2.34 (s, 3H), 2.95 (t, J = 7.1 Hz, 2H), 3.97 (t, J = 6.1 Hz, 2H), 6.88 (d, J = 7.4 Hz, 2H), 6.93 (t, J = 8.2 Hz, 1H), 7.28 (dd, J = 8.2, 7.4 Hz, 2H) FAB-MS m / z = 225 (M ++ 1 ) Process 2 The l-acetylthio-4-phenoxybutane (Compound XIX-1, 1.0 g) obtained in Process 1 above was dissolved in piperidine (8 ml), followed by stirring at room temperature for 16 hours. Toluene is added to the reaction solution and the mixture is concentrated under reduced pressure. The residue and 2-bromo-3 ', 4', 5'-trimethoxyacetophenone (Compound Xla, 1.16 g) obtained in Reference Example 1 were dissolved in a mixed tetrahydrofuran (10 mL) solvent and added to the methanol moiety. (9.8 ml), followed by stirring at room temperature for 20 hours. The reaction solution is subjected to splitting between ethyl acetate and water, and the organic layer is successively washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 3 ', 4', 5'-trimethoxy-2- (4-phenoxybutylthio) acetophenone (Compound IX-17, 353.4 mg). NMR-H (270 MHz, CDCl 3) d 1.73-1.95 (m, 4H), 2.67 (t, J = 6.9 Hz, 2H), 3.77 (s, 2H), 3.92 (e, 6H), 3.93 (s, 3H), 3.97 (t, J = 5.9 Hz, 2H), 6.88 (dd, J = 8.6, 0.7 Hz, 2H), 6.93 (t, J = 7.6 Hz, 1H), 7.24 (s, 2H), 7.26 ( m, 2H), EI-MS m / z = 390 (M +) Reference Example 21 5,6-Dihydroxy-1- (3,4,5-trimethoxyphenyl) hexan-1-one (Compound IXh-1) Process 1 The 3, 4,5-trimethoxybenzaldehyde (25.48 g) is dissolved in tetrahydrofuran (50 ml) and 4-pentenylmagnesium bromide (1M solution in tetrahydrofuran, 200 ml) is added thereto, followed by stirring at room temperature for 30 minutes. IN hydrochloric acid is added to the reaction solution and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated saline solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 1-hydroxy-1- (3, 4, 5-trimethoxyphenyl) -5-hexene (Compound VIII- 1, 34.58 g). I-NMR (270 MHz, CDCl 3) d 1.34-1.89 (m, 4H), 2.12 (c, J = 6.8 Hz, 2H), 3.86 (s, 3H), 3.89 (s, 6H), 4.62 (dd, J = 7.3, 5.6 Hz, 1H), 4.96-5.07 (m, 2H), 5.83 (ddt, J = 17.2, 10.2, 6.8 Hz, 1H), 6.59 (s, 2H), OH; not detected EI-MS m / z = 266 (M +) Process 2 1-Hydroxy-1- (3,4,5-trimethoxyphenyl) -5-hexene (Compound VIII-1, 13.30 g) obtained in Process 1 above was dissolved in acetone (250 ml), and Jone 's reagent (18 ml) was added thereto under cooling with ice, followed by agitation for 30 minutes. 2-Propanol is added to the reaction solution, and the solution is concentrated under reduced pressure, followed by division between ethyl acetate and water. The organic layer is washed successively with water and a saturated solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 1- (3, 4, 5-trimethoxyphenyl) -5-hexen-1-one (Compound IXf-1, 10.80 g). NMR - H (270 MHz, CDCI3) d 1.73 (quintet, J = 7.0 Hz, 2H), 2.04 (c, J = 7.0 Hz, 2H), 2.83 (t, J = 7.0 Hz, 2H), 3.797 (s, 3H), 3.803 (s, 6H), 4.86-4.98 (m, 2H) ), 5.72 (ddt, J = 17.1, 10.2, 7.0 Hz, 1H), 7.10 (s, 2H) EI-MS m / z = 264 (M +) Process 3 1- (3, 4, 5-trimethoxyphenyl) - 5-hexen-l-one (Compound IXf-1, 2.64 g) obtained in Process 2 above was dissolved in chloroform (50 ml), metachloroperbenzoic acid (4.14 g) was added thereto, followed by stirring at room temperature for 32 minutes. The insoluble matter is filtered off and the filtrate is washed successively with a 10% aqueous solution of sodium thiosulfate and a 5% aqueous solution of sodium bicarbonate. The organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is purified or column chromatography on silica gel to give 5,6-epoxy-1- (3, 4, 5-trimethoxyphenyl) hexan-1-one (Compound IXg-1, 2.01 g). RM -iH (270 MHz, CDCl 3) d 1.57 (m, 1H), 1.77 (m, 1H), 1.93 (quint, J = 7.3 Hz, 2H), 2.50 (dd, J = 5.0, 3.0 Hz, 1H), 2.77 (dd, J = 5.0, 4.0 Hz, 'lH), 2.88 (m, 1H), 2.97 (t, J = 7.3 Hz, 2H), 3.92 (s, 9H), 7.23 (s, 2H) EI-MS m / z = 280 (M +) Process 4 The 5,6-epoxy-l- (3, 4, 5-trimethoxyphenyl) hexan-1-one (Compound IXg-1, 1.90 g) obtained in Process 3 above, is dissolved in methanol (30 ml), and sodium acetate (5.57 g) is added thereto, followed by heating under reflux for 40 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give 5,6-dihydroxy-1- (3, 4, 5-trimethoxyphenyl) hexan-1-one (Compound IXh -1, 0.87 g). NMR-! H (90 MHz, CDCl 3) d 1.53 (m, 2H), 1.87 (m, 2H), 2.68 (s, 2H), 3.01 (t, J = 6.7 Hz, 2H), 3.32-3.80 (, 3H) ), 3.92 (s, 9H), 7.22 (s, 2H) EI-MS m / z = 298 (M +) Reference Example 22 3 ', 4', 5 '-Trimethoxy-2- [(2S), (3R) ) -2, 3, 4-trihydroxy-butylthio] acetophenone (Compound IX-18) Process 1 The (-) -2, 3-0-isopropylidene-D-threitol (9.95 g) is dissolved in tetrahydrofuran (270 ml), and sodium hydride (2.70 g, 60% mineral oil dispersion) and then add to it tert-butyldimethylsilyl chloride (10.17 g), followed by stirring at room temperature for one hour. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give (2R), (3R) -4- (tert-butyldimethylsilyloxy) -2, 3-O-isopropylidene-1. , 2, 3-butantriol (15.87 g). R N-! H (270 MHz, CDCl 3) d 0.09 (s, 6H), 0.90 (s, 9H), 1.40 (e, 3H), 1.42 (s, 3H), 2.93 (dd, J = 8.3, 4.6 Hz , 1H), 3.62-3.83 (m, 3H), 3.83-3.93 (m, 2H), 3.99 (dt, J = 7.5, 4.5 Hz, 1H) FAB-MS m / z = 277 (M ++ 1) Process 2 The (2R), (3R) -4- (tert-butyldimethylsilyloxy) -2,3-0-ieopropylidene-1,2,3-butantriol (15.87 g) obtained in Process 1 above was dissolved in pyridine (9.3 ml). ), and toluenesulfonyl chloride (17.5471 g) is added thereto, followed by stirring at room temperature for 18 hours. Tetrahydrofuran (95 mL) and then a 5% aqueous solution of sodium bicarbonate (200 mL) are added to the reaction solution, followed by stirring for 30 minutes. minutes The reaction solution is subjected to splitting between ethyl acetate and water, and the organic layer is washed successively with a 10% aqueous solution of citric acid and a saturated solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give (2R), (3R) -4- (tert-butyldimethylsilyloxy) -2, 3-O-isopropylidene-1-toluenesulfonyloxy-2,3-butanediol (24.96 g). NMR-XH (270 MHz, CDCl 3) d 0.04 (s, 6H), 0.87 (s, 9H), 1.33 (s, 3H), 1.35 (s, 3H), 2.45 (s, 3H), 3.64 (dd, J = 10.4, 6.1 Hz, 1H), 3.75-3.87 (m, 2H), 4.04-4.25 (m, 3H), 7.34 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H) EI-MS m / z = 430 (M +) Process 3 The (2R), (3R) -4- (tert-butyldi ethylsilyloxy) -2,3-0- ieopropylidene-l-toluenesulfonyloxy-2,3-butanediol (5.62) g) obtained in Process 2 above was dissolved in dimethyl sulfoxide (64 ml), and potassium thioacetate is added thereto. (5.62 g), followed by stirring at room temperature for 18 hours. The reaction solution is subjected to partition between ethyl acetate and water, and the organic layer is successively washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give the (2S), (3R) -l-acetylthio-4- (tert-butyldimethylsilyloxy) -2,3-0-isopropylidene-2,3-butanediol (4.04 g-). 1 H NMR (270 MHz, CDCl 3) d 0.01 (s, 6H), 0.83 (s, 9H), 1.31 (s, 3H), 1.34 (s, 3H), 2.28 (s, 3H), 3.01 (dd, J = 13.9, 6.6 Hz, 1H), 3.25 (dd, J = 13.9, 4.3 Hz, 1H), 3.61-3.76 (m, 3H), 4.01 (m, 1H) FAB-MS m / z = 335 (M ++ 1) Process 4 The (2S), (3R) -l-acetylthio-4- (tert-butyldimethylsilyloxy) -2, 3-0-isopropylidene-2,3-butanediol (3.50 g) obtained in Process 3 above was dissolved in piperidine (20 ml), followed by stirring at room temperature for 30 minutes under an atmosphere of. argon. Toluene is added (50 ml) to the reaction solution and the mixture is concentrated under reduced pressure. The residue is dissolved in toluene (50 ml) and the mixture is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give (2S), (3R) -4- (tert-butyldimethylsilyloxy) -2,3-dihydroxy-2,3-isopropylidene-1-butantiol (2.81 g). NMR-! H (270 MHz, CDCl 3) d 0.06 (s, 6H), 0.88 (s, 9H), 1.39 (s, 3H), 1.42 (s, 3H), 1.62 (t, J = 8.2 Hz, 1H), 2.71 (ddd, J = 13.7, 8.0, 5.9 Hz, 1H), 2.82 (ddd, J = 13.7, 8.7, 4.7 Hz, 1H), 3.69 (dd, J = 10.2, 5.9 Hz, 1H), 3.79-3.91 (m, 2H), 4.03 (m, 1H) FAB-MS m / z = 293 (M ++ 1) Process 5 The (2S), (3R) -4- (tert-butyldi-ethylsilyloxy) -2,3-dihydroxy-2,3-isopropylidene-1-butantiol (2.71 g) obtained in Process 4 above was dissolved in a mixed solvent of methanol (50 ml) and water (10 ml), and camphorsulfonic acid (1.08 g) is added thereto, followed by heating under reflux for one hour. The reaction solution is cooled to room temperature, and an aqueous IN solution of sodium hydroxide (13.92 ml) and then a solution (50 ml) of 2-bromo-3 ', 4', 5 '- is added thereto. trimethoxyacetophenone (Compound Xla, 2.68 g) obtained in the Reference Example 1 in tetrahydrofuran, followed by stirring for one hour. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give the 3 ', 4', 5'-trimethoxy-2- [(2S), (3R) -2, 3,4-trihydroxybutylthio] acetophenone (Compound IX-18, 2.60 g). NMR-H (270 MHz, CDCl 3) d 2.49 (t, J = 5.6 Hz, 1H), 2. 78 (dd, J = 13.9, 8.1 Hz, 1H), 2.85 (dd, J = 13.9, 3.6 Hz, 1H), 2.90 (d, J = 6.6 Hz, 1H), 3.56 (d, J = 4.0 Hz, 1H ), 3.66 (m, 1H), 3.74-3.87 (m, 3H), 3.90 (s, 1H), 3.91 (s, 1H), 3.93 (s, 6H), 3.94 (8, 3H), 7.23 (s, 2H) FAB-MS m / z = 347 (M ++ 1) Reference Example 23 3 ', 4', 5 '-Trimethoxy-2- [(2R), (3S) -2, 3, 4 -trihydroxybutylthio] acetophenone (Compound IX-19) Process 1 Substantially the same procedure was repeated as in Process 1 of Reference Example 22 using (+) -2, 3-0-isopropylidene-L-threitol (5.08 g) and tert-butyldimethyleryl chloride (5.19 g) to give (2S), (3S) -4- (tert-Butyldimethylsilyloxy) -2, 3 -O-isopropylidene-1,2,3-butanediol (7.37 g). NMR-XH (270 MHz, CDCl 3) d 0.09 (s, 6H), 0.90 (s, 9H), 1.40 (s, 3H), 1.42 (e, 3H), 2.41 (dd, J = 7.9, 4.6 Hz, 1H ), 3.62-3.83 (m, 3H), 3.83-3.94 (m, 2H), 4.00 (dt, J = 7.7, 4.5 Hz, 1H) FAB-MS m / z = 277 (M ++ 1) Process 2 Se The procedure was repeated in the same manner as in Process 2 of Reference Example 22 using (2S), (3S) -4- (tert-butyldimethylsilyloxy) -2, 3-0-isopropylidene-1,2,3-butanediol (7.37 g) obtained in Process 1 above and toluenesulfonyl chloride (8.13 g) to give (2S), (3S) -4- (tert-butyldimethylethyloxy) -2, 3-0-isopropylidene-1-toluenesulfonyloxy-2, 3 -butandiol (10.57 g). NMR-H (270 MHz, CDCl 3) d 0.04 (s, 6H), 0.86 (s, 9H), 1.33 (s, 3H), 1.36 (s, 3H), 2.45 (s, 3H), 3.66 (dd,J = 10.1, 6.1 Hz, 1H), 3.74-3.90 (, 2H), 4.03-4.29 (m, 3H), 7.34 (d, J = 8.5 Hz, 2H), 7.80_ (d, J = 8.5 Hz, 2H ) FAB-MS m / z = 431 (M ++ 1) Process 3 Substantially the same procedure was repeated as in Process 3 of Reference Example 22 using (2S), (3S) -4- (tert-butyldimethylsilyloxy) -2, 3-0-isopropylidene-l-toluenesulfonyloxy-2,3-butanediol (5.57 g) obtained in Process 2 above and potassium thioacetate (5.57 g) to give (2R), (3S) -l-acetylthio -4- (tert-Butyl-dimethylsilyloxy) -2, 3-0-isopropylidene-2,3-butanediol (4.18 g). I-NMR (270 MHz, CDCl 3) d 0.08 (s, 6H), 0.91 (s, 9H), 1.38 (s, 3H), 1.42 (e, 3H), 2.36 (s, 3H), 3.08 (dd, J = 13.9, 6.3 Hz, 1H), 3.31 (dd, J = 13.9, 4.3 Hz, 1H), 3.68-3.85 (m, 3H), 4.08 (m, 1H) FAB-MS m / z = 335 (M ++ 1) Process 4 The same procedure was repeated substantially as in Process 4 of Reference Example 22 using (2R), (3S) -l-acetylthio-4- (tert-butyldimethylsilyloxy) -2, 3-0- isopropylidene-2,3-butanediol (3.97 g) obtained in Process 3 above and piperidine (22 ml) to give (2R), (3S) -4- (tert-butyldimethylsilyloxy) -2,3-dihydroxy-2, 3-0-isopropylidene-1-butantiol (3.18 g).

NMR-XH (270 MHz, CDCl 3) d 0.07 (s, 6H), 0.90 (s, 9H), 1.40 (e, 3H), 1.43 (s, 3H), 1.63 (t, J = 8.4 Hz, 1H), 2. 72 (ddd, J = 13.9, 8.2, 5.9 Hz, 1H), 2.84 (ddd, J = 13.9, 8. 4, 4.1 Hz, 1H), 3.70 (dd, J = 10.2, 5.9 Hz, 1H), 3.79-3.94 (m, 2H), 4.04 (m, 1H) FAB-MS m / z = 293 '(M ++ 1) Process 5 The same procedure was repeated substantially as in Process 5 of Reference Example 22 using (2R), (3S) -4- (tert-butyldimethylsilyloxy) -2,3-dihydroxy-2,3-O- isopropylidene-1-butantiol (2.97 g) obtained in Process 3 above and 2-bromo-3 ', 4', 5 '-trimethoxyacetophenone (Compound Xla, 2.94 g) obtained in Reference Example 1 to give 3', 4 ', 5'-trimethoxy-2- [(2R), (3S) -2,4,4-trihydroxybutylthio] acetophenone (Compound IX-19, 3.11 g). NMR-! H (270 MHz, CDCl 3) d 2.53 (t, J = 5.9 Hz, 1H), 2. 77 (dd, J = 13.5, 7.4 Hz, 1H), 2.85 (dd, J = 13.5, 3.6 Hz, 1H), 2.94 (d, J = 6.6 Hz, 1H), 3.58 (d, J = 4.0 Hz, 1H), 3.65 (m, 1H), 3.74-3.87 (m, 3H), 3.90 (s, 1H), 3.91 (e, 1H), 3.92 (s, 6H), 3.94 (s, 3H), 7.23 (s, 2H) FAB-MS m / z = 347 (M ++ 1) Reference Example 24 Indole-5-carbaldehyde The indole-5-carboxylic acid (3.10 g) is dissolved in tetrahydrofuran (50 ml) and lithium aluminum hydride (1.50 g) is added thereto, followed by heating under reflux for 20 minutes. hours. The reaction solution is cooled to room temperature, and ethyl acetate and then a 2N aqueous solution of sodium hydroxide are added thereto to terminate the reaction. The reaction solution is dried over anhydrous sodium sulfate and the insoluble matter is removed by filtration. Manganese dioxide is added (30.0 g) to the filtrate, followed by stirring at room temperature for 96 hours. The insolubles are removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give the indole-5-carbaldehyde (1.43 g). NMR-iH (90 MHz, CDC13) d 6.72 (m, 1H), 7.33 (t, J = 3.0 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.97 (dd, J = 8.6, 1.3 Hz, 1H), 8.19 (broad s, 1H), 8.57 (broad s, 1H), 10.04 (e, 1H) EI-MS m / z = 145 (M +) Example 1 (Z) -3- (Indol-3 -yl) -2-methoxy -1- (3,4,5-trimethoxy-phenyl) -2-propen-l-one (Compound 1) The 2-methoxy-3 ', 4', 5 '-trimethoxyacetophenone (300.0 mg) obtained in Reference Example 4 and indole-3-carbaldehyde (362.5 mg) were dissolved in ethanol (10 ml), and added thereto. piperidine (212.9 mg), followed by heating under reflux for 9 hours. The reaction solution is cooled with ice and the precipitated crystals are collected by filtration. To obtain crystals without purification, they were recrystallized from ethyl acetate to give Compound 1 (254.8 mg). NMR-H (270 MHz, CDCl 3) d 3.88 (s, 3H), 3.92 (s, 6H), 3.97 (s, 3H), 7.11 (s, 1H), 7.15-7.29 (m, 2H), 7.19 (s, 2H), 7.43 (dd, J = 7.6, 1.3 Hz, 1H), 7.65 (d , J = 7.6 Hz, 1H), 8.11 (d, J = 2.6 Hz, 1H), 8.67 (s broad, 1H) EI-MS m / z = 367 (M +) Elemental Analysis: C21H21N05 Calculated. (%): C, 68.65; H, 5.76; N, 3.81 Found (%): C, 68.60; H, 5.68; N, 3.75 Example 2 (Z) -2-Ethoxy-3- (indol-3-yl) -1- (3,4,5-trimethoxy-phenyl) -2-propen-l-one (Compound 2) La 2 Ethoxy-3 ', 4', 5'-trimethoxyacetophenone (509.0 mg) obtained in Reference Example 5 and indole-3-carbaldehyde (435.0 mg) were dissolved in ethanol (12 ml), and piperidine (255.5 mg) was added thereto, followed by heating under reflux for 24 hours. The solution of the reaction is concentrate under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (1: 1) to give Compound 2 (112.5 mg). 1 H-NMR (270 MHz, CDCl 3) d 1.42 (t, J = 7.0 Hz, 3H), 3. 92 (s, 6H), 3.96 (s, 3H), 4.11 (q, J = 7.0 Hz, 2H), 7.10 (s, 1H), 7.15-7.32 (m, 2H), 7.21 (s, 2H), 7.43 (d, J = 8.6 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 8.17 (d, J = 2.6 Hz, 1H), 8.58 (broad e, 1H). EI-MS m / z = 381 (M +) Elemental Analysis: C22H23N05 Calculated. (%): C, 69.28; H, 6.08; N, 3.67 Found (%): C, 69.52; H, 6.27; N, 3.57 Example 3 (Z) -3- (Indol-3-yl) -2-propyloxy-1- (3,4,5-trimethoxy-phenyl) -2-propen-l-one (Compound 3) • The 3 ', 4', 5 '-trimethoxy-2-propyloxyacetophenone (690.0 mg) obtained in Reference Example 6 and indole-3-carbaldehyde (373.3 mg) were dissolved in ethanol (10 ml) and piperidine was added thereto ( 254.6 mg), followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from of a mixed solvent of ethyl acetate and isopropyl ether (2: 2: 3) to give Compound 3 (701.5 mg). I-NMR (270 MHz, CDC13) d 1.02 (t, J = 7.2 Hz, 3H), 1.82 (sext, J = 7.2 Hz, 2H), 3.92 (s, 6H), 3.96 (s, 3H), 4.01 ( t, J = 7.2 Hz, 2H), 7.05 (s, 1H), 7.16-7.31 (m, 2H), 7.21 (s, 2H), 7.43 (d, J = 7.9 Hz, 1H), 7.64 (d, J = 7.9 Hz, 1H), 8.15 (d, J = 2.5 Hz, 1H), 8.57 (broad e, 1H) EI-MS m / z = 395 (M +) Elemental Analysis: C23H25 05 Calculated. (%): C, 69.86; H, 6.37; N, 3.54 Found (%): C, 69.88; H, 6.45; N, 3.53 Example 4 (Z) -2-Isopropyloxy-3- (indol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2-propen-l-one (Compound 4) 2-isopropyloxy -3 ', 4', 5 '-trimethoxyacetophenone (443.0 mg) obtained in Reference Example 7 and indole-3-carbaldehyde (360.0 mg) were dissolved in ethanol (10 ml) and piperidine (211.0 mg) was added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (1: 1) to give Compound 4 (386.0 mg).

NMR-XH (270 MHz, CDCl 3) d 1.34 (d, J = 6.2 Hz, 6H), 3. 92 (s, 6H), 3.96 (s, 3H), 4.51 (m, 1H), 7.09 (s, 1H), 7.15- 7.29 (m, 2H), 7.23 (s, 2H), 7.42 (dd, J = 7.3, 1.0 Hz, 1H), 7. 66 (d, J = 7.6 Hz, 1H), 8.21 (d, J = 2.6 Hz, 1H), 8.54 (s broad, 1H) EI-MS m / z = 395 (M +) Elemental Analysis: C23H25N05 Calculated. (%): C, 69.86; H, 6.37; N, 3.54 Found (%): C, 69.88; H, 6.57; N, 3.50 Example 5 (Z) -3- (Indol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2- (2-trimethylsilylethoxy) -2-propen-l-one (Compound 5) The 3 ', 4', 5 '-trimethoxy-2- (2-trimethylsilylethoxy) -acetophenone (720.0 mg) obtained in Reference Example 8 and indole-3-carbaldehyde (640.0 mg) were dissolved in ethanol (15 ml) and piperidine (376.1 mg) is added thereto, followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were purified by preparative high pressure liquid chromatography (CLAP) (ODS packed YMC, SH-343-5, S-5, 120A, 250 x mm, acetonitrile: water = 80:20) to give Compound 5 (83.7 mg).

R -IH (270 MHz, CDCl 3) d 0.01 (s, 9H), 1.23 (m, 2H), 3.92 (s, 6H), 3.96 (s, 3H), 4.14 (m, 2H), 7.07 (e, 1H), 7. 20 (s, 2H), 7.22 (m, 1H), 7.28 (m, 1H), 7.43 (dd, J = 8.1, 0. 9 Hz, 1H), 7.64 (d, J = 7.3 Hz, 1H), 8.22 (d, J = 2.6 Hz, 1H), 8.57 (broad s, 1H) El-MS m / z = 453 (M +) Elemental Analysis : C25H31N05If Calculated. (%): C, 66.20; H, 6.89; N, 3.09 Found (%): C, 66.14; H, 6.72; N, 3.15 Example 6 (Z) -3- (Indol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2- (2-trimethylsilylpropyloxy) -propen-1-one (Compound 6) The 3 ', 4', 5 '-trimethoxy-2- (3-trimethylsilylpropyloxy) -acetophenone (843.0 mg) obtained in Reference Example 9 and indole-3-carbaldehyde (359.5 mg) were dissolved in ethanol (10 ml) and piperidine (211.1 mg) is added thereto, followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane, and isopropyl ether (2: 2: 3) to give Compound 6 (547.1 mg). H NMR (270 MHz, CDCl 3) d -0.01 (s, 9H), 0.57 (m, 2H), 1.80 (m, 2H), 3.93 (s, 6H), 3.97 (s, 3H), 4.01 (m, 2H), 7. 05 (s, 1H), 7.16-7.33 (m, 2H), 7.21 (s, 2H), 7.44 (d, J = 7.4 Hz, 1H), 7.66 (d, J = 7.9 Hz, 1H), 8.16 (d , J = 3.0 Hz, 1H), 8.56 (s, 1H) EI-MS m / z = 467 (M +) Elemental Analysis: C26H33N05Si Calculated. (%): C, 66.78; H, 7.11; N, 3.00 Found (%): C, 66.77; H, 7.30; N, 2.94 Example 7 (Z) -3- (Indol-3-yl) -2- (2-methylphenoxy) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 7) The 3 ', 4', 5 '-trimethoxy-2- (2-methylphenoxy) acetophenone (600.0 mg) obtained in Reference Example 10 and indole-3-carbaldehyde (551.0 mg) were dissolved in ethanol (20 ml) and Piperidine (323.0 mg) is added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The obtained unpurified crystals were purified by means of the CLAP preparation (OMC packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: water = 70:30) to give Compound 7 (601.4 mg ). R N-iH (270 MHz, CDCl 3) d 2.49 (s, 3H), 3.88 (s, 6H), 3.92 (s, 3H), 6.81 (dd, J = 7.9, 1.3 Hz, 1H), 6.89 (dd, J = 7.3, 1.3 Hz, 1H), 7.00 (ddd, J = 7.9, 7.3, 1.3 Hz, 1H), 7.15 (s, 2H), 7.19 (dd, J = 7.3, 1.3 Hz, 1H), 7.23-7.30 (m, 2H), 7.40 (m, 1H), 7.61 (s, 1H), 7.73 (, 1H), 7.86 (d, J = 2.6 Hz, 1H), 8.54 (s broad, 1H) EI-MS m / z = 443 (M +) Elemental Analysis: C27H25N05 Calculated. (%): C, 73.12; H, 5.68; N, 3.16 Found (%): C, 72.87; H, 5.80; N, 2.99 Example 8 (Z) -2- (4-Bromophenoxy) -3- (indol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 8) 2- (4-bromophenoxy) -3 ', 4', 5'-trimethoxyacetophenone (906.8 mg) obtained in Reference Example 11 and indole-3-carbaldehyde (652.5 mg) were dissolved in ethanol (15 ml) and piperidine (382.5 mg) was added thereto, followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel to give Compound 8 (1.18 g). I-NMR (270 MHz, CDCl 3) 8 3.90 (s, 6H), 3.94 (s, 3H), 6.92 (d, J = 9.1 Hz, 2H), 7.18 (s, 2H), 7.21-7.32 (m, 2H), 7.35 (d, J = 9.1 Hz, 2H), 7.42 (dd, J = 6.6 , 2.0 Hz, 1H), 7. 69 (s, 1H), 7.73 (dd, J = 6.2, 2.1 Hz, 1H), 7.83 (d, J = 3.0 Hz, 1H), 8.59 (s broad, 1H) EI-MS m / z = 507, 509 (M +) Elemental Analysis: C26H22BrN05 Calculated. (%): C, 61.43; H, 4.36; N, 2.76 Found (%): C, 61.33; H, 4.41; N, 2.53 Example 9 (Z) -3- (Indol-3-yl) -2-methylthio-l- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 9) 2-methylthio -3 ', 4', 5 '-trimethoxyacetophenone (900.0 mg) obtained in Reference Example 12 and indole-3-carbaldehyde (1.02 g) were dissolved in ethanol (35 ml) and added to the piperidine funnel (598.4 mg), followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were purified by means of the CLAP preparation (OMC packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: water = 70:30) to give Compound 9 (752.9 mg ). I-NMR (270 MHz, CDCl 3) d 2.39 (s, 3H), 3.90 (s, 6H), 3.97 (s, 3H), 7.16-7.30 (m, 2H), 7.20 (s, 2H), 7.44 (d , J = 7.9 Hz, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.67 (s, 1H), 8.33 (d, J = 2.6 Hz, 1H), 8.73 (s broad, 1H) EI-MS m / z = 383 (M +) Elemental Analysis: C21H21N04S Calculated. (%): C, 65.78; H, 5.52; N, 3.65 Found (%): C, 66.04; H, 5.37; N, 3.58 Example 10 (Z) -3- (Indol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2- (2-trimethylsilylethylthio) -2-propen-l-one (Compound 10) The 3 ' , 4 ', 5' -trimethoxy -2- (2-trimethylsilylethylthio) acetophenone (1.0 g) obtained in Reference Example 13 and indole-3-carbaldehyde (0.85 g) were dissolved in ethanol (30 ml) and piperidine (0.50 g) is added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were purified by means of the CLAP preparation (OMC packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile water = 80:20) to give Compound 10 (0.76 g) . NMR-H (270 MHz, CDCl 3) d -0.05 (s, 9H), 0.89 (m, 2H), 2.90 (, 2H), 3.89 (s, 6H), 3.97 (s, 3H), 7.16-7.30 (m, 2H), 7.20 (s, 2H), 7.44 (d, J = 7.9 Hz, 1H) , 7.60 (d, J = 7.6 Hz, 1H), 7.71 (s, 1H), 8.39 (d, J = 3.0 Hz, 1H), 8.67 (broad s, 1H) EI-MS m / z = 469 (M +) Elemental Analysis: C25H31N04SSi Calculated. (%): C, 63.93; H, 6.65; N, 2.98 Found (%): C, 63.95; H, 6.70; N, 2.92 Example 11 (Z) -2- (4-Fluoro-phenylthio) -3- (indol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 11) The 2- (4-fluorophenylthio-3 ', 4', 5'-trimethoxyacetophenone (1.19 g) obtained in Reference Example 14 and indole-3-carbaldehyde (1.03 g) were dissolved in ethanol (35 ml) and added at the same piperidine (0.60 g), followed by heating under reflux for 24 hours.The reaction solution is concentrated under reduced pressure and the residue is purified by silica gel column chromatography.The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (1: 1) to give Compound 11 (0.83 g). RMN - ^ - H (270 MHz, CDCl 3) d 3.89 (s, 6H), 3.93 (s, 3H), 6.89 (t, J = 8.6 Hz, 2H), 7.03 (s, 2H), 7.21-7.33 (m, 4H), 7.44 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 7.3 Hz, 1H ), 8.01 (s, 1H), 8.40 (d, J = 3.0 Hz, 1H), 8.78 (s broad, 1H) EI-MS m / z = 463 (M +) Elemental Analysis: C2gH22FN04S Calculated. (%): C , 67.37; H, 4.78; N, 3.02 Found (%): C, 67.32; H, 4.82; N, 2.95 Example 12 (Z) -2- (2-Hydroxyethylthio) - 3- (indol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 12) 2- (2-hydroxyethylthio) -3 ', 4', 5 ' -trimethoxyacetophenone (858.0 mg) obtained in Reference Example 15 and indole-3-carbaldehyde (435.0 mg) were dissolved in ethanol (10 ml) and piperidine (255.0 mg) was added thereto, followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were purified by means of the CLAP preparation (OMC packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: water = 50:50) to give Compound 12 (636.5 mg ). NMR-1 H (270 MHz, CDCl 3) d 3.04 (t, J = 5.6 Hz, 2H), 3. 16 (t, J = 5.6 Hz, 1H), 3.71 (q, J = 5.6 Hz, 2H), 3.88 (s, 6H), 3.97 (s, 3H), 7.12 (s, 2H), 7.20-7.32 (m , 2H), 7.46 (d, J = 7.9 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.95 (s, 1H), 8.60 d, J = 3.0 Hz, 1H), 8.88 (s broad, 1H) FAB-MS m / z = 414 (M ++ 1) Elemental Analysis: C22H23N05S3 • 0.5H20 Calculated. (%): C, 62.54; H, 5.73; N, 3.32 Found (%): C, 62.56; H, 5.55; N, 3.02 Example 13 (Z) -2- (2-Hydroxyethylthio) -3- (6-methylindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 13) 2- (2-Hydroxyethylthio) -3 ', 4', 5 '-trimethoxyacetophenone (1.0 g) obtained in Reference Example 15 and 6-methylindol-3-carbaldehyde [J. Org. Chem., 44, 3741 (1979)] (0.56 g) were dissolved in ethanol (10 ml) and piperidine (0.30 g) was added thereto, followed by heating under reflux for 72 hours. The reaction solution is concentrate under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (1: 1) to give Compound 13 (911.3 mg). RMN-iH (270 MHz, 'CDCl3) d 2.47 (s, 3H), 3.03 (t, J = 5.4 Hz, 2H), 3.09 (s, 1H), 3.70 (t, J = 5.4 Hz, 2H), 3.88 (s, 6H), 3.97 (s, 3H), 7.04 (d, J = 8.4 Hz, 1H), 7.12 (s, 2H), 7.24 (S, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 8.53 (d, J = 2.5 Hz, 1H), 8.75 (s broad, 1H) EI-MS m / z = 427 (M +) Elemental Analysis: C23H25N05S Calculated. (%): C, 64.62; H, 5.89; N, 3.28 Found (%): C, 64.37; H, 6.13; N, 3.14 Example 14 (Z) -2- (β-D-glucosylthio) -3- (6-methylindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (Compound 14) 2- (β-glucosylthio) -3 ', 4', 5'-trimethoxyacetophenone (1.01 g) obtained in Reference Example 17 and 6-methylindol-3-carbaldehyde (0.40 g) were dissolved in ethanol (10 ml) and piperidine (0.21 g) is added thereto, followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were purified by means of of the CLAP preparation (ODS packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: water = 40:60). The eluted material is concentrated under reduced pressure and the residue is recrystallized from a mixed solvent of ethanol and isopropyl ether (1: 1) to give Compound 14 (322.2 mg). H NMR (270 MHz, DMSO-dg) d 2.40 (s, 3H), 2.78 m, 1H), 3.16-3.32 (m, 5H), 3.79 (e, 3H), 3.80 (s, 3H), 3.81 ( s, 3H), 4.24 (t, J = 5.6 Hz, 1H), 4.76 (d, J = 8.6 Hz, 1H), 4.82 (d, J = 4.6 Hz, 1H), 5.09 (d, J = 2.9 Hz, 1H), 5.46 (d, J = 5.0 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 7.09 (s, 2H), 7.26 (s, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.52 (e, 1H), 8.12 (d, J = 2.5 Hz, 1H), 11.73 (s, 1H) FAB-MS m / z = 545 (M ++ 1) Elemental Analysis: C27H31N09S • 0.8H20 Calculated . (%): C, 57.91; H, 5.87; N, 2.50 Found (%): C, 57.88; H, 5.77; N, 2.40 Example 15 (Z) -2-Carboxymethylthio) -3- (indol-3-yl) -1- (3,4,5- -trimethoxyphenyl) -2-propen-l-one (Compound 15) La 2 -carboxymethylthio) -3 ', 4', 5'-trimethoxyacetophenone (0.60 g) obtained in Reference Example 18 and indole-3-carbaldehyde (0.29 g) were dissolved in ethanol (5 ml) and piperidine (0.34 g) was added thereto, followed by heating under reflux for 40 hours. The reaction solution is concentrated under reduced pressure and the residue purify by column chromatography on silica gel. The unpurified crystals obtained were purified by means of the CLAP preparation (ODS packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: water = 30:70). The eluted material is concentrated under reduced pressure and the residue is subjected to be divided between chloroform and a 10% aqueous solution of citric acid. The organic layer is concentrated under reduced pressure to give Compound 15 (343.3 mg). H NMR (270 MHz, CDCl 3) d 3.62 (s, 2 H), 3.88 (s, 6 H), 3.99 (s, 3 H), 7.11 (s, 2 H), 7.21 (m, 1 H), 7.31 (m, 1 H) ), 7.47 (d, J = 7.9 Hz, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.99 (s, 1H), 8.52 (d, J = 3.0 Hz, 1H), 9.10 (s broad, 1H), C02H; undetected FAB-MS m / z = 428 (M ++ 1) Elemental Analysis: C22H2? N06S • 0.4H20 Calculated. (%): C, 60.79; H, 5.05; N, 3.22 Found (%): C, 60.76; H, 4.86; N, 3.17 Example 16 (Z) -3- (indol-3-yl) -2-methoxycarbonylmethylthio-1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 16) Compound 15 ( 50.0 mg) obtained in Example 15 is dissolved in a mixed solvent of chloroform (10 ml) and methanol (5 ml), and a solution (0.5 ml) of trimethylsilyldiazomethane in hexane, followed by stirring for 10 minutes. Acetic acid (20.0 mg) is added to the reaction solution and the mixture is subjected to be divided between chloroform and a 5% aqueous solution of sodium bicarbonate. The organic layer is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from isopropyl ether to give Compound 16 (36.9 mg). RMN-1 !! (270 MHz, CDCI3) d 3.58 (s, 3H), 3.68 (s, 2H), 3.90 (s, 6H), 3.97 (s, 3H), 7.15 (s, 2H), 7.19 (m, 1H), 7.28 (m, 1H), 7.48 (m, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.83 (s, 1H), 8.46 (d, J = 2.7 Hz, 1H), 8.78 (s, 1H) EI-MS m / z = 441 (M +) Elemental Analysis: C23H23NOgS Calculated. (%): C, 62.57; H, 5.25; N, 3.17 Found (%): C, 62.40; H, 5.26; N, 3.13 Example 17 (Z) -2- (2-Diethylaminoethylthio) -3- (indol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2-propen-l-one (Compound 17) The 2- (2-diethylaminoethylthio) -3 ', 4', 5'-trimethoxy-acetophenone (671.0 mg) obtained in the Reference Example 19 and indole-3-carbaldehyde (290.0 mg) were dissolved in ethanol (5 ml) and piperidine (170.0 mg) is added to the mero, followed by heating under reflux for 44 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel.

The unpurified crietals obtained were purified by means of the CLAP preparation (packed ODS YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: 0.1M aqueous solution of ammonium acetate = 50:50) . The eluted material is concentrated under reduced pressure and the residue is subjected to be divided between chloroform and a 5% aqueous solution of sodium bicarbonate. The organic layer is concentrated under reduced pressure to give Compound 17 (410.6 mg). RMN-1 !! (270 MHz, CDCI3) d 0.95 (t, J = 7.1 Hz, 6H), 2.49 (q, J = 7.1 Hz, 4H), 2.71 (m, 2H), 2.94 (m, 2H), 3.89 (s, 6H) ), '3.97 (s, 3H), 7.18 (s, 2H), 7.19 (m, 1H), 7.27 (m, 1H), 7.44 (d, J = 7.9 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.73 (s, 1H), 8.43 (d, J = 2.3 Hz, 1H), 8.87 (s, 1H) FAB-MS m / z = 469 (M ++ 1) Elemental Analysis: C26H32 204S • 0.6H20 Calculated. (%): C, 65.14; H, 6.98; N, 5.84 Found (%): C, 65.25; H, 7.16; N, 5.86 Example 18 (Z) -3- (Indol-3-yl) -2- (4-phenoxybutylthio) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 18) The 2- (4-phenoxybutylthio) -3 ',', 5 '-trimethoxyacetophenone (195.0 mg) obtained in Reference Example 20 and indole-3-carbaldehyde (72.5 mg) were dissolved in ethanol (3 ml) and added at the same piperidine (42.6 mg), followed by heating under reflux for 4 hours. The solution of The reaction is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were purified by means of the CLAP preparation (packed ODS YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile-water = 70:30). The eluted material is concentrated under reduced pressure and the crystals without purifying obtained were recrystallized from isopropyl ether to give Compound 18 (94.0 mg). I-NMR (270 MHz, CDCl 3) d 1.71-1.93 (m, 4H), 2.95 (t, J = 7.1 Hz, 2H), 3.87 (s, 6H), 3.89 (t, J = 6.9 Hz, 2H), 3.97 (s, 3H), 6.77 (d, J = 7.9 Hz, 2H), 6.89 (t, J = 7.3 Hz, 1H), 7.16-7.31 (m, 4H), 7.18 (s, 2H), 7.44 (d , J = 8.3 Hz, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.75 (s, 1H), 8.42 (d, J = 1.0 Hz, 1H), 8.68 (s broad, 1H) EI-MS m / z = 517 (M +) Elemental Analysis: Calculated. (%): C, 69.61; H, 6.09; N, 2.71 Found (%): C, 69.57; H, 6.36; N, 2.72 Example 19 (E) -2- (3,4-Dihydroxybutyl) -3- (indol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 19) The 5,6-dihydroxy-1- (3,4,5-trimethoxyphenyl) hexan-1-one (787.2 mg) obtained in Reference Example 21 and indole-3-carbaldehyde (382.8 mg) were dissolved in ethanol (7 ml), 'piperidine is added to it (261.1 mg), followed by heating under reflux for 48 hours. N, N, N'-trimethylethylenediamine (269.8 mg) is added to the reaction solution and the mixture is heated under reflux for an additional 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (3: 2) and then from ethanol to give Compound 19 (98.4 mg). RM -iH (270 MHz, CDCl 3) d 1.67-1.94 (m, 2H), 2.33 (broad t, J = 5.8 Hz, 1H), 2.89 (m, 1H), 3.03 (m, 1H), 3.54 (m, 1H), 3.67 (m, 1H), 3.78 (m, 1H), 3.88 (s) , 6H), 3.96 (broad s, 1H), 3.97 (s, 3H), 7.00 (s, 2H), 7.17-7.31 (m, 2H), 7.44 (d, J = 7.9 Hz, 1H), 7.54 (d , J = 7.9 Hz, 1H), 7.77 (s, 1H), 7.87 (d, J = 2.6 Hz, 1H), 8.92 (s broad, 1H) FAB-MS m / z = 426 (M ++ 1) Analysis Elemental: C24H27 06 • 0.5H20 Calculated. (%): C, 66.35; H, 6.50; N, 3.22 Found (%): C, 66.40; H, 6.67; N, 3.18 Example 20 (E) -2- (3,4-Dihydroxybutyl) -3- (6-methylindol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2-propenyl-one (Compound 20) 5,6-Dihydroxy-1- (3,4,5-trimethoxyphenyl) hexan-1-one (870.0 mg) obtained in Reference Example 21 and 6-methylindol-3-carbaldehyde (465.0 mg) they dissolved in ethanol (8 ml), piperidine (288.8 mg) is added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (5: 3) and then from a mixed solvent of ethanol and water (1: 1) to give Compound 20 (142.7 mg) . I-NMR (270 MHz, CDCl 3) d 1.70-1.95 (m, 2H), 2.36 (s broad, 1H), 2.47 (s, 3H), 2.87 (m, 1H), 3.03 (m, 1H), 3.54 (m, 1H), 3.65 (m, 1H), 3.77 (m, 1H), 3.88 (s, 6H), 3.96 (s, 3H), 4.04 (s broad, 1H), 7.00 (s, 2H), 7.02 (d, J = 8.8 Hz, 1H), 7.22 (s, 1H), 7.41 (d , J = 8.8 Hz, 1H), 7.75 (s, 1H), 7.79 (d, J = 2.3 Hz, 1H), 8.79 (s, 1H) FAB-MS m / z = 440 (M ++ 1) Elemental Analysis : C25H29N0g • 0.3H20 Calculated. (%): C, 67.49; H, 6.71; N, 3.15 Found (%): C, 67.55; H, 6.93; N, 3.15 Example 21 (Z) -2- (2,3-Dihydroxypropylthio) -3- (indol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 21) 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (3.16 g) obtained in Reference Example 16 and indole-3-carbaldehyde (1.45 g) were dissolved in ethanol (50 ml), piperidine (0.85 g) is added to the mixture, followed by heating under reflux for 72 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The crystals without purifying obtained were recrystallized from a mixed solvent of ethanol and water (1: 4) to give Compound 21 (2.04 g). RMN-1 !! (270 MHz, CDCI3) d 2.31 (t, J = 5.9 Hz, 1H), 2.83 (dd, J = 13.9, 8.9 Hz, 1H), 3.09 (dd, J = 13.9, 4.0 Hz, 1H), 3.58 (dt) , J = 11.2, 5.9 Hz, 1H), 3.69 (m, 1H), 3.79 (m, 1H), 3.88 (s, 6H), 3.97 (s, 3H), 4.11 (d, J = 3.5 Hz, 1H) , 7.11 (s, 2H), 7.21 (m, 1H), 7.29 (m, 1H), 7.46 (broad d, J = 7.9 Hz, 1H), 7.54 (broad d, J = 7.4 Hz, 1H), 7.97 ( s, 1H), 8.61 (d, J = 3.0 Hz, 1H), 9.01 (s, 1H) EI-MS m / z = 443 (M +) Elemental Analysis: C23H25N06S • 0.9H20 Calculated. (%): C, 60.09; H, 5.88; N, 3.05 Found (%): C, 60.11; H, 6.01; N, 3.03 Example 22 (Z) -2- (2,3-Dihydroxypropylthio) -3- (1-methylindol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2-propenyl-one (Compound 22) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (1.0 g) obtained in Reference Example 16 and l-methylindol-3-carbaldehyde (0.50 g) were dissolved in ethanol (8 ml), piperidine (0.31 g) is added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethanol and water (1: 1) to give Compound 22 (844.8 mg). R N-iH (270 MHz, CDCl 3) d 2.24 (t, J = 6.3 Hz, 1H), 2.82 (dd, J = 13.6, 8.7 Hz, 1H), 3.10 (dd, J = 13.6, 3.5 Hz, 1H) , 3.57 (m, 1H), 3.69 (m, 1H), 3.78 (m, 'lH), 3.87 (s, 6H), 3.94 (s, 3H), 3.97 (s, 3H), 4.24 (d, J = 4.0 Hz, 1H), 7.08 (s, 2H), 7.22 (m, 1H), 7.33 (m, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H) , 8.00 (s, 1H), 8.52 (e, 1H) FAB-MS m / z = 458 (M ++ 1) Elemental Analysis: C 4H27NOgS Calculated. (%): C, 63.00; H, 5.95; N, 3.06 Found (%): C, 62.85; H, 5.97; N, 3.02 Example 23 (Z) -2- (2,3-Dihydroxypropylthio) -3- (4-methyl-indol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (Compound 23) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (397.5 mg) obtained in Reference Example 16 and 4-methylindol-3-carbaldehyde (WO95 / 14003) ( 200.0 mg) were dissolved in ethanol (2 ml) and piperidine (107.3 mg) was added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under pressure reduced and the residue purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (2: 1) and purified by means of the preparative CLAP (ODS packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile water = 40:60). The eluted material is concentrated under reduced pressure and the residue is recrystallized from isopropyl ether to give Compound 23 (249.0 mg). RM -iH (270 MHz, CDCl 3) d 2.38 (t, J = 5.8 Hz, 1H),2. 41 (s, 3H), 2.83 (dd, J = 13.9, 8.6 Hz, 1H), 3.08 (dd, J = 13.9, 4.0 Hz, 1H), 3.57 (dt, J = 11.3, 5.8 Hz, 1H), 3.70 (m, 1H), 3.81 (m, 1H), 3.88 (s, 6H), 3.94 (s, 3H), 4.13 (d, J = 3.3 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H) , 7.05 (s, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 8.32 (s, 1H), 8.69 (d, J = 3.0 Hz, 1H) , 9.07 (s, 1H) FAB-MS m / z = 458 (M ++ 1) Elemental Analysis: C24H27NOgS Calculated. (t) r C, 63.00; H, 5.95; N, 3.06 Found (%) r C, 63.00; H, 5.96; N, 3.05 Example 24 (Z) -3- (4-chloroindol-3-yl) -2- (2,3-dihydroxypropylthio) -1- (3,4,5-trimethoxyphenyl) -2-propen-1 -one (Compound 24) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxy-acetophenone (948.0 mg) obtained in the Reference Example 16 and chloroindol-3-carbaldehyde [Can. J. Chem., 4_1, 1585 (1963)] (537.0 mg) were dissolved in ethanol (6 ml) and piperidine (296.7 mg) was added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (5r3) to give Compound 24 (909.9 mg). NMR-XH (270 MHz, CDCI3) d 2.48 (broad s, 1H), 2.87 (dd, J = 13.6, 8.4 Hz, 1H), 3.08 (dd, J = 13.6, 4.0 Hz, 1H), 3. 58 (m, 1H), 3.72 (m, 1H), 3.83 (m, 1H), 3.91 (s, 6H), 3.94 (s, 3H), 4.00 (d, J = 3.6 Hz, 1H), 7.11 (s, 2H), 7.15-7.17 (m, 2H), 7.38 (m, 1H), 8.64 (d, J = 2.6 Hz, 1H), 8.77 (s, 1H), 9.37 (s, 1H) FAB-MS m / z = 478, 480 (M ++ 1) Elemental Analysis r C23H24ClNOgS Calculated. (%) r C, 57.80; H, 5.06; N, 2.93 Found (%) r C, 58.08; H, 5.16; N, 2.86 Example 25 (Z) -2- (2,3-Dihydroxypropylthio) -3- (5-methylindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (Compound 25) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (948.0 mg) obtained in Reference Example 16 and 5-methylindol-3-carbaldehyde (O95 / 14003) ( 477.0 mg) They were dissolved in ethanol (6 ml) and piperidine (255.5 mg) was added thereto, followed by heating under reflux for 36 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The crystals without purifying obtained were recrystallized from a mixed solvent of ethanol and water (2r3) to give Compound 25 (710.9 mg). RMN-1 !! (270 MHz, CDCI3) d 2.32 (t, J = 5.9 Hz, 1H), 2.43 (s, 3H), 2.81 (dd, J = 13.7, 8.6 Hz, 1H), 3.08 (dd, J = 13.7, 3.8 Hz , 1H), 3.56 (m, 1H), 3.68 (m, 1H), 3.78 (m, 1H), 3.89 (s, 6H), 3.97 (s, 3H), 4.15 (d, J = 3.6 Hz, 1H) , 7.11 (m, 1H), 7.12 (s, 2H), 7.30 (s broad, 1H), 7.34 (d, J = 8.3 Hz, 1H), 7.95 (s broad, 1H), 8.58 (d, J = 3.0 Hz, 1H), 8.90 (s, 1H) FAB-MS m / z = 458 (M ++ 1) Elemental Analysis r C24H27NO S Calculated. (%) r C, 63.00; H, 5.95; N, 3.06 Found (%): C, 63.33; H, 6.10; N, 3.13 Example 26 (Z) -3- (5-Chloroindol-3-yl) -2- (2,3-dihydroxypropylthio) -1- (3, 4, 5-trimethoxyphenyl) -2-propen-l -one (Compound 26) 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (948.0 mg) obtained in Reference Example 16 and 5-chloroindol-3-carbaldehyde (O95 / 14003 ) (537.0 mg) were dissolved in ethanol (6 ml) and piperidine was added thereto (296.7 mg), followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from ethyl acetate to give Compound 26 (837.2 mg). I-NMR (270 MHz, DMSO-dg) d 2.78 (dd, J = 13.2, 7.3 Hz, 1H), 2.90 (dd, J = 13.2, 4.6 Hz, 1H), 3.29-3.39 (, 2H), 3.55 ( m, 1H), 3.80 (s, 3H), 3.82 (s, 6H), 4.55 (t, J = 5.6 Hz, 1H), 4.86 (d, J = 5.3 Hz, 1H), 7.13 (s, 2H), 7.18 (dd, J = 8.8, 2.0 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.54 (s, 1H), 7.59 (d, J = 2.0 Hz, 1H), 8.45 (s, 1H) ), 12.00 (s broad, 1H) FAB-MS m / z = 478, 480 (M ++ 1) Elemental Analysis: C23H24ClNOgS Calculated. (%): C, 57.80; H, 5.06; N, 2.93 Found (%) r C, 57.86; H, 5.13; N, 2.76 Example 27 (Z) -2- (2,3-Dihydroxypropylthio) -3- (5-fluoroindol-3-yl) -1- (3, 4, 5-trimethoxyphenyl) -2-propen-1-one (Compound 27) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (948.0 mg) obtained in Reference Example 16 and 5-fluoroindole-3-carbaldehyde (O95 / 14003) ( 489.0 mg) were dissolved in ethanol (20 ml) and piperidine (85.0 mg) was added thereto, followed by heating under reflux for 36 hours. The reaction solution is concentrated under pressure reduced and the residue purified by column chromatography on silica gel. The crystals without purifying obtained were recrystallized from a mixed solvent of ethanol and water (1: 1) to give Compound 27 (618.1 mg). RMN-1 !! (270 MHz, DMSO-dg) d 2.78 (dd, J = 13.1, 7.2 Hz, 1H), 2.90. { dd, J = 13.1, 4.7 Hz, 1H), 3.25-3.40 (m, 2H), 3.54 (m, 1H), 3.79 (s, 3H), 3.81 (s, 6H), 4.56 (t, J = 5.7 Hz , 1H), 4.87 (d, J = 5.4 Hz, 1H), 7.02 (td, J = 9.0, 2.5 Hz, 1H), 7.11 (s, 2H), 7.31 (dd, J = 9.9, 2.5 Hz, 1H) , 7.48 (dd, J = 9.0, 4.0 Hz, 1H), 7.53 (s, 1H), 8.48 (s, 1H), 11.96 (s broad, 1H) EI-MS m / z = 461 (M +) Elemental Analysis: C23H24FNOgS • 0.9H20 Calculated. (%) r C, 57.83; H, 5.44; N, 2.93 Found (%) r C, 57.89; H, 5.53; N, 2.93 Example 28 (Z) -2- (2,3-Dihydroxypropylthio) -3- (6-methylindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (Compound 28) 2- (2,3-Dihydroxypropylthio) -3 ', 4', 5'-trimethoxy-acetophenone (1.58 g) obtained in Reference Example 16 and 6-methylindol-3-carbaldehyde (975.0 mg) they were dissolved in ethanol (10 ml) and piperidine (494.5 mg) was added thereto, followed by heating under reflux for 36 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by gel column chromatography. silica. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (5r3) to give Compound 28 (1.23 g). NMR-iH (270 MHZ, CDC13) d 2.36 (s, 1H), 2.46 (s, 3H), 2.82 (dd, J = 13.9, 8.9 Hz, 1H), 3.08 (dd, J = 13.9, 4.0 Hz, 1H), 3.55 (m, 1H), 3.68 (m, 1H), 3.77 (m, 1H), 3.87 (s, 6H), 3.97 (s, 3H), 4.16 (s, 1H), 7.04 (d, J = 7.7 Hz, 1H), 7. 10 (s, 2H), 7.24 (s, 1H), 7.41 (d, J = 7.7 Hz, 1H), 7.96 (s, 1H), 8.54 (d, J = 3.0 Hz, 1H), 8.96 (e, 1H) EI-MS m / z = 457 (M +) Analysis Elemental r C24H27NOgS- 0.2H20 Calculated. (%): C, 62.51; H, 5.99; N, 3.04 Found (%): C, 62.46; H, 6.11; N, 2.95 Example 29 (Z) -2- (2,3-Dihydroxypropylthio) -3- (6-ethylindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propenyl-one (Compound 29) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (2.21 g) obtained in Reference Example 16 and 6-ethylindole-3-carbaldehyde (O95 / 14003) ( 1.21 g) were dissolved in ethanol (14 ml) and added to the piperidine funnel (596.1 mg), followed by heating under reflux for 30 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. Unpurified crystals obtained were recrystallized from a mixed solvent of ethanol and water (2: 3) to give Compound 29 (1.48 g). NMR-1H (270 MHz, DMSO-dg) d 1.22 (t, J = 7.6 Hz, 3H), 2.70 (q, J = 7.6 Hz, 2H), 2.80 (dd, J = 13.3, 7.3 Hz, 1H), 2.91 (dd, J = 13.3, 4.6 Hz, 1H), 3.33 (m, 2H), 3.55 (m, 1H), 3. 79 (s, 3H), 3.81 (s, 6H), 4.57 (t, J = 5.5 Hz, 1H), 4.87 (d, J = 5.5 Hz, 1H), 6.98 (d, J = 8.1 Hz, 1H), 7.10 (s, 2H), 7. 28 (s, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.60 (s, 1H), 8.37 (d, J = 2.3 Hz, 1H), 11.79 (d, J = 2.3 Hz, 1H) FAB-MS m / z = 472 (M ++ 1) Elemental Analysis: C25H29NOgS Calculated. (%): C, 63.68; H, 6.20; N, 2.97 Found (90) C, 63.79; H, 6.34; N, 2.93 Example 30 (Z) -2- (2,3-Dihydroxypropylthio) -3- (6-isopropylindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (Compound 30) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (1.58 g) obtained in Reference Example 16 and 6-isopropylindole-3-carbaldehyde (WO95 / 14003) (935.0 mg) is dissolved in ethanol (10 ml) and piperidine (425.8 mg) is added thereto, followed by heating under reflux for 24 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (1: 1) to give Compound 30 (1.23 g). RM -iH (270 MHz, CDC13) d 1.30 (d, J = 6.9 Hz, 6H), 2. 33 (t, J = 6.1 Hz, 1H), 2.81 (dd, J = 13.5, 8.7 Hz, 1H), 3.03 (m, 1H), 3.08 (dd, J = 13.5, 3.6 Hz, 1H), 3.56 (m , 1 HOUR) , 3. 63-3.83 (m, 2H), 3.88 * (s, 6H), 3.97 (s, 3H), 4.19 (d, J = 3.0 Hz, 1H), 7.10 (s, 2H), 7.13 (d, J = 8.3Hz, 1H), 7.30 (s, 1H), 7.43 (d, J = 8.3 Hz, 1H), 7.97 (s, 1H), 8.57 (d, J = 3.0 Hz, 1H), 8.92 (broad s, 1H) FAB-MS m / z = 486 (M ++ 1) Elemental Analysis: C26H31 OgS - 0.6H20 Calculated. (%): C, 63.45; H, 6.62; N, 2.69 Found (%): C, 63.66; H, 6.71; N, 2.90 Example 31 (Z) -3- (6-Chloroindol-3-yl) -2- (2,3-dihydroxypropylthio) -1- (3, 4, 5-trimethoxyphenyl) -2-propen-1 -one (Compound 31) 2- (2,3-dihydroxypropylthio) -3 ', 4', 5'-trimethoxyacetophenone (948.0 mg) obtained in Reference Example 16 and 6-chloroindol-3-carbaldehyde (WO95 / 14003 ) (538.5 mg) were dissolved in ethanol (20 ml) and piperidine (255.0 mg) was added thereto, followed by heating under reflux for 38 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane (1: 1) to give Compound 31 (270.3 mg). NMR-1H (270 MHz, CDCl 3) d 2.51 (s, 1H), 2.86 (dd, J = 13.9, 8.4 Hz, 1H), 3.06 (dd, J = 13.9, 4.0 Hz, 1H), 3.56 (m, 1H) ), 3.68 (m, 1H), 3.78 (m, 1H), 3.88 (s, 6H), 3.97 (e, 3H), 4.04 (e, 1H), 7.11 (s, 2H), 7.16 (dd, J = 8.9, 1.8 Hz, 1H), 7.43 (d, J = 8.9 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 7.83 (s, 1H), 8.57 (d, J = 3.0 Hz, 1H) , 9.25 (s, 1H) FAB-MS m / z = 478, 480 (M ++ 1) Elemental Analysis: C23H24ClNOgS • 0.9H20 Calculated. (%): C, 57.83; H, 5.44; N, 2.93 Found (9): C, 57.89; H, 5.53; N, 2.93 Example 32 (Z) -2- (2,3-Dihydroxypropylthio) -3- (6-fluoroindol-3-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (Compound 32) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5 '-trimethoxyacetophenone (1.62 g) obtained in Reference Example 16 and 6-fluoroindole-3-carbaldehyde [J. Med. Chem., 6., 716 (1963)] (838.2 mg) were dissolved in ethanol (10 ml) and piperidine (437.7 mg) was added thereto, followed by heating under reflux for 36 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from ethanol to give Compound 32 (638.8 mg).

NMR-XH (270 MHz, CDCl 3) d 2.34 (t, J = 6.3 Hz, 1H), 2.84 (dd, J = 13.8, 8.6 Hz, 1H), 3.08 (dd, J = 13.8, 3.8 Hz, 1H), 3.58 (m, 1H), 3.69 (m, 1H), 3.79 (m, 1H), 3.88 (s, 6H), 3.97 (s, 3H), 3.99 (d, J = 4.0 Hz, 1H), 6.97 (td, J = 8.9, 2.2 Hz, 1H), 7.11 (s, 2H), 7.15 (dd, J = 9.1, 2.2 Hz, 1H), 7.45 (dd, J = 8.9, 5.0 Hz, 1H), 7.84 ( s, 1H), 8.55 (d, J = 2.6 Hz, 1H), 9.10 (s broad, 1H) FAB-MS m / z = 462 (M ++ 1) Elemental Analysis: C23H24FNO S Calculated. (%): C, 59.86; H, 5.24; N, 3.04 Found (%): C, 59.68; H, 5.17; N, 2.89 Example 33 (Z) -3- (6-Acetamidoindol-3-yl) -2- (2,3-dihydroxy-propylthio) -1- (3,4,5-trimethoxyphenyl) -2-propen-1 -one (Compound 33) 2- (2,3-dihydroxypropylthio) -3 ', 4', 5 '-trimethoxyacetophenone (1.58 g) obtained in Reference Example 16 and 6-acetomidoindole-3-carbaldehyde (O95 / 14003 ) (1.64 g) were dissolved in ethanol (20 ml) and piperidine (690.0 mg) was added thereto, followed by heating under reflux for 38 hours. The crystals were precipitated, collected by filtration and the crystals without purifying obtained were recrystallized from a mixed solvent of ethanol, methanol, N, N-dimethylformamide and water to give Compound 33 (707.3 mg).

R N-ÍH (270 MHz, DMSO-dg) d 2.05 (S, 3H), 2.79 (dd, J = 13.4, 6.9 Hz, 1H), 2.91 (dd, J = 13.4, 5.0 Hz, 1H), 3.27- 3.38 (m, 2H), 3.54 (m, 1H), 3.79 (s, 3H), 3.81 (s, 6H), 4.55 (t, J = 5.7 Hz, 1H), 4.86 (d, J = 5.0 Hz, 1H ), 7.09 (s, 2H), 7.10 (dd, J = 8.9, 1.5 Hz, 1H), 7.38 (d, J = 8.9 Hz, 1H), 7.57 (s, 1H), 8.07 (d, J = 1.5 Hz) , 1H) 8.36 (s, 1H), 9.92 (s, 1H), 11.80 (s, 1H) EI-MS m / z = 500 (M +) Elemental Analysis: C25H28N207S Calculated. (%): C, 59.99; H, 5.64; N, 5.60 Found (%): C, 59.97; H, 5.74; N, 5.72 Example 34 (Z) -3- (6-Acetamido-l-methylindol-3-yl) -2- (2,3-dihydroxypropylthio) -1- (3,4,5-trimethoxyphenyl) -2-propen -l-one (Compound 34) Compound 33 (300.0 mg) obtained in Example 33 was dissolved in a mixed solvent of N, N-dimethylformamide and tetrahydrofuran (1: 1), and methyl iodide (93.6) was added thereto. mg) and then sodium hydride (26.4 mg, 60% mineral oil dispersion), followed by stirring for 1.5 hours. The reaction solution is subjected to splitting between chloroform and water, and the organic layer is washed successively with water and a saturated saline solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Unpurified crystals obtained were washed with chloroform and recrystallized from a mixed solvent of ethanol, N, N-dimethylformamide and water to give Compound 34 (249.7 mg). I-NMR (270 MHz, DMSO-dg) d 2.06 (s, 3H), 2.80 (dd, J = 13.2, 7.3 Hz, 1H), 2.91 (dd, J = 13.2, 4.6 Hz, 1H), 3.27-3.38 (m, 2H), 3.53 (m, 1H), 3.79 (s, 3H), 3.80 (s, 6H), 3.86 (s, 3H), 4.54 (s broad, 1H), 4.85 (d, J = 4.6 Hz , 1H), 7.09 (s, 2H), 7.14 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.54 (s, 1H), 8.01 (s, 1H), 8.37 (s, 1H), 9.92 (e, 1H) EI-MS m / z = 514 (M +) Elemental Analysis: C2gH30N2O7S Calculated. (%): C, 60.69; H, 5.88; N, 5.44 Found (%): C, 60.73; H, 5.99; N, 5.29 Example 35 3- (Indol-3-yl) -2- [(2S), (3R) -2, 3, -trihydroxybutyl-thio] -1- (3, 4, 5-trimethoxyphenyl) -2- propen-l-one (Compound 35) The 3 ', 4', 5 '-trimethoxy-2- [(2S), (3R) -2,3,4-tri-hydroxybutylthio] acetophenone (268.0 mg) obtained in the Reference Example 22 and indole-3-carbaldehyde (112.3 mg) were dissolved in ethanol (4 ml) and piperidine was added thereto. (66.0 mg), followed by heating under reflux for 96 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane to give Compoteto 35 (56.9 mg) .- 1H-NMR (270 MHz, CDCl 3) d 2.96 (dd, J = 13.6, 8.7 Hz, 1H), 3.09 (dd, J = 13.6, 4.0 Hz, 1H), 3.23 (broad s, 1H), 3.52 - 3.82 (m, 5H), 3.84 (s, 6H), 3.96 (s, 3H), 4.81 (d, J = 2.0 Hz, 1H), 7.08 (s, 2H), 7.17 (m, 1H), 7.24 (m, 1H), 7. 42 (d, J = 7.6 Hz, 1H), 7.49 (d.J = 7.6 Hz, 1H), 7.98 (s, lH), 8.65 (d, J = 2.6 Hz, 1H), 9.56 (s broad, 1H) FAB-MS m / z = 474 (M ++ 1) Elemental Analysis: C24H2? N07S • 0.6H20 Calculated. (%): C, 59.52; H, 5.88; N, 2.89 Found (%): C, 59.60; H, 5.96; N, 2.86 Example 36 3- (6-Methylindol-3-yl) -2- [(2S), (3R) -2, 3, 4 -trihydroxybutylthio] -1- (3, 4, 5-trimethoxyphenyl) -2 -propen-1-one (Compound 36) The 3 ', 4 *, 5'-trimethoxy-2- [(2S), (3R) -2, 3, 4 -trihydroxybutylthio] acetophenone (1.73 g) obtained in the Example Reference 22 and 6-methylindol-3-carbaldehyde (0.80 g) were dissolved in ethanol (10 ml) and piperidine (0.43 g) was added thereto, followed by heating under reflux for 26 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane to give Compound 36 (1.22 g). RM -iH (270 MHz, CDCl 3) d 2.43 (s, 3H), 2.96 (dd, J = 13.6, 8.7 Hz, 1H), 3.10 (dd, J = 13. 6, 4.0 Hz, 1H), 3.23 (s) broad, 1H), 3.53-3.82 (m, 5H), 3.84 (e, 6H), 3.96 (e, 3H), 4.84 (broad e, 1H), 7:00 (d, J = 8.2 Hz, 1H), 7.07 (e, 2H), 7.20 (e, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.97 (s, 1H), 8.59 (d, J = 2.6 Hz, 1H), 9.39 (s broad, 1H) FAB-MS m / z = 488 (M ++ 1) Elemental Analysis: C25H29N07S Calculated. (%): C, 61.59; H, 6.00; N, 2.87 Found (%): C, 61.26; H, 6.12; N, 2.82 Example 37 3- (6-Methylindol-3-yl) -2- [(2R), (3S) -2, 3, 4-trihydroxybutylthio] -1- (3,4,5-trimethoxyphenyl) -2 -propen-1-one (Compound 37) The 3 ', 4', 5'-trimethoxy-2- [(2R), (3S) -2, 3, 4 -trihydroxybutylthio] acetophenone (1.73 g) obtained in the Example Reference 23 and 6-methylindol-3-carbaldehyde (0.80 g) were dissolved in ethanol (10 ml) and piperidine (0.43 g) was added thereto, followed by heating under reflux for 48 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The unpurified crystals obtained were recrystallized from a mixed solvent of ethyl acetate and hexane to give Compound 37 (1.12 g). 1 H-NMR (270 MHz, CDCl 3) d 2.43 (s, 3H), 2.95 (dd, J = 13.6, 8.7 Hz, 1H), 3.10 (dd, J = 13.6, 4.0 Hz, 1H), 3.17 (broad s, 1H), 3.53 (d, J = 6.3 Hz, 1H), 3.64-3.82 (m, 4H), 3. 84 (s, 6H), 3.96 (e, 3H), 4.83 (d, J = 4.0 Hz, 1H), 7. (d, J = 8.2 Hz, 1H), 7.07 (s, 2H), 7.20 (s, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.97 (s, 1H), 8.59 (d, J = 2.6 Hz, 1H), 9.36 (s broad, 1H) FAB-MS m / z = 488 (M ++ 1) Elemental Analysis: C25H29 07S Calculated. (%): C, 61.59; H, 6.00; N, 2.87 Found (%): C, 61.56; H, 6.14; N, 2.82 Example 38 2- (2,3-Dihydroxypropylthio) -3- (indol-5-yl) -1- (3,4,5-trimethoxyphenyl) -2-propen-l-one (Compound 38a, Compound 38b ) The 2- (2,3-dihydroxypropylthio) -3 ', 4', 5 '-trimethoxyacetophenone (316.0 mg) obtained in Reference Example 16 and indole-5-carbaldehyde (145.0 mg) obtained in Reference Example 24 they were dissolved in ethanol (5 ml) and piperidine (850.0 mg) was added thereto, followed by heating under reflux for 72 hours. The reaction solution is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel. The obtained mixture is purified by means of the preparative CLAP (ODS packed YMC, SH-343-5, S-5, 120A, 250 x 20 mm, acetonitrile: water = 35:65) and the eluted materials are concentrated under reduced pressure to give Compound 38a (36.4 mg, Form Z) and Compound 38b (17.0 mg, form E). Compound 38a: NMR-1H (270 MHz, CDCl 3) d 2.01 (broad s, 1H), 2.62 (broad e, 1H), 2.82 (dd, J = 13.8, 8.4 Hz, 1H), 2.99 (dd, J = 13.8, 4.0 Hz, 1H), 3.54 (dd, J = 11.8, 5.8 Hz, 1H), 3.66 (dd, J = 11.4, 3.5 Hz, 1H), 3.78 (m, 1H), 3.92 (s, 6H), 3.99 (s, 3H), 6.64 (s broad, 1H), 7.21 (s, 2H), 7.28 -7.31 (m, 2H), 7.46 (broad d, J = 8.6 Hz, 1H), 7.84 (dd, J = 8.6, 1.3 Hz, 1H), 8.25 (s, 1H), 8.85 (s, 1H) FAB- MS m / z = 444 (M ++ 1) Compound 38b: RM -iH (270 MHz, CDCl 3) d 2.66 (broad s, 1H), 2.81 (dd, J = 14.3, 6.9 Hz, 1H), 2.89 (dd, J = 14.3, 5.5 Hz, 1H), 3.23 (broad s, 1H), 3.67-3.98 (m, 3H), 3.83 (s, 6H) , 3.90 (s, 3H), 6.47 (broad s, 1H), 7.03 (dd, J = 8.6, 1.3 Hz, 1H), 7.17-7.22 (m, 2H), 7.28 (s, 2H), 7.45 (s, 1H), 7.52 (s, 1H), 8.39 (s, 1H) FAB-MS m / z = 444 (M ++ 1) In accordance with the present invention, propenone derivatives having excellent antitumor activity can be provided.

Claims (4)

1. CLAIMS 1. A propenone derivative repreened by the following formula (I): characterized in that R1 represents a lower alkyl substituted or YR5 (in which Y represents S or O, and R5 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or a substituted or unsubstituted cyclic ether residue substituted), R2 and R3 independently represents hydrogen, substituted or unsubstituted lower alkyl or aralkyl, or R2 and R3 are combined to represent substituted or unsubstituted methylene or ethylene, R4 represents hydrogen, hydroxy, lower alkyl, substituted or unsubstituted aralkyl, lower alkoxy, substituted or unsubstituted aralkyloxy or halogen, and X represents substituted or unsubstituted indolyl or a pharmaceutically acceptable salt thereof.
2. 2. A propenone derivative or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that R1 represents YR ^ (in that Y and R ^ have the same meanings as defined in the above).
3. 3. A propenone derivative or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that R1 represents lower alkyl substituted.
4. 4. A pharmaceutically acceptable derivative of propenone or eal of the myelin according to claims 1 to 3, characterized in that X represents substituted or unsubstituted indole-3-yl.