MXPA97006585A - Derivatives of imidazol and medicinal composition of mis - Google Patents

Abstract

Underivate of imidazole represented by the following general formula (I), a salt thereof, or a hydrate thereof, or a solvate thereof. (See Formula) wherein: A: represents a lower alkylene group unsubstituted or substituted by a hydroxyl group, an aryl group, a lower alkylidene group, or an oxo group (= 0), X: a methylene group or a group represented by the formula -NR2-, R1: a hydrogen atom, a lower alkyl group, or an aralkyl group, and R2: a hydrogen atom or a lower alkyl group. The compounds have a steroid lyase inhibitory activity 17 = 20, and are useful in the treatment and prevention of diseases such as prostate cancer, benign prostatic hyperplasia, breast cancer, mastopathy, hysteromyoma, endometriosis, and the like.

Description

DERIVATIVES OF IMIDAZOL AND MEDICINAL COMPOSITION OF THE SAME TECHNICAL FIELD This invention relates to a novel imidazole derivative particularly to a novel imidazole derivative having carbazole or fluorene • or a salt thereof, which shows a steroid lyase inhibitory activity 17-20, and is useful as a medicine.

BACKGROUND TECHNIQUE It is known that an enzyme called steroid lyase 17-20, has a role in the production of androgen from cholesterol in the body, in the final stage of its biosynthetic trajectory. The steroid lyase 17-20 uses 17a-hydroxypregnenolone and 17o: -hydroxyprogesterone as the substrates, which are synthesized from cholesterol, and have a carbon substituent at the 17β position, and dissociates the bond between the carbon at position 17 and carbon at position 20 of the carbon substituent, thus forming idroepiandrosterone and androstenedione, respectively. Consequently, the production of androgen, as well as that of rheogen, which is synthesized from androgen as the substrate, could decrease by inhibiting the enzymatic activity of steroid lyase 17-20, which makes it possible to prevent and treat different diseases. where the androgen and / or the estrogen takes part as an aggravating factor. Examples of these diseases wherein androgen and estrogen take part as aggravating factors include prostate cancer, and benign prostatic hyperplasia, virilism, hirsutism, breast cancer, mastopathy, hysteromyoma, endometriosis and the like. On the other hand, it is well established that the reduction of serum androgen level is useful for the treatment of different diseases, such as prostate cancer and the like. Orchiotomy, an LH-RH agonist, or an androgen antagonist, is used in clinical practice. However, oiquotomy is mentally unacceptable, and the LH-RH agonist can block the androgen of the testicles but not of other organs, and exhibits a transient reprimand phenomenon due to its agonist action. In the case of the androgen antagonist, it has recently been known that its effect is attenuated by the mutation of the androgen receptors.As a consequence, it has been proposed to block the effects of the androgen on the receptors (blocked total androgen), and have made attempts to use an LH-RH agonist and an androgen antagonist in combination.A compound that inhibits steroid lyase 17-20 is considered a drug that can perform a total androgen blockade, through strong inhibition of the action of androgen due to its function, and consequently, it is expected to be a useful drug for the treatment of prostate cancer and the like.In addition, by being able to reduce estrogen, a lyase inhibitor is expected to steroid 17-20 is a more effective therapeutic agent than a therapeutic agent that can only block the action of androgen in the treatment of benign prostatic hyperplasia, and is expected to make it a drug with fewer side effects. As inhibitors of steroid lyase 17-20, steroidal non-steroidal compounds have been synthesized. As an example of the non-steroidal steroid lyase inhibitor 17-20, a benzimidazole derivative substituted by (1H-imidazol-1-ylmethyl) disclosed in a Japanese Published Unexamined Patent Application (Kokai) No. is known. 64-85975, which is a compound wherein a substituted benzimidazolyl group and an imidazolyl group are linked by a methine carbon or a methylene carbon. Also, International Publication Number WO 94/27989 discloses that a carbazole derivative substituted by a pyridin-3-ylmethyl group, a pyridin-4-ylmethyl group, or a [1, 2,4] triazol-1-ylmethyl group, has a 17-20 steroid lyase inhibitory activity. However, the inhibitory activity of these compounds towards the steroid lyase 17-20 is still insufficient. In addition, the inventors of the present invention have reported that an imidazolylalkyl amine derivative represented by the following general formula (A): as disclosed in the previously published International Publication Number WO 95/04723, it has a steroid lyase inhibitor activity 17-20. The R of this general formula (A) is "a substituted or unsubstituted phenyl group, a substituted or unsubstituted bicyclic or tricyclic hydrocarbon ring group having a fused benzene ring, or a substituted bicyclic or tricyclic fused heterocyclic ring group or unsubstituted having a heterocyclic ring containing an oxygen atom and / or a sulfur atom and / or a nitrogen atom such as the heteroatom and a condensed benzene ring 11, and the carbazolyl group and the fluorenyl group are disclosed as their However, although these compounds have an excellent activity to inhibit steroid lyase 17-20 in vi tro, their pharmacological effect in vivo is still insufficient.As described above, different studies have been made, but the development of an excellent steroid lyase inhibitor 17-20 is still an important object in the field of medical treatment, DISCLOSURE OF THE INVENTION The inventors of the present invention conducted extensive studies, and as a result, discovered that the inhibitory activity of steroid lyase 17-20 of an imidazole derivative represented by the following general formula (I), wherein a imidazole ring with a carbazole ring or A fluorene ring by means of a lower alkylene group, or a salt thereof, is excellent not only in vi tro but also in vivo, thus resulting in the embodiment of the present invention. In accordance with the above, the present invention is an imidazole derivative represented by the following general formula (I), a salt thereof, or hydrate thereof, or a solvate thereof: (The symbols in the formula have the following meanings: A: a lower alkylene group unsubstituted or substituted by a hydroxyl group, an aryl group, a lower alkylidene group, or an oxo group (= 0), X: a methylene group or a group represented by the formula -NR2-, R: a hydrogen atom, a lower alkyl group, or an aralkyl group, and R: a hydrogen atom or a lower alkyl group). Among the compounds (I) of the present invention, a preferable compound is a compound wherein A is linked in the 4-position or the 5-position of the imidazole ring, a salt thereof, a hydrate thereof, or a solvate of the same; more preferably, an imidazole derivative wherein A is linked in the 2-position or the 3-position of the ring: a salt thereof, a hydrate thereof, or a solvate thereof; an imidazole derivative wherein A is a lower alkylene group unsubstituted or substituted by an aryl group or a lower alkylidene group, a salt thereof, a hydrate thereof, or a solvate thereof; in a particularly preferred manner, an imidazole derivative wherein 'A is a lower alkylene group unsubstituted or substituted by a lower alkylidene group, a salt thereof, a hydrate thereof, or a solvate thereof; an imidazole derivative wherein X is a group represented by the formula NR i; more preferably, 2- [1- (1H-imidazol-4-yl) ethyl] -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof; 3- [1- (1H-imidazol-4-yl) ethyl] -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof; 2- (1H-imidazol-4-ylmethyl) -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof; and 3- (1H-imidazol-4-ylmethyl) -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof. Also, the pharmaceutical composition containing the compound of the present invention, as another object of the present invention, is a pharmaceutical composition comprising a compound represented by the above-mentioned general formula (I), or a pharmaceutically acceptable salt thereof as its active ingredient; a pharmaceutical composition that is a 17-20 steroid lyase inhibitor; especially a pharmaceutical composition that an agent for the prevention or treatment of diseases caused by androgen and / or estrogen; illustratively, a pharmaceutical composition that is an agent for the prevention or treatment of prostate cancer, benign prostatic hyperplasia, virilism, hirsutism, breast cancer, mastopathy, hysteromyoma, and endometriosis. The following describes the present invention in detail. Unless otherwise noted, the term "lower" as used herein, in the definition of the general formula, means a straight or branched carbon chain having from 1 to 6 carbon atoms. Illustrative examples of the "lower alkyl group" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, tertiary butyl, pentyl, isopentyl, neopentyl, tertiary pentyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl. , hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-di-ethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3, 3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl and the like. Among these groups, alkyl groups having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, and the like, are preferable. Illustrative examples of the "lower alkylene group" include methylene, ethylene, methylmethylene, trimethylene, 1-methylethylene, 2-methylethylene, ethylmethylene, tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, 1-ethylethylene, 2-ethylethylene. , 1,2-dimethylethylene, propyl ethylene, isopropylmethylene, pentamethylene, 1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene, 4-methyltetramethylene, 1-ethyltrimethylene, 2-ethyltrimethylene, 3-ethyltrimethylene, 1,1-dimethyltrimethylene, 2 , 2-dimethyl-rilethylene, 3, 3-dimethyltrimethylene, hexamethylene, 1-metylpentane-1-ylene, 2-methylpentane-1-ene, 3-me t -ylpentane-1-ene, 4 -methylpentane-1-ene, -methylpentamethylene, 1,1-dimethyltetramethylene, 4,4-dimethyltetramethylene, and the like. Among these groups, alkylene groups having 1 to 4 carbon atoms are preferred, and more methylene, methylmethylene, ethylmethylene, propylmethylene, isopropylmethylene, and the like are preferred. The "lower alkylidene group" is a straight or branched alkylidene group having from 2 to 6 carbon atoms, and its illustrative examples include methylidene (CH2 =), ethylidene (CH3-CH =), propylidene (CH3-CH2-CH = ), CH3 \ isopropylidene (Crin) > Butylidene (CH3-CH2- CH2-CH =), methylpropylidene, pentylidene, methylbutylidene, ethylpropylidene, hexylidene, methylpentylidene, ethylbutylidene, propylpropylidene and the like, of which methylidene, ethylidene, or isopropylidene are preferred. The lower alkylene group substituted by a lower alkylidene group is a group wherein two hydrogen atoms bonded with an optional carbon atom of a lower alkylene group are substituted by the double bond of a lower alkylidene group, and their preferred examples include vinylidene ( -C-) II CH2 exoisopropylidenemethylene (-C-), C (CH3) 2 exoethylidenemethylene (-c-), II CHCH3 exornetilenetileño (), and exopropylidenethylene (_C_ H2-) • II (CH3) 2 The "lower alkylene group" mentioned above may be substituted by a hydroxyl group, an aryl group, or an oxo group (= 0) in an optional position. * In this case, the term "aryl group" means a carbon ring aryl, and its illustrative examples include phenyl, biphenyl, naphthyl, and the like, of which phenyl is preferred. Accordingly, illustrative examples of the lower alkylene group which may be substituted by a hydroxyl group, an aryl group, or an oxo group, include hydroxy ethylene (-CH-) »(hydroxy) (methyl) methylidene (, hydroxyethylene (-CH2-CH-f -CH-CH2), I I OH OH hydroxytrimethylene (_CH_CH2_CH2_ _CH2-CH-CH2-, -CH2-CH2-CH-) OH OH OH phenylmethylene ( phenylethylene ( benzylethylene ( f enyltrimethylene ( naphthalethylene (), carbonyl - C -) carbonylmethylene (_r_r.} {. - -), carbonylethylene or (-C- (CH2) 2 -, - (CH2) 2 -C-), and the like. || II o, 0 As the substituent for the "lower alkylene group", a lower alkylidene group having from 1 to 3 carbon atoms, a phenyl group, or the like is preferable. The "aralkyl group" means a group wherein the aforementioned aryl group is substituted at an optional position of the aforementioned lower alkyl group, and its illustrative examples include benzyl, phenethyl, naphthylmethyl and the like. The compound of the present invention can form a salt with inorganic acid or an organic acid in some cases, and these salts also have the inhibitory activity of steroid lyase 17-20, as well as the free base. Examples of the preferable salts include salts with inorganic acid, such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, and with organic acid such as formic acid, acetic acid, acid propionic, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, and the like. Depending on the class of substituents, it may also form a salt with an alkaline metal or a pharmaceutically acceptable alkaline earth metal (eg, sodium, potassium or magnesium, or calcium), or a salt with ammonia or an organic amine, such as triethyl amine or similar. The compound of the present invention may have an asymmetric carbon atom, depending on the class of the aforementioned group A, or depending on the substituents, and this compound exists in forms of optical isomers, based on the asymmetric carbon atom, or else in diastereomeric forms when it has two or more asymmetric carbon atoms. In addition, it can also exist in geometrical isomer forms (cis form and trans form), or in tautomeric forms, based on the double bond. The isolated forms of these different isomers and mixtures thereof are all included in the present invention. Also, the compound of the present invention may exist in the form of different hydrates, different solvates such as with methanol, ethanol, and the like, tautomers, polymorphic forms and the like, and the isolated forms of these compounds and mixtures thereof. all are included in the present invention. The compound of the present invention can be produced by the use of different synthetic methods. Their typical methods of production are exemplified in the following. In relation to this, when X in the compound (I) of the present invention, prevents the reactions described below, the reactions can be carried out using appropriate protecting groups. For example, when X is -NH-, it is converted to -NP- using a protecting group P. The group P is a conventional amino protecting group, and its illustrative examples include a benzyl type protecting group such as benzyl, benzhydryl, trityl, 4-methoxybenzyl or the like, an acyl group such as formyl, acetyl, propionyl, or the like , an aralkyloxycarbonyl group such as benzyloxycarbonyl or the like, a lower alkoxycarbonyl group such as tertiary butoxycarbonyl or the like, a sulfonyl group such as tosyl, benzenesulfonyl, methanesulfonyl, or the like, an aminoacetal type protecting group, such as methoxymethyl , tetrahydropyranyl or the like, a trialkylsilyl group such as trimethylsilyl, tertiary butyl-dimethylsilyl, or the like.

Method 1 (The symbols of the form are as follows: Hal: a halogen atom, B: a single bond or an alkylene group having from 1 to 5 carbon atoms, and may be substituted by an aryl group, P2: a protecting group of the benzyl type such as trityl or the like, R3a: a lower alkyl group or an aryl group, RJ: a hydrogen atom, a lower alkyl group, or an aryl group, and R -M: an organometallic reagent such as a lithium alkyl, an aryl lithium, a Grignard reagent or the like, (M is lithium, -Mg-Hal, or the like) will be applied the same later herein). The halogen atom means a fluorine atom, a chlorine atom, a bromine atom, an iodine atom. This production method is carried out in the following way. First step: This is a step where a secondary (IV) alcohol is obtained by allowing a halogen (II) compound to react with a metal reagent (an alkyl lithium such as normal butyl lithium or the like, or metallic magnesium or the like) in an organic solvent such as tetrahydrofuran (THF), dioxane, diethyl ether, dimethoxyethane, or the like, and then the resulting organometallic reagent is allowed to react with its corresponding amount of the reaction, preferably 1 to 2 equivalents, of an aldehyde (III) compound at low temperature, -the preference of -100 ° C to 0 ° C. Second step: This is a step where a ketone compound (V) is obtained from the secondary alcohol (IV), by means of a conventional oxidation reaction with an oxidizing agent (manganese dioxide, chromic acid, or the like), in an organic solvent such as dichloromethane, dichloroethane, chloroform, tetrahydrofuran, dioxane, benzene, or the like. Third step: This is a step where a tertiary alcohol (VII) is obtained by allowing the ketone compound (V) to react with its corresponding amount of the reaction, from 1 to 2 equivalents, of an organometallic reagent (VI) (reactive of Grignard, alkyl lithium reactive, or the like) in an organic solvent such as tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, or the like, from 0 ° C to room temperature. The above second and third steps are performed when R is a lower alkyl group or an aryl group. Step Four: This is a step where an imidazole compound (la ') is obtained by allowing the secondary alcohol (IV) or the tertiary alcohol (VII) to undergo the reaction in the presence of 10 to 100 weight percent of a catalyst (palladium on 10 percent carbon, palladium, palladium hydroxide, palladium oxide, platinum, platinum oxide, or the like) in an organic solvent such as methanol, ethanol, acetic acid, or the like, under a hydrogen atmosphere , from the ambient temperature to the reflux temperature. In this connection depending on the class of the protecting group P2 (for example, trityl group), a deprotection reaction can be carried out by treating it under an acidic condition after the completion of the reaction of the first step (when RJ is an hydrogen) or the third step (when R is a lower alkyl group or an aryl group), thereby preparing a secondary alcohol (IVa) or a tertiary alcohol (Vlla) shown below, from which the compound (the ') by the fourth step.

(IV a) (VII a) Also, tertiary alcohol (VII) can be obtained without employing the second step and the third step, by using a ketone compound (the following formula Illa) in place of the aldehyde compound (III) in the first step. In the same way, a substituted imidazole (Ib) can be obtained without using Method 2, by using an aldehyde compound (Illb) in place of the aldehyde compound (III) in the first step.

P2 (In the above formulas, R a represents a lower alkyl group or an aralkyl group, the same will apply hereinafter).

Method 2 (I b) In this production method, a substituted imidazole (Ib) is obtained. First step: This is a step where a carbamoyl compound (VIII) is obtained by allowing the imidazole compound (la) to react with its corresponding amount of the reaction, from 1 to 5 equivalents, of dimethylcarbamoyl chloride in a solvent organic compound such as acetonitrile, tetrahydrofuran, dimethyl formamide (DMF) or the like, from room temperature to reflux temperature. Second step: This is a step where the substituted imidazole compound (Ib) is obtained by allowing the carbamoyl compound (VIII) to react with a corresponding amount of the reaction or an excessive amount of an alkyl halide or an aralkyl halide (IX) in an organic solvent, such as acetonitrile, tetrahydrofuran, dimethyl formamide, or the like, from room temperature to reflux temperature, to give an onium compound, and then allowing the resulting onium compound to react with ammonia .

Method 3 aso He passed (The symbols in the formula are as follows: PJ: a protecting group, such as a thioalkyl group, a thioaryl group, or the like, and R: a hydrogen atom, a lower alkyl group, or an aryl group; same later in the present).

In this production method, a substituted imidazole (le) is obtained. First step: This is a step in which a protected imidazolyl substituted alcohol (XII) is obtained, allowing an imidaz l '(X) protected with a thioalkyl group or a group, thioaryl, to react with a base (an alkyl lithium such as normal butyl lithium or the like, or a lithium amide reagent such as di-isopropyl lithium amide or the like (in an organic solvent such as tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane or the like, and then the organometallic reagent is allowed The resulting reaction reacts with its corresponding amount of the reaction, from 1 to 2 equivalents, of an aldehyde or ketone (XI) at a low temperature, preferably from -100 ° C to 0 ° C. Second step: This is a step in where an alcohol substituted by imidazolyl (XIII) is obtained, by removing the protective group of the imidazole ring of the compound (XII), allowing it to undergo the reaction in an organic solvent such as methanol, ethanol, or the like, in the presence of Raney nickel or the like, from room temperature, to reflux temperature. Third step: This is a step where a compound (le) of the present invention is obtained, allowing the alcohol substituted by imidazolyl (XIII) to undergo the reaction in the presence of 10 to 100 weight percent of a catalyst (palladium) on carbon, at 10 percent, palladium, palladium hydroxide, palladium oxide, platinum, platinum oxide, or the like) in an organic solvent such as methanol, ethanol, acetic acid, or the like, under an atmosphere of hydrogen, the ambient temperature at the reflux temperature.

(Alternative Method) The compound (le) of the present invention can be obtained by the addition of an acid such as a trifluoroacetic acid, trifluoroborane or the like, to the alcohol substituted by imidazolyl (XIII) in an organic solvent such as dichloromethane, dichloroethane, chloroform, tetrahydrofuran, dioxane, benzene, trifluoroacetic acid, or the like, and the reaction is carried out at 0 ° C to the reflux temperature in the presence of the corresponding amount of the reaction or of an excessive amount of a reducing agent, such as a trialkylsilane or the like.

Method 4 (I f) (In the above formulas, R and R ° may be the same or different from each other, and each represents a hydrogen atom or a lower alkyl group). This is a method for preparing a compound (le) or (If) of the present invention, which has a lower alkylidene group. The compound (le) or (If) can be prepared by performing the dehydration of the tertiary alcohol (VII) or (XIII) mentioned above of Method 1 or 3, under an acidic condition, with an acid such as hydrochloric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, or the like, in an organic solvent such as methanol, ethanol, tetrahydrofuran, dioxane, dichloromethane, dichloroethane, chloroform, benzene, acetic acid, trifluoroacetic acid or the like, - and then the steps shown in the respective production methods are performed as the occasion demands.

Method 5 P2 (In the above formulas, R7 is a lower alkyl group). First step: This is a step where a phosphonate compound (XV) is obtained, allowing a halomethyl compound (XIV) to react with its corresponding amount of the reaction of a trialkyl phosphite in an organic solvent such as tetrahydrofuran, dioxane , benzene, dimethyl formamide, or the like, from room temperature to reflux temperature. Second step: It is a step where an olefinic compound (XVI) is obtained (it includes two geometric isomers), allowing the phosphonate (XV) to react with its corresponding amount of the reaction, from 1 to 2 equivalents, of an aldehyde compound (III) from 0 ° C to the reflux temperature, in an organic solvent such as tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether, benzene or the like, in the presence of a base (sodium hydride, potassium hydride, tertiary butoxide potassium, potassium bistrimethylsilyl amide, an alkyl lithium such as normal butyl lithium or the like, or a lithium amide such as diisopropyl amide of lithium or the like, etc.). Third step: This is a step where the deprotection of the imidazole ring is carried out, allowing the olefinic compound (XVI) obtained in the second step to undergo the reaction under an acidic condition (hydrochloric acid, acetic acid, trifluoroacetic acid, acid). p-toluenesulfonic, or the like), in an organic solvent such as methanol, ethanol, tetrahydrofuran, dioxane, acetic acid, trifluoroacetic acid, or the like, from room temperature to reflux temperature. Fourth step: This step is carried out by a conventional catalytic hydrogenation method. In this step, a compound (Id) of the present invention is obtained by reducing the olefinic compound (XVII) obtained in the third step, in the presence of a catalyst (palladium, palladium hydroxide, palladium oxide, platinum, oxide). of platinum, or the like) in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, dioxane, or the like, under an atmosphere of hydrogen. When the protecting group P can be removed by catalytic hydrogenation, the compound (Id) can be obtained by the fourth step directly from the compound (XVI), without using the third step.

Method 6 N N-P4 (In the above formulas, P represents a protecting group, such as trimethylsilyl or the like). This production method is an alternative method for the production of the compound (Ig) of the present invention, which has a methylene group. The compound (Ig) can be prepared by allowing a halomethyl compound (XIV) to react with an imidazole (XVIII) protected with a protecting group such as a trimethylsilyl group or the like, in an organic solvent such as chloroform or the like, in the presence of a Leyis acid catalyst such as titanium tetraoxide or the like, with cooling or at room temperature. In any of these production methods, the removal of the protecting groups is carried out in a conventional manner. For example, it can be carried out by an oxidation reaction, a reduction reaction, or a hydrolysis reaction under an acidic or basic condition. The compounds thus prepared of the present invention are isolated and purified as a free compound or as a salt thereof, a hydrate thereof, different types of solvates thereof, or in a polymorphic form. A pharmaceutically acceptable salt of the compound (I) of the present invention can be produced, by applying the compound to a salt formation reaction, normally employed. The isolation and purification are carried out by the application of usual chemical procedures, such as extraction, fractional crystallization, different types of fractional chromatography, and the like. In addition, the optical isomers can be separated as a stereochemically pure isomer, by the selection of an appropriate starting material compound, or by the use of a racemic resolution method of racemic compounds (such as a method wherein it is formed a diastereomeric salt with a general optically active acid, and then subjected to optical resolution).

INDUSTRIAL APPLICABILITY The compound of the present invention has a function to inhibit the activity of steroid lyase 17-20, which is an enzyme that has a role in the formation of androgen from cholesterol in the body. Accordingly, due to its action to inhibit the synthesis of androgen and of estrogen that is synthesized from androgen as the substrate, the compound of the present invention is useful as an agent for the prevention and treatment of different diseases where they take part the androgen and estrogen as aggravating factors, such as prostate cancer, benign prostatic hyperplasia, virilism, hirsutism, breast cancer, mastopathy, hysteromyoma, endometriosis and the like.

The utility of the compound of the present invention has been confirmed by the following tests. (1) Measurement of the inhibition of rat steroid lyase activity 17-20 [in vitro]. This was done according to the method described in J. Steroid Bioche. , volume 33, number 6, 1191-1195, (1989). The testicles of male Wistar rats were cut from weeks of age, they were homogenized, and then centrifuged to give microsomes. The microsomal protein (50 micrograms), [1, 2-H] -17a-h? Drox? Progesterone were dissolved 1 μM (5.55 x 10 dpm), and a test compound, in 150 microliters of 50 mM phosphate buffer (pH 7.4), a solution of NADPH was added and then the mixture was incubated 37 ° C for 60 minutes 4 Then 400 microliters of a mixed solution of methanol and tetrahydrofuran (2: 3) were added, and the mixture was subjected to centrifugation, and then the radioactivities of the substrate and the product formed (androstenedione and testosterone) were measured. ), in the resulting supernatant by high performance liquid chromatography (HPLC) equipped with a radioisotope detector to examine the activity of the test compound to inhibit steroid lyase 17-20.

The results are shown in Table 1.

Table 1 1) (WO 94/27989, Example 2) From the above results, it was confirmed that the compounds of the present invention have excellent effects compared to the control compound. (2) Measurement of inhibition of rat testosterone synthesis [in vivo]. This was done according to the method described in J. Steroid Bioche. , volume 32, Number 6, 781-788 (1989). Each test compound was "orally administered to male Wistar rats at 10 weeks of age." After a predetermined period of drug administration, each animal was decapitated to collect the blood, and the testosterone concentration in the sample was measured. serum thus prepared by a radioisotope assay, to calculate the inhibition of testosterone synthesis.As a result, the compound of the present invention showed a strong activity to inhibit the synthesis of testosterone. (3) Reduction in the weight of the prostate in Each test compound was orally administered every day to male Wistar rats at 10 weeks of age, and the weight of the prostate was measured two weeks later As a result, the compound of the present invention showed strong action to reduce the weight of the prostate As the results of these pharmacological tests, it was confirmed that the compound of the present invention has a excellent activity to inhibit steroid lyase 17-20 both in vi tro and in vivo. In addition, the compound of the present invention is also excellent in terms of duration of action and specificity of the enzyme. The pharmaceutical composition containing one or two more of the compounds of the present invention, represented by the general formula (I), and pharmaceutically acceptable salts, hydrates, and the like thereof, as the active ingredient, is prepared in tablets, powders, fine granules, granules, capsules, pills, solutions, injections, suppositories, and the like, using pharmaceutical carriers, excipients, and other additives generally used, and administered orally or parenterally. The dose is optionally decided, taking into consideration the symptoms, age, sex, weight, and the like of each patient to be treated, but the drug is administered orally within the scale of 0.1 to 100 milligrams, Preference of 0.1 to 10 milligrams per day per adult, dividing the daily dose by one to several doses per day, or administered parenterally within the range of 0.1 to 100 milligrams per day per adult by dividing the daily dose by one to several doses per day. day, or within the scale of 1 to 24 hours a day by continuous intravenous infusion. As a matter of course, since the dose varies under different conditions as described above, in some cases a smaller dose than the previous range may be sufficient. The solid composition for use in oral administration in accordance with the present invention includes tablets, powders, granules and the like. In this solid composition one or more active substances are mixed with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinyl pyrrolidone, aluminum magnesium silicate. In the usual manner, the composition may contain other additives than the inert diluent, such as a lubricant (e.g., magnesium stearate or the like) a disintegrating agent, (e.g., calcium cellulose glycolate or the like), a stabilizing agent , (for example, lactose or 'similar), and a solubilization aid (eg, glutamic acid, aspartic acid, or the like). If necessary, the tablets or pills may be coated with a film of a gastric or enteric substance such as sucrose, gelatin, hydroxypropyl cellulose, cellulose phthalate, hydroxypropylmethyl, and the like. or similar. The liquid composition for oral administration includes pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, and the like, and contains an inert diluent generally used, such as purified water or ethanol. In addition to the inert diluent, this composition may also contain auxiliary agents such as a wetting agent, a suspending agent, and the like, as well as sweeteners, flavors, flavors and antiseptics. Injections for parenteral administration include solutions, suspensions, and aqueous or non-aqueous aseptic emulsions. Examples of the aqueous solutions and suspensions include distilled water for use in injection, and physiological saline. Examples of the non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil or the like, alcohols such as ethanol or the like, and surface active agents such as polysorbate 80 (tradename) or Similary. This composition may further contain additive agents such as an antiseptic, a wetting agent, an emulsifying agent, a dispersing agent, a stabilizing agent (for example, lactose), and an auxiliary agent of the solubilization (for example, glutamic acid or aspartic acid). ). These compositions are sterilized by filtration through a bacteria retention filter, a germicide mixture, or irradiation. Alternatively, they can be used by first forming them into sterile solid compositions, and dissolving them in sterile water or in a sterile solvent for use in injections before use.

BEST MODE FOR CARRYING OUT THE INVENTION The following illustratively describes the present invention with reference to the examples. In connection with this, the present invention is not limited by the compounds of the examples. Also, the novel materials to be used in the present invention are described as reference examples.

Reference Example 1 2-bromo-9-tosyl-9H-carbazole 1.32 grams (33.0 mmol) of sodium hydride (60 percent in oil) were added to a solution of 2-bromo-9H-carbazole (7.39 grams, 30.0 millimoles) in tetrahydrofuran (110 milliliters), and the mixture was heated to reflux for 30 minutes. After cooling to room temperature, 5.72 grams (30.0 mmol) of tosyl chloride was added to this solution, and the mixture was stirred at room temperature for 20 minutes. This solution was poured into 5 percent aqueous citric acid, and extracted with vinyl acetate. The organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was then evaporated under reduced pressure to give 12.42 grams of crude crystals. The crude crystals were recrystallized from normal ethyl acetate-hexane, to give 8.21 grams of the title compound as white crystals. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.26 (3H, s) f 7.32 (2H, d, J = 9Hz), 7.46 (1H, t, J = 8Hz), 7.59-7.65 (2H, m), 7.76 (2H, d, J = 9Hz) , 8.12-8.17 (2H, m), 8.22 (1H, d, J = 9Hz), 8.39 (1H, d, J = 2Hz).

Reference Example 2 The compound of Reference Example 2 was obtained in the same manner as Reference Example 1. 9-Benzenesulfonyl-3-bromo-9H-carbazole Starting compounds: 3-bromo-9H-carbazole and benzenesulfonyl chloride . Spectrum of nuclear magnetic resonance (DMS0-d6 internal standard TMS). d: 7.45-7.53 (3H, m), 7.61-7.66 (2H,), 7.74 (1H, dd, J = 2Hz, 9Hz), 7.85-7.87 (2H, m), 8.21-8.26 (3H, m), 8.46 (1H, d, J = 2Hz).

Reference Example 3 2-bromo-9-tetra idropyranyl-9H-carbazole A mixture of 24.61 grams (100 millimoles) of 2-bromo-9H-carbazole, 250 milliliters of methylene chloride, 11.4 milliliters (125 millimoles) of 3, 4-dihydro-2H-pyran, and 1.16 grams (5.0 mmol) of camphorsulfonic acid, was stirred at room temperature for 30 minutes. The reaction solution was poured into 1N aqueous sodium hydroxide, and partitioned. The resulting organic layer was washed with water and brine, and dried over sodium sulfate. The solvent was then evaporated under reduced pressure, to give a crude yellow and oily product. The crude product was crystallized from methanol, to give 23.80 grams of the title compound as white crystals. Nuclear magnetic resonance spectrum (DMSO-d ^ internal standard TMS). 6: 1.62 (1H, d, J = 13Hz), 1.72-1.89 (3H, m), 1.96-1.98 (1H,), 2.26-2.34 (1H, m), 3.78-3.83 (1H, m), 4.14- 4.16 (1H, m), 6.00 (1H, dd, J = 2Hz, 11Hz), 7.24 (1H, t, J = 7Hz), 7.36 (1H, dd, J = 2Hz, 9Hz), 7.45-7.48 (1H, m), 7.80 (1H, d, J = 8Hz), 8.00 (1H, d, .J = lHz), 8.10 (1H, d, J = 8Hz), 8.16 (1H, d, J = 7Hz).

Reference Example 4 The compound of Reference Example 4 was obtained in the same manner as Reference Example 1. 3-bromo-9-tosyl-9H-carbazole Starting compounds: 3-bromo-9H-carbazole and tosyl chloride . Fjpectro of nuclear magnetic resonance (DMS0-d6, internal standard TMS). d: 2.24 (1H, s), 7.28 (2. |, d, J = 8Hz), 7.46 (1H, t, J = 7Hz), 7.62 (1H, t, J =? 7Hz), 7.72-7.75 (3H , m), 8. 07-8.30 (3H, m), 8.45 (1H, d, J = 2Hz).

Example 1 a) (9-tosyl-9H-carbazol-2-yl) (1-triyl-1H-imidazol-4-yl) methanol A solution of 2-bromo-9-tosyl-9H-carbazole (6.00 grams, 15.0 mmol) in tetrahydrofuran (60 milliliters), cooled to -70 ° C under an argon atmosphere. Normal butyl lithium (9.2 milliliters of a 1.64 M solution in hexane, 15.1 mmol) was added dropwise and then a solution of l-trityl-lH-imidazole-4-carbaldehyde (5.08 grams, 15.0 mmol) in tetrahydrofuran (60 milliliters) to this solution, less than -70 ° C. The reaction mixture was allowed to warm to room temperature, then poured into 5 percent aqueous citric acid, and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution with chloroform-ethyl acetate) to give 4.69 grams (7.11 mmol) of the title compound as white crystals. Spectrum of nuclear magnetic resonance (DMS0-d6, standard ii ^ erno TMS). d: 2.20 (3H, s), 5.79 (1H, d, J = 5Hz), 5.86 (1H, d, J = 5Hz), 6.87 (1H, s), 7.12-7.14 (8H, m), 7.34-7.45 (12H, m), 7.54 (1H, t, J = 7Hz),; 7.64 (2H, d, J = 8Hz), 8.02 (1H, d, J = 8Hz), 8.07 (1H, d, J = 7Hz) , 8.23 (1H, d, J = 9Hz), 8. 27 (1H, s). b) ketone (9-tosyl-9H-carbazol-2-yl) (1-trityl-lH-imidazole-4-yl) A mixture of 4.00 grams (6.06 mmol) of (9-tosyl-9H-carbazole-2-) il) (] -trityl-lH-imidazol-4-yl) methanol, 15.1 grams (124 millimoles) of manganese dioxide (70 percent), and 80 milliliters of chloroform, was heated under reflux for 16 hours. The reaction mixture was cooled and filtered, and the resulting filtrate was concentrated under reduced pressure and dried. Ethyl acetate (40 milliliters) was added to the resulting residue, and the white crystals thus precipitated were collected by filtration, and dried to give 2.98 grams (4.53 mmol) of the title compound. Spectrum of nuclear magnetic resonance (DMS0-d6, internal standard TMS). d: 2.23 (3H, s), 7.21-7.27 (8H, m), 7.42-7.49 (10H, m), 7.64-7.67 (1H, m), '7.74 (1H, s), 7.78-7.83 (3H, ni), 8.22-8.30 (4H, m), 9.32 (1H s). c) 1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-lH-imidazol-4-yl) ethanol. Methyl magnesium bromide (1.70 milliliters of a solution of 3.0 M in diethyl ether, 5.10 mmol) was added dropwise to a solution of ketone (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-). imidazole-4-ethyl) (2.80 grams, 4.26 mmol) in tetrahydrofuran (42 milliliters) under an argon atmosphere with ice cooling. After stirring for 10 minutes, the reaction mixture was poured into 5 percent aqueous citric acid, and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution with chloroform-hexane -> chloroform-ethyl acetate), to give 1.85 grams (2.75 millimoles) of the title compound as white crystals. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). , 6: 1.81 (3H, s), 2.19 (3H, s), 5.71 (1H, s), 6.87 (1H, s), 7.12-7.14 (8H, m), 7.36-7.44 (11H, m), 7.51 -7.59 (2H, ra), 7.64 (2H, d, J = 8Hz), 7.98 (1H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz), 8.24 (1H, d, J = 8Hz ), 8.37 (1H, s). d) 2- [1- (1H-imidazol-4-yl) ethyl] -9-tosyl-9H-carbazole 1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl) was dissolved -lH-imidazol-4-yl) ethanol (1.80 grams, 2.67 mmol) in 18 milliliters of acetic acid, 180 milligrams of palladium-carbon (10 percent) was added, and the mixture was stirred at 70 ° C for 16 minutes. hours at a pressure of 3 atmospheres of hydrogen. After cooling, the palladium-carbon was removed by filtration, and the filtrate was concentrated under reduced pressure. Ethyl acetate was added to the resulting residue, and the mixture was washed with 1 M aqueous potassium carbonate, water, and brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution with chloroform-methanol-29 percent aqueous ammonia), to give 1.03 grams (2.48 mmol) of the title compound as a white foam. Spectrum of nuclear magnetic resonance (DMSO-df ,, internal standard TMS). 6: 1.63 (3H, d, J = 7Hz), 2.24 (3H, s), 4.26-4.28 (1H, m), 6.87 (1H, s), 7.24 (2H, d, J = 9Hz), 7.33-7.34 (1H, ra), 7.40 (1H, t, J = 7Hz), 7.53 (1H, t, J = 7Hz), 7.62-7.63 (3H, ra), 7.98 (1H, d, J = 8Hz), 8.05 ( 1H, d, J = 7Hz), 8.10 (1H, s), 8.24 (1H, d, J = 9Hz), 11.87 (1H, s). e) 2- tid-H-imidazol-4-yl) ethyl] -9H-carbazole A mixture of 1.00 grams (2.41 mmol) of 2- [1- (1H-imidazol-4-yl) ethyl] -9-tosyl -9H-carbazole, 30 milliliters of ethanol, and 30 milliliters of 2 N aqueous sodium hydroxide, was heated under reflux for 40 hours. After cooling, the reaction mixture was neutralized with acetic acid (4.1 milliliters), and the solvent was evaporated under reduced pressure. Ethyl acetate was added to the resulting residue, and the mixture was washed with 1 M aqueous potassium carbonate, water, and brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated under reduced pressure, and then the resulting residue was purified by silica gel column chromatography (elution with chloroform-methanol-29 percent aqueous ammonia), give 0.41 grams (1.57 millimoles) of the title compound. By recrystallization from ethyl acetate, white crystals were obtained. Melting point: 216-218 ° C Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 1.60 (3H, d, J = 7Hz), 4.19-4.21 (1H, m), 6.79 (1H, s), 7.06 (1H, d, J = 8Hz), 7.11 (1H, t, J = 7Hz), 7.29 (1H, s), 7.32 (1H, t, J = 8Hz, 7.43 (1H, d, J = 8Hz), 7.51 (1H, s), 7.97 (1H, d, J = 8Hz), 8.03 (1H, d, J = 7Hz), 11.08 (1H, s), 11.79 (1H, s). f) 2- [1- (1H-imidazol-4-yl) ethyl] -9H-carbazole monochlorohydrate 2- [1- (1H-imidazol-4-yl) ethyl] -9H-carbazole was dissolved (8.6 grams, 32.9 mmol) in 200 milliliters of ethanol, and with ice cooling, 24.7 milliliters (98.7 millimoles) of 4N hydrogen chloride in ethyl acetate were added. 9.9 grams of crude crystals were obtained by evaporating the solvent under reduced pressure. The crude crystals were recrystallized from ethanol-ethyl acetate, to give 8.69 grams of the title compound as white crystals.

Mass spectrometry (m / z): (262 (M + M) +, APCI) Elemental analysis (for C? 7H] 5N3"HCl) C (,%) H (%) N (%) Cl (%) Calculated: 68.57 5.42 14.11 11.91 Found: 68.39 5.49 14.02 12.07 'Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 1.69 (3H, d, J = 7Hz), 4.43 (1H, q, J = 7Hz), 7.07 (1H, d, J = 8Hz), 7.12-7.15 (1H, m), 7.34-7.37 (2H, m), 7.47 (1H, d, J = 8Hz), 7.57 (1H, s), 8.04-8.08 (2H, m), 9.03 (1H, s), 11.28 (1H, s), 14.43 (2H, br) .

Example 2 a) 2- (lH-imidazol-4-ylmethyl) -9-tosyl-9H-carbazole It was dissolved (9-tosyl-9H-carbazol-2-yl) (1-trityl-lH-imidazol-4-yl) ) methanol (530 milligrams, 0.8 millimoles) in 16 milliliters of acetic acid, 60 milligrams of palladium-carbon (10 percent) were added, and the mixture was stirred at 70 ° C for 2 days at a pressure of 3 atmospheres hydrogen.

After cooling, the palladium-carbon was removed by filtration, the filtrate was concentrated under reduced pressure, and ethyl acetate was added to the residue. The mixture was washed with 1 M aqueous potassium carbonate, water, and brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution with chloroform-methanol-29 percent aqueous ammonia), to give 280 milligrams (0.7 mmol) of the title compound as a white foam. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.24 (3H, s), 4.06 (2H, s), 6.84 (1H, br), 7.24 (2H, d, J = 9Hz), 7.31-7.33 (1H, m), 7.39-7.41 (1H, m ), 7.51-7.55 (1H, m), 7.63-7.67 (3H, m), 7.99 (1H, d, J = 8Hz), 8.06 (1H, d, J = 8Hz), 8.13 (l? S), 8.23 (1H, d, J = 9Hz), 11.90 (1H, br). b) 2- (lH-imidazol-4-ylmethyl) -9H-carbazole A mixture of 280 milligrams (0.7 mmol) of 2- (lH-imidazol-4-ylmethyl) -9-tosyl-9H-carbazole, 30 milliliters of Ethanol, and 4 milliliters of 1 N aqueous sodium hydroxide, was heated under reflux for 5 hours. After cooling, the reaction mixture was neutralized with acetic acid, and the solvent was evaporated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was washed with 1 M aqueous potassium carbonate, water, and brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and then the resulting residue was purified by silica gel column chromatography. (elution with chloroform-ethanol-29 percent aqueous ammonia), to give 140 milligrams (0.57 millimoles) of the title compound, which was recrystallized from ethyl acetate, to give white crystals. Fission point: 230-232 ° C (decomposition). Spectrum of nuclear magnetic resonance (DMS0-d6, internal standard TMS). d: 4.00 (2H, s), 6.78 (.1H, s), 7.05 (1H, d, J = 8Hz), 7.11 (1H, t, J = 7Hz), 7.29-7.34 (2H, m), 7.42- 7.44 (1H, m), 7.53 (1H, s), 7.98 (1H, d, J = 8Hz), 8.04 (1H, d, J = 7Hz), 11.10 (1H, s), 11.82 (1H, br). c) 2- (lH-imidazol-4-ylmethyl) -9H-carbazole monochloride A mixture of 1.02 grams (4.12 mmol) of 2- (lH-imidazol-4-ylmethyl) -9H-carbazole and 20 milliliters of ethanol, it was heated under reflux to give a homogeneous solution. With cooling with ice, 1.6 milliliters of 4 N hydrogen chloride in ethyl acetate was added to this solution. The solvent was evaporated under reduced pressure, and the crude crystals thus formed were recrystallized twice from ethanol, to give 563 milligrams of the title compound as white crystals.

Elementary analysis (for C (%) H (%) N (%) Cl (%) Calculated: 67.72 4.97 14.81 12.49 Found: 67.73 5.15 14.81 12.53 'Mass spectrometry (m / z): (248 (M + M), APCI) Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 4.20 (2H, s), 7.09 (1H, d, J = 8Hz), 7.14 (1H, t, J = 8Hz), 7.36 (1H, t, J = 8Hz), 7.40 (1H, s), 7.46 -7.48 (2H, ra), 8.04-8.08 (2H, m), 9.04 (1H, d, J = lHz), 11.34 (1H, s), 15.58 (2H, br). d) 2- (1H-Imidazol-4-ylmethyl) -9H-carbazole monohydrochloride monohydrate. A mixture of 5.00 grams of 2- (lH-imidazol-4-ylmethyl) -9H-carbazole monohydrochloride and 125 milliliters of water-ethanol (10: 1) was stirred at 60 ° C to give a homogeneous solution. This solution was allowed to cool to room temperature with stirring, and then stirred overnight at 5 ° C. The crystals thus precipitated were collected by filtration, washed with 20 milliliters of cold water, and then dried to give 4.49 grams of the title compound as white crystals.

Elemental analysis (for C (%) H (%) N (%) Cl (%) Calculated: 63.68 5.34 13.92 11.75 Found: 63.76 5.29 13.97 11.68 Mass spectrometry (m / z): 248 ((M + M) +, FAB) Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 4.20 (2H, s), 7.10 (1H, dd, J = lHz, 8Hz), 7.14 (1H, t, J = 8Hz), 7.34-7.38 (1H, m), 7.41 (1H, s), 7.47-7.48 (2H, ra), 8.04-8.08 (2H, m), 9.05 (1H, d, J = lHz), 11.38 (1H, s), 14.66 (2H, br).

Example 3 a) The following compound of Example 3 (a) was obtained in the same manner as in Example 1 (a). (9-Benzenesulfonyl-9H-carbazol-3-yl) (1- trityl-lH-imidazol-4-yl) methanol Starting compounds: 9-benzenesulfonyl-3-bromo-9H-carbazole and l-trityl-lH-imidazole -4-carbaldehyde Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 5.73-5.74 (1H, m); 5.77-5.78 (1H, m), b.79 (1H, s), 7.06-7.11 (6H, m), 7.28 (1H, d, J = lHz), 7.36-7.50 (12H, m), 7.54-7.63 '3H, m), 7.84-7.86 (2H,), 8.05-8.08 (2H, m), 8.17 (1H, d, J = 9Hz), 8.26 (1H, d, J = 9Hz). b) The following compound of Example 3 (b) was obtained in the same manner as Example 1 (d). 9-Benzenesulfonylj3 - (lH-imidazol-4-ylmethyl) -9H-carbazole. Starting compound: (9-benzenesulfonyl-9H-carbazol-3-yl) (1-trityl-1H-imidazol-4-yl) methanol Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 3.99 (2H, s), 6.80 (1H, s), 7.40-7.50 (4H, m), 7.54-7.62 (3H, m), 7.84-7.85 (2H, ra), 7.98 (1H, s), 8.07 (1H, d, J = 8Hz), 8.17 (1H, d, J = 9Hz), 8.25 (1H, d, J = 9Hz), 11. 85 (1H, s). *) The following compound of Example 3 (c) was obtained in the same manner as in Example 1 (e). 3- (lH-imidazol-4-ylmethyl) -9H-carbazole Starting compound: 9-benzenesulfonyl-3- (1H-imidazol-4-ylmethyl) -9H-carbazole Melting point: 218-220 ° C Resonance spectrum Nuclear magnetic (DMSO-d0, internal standard TMS). d: 3.99 (1H, s), 6.72 (1H, s), 7.12 (1H, t, J = 7Hz), 7.26 (1H, d, J = 8Hz), 7.33-7.39 (2H, m), 7.44 (1H , d, J = 8Hz), 7.51 (1H, s), 7.94 (1H, s), 8.04 (1H, d, J = 8Hz), 11.11 (1H, s), 11.80 (1H, s).

Example 4 a) The following compound of Example 4 (a) was obtained in the same manner as in Example 1 (a). (9-tetrahydropyranyl-9H-carbazol-2-yl) (1-trityl-lH-imidazol-4-yl) ethanol Starting compounds: 2-bromo-9-tetrahydropyranyl-9H-carbazole and l-trityl-lH-imidazoi -4-carbaldehyde Nuclear magnetic resonance spectrum (DMSO-d ^, internal standard TMS). d: 1.60-1.69 (3H, m), 1.82-1.85 (1H, m), 2.32-2.37 (1H, m), 3.79 (1H, t, J = 9Hz), 4.11 (1H, br), 5.70-5.71 (1H, m), 5.74-5.76 (1H, m), 5.92 (1H, d, J = 9Hz), 6.77 (1H, s),, 7v "'. 08-7.10 (7H, ra), 7.16-7.21 (2H, m), 7.28 (1H, d, J = lHz), 7.35-7.41 (9H, m), 7.73-7.76 (2H, ra), 8.02 (1H, d, J = 8Hz), 8.08 (1H, d, J = 8Hz). b) The following compound of Example 4 (b) was obtained in the same manner as in Example 1 (b).

Ketone (9-tetrahydropyranyl-9H-carbazol-2-yl) (1-trityl-lH-imidazole-4-yl). Starting compound: (9-tetrahydropyranyl-9H-carbazol-2-yl) (1-trityl-lH-imidazol-4-yl) methanol Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 1.60-1.99 (5H, m), 2.35-2.38 (1H, m), 3.78-3.82 (1H, m), 4.11-4.13 (1H, m), 6.00-6.03 (lH, .m), 7.19 (6H, d, J = 7Hz), 7.26 (1H, t, J-7Hz), 7.41-7.52 (10H, m), 7.63 (1H, d, J = lHz), 7.73 (1H, d, J = lHz), 7.82 (1H, d, J = 9Hz), 8. 08-8.09 (1H, ra), 8.21-8.25 (2H, m), 8.75 (1H, s). c) Ketone (9H-carbazol-2-yl) (lH-imidazole-4-yl) Ketone (9-tetrahydropyranyl-9H-carbazol-2-yl) (l-trityl-lH-imidazole-4-yl) was dissolved (0.587 grams, 1 millimole) in 10 milliliters of dioxane, and 10 milliliters of 1 N hydrochloric acid was added to the solution at room temperature. The mixture was stirred at 60 ° C for 2 hours, cooled to room temperature, and diluted by the addition of 100 milliliters of ethyl acetate. Then 100 milliliters of 3 N hydrochloric acid was added, and then stirred. After removing the organic layer, the aqueous layer was neutralized with potassium carbonate, extracted with ethyl acetate, and then washed with brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated under reduced pressure, and then the resulting residue was recrystallized from methanol to give 0.164 grams (0.63 millimoles) (63 percent) of the title compound as yellow crystals. Melting point: 274 ° C (decomposition). Spectrum of nuclear magnetic resonance (DMSO-d6 internal standard TMS). d: 7.22 (1H, t, J = 8Hz), 7.47 (1H, t, J = 8Hz), 7.56 (1H, d, J = 9Hz), 7.92-7.97 (3H, ra), 8.21 (1H, d, J = 8Hz), 8.24 (1H, d, J = 8Hz), 8.40 (1H, bs), 11.52 (1H, s), 12.90 (1H, bs).

Example 5 a) The following compound of Example 5 (a) was obtained in the same manner as in Example 1 (a). (9-ethyl-9H-carbazol-2-yl) (1-trityl-1H-imidazol-4-yl) methanol Starting compounds: 2-bromo-9-ethyl-9H-carbazole and 1-trityl-1H-imidazole -4-carbaldehyde Nuclear magnetic resonance spectrum (DMSO-d6 internal standard TMS) d: 1.29 (3H, t, J = 7Hz), 4.39 (2H, q, J = 7Hz), 5.67 ( 1H, d, J = 5Hz), 5.76 (1H, d, J = 5Hz), 6.75 (1H, s), 7.08-7.11 (6H, m), 7.13-7.21 (2H, m), 7.28 (1H, s), 7.35-7.43 (10H, m), 7. 52 (1H, s), 7.57 (1H, d, J = 8Hz), 8.02 (1H, d, J = 8Hz), 8.09 (1H, d, J = 7Hz). b) The following compound of Example 5 (b) was obtained in the same manner as in Example 1 (d). 9-Ethyl-2- (1H-imidazol-4-ylmethyl) -9H-carbazole Starting compound: (9-ethyl-9H-carbazol-2-yl) (1-trityl-1H-imidazol-4-yl) methanol Melting point: 173-174 ° C. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.30 (3H, t, J = 7Hz), 4.04 (2H, s), 4.39 (2H, q, J = 7Hz), 6.77 (1H, s), 7.08 (1H, d, J = 8Hz), 7.14 -7.18 (1H, ra), 7.38-7.43 (1H, ra), 7.46 (1H, s), 7.54-7.57 (2H, m), 8.02 (1H, d, J = 8Hz), 8.08 (1H, d, J = 8Hz), 11.85 (1H, bs).

Example 6 a) 2- [(1-dimethylcarbamoyl-1H-imidazol-4-yl) methyl] -9H-carbazole A mixture of 2- (1H-imidazol-4-ylmethyl) -9H-carbazole (950 milligrams, 3.9 millimoles), anhydrous dlmethyl formamide (20 milliliters), triethyl amine (580 milligrams, 5.7 millimoles), and N, N-dimethylcarbamoyl chloride (620 milligrams, 5.8 millimoles), was heated overnight at 50 ° C. After cooling the reaction mixture, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by chromatography on a silica gel column (chloroform: methanol: 28 percent aqueous ammonia = 50: 1: 0.1), to give 2- [(1-dimethylcarbamoyl-1H-imidazol-4-yl) methyl] -9H-carbazole (950 milligrams), which was recrystallized from ethyl acetate, to give white crystals .

Spectrum of nuclear magnetic resonance (DMSO-d6 internal standard TMS). d: 3.00 (6H, s), 3.98 (2H, s), 7.07 (1H, d, J = 8Hz), 7.12 (1H, t, J = 7Hz), 7.22 (1H, s), 7.32-7.34 (2H , m), 7.44 (1H, d, J = 8Hz), 7.99 (2H, d, J = 6Hz), 8 04 (1H, d, J = 7Hz), 11.11 (1H, s). b) 2 - [(1-ethyl-1H-imidazol-5-yl) methyl] -9H-carbazole. A mixture of 2- [(1-dimethylcarbamoyl-lH-imidazol-4-yl) methyl] -9H-carbazole (510 milligrams, 1.6 mmol), anhydrous dimethyl formamide (10 milliliters), and ethyl iodide (5.0 grams, 32 mmol), was heated at 100 ° C for 4 days. After cooling the reaction mixture, ethyl acetate saturated with ammonia gas (30 milliliters) was added. The mixture was stirred at room temperature for 1 hour, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (chloroform: methanol: 28 percent aqueous ammonia 30: 1: 0.1), to give 2- [(l-ethyl- lH-imidazol-5-yl) methyl] -9H-carbazole (110 milligrams), which was recrystallized from ethyl acetate, to give white crystals. Melting point: 205-206 ° C.

Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS) d: 1.13 (3H, t, J = 7Hz), 3.81 (2H, q, J = 7Hz), 4.11 (2H, s), 6.70 (1H, s ), 7.02 (1H, d, J = 8Hz), 7.11-7.14 (1H, ra), 7.25 (1H, s), 7.33-7.36 (1H, ra), 7.44 (1H, d, J = 8Hz), 7.59 (1H, s), 8.02 (1H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz).

Example 7 a) 1- (9H-Fluoren-2-yl) -1- (1-methyl-2-thiophenyl-1H-imidazol-5-yl) ethanol. A mixture of 2,2,6,6,6-tetramethyl piperidine (2.05 grams, 14.5 mmol), tetrahydrofuran (50 milliliters), and ethylene glycol dimethyl ether (25 milliliters) was cooled to -78 ° C under an atmosphere of argon, normal butyl lithium (normal 1.6M hexane solution, 9 milliliters) was added dropwise to the solution, and the mixture was stirred at the same temperature for 20 minutes. A solution of l-methyl-2-thiophenyl-1H-imidazole (2.5 grams, 13.2 mmol) in tetrahydrofuran (25 milliliters) was added dropwise to this solution, and the mixture was stirred at the same temperature for 1 hour. A solution of 2-acetyl-9H-fluorene (3.0 grams, 14.5 mmol) in tetrahydrofuran (50 milliliters) was added dropwise, and the mixture was allowed to warm to room temperature, and was stirred overnight. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (normal hexane: ethyl acetate = 2: 1), to give 1- (9H-fluoren-2-yl) -1- (1-methyl-2-thiophenyl) -lH-imidazol-5-yl) ethanol (1.7 grams), which was recrystallized from ethyl acetate to give white crystals. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.84 (3H, s), 3.20 '(3H, s), 3.85 (1H, d, J = 22Hz), 3.91 (1H, d, J = 22Hz), 6.09 (1H, s), 7.02 (2H, d, J = 8Hz), 7.17-7.20 (1H, m), 7.28-7.31 ('5H, m), 7.35-7.38 (1H, m), 7.50 (1H, s), 7.56 (1H, d, T = 7Hz), 7.82 (1H, d, J = 8Hz), 7.85 (1H, d, J = 7Hz). b) 1- (9H-fluoren-2-yl) -1- (1-methyl-1H-imidazol-5-yl) ethanol. A mixture of 1- (9H-fluoren-2-yl) -1- (1-methyl-2-thiophenyl-1H-imidazol-5-yl) ethanol (590 milligrams, 1.5 mmol), Raney nickel (Raney NDHT- 90: manufactured by kawaken Fir, e Chemical) (approximately 4.5 grams) and ethanol (60 milliliters), was heated under reflux for 2 hours. The reaction mixture was cooled to room temperature, and filtered. The resulting filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform: methanol = 50: 1), to give 1- (9H-fluoren-2-yl) -1- (1 methyl-lH-imidazol-5-yl) ethanol (310 milligrams), which was crystallized and washed with diethyl ether to give white crystals. Melting point: 264-265 ° C. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.81 (3H, s), 3.23 (3H, s), 3.88 (2H, s), 5.90 (1H, s), 7.03 (1H, s), 7.27-7.30 (2H, m), 7.36 (1H, t, J = 7Hz), 7.51 (2H, s), 7.56 (1H, d, J = 7Hz), 7.81 (1H, d, J = 8Hz), 7.84 (1H, d, J = 7Hz). c) 5- [1- (9H-f-luoren-2-yl) inyl] -1-methyl-lH-i-idazole (7cl) and 5- [1- (9H-fluoren-2-yl) ethyl] -1 -methyl-lH-imidazole (7c2). Under an argon atmosphere, triethylsilyl hydride (550 milligrams, 4.7 mmol) was added dropwise to a mixture of 1- (9H-fluoren-2-yl) -1- (1-methyl-1H-imidazol-5-yl). ) ethanol (230 milligrams, 0.8 mmol) and trifluoroacetic acid (3 milliliters) with ice cooling, and the mixture was stirred for 1 hour at the same temperature. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform: methanol: 28 percent aqueous ammonia = 200: 1: 0.1) to give 5- [1- (9H-fluoren-2-yl) vinyl] - 1-methyl-lH- <Imidazole (170 milligrams) and 5- [1- (9H-Fluoren-2-yl) ethyl] -1-methyl-1H-imidazole '(30 milligrams). They were recrystallized respectively from ethyl acetate to give respective white crystals. 5- [1- (9H-Fluoren-2-yl) vinyl] -1-methyl-1H-imidazole Melting point: 150 ° C. 5- [1- (9H-Fluoren-2-yl) ethyl] -1-methyl-1H-imidazole Melting point: 161-162 ° C. Spectrum of nuclear magnetic resonance (CDC13, internal standard TMS). 5- [1- (9H-Fluoren-2-yl) vinyl] -1-methyl-1H-imidazole. . d: 3.29 (3H, s), 3.89 (2H, s), 5.43 (1H, d, J = lHz), . 70-5.72 (1H, m), 7.13 (1H, s), 7.30-7.40 (3H, m), 7.47 (2H, d, J = 3Hz), 7.55 (1H, d, J = 7Hz), 7.74 (1H , d, J = 8Hz), 7. 78 (1H, d, J = 7Hz). - [1- (9H-Fluoren-2-yl) ethyl] -1-methyl-1H-imidazole. 6: 1.56 (3H, d, J = 7Hz), 3.29 (3H, s), 3.87 (2H, s), 4. 19-4.24 (1H, m), 6.92 (1H, s), 7.19 (1H, d, J = 7Hz), 7.28 (1H 'fc' J = 7Hz), 7.34-7.37 (2H, ra), 7.51-7.56 (2H, m), 7.80-7.85 (2H, m).

Example. 8 a) The following compound of Example 8 (a) was obtained in the same manner as in Example 7 (a). (9H-fluoren-2-yl) (1-methyl-2-thiopheni-1H-imidazol-5-yl) methanol. Starting compounds: l-methyl-2-thiophenyl-lH-imidazole and 9H-fluoren-2-carbaldehyde Nuclear magnetic resonance spectrum (DMSO-d ^, internal standard TMS). d: 3.55 (3H, s), 3.88 (2H, s), 5.93 (1H, s), 6.91 (1H, s), 7.15-7.56 (10H, ra), 7.73-7.81 (2H, m). b) The following compound of Example 8 (b) was obtained in the same manner as in Example 7 (b). (9H-Fluoren-2-yl) (1-methyl-1H-imidazol-5-yl) methanol Starting compound: (9H-fluoren-2-yl) (1-methyl-2-thiophenyl-1H-imidazole-5 -il) methanol Melting point: 232-233 ° C Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). : 3.56 (3H, s), 3.92 (2H, s), 5.86 (1H, d, J = 5Hz), . 94 (1H, d, J = 5Hz), 6.47 (1H, s), 7.29-7.32 (1H, ni), 7.37-7.41 '(2H, m), 7.53 (1H, s), 7.57-7.60 (2H, m), 7.87 (2H, t, J = 7Hz). c) The following compound of Example 8 (c) was obtained in the same manner as in Example 7 (c). - (9H-Fluoren-2-ylmethyl) -1-methyl-1H-imidazole Starting compound: (9H-fluoren-2-yl) (1-methyl-1H-imidazol-5-yl) methanol Melting point: 155-156 ° C Nuclear magnetic resonance spectrum (CDCl ?, internal standard TMS). d: 3.44 (3H, s), 3.85 (2H, s), 4.01 (2H, s), 6.91 (1H, s), 7.17 (1H, d, J = 8Hz), 7.26-7.30 (2H, ra), 7.36 (1H, t, J = 7Hz), 7.49-7.53 (2H, m), 7.70 (1H, d, J = 8Hz), 7.75 (1H, d, J = 7Hz).

Example 9 a) The following compound of Example 9 (a) was obtained in the same manner as in Example 7 (a). (l-ethyl-2-thiophenyl-1H-imidazol-5-yl) (9H-fluoren-2-yl) methanol Starting compounds: (1-ethyl-2-thiophenyl-1H-imidazole and 9H-fluoren-2 carbaldehyde: Nuclear magnetic resonance spectrum (CDCI3, internal standard TMS) d: 1.09 (3H, t, J = 7Hz), 3.88 (2H, s), 4.03-4.11 (2H, m), 5.93 (1H, s), 6.91 (1H, s), 7.15-7.26 (5H, m), 7. 30-7.41 (3H, m), 7.53-7.58 (2H, m), 7.77-7.79 (2H, m). b) The following compound of Example 9 (b) was obtained in the same manner as in Example 7 (b). (l-ethyl-lH-imidazol-5-yl) (9H-fluoren-2-yl) methanol Starting compound: (l-ethyl-2-thiophenyl-lH-imidazol-5-yl) (9H-fluoren-2 -yl) methanol. Melting point: 188-189 ° C Nuclear magnetic resonance spectrum (CDC13, internal standard TMS). d: 1.28 (3H, t, J = 7Hz), 3.87 (2H, s), 3.88-3.99 (2H, ra), 5.94 (1H, s), 6.70 (1H, s), 7.29-7.41 (4H, ra), 7. 52-7.57 (2H, m), 7.74-7.78 (2H, m). c) The following compound of Example 9 (c) was obtained in the same manner as in Example 7 (c). l-ethyl-5- (9H-flulen-2-ylmethyl) -lH-imidazole. Compound of, starting: (l-ethyl-lH-imidazol-5-yl) (9H-fluoren-2-yl) methanol. Melting point: 158-159 ° C Nuclear magnetic resonance spectrum (CDCI3, internal standard TMS). d: 1.25 (3H, t, J = 7Hz), 3.74-3.79 (2H, m), 3.85 (2H, s), 4.02 (2H, s), 6.89 (1H, s), 7.18 (1H, d, J = 7Hz), 7.26-7.38 (3H, m), 7.48-7.53 (2H, m), 7.70 (1H, d, J = 7Hz), 7.75 (1H, d, J = 8Hz).

Example 10 a) The following compound of Example 10 (a) was obtained in the same manner as in Example 7 (a). 1- (1-ethyl-2-thiophenyl-1H-imidazol-5-yl) -1- (9H-fluoren-2-yl) ethanol. Starting compounds: 1-ethyl-2-thiophenyl-1H-imidazole and 2-acetyl-9H-fluorene. Spectrum of nuclear magnetic resonance (CDC13, internal standard TMS). d: 0.80 (3H, t, J = 7Hz), 1.98 (3H, s), 3.67-3.74 (1H, ra), 3.83 (1H, d, J = 22Hz), 3.89 '(1H, d, J = 22Hz ), 3.94-4.01 (1H, m), 7.15-7.20 (2H, m), 7.23-7.26 (3H, ra), 7.28-7.38 (4H, m), 7.51-7.54 (2H, m), 7.71 (1H , d, J = 8Hz), 7.76 (1H, d, J = 7Hz). • b) The following compound of Example 10 (b) was obtained in the same manner as in Example 7 (b). 1- (1-ethyl-1H-imidazol-5-yl) -1- (9H-f luoren-2-yl) ethanol. Starting compound: 1- (1-ethyl-2-thiophenyl-1H-imidazol-5-yl) -1- (9H-fluoren-2-yl) ethanol. Spectrum of nuclear magnetic resonance (DMSO-d ^, internal standard TMS). d: 0.90 (3H, t, J = 7Hz), 1.81 (3H, s), 3.68-3.73 (2H, m), 3.88 (2H, s), 5.96 (1H, s), 7.01 (1H, s), 7.27-7.30 (2H, m), 7.36 (1H, t, J = 7Hz), 7.51-7.59 (3H, m), 7.80 (1H, d, J = 8Hz), 7.84 (1H, d, J = 7Hz). c) l-ethyl-5- [1- (9H-f luoren-2-yl) vinyl] -1H-i idazole. A mixture of 1- (1-ethyl-1H-imidazol-5-yl) -1- (9H-fluoren-2-yl) ethanol (80 milligrams, 0.26 mmol) and trifluoroacetic acid (4 milliliters) was stirred for 1 hour. hour with cooling with ice, and then warmed to room temperature and stirred for 4 hours. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1), to give l-ethyl-5- [1- (9H-fluoren-2-yl) vinyl] -lH-imidazole (70 milligrams), which was recrystallized and washed with normal hexane to provide white crystals. Melting point: 128-129 ° C. Spectrum of nuclear magnetic resonance (CDCI3, internal standard TMS). d: 1.20 (3H, t, J = 7Hz), 3.61 (2H, q, J = 7Hz), 3.88 (2H, s), 5.44 (1H, d, J = lHz), 5.70 (1H, d, J = lHz), 7.13 (1H, s), 7.30-7.40 (3H, m), 7.47 (1H, s) , 7.54-7.55 (2H, ra), .73 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz). d) l-ethyl-5- [1- (9H-fluoren-2-yl) ethyl] -lH-imidazsl. L-ethyl-5- [1- (9H-fluoren-2-yl) vinyl] -1H-imidazole (690 milligrams, 2.4 mmol) was dissolved in 10 milliliters of methanol, 70 milligrams of palladium-carbon (10% strength) was added. percent), and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 days. After removing the palladium-carbon by filtration, the resulting filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution with chloroform-methanol), to give 120 milligrams (0.4 mmol) of the composed of the title as white crystals. Fission point: 134-135 ° C. Nuclear magnetic resonance spectrum '(DMSO-dβ, internal standard TMS). d: 1.01 (3H, t, J = 7Hz), 1.56 (3H, d, J = 6Hz), 3.63-3.71 (2H, m), 3.87 (2H, s), 4.19-4.23 (1H, m), 6.93 (1H, s), 7.20 (1H, d, J = 8Hz), 7.27-7.30 (1H, m), 7.34-7.37 (2H, m), 7.54-7.58 (2H, m), 7.80-7.84 (2H, ra).

Example 11 a) The following compound of Example 11 (a) was obtained in the same manner as in Example 7 (a). (9-Benzenesulfonyl-9H-carbazol-2-yl) (1-methyl-2-thiophenyl-1H-imidazol-5-yl) methanol. Compounds, starting material: l-methyl-2-thiophenyl-lH-imidazole and 9-benzenesulfonyl-9H-carbazole-2-carbaldehyde. Spectrum of nuclear magnetic resonance (DMSO-d ^, internal standard TMS). d: 3.56 (3H, s), 6.09 (1H, d, J = 6Hz), 6.35 (1H, d, J = 6Hz), 6.63 (1H, s), 7.12 (2H, d, J = 7Hz), 7.22 (1H, t, J = 7Hz), 7.30-7.34 (2H, m), 7.43-7.47, (4H, m), 7.58 (1H, t, J = 7Hz), 7.62 (1H, t "J = 7Hz) , 7.76 (2H, d, J = 8Hz), 8.11-8.13 (2H, ra), 8.27 (1H, d, J = 8Hz), 8.35 (1H, s). b) The following compound of Example 11 (b) was obtained in the same manner as in Example 7 (b). (9-Benzenesulfonyl-9H-carbazol-2-yl) (1-methyl-lH-imidazol-5-yl) methanol. Starting compounds: (9-Benzenesulfonyl-9H-carbazol-2-yl) (1-methyl-2-thiophenyl-1H-imidazol-5-yl) methanol. Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 3.32 (3H, s), 6.22 (1H, bs), 6.42 (1H, bs), 7.43-7.45"(5H, ra), 7.56-7.62 (3H, ra), 7.74-7.76 (2H, m) , 8.10-8.11 (2H, m), 8.26 (1H, d, J = 8Hz), 8.35 (1H, bs). c) 9-Benzenesulfonyl-2- [ethoxy (1-methyl-lH-imidazol-5-yl) methyl] -9H-carbazole. Triethylsilane (3.44 milliliters) was added., 21-54 millimoles) and trifluoroborane etherate (1.32 milliliters, 10.77 millimoles) to 160 milliliters of a chloroform solution containing 1,500 grams (3.59 millimoles) of (9-benzenesulfonyl-9H-carbazole-2-yl) (1 - methyl-1H-imidazol-5-yl) methanol, and the mixture was stirred at room temperature for 1 hour. Then 3.44 milliliters (21.54 millimoles) of triethylsilane and 1.32 milliliters (10.77 millimoles) of trifluoroborane etherate were added again, followed by 1 hour of stirring at the same temperature. The reaction mixture was heated to 50 ° C, and stirred for 18 hours, 1.00 milliliters (6.26 millimoles) of triethylsilane and 0.50 milliliters were added. (4.08 millimoles) of trifluoroborane etherate, and then the mixture was stirred for an additional 1 hour. The reaction mixture was washed with saturated aqueous sodium bicarbonate and brine, and the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography. The crude product was obtained from a fraction eluted with chloroform-methanol (100: 1), and then recrystallized from ethyl acetate, to give 0.768 grams (1.72 millimoles) (48 percent) of the title compound as white crystals.

Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.24 (3H, t, J = 7Hz), 3.47 (1H, dq, J = 7Hz, 7Hz), .57 (3H, s), 3.58 (1H, dq, J = 7Hz, 7Hz), 5.82 (1H , s), 6.37 (1H, s), 7.44-7.49 (4H, ra), 7.59-7.63 (3H, m), 7.65 (1H, s), .72 (2H, d, J = 7Hz), 8.14 ( 2H, d, J = 8Hz), 8.28 (1H, s), 8.30 (1H, d, J = 8Hz). d) 9-Benzenesulfonyl-2- [(1-methyl-1H-imidazol-5-ylmethyl] -9H-carbazole.) 9-Benzenesulfonyl-2- [ethoxy (1-methyl-1H-imidazol-5-yl) was dissolved. methyl] -9H-carbazole (0.730 grams, 1.64 millimoles) in 60 milliliters of acetic acid, were added 1. 200 grams of palladium-carbon (10 percent), and the mixture was stirred at 70 ° C for 19 hours under a pressure of 4 atmospheres of hydrogen. The reaction mixture was cooled to room temperature, and filtered. The resulting filtrate was concentrated under reduced pressure. Chloroform was added to the resulting residue, the mixture was washed with saturated aqueous sodium bicarbonate and brine, and then the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography, to give 0.470 grams (1.17 millimoles) (71 percent) of the title compound as white crystals. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). 6: 3.41 (3H, s), 4.18 (2H, s), 6.72 (1H, s) ,. 7.28 (1H, d, J = 8Hz), 7.43 (1H, t, J = 7Hz), 7.47 (2H, t, J = 8Hz), 7. 56 (1H, t, J = 8Hz), 7.60 (1H, s), 7.62 (1H, t, J = 7Hz), 7. 71-7.73 (2H, ra), 8.04 (1H, s), 8.05 (1H, d, J = 8Hz), 8.09 (1H, d, J = 7Hz), 8.26 (1H, d, J = 9Hz). e) The following compound of Example 11 (e) was obtained in the same manner as in Example 1 (e). 2- [(1-methyl-1H-imidazol-5-yl) methyl] -9H-carbazole Starting compound: 9-benzenesulfonyl-2- [(1-methyl-1H-imidazol-5-yl) methyl] -9H -carbazole Melting point: 242.5-244 ° C Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 3.44 (3H, s), 4.10 2H, s), 6.71 (1H, s), 7.01 (1H, d, J = 8Hz), 7.13 (1H, t, J = 8Hz), 7.23 (1H, s) , 7.34 (1H, t, J = 8Hz), 7.44 (1H, d, J = 8Hz), 7.52 (1H, s), 8.02 (1H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz ), 11.13 (1H, s).

Example 12 a) (9-b in c on its 1 foni 1 - 9 H - carbazo 1 - 2 -i Diethyl dimethylphosphonate A mixture of 9-benzenesulphonyl-2-bromomethyl-9H-carbazole (833 milligrams, 2.08 millimoles) and Triethyl phosphite (0.36 milliliter, 2.08 mmol) was stirred at 80 ° C. for 5 days The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (eluent: chloroform: methanol = 10 : 1), to give the title compound (526 milligrams, 1.19 millimoles, 43 percent) as colorless crystals Nuclear magnetic resonance spectrum (CDCI3, internal standard TMS) d: 1.25 (6H, t, J = 7Hz) , 3.36 (2H, d, J = 22Hz), 4.04 (4H, dq, J = 7Hz, 7Hz), 7.26-7.50 (6H, m), 7.79-7.90 (4H, ra), 8.29-8.36 (2H, m). b) (E) -9-Benzenesulfonyl-2- [2- (1-riyl-1H-imidazol-4-yl) ethenyl] -9H-carbazole Sodium hydride (60 weight percent, 49 milligrams, 1.22 mmol) at 0 ° C, to a mixture of diethyl (9-benzenesulfonyl-9H-carbazol-2-yl) methylphosphonate (515 milligrams, 1.16 millimoles), 1-trityl-1H-imidazole-4-carbaldehyde (397 milligrams , 1.16 mmol), a catalytic amount of 15-crown-5-ether and tetrahydrofuran (12 milliliters), and the resulting mixture was heated under reflux for 5 hours. Brine (10 milliliters) was added to the reaction mixture, and the product was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (703 milligrams, 1.10 mmol, 94 percent) as colorless crystals. Spectrum of nuclear magnetic resonance (CDCI3, internal standard TMS). d: 6.96 (1H, d, J = lHz), 7.13-7.54 (24H, IU), 7.75-7.85 (3H, m), 8.30 (1H, d, J = 8Hz) 8.43 (1H, s). c) (E) -9-Benzenesulfonyl-2 - [2- (lH-imidazol-4-yl) ethenyl] -9H-carbazole. A mixture of (E) -9-benzenesulfonyl-2- [2- (1-trityl-lH-imidazol-4-yl) ethenyl] -9H-carbazole '(693 milligrams, 1.08 mmol), and aqueous acetic acid at 90 percent (20 milliliters), was stirred at 60 ° C for -2 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate (20 milliliters) and saturated aqueous sodium bicarbonate (20 milliliters) were added to the resulting residue, and then the product was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform: methanol: 17 percent ammonia = 100: 3: 0.3) to give the title compound (387 milligrams, 0.97 millimoles, 90 percent) as colorless crystals. Spectrum of nuclear magnetic resonance (CDCI3, internal standard TMS). d: 7.16-7.49 (9H, m), 7.55 (1H, s), 7.65 (1H, s), 7.76-7.88 (3H, ra), 8.28 (1H, dd, J = 2Hz, 7Hz), 8.42 (1H , s). d) 9-Benzenesulfonyl-2- [2- (lH-imidazol-4-yl) ethyl] -9H-carbazole. A mixture of (E) -9-benzenesulfonyl-2- [2- (1H-imidazol-4-yl) ethenyl] -9H-carbazole (387 milligrams, 0.97 mmol), a catalytic amount of palladium-carbon (up to 10%). percent) and dioxane (8 milliliters), was stirred at room temperature for 3 days under a hydrogen atmosphere. The reaction mixture was filtered, and the resulting filtrate was concentrated to give the title compound (322 milligrams, 0.80 millimole, 83 percent) as colorless crystals. Spectrum of nuclear magnetic resonance (CDCI3, internal standard TMS). d: 2.89-3.23 (4H, m), 6.77-6.83 (1H, m), 7.24-8.29 (13H, m) e) 2- [2- (lH-imidazol-4-yl) ethyl] -9H-carbazole A mixture of 9-benzenesulfonyl-2- [2- (lH-imidazol-4-yl) ethyl] -9H-carbazole (322 milligrams, 0.80 mmol), ethanol (15 milliliters), and 2 N aqueous sodium hydroxide (7.5 milliliters), was heated under reflux for 12 hours. The reaction mixture was concentrated under reduced pressure, and purified by silica gel column chromatography. (eluent: chloroform: methanol: 17 percent ammonia = 100: 10: 1), and then recrystallized from ethanol, to give the title compound (110 milligrams, 0.27 mmol, 34 percent) as colorless crystals. Melting point: 239-241 ° C Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS): d: 2.82-2.93 (2H, m), 3.02-3.07 (2H, m), 6.74 (1H, s), 7.03 (1H, d, J = 8Hz), 7.10-7.14 (1H, ra), 7.29-7.35 (2H, m), '7.44 (1H, d, J = 8Hz), 7.52 (1H, s), 7.97-8.05 (2H, m), 11.11 (1H, br), 11.71 (1H, br).

Example 13 a) The following compound of Example 13 was obtained in the same manner as Example 6 (b). 2- [(1-propyl-1H-imidazol-5-yl) methyl] -9H-carbazole. "Starting compounds: 2- [(1-dimethylcarbamoyl-1H-imidazol-4-yl) methyl] -9H-carbázole and propyl iodide, melting point: 189-191 ° C Nuclear magnetic resonance spectrum (DMSO-d0) , internal standard TMS). d: 0.73 (3H, t, J = 7Hz), 1.36-1.53 (2H, ra), 3.74 (2H, t, J = 7Hz), 4.10 (2H, s), 6.70 (1H, s), 7.01-7.02 (1H, m), 7.13 (1H, t, J = 7Hz), 7.25 (1H, s), 7.34 (1H, dd, J = 7Hz, 7Hz), 7.44 (1H, d, J = 8Hz), 7.56 ( 1H, s), 8.01 (1H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz), 11.13 (1H, s).

Example 14 a) The following compound was obtained in the same manner as in Example 1 (a). , l-isopropyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) ethanol. Starting compounds: 2-bromo-9-tosyl-9H-carbazole and l-isopropyl-lH-imidazole-5-carbaldehyde. Spectrum of nuclear magnetic resonance (DMSO-d ^, internal standard TMS). 6: 1.12 (3H, d, J = 7Hz), 1.33 (311, d, J = 6Hz), 2.26 (3H, s), 4.44-4.50 (1H, m), 6.04 (1H, d, J = 5Hz), 6.24 (1H, d, J = 5Hz), 6.47 (1H, s), 7.25 (2H, d, J = 8Hz), 7.40-7.45 (2H, m), 7.54-7.59 (1H, m), 7.62 (2H, d, J = 8Hz), 7.81 (1H, s), 8.07-8.12 (2H, m), 8.26 (1H, d, J = 8Hz), 8.33 (1H 's) - b) 2- [(1- isopropyl-1H-imidazol-5-yl) methyl] -9-tosyl-9H-carbazole. (L-isopropyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) methanol (1.56 grams, 3.4 mmol) in 20 milliliters of trifluoroacetic acid was dissolved, 2.4 grams (20.4 millimoles) were added. ) of triethylsilyl hydride, and the mixture was stirred for 1 hour under cooling with ice. The solvent was evaporated under reduced pressure, and ethyl acetate was added to the residue, followed by washing with saturated aqueous sodium bicarbonate, water, and brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and then the resulting residue was recrystallized from ethyl acetate, to give 1.36 grams (3.1 mmol) of the title compound as white crystals. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 1.18 (6H, d, J = 7Hz), 2.25 (3H, s), 4.19 (2H, s), 4.22-4.25 (1H, m), 6.72 (1H, s), 7.24 (2H, d, J = 8Hz), 7.29 (1H, d, J = 8Hz), 7.42 (1H, t, J = 7Hz), 7.55 (1H, t, J = 7Hz), 7.60 (2H, d, J = 8Hz), 7.79 ( 1H, s), 8.04 (2H, d, J = 7Hz), 8.08 (1H, d, J = 7Hz), 8.24 (1H, d, J = 8Hz). c) The following compound was obtained in the same manner as Example 1 (e). 2- [(l-isopropyl-lH-imidazol-5-yl) methyl] -9H-carbazole Starting compound: 2- [(l-isopropyl-lH-imidazol-5-yl) methyl] -9-tosyl-9H -carbazole. Melting point: 181-182 ° C Nuclear magnetic resonance spectrum (DMSO-d (), internal standard TMS). d: 1.23 (6H, d, J = 7Hz), 4.12 (2H, s), 4.18-4.23 (1H, ra), 6.70 (1H, s), 7.01 (1H, d, J = 8Hz), 7.11-7.15 (1H, m), 7.23 (1H, s), 7.32-7.36 (1H, ra), 7.44 (1H, d, J = 8Hz), 7.73 (1H, s), 8.01 (1H, d, J = 8Hz) , 8.05 (1H, d, J = 8Hz), 11.13 (1H, s).

The following compound of Example 15 (a) was obtained in the same manner as in Example 1 (a).

Example 15 a) (l-benzyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) ethanol. Starting compounds: 2-bromo-9-tosyl-9H-carbazole and l-benzyl-lH-imidazole-5-carbaldehyde. Spectrum of nuclear magnetic resonance (DMSü-d6, internal standard TMS). d: 1.99 (3H, s), 5.18 (1H, d, J = 15Hz), 5.26 (1H, d, J = 15Hz), 5.86 (1H, d,, J = 6Hz), 6.24 (1H, d, J = faHz), 6.44 (1H, s), 7.09 (2H, d, J = 7Hz), 7.21-7.29 (6H, m), 7.41-7.44 (1H, m), 7.55-7.58 (1H, m), 7.61 (2H, d, J = 8Hz), 7.68 (1H, s), 8.01 (1H, d, J = 8Hz), 8.09 (1H, d, J = 7Hz), 8.24-8.27 (2H, m).

The following compound of Example 15 (b) was obtained in the same manner as in Example 14 (b). b) 2- [(1-Benzyl-1H-imidazol-5-yl) methyl] -9-tosyl-9H-carbazole. Starting compound: (1-benzyl-1H-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) methanol. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 2.22 (3H, s), 4.04 (2H, s), 5.07 (2H, s), 6.74 (1H, s), 7.00-7.01 (2H, m), 7.15-7.17 (1H, ra), 7.20-7.26 (5H, m), 7.40-7.43 (1H, m), 7.53-7.57 (1H, ra), 7.61 (2H, d, J = 9Hz), 7.76 (1H, s), 7.96-8.00 (2H , m), 8.07 (1H, d, J = 7Hz), 8.24 (1H, d, J = 9Hz). The following compound of Example 15 (c) was obtained in the same manner as in Example 1 (e). c) 2- [(1-benzyl-1H-imidazol-5-yl) methyl] -9H-carbazole. Starting compound: 2- [(1-benzyl-lH-imidazol-5-yl) methyl] -9-tosyl-9H-carbazole. Melting point: 237-238 ° C. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 3.95 (2H, s), 5.06 (2H, s), 6.72 (1H, s), 6.93 (1H, d, J = 8Hz), 7.06 (2H, d, J = 7Hz), 7.12-7.15 (1H, m), 7.18 (1H, s), 7.25-7.28 (1H, m), 7.31-7.36 (3H, ra), 7.44 (1H, d, J = 8Hz), 7.70 (1H, s), 8.00 (1H, d, J = 8Hz), 8.06 (1H, d, J = 8Hz), 11.16 (lll, s).

The following compound of Example 16 (a) was obtained in the same manner as Example 1 (c). Example 16 a) 1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-1H-imidazol-4-yl) propanol. Starting compounds: ketone (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-imidazole-4-yl) and ethyl magnesium bromide. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 0.71-0.75 (3H, ra), 1.16-1.19 (2H, ra), 2.19 (3H, s), 5.49 (1H, s), 6.87 (1H, s), 7.10-7.12 (8H, m), 7. 36-7.43 (11H, ra), 7.51-7.55 (1H, ra), 7.61-7.67 (3H, ra), 7. 97 (1H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz), 8.25 (1H, d, J =; 3Hz), 8.49 (1H, s).

The following compound of Example 16 (b) was obtained in the same manner as Example 1 (d). b) 2- [1- (1H-imidazol-4-yl) propyl] -9-tosyl-9H-carbazole. Starting compound: 1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-1H-imidazol-4-yl) propanol. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). 6: 0.85 (3H, t, J = 7Hz), 1.97-1.99 (1H, m), 2.14-2.20 (1H, m), 2.24 (3H, s), 4.02-4.04 (1H, m), 6.90 (1H , br), 7.22 (2H, d, J = 8Hz), 7.33 (1H, d, J = 7Hz), 7.39-7.42 (1H, m), 7.51-7.54 (1H, m), 7.62-7.64 (3H, m), 7.98. (1H, br), 8.05 (1H, d, J = 7Hz), 8.17 (1H, br), 8.23-8.25 (1H, m), 11.81 (1H, br).

The following compound of Example 16 (c) was obtained in the same manner as Example 1 (e). c) 2- [1- (1H-imidazol-4-yl) propyl] -9H-tosyl-9H-carbazole. Starting compound: 2- [1- (lH-imidazol-4-idpropyl] -9-tosyl-9H-carbazole) Melting point: 229-230 ° C. Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS ). d: 0.84 (3H, t, J = 7Hz), 1.91-1.99 (1H, ra), 2.08-2.15 (1H, m), 3.89 (1H, br), 6.81 (1H, s), 7.07-7.12 (2H , m), 7.31-7.34 (2H, m), 7.43 (1H, d, J = 8Hz), 7.50 (1H, s), 7.96 (1H, d, J = 8Hz), 8.03 (1H, d, J = 8Hz), 11.07 (1H, s), 11.77 (1H, br).

The following compound of Example 17 (a) was obtained in the same manner as Example 1 (c).

Example 17 a) 1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-lH-imidazol-4-yl) butanol. Starting compounds: ketone (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-imidazole-4-yl) and magnesium propyl bromide. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 0.80-0.83 (3H, m), 1.08-1.11 (1H, ra), 1.23-1.28 (1H, ra), 2.04-2.08 (1H, ra), 2.13-2.15 (1H, ra), 2.20 (3K , s), 5.49 (1H, s), 6.85 (1H, s), 7.10-7.13 (8H, m), 7.37-7.42 (11H, ra), 7.51-7.56 (1H, m), 7.60-7.65 (3H , m), 7.96 (1H, d, J = 9Hz), 8.04 (1H, d, J = 7Hz), 8.24 (1H, d, J = 8Hz), 8.47 (1H, s).

The following compound of Example 17 (b) was obtained in the same manner as Example 1 (d). b) 2- [1- (1H-imidazol-4-yl) butyl] -9-tosyl-9H-carbazole. Starting compound: 1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-1H-imidazol-4-yl) butanol Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS) . d: 0.91 (3H, t, J = 7H'z), 1.14-1.25 (2H, ra), 1.94 (1H, br), 2.11 (1H, br), 2.23 (3H, s), 4.01-4.05 (1H , ra), 6.91 (1H, s), 7.22 (2H, d, J = 8Hz), 7.33-7.35 (1H, m), 7.39-7.42 (1H, m), 7-51-7.54 (1H, ra) , 7.62-7.64 (3H, m), 7.94-7.96 (1H, m), 8.04-8.05 (1H, m), 8.19-8.26 (2H, m), 11.81 (1H, br).

The following compound of Example 17 (c) was obtained in the same manner as Example 1 (e). c) 2- [1- (1H-imidazol-4-yl) butyl] -9H-carbazole Starting compound: 2- [1- (1H-imidazol-4-yl) butyl] -9-tosyl-9H-carbazole Melting point: 220 ° C Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 0.88 (3H, t, J = 7Hz), 1.17-1.28 (2H, ra), 1.87-1.95 (1H, m), 2.04-2.11 (1H, m), 3.99-4.02 (1H, ra), 6.81 (1H, s), 7.07-7.12 (2H, m), 7.31-7.34 (2H, m), 7.43 (1H, d, J = 9Hz), 7.50 (1H, s), 7.96 (1H, d, J = 8Hz), 8.03 (1H, d, J = 8Hz), 11.07 (1H, s), 11.78 (1H, br).

The following compound of Example 18 (a) was obtained in the same manner as Example 1 (c). Example 18 a) 2-methyl-1- (9-tosyl-9H-carbazol-2-yl) -1- (1 -trityl-1H-imidazol-4-yl) -propanol. Starting compounds: ketone (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-imidazole-4-yl) and isopropyl magnesium chloride. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 0.63 (3H, d, J = 7Hz), 0.82 (3H, d, J = 7Hz), 2.19 (3H, s), 2.65-2.68 (1H, m), 5.30 (1H, s), 6.92 (1H, s), .07-7.10 (7H, m), 7.20-7.22 (1H, ra), 7.38- 7.48 (11H, m), 7. 51-7.55 (1H, m), 7.69 (2H, d, J = 8Hz) -, 7.74 (1H, d, J = 8Hz), .95 (1H, d, J = 8Hz), 8.04 (1H, d, J = 8Hz), 8.26 (1H, d, J = 8Hz), 8.69 (1H, s).

The following compound of Example 18 (b) was obtained in the same manner as Example 1 (d). b) 2- [1- (1H-imidazol-4-yl) -2-methylpropyl] -9-tosyl-9H-carbazole. Starting compound: 2-methyl-1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-1H-imidazol-4-yl) propanol. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 0.76 (3H, d, J = 7Hz), 0.92 (3H, d, J = 6Hz), 3.67 (1H, br), 6.96 (1H, s), 7.20 (2H, d, J = 8Hz), 7.38 -7.41 (2H, m), 7.51-7.55 (1H, ra), 7.63-7.68 (3H, nt), 7.95 (1H, d, J = 8Hz), 8.03 (1H, d, J = 8Hz), 8.25 ( 1H, d, J = 8Hz), 8.32 (1H, s), 11.80 (1H, br).

The following compound of Example 18 (c) was obtained in the same manner as Example 1 (e). c) 2- [1- (1H-imidazol-4-yl) -2-methylpropyl] -9H-carbazole. Starting compound: 2- [1- (lH-imidazol-4-yl) -2-methylpropyl] -9-tosyl-9H-carbazole Mass spectrometry (m / z): 289 (M +, El) Magnetic resonance spectrum nuclear (DMSO-d6, internal standard TMS). d: 0.75 (3H, d, J = 7Hz), 0.89 ('3H, d, J = 6Hz), 2.41-2.47 (1H, m), 3.60 (1H, d, J = 10Hz), 6.88 (1H, s ), 7.08-7.16 (2H, m), 7.30-7.34 (1H, m), 7.41-7.43 (2H, m), 7.51 (1H, s), 7.94 (1H, d, J = 8Hz), 8.02 (1H , d, J = 8Hz), 11.08 (1H, s), 11.79 (1H, br).

Example 19 a) 1- (1H-imidazol-4-yl) -2-methyl-1- (9-tosyl-9H-carbazole-2-y1) propanol. 2-Methyl-1- (9-tosyl-9H-carbazol-2-yl) -1- (1-trityl-1H-imidazol-4-yl) -propanol (1.89 grams, 2.7 mmol) was dissolved in aqueous acetic acid at 90 percent, and the mixture was heated at 60 ° C for 3 hours. After cooling, the solvent was evaporated under reduced pressure, ethyl acetate was added to the resulting residue, and the mixture was extracted with 1 N hydrochloric acid. The water layer was neutralized with saturated aqueous sodium bicarbonate, extracted with acetate of ethyl, and then washed with water and brine. - * The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and then the resulting residue was purified by silica gel column chromatography ( elution with chloroform-methanol-aqueous 29% ammonia), to give 1.08 grams (2.4 mmol) of the title compound as a white foam. Spectrum of nuclear magnetic resonance (CDCI3, internal standard TMS). d: 0.79 (3H, d, J = 7Hz) f 1.02 (3H, d, J = 7Hz), 2.21 (3H, s), 2.57-2.86 (1H, m), 6.95-7.08 (3H, m), 7.31-7.47 (2H, m), 7.55-7.64 (4H, m), 7.75-7.84 (2H, m) , 8.28-8.35 (1H, m), 8.49 (1H, s). b) 2-ti- (lH-imidazol-4-yl) -2-methyl-l-propenyl] -9-tosyl-9H-carbazole. 1- (1H-imidazol-4-yl) -2-methyl-1- (9-tosyl-9H-carbazol-2-yl) propanol (1.08 grams, 2.4 mmol) was dissolved in 50 milliliters of methylene chloride, they added 3 grams (24 millimoles) of trifluoroacetic acid with ice cooling, and then the mixture was stirred at room temperature for 4 days. The solvent was evaporated under reduced pressure, ethyl acetate was added to the residue, and the mixture was washed with saturated aqueous sodium bicarbonate, water, and brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and then the resulting residue was purified by silica gel column chromatography (elution with chloroform-methanol-29 percent aqueous ammonia), give 950 milligrams (2.2 millimoles) of the title compound as a white foam. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.72 (3H, br), 2.15 (3H, br), 2.26 (3H, s), 6.73 (1H > br) i 7.16-7.18 (1H, m), 7.27 (2H, d, J = 8Hz) , 7.43 (1H, t, J = 7Hz), 7.54-7.62 (4H, m), 7.95 (1H, s), 8.05 (1H, d, J = 8Hz), 8.10 (1H, d, J = 7Hz), 8.26 ( 1H, d, J = 8Hz), 12. 01 (1H, br). c) 2- [1- (1H-imidazol-4-yl) -2-methyl-1-propenyl] -9H-carbazole monochlorohydrate.

A mixture of 2- [1- (1H-imidazol-4-yl) -2-methyl-1-propenyl] -9-tosyl-9H-carbazole (950 milligrams, 2.15 mmol), ethanol (100 milliliters) and hydroxide aqueous potassium 2 N (11 milliliters, 21.5 millimoles), heated under reflux for 14 hours. After cooling, the reaction mixture was neutralized with acetic acid (2.6 grams, 43 mmol), and the solvent was evaporated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was washed with 1 M aqueous potassium carbonate, water, and brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography. (elution with chloroform-ethanol-aqueous ammonia at 29 percent), to give 550 milligrams of a white foam. This was dissolved in ethyl acetate, 1 milliliter of 4 N hydrogen chloride in ethyl acetate was added with ice cooling) and the crystals thus precipitated were collected by filtration to give 480 milligrams (1.5 millimoles) of the title compound as crystals. whites. Melting point: 165-167 ° C. Spectrum of nuclear magnetic resonance (DMSO-d (), internal standard TMS). d: 1.86 (3H, s), 1.95 (3H, s), 6.92-6.94 (1H, ra), 7. 14-7.17 (1H, ra), 7.27 (TH, s), 7.36-7.40 (1H, m), 7.49 (1H, d, J = 8Hz), 7.59 (1H, s), 8.08-8.11 (2H, ra ), 9.01 (1H, s), 11.38 (1H, s), 14.40 (2H, br).

The following compound of Example 20 (a) was obtained in the same manner as in Example 1 (c). Example 20 a) Phenyl (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-imidazol-4-yl) methanol. Starting compounds: ketone (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-imidazole-4-yl) and phenyl magnesium bromide. Spectrum of nuclear magnetic resonance (DMSO-d, internal standard TMS). d: 2.22 (3H, s), 6.35 (1H, s), 6.81 (1H, s), 7.15-7.18 (8H, m), 7.22-7.24 (1H, m), 7.28-7.32 (2H, ra), 7. 37-7.47 (14H, m), 7.52-7.57 (3H, m), 7.95 (1H, d, J = 8Hz), 8. 04 (1H, d, J = 8Hz), 8.24-8.27 (2H, m).

The following compound of Example 20 (b) was obtained in the same manner as Example 1 (d). : b) 2- [(lH-imidazol-4-yl) (phenyl) ethyl] -9-tosyl-9H-carbazole. Starting compound: phenyl (9-tosyl-9H-carbazol-2-yl) (1-trityl-1H-imidazol-4-yl) methanol. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.24 (3H, s), 5.63 (1H, s), 6.72 (1H, br), 7.20-7.27 (3H, ra), 7.32-7.42 (6H, ra), 7.53-7.55 (3H, m), 7.72 (1H, s), 7.98 (1H, d, J = 8Hz) 8.05 (1H, d, J = 7Hz), 8.13 (1H, br), 8.26 (1H, d, J = 9Hz), 11.97 (1H, br ).

The following compound of Example 20 (c) was obtained in the same manner as in Example 19 (c). c) 2- [(1H-Imidazol-4-yl) (phenyl) methyl] -9H-carbazole monochlorohydrate. Starting compound: 2- [1- (1H-imidazol-4-yl) (phenyl) methyl] -9-tosyl-9H-carbazole. Melting point: 182-187 ° C. Spectrum of nuclear magnetic resonance (DMS0-d6, internal standard TMS). d: 5.87 (1H, s), 7.03-7.05 (1H, ra), 7.13-7.18 (2H, ra), 7.28-7.31 (1H, m), 7.35-7.39 (3H, m), 7.46-7.48 (1H , m), 8.07-8.09 (2H, m), 9.13 (1H, s), 11.34 (III, s), 14.62 (2H, br).

The following compound of Example 21 (a) was obtained in the same manner as Example 1 (a). Example 21 I) (9-tosyl-9H-carbazol-3-yl) (1-triyl-1H-imidazol-4-yl) methanol. Starting compounds: .3-bromo-9-tosyl-9H-carbazole and 1-ri-1-lH-imidazole -4-carbaldehyde. Spectrum of nuclear magnetic resonance (DMS0-d6, internal standard TMS). d: 2.23 (3H, s), 5.73 (1H, d, J = 5Hz), 5.76 (1H, d, J = 5Hz), 6.79 (1H, s), 7.09-7.11 (6H, ra), 7.25-7.28 (3H, m), 7.35-7.45 (10H, ra), 7.53-7.58 (2H, m), 7.73 (2H, d, J = 9Hz), 8.04-8.07 (2H, ra), 8.16 (1H, d, J = 9Hz), 8.25 (1H, d,, J = 8Hz). The following compound of Example 21 (b) was obtained in the same manner as in Example 1 (b). b) Ketone (9-tosyl-9H-carbazol-3-yl) (1-trityl-1H-imidazole-4-yl). Starting compound: (9-tosyl-9H-carbazol-3-yl) (1-trityl-1H-imidazol-4-yl) methanol. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.24 (3H, s), 7.18-7.20 (6H, m), 7.30 (2H, d, J = 9Hz), 7.40-7.49 (10H, m), 7.61-7.64 (1H, m), 7.69 (1H, d, J = lHz), 7.75 (1H, d, J = lHz), 7.81 (2H, d, J = 9Hz), 8.19 (1H, d, J = 8Hz), 8.29 (1H, d, J = 9Hz), 8.37 (1H, d, J = 9Hz), 8.48-8.50 (1H, m), 9.00 (1H, d, J = lHz) The following compound of Example 21 (c) was obtained in the same manner as in Example 1 (c). c) 1- (9-tosyl-9H-carbazol-3-yl) -1- (1-trityl-1H-imidazol-4-yl) ethanol. Starting compounds: ketone (9-tosyl-9H-carbazol-3-yl) (1-trityl-1H-imidazole-4-yl) and methyl magnesium bromide. , * • Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). 6: 1.80 (3H, s), 2.23 (3H, s), 5.70 (1H, s), 6.81 (1H, s), 7.09-7.11 (6H, m), 7.26 (1H, d, J = 8Hz), 7.35-7.45 (11H, mj, 7.54-7.58 (1H, m), 7.63-7.66 (1H, ra), 7.74 (2H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz), 8.11- 8.13 (2H, m), 8.25 (1H, d, J = 8Hz).

The following compound of Example 21 (d) was obtained in the same manner as Example 1 (d). d) 3- [1- (1H-imidazol-4-yl) ethyl] -9-tosyl-9H-carbazole. Starting compound: 1- (9-tosyl-9H-carbazol-3-yl) -1- (1-trityl-1H-imidazol-4-yl) ethanol. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.60 (3H, d, J = 7Hz), 4.21 (1H, q, J = 7Hz), 6.80 (1H, s), 7.26 (2H, d, J = 8Hz), 7: 39-7.46 (2H, m), 7.53-7.57 (2H, ra), 7.73 (2H, d, J = 8Hz), 8.00 ( 1H, d, J = lHz), 8.08 (1H, d, J = 7Hz), 8.14 (1H, d, J = 9Hz), 8.25 (1H, d, J = 9Hz), 11.82 (1H, s).

The following compound of Example 21 (e) was obtained in the same manner as Example 1 (e). ?) 3- [1- (lH-imidazol-4-yl) ethyl] -9H-carbazole. Starting compound: 3- [1- (1H-imidazol-4-yl) ethyl] -9-tosyl-9H-carbazole.

Melting point: 197-198 ° C. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 1.62 (3H, d, J = 7Hz), 4.20 (1H, q, J = 7Hz), 6.74 (1H, s), 7.12 (1H, t, J = 7Hz), 7.26-7.28 (1H, m) , 7.32-7.38 (2H, ra), 7.44 (1H, d, J = 8Hz), 7.50 (1H, s), 7.96 (1H, s), 8.04 (1H, d, J = 8Hz), 11.10 (1H, s), 11.76 (1H, s).

The following compound of Example 22 (a) was obtained in the same manner as in Example 1 (a). Example 22 a) (l-methyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) methanol. Starting compounds: 2-bromo-9-tosyl-9H-carbazole and l-methyl-lH-imidazole-5-carbaldehyde. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.25 (3H, s), 3.54 (3H, s), 6.05 (1H, d, J = 5Hz), 6.19 (1H, d, J = 5Hz), 6.44 (1H, s), 7.26 (2H, d , J Bllz), 7.42-7.45 (2H, m), 7.56-7.64 (4H, m), 8.08-8.16 (2H, ra), 8.27 (1H, d, J = 8Hz), 8.33 (1H, s).

The following compound of Example 22 (b) was obtained in the same manner as in Example 1 (b). b) Ketone (l-methyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazole-2-yl). Compounds of art: (l-methyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) methanol. Nuclear magnetic resonance spectrum (DMSO-dg, internal standard TMS). d: 2.26 (3H, s), 4.00 (3H, s), 7.32 (2H, d, J = 8Hz), 7.48-7.52 (1H, m), 7.59 (1H, 'S), 7.65-7.68 (1H, m), 7.75 (2H, d, J = 8Hz), 7.91 (1H, d; J = 8Hz), 8.11 (1H, s), 8.26-8.29 (2H, m), 8.32 (1H, d, J = 8Hz ), < 8.71 (1H, s).

The following compound of Example 22 (c) was obtained in the same manner as in Example 1 (c). c) 1- (1-methyl-1H-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) ethanol. Starting compounds: ketone (1-methyl-1H-imidazol-5-yl) (9-tosyl-9H-carbazole-2-ylac) and methyl magnesium bromide. * Spectrum of nuclear magnetic resonance (DMSO-d ^, internal standard TMS). d: 1.88 (3H, s), 2.25 (3H, s), 3.15 (3H, s), 6.22 (1H, s), 7.21 (1H, s), 7.26 (2H, d, J-8Hz), 7.31-7.33 (1H, m), 7.43 (1H, t, J = 7Hz), 7.51-7.58 (3H, m), 7.75 (1H, s), 8.03 (1H, d, J = 9Hz), 8.08 (1H, d, J = 8Hz), 8.25-8.28 (2H, m).

. The next compound of Example 22 (d) was obtained in the same manner as in Example 1 (d). d) 2- [1- (1-methyl-1-thimidazol-5-yl) ethyl] -9-tosyl-9H-carbazole. Compounds: 1- (1-methyl-1H-imidazol-5-yl) -1- (9-tosyl-9H-carbazol-2-yl) ethanol. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.61 (3H, d, J = 7Hz), 2.25 (3H, s), 3.19 (3H, s) 4.37-4.42 (1H, m), 7.00 (1H, s), 7.24-7.27 (3H, ra) , 7.42 (1H, t, J = 7Hz), 7.50-7.57 (3H, m), 7.61 (1H, s), 7.94 (1H, s), 8.03 (1H, d, J = 8Hz), 8.07, (1H , d, J = 7Hz), 8.26 (1H, d, J = 9Hz).

The following compound of Example 22 (e) was obtained in the same manner as in Example 1 (e). e) 2- ti- (l-methyl-lH-imidazol-5-yl) ethyl] -9H-carbazole. Starting compounds: 2- ti- (l-methyl-lH-imidazol-5-yl) ethyl] -9-tosyl-9H-carbazole. Melting point: '204-205 ° C. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.60 (3H, d, J = 7Hz), 3.25 (3H, s), 4.27-4.31 (1H, m), 6.94 (1H, s), 6.98-7.00 (1H, m), 7.11-7.14 (1H, in), 7.16 (1H, 'S), 7.32-7.36 (1H, m), 7.43 ( 1H, d, J = 9Hz), 7.50 (1H, s), 8.00-8.05 (2H, m), 11.11 (1H, s).

The following compound of Example 23 (a) was obtained in the same manner as in Example 1 (a). Example 23 a) (9-methyl-9H-carbazol-2-yl) (1-triyl-1H-imidazol-4-yl) methanol. Starting compounds: 2-bromo-9-methyl-9H-carbazole and l-trityl-lH-imidazole-4-carbaldehyde. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 3.83 (3H, s), 5.68-5.70 (1H, br), 5.76-5.77 (1H, ra), 6.78 (1H, s), 7.09-7.20 (8H, m), 7.28 (1H, s), 7. 35-7.45 (9H, ra), 7.52 (1H, s), 7.56 (1H, d, J = 8Hz), 8.03 (1H, d, J = 8Hz), 8.09 (1H, d, J = 8Hz), 8.32 (1H, s).

The following compound of Example 23 (b) was obtained in the same manner as Example 1 (b). b) Ketone (9-methyl-9H-carbazol-2-yl) (1-trityl-1H-imidazole-4-yl) Starting compound: (9-methyl-9H-carbazol-2-yl) (1-trityl) lH-imidazole-4-yl) methane Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS) d: 3.91 (3H, s), 7.19-7.30 (7K, ra), 7.41-7.48 (9H , m), 7.53-7.56 (1H, m), 7.65-7.66 (2H, m), 7.75 (1H, s), 8.08 (1H, d, J = 9Hz), 8.22-R.26 (2H, m) , 8.52 (1H, s).

The following compound of Example 23 (c) was obtained in the same manner as Example 1 (c). c) 1- (9-methyl-9H-carbazol-2-yl) (1-rityl-lH-imidazol-4-yl) ethanol. Ketone starting compounds (9-methyl-9H-carbazol-2-yl) (1-trityl-1H-imidazole-4-yl) and methyl magnesium bromide. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.82 (3H, s), 3.82 (3H, s), 5.53 (1H, br), 6.75 (1H, s), 7.08-7.10 (6H, m), 7.14-7.18 (1H, ra), 7.28-7.31 (2H, m), 7.34-7.44 (10H, m), 7.56 (1H, d, J = 8Hz), 7.60 (1H, s), 7.99 (1H, d, J = 8Hz), 8.07 (1H, d, J = 8Hz).

The following compound of Example 23 (d) was obtained in the same manner as Example 1 (d). d) 2- ti- (l-lH-imidazol-4-yl) ethyl] -9-methyl-9H-carbazole. Starting compound: 1- (9-methyl-9H-carbazol-2-yl) -1- (1-trityl-lH-imidazol-4-yl) ethanol.

Melting point: 215 ° C (decomposition). Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.64 (3H, d, J = 7Hz), 3.83 (3H, s), 4.25 (1H, q, J = 7Hz), 6.78 (1H, s), 7.10 (1H, d, J = 8Hz), 7.16 (1H, t, J = 7Hz), 7.40-7.43 (1H, m), 7.45 (1H, s), 7.52-7.55 (2H, ra), 8.01 (1H, d, J = 8Hz), 8.07 (1H, d, J = 8Hz), 11.82 (1H, br). The following compound of Example 24 (a) was obtained in the same manner as Example 1 (a). Example 24 a) Ketone (l-benzyl-lH-imidazol-5-yl) (9-tosyl-9H-carbazole-2-yl). Starting compound: (1-benzyl-1H-imidazol-5-yl) (9-tosyl-9H-carbazol-2-yl) methanol. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.26 (3H, s), 5.69 (2H, s), 7.25-7.31 (5H, m), 7. 35-7.38 (2H, ra), 7.48-7.5 l '(1H, m), 7.64-7.71 (4H, m), 7. 85-7.87 (1H, m), 8.24-8.30 (3H, m), 8.34 (1H, s), 8.61 (1H, s).

The following compound of Example 24 (b) was obtained in the same manner as Example 1 (c). b) 1- (1-benzyl-1H-imidazol-5-yl) -1- (9-tosyl-9H-carbazol-2-yl) ethanol. Starting compounds: ketone (1-benzyl-1H-imidazol-5-yl) (9-tosyl-9H-carbazole-2-yl) and methyl magnesium bromide. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 1.90 (3H, s), 2.13 (3H, s), 4.72 (1H, d, J = 15Hz), 4. 91 (1H, d, J = 15Hz), 6.30 (1H, s), 6.74 (2H, d, J = 7Hz), 6. 96-7.04 (3H, m), 7.11 (2H, d, J = 9Hz), 7.17 (1H, s), 7.22-7.24 (1H, m), 7.42 (1H, t, J = 8Hz), 7.46 (1H , s), 7.54-7.57 (3H, ra), 7.91 (1H, d, J = 8Hz), 8.05 (1H, d, J = 8Hz), 8. 26 (1H, d, J = 8Hz), 8.32 (1H, s). c) 2- [1- (1-Benzyl-1H-imidazol-5-yl) inyl] -9-tosyl-9H-carbazole. 1- (1-Benzyl-1H-imidazol-5-yl) -1- (9-tosyl-9H-carbazol-2-yl) ethanol (810 milligrams, 1.6 mmol) was dissolved in 10 milliliters of toluene, 1.8 was added. grams (16 mmol) of trifluoroacetic acid to the solution, and the mixture was heated under reflux for 14 hours. After cooling, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. Then, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (c 'chloroform-methanol elution), to give 570 milligrams (1.1 mmol) of the title compound as a white foam. Spectrum of nuclear magnetic resonance (DMSO-d6, internal standard TMS). d: 2.25 (3H, s), 4.87 (2H, s), 5.42 (1H, s), 5.71 (1H, s), 6.91 (2H, d, J = 7Hz), 7.04 (1H, s), 7.19- 7.26 (3H, m), 7.29 (2H, d, J = 7Hz), 7.32-7.34 (1H, ra), 7.43-7.46 (1H, m), 7.57-7.60 (3H, m), 7.96-7.99 (2H, ra), 8.09 (1H, d, J = 8Hz), 8.14 (1H, d, J = 8Hz), 8.25 (1H, d, J = 9Hz).

The following compound of Example 24 (d) was obtained in the same manner as in Example 19 (c) d) 2- ti- (1-benzyl-lH-imidazol-5-yl) inyl] -9H-carbazole monohydrochloride . Starting compound: 2- [1- (1-benzyl-1H-imidazol-5-yl) vinyl] -9-tosyl-9H-carbazole. Melting point: Í37-140 ° C. Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS) • d: 5.08 (2H, s), 5.52 (1H, s), 6.01 (1H, s), 7.03-7.05 (2H, m), 7.09- 7.10 (1H, m), 7.17-7.20 (1H, ra), 7. 26-7.31 (4H, ra), 7.39-7.43 (1H, m, 7.51 (1H, d, J = 8Hz), 7.92 (1H, d, J = 2Hz), 8.11-8.14 (2H, m), 9.45 ( 1H, s), 11.37 (1H, s) Example 25 4- (9H-Fluoren-2-ylmethyl) -lH-imidazole.

A solution in chloroform (100 milliliters) containing 10 grams (71 millimoles) of 1-trimethylsilyl-1H-imidazole was added to another solution in chloroform (200 milliliters) containing 13.5 grams (71 millimoles) of titanium tetrachloride., with cooling with ice, and the mixture was stirred at room temperature for 30 minutes. A solution in chloroform (100 milliliters) containing 3 grams (14 millimoles) of 2-chloromethyl-9H-fluorene was added and the mixture was stirred at room temperature for 14 hours. The reaction mixture was poured into ice water, and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution with chloroform-methanol-29 percent aqueous ammonia), to give 180 milligrams (0.7 mmol) of the title compound, which was recrystallized from ethyl acetate, to give crystals, white. Melting point: 205-206 ° C Nuclear magnetic resonance spectrum (DMSO-d6, internal standard TMS). d: 3.86 (2H, s), 3.91 (2H, s), 6.77 (1H, s), 7.25-7.29 (2H, m), 7.34-7.37 (1H, m), 7.43 (1H, s), 7.53- 7.56 (2H, m), 7.78 (1H, d, J = 8Hz), 7.83 (1H, d, J = 7Hz), 11.83 < 1H 'b ^) - The chemical structures of the compounds obtained in the Examples are shown in Table 2. In the table, the bonding position "a" means the binding position of A on the imidazole ring, and the position link "b" means the link position of A on the ring Also, the abbreviations in the table represent the following groups. I methyl Ethyl n-Pr normal propyl iso-Pr isopropyl n-Bu butyl normal Table 2 Table 2 (continued) Table 2 (continued) Table 2 (continued) Example R Position A Position X Salt, etc. link to link bl CH2 2 4 d -CH. -Q II 2 'NH HCl • c - 2 5 -CH, 2 'CH, Other compounds shown in Table 3 can be synthesized by making use of the production methods of the compounds of the present invention described in the present specification, the production methods of the Example, other methods well known to those skilled in the art and methods modified from them, without requiring special experiments Po Table 3 (continued) Table 3 (continued) Table 3 (continued) Table 3 (continued) Formulation example of oral preparation Composition Tablet materials Compound of the present invention 1.0 mg. Lactose 76.4 mg. Corn starch 19.3 mg. Hydroxypropyl cellulose 3.0 mg. Magnesium stearate 0.3 mg.

Subtotal 100.0 mg. Coating materials hydroxypropylmethyl cellulose 2919 2.9 mg. Polyethylene glycol 6,000 0.4 mg. Titanium oxide 1.6 mg. Talc 0.1 mg.

• Subtotal mg, Total 105 mg Tablets of 1 milligram The compound of the present invention (7 grams) and 534.8 grams of lactose were mixed in a polyethylene bag. This mixture was pulverized using a Sample Mili, (manufactured by Hosoka to Micron). The pulverized mixture (541.8 grams) was mixed uniformly with 135.1 grams of corn starch in a fluidized granulation coating apparatus (manufactured by Ohkawara Seisakusho). This was formed into granules by spraying 210 grams of a 10 percent hydroxypropyl cellulose solution. After drying, the granules were passed through a 20 mesh, mixed with 2.1 grams of magnesium stearate, and then formed into tablets of 100 milligrams per tablet using a die / perforator system of 0. 6.5 millimeters by 7.8 R , by means of a rotating tablet-forming machine (manufactured by Hata Tekko-sho). Using a coating machine (manufactured by Freund Sangyo), 350 grams of a coating solution containing 20.3 grams of hydroxypropylmethyl cellulose, 2.8 grams of 6,000 polyethylene glycol, 11.2 grams of titanium oxide, and 0.7 grams of talc were sprayed. , to the tablets thus prepared, thereby obtaining film-coated tablets, wherein each tablet was coated with 5 milligrams of the coating materials.

Claims (14)

1. •1. An imidazole derivative represented by the following general formula (I), a salt thereof, a hydrate thereof, or a solvate thereof:
2. (The symbols in the formula have the following meanings: A: a lower alkylene group unsubstituted or substituted by a hydroxyl group, an aryl group, a lower alkylidene group, or an oxo group (= 0), X: a methylene group or a group represented by the formula -NR2-, R: a hydrogen atom, a lower alkyl group, or an aralkyl group, and R: a hydrogen atom or a lower alkyl group). 2. A compound, a salt thereof, a hydrate thereof, or a solvate thereof according to claim 1, wherein A is linked in the 4-position or the 5-position of the imidazole ring.
3. 3. A compound, a salt thereof, a hydrate thereof, or a solvate thereof according to claim 2, wherein A is linked in the 2 or 3 position of the ring:
4. 4. A compound, a salt thereof, a hydrate thereof, or a solvate thereof according to claim 3, wherein A is a lower alkylene group unsubstituted or substituted by an aryl group or a lower alkylidene group.
5. 5. A compound, a salt thereof, a hydrate thereof, or a solvate of the mirmo according to the claim 4, wherein A is a lower alkylene group unsubstituted or substituted by a lower alkylidene group.
6. 6. A compound, a salt thereof, a hydrate thereof, or a solvate thereof according to the claim 5, wherein X is a group represented by the formula NR.
7. 7. 2- [1- (1H-imidazol-4-yl) ethyl] -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof.
8. 8. 3- [1- (1H-imidazol-4-yl) ethyl] -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof.
9. 9. 2 - (lH-imidazol-4-ylmethyl) -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof.
10. 10. 3- (1H-imidazol-4-ylmethyl) -9H-carbazole, a salt thereof, a hydrate thereof, or a solvate thereof.
11. 11. A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof as its active ingredient.
12. 12. A pharmaceutical composition as described in claim 11, which is a 17-20 steroid lyase inhibitor.
13. 13. The pharmaceutical composition as described in claim 12, which is an agent for the prevention or treatment of diseases, caused by androgen and / or estrogen.
14. 14. The steroid lyase inhibitor 17-20 according to claim 13, which is an agent for the prevention or treatment of prostate cancer, benign prostatic hyperplasia, virilism, hirsutism, breast cancer, mastopathy, hysteromyoma, and endometriosis.