MXPA98004743A - Derivativo de pirazol tricicl - Google Patents

Abstract

A tricyclic pyrazole derivative represented by the following general formula (I), or a pharmaceutically acceptable salt thereof, which shows strong affinity and selectivity for the 5HT2c receptor and is useful for the treatment of diseases of the central nervous system (v. ., sexual disorders, eating disorders, anxiety, depression, sleeping disorders and the like) (See Formula) (In the above formula, each symbol means the following: Ring Het: a five-membered unsaturated heterocyclic ring containing from 1 to 3 heteroatoms each selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, A: a straight or branched lower alkylene group, and R: a hydrogen atom, a lower alkyl group, a halogen atom, a group hydroxyl or a lower alkoxy group

Description

TRICYCLIC PIRAZOL DERIVATIVE TECHNICAL FIELD The present invention relates to a novel tricyclic pyrazole derivative or a pharmaceutically acceptable salt thereof. The present invention also relates to a pharmaceutical composition comprising said tricyclic pyrazole derivative or a salt thereof and a pharmaceutically acceptable carrier, especially a pharmaceutical composition that is useful as a drug for the prevention and treatment of diseases of the central nervous system. such as sexual disorders, appetite disorders, anxiety, depression and sleeping disorders. TECHNICAL BACKGROUND With the advancement of the older society, the improvement of living conditions for the elderly has been reconsidered, so that attention has been focused on the prevention and treatment of diseases that have long been considered as diseases (e.g., sexual disorders and the like). Although the role of the 5-HT2c receptor that is mainly distributed in the central nerve has not been sufficiently disclosed, it is considered that this receptor refers to diseases of the central nervous system such as sexual disorders, appetite disorders, anxiety, depression, disorders when sleeping and the like (Curr Opin Opin Invest Drugs, 2 (4), 317 (1993)). Accordingly, it is thought that the ligand of the 5-HT2c receptor is effective for the prevention or treatment of the diseases mentioned above, particularly diseases that have been considered as diseases that do not have an effective therapeutic method (eg, sexual disorders). and similar). With respect to the tricyclic pyrazole derivatives which are 5-HT2C receptor agonists, only one tricyclic pyrazole derivative fused to a benzene ring (EP 700905-A) and the like has been reported, but reports on a a tricyclic pyrazole derivative that fuses with the unsaturated heterocyclic ring. In addition, a compound having a tricyclic pyrazole nucleus which is fused to a pyrazine ring, a pyridine ring, a thiophene ring, a furan ring or a pyrrole ring is reported in the international publication WO 96/13478, and a compound having a tricyclic pyrazole nucleus that is fused with an aromatic heterocyclic ring and also has a substituent on a carbon atom of the pyrazole ring in the core, is reported in International Publication WO 95/07893. However, these references do not disclose a compound in which the amine is linked to the 1-position of the tricyclic pyrazole nucleus via an alkylene cadmium and also about the ratio between the reported compounds and the 5-HT2C receptor-DESCRIPTION OF THE INVENTION As a result of extensive studies on compounds having 5-HT2c receptor activity, the inventors of the present invention find that the novel tricyclic pyrazole derivative has high selectivity and high affinity for the 5-HT2c receptor and achieved the present invention based on this finding. Accordingly, the present invention relates to a novel tricyclic pyrazole derivative represented by the following general formula (I) which shows high selectivity and high affinity for the 5-HT2C receptor or a pharmaceutically acceptable salt thereof. (each symbol in the above formula means the following: Ring Het: a five-membered unsaturated heterocyclic ring containing from 1 to 3 heteroatoms each selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom A: a straight or branched lower alkylene group, and R: a hydrogen atom, a lower alkyl group, a halogen atom, a hydroxyl group or a lower alkoxy group). The compound (I) of the present invention is characterized by its chemical structure in which an amine is linked to the 1-position of the tricyclic pyrazole nucleus fused to a five-membered unsaturated heterocyclic ring, always via an alkylene chain.

Among the compounds (I) of the present invention, the compounds in which A is an ethylene group or a propylene group are preferred, and are particularly acceptable (S) -2- (1 H-furo [2,3-g] indazol-1-yl) -1-methylethylamine, 2- (7-bromo-1 H -thieno [2,3-g] indazol-1-yl) ethylamine, 2- (7-iodo-1 H-thieno [2, 3-g] indazol-1-yl) ethylamine, 2- (7-methoxy-1H-thieno [2,3-g] indazol-1-yl) ethylamine, 2- (1 H-furo [2,3-g ] indazol-1-yl) ethylamine or pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition comprising a tricyclic pyrazole derivative or a salt thereof and a pharmaceutically acceptable carrier. Particularly, it relates to a pharmaceutical composition which is a 5-HT2C ligand and is a useful as a drug for the prevention and treatment of diseases of the central nervous system such as sexual disorders, appetite disorders, anxiety, depression, sleeping disorders and similar. Hereinafter, the compound (I) of the present invention is described more in detail. The term "5-HT2c receptor ligands" means a compound that has the affinity for the 5-HTc receptor and shows agonism or antagonism. In the definition of the general formula as used herein, unless otherwise noted, the term "lower" means a straight or branched carbon chain having from 1 to 6 carbon atoms.

Illustrative examples of the "lower alkylene group" include methylene, ethylene, tmethylene, propylene, tetramethylene, ethylethylene, pentamethylene, hexamethylene and the like and ethylene and propylene are preferred. Illustrative examples of the "lower alkyl group" include methyl, ethyl, propyl, isopropyl. , butyl, isobutyl, sec-butyl, tert-butyl, pentyl (amyl), isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl and the like of which alkyl groups having from 1 to 4 carbon atoms are preferred and particularly a methyl group is preferred Examples of the "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, of which a bromine atom and an iodine atom are preferred. The term " "lower alkoxy group" means an oxy-group substituted with the lower alkyl group mentioned above Illustrative examples of the "five-membered unsaturated heterocyclic ring containing from 1 to 3 heteroatoms sele Each of the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom "includes thiophene, furan, pyrrole imidazole, pyrazole, tlazole, oxazole, isothiazole, isoxazole, thiazole thiazole, oxadiazole and the like, which are preferred thiophene and furan The compound (I) of the present invention may contain an asymmetric atom depending on the kinds of groups Accordingly, a mixture or isolated form of optical isomers is also included in the compound (I) of the present invention The compound (I) of the present invention can form acid addition salts. These salts are also included in the compound of the present invention. Illustrative examples of the salts include acid addition salts with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid and the like), with organic acids (e.g. , formic acid, acetic acid, propionic acid, 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) and with acidic amino acids ( e.g., aspartic acid, glutamic acid and the like). In addition, the compound (I) of the present invention or a pharmaceutically acceptable salt thereof can be isolated as hydrates, various types of solvates (e.g., ethanol solvate and the like) or polymorphic forms thereof, and these various Hydrates, solvates and polymorphic forms are also included in the compound of the present invention. (Production Method) The compound (I) of the present invention can be prepared using various synthetic methods making use of the properties characteristic of its basic nucleus or substituents. The normal production methods are described in the following: Production Method 1 (In the above reaction scheme, the ring Het, R and A are as defined in the above and X means an alkylene group having smaller carbon atoms per one atom than those of A). The compound (I) of the present invention can be prepared by reducing a nitrile compound represented by the formula (II). This reaction may be carried out under a condition of cooling to heating, preferably at room temperature, using a reducing agent suitably in the presence or absence of a suitable inert solvent such as diethyl ether, t-butylmethylether, tetrahydrofuran, dioxane, 1, 2-dimethoxyethane, methylene chloride, benzene or toluene, preferably in ethers (e.g., tetrahydrofuran and the like), and if necessary in the presence of an appropriate Lewis acid. Aluminum chloride or the like can be used as Lewis acid, and complex hydride, such as lithium aluminum hydride or the like can be used as a reducing agent. Alternatively, this reaction may be carried out by catalytic hydrogenation over a metal catalyst, preferably palladium-carbon, platinum oxide, Raney nickel or the like using an appropriate solvent such as ethyl acetate, an alcohol, tetrahydrofuran, dioxane, acetic acid or a mixture thereof. Production Method 2 (In the above reaction scheme, the ring of Het, R and A are as defined in the above, and Y means a protected amino group such as acid group, acetamido group or the like). The compound (I) of the present invention can be prepared by reduction or deprotection of the compound (III). When Y is an azido group or the like, this reduction can be carried out under a cooling to heating condition, preferably at room temperature, using an appropriate reducing agent in the presence or absence of the same appropriate inert solvent used in the production method. , preferably in ethers (e.g., tetrahydrofuran and the like), and if necessary in the presence of an appropriate Lewis acid such as aluminum chloride or the like. As the reducing agent, the complex hydride, such as lithium aluminum hydride or the like can be used. Alternatively, this reaction may be carried out by catalytic hydrogenation over a metal catalyst, preferably palladium-carbon, platinum oxide or nickel similar Raney, using an appropriate solvent such as ethyl acetate, an alcohol, tetrahydrofuran, dioxane , acetic acid or a mixture thereof or using triphenylphosphine. When Y is an acetamido group or the like, a similar method described in Protecting Groups in Organic Synthesis, John Wiley & Sons, Inc. Preferably, the reaction can be carried out under a cooling condition to heating, preferably under heating, in a suitable solvent such as water, ethylene glycol, dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane or a alcohol (eg, methanol, ethanol, propanol, isopropanol or the like) in the presence of an appropriate base such as potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, lithium carbonate, ammonia, sodium methoxide, sodium ethoxide or the like, and preferably metal oxide such as potassium hydroxide, sodium hydroxide or the like. The starting compounds of each of the above-mentioned production methods 1 and 2 can be easily obtained by using the methods of the Reference Examples and Examples which will be described later directly by modifying or applying them. The compound of the present invention produced in this form was isolated in its free form or as its salt. A salt of the compound of the present invention can be produced by subjecting the compound of the invention in the free base form to the usual salt formation reaction. The compound (I) of the present invention or a salt thereof, it can also be isolated and purified as a hydrate or solvate or in its polymorphic form. The isolation and purification can be carried out using generally used chemical methods such as extraction, concentration, evaporation, crystallization, filtration, recrystallization and various chromatographic techniques. Various types of isomers can be separated by selecting the compound from appropriate materials or making use of the difference in physical properties between isomers. For example, optical isomers can be prepared as stereochemically pure isomers by selecting the appropriate material or can be separated by carrying out racemic resolution of racemic compound (for example, a method in which a compound is derived in diastereomeric salts with an optically general acid. active and then subjected to optical resolution). INDUSTRIAL APPLICABILITY Since the compound of the present invention has high affinity and selectivity for the 5-HT2c receptor and is effective in animal models, it is useful for the treatment of diseases of the central nervous system such as sexual disorders (v.gr, impotence and similar), obesity, appetite disorders (e.g., hyperphagia, hypophagia), anxiety, depression and sleeping disorders. The selectivity and affinity of the compound of the present invention for the 5-HT2C receptor and its evaluation in an animal model using rats was confirmed by the following methods. A. Binding analysis The 5-HT2C and 5-HT2A receptors: Carried out by the binding analysis of 5-HT [3H] according to the method of A. Pazos et al., Eur. J. Pharmacol., 106 , 539 - 546 (1985) or S. Havlik and SJ Peroutka, Brain Res., 584, 191 -196 (1992). Using the above method, the concentration of a drug that inhibits 50% of the receptor binding ligand (IC 50 value) was calculated and the Ki value representing the affinity of the receptor was obtained by the following formula. Ki = IC50 / (1 + [L] / [Kd]) ([L]: ligand concentration, [Kd]: dissociation constant) The results are shown in Table 1. Table 1 Union Analysis (Ki, nM) Therefore, the compound of the present invention showed high affinity for the 5-HT2C receptor and approximately 20 times higher selectivity compared to that of the 5-HT2A receptor. B. In vivo test using rats Induction of penile erection in rats: it is known that penile erection is induced by the stimulation of the 5-HT2C receptor (Berendsen &Broekkamp, Eur. J. Pharmacol., 135, 179- 184 (1987)). This compound was administered to rats and the frequency of penile erection for 30 minutes after administration was measured to obtain the minimum effective dose by which a statistically significant reaction was observed. The results are shown in Table 2. Table 2 In vivo test using rats Therefore, the compound of the present invention is effective in an animal model using rats and is therefore useful for the treatment of diseases of the central nervous system such as sexual disorders (e.g., impotence and the like). The pharmaceutical composition containing one or two or more of the compound (I) of the present invention, pharmaceutically acceptable salts thereof, hydrates thereof, solvates thereof and the like and the active ingredient is prepared in tablets, powders, fine granules, granules , capsules, pills, solutions, injections, suppositories, ointments, adhesive preparations and the like using generally filled pharmaceutical vehicles and other additives and administered orally (including sublingual administration) or parenterally.

The clinical dose of compound (I) of the present invention in humans is optionally decided upon taking into account the symptoms, weight, age, sex and the like of each patient to be treated, as well as the route of administration and the like, but the compound it can be administered orally in a dose of generally 10 mg to 1,000 mg, preferably 50 mg to 200 mg, per day per adult, and the daily dose can be divided from 1 to several doses per day or administered by intravenous injection in a dose generally of 1 mg to 500 mg, preferably 5 mg to 100 mg per day per adult and the daily dose can be divided into 1 at several doses per day or administered by intravenous drip infusion within the range of 1 hour to 24 hours per day. Since the dose varies under several conditions as described in the previous one, a smaller dose than the previous scale may be sufficient in some cases. The solid composition for use in oral administration according to the present invention is used in the form of tablets, powders, granules and the like. In said solid composition, one or more active substances are mixed with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropylceiulose, microcrystalline cellulose, starch, polyvinyl pyrrolidone or aluminum magnesium silicate. In the usual manner, the composition may contain other additives than the inert diluent, such as magnesium stearate or similar lubricant, calcium cellulose glycolate or similar disintegrating agent, lactose or similar stabilizing agent and glutamic acid, aspartic acid or the solubilizing auxiliary agent. If necessary, tablets or pills can be coated by sugar coating with a film of a gastric or enteric substance such as sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate or the like. The liquid composition for use in oral administration includes pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like and contains a generally used inert diluent such as purified water or ethyl alcohol. In addition to the inert diluent, this composition also contains auxiliary agents (e.g., a solubilizing agent or solubilization aid, a wetting agent, a suspending agent and the like), as well as sweeteners, flavorings, aromatics and antiseptics. Injections for use in parenteral administration include aqueous or non-aqueous solutions, suspensions and emulsions. Examples of the diluent for use in aqueous solutions and suspensions include distilled water for the use of the injection and physiological saline. Examples of the diluent for use in non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, olive oil or oil from similar plants, ethanol or similar alcohol, polysorbate 80 (trade name) and the like. Said composition may further contain additive agents such as a tonicity agent, an antiseptic, a wetting agent, an emulsifying agent, a dispersing agent, a stabilizing agent (e.g., lactose) and a solubilizing or auxiliary solubilizing agent. These compositions are sterilized by filtration through a filter that retains bacteria, mixing a germicide or irradiation. Alternatively, they can be used first by forming sterile solid compositions and then dissolving them in sterile water or a sterile solvent for injection use before use. BEST MODE FOR CARRYING OUT THE INVENTION Examples of the present invention are given below by way of illustration and not only by way of limitation. In this relation, the compounds of materials can be used in the Examples described as reference examples. Reference Example 1. To a solution of tetrahydrofuran (80 ml) containing 7.29 g of tert-butoxy potassium was added dropwise and under ice cooling a solution of tetrahydrofuran (40 ml) containing 4.42 g of 6,7-dihydro- 5H-benzofuran-4-one and 10.47 ml of ethyl formate, and the mixture was stirred for 1 hour. Then, 6.97 ml of hydrazinoethanol was added to the reaction solution, 1N hydrochloric acid was added to adjust a pH value of about 9, and then the mixture was stirred at room temperature for 17 hours. The reaction solution was adjusted to a basic condition by adding aqueous sodium hydroxide solution and then extracted with chloroform. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (eluent: chloroform / methanol = 95/5) to give 4.67 g of 2- (4-5-dihydro-1 H-furo [ 2,3-g] indazol-1-yl) ethanol in the form of a pale yellow solid. Reference Example 2 In the same manner as Reference Example 1 was described, 2- (4,5-dihydro-1 H-furo [3,2-g] indazol-1-yl) ethanol was obtained. Reference Example 3 In a solution of tetrahydrofuran (20 ml) containing 2.95 g of tert-butoxipotassium, a solution of tetrahydrofuran (10 ml) containing 2.00 g of 4-oxo-4,5 was added dropwise and cooled in ice. 6,7-tetrahydrobenzo [b] thiophene and 3.89 g of ethyl formate and the mixture was stirred at room temperature for 30 minutes. After completing the reaction, 26 ml of 1N hydrochloric acid was added. Then, 3.16 hydrazinoethane was added under cooling with ice, and the mixture was stirred at room temperature for 2 hours. The reaction solution was extracted with methylene chloride. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the filtrate was concentrated under reduced pressure to give 1.56 g of 2- (4,5-dihydro-1 H-thieno [2,3-g] indazol-1-yl) ethanol in shape of a yellow solid.

The compounds of Reference Examples 4 to 7 were obtained in the same manner as described in Reference Example 3. Reference Example 4: 2- (7-Bromo-4,5-dihydro-1 H-thieno [2 , 3-g] indazol-1-yl) ethanol. Reference Example 5: 2- (4,5-Dihydro-7-iodo-4,5-dihydro-1 H -thieno [2,3-g] indazol-1-yl) ethanol. Reference Example 6: 2- (7-Chloro-4,5-dihydro-1 H-thieno [2,3-g] indazol-1-yl) ethanol. Reference Example 7: 2- (7-Methoxy-4,5-dihydro-1 H -thieno [2,3-g] indazol-1-yl) ethanol. Reference Example 8 2.04 g of 2- (4,5-dihydro-1 H-furo [2,3-g] indazol-1-yl) ethanol were dissolved in 40 ml of methylene chloride, and 4.18 ml of triethylamine and 1.16 ml of methanesulfonyl chloride and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water and extracted with chloroform. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the resulting filtrate was concentrated under reduced pressure to give 3.23 methanesulfonate of 2- (4,5-dihydro-1H-furo [2,3-g] indazol-1-yl. )ethyl. Reference Example 9 3.23 g of 2- (4,5-dihydro-1 H-furo [2,3-g] indazol-1-yl) ethyl methanesulfonate were dissolved in 20 ml of dimethylformamide, 1.95 g of azide was added. of sodium and the mixture was stirred at 70 ° C for 17 hours. The reaction solution was cooled, poured into ice water and then extracted with ether. The organic layers were combined, washed with brine and then dried with anhydrous magnesium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to give 1.64. g of 1- (2-azidoethyl) -4,5-dihydro-1 H-furo [2,3-g] indazole. Reference Example 10 1.35 g of 2- (4-5-dihydro-1 H-furo [3,2-g] indazol-1-l) ethanol were dissolved in 20 ml of methylene chloride, 2.76 ml of triethylamine and 0.77 ml of methanesulfonyl chloride were added and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into ice water and then extracted with chloroform. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After the drying agent was removed by filtration, the solvent was concentrated under reduced pressure, the resulting residue was dissolved in 20 ml of dimethylformamide. Then, 1.29 g of sodium azide was added and the mixture was stirred at 80 ° C for 5 hours. After cooling, the reaction solution was poured into ice water and then extracted with ether. The combined organic layers were washed with brine and then dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure to give 1.30 g of 1- (2-azidoethyl) -4,5-dihydro-1 H-furo [3,2-g-] indazoi Reference Example 11 5.10 g of 2- (4,5-dihydro-1 H-thieno [2,3-g] indazol-1-yl) ethanol were dissolved in 50 ml of 1,2-dichloroethane, 7.74 ml was added. of triethylamine and 2.15 ml of methanesulfonyl chloride at 0 ° C and the mixture was stirred for 2 hours. The reaction solution was poured into ice water and extracted with chloroform. The organic layers were combined and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure, and the resulting residue was dissolved in 30 ml of dimethylformamide. Then, 3.01 g of sodium azide was added and the mixture was stirred at 80 ° C for 3 hours. The reaction solution was cooled, poured into ice water and then extracted with ethyl acetate. The organic layers were combined, washed with water and brine in that order and dried over anhydrous magnesium sulfate. After the removal the drying agent by filtration, the solvent was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: toluene / ethyl acetate = 5) to give 3.39 g of 1- (2-azidoethyl) -4.5- dihydro-1 H-thieno [2,3-g] indazole as a yellow oil. Reference Example 12 1.00 g of 1- (2-azidoethyl) -4,5-dihydro-1 H-thieno [2,3-g] indazole was dissolved in 30 ml of dioxane, 2.80 g of 2.3- was added. dichloro-5,6-dicyano-1,4-benzoquinone at room temperature and the mixture was heated under reflux for 8 hours. The reaction solution was poured into aqueous sodium bicarbonate solution and then extracted with chloroform. The organic layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: toluene / ethyl acetate = 6) to give 0.73 g of 1- (2-azidoethyl) -1 H -thieno [2,3-g] indazole as a pale brown oil. Reference Example 13 1- (2-Azidoethyl) -7-bromo-4,5-dihydro-1 H-thieno [2,3-gyndazole was obtained in the same manner as described in Reference Example 10. Example of Reference 14 1- (2-Azidoethyl) -1H-thieno [2,3-g] indazole was obtained in the same manner as described in Reference Example 12. Reference Example 15 1- (2-azidoethyl) was obtained ) -7-bromo-4,5-dihydro-7-iodo-1 H-thieno [2,3-g] indazole in the same manner as described in Reference Example 10. Reference Example 16 Obtained 1- (2-azidoethyl) -7-iodo-1 H-thieno [2,3-g] indazole in the same manner as described in Reference Example 12. Reference compounds 17 to 18 were obtained therein as described in reference example 10. Reference Example 17: 1- (2-Azidoethyl) -7-chloro-4,5-dihydro-1 H -thieno [2,3-g] indazole. Reference Example 18: 1- (2-Azidoethyl) -7-methoxy-4,5-dihydro-1 H-thieno [2,3-g] indazole. Reference Example 19 0.51 g of lithium aluminum hydride in 20 ml of tetrahydrofuran was suspended under argon. Under cooling with ice, a solution of tetrahydrofuran (10 ml) containing 1.55 g of 1- (2-azidoethyl) -4,5-dihydro-1 H-furo [2,3-g] indazole was added to the suspension. sic .i "and the mixture was stirred for 1 hour, methanol was added to the reaction solution to decompose the excess lithium aluminum hydride and then 0.51 ml of water, 0.51 ml of 15% aqueous sodium hydroxide solution. and 1.53 ml of water were added in that order.The resulting mixture was stirred for 30 minutes, anhydrous sodium sulfate and "celite" were added and then the mixture was stirred further for 30 minutes.The resulting soluble matter was removed by filtration of "celite", the resulting filtrate was concentrated and the resulting residue was purified by column chromatography on silica gel (eluent: chloroform / methanol = 9/1) to give 1.26 g of 2- (4,5-diohydro-1 H) -furo [2,3-g] indazol-1-yl) ethylamine 0.11 g of 2- (4,5-dihydro-1 H -fuoro [2,3-g] indazol-1-yl) ethylamine was dissolved in a mix of ethanol and ethyl acetate. Then, 4N hydrochloric acid in ethyl acetate was added and the resulting precipitate was collected by filtration and dried under reduced pressure to give 0.092 g of 2- (4,5-dihydro-1 H-furo [2,3-] hydrochloride. g] indazol-1-yl) ethylamine. Reference Example 20 2- (4,5-Dihydro-1 H-furo [3,2-g] indazol-1-yl) ethylamine hydrochloride was obtained, in the same manner as described in Reference Example 19. Reference Example 21 1.15 g of 2- (4,5-dihydro-1 H-furo [2,3-g] indazoI-1-yl) ethyiamine were dissolved in 40 ml of methylene chloride, 0.64 ml of acetic anhydride , 1.91 m of triethylamine and 30 mg of dimethylaminopyridine and the mixture was stirred at room temperature for 18 hours. The solvent was evaporated and the resulting residue was purified by silica gel column chromatography (eluent: chloroform / methanol = 98/2) to give 1.28 g of N- [2- (4,5-dihydro-1 H-furo [2, 3-g] indazol-1-yl) ethyl] acetamide. Reference Example 22 N- [2- (4,5-Dihydro-1H-furo [3,2-g] indazol-1-yl) ethyl] acetamide was obtained in the same manner as described in Reference Example 21 Reference Example 23 1 24 g of N- [2- (4,5-d? H? Dro-1 H-furo [2,3-g]? Ndazol-1-? L) et? L] was dissolved. acetamide in 20 m of dioxane, 1 16 g of 2,3-d? chlor-5,6-d? c? ano-1,4-benzoquinone was added and the mixture was heated under reflux for 4 hours Then, 058 g of 2,3-d-chloro-5,6-d-cyano-1,4-benzoquinone was added and the mixture was further heated under reflux for 17 hours. The reaction solution was cooled, it was poured into aqueous sodium bicarbonate solution and then extracted with ethyl acetate. The organic layers were combined, washed with brine and then dried over magnesium sulfate anhydride. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography. (hexane / ethyl acetate = 1/4) to give 0 53 g of N- [2- (1H-furo [2,3-g] ndazol-1-? l) et? lo] acetam? da Reference Example 24 044 g of lithium aluminum hydride in 50 ml of tetrahydrofuran under argon, a solution of tetrahydrofuran (10 ml) containing 260 g of (1 H-furo [2,3-g] ndazole-) acetate were suspended. 1-) ethyl was added dropwise and the mixture was stirred at room temperature for 1 hour. Methanol was added under cooling with ice to the reaction solution to decompose excess lithium aluminum hydride and then 044 ml of water was added. , 044 ml of 15% aqueous solution of sodium hydroxide and 1 30 ml of water in that order The resulting mixture was stirred for 30 minutes, anhydrous magnesium sulfate and "celite" were added and the mixture was further stirred for 30 minutes After removal of insoluble matter by filtration, the resulting filtrate was concentrated under reduced pressure to give 1.82 g of 2- (1 H-furo [2,3-g] ndazole- 1-?) Ethanol reference example 25 A solution of dimethyl sulfoxide (15 ml) containing 420 ml of tetylamine and 474 g of the SO3-p? R? D? Na complex was added to a solution of dimethyl sulfoxide ( 15 ml) containing 1 80 g of 2- (1 H-furo [2,3-g]? Ndazol-1-? L) ethanol and the mixture was stirred at room temperature for 30 minutes The reaction solution was poured into water, it was acidified with 1N hydrochloric acid and then extracted with ethyl acetate. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration the solvent was concentrated under a reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1) to give 089 g of (1H-furo [2,3-g]? ndazo-1-? l) acetaldehyde Referential Example 26 Under cooling with ice, a solution of dimethylformamide (5 ml) was added dropwise. 100 g of 1H-furo [2,3-gjindazole was added to a solution of dimethylformamide (10 ml) containing 027 g of sodium hydride under argon and the mixture was stirred for 30 minutes. 052 ml of propylene oxide was added thereto. The reaction solution was cooled with ice and the mixture was stirred at room temperature for 41 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2) to give 0.59 g of 1- (1 H-furo [2,3-g] indazol-1-yl) propane-2-ol. Reference Example 27 Under an argon atmosphere, 5 ml of 1.0 M tetrahydrofuran solution of ethylmagnesium bromide was diluted with 5 ml of tetrahydrofuran, a solution of tetrahydrofuran (5 ml) of 0.30 g of (1 H-furo [2, 3-g] indazol-1-yl) acetaldehyde was added dropwise and the mixture was stirred at room temperature for 3 days. The reaction solution was poured into aqueous ammonium chloride solution and extracted with ethyl acetateThe organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1) to give 0.29 g of 1- (1H-furo [2,3-g] indazoi -1-yl) butanol. The compounds of Examples 28 and 29 were obtained in the same manner as described in Reference Example 27. Reference Example 28: 1- (1 H-furo [2,3-g] indazol-1-yl) pentanol.

Reference Example 29: 1- (1 H-furo [2,3-g] indazol-1-yl) -3-methyl-2-butanol. The compounds of Reference Examples 30 to 32 were obtained in the same manner as described in Reference Example 8. Reference Example 30: 2- (1 H -furo [2,3-g] indazol-1 methanesulfonate -yl) -1-methylethyl. Reference Example 31: 1- (1 H -furo [2,3-g] indazol-1-ylmethyl) butyl methanesulfonate. Reference Example 32: 1- (1 H -furo [2,3-g] indazol-1-ylmethyl) -2-methylpropyl methanesulfonate. Reference Example 33 1- (2-azidopropyl) -1 H-furo [2,3-g] indazole was obtained in the same manner as described in Reference Example 9. Reference Example 34 1- (2 -zidobutyl) -1 H-furo [2,3-g] indazole in the same manner as described in Reference Example 10. Reference Example 35 2- (8-methyl-4,5-dihydro-1H was obtained -pyrazolo [3,4-e] [1,2] benzyl-isoxazole in the same manner as described in Reference Example 3, Reference Example 36 1- (2-azidoethyl) -8-methyl-4 was obtained , 5-dihydro-1H-pyrazole [3,4-e] [1,2] benzyl-isoxazole in the same manner as described in Reference Example 10. Reference Example 37 1- (2-azidoethyl) was obtained -8-methyl-1 H-pyrazole [3,4-e] [1,2] benzyl-isoxazole in the same manner as described in Reference Example 12. Reference Example 38 0.14 g of sodium hydride were washed with hexane under argon and 5 ml of dimethylformamide were added.With cooling under ice, 0.50 of 1 H-furo [2] was gradually added. , 3-g] indazole in 5 ml of dimethylformamide and the mixture was stirred for 1 hour. 0.33 ml of 2-bromopropiononitrile was added to the reaction solution under cooling with ice and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layers were combined, washed, brine and then dried over anhydrous sodium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4) to give 0.45 g of 2- (1H-fu ro [2.3 g] indazoi-1 -i I) propionitrile. Reference Example 39 (S) -1- (2-azidopropyl) -1H-furo [2,3-g] indazole was obtained in the same manner as described in Reference Examples 26 and 10. Example 1 1.60 was added of potassium hydroxide to a solution of ethylene glycol (20 ml) containing 0.51 g of N- [2- (1 H-furo [2,3-g] indazol-1-yl) ethyl] acetamide, and the mixture was stirred at 170 ° C for 2 hours. The reaction solution was cooled, diluted with water and then extracted with ethyl acetate. The organic layers were combined, washed with water and brine and then dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the resulting filtrate was concentrated and the resulting residue was purified by column chromatography on silica gel (eluent: chloroform / methanol = 95/5) to give 2- (1 H-furo) [2,3-g] indazol-1-yl) ethylamine. The resulting 2- (1 H-furo [2,3-g] indazol-1-yl) ethylamine was dissolved in a mixture of ethanol and ethyl acetate, 4N hydrochloric acid in ethyl acetate was added to the resulting solution, and the resulting precipitate was collected by filtration and dried under reduced pressure to give 0.06 g of 2- (1H-furo [2,3-g] indazol-1-yl) ethylamine hydrochloride. Example 2 0.94 g of N- [2- (4,5-dihydro-1 H-furo [3,2-g] indazol-1-yl) ethyl] acetamide was dissolved in 20 ml of dioxane, 0.86 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, and the mixture was heated under reflux for 4 hours. Then, 0.86 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone was added and the mixture was heated under reflux for 17 hours. The reaction mixture was cooled, poured into aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration the resulting filtrate was concentrated under a reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 4) to give 0.075 g of N - [2- (1 H-furo [3, 2-g] indazol-1-yl) ethyl] ac, ethamide. This was dissolved in 10 ml of ethylene glycol, 0.40 g of. Potassium hydroxide were added and the mixture was stirred at 170 ° C for 2 hours. The reaction solution was cooled, diluted with water and then extracted with ethyl acetate. The organic layers were combined, washed with water and brine and then dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the resulting filtrate was concentrated and the resulting residue was purified by column chromatography on silica gel (eluent: chloroform / methanol = 95/5) to give 2- (1 H-furo [3,2-g] indazol-1-yl) ethylamine. The resulting 2 - (? H -furo [3,2-g] indazol-1-yl) ethylamine was dissolved in a mixture of ethanol and ethyl acetate, 4N hydrochloric acid in ethyl acetate was added to the resulting solution and the resulting precipitate was collected by filtration and dried under reduced pressure to give 0.03 g 2- (1 H-furo [3,2-g] indazol-1-yl) ethylamine hydrochloride.

The compounds of Examples 3 and 4 were obtained in the same manner as described in Reference Example 19. Example 3: 2- (1 H-furo [2,3-g] indazol-1-yl) hydrochloride -1-methylethylamine. Starting compound: 1 (2-azidopropyl) -1 H-furo [2,3-g] indazole Example 4: 1-Ethyl-2- (1 H-furo [2,3-g] indazol-1-yl) ethylamine hydrochloride. Starting compound: (1- (2-Azidobutyl) -1 H-furo [2,3-g] indazole Example 5 0.045 g of sodium azide was added to 0.088 g of methanesulfonate of 1- (1 H-furo [ 2,3-g] indazol-1-ylmethyl) butyl in 5 ml of dimethylformamide and the mixture was stirred at 80 ° C. for 16 hours.The reaction solution was cooled, poured into ice water and then extracted with ether The organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate.After removal of the drying agent by filtration, the resulting filtrate was concentrated under reduced pressure to give 0.063 g of 1- (2- azido pentyl) -1 H-furo [2,3-g] indazole. Under argon, 0.018 g of lithium aluminum hydride were suspended in 5 ml of tetrahydrofuran, a solution of tetrahydrofuran (5 ml) containing 0.063 g of 1 - (2 -zidopentyl) -1 H-furo [2,3-g] indazole was added dropwise to the resulting suspension under cooling with ice and the resulting mixture was stirred for 30 minutes. Methanol was added to the reaction solution to decompose excess lithium aluminum hydride. Then, 0.018 ml of water, 0.018 ml of 15% aqueous sodium hydroxide solution and 0.054 ml of water were added in that order and the resulting mixture was stirred for 30 minutes. Then, anhydrous sodium sulfate and "ceiite" were added and the mixture was further stirred for 30 minutes. The resulting insoluble matter was removed by filtration with celite, the resulting filtrate was concentrated and then the resulting residue was purified by silica gel column chromatography (eluent: chloroform / methanol = 95/5) to give 1- (1H- furo [2,3-g] indazol-1-ylmethyl) butylamine. The resulting 1- (1 H-furo [2,3-g] indazol-1-yl) methyl-1-butylamine was dissolved in a mixture of ethanol and ethyl acetate, 4 N hydrochloric acid in ethyl acetate was added to The resulting solution and the resulting precipitate was collected by filtration and dried under a reduced pressure to give 0.04 g of 1- (1H-furo [2,3-g] indazol-1-ylmethyl) butylamine hydrochloride. Example 6 1- (1 H -furo [2,3-g] indazol-1-ylmethyl) -2-methylpropylamine hydrochloride was obtained in the same manner as described in Example 5 from 1 (1H-methanesulfonate. -furo [2,3-g] indazol-1-ylmethyl) -2-methylpropyl Example 7 2- (1 H -thieno [2,3-g] indazol-1-yl) ethylamine hydrochloride was obtained in the same manner as described in Reference Example 19 from 1- (2-azidoethyl) -1 H -thieno [2,3-g] indazole.

Example 8 0.91 triphenylphosphine was added to 0.93 g of 1- (2-azidoethyl) -7-bromo-1 H-thieno [2,3-g] indazole dissolved in 20 ml of tetrahydrofuran and the solution was heated under reflux for 1.5 hours. Then, 0.08 g of water was added and the mixture was heated under reflux for 3 hours. The reaction mixture was cooled, concentrated under reduced pressure and then diluted with a mixture of methanol and methylene chloride. The resulting solution was acidified by adding 1N hydrochloric acid and washed with chloroform and the resulting water layer was made alkaline with 40% aqueous sodium hydroxide solution and again extracted with chloroform. The organic layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the resulting filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: chloroform / methanol / saturated aqueous ammonia = 20/1 / 0.1 - 10/1 / 0.1) to give 0.73 g of 2- (7-bromo-1 H-thieno [2,3, g] indazol-1-yl) ethylamine as a pale yellow oil The 2- (7-bromo- The resulting 1 H-thieno [2,3-g] indazol-1-yl) ethylamine was dissolved in 8 ml of ethanol0.6 ml of 4 N hydrochloric acid in ethyl acetate was added to the resulting solution and the resulting precipitate was collected by filtration and dried under reduced pressure to give 0.59 g of 2- (7-bromo-1 H- hydrochloride. thieno [2,3-g]? ndazol-1-yl) ethylamine. Example 9 2- (i7-Iodo-1H-thieno [2,3-g] indazo! -1-ii) ethylamine hydrochloride was obtained in the same manner as described in Example 8 from 1- (2 -azidoethyl) -7-iodo-1 H-thieno [2,3-g] indazole. Example 10 1.48 of 1- (2-azidoethyl) -7-methoxy-4,5-dihydro-1 H-thieno [2,3-g] indazole was dissolved in 20 ml of dioxane, 3.66 g of 2,3-dichloro 5,6-dicyano-1,4-benzoquinone were added at room temperature, and the resulting mixture was heated under reflux for 8 hours. The reaction solution was cooled and poured into aqueous sodium bicarbonate solution, the resulting insoluble matter was removed by filtration with "celite", and then the resulting filtrate was extracted with ethyl acetate. The organic layers were combined, washed with brine, mixed with activated charcoal and then dried over anhydrous magnesium sulfate, the resulting filtrate was concentrated under reduced pressure, the resulting residue was dissolved in 4 ml of tetrahydrofuran. Then, 0.85 g of triphenylphosphine was added, and the resulting mixture was heated at 50 ° C for 30 minutes. Then, 0.18 g of water was added and the mixture was further heated to 50 ° C for 1 hour. After cooling, 1 ml of hydrochloric acid in 4 N ethyl acetate was added to the resulting solution and the resulting precipitate was recovered by filtration and dried under reduced pressure. The product obtained was recrystallized from ethanol to give 0.34 g of 2- (7-methoxy-1 H-furo [2,3-g] indazol-1-yl) ethylamine hydrochloride as a white powder. Example 11 2- (7-Chloro-1 H-thieno [2,3-g] indazo! -1-yl) ethylamine hydrochloride was obtained in the same manner as described in Example 10 from 1- (2 -azidoethyl) -7-chloro-4,5-dihydro-1 H -thieno [2,3-g] indazole. Example 12 2- (8-Methyl-1 H-pyrazole [3,4-e] [1,2] benzoisoxazol-1-yl) ethylamine hydrochloride was obtained in the same manner as described in Example 8 from 1- (2-azidoethyl) -8-methyl-1 H-pyrazole [3,4-e] [1,2] benzoisoxazole. Example 13 Under argon, 0.08 g of lithium aluminum hydride was suspended in 20 ml of tetrahydrofuran, 0.29 g of aluminum chloride was added under cooling with ice and the mixture was stirred for 15 minutes. To this suspension was added a solution of tetrahydrofuran (5 ml) of 0.42 g 2- (1 H-furo [2,3-g] indazol-1-yl) propiononitrile under cooling with ice and the mixture was stirred at room temperature for 30 minutes. Methanol was added to the reaction solution to decompose the excess amount of the reagent. 10 ml of 40% aqueous sodium hydroxide solution were added and then the mixture was stirred for 10 minutes. The resulting insoluble matter was removed by filtration with "celite", the resulting filtrate was extracted with chloroform and then the organic layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography (eluent; chloroform / methanol / saturated aqueous ammonium = 10/1 / 0.1) to give 0. 39 g of 2- (1 H-furo [2,3-g] indazol-1-yl) propylamine. The resulting 2- (1H-furo [2,3-g] indazol-1-yl) propylamine was dissolved in ethanoi, 4N hydrochloric acid in ethyl acetate was added to the resulting solution and the resulting precipitate was recovered by filtration and dried under reduced pressure to give 0.22 g of 2- (1 H-furo [2,3-g] indazol-1-yl) propylamine hydrochloride as a white solid. Example 14 (S) -2- (1 H -furo [2,3-g] indazol-1-yl) -1-methylethylamine hydrochloride was obtained in the same manner as described in Example 19, from (S) -1- (2-azidopropyl) -1 H-furo [2,3-g] indazole. The chemical structural formulas and the physicochemical properties of the compounds obtained in the reference and Examples are shown in the following tables. Each of the symbols used in the tables means the following: Rf: Reference Example No. Ex: Example No. NMR: Nuclear magnetic resonance spectrum (internal standards DMSO-d6 and TMS, unless otherwise indicated) d: m / z: Mass spectrometry data (m / z) Me: Methyl group Et: Ethyl group Pr: Propyl group Pr: Soapyl group Table 3-1 Table 3-2 Rf. NMR: 2.81-2.93 (4H, m) .3.15-3.24 (2a num.4.50 (2H.t), 7. I40H, d), 7.350R s), 7.71 OH. d) .8.33 (3H, brs) NMR (CDClj): 1.91 (3H, s), 2.89-2.92 (4H, t), 3.72 (2H, t), 4.34 (2H.t), 6.67 H. d). 21 7.310H. s) .7.37 OH. d) NMR (CDCI3): 1.91 (3H, s) .2.79 (4H.t) .3.71-3.76 (2H.m) .4.46-4.50 (2H.m) .6.23 22 OH. brs) .6.390H. d), 7.30 GR s) .7.38 OH. d) 'NMR (CDCIj): l S7 (3H. s), 3.79-3.85 (2Rm), 4.69-4.73 (2Rpü.5.92 (IR brs) .7.24 23 OH. dd) .7.380R dd), 7.58 OH. d) .7.74 OH. d), 8.06GH. s) NMR (CDCl 3): 3.01 (IR t) .4.18-4.23 (2R m), 4.68-4.71 (2R m) .7.11 (IR dd), 7.39 24 OR dd) .7.60 OR d) .7.75 OH. d) .8.06 OH, s) NMR: 5.67 (2R s), 7.40-7.42 OH. m). 7.46 (IR d), 7.68 (IR d) .8.08-8.10 (IR m), 8.180H, s), 9.79 OH, s) NMRCCDClj): 1.33 (3R d) .3.30 OH. d) .4.41-4.63C3H. m), 7.11 (IR d), 7.39 (IR d), 26 7.60 OH, d) .7.75 OR d) .8.07 (IR s) NMRCCDClj): 1.05C3H. t) .1.54-1.66 (2Hjn .3.37 (IR brs), 4.07-4.15 (1H.m), 4.46 27 OH, dd), 4.61 OH, dd), 7.08-7. lOORpú, 7.37 OH, d) .7.57 OH. d) .7.73 OH. d), 8.04 (lH, s) NMR (CDCI,): 0. 95 (3R t) .1.38-1.66 (4ft m) .3.36 Oa brs) .4.16-4.220H. m) .4.45 28 (1H. Dd) .4.590R dd), 7.09 (IH. Dd), 7.37 (1H. Dd), 7.57 (1R d), 7.72 OH. d), 8.03 OH. s) NMRCCDClj): 1. 09 (3H.t), 1.82-1.93C1H. m) .3.21 OH. d), 3.91-3.96 (IH, m) .4.51 29 ORdd), 4.690R dd), 7.10 (1R dd) .7.38 OH. dd), 7.60 OH, d) .7.74 OH. d). 8.07 (IR s) NMR (CDClj): l. 57 (3R d) .2.31 (3Rs), 4.68 OH. dd) .4.82 OR dd) .5.20-5.31 OH. m) .7.20- 7.21 OH, m) .7.40 OH. dd), 7.58 OH. d) .7.77 (lH, d) .8.09 (IR s) NMR (CDC13): 0. 99C3R t), 1.47-1.68 (2R m) .1.73-1.93 (2R m), 2.27 (3H. S) .4.71 31 ORdd) .4.85 OH. dd) .5.13-5.21 (IR m) .7.22 OH, dd) .7.40OR dd) .7.58 OH. d) .777ÜH.d), 8.08 OR s) 32 NMR (CDC13): 1. 17-1.21 (6R m) .2.15 (3R s), 4.70-4.89 (2R m), 5.06-5. ORm), 7.19 OH. dd) .7.40 OR dd) .7.58 (IR d) .7.77 OR d) .8.09 (IR s) NMRCCDC1,):!. 36C3H. d) .4.12-4.230R m), 4.55-4.58C2H. m) .7.10-7. OH. m). 33 7.38-7.41 (IR m) .7.60 OH, d) .7.76 (IR d), 8.09 (IR s) NMRCCDClj):!. 10C3H. t) .1.61-1.80 (2R m) .3.91-4.00 OH. m) .4.53-4.67 (2H. m), 34 7.10OR dd) .7.39 OH. dd) .7.60 OH, d) .7.75 OR d) .8.09 OH. s) NMRCCDClj): 7. 370R s) .4.39C2H. t) .4.08C2H. q), 3.51 (IR t) .3.02-2.96 (2H, m) .2.89- 2.83C2H.m) .2.57C3H. s) 36 NMRCCDClj): 7 .43C1H. s), 4.44C2R t) .4.22 (2H.), 3.03-2.98 (2H.m), 2.89- 2.84 (2H.m) .2.59 (3Rs) Table 3-3 MRCCDC13): 8.16 OH, s), 7.82 ClRd) .7.390H.d), 4.81 (2H, t), 3.91 (2H.t), 37 2.9IC3H. s) 1.94 (3H, d) .6.46 OH. q) .7.56 (1H, dd), 7.67 (ia dd) .7.740H. d) .8.20 OH. 38 d) .8.330H, s) ÍMR: 1.32 (3R d) .4.15-4.22 (IR m), 4.60-4.78 (2R m>, 7.44-7.48 OH, m). 39 7.50-7.580H. m) .7.670R d), 8.13 OH, d) .8.190R s) Table 4-1 Table 4-2

Claims (5)

1. CLAIMS 1. A tricyclic pyrazole derivative represented by the following general formula (I) (each symbol in the above formula means the following: Ring Het: a five-membered unsaturated heterocyclic ring containing from 1 to 3 heteroatoms each selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom A: a straight or branched lower alkylene group, and R: a hydrogen atom, a lower alkyl group, a halogen atom, a hydroxyl group or a lower alkoxy group), or a pharmaceutically acceptable salt thereof. 2. (S) -2- (1 H -furo [2,3-g] indazol-1-yl) -1-methylethylamine, 2- (7-bromo-1 H -thieno [2,3-g] indazol-1 -yl) ethanamine, 2- (7-iodo-1H-thieno [
2. 2.3-g] indazol-1-yl) ethylamine, 2- (7-methoxy-1H-thieno [2,3-g] indazol-1 -yl) ethylamine, 2- (1 H-furo [2,3-g] indazol-1-yl) ethylamine or pharmaceutically acceptable salts thereof.
3. 3. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
4. 4. The pharmaceutical composition according to claim 3, wherein this is a 5-HT2C ligand.
5. 5. The pharmaceutical composition according to claim 4, wherein this is a therapeutic impotence drug.