KR890008138A - Azaspiro compounds, preparation method and use thereof - Google Patents

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Azaspiro compounds, preparation method and use thereof

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Claims (19)

Azaspiro compounds and salts thereof of the general formula: [Wherein R ₁ and R ₂ independently represent hydrogen, a hydrocarbon residue which may have a substituent, or an acyl group which may have a substituent; R ₃ represents a hydrocarbon moiety which may have hydrogen or a substituent; Each of X ₁ and X ₂ is oxygen or sulfur; Y represents an oxygen, sulfur or a group of the general formula: -N (R ₄ )-(wherein R ₄ represents hydrogen or a lower alkyl group); m represents 0 or 1: n represents 0 or 1.] The azaspiro compound and salt thereof according to claim 1, wherein the salt is a physiologically acceptable salt. The azaspiro compound and salt thereof according to claim 1, wherein R ₃ is hydrogen. The azaspiro compound and salt thereof according to claim 1, wherein Y is oxygen. The azaspiro compound according to claim 1, wherein m is 0 and a salt thereof. The azaspiro compound and salt thereof according to claim 1, wherein X ₁ is oxygen. The azaspiro compound and salt thereof according to claim 1, wherein X ₂ is oxygen. The azaspiro compound according to claim 1, wherein n is 0 and a salt thereof. The compound of claim 1, wherein R ₁ and R ₂ independently represent (1) hydrogen, (2) hydrocarbon residue or acyl, and each hydrocarbon residue or acyl is halogen, nitro, cyano, hydroxy, (C _1-4) alkoxy (C _1-4) alkylthio, amino, mono- or di (C _1-4) alkyl-substituted amino, mono- or di-aralkyl-substituted amino, mono- or di-pyridyl carbonate carbonyl-substituted amino, (C ₁ ~ ₄₎ alkoxycarbonyl, hydroxy-carbonyl, (C ₁ ~ ₆₎ alkyl-carbonyl, cycloalkyl-carbonyl, carbamoyl, mono- or di (C ₁ ~ ₄₎ alkyl -aza-spiro compounds and salts thereof which may be substituted by carbamoyl, and phenyl-carbamoyl-substituted carbamoyl, phenyl, phenoxy, benzoyl, page ethoxycarbonyl, phenyl (C ₁ ~ ₄₎ alkyl. 10. The method of claim 9, wherein the hydrocarbon moiety is a (C ₁ ~ ₆₎ alkyl, (C ₂ ~ ₄₎ alkenyl, (C ₂ ~ ₄₎ alkynyl, (C ₃ ~ ₇₎ a single cyclic cycloalkyl, ( C ₈ ~ ₁₄₎ bridge cyclic saturated hydrocarbon residue or a (C ₈ ~ ₁₄₎ bridge the annular-aza-spiro compounds and salts thereof unsaturated hydrocarbon residues spanning over. 10. The method of claim 9, wherein the (C ₁ ~ ₆₎ carboxylic acyl, carboxylic bamik acyl, sulfonic acyl or a substituted acyl-butyloxycarbonyl a-aza-spiro compounds and salts thereof. According to claim 1, wherein, R ₁ is hydrogen, (C ₁ ~ ₆₎ alkyl, optionally substituted by halogen or unsubstituted (C ₁ ~ ₄₎ alkyloxycarbonyl or (C ₁ ~ ₆₎ aromatic group- Azaspiro compounds that are oxycarbonyl and salts thereof. According to claim 1, wherein, R ₁ is-aza spiro compounds and salts thereof are hydrogen or alkyl (C ₁ ~ _4). According to claim 1, wherein, R ₂ is unsubstituted (C ₁ ~ ₆₎ alkyl-aza-spiro compounds and salts thereof. The azaspiro compound and salt thereof according to claim 1, wherein the compound is 2-methoxy-2,8-diazaspiro [4,5] decane-1,3-dione hydrochloride. The azaspiro compound according to claim 1, wherein the compound is 2-methoxy-8- (2-bromoethylcycarbonyl) -2,8-diazaspiro [4,5] decane-1,3-dione and His salt. A pharmaceutical composition for the treatment and / or prophylaxis of dementia, which comprises, as an active ingredient, an effective amount of a compound of formula (I) or a physiologically acceptable salt thereof, and a physiologically acceptable carrier or diluent: [Wherein, R ₁ and R ₂ independently represent hydrogen, a hydrocarbon residue which may have a substituent, or an acyl group which may have a substituent; R ₃ represents a hydrocarbon moiety which may have hydrogen or a substituent; Each of X ₁ and X ₂ is oxygen or sulfur; Y represents an oxygen, sulfur or a group of the general formula: -N (R ₄ )-(wherein R ₄ represents hydrogen or a lower alkyl group); m represents 0 or 1; n represents 0 or 1] Treatment and / or prophylaxis of dementia characterized by administering to a mammal an effective amount of a compound of formula (I) or a physiologically acceptable salt thereof: [Wherein, R ₁ and R ₂ independently represent hydrogen, a hydrocarbon residue which may have a substituent, or an acyl group which may have a substituent; R ₃ represents a hydrocarbon moiety which may have hydrogen or a substituent; Each of X ₁ and X ₂ is oxygen or sulfur; Y represents an oxygen, sulfur or a group of the general formula: -N (R ₄ )-(wherein R ₄ represents hydrogen or a lower alkyl group); m represents 0 or 1; n represents 0 or 1.] As a method for preparing the compound of formula (I) and salts thereof: [Wherein, R ₁ and R ₂ independently represent hydrogen, a hydrocarbon residue which may have a substituent, or an acyl group which may have a substituent; R ₃ represents a hydrocarbon moiety which may have hydrogen or a substituent; Each of X ₁ and X ₂ is oxygen or sulfur; Y represents an oxygen, sulfur or a group of the general formula: -N (R ₄ )-(wherein R ₄ represents hydrogen or a lower alkyl group); m represents 0 or 1; n represents 0 or 1.] (1) After reacting a compound of formula (II) with a compound of formula (III), the resulting compound is cyclized and, if necessary, R ₁ ′. Or removing the protecting group contained in R _{2 /} itself or R ₁ ′ or R ₂ ′ to prepare the compound of formula (I) wherein m is 0 and a salt thereof; [Wherein, X ₁ , X ₂ , R ₃ , Y and n have the same meaning as above; R ₁ 'has the same meaning as the above R ₁ or or R ₁ is a R ₁ is protected by a protecting group whose functional group is a functional group gajilttae; R ₂ ′ has the same meaning as R ₂ above, or when R ₁ has a functional group, the functional group thereof is R ₂ protected by a protecting group: and Z represents a leaving group.] (2) The following general formula (Ia) Reacting the compound with a compound of formula (IV) below and, if necessary, removing a protecting group to prepare the compound of formula (I) wherein m is 0 and salts thereof; In the above formulas, [R ₁ ′, R ₂ ′, R ₃ ′, X ₁ , X ₂ , Y, Z and n have the same meanings as above.] (3) The compound of formula (Ia) Rebound with a compound of formula (V) and, if necessary, a protecting group to remove the compound of formula (I) wherein m is 0 and a salt thereof: R ₁ '-N = C = 0; (Ⅴ) In the above formula, [R ₁ ′ means the same as above.], (4) The compound of formula (Ib) is reacted with the compound of formula (IV). To prepare a compound of formula (I) wherein m is 0 and a salt thereof: [Wherein, R ₂ ′, R ₃ , X ₁ , X ₂ , Y and n have the same meanings as above; R ₅ represents hydrogen or hydroxy; And Z 'represents halogen.] (5) A compound of formula (Ic) is reacted with a compound of formula (VII) and, if necessary, a protecting group is removed to remove the general formula (I) , m is 0.) or a salt thereof [Wherein, R ₁ ′, R ₂ ′, R ₃ ′, Z ′ and n have the same meanings as above.] Or (6) by reacting a compound of formula (Ie) with an oxidizing agent, A process for producing a compound of formula (I) wherein m is 1 and R ₁ is lower alkyl which may be substituted. [Wherein, R ₂ ′, R ₃ , X ₁ , X ₂ , Y and n have the same meaning as above, and R ₁ ″ is lower alkyl which may be substituted.] ※ Note: The disclosure is based on the initial application.