KR880012629A - New Ribofuranuronic Acid Derivatives - Google Patents

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Description

New Ribofuranuronic Acid Derivatives

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Claims (15)

1'-deoxy-1 '-(6-amino-9-furinyl)-substituted at the 2 position -D-ribofuranuronic acid amide and thioamide. 1'-deoxy-1 '-(6-amino-9-purinine)-substituted at the 2-position of the following general formula (I) -D-ribofuranuronic acid amide and thioamide. Wherein R ₁ represents hydrogen, (C _1-6 ) alkyl, which is hydroxyl, -SH- or A group (wherein R ₄ and R ₅ each represent another hydrogen or (C _1-4 ) alkyl) can be optionally monosubstituted; (C _3-7 ) alkenyl, (C _3-7 ) alkynyl, (C _3-7 ) cycloalkyl is hydroxyl, -SH- or _May optionally be mono- or disubstituted in the cycloalkyl ring by a group wherein R ₄ and R ₅ are as defined above; (C _3-7 ) cycloalkyl (C _1-3 ) alkyl is hydroxyl, -SH- or _May optionally be mono- or disubstituted in the cycloalkyl ring by a group wherein R ₄ and R ₅ are as defined above; Phenyl is halogen having an atomic number of 9-35, (C _1-4 ) alkyl, (C _1-4 ) alkoxy, hydroxyl, —SH—, —S— (C _1-4 ) alkyl, —SO ₂ — (C _1-4 ) alkyl, trifluoro) methyl, or _May be optionally single or double substituted by a group wherein R ₄ and R ₅ are as defined above; Phenyl- (C _1-6 ) alkyl is halogen having an atomic number of 9-35, (C _1-4 ) alkyl, (C _1-4 ) alkoxy, hydroxyl, -SH-, -S- (C _{1- 4} ) alkyl, -SO _2- (C _1-4 ) alkyl or Groups, wherein R ₄ and R ₅ are as defined above, are optionally mono- or disubstituted in the phenyl ring, and the (C _1-6 ) alkylene chain is straight or branched chain, May be optionally substituted; Phenyl- (C _3-7 ) alkenyl is halogen having an atomic number of 9-35, (C _1-4 ) alkyl, (C _1-4 ) alkoxy, hydroxyl, -SH-, -S- (C _{1 -4} ) alkyl, -SO _2- (Ci_ ₄ ) alkyl or _May be optionally substituted in the phenyl ring by a group wherein R ₄ and R ₅ are as defined above; 5-or 6-membered, monocycle heterocycle heteroaryl contains one or two nitrogen atoms or one oxygen atom or one sulfur atom and each nitrogen atom; Or 5, 6, monosacyl heteroaryl- (Ci_ ₅ ) alkyl contains one or two nitrogen atoms or one oxygen atom or one sulfur atom and each nitrogen atom in the heteroaryl moiety, wherein The alkylene moiety is straight or branched, optionally substituted by a hydroxyl group, and R ₂ is hydrogen, (C _1-4 ) alkyl [this is hydroxyl, SH- or Optionally substituted by a group wherein R ₄ and R ₅ are as defined above] or (C _3-8 ) cycloalkyl, and R ₃ represents hydrogen or (C _1-4 ) Alkyl, which is hydroxyl, -SH- or Optionally substituted by a group wherein R ₄ and R ₅ are as defined above, and R ₅ is halogen, (C _1-4 ) alkyl, (C _3-7 ) cycloalkyl, cyano Or the formulas -OR ₄ , -SR ₄ , Group where R ₄ and R ₅ are as defined above, and X is O or S. A compound of the following general formula (Ia). Wherein R ₁ ^a represents hydrogen, (C _1-6 ) alkyl, (C _3-7 ) cycle, which is hydroxyl, -SH- or _May be optionally mono- or double substituted by groups wherein R ₄ and R ₅ are as defined above; Phenyl- (C _1-6 ) alkyl is halogen having an atomic number of 9-35, (C _1-4 ) alkyl, (C _1-4 ) alkoxy, hydroxyl, -SH-, -S- (C _{1- 4} ) alkyl, -SO _2- (C _1-4 ) alkyl or Groups, where R ₄ and R ₅ are as defined above, may optionally be mono- or disubstituted in the phenyl ring, wherein the (C _1-6 ) alkylene chain is straight or branched, and a hydroxyl group Or phenyl may be optionally substituted with halogen, (C _1-4 ) alkyl-, (C _1-4 ) alkoxy, hydroxyl, -SH-, -S- (C _1-4 ) alkyl-, trifluoromethyl- or Optionally single or double substituted by groups (wherein R ₄ and R ₅ are as defined above), R ₂ ^a is hydrogen, (C _1-4 ) alkyl [which is hydroxyl, -SH- or Optionally optionally single substituted by a group wherein R ₄ and R ₅ are as defined above; Or (C _3-8 ) cycloalkyl, and R ₃ ^a is hydrogen or (C _1-4 ) alkyl, which is hydroxyl, -SH- or Optionally optionally mono-substituted by a group wherein R ₄ and R ₅ are as defined above, and R _5Q is halogen having 9-35 atomic number, (C _1-4 ) alkyl or a formula —OR, -SR, or Group where R ₄ and R ₅ are as defined above, and X is O or S. Compounds of the general formula (lb) Wherein R ₁ ^b is hydrogen, (C _1-6 ) alkyl, (C _3-7 ) cycloalkyl as hydroxyl, —SH- or Halogen, (C _1-4 ) alkyl, (C _1-4 ), optionally mono- or double-substituted, or having a 9-35 atom number, by a group wherein R ₄ and R ₅ are as defined above Alkoxy, hydroxyl, -SH-, S- (C _1-4 ) alkyl, -SO ₂ (C _1-4 ) alkyl-, trifluoromethyl- or -SO ² _May be optionally substituted by a group, where R ₄ and R ₅ are as defined above, wherein R ₂ ^b is hydrogen, (C _1-4 ) alkyl [which is hydroxyl, —SH— or Optionally substituted by a group wherein R ₄ and R ₅ are as defined above; or (C _3-8 ) cycloalkyl, and R ₃ ^b is (C _1-4 ) alkyl and, R ₆ ^b is (C _1-4) alkyl, chlorine, bromine, methoxy, methylthio, methyl amino or dimethylamino, X represents O or S. The compound according to claim 1, which is selected from the following compounds. 1'-deoxy-1 '-(2-methyl-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylthioamide. 1'-deoxy-1 '-(2-chloro-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-bromo-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-ethyl-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-isopropyl-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-methoxyphenylamimino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methylamino-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methylthio-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-dimethylamino-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methoxy-6-cyclopentylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1′-deoxy-1 ′-(2-bromo-6-amino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-ethoxyphenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6- (3,4-dimethoxyphenyl) amino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6- (3-pentyl) amino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-m-flufurophenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-Fluorophenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-chlorophenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-isopropylamino-9-furinyl) -βD-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-triplefuorophenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6- (3 phenyl) -amino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-ethoxyphenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6-P-methoxyphenylamino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6- (4-dimethoxyphenyl) -amino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. 1'-deoxy-1 '-(2-methyl-6- (4-methylsulfonylphenyl) -amino-9-furinyl) -β-D-ribofuranuronic acid-N-ethylamide. In the method for preparing 1'-deoxy-1 '-(6-amino-9-furinyl) -β-D-ribofuranuronic acid amide and thioamide substituted at the 2-position, the isopropylidene protecting group is Characterized in that it is segmented from 1'-deoxy-1 '-(6-amino-9-furinyl) -2', 3'-isopropylidene-β-D-ribofuranuronic acid and thioamide substituted at How to. Preparation of 1'-deoxy-1 '-(6-amino-9-furinyl) -β-D-ribofuranuronic acid amide and thioamide of formula (I) according to claim 2 substituted at the 2-position 1) -deoxy-1 '-(6-amino-9-furinyl) -2', 3'-isopropylidene of the following general formula (II) wherein the isopropylidene protecting group is substituted at the 2-position and-segmented from -β-D-ribofuranuronic acid and thioamide. Wherein R ₁ , R ₂ and R ₃ are as defined in claim 2. Preparation of 1'-deoxy-1 '-(6-amino-9-furinyl) -β-D-ribofuranuronic acid amide and thioamide substituted at the 2-position by any of the methods described in the Examples How to feature. A 1'-deoxy-1 '-(6-amino-9-furinyl) -β-D-ribofuranuronic acid amide and thioamide substituted at the 2-position, which is prepared by the method of claim 7. 1'-deoxy-1 '-(6-amino-9-furinyl) -β-D-ribofuranuronic acid amide and thio substituted in position 2 as active agent in combination with pharmacologically acceptable adjuvant and / or diluent Containing an amide. A pharmaceutical composition comprising the compound of any one of claims 1 to 5 as an active agent in combination with a pharmacologically acceptable adjuvant and / or diluent. In the treatment of hypertension, 1'-deoxy-1 '-(6-amino-9-furinyl) -β-D-ribofuranuronic acid amide and thioamide substituted at the 2-position are used. Way. In the treatment of hypertension, 1'-deoxy-1 '-(6-amino-9-purinyl)-substituted at the 2-position of general formula (I) according to any one of claims 2 to 5 (beta) -D-ribofuranuronic acid amide and thioamide. 1'-deoxy-1'- (6-amino-9- substituted at the 2-position of general formula (I) according to any one of claims 2 to 5 in order to prepare a medicine suitable for the treatment of hypertension Furinyl) -β-D-ribofuranuronic acid amide and thioamide. 1'-deoxy-1 '-(6-amino-9-fury substituted at the 2-position of general formula (I) according to any one of claims 2 to 5 to prepare a medicine suitable for treating hypertension Yl) -β-D-ribofuranuronic acid amide and thioamide. ※ Note: The disclosure is based on the initial application.