Ribofuranosyl Purine Compounds, Methods for Preparing the Same and Use Thereof
AssigneesBeijing Kbd Pharmaceuticals Co., Ltd., Beijing University of Chemical Technology
InventorsHongguang Du, Guocheng Liu, Zhongren Ding, Shuming Wang
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Abstract
The present invention relates to the compounds of the formulae (I) and (I-1) and the process for preparing the same, uses of the compounds for the treatment of diseases associated with platelet aggregation and in the manufacture of a medicament for the treatment of diseases associated with platelet aggregation, and relates to a pharmaceutical composition and a pharmaceutical formulation containing the compounds, wherein the definitions of R1, R2, R3 and R2a in the formulae are the same as those in the description.
Claims16
A compound represented by the formula (I-1) or a pharmaceutically acceptable salt thereof
- wherein
- R1 represents an unsubstituted or R4-substituted C1-C8 hydrocarbyl, or an unsubstituted or R5-substituted 5- to 6-membered cyclic group;
- R2a represents an unsubstituted or R5-substituted C3-C8 saturated or unsaturated aliphatic hydrocarbyl, an unsubstituted or R5-substituted C3-C8 alicyclic group, an unsubstituted or R6-substituted C6-C10 aryl-C2-C4 alkyl, an unsubstituted or R6-substituted 5- to 10-membered heterocyclyl-C1-C4 alkyl, or an unsubstituted or R6-substituted 5- to 10-membered heteroaryl-C1-C4 alkyl;
- R3 represents H or R2a;
- R4 represents halogen, C1-C4 alkyl, C1-C4 alkoxyl, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxyl, hydroxyl, hydroxyl C1-C4 alkyl, carboxyl, nitro, cyano, C1-C4 alkylthio, or C1-C4 alkyl-CO—;
- R5 represents C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, hydroxyl C1-C4 alkyl, carboxyl, nitro, cyano, C1-C4 alkylthio or C1-C4 alkyl-CO—;
- and
- R6 represents halogen, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, hydroxyl C1-C4 alkyl, carboxyl, nitro, cyano, C1-C4 alkylthio, or C1-C4 alkyl-CO—;
- provided that
- when R1 is —CH3 and R3 is H, R2a is not cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, decalinyl, 3-methyl-2-pentenyl, 2-methyl-3-hydroxyl-1-propenyl, 3-methyl-4-hydroxyl-1-butenyl, furfurylmethylene, 3-methyl-1-butenyl, 3-methyl-2-butenyl, 3-methylbutyl, 3-methyl-4-hydroxylbutyl, 3-methyl-4-hydroxyl-2-butenyl or 3-methyl-4-hydroxyl-3-butenyl;
- or
- when R1 is propyl, R2a is not cyclopentyl, isopropyl, n-propyl or n-butyl.
The following compounds or pharmaceutically acceptable salts thereof:
- 2-propylthio-6-n-hexylamino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-cyclohexylamino-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-cyclohexylamino-9-β-D-ribofuranosyl purine;
- 2-isopropylthio-6-cyclohexylamino-9-β-D-ribofuranosyl purine;
- 2-butylthio-6-cyclohexylamino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-benzylamino-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-benzylamino-9-β-D-ribofuranosyl purine;
- 2-butylthio-6-benzylamino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-(1-phenylethyl)amino-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-([4-methoxylbenzyl]amino)-9-β-D-ribofuranosyl purine;
- 2-methylthio-6-phenylethylamino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-phenylethylamino-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-phenylethylamino-9-β-D-ribofuranosyl purine;
- 2-butylthio-6-phenylethylamino-9-β-D-ribofuranosyl purine;
- 2-methylthio-6-([4-methoxylphenylethyl]amino)-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-([4-methoxylphenylethyl]amino)-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-([4-methoxylphenylethyl]amino)-9-β-D-ribofuranosyl purine;
- 2-butylthio-6-([4-methoxylphenylethyl]amino)-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-([3-methoxylphenylethyl]amino)-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-([3-methoxylphenylethyl]amino)-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6,6-(dibutylamino)-9-β-D-ribofuranosyl purine;
- 2-propylthio-6-(2-thienylethyl)amino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-(3-phenylpropyl)amino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-(4-phenylbutyl)amino-9-β-D-ribofuranosyl purine;
- 2-ethylthio-6-(2-furylmethyl)amino-9-β-D-ribofuranosyl purine;
- and
- 2-ethylthio-6-(2-tetrahydrofurylmethyl)amino-9-β-D-ribofuranosyl purine.
A method for the treatment or prevention of diseases associated with platelet aggregation in a mammal in need thereof, comprising administering an effective amount of the compound of the formula (I) or a pharmaceutically acceptable salt thereof,
- wherein
- R1 represents an unsubstituted or R4-substituted C1-C8 hydrocarbyl, or an unsubstituted or R5-substituted 5- to 6-membered cyclic group;
- R2 represents an unsubstituted or R5-substituted C3-C8 saturated or unsaturated aliphatic hydrocarbyl, an unsubstituted or R5-substituted C3-C8 alicyclic group, an unsubstituted or R6-substituted C6-C10 aryl-C1-C4 alkyl, an unsubstituted or R6-substituted 5- to 10-membered heterocyclyl-C1-C4 alkyl, or an unsubstituted or R6-substituted 5- to 10-membered heteroaryl-C1-C4 alkyl;
- R3 represents H or R2;
- R4 represents halogen, C1-C4 alkyl, C1-C4 alkoxyl, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxyl, hydroxyl, hydroxyl C1-C4 alkyl, carboxyl, nitro, cyano, C1-C4 alkylthio, or C1-C4 alkyl-CO—;
- R5 represents C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, hydroxyl C1-C4 alkyl, carboxyl, nitro, cyano, C1-C4 alkylthio or C1-C4 alkyl-CO—;
- and
- R6 represents halogen, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, hydroxyl C1-C4 alkyl, carboxyl, nitro, cyano, C1-C4 alkylthio, or C1-C4 alkyl-CO—.
Dependencies are inferred from the claim text.