Purine derivatives and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes
Inactive Publication Date: 2006-05-30
EISIA R&D MANAGEMENT CO LTD
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However, the biguanide compounds induce a lactic acidosis and, therefore, their use is limited while the sulfonylurea compounds often result in a severe hypoglycemia due to their strong hypoglycemic action and, therefore, their use is to be careful.
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[0175]To a solution of 2.54 g of 3-cyanoaniline in 25 ml of tetrahydrofuran were gradually added 1.23 ml of acetic acid at 0° C. To this solution were added 2 g of 4-chloro-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinylacetamide at 0° C. and the mixture was stirred for 3.5 hours. The reaction solution was filtered and the solid collected thereby was washed with 10 ml each of water, methanol, tetrahydrofuran and ether successively. The resulting product was dried at room temperature to give 2.58 g of N1-[4-(3-cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide. The yield was 96%.
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Abstract
The present invention provides a preventive or therapeutic agent of a new type for diabetes mellitus and diabetic complications on the basis of an adenosine A2 receptor antagonist action.A purine compound represented by the formula (I), its pharmacologically acceptable salt or hydrates thereof has an adenosine A2 receptor antagonistic action and is useful for prevention or therapy of diabetes mellitus and diabetic complications. In addition, adenosine A2 receptor antagonists having different structures from those of the compounds described above, for example KW6002, are also effective for prevention or therapy of diabetes mellitus and diabetic complications. In the formula, W is —CH2CH2—, or —CH═CH— or —C≡C—; R1 is: (in the formula, X is hydrogen atom, hydroxyl group, a lower alkyl group, a lower alkoxy group, etc.; and R5 and R6 are the same as or different from each other and each represents hydrogen atom, a lower alkyl group, a cycloalkyl group, etc.) and the like; R2 is an amino group, etc. which maybe substituted with a lower alkyl group, etc.; R3 is a cycloalkyl group, an optionally substituted aryl group, etc.; and R4 is a lower alkyl group etc.
Description
[0001]This application is the national phase under 35 U.S.C. §371 or PCT International Application No. PCT / JP98 / 05870 which has an International filing date of Dec. 24, 1998, which is designated the United States of America.TECHNICAL FIELD TO WHICH THE INVENTION BELONGS[0002]The present invention relates to a novel purine compound having an adenosine receptor antagonism and to a preventive or therapeutic agent for diabetes mellitus and diabetic complication comprising an adenosine receptor antagonist having a hypoglycemic action and a glucose tolerance improving action on the basis of an inhibiting action to saccharogenesisglucose production and a promoting action to saccharideglucose utilization at the periphery. More particularly, it relates to a preventive or therapeutic agent for diabetes mellitus and diabetic complications in which an adenosine receptor antagonist is an adenosine A2 receptor antagonist.PRIOR ART[0003]With regard to therapeutic agents for diabetes mellitus, vari...
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