232252-56-1Relevant articles and documents
Purine derivatives and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes
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, (2008/06/13)
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 antagonistic 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—, —CH═CH— or —C≡C—; R1is: (in the formula, X is hydrogen atom, hydroxyl group, a lower alkyl group, a lower alkoxy group, etc.; and R5and R6are the same as or different from each other and each represents hydrogen atom, a lower alkyl group, a cycloalkyl group, etc.) and the like; R2is an amino group, etc. which maybe substituted with a lower alkyl group, etc.; R3is a cycloalkyl group, an optionally substituted aryl group, etc.; and R4is a lower alkyl group etc.
2-Alkynyl-8-aryladenines possessing an amide moiety: Their synthesis and structure-activity relationships of effects on hepatic glucose production induced via agonism of the A2B adenosine receptor
Harada,Asano,Kawata,Inoue,Horizoe,Yasuda,Nagata,Murakami,Nagaoka,Kobayashi,Tanaka,Abe
, p. 2709 - 2726 (2007/10/03)
A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The m-primary benzamide derivative 15f was the most potent compound (IC50 = 0.017 μM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A2B receptor versus human A1 and A2A receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A2B antagonistic activity and selectivity. The IC50 values in rat hepatocyte glucose assay correlated well with the IC50 values in cAMP assay using Chinese hamster ovary cells stably transfected with human A2B receptors (r2 = 0.94). The A1 and A2A affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A2B receptor.
