109403-64-7

The crystal and molecular structure of 6-(furfurylamino)-9-(tetrahydropyran-2-yl)purine (1) was determined at 150(2) K. The compound crystallizes in monoclinic P21/c space group with a = 10.5642(2), b = 13.6174(3), c = 10.3742(2) ?, V = 1460.78(5) ?3, Z = 4, R(F) = for 3344 unique reflections. The purine moiety and furfuryl ring are planar and the tetrahydropyran-2-yl is disordered in the ratio 1:3, probably due to the chiral carbon atom C(17). The individual 1H and 13C NMR signals were assigned by 2D correlation experiments such as 1H-1H COSY and ge-2D HSQC. Stability-in-solution was determined in methanol/water in acidic pH (3-7).

Naturally occurring cytokinins are adenine-based plant hormones. Although, the effect of various substituents at positions N1, C2, N3, N6, N7, or N9 on the biological activity of cytokinins has been studied, the C8-substituted compounds have received little attention. Here, we report the synthesis and in vitro biological testing of thirty-one cytokinin derivatives substituted at the C8 position of the adenine skeleton and twenty-seven compounds which served as their N9-tetrahydropyranyl protected precursors. The cytokinin activity of all the compounds was determined in classical cytokinin biotests (wheat leaf senescence, Amaranthus and tobacco callus assays). With some exceptions, the compounds with a N9-tetrahydropyranyl group were generally less active than their de-protected analogs. The latter were further tested for their ability to activate the Arabidopsis cytokinin receptors AHK3 and CRE1/AHK4 in bacterial receptor activation assays. Using this approach, we identified derivatives bearing short aliphatic chains and retaining high cytokinin activity. Such compounds are suitable candidates for fluorescence labeling or as protein-affinity ligands. We further found that some C8-substituted cytokinins exhibited no or lower cytotoxicity toward tobacco cells when compared to their parent compound. Therefore, we also present and discuss the cytotoxicity of all the compounds against three normal human cell lines.

6,8-Disubstituted-9-(heterocyclyl) purines which can be used in pharmaceutical and cosmetic compositions and/or applications are provided. These 6,8-disubstituted-9-(heterocyclyl) purines have a wide range of biological activities, including for example antioxidant, anti-inflammatory, anti-senescent, as well as well as other activities which are especially useful in pharmaceutical and cosmetic applications.

The present invention provides methods and compositions for countering the adverse effects of aging on mammalian cells in vitro and in vivo, especially human skin cells and human skin, and treatment of hyperproliferative and related skin diseases in mammals by administering compositions containing 6,9-disubstituted purine derivatives.

A series of six potential plant hormones, 6-alky- and arylamino-9- (tetrahydro-2-pyranyl)purines were prepared in three steps in 35 to 45% overall yield from 6-methylthiopurine via 6-methylsulfonylpurine.