Synthesis and protein-tyrosine kinase inhibitory activity of polyhydroxylated stilbene analogs of piceatannol
摘要:
A series of hydroxylated trans-stilbenes related to the antileukemic natural product trans-3,3',4,5'-tetrahydroxystilbene (piceatannol) (1) has been prepared and tested for inhibition of the lymphoid cell lineage-specific protein-tyrosine kinase p56lck, which plays an important role in lymphocyte proliferation and immune function. A number of the analogues displayed enhanced enzyme inhibitory activity relative to the natural product. Reduction of the double bond bridging the two aromatic rings and benzylation of the phenolic hydroxyl groups was found to decrease activity significantly. The most potent compounds in the series proved to be trans-3,3',5,5'-tetrahydroxystilbene, trans-3,3',5-trihydroxystilbene, and trans-3,4,4'-trihydroxystilbene.
The present invention relates to compounds of Formula (I)
or a pharmaceutically acceptable salt thereof; processes for the preparation of the compounds; intermediates used in the preparation of the compounds; compositions containing the compounds; and uses of the compounds in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity.
Abstract Two new bis(bibenzyl) ethers, perrottetin E-11′-methyl ether and 14-hydroxyperrottetin E-11′-methyl ether were isolated from an ethyl acetate extract of the liverwort Pelliaendiviifolia together with the previously known bis(bibenzyl) ether, perrottetin E and their structures characterized by spectroscopic methods, chemical evidence and total synthesis. The present results strongly support
The present invention relates to compounds of Formula (I)
or a pharmaceutically acceptable salt thereof; processes for the preparation of the compounds; intermediates used in the preparation of the compounds; compositions containing the compounds; and uses of the compounds in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity.