Analogues of S-adenosylhomocysteine as potential inhibitors of biological transmethylation. Synthesis of analogues with modifications at the 5'-thioether linkage.
The synthesis of S-adenosylhomocysteine analogues, in which the 5'-thioether linkage is replaced by an oxygen or nitrogen isostere, has been investigated. These compounds were disigned to be resistant to enzyme-catalyzed hydrolytic cleavage of the 5'-substituent. The amine analogue Id and two amide analogues 20 were prepared via alkylation or acylation of appropriately blocked adenosine derivatives. These new analogues were evaluated as inhibitors of catechol O-methyltransferase and tRNA methylases and found to have poor inhibitory activity.
D000478:Alkylation; D065098:Catechol O-Methyltransferase Inhibitors; D006710:Homocysteine / Q000031:analogs & derivatives*; D008745:Methylation; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D012359:tRNA Methyltransferases / Q000037:antagonists & inhibitors
D065098:Catechol O-Methyltransferase Inhibitors; D006710:Homocysteine; D012435:S-Adenosylhomocysteine; D012359:tRNA Methyltransferases