68329-42-0Relevant articles and documents
The Synthesis of 8,10,12-Triazaprostaglandin Analogues: 1,2,4-Triazolidine-3,5-dione Derivatives
Adams, David R.,Barnes, Alan F.,Cassidy, Frederick,Thompson, Mervyn
, p. 2061 - 2068 (2007/10/02)
In the search for active, more selective prostaglandin analogues, the synthesis of 8,10,12-triazaprostaglandin analogues has been achieved from readily available 4-methyl-1,2,4-triazolidine-3,5-dione.The general approach involved introduction of the α- and ω-side-chain as entire units by step-wise N-alkylation.The problems encountered with this approach of competing N- and O-mono- and di-alkylation were overcome, eventually, such that judicious choice of the initial mono-N-alkylation step enabled the synthesis of analogues incorporating wide variations in the α- and ω-side-chain.Important structural modifications included introduction of unsaturation into the α-side-chain at the 5,6-position and of methyl groups into the ω-side-chain at the 15- and 16-position as exemplified by the synthesis of 1--2-(3-hydroxy-3,4-dimethyloctyl)-4-methyl-1,2,4-triazolidine-3,5-dione (19).The stable triazaprostaglandin analogues were synthesized as racemic compounds but, nevertheless, compound (19) possessed bronchodilator activity of a similar order to that of the natural prostaglandins PGE1 and PGE2.
