139721-85-0Relevant academic research and scientific papers
Nonpeptidic inhibitors of human leukocyte elastase. 5. Design, synthesis, and X-ray crystallography of a series of orally active 5-aminopyrimidin-6- one-containing trifluoromethyl ketones
Veale,Bernstein,Bryant,Ceccarelli,Damewood Jr.,Earley,Feeney,Gomes,Kosmider,Steelman,Thomas,Vacek,Williams,Wolanin,Woolson
, p. 98 - 108 (2007/10/02)
The effects of changes in substitution in a series of 5-amino-2- pyrimidin-6-ones on both in vitro activity and oral activity in an acute hemorrhage assay have been explored. These compounds contained either a trifluoromethyl ketone or a boronic acid moiety to bind covalently to the Ser-195 hydroxyl of human leukocyte elastase (HLE). Boronic acid-containing inhibitors were found to be more potent than the corresponding trifluoromethyl ketones in vitro but were less active upon oral administration. Compound 13b was found to offer the best combination of oral potency, duration of action, and enzyme selectivity and, as such, was selected for further biological testing. X-ray crystallography of a cocrystallized complex of compound 19m and porcine pancreatic elastase demonstrated that the inhibitor is bound to the enzyme in a manner similar to that found previously for a closely related series of pyridone-containing inhibitors of HLE.
Conversion of Amides and Lactams to Thioamides and Thiolactams Using Hexamethyldisilathiane
Smith, D. C.,Lee, S. W.,Fuchs, P. L.
, p. 348 - 354 (2007/10/02)
Amides and lactams were converted to their corresponding thioamides and thiolactams employing a new protocol using hexamethyldisilathiane (TMS2S).Oxophilic promoters were employed to generate Vilsmeier-type intermediates, the most efficient reagents being phosphorus oxychloride, triphosgene, and oxalyl chloride.Thionation of intermediate chloro iminium ions was accomplished in situ with TMS2S.Yields were good to excellent for secondary and tertiary amides and lactams while yields for primary systems were poor.
