1295542-07-2Relevant academic research and scientific papers
N-Benzylimidazole carboxamides as potent, orally active stearoylCoA desaturase-1 inhibitors
Atkinson, Karen A.,Beretta, Elena E.,Brown, Janice A.,Castrodad, Mayda,Chen, Yue,Cosgrove, Judith M.,Du, Ping,Litchfield, John,Makowski, Michael,Martin, Kelly,McLellan, Thomas J.,Neagu, Constantin,Perry, David A.,Piotrowski, David W.,Steppan, Claire M.,Trilles, Richard
body text, p. 1621 - 1625 (2011/05/05)
A potent, small molecule inhibitor with a favorable pharmacokinetic profile to allow for sustained SCD inhibition in vivo was identified. Starting from a low MW acyl guanidine (5a), identified with a RapidFire High-Throughput Mass Spectrometry (RF-MS) assay, iterative library design was used to rapidly probe the amide and tail regions of the molecule. Singleton synthesis was used to probe core changes. Biological evaluation of a SCD inhibitor (5b) included in vitro potency at SCD-1 and in vivo modulation of the plasma desaturation index (DI) in rats on a low essential fatty acid (LEFA) diet. In addition to dose-dependent decrease in DI, effects on rodent ocular tissue were noted. Therefore, in rat, these SCD inhibitors only recapitulate a portion of phenotype exhibited by the SCD-1 knockout mouse.
