1295541-89-7Relevant articles and documents
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
scheme or table, 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.
