Discovery of spirocyclic-diamine inhibitors of mammalian acetyl CoA-carboxylase. Issue 22 (15th November 2015)

• Record Type: Journal Article
• Authors: Kung, Daniel W.; Griffith, David A.; Esler, William P.; Vajdos, Felix F.; Mathiowetz, Alan M.; Doran, Shawn D.; Amor, Paul A.; Bagley, Scott W.; Banks, Tereece; Cabral, Shawn; Ford, Kristen; Garcia-Irizarry, Carmen N.; Landis, Margaret S.; Loomis, Kathrine; McPherson, Kirk; Niosi, Mark; Rockwell, Kristin L.; Rose, Colin; Smith, Aaron C.; Southers, James A.; Tapley, Susan; Tu, Meihua; Valentine, James J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 22(2015)
• Page Start: 5352
• Page End: 5356
• Publication Date: 2015-11-15
• Subjects: Spirocycle -- Diamine -- ACC -- Acetyl CoA-carboxylase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.09.035
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A novel series of spirocyclic-diamine based, isoform non-selective inhibitors of acetyl-CoA carboxylase (ACC) is described. These spirodiamine derivatives were discovered by design of a library to mimic the structural rigidity and hydrogen-bonding pattern observed in the co-crystal structure of spirochromanone inhibitorI . The lead compound3.5.1 inhibited de novo lipogenesis in rat hepatocytes, with an IC50 of 0.30 μM.