Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors.

Abstract We identified a series of structurally novel SCD (Δ9 desaturase) inhibitors via high-throughput screening and follow-up SAR studies. Modification of the central bicyclic scaffold has proven key to our potency optimization effort. The most potent analog ( 8g ) had IC 50 value of 50 pM in a HEPG2 SCD assay and has been shown to be metabolically stable and selective against Δ5 and Δ6 desaturases.