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

We identified a series of structurally novel SCD (Delta9 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 Delta5 and Delta6 desaturases.