A highly efficient synthesis of potent and selective butyrolactam inhibitors of 11beta-HSD1.
A convergent synthesis of structurally novel butyrolactam 11beta-HSD1 inhibitors is described. The approach features an efficient Ireland-Claisen reaction to construct a highly substituted aldehyde building block which is converted to a lactam via a tandem reductive amination/cyclization sequence. The generality of the synthetic sequence is demonstrated during the preparation of two additional potent 11beta-HSD1 inhibitors.
Yeh
Vince S C
VS
Metabolic Disease Research, Target and Lead Discovery Research, and Process Chemistry Research, Abbott Laboratories, 100 Abbott Park Road, Dept R4MC, AP-10, Abbott Park, IL 60064-6113, USA. vince.yeh@abbott.com
Kurukulasuriya
Ravi
R
Kerdesky
Francis A
FA
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure
D007769:Lactams; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1