Discovery of orally active butyrolactam 11beta-HSD1 inhibitors

Vince S C Yeh; Ravi Kurukulasuriya; Steven Fung; Katina Monzon; William Chiou; Jiahong Wang; Deanne Stolarik; Hovis Imade; Robin Shapiro; Victoria Knourek-Segel; Eugene Bush; Denise Wilcox; Phong T Nguyen; Michael Brune; Peer Jacobson; J T Link

doi:10.1016/j.bmcl.2006.08.034

Discovery of orally active butyrolactam 11beta-HSD1 inhibitors

Bioorg Med Chem Lett. 2006 Nov 1;16(21):5555-60. doi: 10.1016/j.bmcl.2006.08.034. Epub 2006 Aug 23.

Authors

Vince S C Yeh¹, Ravi Kurukulasuriya, Steven Fung, Katina Monzon, William Chiou, Jiahong Wang, Deanne Stolarik, Hovis Imade, Robin Shapiro, Victoria Knourek-Segel, Eugene Bush, Denise Wilcox, Phong T Nguyen, Michael Brune, Peer Jacobson, J T Link

Affiliation

¹ Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, AP-10-304B, Abbott Park, IL 60064, USA. [email protected]

PMID: 16931002
DOI: 10.1016/j.bmcl.2006.08.034

Abstract

A series of metabolically stable butyrolactam 11beta-HSD1 inhibitors have been synthesized and biologically evaluated. These compounds exhibit excellent HSD1 potency and HSD2 selectivity, pharmacokinetic, and pharmacodynamic profiles.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
Administration, Oral
Animals
Humans
Lactams / administration & dosage
Lactams / chemical synthesis
Lactams / pharmacokinetics
Lactams / pharmacology*
Metabolic Syndrome / drug therapy
Mice

Substances

Lactams
11-beta-Hydroxysteroid Dehydrogenase Type 1