Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy

Christopher F Thompson; Nazia Quraishi; Amjad Ali; James R Tata; Milton L Hammond; James M Balkovec; Monica Einstein; Lan Ge; Georgianna Harris; Theresa M Kelly; Paul Mazur; Shilpa Pandit; Joseph Santoro; Ayesha Sitlani; Chuanlin Wang; Joanne Williamson; Douglas K Miller; Ting-ting D Yamin; Chris M Thompson; Edward A O'Neill; Dennis Zaller; Michael J Forrest; Ester Carballo-Jane; Silvi Luell

doi:10.1016/j.bmcl.2005.02.009

Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy

Bioorg Med Chem Lett. 2005 Apr 15;15(8):2163-7. doi: 10.1016/j.bmcl.2005.02.009.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. christopher_thompson@merck.com <christopher_thompson@merck.com>

PMID: 15808489
DOI: 10.1016/j.bmcl.2005.02.009

Abstract

A series of novel ligands for the glucocorticoid receptor containing two heterocycles were synthesized. These compounds were investigated for a dissociative profile using transrepression and transactivation assays. Several compounds were tested in vivo and showed the ability to reduce inflammation in a mouse.

MeSH terms

Animals
Anti-Inflammatory Agents / administration & dosage
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology
Cell Line
Glucocorticoids / administration & dosage
Glucocorticoids / chemistry*
Glucocorticoids / pharmacology
Heterocyclic Compounds / administration & dosage
Heterocyclic Compounds / chemistry*
Heterocyclic Compounds / pharmacology
Humans
Lipopolysaccharides / pharmacology
Mice
Mice, Inbred C57BL
Rats
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Tumor Necrosis Factor-alpha / biosynthesis

Substances

Anti-Inflammatory Agents
Glucocorticoids
Heterocyclic Compounds
Lipopolysaccharides
Tumor Necrosis Factor-alpha