2. Academic Validation
  3. Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate

Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate

  • ACS Med Chem Lett. 2014 Nov 20;5(12):1318-23. doi: 10.1021/ml500387y.
Christian Harcken 1,  Doris Riether 1,  Pingrong Liu 1,  Hossein Razavi 1,  Usha Patel 1,  Thomas Lee 1,  Todd Bosanac 1,  Yancey Ward 1,  Mark Ralph 1,  Zhidong Chen 1,  Donald Souza 1,  Richard M Nelson 1,  Alison Kukulka 1,  Tazmeen N Fadra-Khan 1,  Ljiljana Zuvela-Jelaska 1,  Mita Patel 1,  David S Thomson 1,  Gerald H Nabozny 1
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
PMID: 25516791 DOI: 10.1021/ml500387y
Abstract

A series of nonsteroidal "dissociated" Glucocorticoid Receptor agonists was optimized for drug-like properties such as Cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound ( R )-39.

Keywords

Glucocorticoid mimetics; anti-inflammatory agents; azaindoles; drug-like properties; glucocorticoid-induced osteoporosis; nonsteroidal glucocorticoids.

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