|
|||||
|
|
Function-regulating pharmacophores in a sulfonamide class of glucocorticoid receptor agonists |
|
| Authors: | Daniel Kuzmich Jörg Bentzien Raj Betageri Darren DiSalvo Tazmeen Fadra-Khan Christian Harcken Alison Kukulka Gerald Nabozny Richard Nelson Edward Pack Donald Souza David Thomson |
| Affiliation: | 1. Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA;2. Department of Immunology & Inflammation, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA |
| Abstract: | A class of α-methyltryptamine sulfonamide glucocorticoid receptor (GR) modulators was optimized for agonist activity. The design of ligands was aided by molecular modeling, and key function-regulating pharmacophoric points were identified that are critical in achieving the desired agonist effect in cell based assays. Compound 27 was profiled in vitro and in vivo in models of inflammation. Analogs could be rapidly prepared in a parallel approach from aziridine building blocks. |
| Keywords: | Glucocorticoids Glucocorticoid receptor Nuclear hormone receptor Mineralocorticoid receptor Progesterone receptor Inflammation Collagen induced arthritis Arylsulfonamide |
| 本文献已被 ScienceDirect 等数据库收录！ | |