Function-regulating pharmacophores in a sulfonamide class of glucocorticoid receptor agonists
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- 作者：Daniel Kuzmich ; J枚rg Bentzien ; Raj Betageri ; Darren DiSalvo ; Tazmeen Fadra-Khan ; Christian Harcken ; Alison Kukulka ; Gerald Nabozny ; Richard Nelson ; Edward Pack ; Donald Souza ; David Thomson
- 关键词：Glucocorticoids ; Glucocorticoid receptor ; Nuclear hormone receptor ; Mineralocorticoid receptor ; Progesterone receptor ; Inflammation ; Collagen induced arthritis ; Arylsulfonamide
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：15 December, 2013
- 年：2013
- 卷：23
- 期：24
- 页码：6640-6644
- 全文大小：912 K
文摘
A class of 伪-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.