Discovery of Phenyl Acetic Acid Substituted Quinolines as Novel Liver X Receptor Agonists for the Treatment of Atherosclerosis
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- 作者：Baihua Hu ; Michael Collini ; Rayomand Unwalla ; Christopher Miller ; Robert Singhaus ; Elaine Quinet ; Dawn Savio ; Anita Halpern ; Michael Basso ; James Keith ; Valerie Clerin ; Liang Chen ; Christine Resmini
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：October 19, 2006
- 年：2006
- 卷：49
- 期：21
- 页码：6151 - 6154
- 全文大小：173K
- 年卷期：v.49,no.21(October 19, 2006)
- ISSN：1520-4804
文摘
A structure-based approach was used to optimize our newclass of quinoline LXR modulators leading to phenyl acetic acidsubstituted quinolines 15 and 16. Both compounds displayed goodbinding affinity for LXR
and LXR
and were potent activators inLBD transactivation assays. The compounds also increased expressionof ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline16 showed good oral bioavailability and in vivo efficacy in a LDLrknockout mouse model for lesions.
and LXR and were potent activators inLBD transactivation assays. The compounds also increased expressionof ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline16 showed good oral bioavailability and in vivo efficacy in a LDLrknockout mouse model for lesions.