Synthesis. of new molecular probes for investigation of steroid biosynthesis induced by selective interaction with peripheral type benzodiazepine receptors (PBR)

被引：29

作者：

Campiani, G

Ramunno, A

Fiorini, I

Nacci, V

Morelli, E

Novellino, E

Goegan, M

Mennini, T

Sullivan, S

Zisterer, DM

Williams, CD

机构：

[1] Univ Siena, Dipartimento Farmaco Chim Tecnol, I-53100 Siena, Italy

[2] Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[3] Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy

[4] Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 19期

关键词：

D O I：

10.1021/jm020849l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the present study, we have synthesized and tested novel pyridopyrrolo- and pyrrolobenzoxazepine derivatives, as novel and selective peripheral type benzodiazepine receptor (PBR) ligands, and their ability to modulate steroid biosynthesis has been investigated. A subset of new ligands bind the PBR (rat brain and testis) with picomolar affinity, representing the most potent ligands that have been identified to date: and elicited effects on endogenous rate of steroidogenesis in MA10 Leydig cells, having similar potency and effect as PK11195. Several compounds, differently substituted at C-7, were used as molecular yardsticks to probe the spatial dimension of the lipophilic pocket L4 in the receptor binding site.

引用

页码：4276 / 4281

页数：6

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