Design, synthesis, and structure-activity relationships of novel tetracyclic compounds as peripheral benzodiazepine receptor ligands

被引：51

作者：

Okubo, T

Yoshikawa, R

Chaki, S

Okuyama, S

Nakazato, A

机构：

[1] Taisho Pharmaceut Co Ltd, Med Res Labs, Med Chem Lab, Kita Ku, Saitama 3319530, Japan

[2] Taisho Pharmaceut Co Ltd, Med Res Labs, Med Pharmacol Lab, Kita Ku, Saitama 3319530, Japan

[3] Taisho Pharmaceut Co Ltd, Eth Business Strategy Div, Kita Ku, Saitama 3319530, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 13期

关键词：

PBR (peripheral benzodiazepine receptor); tetracyclic ring; SAR; PBR ligands;

D O I：

10.1016/j.bmc.2004.04.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The peripheral benzodiazepine receptor (PBR) is pharmacologically distinct from the central benzodiazepine receptor (CBR) and has been identified in a wide range of peripheral tissues as well as in the central nervous system. Although numerous studies have been performed of it, the physiological roles and functions of the PBR are Still unclear. In the present study, in exploring new types of ligands for PBR, we found that a new series of compounds having a tetracyclic ring system, which were designed from FGIN-1-27, exhibited high affinities for PBR. We prepared and evaluated them for PBR affinities. The results of binding tests showed that 12e and 12f were the most potent PBR ligands among them (12e: IC50 = 0.44 nM, 12f: IC50 = 0.37 nM). In this paper, we present the design, synthesis, and structure-activity relationships (SARs) of novel tetracyclic compounds. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3569 / 3580

页数：12

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