Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands
Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands
复制标题
DOI：
10.1016/j.bmc.2003.10.050
复制
发表时间：
2004-01-15
影响因子：
3.5
通讯作者：
Nakazato, A
中科院分区：
文献类型：
--
作者：
Okubo, T;Yoshikawa, R;Nakazato, A
由于外周苯二氮卓受体（PBR）是地西泮在大鼠肾脏的高亲和力结合位点，因此对其进行了大量的研究。然而，PBR的生理作用和功能尚未完全阐明。目前，我们提出了两种高选择性PBR配体的药理学特征，N-（2，5-二甲氧基苄基）-N-（4-氟-2-苯氧基苯基）乙酰胺（7-096，DAA 1106）（PBR：IC 50 = 0.28 nM）和N-（4-氯-2-苯氧基苯基）-N-（2-异丙氧基苄基）乙酰胺（7-099，DAA 1097）（PBR：IC 50 =0.92 nM）。这些化合物是芳氧基苯胺衍生物，并且与已知的PBR配体如苯并二氮杂（1，Ro 5 -4864）、异喹啉（2，PK 11195）、咪唑并吡啶（3，Alpidem）和吲哚（5，FGIN-1-27）衍生物一起鉴定。芳氧基苯胺衍生物是一类新型的苯并二氮杂卓类受体配体，通过打开1的二氮杂卓环而衍生，对外周苯并二氮杂卓类受体（PBRs）表现出高的选择性亲和力。这些新的衍生物将有助于探索PBR的功能。本文综述了芳氧基苯胺类化合物的设计、合成及其构效关系。(C)2003爱思唯尔有限公司。保留所有权利。
Since the peripheral benzodiazepine receptor (PBR) has been primarily found as a high-affinity binding site for diazepam in rat kidney, numerous studies of it have been performed. However, the physiological role and functions of PBR have not been fully elucidated. Currently, we presented the pharmacological profile of two high and selective PBR ligands, N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)acetamide (7-096, DAA1106) (PBR: IC50 = 0.28 nM) and N-(4-chloro-2-phenoxyphenyl)-N-(2-isopropoxybenzyl)acetamide (7-099, DAA1097) (PBR: IC50=0.92 nM). The compounds are aryloxyanilide derivatives, and identified with known PBR ligands such as benzodiazepine (1, Ro5-4864), isoquinoline (2, PK11195), imidazopyridine (3, Alpidem), and indole (5, FGIN-1-27) derivatives. The aryloxyanilide derivatives, which have been derived by opening the diazepine ring of 1, are a novel class as PBR ligands and have exhibited high and selective affinity for peripheral benzodiazepine receptors (PBRs). These novel derivatives would be useful for exploring the functions of PBR. In this paper, the design, synthesis and structure-affinity relationships of aryloxyanilide derivatives are described. (C) 2003 Elsevier Ltd. All rights reserved.