Design and synthesis of boron containing potential pan-RAR inverse agonists

被引：8
作者：
Das, Bhaskar C. [1 ]
Tang, Xiang-Ying [2 ]
Evans, Todd [1 ]
机构：
[1] Cornell Univ, Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA
[2] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA
来源：
TETRAHEDRON LETTERS | 2012年 / 53卷 / 11期
关键词：
RAR-inverse agonist; Boron containing retinoids; Peptidomimetics; Wittig reaction; Oxadiazole; UNION-OF-PHARMACOLOGY; NUCLEAR RECEPTORS; 4-HPR DERIVATIVES; ANALOGS; ACIDS;
D O I：
10.1016/j.tetlet.2011.12.118
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
We designed and successfully synthesized the compounds 5 and 8 as potential pan-RAR (retinoic acid receptor) agonists. These two compounds were designed based on an existing pan-RAR agonist (BMS493). We synthesized compound 5, in which the carboxylic acid group in BMS 493 was replaced by boronic ester; and compound 8, in which the double bond of BMS 493 was changed to an oxadiazole (as bioisosteres of double bond) ring. The two target molecules 5 and 8 were synthesized from the commercially available 7-bromo-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one 1. Compound 1 was derivatized to intermediate 5,5-dimethyl-8-(phenylethynyl)-5,6-dihydronaphthalene-2 carbaldehyde 4 by using alkylation, dehydration, and metal exchange reactions. The intermediate 4 was further converted to 5 by using a Wittig reaction and to 8 by amide coupling and dehydration to give overall 18% and 33% yields, respectively, after 8 steps in each case. (C) 2011 Elsevier Ltd. All rights reserved.
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收藏
页码：1316 / 1318
页数：3
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