Design, synthesis and evaluation of retinoids with novel bulky hydrophobic partial structures
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- 作者：Yohei Amano ; yamano@itsuu.or.jp ; Masayuki Noguchi ; Madoka Nakagomi ; Hideaki Muratake ; Hiroshi Fukasawa ; Koichi Shudo
- 关键词：Retinoid ; RAR ; Agonist ; Bulky hydrophobic fragment ; Amide
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2013
- 出版时间：15 July, 2013
- 年：2013
- 卷：21
- 期：14
- 页码：4342-4350
- 全文大小：1273 K
文摘
Many synthetic retinoids contain an aromatic structure with a bulky hydrophobic fragment. In order to obtain retinoids with therapeutic potential that do not bind to or activate retinoic acid X receptors (RXRs), we focused on the introduction of novel hydrophobic moieties, that is, metacyclophane, phenalene and benzoheptalene derivatives. The designed compounds were synthesized and their agonistic activities towards RARs and RXRs were evaluated. Most of the active compounds showed selectivity for RAR¦Á and RAR¦Â over RAR¦Ã, and higher RAR¦Â transactivating activity seemed to correlate with higher cell differentiation-inducing activity towards promyelocytic leukemia cell line HL-60. These compounds showed no agonistic activity towards RXRs.