Teng M, Duong T T, Johnson A T, Klein E S, Wang L, Khalifa B, Chandraratna R A
Department of Chemistry, Allergan Incorporated, Irvine, California 92623-9534, USA.
J Med Chem. 1997 Aug 1;40(16):2445-51. doi: 10.1021/jm9703911.
The syntheses and full retinoid receptor characterization of a novel series of retinoic acid receptor alpha (RAR alpha) antagonists, 1-5, are described. These compounds bind with high affinity to RAR alpha but were completely inactive in gene transactivation. They were also potent and effective antagonists of retinoic acid (RA) induced gene transcription at RAR alpha. Compounds 1-5 exhibited varying degrees of selectivity for RAR alpha relative to RAR beta/gamma, with compound 5 being the most selective in both binding and functional antagonism assays. These compounds will be invaluable tools in delineating the physiological roles of RAR alpha in development and in the adult animal and may themselves be useful therapeutic agents in human diseases associated with RAR alpha.
描述了一系列新型视黄酸受体α（RARα）拮抗剂1 - 5的合成及完整的类视黄醇受体特性。这些化合物与RARα具有高亲和力结合，但在基因反式激活中完全无活性。它们也是视黄酸（RA）诱导的RARα基因转录的强效有效拮抗剂。化合物1 - 5相对于RARβ/γ对RARα表现出不同程度的选择性，化合物5在结合和功能拮抗试验中是最具选择性的。这些化合物将是阐明RARα在发育和成年动物中的生理作用的宝贵工具，并且它们本身可能是与RARα相关的人类疾病的有用治疗剂。
