Yu K L, Spinazze P, Ostrowski J, Currier S J, Pack E J, Hammer L, Roalsvig T, Honeyman J A, Tortolani D R, Reczek P R, Mansuri M M, Starrett J E
Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
J Med Chem. 1996 Jun 7;39(12):2411-21. doi: 10.1021/jm9502293.
In search for retinoic acid receptor (RAR) selective ligands, a series of 6-substituted 2-naphthoic acid retinoids were synthesized and evaluated in vitro in a transactivation assay and a competition binding assay for all RARs. These derivatives, in general, showed RAR beta,gamma selectivity. Among these naphthoic acids, oxime derivative 12 was identified as a potent RAR gamma-selective retinoid, while olefinic derivative 11 was found to be comparable to retinoic acid and slightly RAR beta,gamma selective. For the bioassays, a general correlation was observed between the binding affinity of the ligand to the receptors and the potency of the compounds in the transactivation assay. The structure-activity relationship of these naphthoic acids will be discussed.
为了寻找视黄酸受体（RAR）选择性配体，合成了一系列6-取代的2-萘甲酸类视黄酸，并在体外针对所有RAR进行了反式激活测定和竞争结合测定。总体而言，这些衍生物表现出RARβ、γ选择性。在这些萘甲酸中，肟衍生物12被鉴定为一种有效的RARγ选择性视黄酸，而烯烃衍生物11被发现与视黄酸相当，且具有轻微的RARβ、γ选择性。对于生物测定，观察到配体与受体的结合亲和力与化合物在反式激活测定中的效力之间存在普遍相关性。将讨论这些萘甲酸的构效关系。
