通过修饰哌啶并[3,2-g]喹啉酮上的C环取代基将雄激素受体拮抗剂转变为激动剂。
Switching androgen receptor antagonists to agonists by modifying C-ring substituents on piperidino[3,2-g]quinolinone.
作者信息
Zhi L, Tegley C M, Marschke K B, Jones T K
机构信息
Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
出版信息
Bioorg Med Chem Lett. 1999 Apr 5;9(7):1009-12. doi: 10.1016/s0960-894x(99)00119-5.
New nonsteroidal human androgen receptor (hAR) agonists were developed from an hAR antagonist pharmacophore, 2(1H)-piperidino[3,2-g]quinolinone. (+/-)-trans-7,8-Diethyl-4-trifluoromethyl-2(H)-piperidino-[3,2-g]quinoli none was synthesized and demonstrated potent hAR agonist activity (EC50=3 nM) in the cell-based cotransfection assay and high binding affinity (Ki=16 nM) in the competitive receptor binding assay.
新型非甾体类人雄激素受体（hAR）激动剂是从hAR拮抗剂药效团2(1H)-哌啶并[3,2-g]喹啉酮开发而来。合成了(±)-反式-7,8-二乙基-4-三氟甲基-2(H)-哌啶并[3,2-g]喹啉酮，其在基于细胞的共转染试验中显示出强效的hAR激动剂活性（EC50 = 3 nM），在竞争性受体结合试验中具有高结合亲和力（Ki = 16 nM）。
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