Lee Kyo Chul, Moon Byung Seok, Lee Jae Hak, Chung Kyoo-Hyun, Katzenellenbogen John A, Chi Dae Yoon
Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, 402-751, Inchon, South Korea.
Bioorg Med Chem. 2003 Aug 15;11(17):3649-58. doi: 10.1016/s0968-0896(03)00362-6.
Three fluoroalkylated derivatives (1-3) of the selective estrogen receptor modulator (SERM), raloxifene, have been synthesized. The key step in the synthesis is the C-C bond formation of benzo[b]thiophene and a substituted phenyl group (ring C) using a Stille reaction. The in vitro binding affinities of the substituted raloxifenes 1-3 are 45, 60, 89%, respectively, relative to the affinity of estradiol, which is higher than the affinity of raloxifene itself (25%). When labeled with the positron-emitting radionuclide, these compounds might be useful as PET imaging agents for estrogen receptor-positive breast tumors.
已合成了选择性雌激素受体调节剂（SERM）雷洛昔芬的三种氟烷基化衍生物（1-3）。合成中的关键步骤是使用Stille反应形成苯并[b]噻吩与取代苯基（C环）之间的C-C键。相对于雌二醇的亲和力，取代雷洛昔芬1-3的体外结合亲和力分别为45%、60%、89%，高于雷洛昔芬本身的亲和力（25%）。当用发射正电子的放射性核素标记时，这些化合物可能可用作雌激素受体阳性乳腺肿瘤的PET显像剂。
