A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs were synthesized. Among them, WC-26 and WC-59 were identified as the most potent σ₂ receptor ligands (K_i = 2.58 and 0.82 nM, respectively) with high selectivity against σ₁ (K_i of σ₁/σ₂ ratio = 557 and 2087, respectively). [¹⁸F]WC-59 was radiolabeled via a nucleophilic substitution of a mesylate precursor by [¹⁸F]fluoride, and in vitro direct binding studies of [¹⁸F]WC-59 were conducted using membrane preparations from murine EMT-6 solid breast tumors. The results indicate that [¹⁸F]WC-59 binds specifically to σ₂ receptors in vitro (K_d = ∼2 nM). Biodistribution studies of [¹⁸F]WC-59 in EMT-6 tumor-bearing mice indicated that the tracer was a less suitable candidate for clinical imaging studies than existing F-18 labeled σ₂ receptor ligands. The ability of WC-26 to enhance the cytotoxic effects of the chemotherapy drug, doxorubicin, was evaluated in cell culture using the mouse breast tumor EMT-6 and the human tumor MDA-MB435. WC-26 greatly increased the ability of doxorubicin to kill these two tumor cell lines in vitro. These results indicate that WC-26 is potentially a useful chemosensitizer for the treatment of cancer when combined with conventional chemotherapeutics.

合成了一系列N-取代的9-氮杂双环[3.3.1]壬烷-3α-基苯基氨基甲酸酯类似物。其中，WC-26和WC-59被鉴定为最有效的σ ₂受体配体（ķ_我 分别= 2.58和0.82nM的，）以高选择性对σ ₁（ķ_我的σ ₁ / σ ₂比= 557和2087 年）。[ ¹⁸ F] WC - 59通过甲磺酸盐前体被[ ¹⁸ F] 氟化物的亲核取代以及[ ¹⁸ F] 氟化物的体外直接结合研究进行放射性标记。¹⁸ F] WC - 59使用来自鼠EMT-6实体乳腺肿瘤的膜制剂进行。结果表明[ ¹⁸ F] WC-59在体外与σ ₂受体特异性结合（K _d  = ∼2 nM）。[ ¹⁸ F] WC - 59在荷有 EMT-6 肿瘤的小鼠中的生物分布研究表明，与现有的 F-18 标记的σ ₂受体配体相比，示踪剂不太适合用于临床成像研究。WC的能力- 26使用小鼠乳腺肿瘤 EMT-6 和人肿瘤 MDA-MB435 在细胞培养中评估了增强化疗药物阿霉素的细胞毒性作用。WC - 26大大增加了阿霉素在体外杀死这两种肿瘤细胞系的能力。这些结果表明，WC - 26与常规化学治疗剂联合使用时，可能是治疗癌症的有用化学增敏剂。