[(Cp-R)M(CO)3] (M=Re or 99mTc) Arylsulfonamide, Arylsulfamide, and Arylsulfamate Conjugates for Selective Targeting of Human Carbonic Anhydrase IX
[(Cp-R)M(CO)3] (M=Re or 99mTc) Arylsulfonamide, Arylsulfamide, and Arylsulfamate Conjugates for Selective Targeting of Human Carbonic Anhydrase IX
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DOI：
10.1002/anie.201107333
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Alberto, Roger
中科院分区：
文献类型：
--
作者：
Can, Daniel;Spingler, Bernhard;Alberto, Roger
疾病的诊断和治疗需要针对特定受体设计的分子。由于自然界已经开发了一个功能和结构相似的受体领域，因此对特定靶标的选择性是抑制剂的关键标准。[1]抑制剂通常是有机的，但Meggers等人表明，高选择性不仅取决于分子间的相互作用，还取决于不同官能团的定向3D排列，如有机金属蛋白激酶抑制剂所例示的。[2-4]惰性复合物提供了填充生物相关空间的机会。因此，生物有机金属配合物是多用途的化学探针[2，5-8]，例如Jaouen及其同事开发了基于二茂铁的选择性雌激素受体抑制剂。[9-11]例如，用[（Cp-R）Re（CO）3]（CP= Re）取代他莫昔芬中的苯环导致对雌激素受体的高亲和力的保留。[12]这些有机金属化合物具有治疗潜力，但它们用于体内诊断是有限的，因为放射性核素，如18 F的PET（正电子发射断层扫描）不能被引入而不改变化学真实性。鉴于Cp-基配合物可以取代苯环而不影响生物活性，相同的化合物的联合治疗和非侵入性诊断是治疗诊断学所希望的。[13铼和锝属于同一三元组。尽管基于Re的化合物可用于治疗，但它们的99 mTc同系物在单光子发射计算机断层扫描（SPECT）中用作成像剂。[15-17日]
Diagnosis and treatment of diseases requires molecules designed for targeting specific receptors. Since nature has developed a realm of functionally and structurally similar receptors, selectivity for a specific target is a key criterion for inhibitors.[1] Inhibitors are typically organic but Meggers et al. showed that high selectivity does not only depend on intermolecular interactions but also on a directed 3D arrangement of different functionalities as exemplified with organometallic protein kinase inhibitors.[2–4] Inert complexes offer the opportunity to populate biologically relevant space. Thus, bio-organometallic complexes are versatile chemical probes [2, 5–8] as pioneered by for example, Jaouen and coworkers who developed ferrocene-based, selective estrogen receptor inhibitors.[9–11] Replacing a phenyl ring in for example, tamoxifen by [(Cp-R) Re (CO) 3](CP= cyclopentadienyl) resulted in retention of high affinity for the estrogen receptor.[12] These organometallic compounds have therapeutic potential but their use for in vivo diagnosis is limited since radionuclides such as 18F for PET (positron emission tomography) cannot be introduced without alteration of chemical authenticity.Given that Cp-based complexes can replace phenyl rings without affecting the bioactivity, identical compounds for combined therapy and noninvasive diagnosis are desirable for theragnostics.[13, 14] Rhenium and technetium belong to the same triad. Whereas Re-based compounds can be used for therapy, their 99mTc homologous serve as imaging agents in single photon emission computed tomography (SPECT).[15–17]