Novartis Institutes for BioMedical Research, Global Discovery Chemistry Oncology, Postfach, CH-4002 Basel, Switzerland.
Bioorg Med Chem Lett. 2012 Mar 1;22(5):1860-3. doi: 10.1016/j.bmcl.2012.01.076. Epub 2012 Jan 28.
Aromatase inhibition is the new standard of care for estrogen receptor positive breast cancer and has also potential for treatment of other diseases such as endometriosis. Simple and readily available 3-pyridyl arylethers and 1-aryl pyrrolo[2,3-c]pyridines recapitulating the key pharmacophore elements of Letrozole (1) are described and their structure-activity relationships are discussed. Potent and ligand efficient leads such as compound 23 (IC(50)=59nM on aromatase) have been identified.
芳香酶抑制是治疗雌激素受体阳性乳腺癌的新标准，也有可能用于治疗子宫内膜异位症等其他疾病。本文描述了简单易得的 3-吡啶芳基醚和 1-芳基吡咯并[2,3-c]吡啶，它们重现了来曲唑（1）的关键药效团元素，并讨论了它们的构效关系。已经确定了一些有效的先导化合物，如化合物 23（对芳香酶的 IC50=59nM）。
