Grau Benedikt W, Dheeraj Arpit, Mathews Irimpan I, Tailor Dhanir, Malhotra Sanjay V
Center for Experimental Therapeutics, Oregon Health and Science University, Portland, OR, 97201, USA.
Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA.
ChemMedChem. 2025 Aug 2;20(15):e202400936. doi: 10.1002/cmdc.202400936. Epub 2025 May 14.
The N-bridgehead heterocyclic structure is an abundant motif in a multitude of natural products. This structural feature is of high interest because it is present in many different bioactive molecules, many of which are well-established pharmaceuticals. The introduction of a sulfone group into the N-bridgehead system yields a new core structure containing a N-bridgehead sulfonamide. While linear sulfonamides can be found in natural products, only artificial cyclic sulfonamides are known to date. Applications of related cyclic sulfonamide compounds include matrix metalloproteinase inhibitors, potential HIV and cancer therapeutics, and anti-inflammatory compounds. To explore the potential bioactivity of the N-bridgehead sulfonamide scaffold, a synthetic route toward these scaffolds is developed and their bioactivity is explored against different cancer cell lines.
N-桥头杂环结构是众多天然产物中丰富的结构基序。这一结构特征备受关注，因为它存在于许多不同的生物活性分子中，其中许多是成熟的药物。将砜基引入N-桥头体系可产生一种包含N-桥头磺酰胺的新核心结构。虽然线性磺酰胺可在天然产物中找到，但迄今为止已知的只有人工合成的环状磺酰胺。相关环状磺酰胺化合物的应用包括基质金属蛋白酶抑制剂、潜在的HIV和癌症治疗药物以及抗炎化合物。为了探索N-桥头磺酰胺支架的潜在生物活性，开发了一条通向这些支架的合成路线，并研究了它们对不同癌细胞系的生物活性。
