A new class of isoxazole-tethered diarylheptanoids having characteristic 1,3-syn-diol and 1,3-anti-diol chemophoric moieties, e.g. 4a–d and 5a–c respectively, have been designed and synthesized starting from d-glucose following a stereo-conserved general synthetic strategy. The isoxazole heterocycle was installed using our recently elaborated methodology deploying Magtrieve™ as a selective oxidizing agent. Two of these new analogs 4a and 5a exhibited significantly improved in vitro drug-like properties including solubility, metabolic stability, cell permeability and lack of nonspecific cytotoxicity when compared with curcumin-I. In a HEK293 cell-based intracellular calcium [Ca²⁺]_i release assay, 4a and 5a, when tested at 30 μM, inhibited the trypsin agonist induced protease-activated receptor-2 (PAR2) activity by 80% and 70% respectively. IC₅₀ of 4a (SB70) has been determined as 6 μM which is in the same range of current benchmarks for PAR2 antagonists.

从d-葡萄糖开始合成了新型的具有1,3-顺二醇和1,3-抗二醇化学发光特性的异恶唑系联的二芳基庚烷类，例如4a - d和5a - c。立体保守的一般合成策略。异恶唑杂环化合物是使用我们最近精心设计的方法进行安装的，该方法将Magtrieve™用作选择性氧化剂。这些新的类似物4a和5a中的两个在体外表现出显着改善与姜黄素I相比，具有类似药物的特性，包括溶解度，代谢稳定性，细胞通透性和缺乏非特异性细胞毒性。在基于HEK293细胞的细胞内钙[Ca ²⁺ ] _i释放试验中，当在30μM下进行测试时，4a和5a分别抑制了胰蛋白酶激动剂诱导的蛋白酶激活的受体2（PAR2）活性，分别为80％和70％。IC ₅₀的图4a（SB70）已被确定为6μM这是在相同的范围内的电流基准PAR2拮抗剂。