Ischemia reperfusion injury is responsible for impaired graft functioning in organ transplants, cerebral dysfunction, ischemic heart diseases, systemic inflammatory response syndrome, gastrointestinal dysfunction, and multiple organ dysfunction syndromes. Intracellular pH is critical for cell survival in ischemia reperfusion injury. Sodium hydrogen exchanger I and carbonic anhydrase II are critical in the regulation of intracellular pH. Inhibition of sodium hydrogen exchanger I and carbonic anhydrase II during reperfusion is found to ameliorate ischemia reperfusion injury separately. An attempt is made to synthesize dual inhibitors of sodium hydrogen exchanger and carbonic anhydrase to have better potential drug molecule in ischemia reperfusion injury treatment. The hydroxybenzotriazole is considered as a central pharmacophore for this dual activity and 12 derivatives are synthesized. All derivatives are tested for sodium hydrogen exchanger I and carbonic anhydrase II inhibitory activity. The tosylate derivative (12) is found to be the most potent derivative with IC50 158.7± 8.4 μM for carbonic anhydrase II and 31.07 ± 1.06 μM for sodium hydrogen exchanger I. Although the potency is less than standard drugs but this is the first report of dual inhibitor of carbonic anhydrase II and sodium hydrogen exchanger.

缺血再灌注损伤是器官移植、脑功能障碍、缺血性心脏病、全身炎症反应综合征、胃肠功能障碍和多器官功能障碍综合征中移植物功能受损的原因。细胞内 pH 值对于缺血再灌注损伤中的细胞存活至关重要。钠氢交换剂 I 和碳酸酐酶 II 在调节细胞内 pH 值方面至关重要。发现在再灌注期间抑制钠氢交换剂 I 和碳酸酐酶 II 分别改善缺血再灌注损伤。尝试合成钠氢交换剂和碳酸酐酶双重抑制剂，以在缺血再灌注损伤治疗中具有更好的潜在药物分子。羟基苯并三唑被认为是这种双重活性的中心药效团，合成了 12 种衍生物。测试所有衍生物的钠氢交换剂 I 和碳酸酐酶 II 抑制活性。甲苯磺酸衍生物 (12) 被发现是最有效的衍生物，对碳酸酐酶 II 的 IC50 为 158.7± 8.4 μM，对钠氢交换剂 I 的 IC50 为 31.07 ± 1.06 μM。虽然效力低于标准药物，但这是首次报道碳酸酐酶II和钠氢交换剂的双重抑制剂。