Novel N 4 -substituted decitabine analogs are disclosed that exhibit promising in vitro and in vivo therapeutic activity. These novel compounds were shown to be resistant to deamination via cytidine deaminase (CDA) metabolism and provide a unique pharmacokinetic profile versus decitabine, while retaining the ability to induce DNA demethylation in target cells. These novel compounds can be used for treating hematological cancers, as well for new therapeutic interventions, including bacterial or viral pneumonia, acute respiratory distress syndrome, pulmonary fibrosis, transplantation and checkpoint inhibitor-induced adverse events, including pneumonitis.
                            本文披露了一种新型的N 4 -取代脱氧
胞苷类似物,其在体外和体内表现出有前途的治疗活性。这些新化合物被证明能够抵抗通过
胞苷脱
氨酶(
CDA)代谢引起的脱
氨作用,并提供了与脱氧
胞苷不同的药代动力学特征,同时保留了在靶细胞中诱导DNA去甲基化的能力。这些新化合物可用于治疗血液系统肿瘤,以及新的治疗干预措施,包括细菌或病毒性肺炎、急性呼吸窘迫综合症、肺纤维化、移植和检查点
抑制剂引起的不良事件,包括肺炎。