公开(公告)号：WO2016123397A2

公开(公告)日：2016-08-04

申请号：PCT/US2016/015456

申请日：2016-01-28

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： ESSIGMANN, John, M. ,  TOKMAKOFF, Andrei ,  FEDELES, Bogdan, I. ,  SINGH, Vipender ,  PENG, Chunte

IPC: C07H19/173 ,  C07H19/04 ,  C07H19/23 ,  A61K31/7052 ,  A61K31/706 ,  A61K31/7076 ,  A61K31/708 ,  A61P31/12 ,  A61P31/18 ,  A61P31/20 ,  A61P35/00

CPC classification number: C07H19/12 ,  A61K31/7052 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7076 ,  A61K31/708 ,  A61K45/06 ,  C07H19/04 ,  C07H19/173 ,  C07H19/23 ,  C12Q1/6811 ,  G01N21/3577 ,  G01N33/15

Abstract: The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs may show multiple tautomerism and may increase the mutation of an RNA and/or DNA (be mutagenic) of a virus or cancer cell. The multiple tautomerism and mutagenesis of the nucleoside analogs may be adjusted by substituting the nucleoside analogs with one or more electron-donating groups and/or electron-withdrawing groups to increase or decrease the p K a ( e.g ., to a p K a between 5.5 or 8.5). The present disclosure also provides pharmaceutical compositions and kits including the nucleoside analogs and methods of treating a viral infection ( e.g ., influenza, HIV infection, or hepatitis) or cancer using the nucleoside analogs, pharmaceutical compositions, or kits.

Abstract translation: 本公开提供式（I）或（II）的核苷类似物。 核苷类似物可能显示多种互变异构体，并且可能增加病毒或癌细胞的RNA和/或DNA（致突变）的突变。 可以通过用一个或多个给电子基团和/或吸电子基团取代核苷类似物来增加或减少pK a（例如，在5.5或8.5之间的pK a）来调节核苷类似物的多重互变异构和诱变 ）。 本公开还提供药物组合物和试剂盒，其包括核苷类似物和使用核苷类似物，药物组合物或试剂盒治疗病毒感染（例如流感，HIV感染或肝炎）或癌症的方法。