- 专利标题: HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF
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申请号: US18343319申请日: 2023-06-28
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公开(公告)号: US20230357221A1公开(公告)日: 2023-11-09
- 发明人: Yves GAREAU , Stéphane GINGRAS , Yves CHANTIGNY , Gaoqiang YANG , Guy SAUVAGEAU , Irène BACCELLI , Anne MARINIER
- 申请人: UNIVERSITÉ DE MONTRÉAL
- 申请人地址: CA Montréal
- 专利权人: UNIVERSITÉ DE MONTRÉAL
- 当前专利权人: UNIVERSITÉ DE MONTRÉAL
- 当前专利权人地址: CA Montréal
- 优先权: CA 95617 2018.02.16
- 主分类号: C07D417/12
- IPC分类号: C07D417/12 ; C07D249/04 ; C07D263/32 ; C07D263/34 ; C07D277/24 ; C07D413/12 ; G01N33/50
摘要:
Heterocyclic compounds of Formula I:
and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NK), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.
and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NK), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.
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