公开(公告)号：US11319300B2

公开(公告)日：2022-05-03

申请号：US16480599

申请日：2018-01-19

申请人： ZHEJIANG UNIVERSITY

发明人： Xiaowu Dong ,  Bo Yang ,  Yongzhou Hu ,  Qiaojun He ,  Qinjie Weng ,  Wenhu Zhan ,  Tao Liu

IPC分类号： A61P35/00 ,  A61P35/04 ,  C07D401/12 ,  C07D403/12

摘要： A polyfluoro-substituted aromatic heterocyclic derivative having the structure as represented by formula I or formula I′, wherein at least one of R1 and R2 is a fluorine atom, and at least two substituents of Rc, Rd, Re, and Rf are fluorine atoms; and an optical isomer of the derivative, or a pharmaceutically acceptable salt or solvate of the same, or a pharmaceutically acceptable salt or solvate of the optical isomer of the same. A composition containing the polyfluoro-substituted aromatic heterocyclic derivative and an application of the composition in preparing an anti-tumour medicament. The compound provides significant inhibitory effects with respect to Akt1 and demonstrates strong proliferation inhibitory activity with respect to tumour cell lines such as an ovarian cancer cell line, a colon cancer cell line, and a prostate cancer cell line. Therefore, the compound may be used as an Akt inhibitor in the medicament for treating a cell proliferation-related solid tumour or blood cancer in the human or animal body.

公开(公告)号：US20230295144A1

公开(公告)日：2023-09-21

申请号：US18100782

申请日：2023-01-24

申请人： ZHEJIANG UNIVERSITY ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Tao Liu ,  Jia Li ,  Yongzhou Hu ,  Yubo Zhou ,  Xiaowu Dong ,  Anhui Gao ,  Pinrao Song ,  Peipei Wang ,  Lexian Tong ,  Xiaobei Hu ,  Mingbo Su

IPC分类号： C07D413/14 ,  A61P35/02 ,  A61P35/00 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14

CPC分类号： C07D413/14 ,  A61P35/00 ,  A61P35/02 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14

摘要： The present invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative and an optical isomer thereof, or a pharmaceutically acceptable salt or solvate thereof, the compound, and an optical isomer thereof or a pharmaceutically thereof acceptable salts or solvates can be used in the preparation of anti-tumor drugs. The invention designs and synthesizes a series of novel small molecule Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained by structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess potent anticancer activity, Chk1 kinase inhibitory activity, and are promising Chk1 inhibitors, and can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal. The 2-polysubstituted aromatic ring-pyrimidine derivatives provided by the present invention has the structure of the formula I:

公开(公告)号：US20210284625A1

公开(公告)日：2021-09-16

申请号：US16348499

申请日：2017-11-08

申请人： ZHEJIANG UNIVERSITY ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Tao Liu ,  Jia Li ,  Yongzhou Hu ,  Yubo Zhou ,  Xiaowu Dong ,  Anhui Gao ,  Pinrao Song ,  Peipei Wang ,  Lexian Tong ,  Xiaobei Hu ,  Mingbo Su

IPC分类号： C07D401/14 ,  C07D417/14 ,  C07D413/14 ,  C07D409/14 ,  C07D405/14 ,  A61P35/00 ,  A61P35/02

摘要： The present invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative and an optical isomer thereof, or a pharmaceutically acceptable salt or solvate thereof, the compound, and an optical isomer thereof or a pharmaceutically thereof acceptable salts or solvates can be used in the preparation of anti-tumor drugs. The invention designs and synthesizes a series of novel small molecule Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained by structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess potent anticancer activity, Chk1 kinase inhibitory activity, and are promising Chk1 inhibitors, and can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal. The 2-polysubstituted aromatic ring-pyrimidine derivatives provided by the present invention has the structure of the formula I:

公开(公告)号：US11591325B2

公开(公告)日：2023-02-28

申请号：US16348499

申请日：2017-11-08

申请人： ZHEJIANG UNIVERSITY ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Tao Liu ,  Jia Li ,  Yongzhou Hu ,  Yubo Zhou ,  Xiaowu Dong ,  Anhui Gao ,  Pinrao Song ,  Peipei Wang ,  Lexian Tong ,  Xiaobei Hu ,  Mingbo Su

IPC分类号： C07D413/14 ,  A61P35/02 ,  A61P35/00 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14

摘要： The present invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative and an optical isomer thereof, or a pharmaceutically acceptable salt or solvate thereof, the compound, and an optical isomer thereof or a pharmaceutically thereof acceptable salts or solvates can be used in the preparation of anti-tumor drugs. The invention designs and synthesizes a series of novel small molecule Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained by structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess potent anticancer activity, Chk1 kinase inhibitory activity, and are promising Chk1 inhibitors, and can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal. The 2-polysubstituted aromatic ring-pyrimidine derivatives provided by the present invention has the structure of the formula I:

公开(公告)号：US10233180B2

公开(公告)日：2019-03-19

申请号：US15128298

申请日：2015-03-21

申请人： ZHEJIANG UNIVERSITY ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Xiaowu Dong ,  Jia Li ,  Bo Yang ,  Yongzhou Hu ,  Yubo Zhou ,  Qinjie Weng ,  Wenhu Zhan ,  Lei Xu ,  Tao Liu ,  Qiaojun He

IPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are new substituted nitrogen-containing heterocyclic derivatives represented by formula (I) as AKT inhibitors, optical isomers, pharmaceutically acceptable salts or solvates thereof, wherein the definition of R1, R2, R3, R4, R5, R6, ring A, ring C, B, Q, Y, Z and m is shown in the description for details. In addition, medicaments comprising the derivatives as active components are also disclosed, which can be useful for treating proliferative diseases, such as cancer and inflammation, especially diseases relating to AKT kinase.

公开(公告)号：US10822327B2

公开(公告)日：2020-11-03

申请号：US16348502

申请日：2017-11-08

申请人： ZHEJIANG UNIVERSITY ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Tao Liu ,  Jia Li ,  Yongzhou Hu ,  Yubo Zhou ,  Xiaowu Dong ,  Anhui Gao ,  Pinrao Song ,  Peipei Wang ,  Lexian Tong ,  Xiaobei Hu ,  Mingbo Su

IPC分类号： C07D401/14 ,  A61P35/00 ,  C07D401/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： A 2-substituted aromatic ring-pyrimidine derivative as shown in a general formula I, and an optical isomer or a pharmaceutically acceptable salt or a solvate thereof are provided. The present invention designs and synthesizes a series of novel small molecular Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained through structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess strong anti-cancer effect, Chk1 kinase inhibitory activity and are promising Chk1 inhibitors. The compounds can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal.

公开(公告)号：US20190375727A1

公开(公告)日：2019-12-12

申请号：US16348502

申请日：2017-11-08

申请人： ZHEJIANG UNIVERSITY ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Tao Liu ,  Jia Li ,  Yongzhou Hu ,  Yubo Zhou ,  Xiaowu Dong ,  Anhui Gao ,  Pinrao Song ,  Peipei Wang ,  Lexian Tong ,  Xiaobei Hu ,  Mingbo Su

IPC分类号： C07D401/14 ,  C07D401/12 ,  C07D417/14 ,  C07D413/14 ,  C07D405/14 ,  C07D409/14 ,  A61P35/00

摘要： A 2-substituted aromatic ring-pyrimidine derivative as shown in a general formula I, and an optical isomer or a pharmaceutically acceptable salt or a solvate thereof are provided. The present invention designs and synthesizes a series of novel small molecular Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained through structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess strong anti-cancer effect, Chk1 kinase inhibitory activity and are promising Chk1 inhibitors. The compounds can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal.