-
公开(公告)号:US20230303586A1
公开(公告)日:2023-09-28
申请号:US18178452
申请日:2023-03-03
申请人: Araxes Pharma LLC
发明人: Liansheng LI , Jun FENG , Tao WU , Pingda REN , Yi LIU , Yuan Liu , Yun Oliver Long
IPC分类号: C07D495/04 , C07D239/94 , C07D401/12 , C07D217/22 , C07D215/46 , C07D215/54 , C07D239/84 , C07D487/04 , C07D239/95 , C07D403/04 , C07D241/44 , C07D401/04 , C07D409/04
CPC分类号: C07D495/04 , C07D215/46 , C07D215/54 , C07D217/22 , C07D239/84 , C07D239/94 , C07D239/95 , C07D241/44 , C07D401/04 , C07D401/12 , C07D403/04 , C07D409/04 , C07D487/04
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.-
公开(公告)号:US20210380595A1
公开(公告)日:2021-12-09
申请号:US17287473
申请日:2019-10-23
申请人: ARAXES PHARMA LLC
发明人: Liansheng LI , Yuan LIU , Tao WU , Jun FENG , Pingda REN , Yi LIU
IPC分类号: C07D487/10
摘要: The present invention provides e.g. 2-(2-acryloyl-2, 6-diazaspiro[3.4]octan-6-yl)-6-(1H-indazol-4-yl)-benzonitrile and e.g. 2-(2-acryloyl-2,7-diazaspiro[3.5]nonan-7-yl)-6-(1H-indazol-4-yl)-benzonitrile derivatives and related compounds of formula (I) as inhibitors of G12C mutant KRAS protein for treating tumor metastasis. The present description discloses exemplary compounds (e.g. pages 53 to 90; table 1; compounds I-1 to I-141), pharmacological data (e.g. page 125 to 128; table 2; example 1) and synthesis thereof (e.g. pages 129 to 143; examples 2 to 7). Exemplary compounds are e.g. 2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(5-methyl-1H-indazol-4-yl)-4-morpholinobenzonitrile (example 2; compound I-1) and 6-(2-acryloyl-2,7-diazaspiro[3.5]nonan-7-yl)-3-methoxy-2-(5-methyl-1H-indazol-4-yl)-4-morpholinobenzonitrile (example 7; compound I-84).
-
公开(公告)号:US20240043441A1
公开(公告)日:2024-02-08
申请号:US18183870
申请日:2023-03-14
申请人: Araxes Pharma LLC
发明人: Liansheng LI , Jun FENG , Tao WU , Pingda REN , Yi LIU , Yuan Liu , Yun Oliver Long
IPC分类号: C07D495/04 , C07D239/94 , C07D401/12 , C07D217/22 , C07D215/46 , C07D215/54 , C07D239/84 , C07D487/04 , C07D239/95 , C07D403/04 , C07D241/44 , C07D401/04 , C07D409/04
CPC分类号: C07D495/04 , C07D239/94 , C07D401/12 , C07D217/22 , C07D215/46 , C07D215/54 , C07D409/04 , C07D487/04 , C07D239/95 , C07D403/04 , C07D241/44 , C07D401/04 , C07D239/84
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.-
公开(公告)号:US20230212183A9
公开(公告)日:2023-07-06
申请号:US17716707
申请日:2022-04-08
申请人: Araxes Pharma LLC
发明人: Liansheng LI , Jun FENG , Tao WU , Pingda REN , Yi LIU , Yuan Liu , Yun Oliver Long
IPC分类号: C07D495/04 , C07D239/94 , C07D401/12 , C07D217/22 , C07D215/46 , C07D215/54 , C07D239/84 , C07D487/04 , C07D239/95 , C07D403/04 , C07D241/44 , C07D401/04 , C07D409/04
CPC分类号: C07D495/04 , C07D239/94 , C07D401/12 , C07D217/22 , C07D215/46 , C07D215/54 , C07D239/84 , C07D487/04 , C07D239/95 , C07D403/04 , C07D241/44 , C07D401/04 , C07D409/04
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.-
公开(公告)号:US20220112192A1
公开(公告)日:2022-04-14
申请号:US17298409
申请日:2019-11-27
申请人: ARAXES PHARMA LLC
发明人: Liansheng LI , Yuan LIU , Tao WU , Pingda REN , Yi LIU
IPC分类号: C07D471/10 , A61P35/00 , C07D487/10
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (I) or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein A, B, R1, R3, L1, L2, L3, E, A1, A2, A3, A4, G1, G2, W, X, Y, Z, m1, m2, n1, and n2 are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
-
公开(公告)号:US20170247376A1
公开(公告)日:2017-08-31
申请号:US15508387
申请日:2015-09-25
申请人: ARAXES PHARMA LLC
发明人: Liansheng LI , Jun FENG , Yun Oliver LONG , Pingda REN , Yi LIU
IPC分类号: C07D471/04 , C07D239/94 , A61K31/517 , C07D403/04 , C12N9/14 , C07D403/12 , C07D401/14 , C07D405/12 , A61K9/00 , A61K45/06 , C07D401/04
CPC分类号: C07D471/04 , A61K9/0019 , A61K9/0053 , A61K31/517 , A61K45/06 , C07D239/94 , C07D239/95 , C07D401/04 , C07D401/14 , C07D403/04 , C07D403/12 , C07D403/14 , C07D405/12 , C12N9/14 , C12Y306/05
摘要: Inhibitors of Ras protein, methods to modulate the activity of Ras protein, and methods of treatment of disorders mediated by Ras protein are provided. A method for regulating activity of a K-Ras, H-Ras or N-Ras mutant protein with a compound is described. Disorders that can be treated include cancer, such as hematological cancer, pancreatic cancer, MYH associated polyposis, colorectal cancer, or lung cancer.
-
公开(公告)号:US20210317127A1
公开(公告)日:2021-10-14
申请号:US17264744
申请日:2019-08-01
申请人: ARAXES PHARMA LLC
发明人: Liansheng LI , Jun FENG , Tao WU , Yuan LIU , Yi WANG , Alana K. BORUM , Pingda REN , Yi LIU
IPC分类号: C07D487/10 , C07D519/00
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R1, L1, L2, L3, A1, A2, A3, A4, G1, G2, E, W, X, Y, Z, m, and n are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
-
公开(公告)号:US20210188869A1
公开(公告)日:2021-06-24
申请号:US17125955
申请日:2020-12-17
申请人: Araxes Pharma LLC
发明人: Liansheng LI , Jun FENG , Tao WU , Pingda REN , Yi LIU , Yuan Liu , Yun Oliver Long
IPC分类号: C07D495/04 , C07D239/94 , C07D401/12 , C07D217/22 , C07D215/46 , C07D215/54 , C07D239/84 , C07D487/04 , C07D239/95 , C07D403/04 , C07D241/44 , C07D401/04 , C07D409/04
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
-
公开(公告)号:US20190127336A1
公开(公告)日:2019-05-02
申请号:US16089000
申请日:2017-03-29
申请人: ARAXES PHARMA LLC
发明人: LIANSHENG LI , Jun FENG , Pingda REN , Yi LIU
IPC分类号: C07D239/95 , A61K31/517 , A61K45/06 , C07D403/12 , C07D403/04 , A61P35/00
CPC分类号: C07D239/95 , A61K31/517 , A61K45/06 , A61P35/00 , C07D401/14 , C07D403/04 , C07D403/12 , C07D403/14 , C11D3/50 , A61K2300/00
摘要: The present disclosure provides inhibitors of Ras protein. Also disclosed are methods to modulate the activity of Ras protein and methods of treatment of disorders mediated by Ras protein.
-
公开(公告)号:US20240352028A1
公开(公告)日:2024-10-24
申请号:US18416739
申请日:2024-01-18
申请人: Araxes Pharma LLC
发明人: Liansheng LI , Jun FENG , Tao WU , Pingda REN , Yi LIU , Yuan Liu , Yun Oliver Long
IPC分类号: C07D495/04 , C07D215/46 , C07D215/54 , C07D217/22 , C07D239/84 , C07D239/94 , C07D239/95 , C07D241/44 , C07D401/04 , C07D401/12 , C07D403/04 , C07D409/04 , C07D487/04
CPC分类号: C07D495/04 , C07D215/46 , C07D215/54 , C07D217/22 , C07D239/84 , C07D239/94 , C07D239/95 , C07D241/44 , C07D401/04 , C07D401/12 , C07D403/04 , C07D409/04 , C07D487/04
摘要: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
-
-
-
-
-
-
-
-
-