-
公开(公告)号：US11639346B2
公开(公告)日：2023-05-02
申请号：US16616066
申请日：2018-05-24
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Tao Wu , Yuan Liu , Yi Wang , Pingda Ren , Yi Liu
IPC: C07D403/14 , C07D403/04
Abstract: 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, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5, L1, L2, E, m1 and m2 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：US11021470B2
公开(公告)日：2021-06-01
申请号：US16514675
申请日：2019-07-17
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yun Oliver Long , Yuan Liu , Tao Wu , Pingda Ren , Yi Liu
IPC: C07D403/14 , C07D401/14 , C07D403/04 , C07D405/14 , C07D413/14 , C07D471/04 , C07D487/10 , C07D491/10
Abstract: 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 or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, G1, G2, L1, L2, m1, m2, n, X and E are as defined herein, and wherein at least one of R3a, R3b, R4a or R4b is not H. 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：US10689356B2
公开(公告)日：2020-06-23
申请号：US15764088
申请日：2016-09-28
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yun Oliver Long , Yuan Liu , Pingda Ren , Yi Liu
IPC: C07D401/04 , C07D471/04 , A61P35/00 , A61K9/00 , A61K31/4375 , A61K31/4725
Abstract: 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, stereoisomer or prodrug thereof, wherein A, R1, R3a, R3b, R4a, R4b, G2, G3, G4, m1, m2, m3, m4, L1, L2 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：US20200010454A1
公开(公告)日：2020-01-09
申请号：US16480205
申请日：2018-01-24
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yuan Liu , Pingda Ren , Yi Liu
IPC: C07D403/04 , C07D403/14
Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (Formula (I)) or a pharmaceutically acceptable salt, stereoisomer thereof, wherein G, Y, R, R1, R2a, R2b, R2c, L, L1 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. Preferred compounds are quinazoline and quinazolinone derivatives and in particular 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds.
-
公开(公告)号：US20190382377A1
公开(公告)日：2019-12-19
申请号：US16480195
申请日：2018-01-24
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yuan Liu , Pingda Ren , Yi Liu
IPC: C07D403/04 , A61K9/00 , A61P35/04 , C07D405/04
Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, isotopic form or stereoisomer thereof, wherein A is a five-membered heteroaryl comprising 1 or 2 non-adjacent heteroatoms, inclusive of X and Y; W, X, Y, Z, L, L1, E, R1, R2bR2c and the dotted circle are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and compounds for use in methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. Preferred compounds are e.g. 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and related compounds such as e.g. the corresponding derivatives with e.g. a benzoimidazole, indole, benzooxazole, imidazopyridine or imidazole core structure, substituted on ring A by e.g. azetidine, pyrrolidine, azepane or bicyclopentane-amine (L1) each substituted by e.g. propenone (E), and the core structure substituted on the six-membered ring with e.g. 3-hydroxynaphthalene or indazole or hydroxy-, alkoxy- and/or fluoro-substituted phenyl (R1).
-
公开(公告)号：US20190284144A1
公开(公告)日：2019-09-19
申请号：US16281905
申请日：2019-02-21
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yun Oliver Long , Yuan Liu , Tao Wu , Pingda Ren , Yi Liu
IPC: C07D239/74 , C07F9/6558 , C07D403/12 , C07D487/10 , C07D471/08 , C07D417/04 , C07D413/12 , C07D239/95 , C07D239/94 , C07D409/12 , C07D405/12 , C07D403/14 , C07D403/04 , C07D401/12 , C07D401/04 , C07D405/14 , C07D401/14 , C07D491/10
Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, B, G1, G2, L1, L2, m1, m2, n, x, y, X 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：US20190062313A1
公开(公告)日：2019-02-28
申请号：US15989015
申请日：2018-05-24
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Tao Wu , Yuan Liu , Yi Wang , Pingda Ren , Yi Liu
IPC: C07D403/14 , A61P35/00 , C07D403/04 , C07D401/14 , C07D487/08 , C07D413/14 , C07D471/04 , C07D405/14
Abstract: 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, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5, L1, L2, L3, E, m1, m2 and * 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：US20180273523A1
公开(公告)日：2018-09-27
申请号：US15763806
申请日：2016-09-27
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yun Oliver Long , Pingda Ren , Yi Liu
IPC: C07D417/14 , C07D403/14 , A61P35/04
CPC classification number: C07D417/14 , A61K9/0019 , A61K9/0053 , A61P35/04 , C07D403/14
Abstract: 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, tautomer, stereoisomer or prodrug thereof, wherein A, R3a, R3b, R4a, R4b, G1, G2, G3, G4, m1, m2, m3, m4, L1, L2 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：US20180246102A1
公开(公告)日：2018-08-30
申请号：US15713297
申请日：2017-09-22
Applicant: Araxes Pharma LLC
Inventor： Matthew P. Patricelli , Ulf Peters , Liansheng Li , Pingda Ren , Yi Liu
IPC: G01N33/573 , C12N9/14
CPC classification number: G01N33/573 , C12N9/14 , C12Y306/05002 , G01N33/542 , G01N33/574 , G01N2333/912 , G01N2500/04 , G01N2500/20
Abstract: Provided herein are compositions, reactions mixtures, mutant Ras proteins, kits, substrates, and systems for selecting a Ras antagonist, as well as methods of using the same.
-
公开(公告)号：US20180194748A1
公开(公告)日：2018-07-12
申请号：US15916075
申请日：2018-03-08
Applicant: Araxes Pharma LLC
Inventor： Liansheng Li , Jun Feng , Yun Oliver Long , Yuan Liu , Tao Wu , Pingda Ren , Yi Liu
IPC: C07D403/04 , G01N33/532 , C07D215/46 , C07D239/88 , C07D401/04
CPC classification number: C07D403/04 , C07D215/46 , C07D239/88 , C07D401/04 , G01N33/532
Abstract: 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 or prodrug thereof, wherein R, R1, R2a, R2b, R2c, A, B, L1 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.
