公开(公告)号：US12234244B2

公开(公告)日：2025-02-25

申请号：US17716707

申请日：2022-04-08

Applicant: Araxes Pharma LLC

Inventor： Liansheng Li ,  Jun Feng ,  Tao Wu ,  Pingda Ren ,  Yi Liu ,  Yuan Liu ,  Yun Oliver Long

IPC: A61K31/517 ,  C07D215/46 ,  C07D215/54 ,  C07D217/22 ,  C07D239/84 ,  C07D239/94 ,  C07D239/95 ,  C07D241/44 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D409/04 ,  C07D487/04 ,  C07D495/04

Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, have the following structure: wherein A, L1, L2, Q, R1, R2a, R3a, R3b, R4a, R4b, R9, R10, Y, and Z are as exemplified herein. Pharmaceutical compositions comprising such compounds, methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, and methods associated with preparation of such compounds are also provided.

公开(公告)号：US20190389796A1

公开(公告)日：2019-12-26

申请号：US16355258

申请日：2019-03-15

Applicant: Araxes Pharma LLC

Inventor： Pingda Ren ,  Yi Liu ,  Liansheng Li ,  Jun Feng ,  Tao Wu

IPC: C07D205/04 ,  C07D487/10 ,  C07D211/62 ,  C07D213/64 ,  C07D487/04 ,  C07D295/16 ,  C07D401/04 ,  C07D285/14 ,  G01N33/58 ,  C07D213/74 ,  C07D231/40 ,  C07D401/12 ,  C07D403/04 ,  C07D237/04 ,  C07D403/06 ,  C07D405/06 ,  C07D419/12 ,  C07D471/04 ,  C07D285/16 ,  C07D211/56 ,  C07D211/58 ,  C07D211/60 ,  C07D403/12

Abstract: Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

公开(公告)号：US10370386B2

公开(公告)日：2019-08-06

申请号：US15805716

申请日：2017-11-07

Applicant: Araxes Pharma LLC

Inventor： Liansheng Li ,  Jun Feng ,  Tao Wu ,  Pingda Ren ,  Yi Liu ,  Yuan Liu ,  Yun Oliver Long

IPC: A61K31/4709 ,  C07D215/42 ,  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

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, 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：US20190062314A1

公开(公告)日：2019-02-28

申请号：US15989031

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 ,  C07D401/10

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, isotopic form or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, L1, L2, E, X, Y, Z, 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：US10144724B2

公开(公告)日：2018-12-04

申请号：US15217304

申请日：2016-07-22

Applicant: Araxes Pharma LLC

Inventor： Liansheng Li ,  Jun Feng ,  Yun Oliver Long ,  Yuan Liu ,  Tao Wu ,  Pingda Ren ,  Yi Liu

IPC: C07D215/46 ,  C07D403/04 ,  C07D401/04 ,  C07D239/88 ,  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.

公开(公告)号：US20160159738A1

公开(公告)日：2016-06-09

申请号：US14933734

申请日：2015-11-05

Applicant: Araxes Pharma LLC

Inventor： Pingda Ren ,  Yi Liu ,  Liansheng Li ,  Jun Feng ,  Tao Wu

IPC: C07D205/04 ,  C07D403/12

CPC classification number: C07D205/04 ,  C07D211/56 ,  C07D211/58 ,  C07D211/60 ,  C07D211/62 ,  C07D213/64 ,  C07D213/74 ,  C07D231/40 ,  C07D237/04 ,  C07D285/14 ,  C07D285/16 ,  C07D295/16 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D419/12 ,  C07D471/04 ,  C07D487/04 ,  C07D487/10 ,  G01N33/58

Abstract: Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

Abstract translation: 提供了G12C突变体K-Ras蛋白的不可逆抑制剂。 还公开了调节G12C突变体K-Ras蛋白的活性的方法和治疗由G12C突变体K-Ras蛋白介导的病症的方法。

公开(公告)号：US20140288045A1

公开(公告)日：2014-09-25

申请号：US14212656

申请日：2014-03-14

Applicant: Araxes Pharma LLC

Inventor： Pingda Ren ,  Yi Liu ,  Liansheng Li ,  Jun Feng ,  Tao Wu

IPC: C07D487/10 ,  C07D213/64 ,  C07D487/04 ,  G01N33/58 ,  C07D205/04 ,  C07D401/04 ,  C07D285/14 ,  C07D211/62 ,  C07D295/16

CPC classification number: C07D205/04 ,  C07D211/56 ,  C07D211/58 ,  C07D211/60 ,  C07D211/62 ,  C07D213/64 ,  C07D213/74 ,  C07D231/40 ,  C07D237/04 ,  C07D285/14 ,  C07D285/16 ,  C07D295/16 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D419/12 ,  C07D471/04 ,  C07D487/04 ,  C07D487/10 ,  G01N33/58

Abstract: Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

Abstract translation: 提供了G12C突变体K-Ras蛋白的不可逆抑制剂。 还公开了调节G12C突变体K-Ras蛋白的活性的方法和治疗由G12C突变体K-Ras蛋白介导的病症的方法。

公开(公告)号：US11377441B2

公开(公告)日：2022-07-05

申请号：US16915942

申请日：2020-06-29

Applicant: Araxes Pharma LLC

Inventor： Liansheng Li ,  Jun Feng ,  Tao Wu ,  Yuan Liu ,  Yi Wang ,  Pingda Ren ,  Yi Liu

IPC: C07D403/14 ,  C07D401/14 ,  C07D413/14 ,  A61P35/00 ,  C07D403/04 ,  C07D471/04 ,  C07D417/14 ,  C07D405/14 ,  C07D487/08

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：US10919850B2

公开(公告)日：2021-02-16

申请号：US16355258

申请日：2019-03-15

Applicant: Araxes Pharma LLC

Inventor： Pingda Ren ,  Yi Liu ,  Liansheng Li ,  Jun Feng ,  Tao Wu

IPC: C07D205/04 ,  C07D487/10 ,  C07D211/62 ,  C07D213/64 ,  C07D487/04 ,  C07D295/16 ,  C07D401/04 ,  C07D285/14 ,  G01N33/58 ,  C07D213/74 ,  C07D231/40 ,  C07D401/12 ,  C07D403/04 ,  C07D237/04 ,  C07D403/06 ,  C07D405/06 ,  C07D419/12 ,  C07D471/04 ,  C07D285/16 ,  C07D211/56 ,  C07D211/58 ,  C07D211/60 ,  C07D403/12

Abstract: Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

公开(公告)号：US10736897B2

公开(公告)日：2020-08-11

申请号：US15989031

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: A61K31/517 ,  C07D401/14 ,  A61P35/00 ,  C07D239/94 ,  C07D403/14 ,  C07D401/10

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, isotopic form or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, L1, L2, E, X, Y, Z, 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.