Araxes Pharma LLC

Janssen Biotech, Inc.

Merck Sharp + Dohme Corp.

Yuan Liu

Pingda Ren

Liansheng Li

Yi Liu

Jun Feng

Tao Wu

Yi Wang

Ronald J Doll

Malcolm MacCoss

Timothy J Guzi

Michael D Altman

Thomas Allen Miller

Yun Long

Neelakandha S Mani

Stephane L Bogen

Maria Emilia Di Francesco

Alan B Northrup

Malcolm Maccoss

Michelle R Machacek

Manami Shizuka

Matthew Ernst Voss

Ryan D Otte

Andrew M Haidle

Brian M Andresen

Xiaohu Deng

Michael Hale Reutershan

Craig R Gibeau

Kenneth L Arrington

John Michael Ellis

Brett D Allison

Latha G Nair

Yaolin Wang

Benjamin Wesley Trotter

Weidong Pan

Kaleen Konrad Childers

Jimmy T Liang

Gerald W Shipps

Eric Thomas Romeo

Brendan O'Boyle

Zachary S Sales

Hyun Chong Woo

Yao Ma

Dilrukshi Vitharana

Amin Nomeir

Giovanna Scapin

Brian Robert Lahue

Margarita Kirova-Snover

Danny J Hicklin

Diane Rindgen

Cynthia Seidel-Dugan

Bheemashankar A Kulkarni

Brian Michael Andresen

Brandon M Taoka

Alana K Borum

W Brent Clayton

Graig R Gibeau

Matthew E Voss

Yun Oliver Long

Yuan Tian

Neville John Anthony

Brian R Lahue

Mark A Miccoy

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 R, R, R, R, R, R, R, R, R, R, R, A, B, G, G, L, L, m, m, 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.

Substituted quinazoline compounds and methods of use thereof

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, L, L, Q, R, R, R, R, R, R, R, R, 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.

Substituted piperazines as inhibitors of KRAS G12C

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 R, L, L, L, A, A, A, A, G, G, 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.

Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer

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 R, R, R, R, R, R, G, G, L, L, m, m, 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.

Substituted quinazolines as inhibitors of KRAS G12C

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 R, R, R, R, R, R, R, R, R, L, L, E, mand mare 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. 

Quinazoline derivatives as modulators of mutant KRAS, HRAS or NRAS

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 R, R, R, R, R, R, R, R, R, L, L, L, E, m, mand * 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.

Covalent inhibitors of KRAS

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 B, Z, R, R, R, R, L, Land 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. 

Benzothiophene and benzothiazole compounds and methods of use thereof

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, L, E, R, RRand 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 (L) 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 (R). 

1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1 yl)prop-2-en-1-one derivatives and similar compounds as KRAS G12C modulators for treating cancer

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, isotopic form, stereoisomer or prodrug thereof, wherein A, B, X, 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. 

Fused bicyclic benzoheteroaromatic compounds and methods of use thereof

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, R, R, R, R, L, Land 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. 

Substituted quinazoline and quinazolinone compounds and methods of use thereof

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 A, W, X, Y, Z, 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. 

Fused hetero-hetero bicyclic compounds and methods of use thereof

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, R, R, R, R, R, R, R, R, R, R, A, G, G, L, L, m, m, n, X and E are as defined herein, and wherein at least one of R, R, Ror Ris 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.

2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof

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, B R, R, R, R, R, R, R, G, G, m, m, L, Land 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. 

Inhibitors of KRAS G12C mutant proteins

Substituted cinnolines as inhibitors of KRAS G12C

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San Diego, CA, United States of America

Yuan Liu