Ras inhibitors

Patent metadata

Field	Value
Publication number	US-12202845-B2
Application number	US-202217938890-A
Country	US
Kind code	B2
Filing date	Oct 7, 2022
Priority date	Oct 8, 2021
Publication date	Jan 21, 2025
Grant date	Jan 21, 2025

Abstract

The invention features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

First claim

The invention claimed is:

1. A compound having the structure of Formula I:

or a pharmaceutically acceptable salt thereof,
wherein A is morpholine-diyl;
X 1 , X 2 , and X 3 are each CH 2 ;
m is 1;
n is 1;
R 1 is hydrogen, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted 3 to 10-membered heterocycloalkyl;
R 2 is optionally substituted C 1 -C 6 alkyl; and
R 3 is cyclopentyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is

3. A compound of the following structure:

or a pharmaceutically acceptable salt thereof.

4. A compound of the following structure:

5. A pharmaceutical composition comprising a compound of the following structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

6. A pharmaceutical composition comprising a compound of the following structure:

and a pharmaceutically acceptable excipient.

Assignees

• Revolution Medicines Inc

Inventors

• Knox John E
• Koltun Elena S
• Liu Yang
• Burnett G Leslie
• Cregg James
• Edwards Anne V
• Gill Adrian L
• Buckl Andreas
• Semko Christopher

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K5/06052

  Val-amino acid · CPC title

• C07K5/06078 Primary

  and aromatic or cycloaliphatic · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title