IP Library › Granted Patent US 12,252,497
Granted Patent B2
US 12,252,497 · App. 17/737,218 · Granted Mar 18, 2025

Ras inhibitors

Inventors: G. Leslie Burnett (Redwood City, CA); James Cregg (Belmont, CA); Anne V. Edwards (San Mateo, CA); Adrian L. Gill (Atherton, CA); John E. Knox (Emerald Hills, CA); Elena S. Koltun (Foster City, CA); Jennifer Pitzen (Fremont, CA); Christopher Semko (Fremont, CA)
Assignee: Revolution Medicines, Inc.
C07D519/00C07D498/18
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Quick Facts
Patent No.
US 12,252,497
App. No.
17/737,218
Granted
Mar 18, 2025
Kind
B2
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.

Claims (19)

1. A compound having the structure of Formula I:

or a pharmaceutically acceptable salt thereof, wherein A is, optionally substituted 6-membered arylene, or optionally substituted 5 to 10-membered heteroarylene;

W is a cross-linking group comprising, an epoxide, a carbodiimide, an oxazoline, a thiazoline, a chloroethyl urea, a chloroethyl thiourea, a chloroethyl carbamate, a chloroethyl thiocarbamate, a trifluoromethyl ketone, a boronic acid, a boronic ester, an N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an iso-EEDQ or other EEDQ derivative, an oxazolium, or a glycal;

X 1 is CH 2 or O;

m is 1 or 2;

n is 0 or 1;

R 1 is hydrogen or optionally substituted 3 to 10-membered heterocycloalkyl;

R 2 is optionally substituted C 1 -C 6 alkyl; and

R 3 is optionally substituted C 1 -C 6 alkyl or optionally substituted 3 to 6-membered cycloalkyl.

2. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein A is optionally substituted thiazole, optionally substituted oxazole, or optionally substituted phenyl.

3. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is:

4. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3 is optionally substituted C 1 -C 6 alkyl.

5. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3 is optionally substituted 3 to 6-membered cycloalkyl.

6. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein A is optionally substituted 5 to 10-membered heteroarylene.

7. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein A is optionally substituted phenylene.

8. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W comprises an epoxide.

9. The compound of claim 1 , or pharmaceutically acceptable salt thereof, selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, of claim 1 and a pharmaceutically acceptable excipient.

Assignments (2)
SECURITY INTEREST Recorded Jun 25, 2025
From: REVOLUTION MEDICINES, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS AGENT
Reel/Frame 071721/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 9, 2022
From: BUCKL, ANDREAS; BURNETT, G. LESLIE; CREGG, JAMES; EDWARDS, ANNE V.; GILL, ADRIAN L.; KNOX, JOHN E.; KOLTUN, ELENA S.; PITZEN, JENNIFER; SEMKO, CHRISTOPHER
To: REVOLUTION MEDICINES, INC.
Reel/Frame 060147/0247 →
Continuity (2)
Provisional Application 63184618 · May 5, 2021
Related Publication 20220396589A1 · Dec 15, 2022
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