IP Library Granted Patent US 8,293,752
Granted Patent B2
US 8,293,752 · App. 12/164,762 · Granted Oct 23, 2012

Compounds useful as Raf kinase inhibitors

Assignees: Millennium Pharmaceuticals, Inc.; Sunesis Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 8,293,752
App. No.
12/164,762
Granted
Oct 23, 2012
Kind
B2
Abstract

The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.

Claims (25)

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Cy 1 is an optionally substituted 5 membered-aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

Cy 2 is an optionally substituted 6 membered aromatic ring having 1-2 heteroatoms, independently selected from nitrogen, oxygen, and sulfur;

L 1 is an optionally substituted, straight or branched C 1-6 alkylene chain;

L 2 is —C(O)N(R)—;

each R is independently hydrogen or an optionally substituted C 1-6 aliphatic group;

R 1 is hydrogen or an optionally substituted C 1-6 aliphatic group;

each of R x and R y is independently selected from -halo, or —N(R 2 ) 2 ; and

each R 2 is independently hydrogen or an optionally substituted C 1-6 aliphatic group.

2. The compound according to claim 1 , wherein R y is —N(R 2 ) 2 .

3. The compound according to claim 2 , wherein R y is —NH 2 , —NHCH 3 , —NHCH 2 CH 3 , —NHCH 2 CH 2 CH 3 , —NHCH(CH 3 ) 2 , —NH(C 3 H 5 ), —NHCH 2 CH 2 CH 2 OH, or —NHCH 2 CH 2 CH 2 NH(CH 3 ) 2 .

4. The compound according to claim 1 , wherein R 1 is hydrogen and L 1 is an optionally substituted, straight or branched C 1-4 alkylene chain.

5. The compound according claim 1 , wherein Cy 1 is an optionally substituted pyrrolyl, pyrazolyl, imidazolyl, triazolyl, thiophenyl, furanyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, or oxadiazolyl group.

6. The compound according to claim 1 , wherein L 2 is —C(O)N(H)—.

7. The compound according to claim 1 , wherein Cy 2 is an optionally substituted group selected from pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl.

8. The compound according to claim 1 , wherein said compound is of formula II:

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 8 , wherein said compound of formula II is of formula II-a or II-b:

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

11. The composition of claim 10 , in combination with a therapeutic agent selected from a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory agent, a neurotrophic factor, an agent for treating cardiovascular disease, an agent for treating destructive bone disorders, an agent for treating liver disease, an anti-viral agent, an agent for treating blood disorders, an agent for treating diabetes, and an agent for treating immunodeficiency disorders.

12. The compound according to claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising the compound of claim 12 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

Assignments (10)
SECURITY INTEREST Recorded Jul 14, 2026
From: CYDEX PHARMACEUTICALS, INC.; LIGAND PHARMACEUTICALS INCORPORATED; METABASIS THERAPEUTICS, INC.; XOMA (US) LLC; APEIRON BIOLOGICS GMBH
To: CITIBANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 075969/0966 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 3, 2024
From: VIRACTA THERAPEUTICS, INC.
To: XOMA (US) LLC
Reel/Frame 069474/0049 →
CHANGE OF NAME Recorded Apr 14, 2023
From: SUNESIS PHARMACEUTICALS, INC.
To: VIRACTA THERAPEUTICS, INC.
Reel/Frame 063349/0100 →
MERGER Recorded May 17, 2022
From: DOT THERAPEUTICS-2, INC.; DOT THERAPEUTICS-1, INC.
To: DAY ONE BIOPHARMACEUTICALS, INC.
Reel/Frame 059936/0096 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 1, 2020
From: MILLENNIUM PHARMACEUTICALS, INC.
To: DOT THERAPEUTICS-1, INC.
Reel/Frame 052288/0694 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2011
From: BIOGEN IDEC MA INC.
To: MILLENNIUM PHARMACEUTICALS, INC.
Reel/Frame 027441/0954 →
CONFIRMATION OF ASSIGNMENT-JOINT OWNERSHIP BETWEEN BIOGEN IDEC MA INC. AND SUNESIS PHARMACEUTCIALS, INC. Recorded Jul 17, 2009
From: SUNESIS PHARMACEUTICALS, INC.; BIOGEN IDEC MA INC.
To: SUNESIS PHARMACEUTICALS, INC.; BIOGEN IDEC MA INC.
Reel/Frame 022974/0444 →
CONFIRMATION OF ASSIGNMENT-JOINT OWNERSHIP BETWEEN BIOGEN IDEC MA INC. AND SUNESIS PHARMACEUTICALS, INC. Recorded Jul 17, 2009
From: BIOGEN IDEC MA INC.; SUNESIS PHARMACEUTICALS, INC.
To: SUNESIS PHARMACEUTICALS, INC.; BIOGEN IDEC MA INC.
Reel/Frame 022974/0461 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2008
From: CHEN, WEIRONG; FRANKLIN, LLOYD; GUAN, BING; JONES, JOHN HOWARD; KUMARAVEL, GNANASAMBANDAM; LANE, BENJAMIN; LITTKE, ADAM; LUGOVSKOY, ALEXEY; PENG, HAIRUO; POWELL, NOEL; VESSELS, JEFFREY; WYNN, THOMAS; XIN, ZHILI
To: BIOGEN IDEC MA INC.
Reel/Frame 021707/0639 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2008
From: COSSROW, JENNIFER; RAIMUNDO, BRIAN C.; TANAKA, HIROKO
To: SUNESIS PHARMACEUTICALS, INC.
Reel/Frame 021688/0887 →
Continuity (2)
Provisional Application 60947291 · Jun 29, 2007
Related Publication 20090036419A1 · Feb 5, 2009