IP Library › Granted Patent US 9,796,671
Granted Patent B2
US 9,796,671 · App. 15/056,349 · Granted Oct 24, 2017

Aurora kinase inhibitors

Inventors: Ann M. Bode (Minneapolis, MN); Zigang Dong (Minneapolis, MN); Kanamata Reddy (Minneapolis, MN)
Assignee: REGENTS OF THE UNIVERSITY OF MINNESOTA
C07D209/38A61K31/4015C07D209/34C07D405/06C07D405/12
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Quick Facts
Patent No.
US 9,796,671
App. No.
15/056,349
Granted
Oct 24, 2017
Kind
B2
Abstract

The invention provides compounds of the formula: and salts thereof that are useful as intermediates for preparing corresponding compounds of formula I: that are useful for treating conditions associated with Aurora B kinase activity (e.g. cancer).

Claims (40)

1. A compound of formula:

wherein:

ring A is substituted with one or more groups independently selected from hydroxy, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo;

R 1 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 1 and R 2 taken together are methylenedioxy or ethylenedioxy;

R 2 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 1 and R 2 taken together are methylenedioxy or ethylenedioxy; or R 2 and R 3 taken together are methylenedioxy or ethylenedioxy;

R 3 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 2 and R 3 taken together are methylenedioxy or ethylenedioxy; or R 3 and R 4 taken together are methylenedioxy or ethylenedioxy; and

R 4 is H, fluoro, bromo, iodo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 3 and R 4 taken together are methylenedioxy or ethylenedioxy;

or a salt thereof.

2. A compound of formula:

wherein:

R 1 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 1 and R 2 taken together are methylenedioxy or ethylenedioxy;

R 2 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 1 and R 2 taken together are methylenedioxy or ethylenedioxy; or R 2 and R 3 taken together are methylenedioxy or ethylenedioxy;

R 3 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 2 and R 3 taken together are methylenedioxy or ethylenedioxy; or R 3 and R 4 taken together are methylenedioxy or ethylenedioxy; and

R 4 is H, halo, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 3 and R 4 taken together are methylenedioxy or ethylenedioxy;

or a salt thereof.

3. The compound of claim 1 wherein ring A is substituted with one or more (C 1 -C 6 )alkoxy.

4. The compound of claim 1 wherein ring A is 3,4,5-trihydroxyphenyl or 4-nitrophenyl.

5. The compound of claim 1 wherein at least one of R 1 , R 2 , R 3 , and R 4 is other than H.

6. The compound of claim 1 wherein at least one of R 1 , R 2 , and R 3 is halo, cyano, nitro, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, or (C 2 -C 6 )alkanoyloxy.

7. The compound of claim 1 wherein at least one of R 1 , R 2 , R 3 is halo.

8. The compound of claim 1 wherein at least one of R 1 , R 2 , and R 3 is fluoro or chloro.

9. The compound of claim 1 wherein R 2 is halo.

10. The compound of claim 1 wherein R 2 is fluoro or chloro.

11. The compound of claim 1 wherein R 3 is halo.

12. The compound of claim 1 wherein R 3 is fluoro or chloro.

13. A compound selected from:

wherein THP is tetrahydropyranyl.

14. The compound of claim 1 wherein ring A is substituted with one or more groups independently selected from hydroxy, halo, cyano, nitro, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or b more halo.

15. The compound of claim 1 wherein ring A is substituted with one or more groups independently selected from hydroxy, nitro, (C 1 -C 6 )alkoxy, or methylenedioxy.

16. The compound of claim 1 wherein R 4 is H, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, methylenedioxy, ethylenedioxy, or (C 2 -C 6 )alkanoyloxy, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy is optionally substituted with one or more halo; or R 3 and R 4 taken together are methylenedioxy or ethylenedioxy.

17. A compound of formula:

wherein:

ring A is 3,4,5-trihydroxyphenyl or 4-nitrophenyl; and

each R 1 , R 2 , R 3 , and R 4 are each H;

or a salt thereof.

18. A compound of formula:

wherein:

ring A is 4-nitrophenyl; and

each R 1 , R 2 , R 3 , and R 4 are each H;

or a salt thereof.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 6, 2017
From: BODE, ANN M.
To: REGENTS OF THE UNIVERSITY OF MINNESOTA
Reel/Frame 041178/0648 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 6, 2017
From: DONG, ZIGANG
To: REGENTS OF THE UNIVERSITY OF MINNESOTA
Reel/Frame 041178/0676 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 6, 2017
From: REDDY, KANAMATA
To: REGENTS OF THE UNIVERSITY OF MINNESOTA
Reel/Frame 041178/0740 →
CONFIRMATORY LICENSE Recorded Jun 23, 2016
From: UNIVERSITY OF MINNESOTA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 039128/0087 →
Continuity (3)
Continuation 14434712
Provisional Application 61719215 · Oct 26, 2012
Related Publication 20160176820A1 · Jun 23, 2016