AMINOPYRIMIDINE DERIVATIVES AS LRRK2 INHIBITORS

• US 20110301141A1
• Filed: 06/01/2011
• Published: 12/08/2011
• Est. Priority Date: 06/04/2010
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Chen, Huifen, Estrada, Anthony, Sweeney, Zachary, Wang, Shumei, Baker-Glenn, Charles, Burdick, Daniel Jon, Chambers, Mark, Chan, Bryan K., Gunzner-Toste, Janet, Shore, Daniel, Zhao, Guiling
• Granted Patent: US 8,354,420 B2
• Time in Patent Office: Days
• US Class Current: 514/210.16
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 473/16 two nitrogen atoms
• CPC Class Codes: C07D 498/06 Peri-condensed systems
• CPC Class Codes: C07D 498/08 Bridged systems

Abstract

Compounds of the formula I:

or pharmaceutically acceptable salts thereof,
wherein m, n. X, R¹, R², R³, R⁵, R⁶ and R⁷ are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson'"'"'s disease.

Claims

1. A compound of formula I:

2. The compound of claim 1, wherein said compound is of formula II:

3. The compound of claim 2 wherein m is 0 or 1.

4. The compound of claim 2 wherein X is —

NR^a—

or —

O—

.

5. The compound of claim 2 wherein X is —

NR^a.

6. The compound of claim 2 wherein R¹ is C_1-6alkyl.

7. The compound of claim 2 wherein R² is:

halo;

halo-C_1-6alkyl;

or cyano.

8. The compound of claim 2 wherein R² is:

chloro, trifluoromethyl or cyano.

9. The compound of claim 2 wherein R³ is:

halo;

or —

OR⁴.

10. The compound of claim 2 wherein R³ is:

halo;

C_1-6alkoxy;

or halo-C_1-6alkoxy.

11. The compound of claim 2 wherein R³ is:

R³ is;

methoxy;

chloro;

or fluoro.

12. The compound of claim 2 wherein m is 1 and R⁷ is halo or methoxy.

13. The compound of claim 2 wherein R⁵ and R⁶ together with the nitrogen atom to which they are attached form a three- to six-membered ring that is optionally includes an additional heteroatom selected from O, N and S, and which is optionally substituted with one, two or three groups independently selected from C_1-6alkyl, halo-C_1-6alkyl, C_1-6alkoxy, halo-C_1-6alkoxy, hydroxy, hydroxy-C_1-6alkyl, halo, nitrile, C_1-6alkyl-carbonyl, C_1-6alkyl-sulfonyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-6alkyl, C_3-6cycloalkyl-carbonyl, amino, or heterocyclyl, or two of the groups together with the atoms to which they are attached may form a five or six-membered ring.

14. The compound of claim 2 wherein R⁵ and R⁶ together with the nitrogen atom to which they are attached form a morpholinyl group that is optionally substituted once or twice with groups independently selected from C_1-6alkyl, halo-C_1-6alkyl, C_1-6alkoxy, halo-C_1-6alkoxy, hydroxy, hydroxy-C_1-6alkyl, halo, nitrile, C_1-6alkyl-carbonyl, C_1-6alkyl-sulfonyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-6alkyl, C_3-6cycloalkyl-carbonyl, amino, or heterocyclyl, or the two groups together with the atoms to which they are attached may form a five or six-membered ring.

15. The compound of claim 2 wherein said compound is of formula III

16. The compound of claim 2 wherein p is 1.

17. The compound of claim 2 wherein Y is —

O—

;

—

NR¹⁰;

or —

CR¹¹R¹²—

.

18. The compound of claim 2 wherein Y is —

O—

.

19. A composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of claim 1.

20. A method for treating Parkinson'"'"'s disease, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1.