Aminopyrimidine derivatives as LRRK2 modulators

• US 8,802,674 B2
• Filed: 12/12/2012
• Issued: 08/12/2014
• Est. Priority Date: 06/04/2010
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Baker-Glenn, Charles, Burdick, Daniel Jon, Chambers, Mark, Chan, Bryan K., Estrada, Anthony, Shore, Daniel, Sweeney, Zachary Kevin, Wang, Shumei, Zhao, Guiling, Chen, Huifen, Gunzner-Tate, Janet
• Primary Examiner(s): Wilson, James O
• Assistant Examiner(s): Pagano, Alexander R
• Application Number:
  US13/712,015
• Publication Number:
  US 20130096102A1
• Time in Patent Office: 608 Days
• Field of Search: 514/235.8, 544/122, 544/123
• US Class Current: 514/235.8
• 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 IV:

2. The compound of claim 1, wherein X is —

NH—

.

3. The compound of claim 1, wherein X is —

O—

.

4. The compound of claim 1, wherein R¹ is C_1-6alkyl.

5. The compound of claim 2, wherein R¹ is:

methyl;

ethyl;

or cyclopropyl.

6. The compound of claim 1, wherein R² is trifluoromethyl.

7. The compound of claim 1, wherein R³ is:

halo;

or C_1-6alkoxy.

8. The compound of claim 1, wherein R⁷ is:

halo;

C_1-6alkyl;

or C_1-6alkoxy.

9. The compound of claim 7, wherein R³ is:

methoxy;

chloro;

or fluoro.

10. The compound of claim 8, wherein R⁷ is:

fluoro;

chloro;

methyl;

or methoxy.

11. The compound of claim 10, wherein m is 1.

12. A composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of claim 1.

13. 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.

14. The compound [4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone or a pharmaceutically acceptable salt thereof.

15. A method for treating Parkinson'"'"'s disease, said method comprising administering to a subject in need thereof an effective amount of the compound of claim 14.