# US 2013/0158057 A1 · Aminopyrimidine derivatives as lrrk2 modulators

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- Number: US 2013/0158057 A1
- Document ID: US20130158057A1
- Status: Published application
- Kind: A1
- Application number: 13/687,421
- Filed: 2012-11-28
- Published: 2013-06-20
- Earliest claimed: 2011-11-29
- Assignees: Genentech, Inc.
- Inventors: Charles Baker-Glenn; Mark Chambers; Bryan K. Chan; Anthony Estrada; Zachary Kevin Sweeney
- Web page: https://patentgrep.com/patent/US20130158057A1

## CPC

- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 413/14: containing three or more hetero rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 239/47: One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
- C07D 239/48: Two nitrogen atoms
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R4 and R5 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

### Claim 1

A compound of formula I:
or pharmaceutically acceptable salts thereof,
wherein:
m is from 0 to 3;
X is: —NRa—; —O—; or —S(O)r— wherein r is from 0 to 2 and Ra is hydrogen or C1-6alkyl;
Y is C or N;
R1 is: C1-6alkyl; C1-6alkenyl; C1-6alkynyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C1-6alkylsulfonyl-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
or R1 and Ra together with the atoms to which they are attached may form a three to six membered ring that may optionally include an additional heteroatom selected from O, N and S, and which is substituted with oxo, halo or C1-6alkyl;
R2 is: halo; C1-6alkoxy; cyano; C1-6alkynyl; C1-6alkenyl; halo-C1-6alkyl; halo-C1-6alkoxy; C3-6cycloalkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; acetyl; oxetanyl; or oxetan-C1-6alkyl;
R3 and R4 each independently is: halo; C1-6alkyl; C1-6alkoxy; C3-6cycloalkyloxy; halo-C1-6 alkyl; or halo-C1-6alkoxy; and
R5 is a 5-membered heteroaryl group optionally substituted one or more times with R6; and
R6 is: C1-6alkyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; halo; halo-C1-6alkyl; C1-6alkoxy; heterocyclyl; oxo; or —C(O)—NRbRc wherein Rb and Rc each independently is hydrogen or —C1-6alkyl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein X is —NH— or —O—.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is methyl or ethyl.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is: C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl; or C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R1 is C1-6alkyl.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R2 is: halo; halo-C1-6alkyl; or cyano.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R2 is chloro or trifluoromethyl.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R3 is halo or C1-6alkoxy.

### Claim 8 (depends on 1)

The compound of claim 1, wherein R3 is methoxy.

### Claim 9 (depends on 1)

The compound of claim 1, wherein m is 0 or 1.

### Claim 10 (depends on 1)

The compound of claim 1, wherein R4 is halo or methoxy.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R5 is: pyrazolyl; imidazolyl; oxadiazolyl; thiadiazolyl; triazolyl; or tetrazolyl; each optionally substituted one or more times with R6.

### Claim 12 (depends on 1)

The compound of claim 1, wherein R5 is: pyrazolyl; oxadiazolyl; triazolyl; or tetrazolyl; each optionally substituted one or more times with R6.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R5 is: oxadiazolyl; triazolyl; or tetrazolyl; each optionally substituted one or more times with R6.

### Claim 14 (depends on 1)

The compound of claim 1, wherein R5 is pyrazolyl optionally substituted one or more times with R6.

### Claim 15 (depends on 1)

The compound of claim 1, wherein R5 is oxadiazolyl; thiadiazolyl; triazolyl; or tetrazolyl; optionally substituted one or more times with R6.

### Claim 16 (depends on 1)

The compound of claim 1, wherein R5 is triazolyl optionally substituted one or more times with R6.

### Claim 17 (depends on 1)

The compound of claim 1, wherein R5 is tetrazolyl optionally substituted one or more times with R6.

### Claim 18 (depends on 1)

The compound of claim 1, wherein R5 is: 1-methyl-1H-imidazol-2-yl; 1-methyl-1H-imidazol-5-yl; 1,3,5-trimethyl-1H-pyrazol-4-yl; 1-methyl-1H-pyrazol-5-yl; 1-methyl-1H-pyrazol-4-yl; 1,3-dimethyl-1H-pyrazol-4-yl; 1,5-dimethyl-1H-pyrazol-4-yl; 5-(dimethylaminocarbonyl)-1-methyl-1H-pyrazol-4-yl; 1-(oxetan-3-yl)-1H-pyrazol-4-yl; 5-(methoxymethyl)-3-methyl-1H-pyrazol-1-yl; 1-methyl-1H-1,2,3-triazol-5-yl; 1H-1,2,4-triazol-1-yl; 4-methyl-4H-1,2,4-triazol-3-yl; 5-methyl-1,3,4-oxadiazol-2-yl; 3-methyl-1,2,4-oxadiazol-5-yl; 1-methyl-1H-tetrazol-5-yl; 2-methyl-2H-tetrazol-5-yl; 1H-tetrazol-1-yl; 2H-tetrazol-5-yl; 5-methyl-1H-tetrazol-1-yl; or 5-(methoxymethyl)-1H-tetrazol-1-yl.

### Claim 19 (depends on 1)

A composition comprising:
(a) a pharmaceutically acceptable carrier; and
(b) a compound of claim 1.

### Claim 20 (depends on 1)

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.