# US 8,541,431 B2 · Pyrimidine non-classical cannabinoid compounds and related methods of use

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- Number: US 8,541,431 B2
- Document ID: US8541431B2
- Status: Granted
- Kind: B2
- Application number: 12/468,756
- Filed: 2009-05-19
- Published: 2009-11-19
- Granted: 2013-09-24
- Earliest claimed: 2008-05-19
- Assignees: University of Tennessee Research Foundation
- Applicants: Bob M. Moore, II; Steven Gurley; Suni Mustafa; Patrick Allison
- Inventors: Bob M. Moore, II; Steven Gurley; Suni Mustafa; Patrick Allison
- Web page: https://patentgrep.com/patent/US8541431B2

## CPC

- C07D 239/52: Two oxygen atoms
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 35/00: Antineoplastic agents
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds of the formula I: wherein R1, R2, V, W, X, Y and Z can be as defined herein. The compounds can be used in the treatment of disorders mediated by the cannabinoid receptors.

## Claims

### Claim 1

A compound of the formula:
wherein
X is selected from the group consisting of
cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkylalkyl, wherein the ring portion of each is optionally substituted independently with one, two, three, four or five substituents selected from the group consisting of halo, alkyl, alkoxy, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, thiol, alkylthiol, and haloalkyl;
Y is selected from the group consisting of CH2, CH(CH3), CH(OH), C(CH3)(OH), C(CH3)2, C(—U(CH2)nU—), C(O), S(O), and S(O)2;
n is an integer from 1 to 3;
U is selected from the group consisting of CH2, S, and O;
Z is selected from the group consisting of
C3-C20 alkyl optionally substituted with a substituent selected from the group consisting of halo, alkyl, alkoxy, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, thiol, alkylthiol, and haloalkyl;
cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkylalkyl, wherein the ring portion of each is optionally substituted independently with one, two, three, four or five substituents selected from the group consisting of halo, alkyl, alkoxy, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, thiol, alkylthiol, and haloalkyl; and
R1 and R2 are independently selected from the group consisting of H and alkyl.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein
X is selected from the group consisting of cycloalkyl, phenyl, thiophenyl and pyridinyl, wherein each is optionally substituted with one to five groups independently selected from halo, alkyl and alkoxy;
R1 and R2 are independently selected from the group consisting of H and alkyl;
Y is selected from the group consisting of carbonyl, dimethylmethylene and hydroxymethylene; and
Z is selected from the group consisting of alkyl,
cycloalkyl, phenyl, and thiophenyl, each of which is optionally substituted with a substituent selected from the group consisting of halo, alkyl, alkoxy, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, thiol, alkylthiol, and haloalkyl.

### Claim 3 (depends on 2)

A compound according to claim 2 wherein X is phenyl optionally substituted with one, two or three groups independently selected from chloro, methyl and methoxy.

### Claim 4 (depends on 3)

A compound according to claim 3 wherein X is 3-methylphenyl or dichlorophenyl.

### Claim 5 (depends on 2)

A compound according to claim 2 wherein Y is dimethylmethylene.

### Claim 6 (depends on 2)

A compound according to claim 2 wherein Z is alkyl, phenyl or cycloalkyl.

### Claim 7 (depends on 1)

A compound according to claim 1 of the formula

### Claim 8 (depends on 7)

A compound according to claim 7 wherein
X is selected from the group consisting of phenyl, thiophenyl and pyridinyl, wherein each is optionally substituted with one to five groups independently selected from halo, alkyl and alkoxy;
Y is selected from the group consisting of carbonyl, dimethylmethylene and hydroxymethylene; and
Z is selected from the group consisting of alkyl,
cycloalkyl, phenyl, and thiophenyl each of which is optionally substituted with a substituent selected from the group consisting of halo, alkyl, alkoxy, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, thiol, alkylthiol, and haloalkyl.

### Claim 9 (depends on 8)

A compound according to claim 8 wherein X phenyl optionally substituted with one, two or three groups independently selected from chloro, methyl and methoxy.

### Claim 10 (depends on 9)

A compound according to claim 9 wherein X is 3-methoxyphenyl, 3-methylphenyl or 3,5-dichlorophenyl.

### Claim 11 (depends on 8)

A compound according to claim 8 wherein Y is dimethylmethylene.

### Claim 12 (depends on 8)

A compound according to claim 8 wherein Z is alkyl, phenyl or cycloalkyl.

### Claim 13 (depends on 1)

A compound according to claim 1 selected from
2-Benzyl-5-phenylpyrimidine-4,6-diol;
5-Cyclohexyl-2-(2-phenylpropan-2-yl)pyrimidine-4,6-diol;
5-Cyclohexyl-2-(2-(thiophen-2-yl)propan-2-yl)pyrimidine-4,6-diol;
5-Cyclohexyl-2-(2-cyclohexylpropan-2-yl)pyrimidine-4,6-diol;
5-Cyclohexyl-2-(2-methyloctan-2-yl)pyrimidine-4,6-diol;
5-(3,5-Dichlorophenyl)-2-(2-methyloctan-2-yl)pyrimidine-4,6-diol;
2-(2-Cyclohexylpropan-2-yl)-5-(3,5-dichlorophenyl)pyrimidine-4,6-diol;
5-(3,5-Dichlorophenyl)-2-(2-phenylpropan-2-yl)pyrimidine-4,6-diol;
5-(3,5-Dichlorophenyl)-2-(2-(thiophen-2-yl)propan-2-yl)pyrimidine-4,6-diol;
2-(2-Methyloctan-2-yl)-5-m-tolylpyrimidine-4,6-diol;
2-(2-Cyclohexylpropan-2-yl)-5-m-tolylpyrimidine-4,6-diol;
2-(2-Phenylpropan-2-yl)-5-m-tolylpyrimidine-4,6-diol;
2-(2-(Thiophen-2-yl)propan-2-yl)-5-m-tolylpyrimidine-4,6-diol; and
5-(Pyridin-2-yl)-2-(2-(thiophen-2-yl)propan-2-yl)pyrimidine-4,6-diol.