# US 2018/0022705 A1 · Cannabinoid receptor mediating compounds

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- Number: US 2018/0022705 A1
- Document ID: US20180022705A1
- Status: Published application
- Kind: A1
- Application number: 15/674,333
- Filed: 2017-08-10
- Published: 2018-01-25
- Earliest claimed: 2012-11-13
- Assignees: The United States of America, as represented by the Secretary, Dept. of Health and Human Services
- Applicants: The United States of America, as represented by the Secretary, Dept. of Health and Human Services
- Inventors: George Kunos; Malliga Iyer; Resat Cinar; Kenner C. Rice
- Web page: https://patentgrep.com/patent/US20180022705A1

## CPC

- C07D 231/06: having one double bond between ring members or between a ring member and a non-ring member
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 35/00: Antineoplastic agents
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound, or a pharmaceutically acceptable salt or ester thereof, comprising (i) a CB1 receptor mediating scaffold conjugated to (ii) a second therapeutic scaffold.

## Claims

### Claim 1

A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
wherein A is biguanidino-containing moiety,
R1, R2, and R3 are each independently selected from optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino;
X is SO2 or C═O;
R10, R11, R12, R13 and R20 are each independently selected from H, optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino;
R21 is optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino;
M is S or Se;
a, b, and c are each independently 0, 1, 2, 3, 4 or 5;
m, x, and y are each independently 0, 1, 2, 3, 4, 5 or 6;
d is 0 or 1; and
z is 1 or 2.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the biguanidino-containing moiety has a structure of
wherein R4, R6, R7, and R8 are each independently selected from H, optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino.

### Claim 3 (depends on 2)

The compound of claim 2, wherein R4 and R6 are each H.

### Claim 4 (depends on 2)

The compound of claim 2, wherein R7 and R8 are each independently selected from H or C1-C6 alkyl.

### Claim 5

A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
wherein A is a hydrazino-containing moiety having a structure of
wherein R9 is H, optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino;
R1, R2, and R3 are each independently selected from optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino;
X is SO2 or C═O; and
a, b, and c are each independently 0, 1, 2, 3, 4 or 5.

### Claim 6 (depends on 5)

The compound of claim 5, wherein a and c are each one, R1 is halogen, and R3 is halogen.

### Claim 7 (depends on 5)

The compound of claim 5, wherein b is zero.

### Claim 8 (depends on 5)

The compound of claim 5, wherein X is SO2.

### Claim 9 (depends on 5)

The compound of claim 5, wherein the compound has a structure of:

### Claim 10 (depends on 1)

The compound of claim 1, wherein the compound has a structure of:

### Claim 11 (depends on 1)

The compound of claim 1, wherein the compound has a structure of:
wherein R15 is H, optionally-substituted alkyl, optionally-substituted cycloalkyl, halogen, cyano, nitro, hydroxy, optionally-substituted alkoxy, amino, optionally-substituted sulfonyl, optionally-substituted aryl, optionally-substituted heteroaryl, optionally-substituted carboxyl, acyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted phosphonyl, optionally-substituted phosphinyl, optionally-substituted boronate, optionally-substituted silyl, or imino.

### Claim 12 (depends on 5)

The compound of claim 5, wherein the compound is an S-enantiomer:

### Claim 13

A compound, or a pharmaceutically acceptable salt or ester thereof, comprising (i) a CB1 receptor mediating scaffold and (ii) a second therapeutic scaffold.

### Claim 14 (depends on 13)

The compound of claim 13, wherein the second therapeutic scaffold comprises an antidiabetic agent, an anticancer agent, or an antiobesity agent.

### Claim 15 (depends on 13)

The compound of claim 13, wherein the compound is a 3-phenyl-N′-phenyl-N-imino-1H-pyrazole-1-carboximidiamide compound.

### Claim 16 (depends on 13)

The compound of claim 13, wherein the CB1 receptor mediating scaffold comprises a 3-phenyl-N′-phenyl-1H-pyrazole-1-carboximidiamide scaffold.

### Claim 17 (depends on 1)

A method for treating obesity, diabetes, non-alcoholic and alcoholic fatty liver disease, a co-morbidity of obesity, dyslipidemias that predispose to arteriosclerotic heart disease, diabetic nephropathy, or gout, in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1.

### Claim 18 (depends on 5)

A method for treating obesity, diabetes, non-alcoholic and alcoholic fatty liver disease, a co-morbidity of obesity, dyslipidemias that predispose to arteriosclerotic heart disease, diabetic nephropathy, or gout, in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 5.

### Claim 19 (depends on 18)

The method of claim 18, comprising treating obesity in the subject.

### Claim 20 (depends on 18)

The method of claim 18, comprising treating diabetes in the subject.