# US 2014/0155392 A1 · Methods of utilizing arylpiperazine derivatives

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- Number: US 2014/0155392 A1
- Document ID: US20140155392A1
- Status: Published application
- Kind: A1
- Application number: 13/914,424
- Filed: 2013-06-10
- Published: 2014-06-05
- Earliest claimed: 2009-02-26
- Assignees: Reviva Pharmaceuticals, Inc.
- Applicants: Reviva Pharmaceuticals, Inc.
- Inventors: Laxminarayan Bhat; Prabhu Prasad Mohapatra; Kouacou Adiey
- Web page: https://patentgrep.com/patent/US20140155392A1

## CPC

- C07D 265/36: condensed with one six-membered ring
- A61K 31/538: ortho- or peri-condensed with carbocyclic ring systems
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/24: Antidepressants
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

The present invention provides arylpiperazine derivatives which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder, and depression.

## Claims

### Claim 1

A compound of Formula 1:
or a pharmaceutically acceptable salt, isomer, racemate, diastereomeric mixture thereof,
wherein:
A is —(CH2)n—, —O—(CH2)n—, —S—(CH2)n—, —S(O)(O)—(CH2)n—, —NH—(CH2)n—, —CH2—O—(CH2)n—, —(CH2)n—O—CH2—CH2—, —CH2—S—(CH2)n—, —(CH2)n—S—CH2—CH2—, —CH2—S(O)(O)—(CH2)n—, —(CH2)n—S(O)(O)—CH2—CH2—, —O—C(O)—(CH2)n—, —S—C(O)—(CH2)n—, —NH—C(O)—(CH2)n—, —CH2—C(O)—O—(CH2)n—, —CH2—C(O)—NH—(CH2)n—, —CH2—C(O)—S—(CH2)n—, —(CH2)n—C(O)—O—CH2—CH2—, —(CH2)n—C(O)—NH—CH2—CH2—, —(CH2)n—C(O)—S—CH2—CH2—, —CH2—O—C(O)—(CH2)n—, —CH2—NH—C(O)—(CH2)n—, —CH2—S—C(O)—(CH2)n—, —(CH2)n—O—C(O)—CH2—CH2—, (CH2)n—NH—C(O)—CH2—CH2—, or (CH2)n—S—C(O)—CH2—CH2—, wherein n is an integer from 1 to 7;
B is O, S, S(O)(O), or NR5; and
R1, R2, R3, R4, R5, R6, R7, and R8 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, acylalkyloxycarbonyl, acyloxyalkyloxycarbonyl, acylalkyloxycarbonylamino, acyloxyalkyloxycarbonylamino, alkoxy, alkoxycarbonyl, alkoxycarbonylalkoxy, alkoxycarbonyllalkylamino, alkylsulfinyl, alkylsulfonyl, alkylthio, amino, alkylamino, arylalkylamino, dialkylamino, arylalkoxy, arylalkoxycarbonylalkoxy, arylalkoxycarbonylalkylamino, aryloxycarbonyl, aryloxycarbonylalkoxy, aryloxycarbonylalkylamino, carboxy, carbamoyl, carbamate, carbonate, cyano, halogen, heteroaryloxycarbonyl, hydroxy, phosphate, phosphonate, sulfate, sulfonate, or sulfonamide;
wherein R1, R2, R3, R4, R6, R7 and R8 and A are optionally substituted with isotopes selected from the group consisting of 2H (deuterium), 3H (tritium), 13C, 36Cl, 18F, 15N, 17O, 18O, 31P, 32P, and 35S.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

The compound of claim 1, wherein A is —O—(CH2)n—, —S—(CH2)n—, —CH2—O—(CH2)n—, —(CH2)n—O—CH2—CH2—, —CH2—S—(CH2)n—, or —(CH2)n—S—CH2—CH2—.

### Claim 4 (depends on 1)

The compound of claim 1, wherein A is —NH—C(O)—(CH2)n—, —CH2—NH—C(O)—(CH2)n—, —CH2—C(O)—NH—(CH2)n— or —(CH2)n—C(O)—NH—CH2—CH2—.

### Claim 5 (depends on 1)

The compound of claim 1, wherein A is —(CH2)n—.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R4 is H.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R1 and R2 are independently H, halogen, or alkoxy.

### Claim 8 (depends on 7)

The compound of claim 7, wherein R1 is H, and R2 is methoxy.

### Claim 9 (depends on 1)

The compound of claim 1, wherein R1 and R2 are chloro.

### Claim 10 (depends on 1)

The compound of claim 1, wherein A is —O—(CH2)n—; and R3, R4, R6, R7, and R8 are independently hydrogen or alkyl.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R3, R4, R6, R7, and R8 are hydrogen.

### Claim 12 (depends on 1)

The compound of claim 1, wherein R1, R2, R3, R4, R6, R7 and R8 and A are optionally substituted with 2H (deuterium).

### Claim 13 (depends on 1)

The compound of claim 1, wherein the compound is in the form of a hydrochloride salt.

### Claim 14 (depends on 1)

The compound of claim 1, wherein the compound is enantiomerically pure and/or diastereomerically pure.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1, and a pharmaceutically acceptable carrier, excipient, or diluent.

### Claim 16 (depends on 15)

A method of treating psychosis, schizophrenia, acute mania, bipolar disorder, autistic disorder or depression, the method comprising administering to a patient in need thereof the pharmaceutical formulation claim 15.

### Claim 17 (depends on 16)

The method of claim 16, wherein said method treats depression.

### Claim 18 (depends on 16)

The method of claim 16, wherein said method treats schizophrenia.

### Claim 19 (depends on 16)

The method of claim 16, wherein said method treats psychosis.

### Claim 20 (depends on 16)

The method of claim 16, wherein said method treats autistic disorder.