# US 9,040,715 B2 · 1,2-benzisothiazolinone and isoindolinone derivatives

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,040,715 B2
- Document ID: US9040715B2
- Status: Granted
- Kind: B2
- Application number: 13/120,602
- Filed: 2009-09-23
- Published: 2011-10-13
- Granted: 2015-05-26
- Earliest claimed: 2008-09-23
- Assignees: Georgetown University
- Applicants: Richard A. Calderone; William C. Groutas; Brent E. Korba
- Inventors: Richard A. Calderone; William C. Groutas; Brent E. Korba
- Web page: https://patentgrep.com/patent/US9040715B2

## CPC

- C07D 275/04: condensed with carbocyclic rings or ring systems
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- 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

Novel classes of 1,2-benzisothiazolinone and isoindolinone compounds and compositions are disclosed. These compounds and compositions are useful in treating, preventing, and/or ameliorating viral, yeast, and fungal infections such as, for example, Hepatitis C Virus, Flavivirus infections, Aspergillus fumigatus, and candidiasis.

## Claims

### Claim 1

A compound selected from the group consisting of:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl;
W is —C(O)NR2— or —C(O)NR3—NR4C(O)—, wherein R2, R3, and R4 are each independently selected from hydrogen, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; and
Y is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalky wherein when W is C(O)NH, Y is selected from the group consisting of phenoxy substituted aryl and unsubstituted aryl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R5 is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl;
R3 and R4 are each independently selected from hydrogen, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; and
R6 is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R2 is hydrogen, phenoxy-substituted aryl, or unsubstituted aryl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R5 and R6 are each independently selected from hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; and

### Claim 2 (depends on 1)

The compound of claim 1, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R5 is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl.

### Claim 3 (depends on 1)

The compound of claim 1, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl;
R3 and R4 are each independently selected from hydrogen, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; and
R6 is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R2 is hydrogen, phenoxy-substituted aryl, or unsubstituted aryl.

### Claim 5 (depends on 1)

The compound of claim 1, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R5 and R6 are each independently selected from hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl.

### Claim 6 (depends on 1)

The compound of claim 1, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof.

### Claim 7 (depends on 4)

The compound of claim 4, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof.

### Claim 8 (depends on 2)

The compound of claim 2, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof.

### Claim 9 (depends on 3)

The compound of claim 3, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof.

### Claim 10 (depends on 4)

The compound of claim 4, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof.

### Claim 11 (depends on 4)

The compound of claim 4, wherein the compound has the following formula:
or a pharmaceutically acceptable salt or prodrug thereof.

### Claim 12 (depends on 1)

A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 13

A method of diminishing an infection in a subject comprising administering to the subject a therapeutically effective amount of the compound selected from the group consisting of:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl;
W is —C(O)NR2— or —C(O)NR3—NR4C(O)—, wherein R2, R3, and R4 are each independently selected from hydrogen, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl;
X is S;
Y is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl; and
Z is C═O;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R5 is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl;
R3 and R4 are each independently selected from hydrogen, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; and
R6 is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted heterocycloalkylalkyl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R2 is hydrogen, phenoxy-substituted aryl, or unsubstituted aryl;
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is hydrogen or methyl; and
R5 and R6 are each independently selected from hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thiol, substituted or unsubstituted C1-12 alkyl, substituted or unsubstituted C1-12 haloalkyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted C2-12 alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; and
wherein the infection is Hepatitis C virus, a fungal infection, or a yeast infection
wherein when W is C(O)NH, Y is selected from the group consisting of phenoxy substituted aryl and unsubstituted aryl.

### Claim 14 (depends on 13)

The method of claim 13, wherein the infection is Hepatitis C Virus.

### Claim 15 (depends on 13)

The method of claim 13, wherein the infection is a fungal infection.

### Claim 16 (depends on 15)

The method of claim 15, wherein the fungal infection is candidiasis.