Methods of treating bacterial infections with 1,2-benzisothiazolinone and isoindolinone derivatives

Patent metadata

Field	Value
Publication number	US-9428472-B2
Application number	US-201214238570-A
Country	US
Kind code	B2
Filing date	Aug 16, 2012
Priority date	Aug 16, 2011
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

Abstract

Methods of treating, preventing and ameliorating bacterial infections with 1,2-benzisothiazolinone and isoindolinone derivatives are disclosed. Pharmaceutical compositions containing 1,2-benzisothiazolinone and isoindolinone derivatives are useful for treating bacterial infections caused by drug resistant strains of bacteria, including but not limited to methicillin and vancomycin bacterial organisms.

First claim

What is claimed is:

1. A method of treating a bacterial infection in a subject, wherein a composition comprising a compound of the following formula:

or a pharmaceutically acceptable salt or prodrug, is administered to the subject, wherein:
R 1 is hydrogen or methyl;
W is —C(O)NR 2 — or —C(O)NR 3 —NR 4 C(O)—, wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 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 CH 2 or S;
Y is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted or unsubstituted thio, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 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 SO 2 .

2. A method of treating a bacterial infection to a subject, wherein a composition comprising a compound of the following formula:

or a pharmaceutically acceptable salt or prodrug, is administered to the subject, wherein:
R 1 is hydrogen or methyl;
W is —C(O)NR 2 — or —C(O)NR 3 —NR 4 C(O)—, wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 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 thio, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 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.

3. A method of treating a bacterial infection in a subject, wherein a composition comprising a compound of the following formula:

or a pharmaceutically acceptable salt or prodrug is administered to the subject.

4. The method of claim 1 , wherein the subject is an immunocompromised subject.

5. The method of claim 1 , wherein the bacterial infection being treated is caused by one of more Gram-positive organisms.

6. The method of claim 5 , wherein the bacterial infection is caused by one or more bacterial organisms that belong to genera selected from the group consisting of Staphylococci, Enterrococci, Bacilli and Actinobacteria.

7. The method of claim 6 , wherein the bacterial infection is caused by one or more bacterial organisms selected from the group consisting of Staphylococcus saprophyticus, Staphylococcus aureus, Micrococcus sp., Enterococcus fecalis and Group A Streptococcus.

8. The method of claim 5 , wherein the bacterial organism is an organism resistant to one or more beta-lactam antibiotics, vancomycin, or both one or more beta-lactam antibiotics and vancomycin.

9. The method of claim 8 , wherein the bacterial organism is Staphylococcus aureus.

10. The method of claim 8 , wherein the bacterial organism is Enterococcus fecalis.

11. The method of claim 1 , wherein the compound is

12. The method of claim 1 , wherein the compound is

13. A method of treating a bacterial infection in a subject, wherein a composition comprising a compound of the following formula:

or a pharmaceutically acceptable salt or prodrug, is administered to the subject, wherein:
R 1 is hydrogen or methyl;
W is —C(O)NR 2 —, —C(O)NR 3 —NR 4 C(O)—, or

wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 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 CH 2 or S;
Y is hydrogen, hydroxy, alkoxy, substituted or unsubstituted amino, substituted thio, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 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 SO 2 .

14. A method of treating a bacterial infection in a subject, wherein a composition comprising a compound of the following formula:

or a pharmaceutically acceptable salt or prodrug, is administered to the subject, wherein:
R 1 is hydrogen or methyl;
W is —C(O)NR 2 —, —C(O)NR 3 —NR 4 C(O)—, or

wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 haloalkyl, substituted or unsubstituted C 2-12 alkenyl, substituted or unsubstituted C 2-12 alkynyl, substituted or unsubstitute

Assignees

• Alex Deepu
• Calderone Richard
• Peters Stephen
• Univ Georgetown

Inventors

• Alex Deepu
• Calderone Richard
• Peters Stephen

Classifications

• A61K31/428

  condensed with carbocyclic rings · CPC title

• C07D275/04 Primary

  condensed with carbocyclic rings or ring systems · CPC title