Small molecule N-(alpha-peroxy) carbazole compounds and methods of use

Patent metadata

Field	Value
Publication number	US-10577324-B2
Application number	US-201716099813-A
Country	US
Kind code	B2
Filing date	May 10, 2017
Priority date	May 11, 2016
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

The invention relates to novel N-(α-peroxy)carbazole compounds of Formula I and methods for use. (I) The N-(α-peroxy)carbazole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)carbazole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy)carbazole compounds.

First claim

What is claimed is:

1. A compound of the following formula:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
is a single bond or a double bond;
A 1 , A 2 , A 3 , and A 4 are each independently selected from the group consisting of CR and N, wherein each R is selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
A 5 , A 6 , A 7 , and A 8 are each independently selected from the group consisting of CR, CR 2 , O, SO 2 , N, and NR, wherein each R is selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl; and
R 9 , R 10 , and R 11 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl,
wherein adjacent substituents can combine to form a substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heterocycloalkenyl.

2. The compound of claim 1 , wherein the compound has the following formula:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are each independently selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl; and
R 9 , R 10 , and R 11 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl.

3. The compound of claim 2 , wherein at least one of the group consisting of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 is hydrogen.

4. The compound of claim 1 , wherein R 9 is a substituted or unsubstituted alkyl.

5. The compound of claim 2 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt or prodrug thereof.

6. The compound of claim 5 , wherein the compound is selected from the group consisting of:

7. The compound of claim 1 , wherein the compound has the following structure

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 8 are each independently selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl; and
R 7 is hydrogen, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl.

8. The compound of claim 7 , wherein the compound is

9. The compound of claim 1 , wherein the compound is combined with a pharmaceutically acceptable carrier.

10. A method of treating a parasitic infection in a subject, comprising:
administering to a subject in need thereof an effective amount of a compound having the structure:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
is a single bond or a double bond;
A 1 , A 2 , A 3 , and A 4 are each independently selected from the group consisting of CR and N, wherein each R is selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
A 5 , A 6 , A 7 , and A 8 are each independently selected from the group consisting of CR, CR 2 , O, SO 2 , N, and NR, wherein each R is selected from the group consisting of hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, substituted or unsubstituted carbonyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, s

Assignees

• Univ King Abdullah Sci & Tech

Inventors

• Wang Xinbo
• Lai Zhiping
• Pan Yupeng
• Huang Kuowei

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P33/06

  Antimalarials · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07D471/14

  Ortho-condensed systems · CPC title

• C07D471/22

  in which the condensed systems contains four or more hetero rings · CPC title