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

Patent metadata

Field	Value
Publication number	US-11098013-B2
Application number	US-202016747245-A
Country	US
Kind code	B2
Filing date	Jan 20, 2020
Priority date	May 11, 2016
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

The invention relates to novel N-(α-peroxy)carbazole compounds of Formula I and methods for use.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 method of synthesizing an N-(alpha-peroxy)carbazole compound, comprising: reacting according to Scheme 1:

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, alkoxy, aryloxy, 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 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.

2. The method of claim 1 , wherein the catalyst comprises an acid catalyst.

3. The method of claim 2 , wherein the acid catalyst is p-Toluenesulfonic acid.

4. The method of claim 1 , wherein the solvent is a halogenated or aprotic solvent.

5. The method of claim 1 , wherein the solvent comprises decane and dichloromethane.

6. The method of claim 1 , wherein the reacting step is performed for a period up to 24 hours.

7. The method of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are hydrogen.

8. The method of claim 7 , wherein R 9 is a substituted or unsubstituted alkyl.

9. The method of claim 8 , wherein R 10 is hydrogen and R 9 is selected from the group consisting of methyl, 3-methylbutyl, and benzyl.

10. The method of claim 1 , wherein R 10 is hydrogen and R 11 is t-butyl.

11. The method of claim 10 , wherein R 9 is methyl, ethyl or hexyl.

12. The method of claim 10 , wherein the peroxide is anhydrous tert-Butyl hydroperoxide.

13. A method of synthesizing an N-(alpha-peroxy)carbazole derivative compound, comprising:
reacting, in the presence of a catalyst, a carbonyl compound; a carbazole derivative; and a peroxide, wherein the carbonyl compound is acetaldehyde, the peroxide is tert-Butyl hydroperoxide, and the carbazole derivative has the following structure:

14. The method of claim 1 , wherein the reacting step is performed under air.

15. The method of claim 14 , wherein the reacting step is performed in an open flask.

16. The method of claim 6 , wherein the reacting step is performed for about 1 minute to about 5 minutes.

17. The method of claim 6 , wherein the reaction step comprises stirring.

Assignees

• Univ King Abdullah Sci & Tech

Inventors

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

Classifications

• C07D471/14

  Ortho-condensed systems · CPC title

• C07D209/86 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system · CPC title

• A61K31/5025

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C07D471/22

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