Antifungal compounds and methods of forming the same

Patent metadata

Field	Value
Publication number	US-11851391-B2
Application number	US-201916514276-A
Country	US
Kind code	B2
Filing date	Jul 17, 2019
Priority date	Jul 17, 2018
Publication date	Dec 26, 2023
Grant date	Dec 26, 2023

Abstract

An antifungal composition and a method of treating a systemic fungal infection are provided herein. The antifungal composition includes a diaryl bishydrazone. The method includes administering a therapeutically effective amount of the diaryl bishydrazone to a subject in need thereof.

First claim

What is claimed is:

1. An antifungal composition comprising a compound according to Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein each R is independently selected from the group consisting of H and a lower alkyl; and
wherein each X is independently selected from the group consisting of phenyl, a substituted phenyl, an aromatic heterocycle, and a substituted aromatic heterocycle, so long as when both R are H or methyl then at least one X is not phenyl or meta-methoxy substituted phenyl;
wherein the substituted phenyl comprises a substitution selected from the group consisting of nitro, an alkyl, an alkoxy, a halogen, cyano, a carboxylic acid, a sulfonic acid, aryl sulfoxides, aryl sulfones, a trihalomethyl, and combinations thereof; and
aromatic heterocycle or the substituted aromatic heterocycle comprises one or more heteroatoms selected from the group consisting nitrogen, oxygen, sulfur, and combinations thereof, wherein the aryl sulfoxides include S(═O)C 6 H 4 Z, with Z being selected from the group consisting of alkyl, alkoxy, and halogen.

2. An antifungal composition comprising a compound according to Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein each R is independently selected from the group consisting of H and a lower alkyl; and
wherein each X is independently selected from the group consisting of phenyl, a substituted phenyl, an aromatic heterocycle, and a substituted aromatic heterocycle, so long as when both R are H or methyl then at least one X is not phenyl or meta-methoxy substituted phenyl;
wherein the substituted phenyl comprises a substitution selected from the group consisting of nitro, an alkyl, an alkoxy, a halogen, cyano, a carboxylic acid, a sulfonic acid, aryl sulfoxides, aryl sulfones, a trihalomethyl, and combinations thereof; and
aromatic heterocycle or the substituted aromatic heterocycle comprises one or more heteroatoms selected from the group consisting nitrogen, oxygen, sulfur, and combinations thereof, wherein the aryl sulfones include S(═O) 2 C 6 H 4 Z, with Z being selected from the group consisting of alkyl, alkoxy, and halogen.

3. An antifungal composition comprising a compound according to Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein each R is independently selected from the group consisting of H and a lower alkyl; and
wherein each X is independently selected from the group consisting of phenyl, a substituted phenyl, an aromatic heterocycle, and a substituted aromatic heterocycle, so long as when both R are H or methyl then at least one X is not phenyl or meta-methoxy substituted phenyl;
wherein the substituted phenyl comprises a substitution selected from the group consisting of nitro, an alkyl, an alkoxy, a halogen, cyano, a carboxylic acid, a sulfonic acid, aryl sulfoxides, aryl sulfones, a trihalomethyl, and combinations thereof; and
aromatic heterocycle or the substituted aromatic heterocycle comprises one or more heteroatoms selected from the group consisting nitrogen, oxygen, sulfur, and combinations thereof, wherein the substituent of the first ring according to Formula I is in the 3 position.

4. An antifungal composition comprising a compound according to Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein each R is independently selected from the group consisting of H and a lower alkyl; and
wherein each X is independently selected from the group consisting of phenyl, a substituted phenyl, an aromatic heterocycle, and a substituted aromatic heterocycle, so long as when both R are H or methyl then at least one X is not phenyl or meta-methoxy substituted phenyl;
wherein the substituted phenyl comprises a substitution selected from the group consisting of nitro, an alkyl, an alkoxy, a halogen, cyano, a carboxylic acid, a sulfonic acid, aryl sulfoxides, aryl sulfones, a trihalomethyl, and combinations thereof; and
aromatic heterocycle or the substituted aromatic heterocycle comprises one or more heteroatoms selected from the group consisting nitrogen, oxygen, sulfur, and combinations thereof, wherein the substituent of the first ring according to Formula I is in the 4 position.

5. The composition of claim 4 , wherein the R in the substituent of the first ring is methyl.

6. An antifungal composition comprising a compound according to Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein each R is independently selected from the group consisting of H and a lower alkyl;
wherein X is a substituted phenyl and the substituted phenyl comprises a substitution selected from the group consisting of nitro, an alkyl, an alkoxy, a halogen, cyano, a carboxylic acid, a sulfonic acid, aryl sulfoxides, aryl sulfones, a trihalomethyl, and combinations thereof, wherein the substituted phenyl includes more than one substitution.

7. The composition of claim 6 , wherein the substituted phenyl is disubstituted.

8. The composition of claim 7 , wherein the disubstituted phenyl is halogen substituted.

Assignees

• Univ Kentucky Res Found

Inventors

• Garneau-Tsodikova Sylvie
• Watt David S
• Chandrika Nishad Thamban

Classifications

• C07C243/10 Primary

  Hydrazines · CPC title

• A61P31/10 Primary

  Antimycotics · CPC title

• C07C277/00

  Preparation of guanidine or its derivatives, i.e. compounds containing the group [IMAGE cpc-sch-C07C-0970.gif], the singly-bound nitrogen atoms not being part of nitro or nitroso groups · CPC title

• C07C251/86

  having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07C281/18

  the other nitrogen atom being further doubly-bound to a carbon atom, e.g. guanylhydrazones · CPC title