BIS-cyclic guanidine compound compositions, methods of use and treatment thereof

Patent metadata

Field	Value
Publication number	US-9782388-B2
Application number	US-201515120972-A
Country	US
Kind code	B2
Filing date	Feb 19, 2015
Priority date	Feb 25, 2014
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

The present disclosure provides compositions including a bis-cyclic guanidine compound, pharmaceutical compositions including a bis-cyclic guanidine compound, methods of treatment of a condition {e.g., bacterial infection) or disease, methods of treatment using compositions or pharmaceutical compositions, and the like.

First claim

We claim:

1. A pharmaceutical composition comprising a therapeutically effective amount of a bis-cyclic guanidine compound, or a pharmaceutically acceptable salt of bis-cyclic guanidine compound, and a pharmaceutically acceptable carrier, to treat an infection, wherein the bis-cyclic guanidine compound has the following structure:

R 1 is selected from the group consisting of: 2-(3-trifluoromethyl-phenyl)-ethyl, cyclohexyl-butyl, and adamantan-1-yl-ethyl;
R 2 is selected from the group consisting of: (S or R)-butyl, (S or R)-2-naphthylmethyl, and (S or R)-cyclohexylmethyl;
R 3 is selected from the group consisting of: heptyl, cyclohexyl-butyl, and 2-biphenyl-4-yl-ethyl; and
wherein the infection is caused by one or more bacteria selected from the group consisting of: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter cloacae.

2. The pharmaceutical composition of claim 1 , wherein the bis-cyclic guanidine compound is selected from one of the following structures:

3. A method of treating an infection comprising: delivering to a subject in need thereof, a pharmaceutical composition, wherein the pharmaceutical composition includes a therapeutically effective amount of a bis-cyclic guanidine compound, or a pharmaceutically acceptable salt of the bis-cyclic guanidine compound, and a pharmaceutically acceptable carrier, to treat the infection, wherein the bis-cyclic guanidine compound has the following structure:

R 1 is selected from the group consisting of: 2-(3-trifluoromethyl-phenyl)-ethyl, cyclohexyl-butyl, and adamantan-1-yl-ethyl;
R 2 is selected from the group consisting of: (S or R)-butyl, (S or R)-2-naphthylmethyl, and (S or R)-cyclohexylmethyl;
R 3 is selected from the group consisting of: heptyl, cyclohexyl-butyl, and 2-biphenyl-4-yl-ethyl; and
wherein the infection is caused by one or more bacteria selected from the group consisting of: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter cloacae.

4. The method of claim 3 , wherein the pharmaceutical composition is a broad spectrum antibiotic.

5. The method of claim 3 , wherein the bis-cyclic guanidine compound is selected from one of the following structures:

6. A method of inhibiting the growth of a biofilm or the growth of bacteria, comprising:
exposing a surface having a biofilm thereon or exposed to bacteria to a composition comprising a bis-cyclic guanidine compound, wherein the bis-cyclic guanidine compound has the following structure:

R 1 is selected from the group consisting of: 2-(3-trifluoromethyl-phenyl)-ethyl, cyclohexyl-butyl, and adamantan-1-yl-ethyl;
R 2 is selected from the group consisting of: (S or R)-butyl, (S or R)-2-naphthylmethyl, and (S or R)-cyclohexylmethyl;
R 3 is selected from the group consisting of: heptyl, cyclohexyl-butyl, and 2-biphenyl-4-yl-ethyl; and
wherein the biofilm or the bacteria is selected from the group consisting of: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter cloacae.

7. The method of claim 6 , wherein the bis-cyclic guanidine compound is selected from one of the following structures:

Assignees

• Univ South Florida
• Torey Pines Inst For Molecular Studies
• Torrey Pines Inst For Molecular Studies

Inventors

• Shaw Lindsey Neil
• Fleeman Renee Marie
• Houghten Richard Allen
• Giulianotti Marcello Angelo
• Santos Radleigh G
• Nefzi Adel

Classifications

• A01N43/50

  1,3-Diazoles; Hydrogenated 1,3-diazoles · CPC title

• A61K31/4178 Primary

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• C07D233/46

  with only hydrogen atoms attached to said nitrogen atoms · CPC title