Antimicrobial compounds, compositions, and articles of manufacture for selectively inhibiting pathogenic microbes

Patent metadata

Field	Value
Publication number	US-12202798-B2
Application number	US-202016904370-A
Country	US
Kind code	B2
Filing date	Jun 17, 2020
Priority date	Jun 18, 2019
Publication date	Jan 21, 2025
Grant date	Jan 21, 2025

Abstract

A compound can have a structure of Formula A, or derivative thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combination thereof:

wherein ring A is a phenyl, indolyl, naphthyl, or benzothiazolyl; X is S, SO, or SO 2 ; Y is a linker or bond; Z is CH, CR 2 , or N; Z 1 is C or N to form an imidazopyridine; each Z 2 , Z 3 , or Z 4 is independently CH, CR 2 , or N; each Z 5 or Z 6 is C or CH; each R 1 , R 2 , and R 3 is independently a substituent, and at least one of R 1 , R 2 , or R 3 is a substituent other than a hydrogen; m is 0, 1, 2, 3, or 4; and n is 0 or a positive integer. The compounds can have specific substituent patterns.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:
3-((4-bromophenyl)thio)-6-fluoro-1H-indole (172A);
2-((4-bromophenyl)thio)-3-methyl-1H-indole (172B);
methyl 3-((4-bromophenyl)thio)-1H-indole-5-carboxylate (172G);
5-bromo-3-((4-bromophenyl) sulfinyl)-1H-indole (172I);
5-bromo-3-((4-bromophenyl) sulfonyl)-1H-indole (172J);
6-bromo-3-((4-bromophenyl)thio)-1H-indole (174A);
5,6-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AB);
5,7-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AC);
5-bromo-3-((perchlorophenyl)thio)-1H-indole (174AD);
4,6-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AE);
5-bromo-3-((4-bromophenyl)thio)-6-chloro-1H-indole (174AF);
5-bromo-3-((2,4,6-trichlorophenyl)thio)-1H-indole (174AG);
5-bromo-3-((3,4,5-tribromophenyl)thio)-1H-indole (174AH);
2-((5-bromo-1H-indol-3-yl)thio)phenol (174AI);
5-bromo-3-((2-chlorophenyl)thio)-1H-indole (174AJ);
3-((2-aminophenyl)thio)-2-methyl-1H-indol-5-ol (174AK);
3-((1H-indol-3-yl)thio)-5-bromo-1H-indole (174AL);
3-((2-hydroxyphenyl)thio)-2-methyl-1H-indol-5-ol (174AO);
3-((2-hydroxyphenyl)thio)-1H-indol-5-ol (174AP);
2-((5-methoxy-1H-indol-3-yl)thio)phenol (174AQ);
3-((2-bromophenyl)thio)-1H-indol-5-ol (174AR);
3-((2-bromophenyl)thio)-5-methoxy-1H-indole (174AS);
(2-((5-bromo-1H-indol-3-yl)thio)phenyl) methanol (174AT);
5-bromo-3-((2-(fluorophenyl)thio)-1H-indole (174AU);
5-bromo-3-((2-(trifluoromethyl)phenyl)thio)-1H-indole (174AV);
3-((2-bromophenyl)thio)-5-(trifluoromethyl)-1H-indole (174AX);
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
5-bromo-3-((2-bromophenyl)thio)-2-methyl-1H-indole (174AZ);
4-bromo-3-((4-bromophenyl)thio)-1H-indole (174D);
3-((4-bromophenyl)thio)-5-fluoro-1H-indole (174E);
7-bromo-3-((4-bromophenyl)thio)-1H-indole (174H);
5-bromo-3-((3-bromophenyl)thio)-1H-indole (174N);
5-bromo-3-((4-bromobenzyl)thio)-1H-indole (1740);
3-([1,1′-biphenyl]-4-ylthio)-5-bromo-1H-indole (174R);
5-bromo-3-((2,3-dichlorophenyl)thio)-1H-indole (174T);
5-bromo-3-((2,4-dichlorophenyl)thio)-1H-indole (174V);
5-bromo-3-((3,4-dichlorophenyl)thio)-1H-indole (174W);
5-bromo-2-((5-bromo-1H-indol-3-yl)thio)aniline (174X);
3-((5-bromo-1H-indol-3-yl)thio)aniline (174Y);
2-((5-(trifluoromethyl)-1H-indol-3-yl)thio)phenol (177A);
4-((5-(trifluoromethyl)-1H-indol-3-yl)thio)phenol (177B);
2-((5-(trifluoromethyl)-1H-indol-3-yl)thio)aniline (177C);
3-((2-fluorophenyl)thio)-5-(trifluoromethyl)-1H-indole (177D);
3-((2-bromophenyl)thio)-5-fluoro-1H-indole (177E);
5-(trifluoromethyl)-3-((2-(trifluoromethyl)phenyl)thio)-1H-indole (177F);
3-((2-ethylphenyl)thio)-5-(trifluoromethyl)-1H-indole (177G);
(5-bromo-3-((2-bromophenyl)thio)-1H-indol-2-yl) methanol (177H);
(3-((2-ethylphenyl)thio)-5-(trifluoromethyl)-1H-indol-2-yl) methanol (177I);
N-((3-((4-hydroxyphenyl)thio)-1H-indol-5-yl)methyl)-4-(triethoxysilyl) butanamide (156SI); and
3-((2-aminophenyl)thio)-5-bromo-N-(3-(triethoxysilyl) propyl)-1H-indole-2-carboxamide (174SI),
or salts thereof.

2. A composition comprising:
the compound of claim 1 ; and
a liquid carrier having the compound.

3. An article of manufacture comprising:
the compound of claim 2 ; and
a solid material having the compound on a surface or body of the solid material.

4. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
3-((4-bromophenyl)thio)-6-fluoro-1H-indole (172A);
2-((4-bromophenyl)thio)-3-methyl-1H-indole (172B);
methyl 3-((4-bromophenyl)thio)-1H-indole-5-carboxylate (172G);
5-bromo-3-((4-bromophenyl) sulfinyl)-1H-indole (172I);
5-bromo-3-((4-bromophenyl) sulfonyl)-1H-indole (172J);
6-bromo-3-((4-bromophenyl)thio)-1H-indole (174A);
5,6-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AB);
5,7-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AC);
5-bromo-3-((perchlorophenyl)thio)-1H-indole (174AD); and
4,6-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AE),
or salts thereof.

5. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
5-bromo-3-((4-bromophenyl)thio)-6-chloro-1H-indole (174AF);
5-bromo-3-((2,4,6-trichlorophenyl)thio)-1H-indole (174AG);
5-bromo-3-((3,4,5-tribromophenyl)thio)-1H-indole (174AH);
2-((5-bromo-1H-indol-3-yl)thio)phenol (174AI);
5-bromo-3-((2-chlorophenyl)thio)-1H-indole (174AJ);
3-((2-aminophenyl)thio)-2-methyl-1H-indol-5-ol (174AK);
3-((1H-indol-3-yl)thio)-5-bromo-1H-indole (174AL);
3-((2-hydroxyphenyl)thio)-2-methyl-1H-indol-5-ol (174AO); and
3-((2-hydroxyphenyl)thio)-1H-indol-5-ol (174AP),
or salts thereof.

6. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
2-((5-methoxy-1H-indol-3-yl)thio)phenol (174AQ);
3-((2-bromophenyl)thio)-1H-indol-5-ol (174AR);
3-((2-bromophenyl)thio)-5-methoxy-1H-indole (174AS);
(2-((5-bromo-1H-indol-3-yl)thio)phenyl) methanol (174AT);
5-bromo-3-((2-fluorophenyl)thio)-1H-indole (174AU);
5-bromo-3-((2-(trifluoromethyl)phenyl)thio)-1H-indole (174AV);
3-((2-bromophenyl)thio)-5-(trifluoromethyl)-1H-indole (174AX);
5-bromo-3-((2-bromophenyl)thio)-2-methyl-1H-indole (174AZ);
4-bromo-3-((4-bromophenyl)thio)-1H-indole (174D); and
3-((4-bromophenyl)thio)-5-fluoro-1H-indole (174E),
or salts thereof.

7. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
7-bromo-3-((4-bromophenyl)thio)-1H-indole (174H);
5-bromo-3-((3-bromophenyl)thio)-1H-indole (174N);
5-bromo-3-((4-bromobenzyl)thio)-1H-indole (1740);
3-([1,1′-biphenyl]-4-ylthio)-5-bromo-1H-indole (174R);
5-bromo-3-((2,3-dichlorophenyl)thio)-1H-indole (174T);
5-bromo-3-((2,4-dichlorophenyl)thio)-1H-indole (174V);
5-bromo-3-((3,4-dichlorophenyl)thio)-1H-indole (174W);
5-bromo-2-((5-bromo-1H-indol-3-yl)thio)aniline (174X); and
3-((5-bromo-1H-indol-3-yl)thio)aniline (174Y),
or salts thereof.

8. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
2-((5-(trifluoromethyl)-1H-indol-3-yl)thio)phenol (177A);
4-((5-(trifluoromethyl)-1H-indol-3-yl)thio)phenol (177B);
2-((5-(trifluoromethyl)-1H-indol-3-yl)thio)aniline (177C);
3-((2-fluorophenyl)thio)-5-(trifluoromethyl)-1H-indole (177D);
3-((2-bromophenyl)thio)-5-fluoro-1H-indole (177E);
5-(trifluoromethyl)-3-((2-(trifluoromethyl)phenyl)thio)-1H-indole (177F);
3-((2-ethylphenyl)thio)-5-(trifluoromethyl)-1H-indole (177G);
(5-bromo-3-((2-bromophenyl)thio)-1H-indol-2-yl) methanol (177H);
(3-((2-ethylphenyl)thio)-5-(trifluoromethyl)-1H-indol-2-yl) methanol (177I);
N-((3-((4-hydroxyphenyl)thio)-1H-indol-5-yl)methyl)-4-(triethoxysilyl) butanamide (156SI); and
3-((2-aminophenyl)thio)-5-bromo-N-(3-(triethoxysilyl) propyl)-1H-indole-2-carboxamide (174SI),
or salts thereof.

9. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
3-((4-bromophenyl)thio)-6-fluoro-1H-indole (172A);
2-((4-bromophenyl)thio)-3-methyl-1H-indole (172B);
methyl 3-((4-bromophenyl)thio)-1H-indole-5-carboxylate (172G);
5-bromo-3-((4-bromophenyl) sulfinyl)-1H-indole (1721); and
5-bromo-3-((4-bromophenyl) sulfonyl)-1H-indole (172J),
or salts thereof.

10. The compound of claim 1 , wherein the compound is selected from the group consisting of:
5-bromo-3-(o-tolylthio)-1H-indole (174AY);
6-bromo-3-((4-bromophenyl)thio)-1H-indole (174A);
5,6-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AB);
5,7-dibromo-3-((4-bromophenyl)thio)-1H-indole (174AC);
5-bromo-3-((perchlorop

Assignees

• Cfd Res Corporation
• Univ Oklahoma

Inventors

• Singhal Anuj
• Cichewicz Robert H
• Du Lin
• You Jianlan
• Paritala Hanumantha Rao
• Edwards Abigail Grace

Classifications

• A01N25/08

  containing solids as carriers or diluents · CPC title

• A61K47/54

  the modifying agent being an organic compound · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title

• C07F7/1804

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title