IP Library › Granted Patent US 12,209,082
Granted Patent B2
US 12,209,082 · App. 16/969,529 · Granted Jan 28, 2025

Antibacterial agents: soluble salts and aqueous formulations of pyronins

Inventors: Richard H. Ebright (New Brunswick, NJ); Yon W. Ebright (New Brunswick, NJ)
Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
C07D417/06A01N47/12A61K9/0019A61P31/04A61P31/06C07B2200/05C07B2200/07
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Quick Facts
Patent No.
US 12,209,082
App. No.
16/969,529
Granted
Jan 28, 2025
Kind
B2
Abstract

The invention provides salts of formula Ia, Ib, Ic, or Id: wherein variables are as described in the specification, as well as compositions comprising a salt of formula Ia-Id, methods of making such salts, and methods of using such salts as, e.g., inhibitors of bacterial RNA polymerase and as antibacterial agents.

Claims (17)

1. A composition comprising the salt of formula Ia:

wherein:

W is sulfur oxygen, or nitrogen;

X, Y, and Z are individually carbon, sulfur, oxygen, or nitrogen, wherein at least two of X, Y, and Z are carbon;

one of R 1 and R 2 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 1 -C 10 alkoxy, aryloxy, heteroaryloxy, or NR a R b , wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkoxy, tetrahydrofuranyl, or furanyl, and wherein any aryloxy or heteroaryloxy is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, aryl, or heteroaryl, wherein any C 1 -C 5 alkyl, C 1 -C 5 alkoxy, aryl, and heteroaryl is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkyl, or C 1 -C 5 alkoxy; or one of R 1 and R 2 is a 5-6-membered saturated, partially unsaturated, or aromatic heterocycle that is optionally substituted by at least one of halogen, hydroxy, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy; and the other of R 1 and R 2 is absent or is one of H, halogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy;

R 3 is absent, or is one of H, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 4 is absent, or is one of H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 6 is H, halogen, or methyl that is optionally is substituted by halogen;

G is one of —CH═CH—NHC (O)—R 7 , —CH═CH—NHC(S)—R 7 , —CH 2 CH 2 NHC (O)—R 7 , —CH 2 CH 2 NHC(S)—R 7 , —CH 2 NHNHC(O)—R 7 , or —CH 2 NHNHC(S)—R 7 ;

R 7 is one of C 1 -C 6 alkyl, —O (C 1 -C 6 alkyl), —S(C 1 -C 6 alkyl), or —N(R 8 ) 2 , provided R 7 is not deuterated alkyl;

each R 8 is independently one of hydrogen or —C 1 -C 6 alkyl;

R 9 is C 1 -C 10 alkyl or C 2 -C 10 alkenyl, wherein any C 1 -C 10 alkyl or C 2 -C 10 alkenyl is optionally substituted by at least one of halogen, hydroxy, alkoxy, or NR a R b ;

each R a is C 1 -C 10 alkyl that is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy;

each R b is H or C 1 -C 10 alkyl that is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy; and

M + is a pharmaceutically acceptable cation; and water, wherein the composition is substantially co-solvent free, substantially surfactant free, and has a pH of from about 7 to about 9, and wherein the concentration of the salt is at least about 0.25 mg/mL.

2. The salt:

3. A composition comprising the salt of claim 2 and water, wherein the composition is substantially co-solvent free, substantially surfactant free, and has a pH of from about 7 to about 9, and wherein the concentration of the salt is at least about 0.25 mg/mL.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 3, 2023
From: EBRIGHT, RICHARD; EBRIGHT, YON
To: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Reel/Frame 064137/0702 →
CONFIRMATORY LICENSE Recorded Jan 7, 2021
From: RUTGERS, THE STATE UNIVERSITY OF N.J.
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 054916/0841 →
Continuity (2)
Provisional Application 62630117 · Feb 13, 2018
Related Publication 20210002266A1 · Jan 7, 2021
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