Derivative N-thiolated 2-oxazolidinone antibiotics
This invention describes the discovery and synthesis of N-thiolated 2-oxazolidinones as a new class of anti bacterial agents. These compounds can be synthesized from 2-oxazolidinones by Ndeprotection and N-sulfenylation. These new substances were found to exhibit potent anti-bacterial activity, including bacteriostatic properties against Staphylococcus spp., including methicillin resistant Staphylcoccus aureus (MRSA), and Bacillus spp., including Bacillus anthracis.
1. A N-thiolated 2-Oxazolidinone compound of the formula:
or a salt thereof, wherein:
R 1 is heteroaryl, alkyl, CH 3 , —CH(CH 3 )CH 2 CH 3 , or benzyl;
R 2 is hydrogen, CO 2 CH 3 , CH 2 Cl, or CH 2 N 3 ;
R 3 is acetyl, heteroaryl, heteroaryl(C 1 -C 6 ) alkyl, heteroaryl(C 2 -C 6 )alkenyl, aryl(C 2 -C 6 ) alkynyl, heteroaryl(C 2 -C 6 )alkynyl, a halo-substituted aryl, a nitro-substituted aryl, a cyano-substituted aryl, a hydroxy-substituted aryl, a trifluoromethyl-substituted aryl, a trifluoromethoxy-substituted aryl, a halo-substituted heteroaryl, a nitro-substituted heteroaryl, a cyano-substituted heteroaryl, a hydroxy-substituted heteroaryl, a trifluoromethyl-substituted heteroaryl, a trifluoromethoxy-substituted heteroaryl, (C 2 -C 15 )alkenyl, (C 2 -C 15 )alkynyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 2 -C 15 )alkoxy, (C 3 -C 8 )cycloalkyl-(C 2 -C 15 ) alkenyl, (C 3 -C 8 )cycloalkyl(C 2 -C 15 )alkynyl, (C 1 -C 15 )alkanoyl, (C 1 -C 15 )alkanoyloxy, (S)-phenyl, (R)-phenyl, (S)-isopropyl, (R)-isopropyl, or hydrogen;
wherein R 2 and R 3 are not concurrently hydrogen.
2. The compound of claim 1 , wherein the N-thiolated 2-oxazolidinone compound selected from the group consisting of:
3. The compound of claim 1 , wherein R 3 is (S)-phenyl, (R)-phenyl, (S)-isopropyl, (R)-isopropyl, benzyl or hydrogen.
4. The compound of claim 3 , wherein R 3 is (S)-phenyl, (R)-phenyl, or (S)-isopropyl.
5. The compound of claim 4 , wherein R 3 is (S)-phenyl, or (R)-phenyl.
6. The compound of claim 1 , wherein R 1 is CH 3 , —CH(CH 3 )CH 2 CH 3 , or benzyl.
7. The compound of claim 6 , wherein R 1 is CH 3 .
8. The compound of claim 1 , wherein R 2 is hydrogen, CO 2 CH 3 , or CH 2 Cl.
9. The compound of claim 1 ,
wherein R 1 is CH 3 ;
R 2 is hydrogen or CH 2 N 3 ; and
R 3 is (S)-phenyl, (R)-phenyl, (S)-isopropyl, or (R)-isopropyl.