Potent Oxazolidinone Antibacterials with Heteroaromatic C-Ring Substructure

Abstract

Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C-ring substructure were synthesized as candidate antibacterial agents. Analogues 16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse model of lethal infection. Preliminary safety data (inhibitory effects on cytochrome P450 isoforms and monoamine oxidases) were satisfactory. Further evaluation of 18 and 23 is ongoing.

LASSBio‐1829 Hydrochloride: Development of a New Orally Active N‐Acylhydrazone IKK2 Inhibitor with Anti‐inflammatory Properties

“…The desired aldehyde 8 was obtained through a palladium‐catalyzed cross‐coupling reaction (Suzuki–Miyamura reaction) . The Suzuki reaction is an efficient and economical method for synthesizing new bonds, particularly in the synthesis of new leads . For this synthesis, appropriate aryl bromide 7 and formylbenzene boronic acid 6 reacted in the presence of sodium carbonate and palladium catalyst (PdCl 2 (PPh 3 ) 2 ) in acetonitrile and water under microwave irradiation.…”

“…[38] The Suzuki reaction is an efficient and economical method for synthesizing new C sp 2ÀC sp 2 bonds, particularly in the synthesis of new leads. [39,40] For this synthesis, appropriate aryl bromide 7 and formylbenzeneb oronic acid 6 reactedi nt he presence of sodium carbonate and palladium catalyst( PdCl 2 (PPh 3 ) 2 )i na cetonitrile and water under microwave irradiation. After column chromatography,t he aldehyde 8 was obtained in moderate yield.…”

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

“…The oxazolidinone antibiotics, of which linezolid ( 379 , MMV687803) is the archetype, are reserved antibiotics for the treatment of Gram‐positive bacteria . These antibiotics bind to the 23s portion of the 50s ribosomal subunit which disrupts the formation of the ribosomal initiation complex, thereby inhibiting bacterial protein biosynthesis …”

Novel Oxazolidinone-Based Peroxisome Proliferator Activated Receptor Agonists: Molecular Modeling, Synthesis, and Biological Evaluation

“…10 It is considered a valuable structural motif in medicinal chemistry. 11,12,13 Oxazolidinones as chiral auxiliaries have been used by Miyachi and coworkers for the asymmetric synthesis of chiral α-acid derivatives as 7…”