WCK 4873 (INN: Nafithromycin): Structure–activity relationship (SAR) identifying a novel lactone ketolide with activity against Streptococcus pneumoniae (SPN) and Streptococcus pyogenes (SPY)

A New Process for the Synthesis of R‐nosylate a Key Intermediate of Nafithromycin

“…As a result, Lawesson's reagent at 0.6 mole equivalent yields more effective results when compared with 0.4 and 0.8 mole equivalent. Deprotection of alcohol in 19 was the fifth stage of the current method, and the reaction was carried out utilizing the reported process [10,11] to obtain 14.…”

“…[9] Compound 5 has a side chain of 2-pyridine-1,3,4thiadiazole connected through a relatively hydrophilic spacer of four carbon atoms with cis double bond and a chiral methyl group. [10,11] This particular structural configuration of 5 helps to demonstrate substantial antibacterial activity against strains of Streptococcus pneumoniae that express ermB as well as those that are telithromycin-resistant. Additionally, the unique structural arrangement of 5 contributes to favourable oral absorption, high levels of lung penetration, and minimal propensity for cytochrome P450 inhibition.…”

“…A unique oral and intravenous chiral lactone ketolide drug called nafithromycin (WCK 4873) (chemical name: (11 S ,21 R )‐3‐decladinosyl‐11,12‐dideoxy‐6‐O‐methyl‐3‐oxo‐12,11‐{oxycarbonyl‐[ Z ‐N‐[1‐(5‐pyridin‐2‐yl‐1,3,4‐thiadiazol‐2‐yl)‐( S )‐ethoxy]‐carboxamidino]methylene}‐erythromycin‐A) ( 5 ) was developed by Wockhardt Ltd. to treat a variety of drug resistant common and atypical respiratory bacteria [9] . Compound 5 has a side chain of 2‐pyridine‐1,3,4‐thiadiazole connected through a relatively hydrophilic spacer of four carbon atoms with cis double bond and a chiral methyl group [10,11] . This particular structural configuration of 5 helps to demonstrate substantial antibacterial activity against strains of Streptococcus pneumoniae that express ermB as well as those that are telithromycin‐resistant.…”