title: Synthesis and antibacterial activity of a novel series of acylides active against community acquired respiratory pathogens.
abstract: A novel series of acylides 4 were designed to overcome antibacterial resistance and evaluated for in vitro and in vivo activity. This series of acylides was designed from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. These compounds showed significantly potent antibacterial activity against not only Gram-positive pathogens, including macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens such as Haemophilus influenzae. These acylides also showed better activity against telithromycin resistant Streptococcus pneumoniae strains.
authors.affiliation: Department of Medicinal Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot-20, Sector-18, Udyog Vihar, Gurgaon 122001, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Sujata
authors.initials: S
authors.lastname: Rathy
authors.forename: Atul K
authors.initials: AK
authors.lastname: Hajare
authors.forename: Yogesh B
authors.initials: YB
authors.lastname: Surase
authors.forename: Jyoti
authors.initials: J
authors.lastname: Dullu
authors.forename: Jitendra S
authors.initials: JS
authors.lastname: Jadhav
authors.forename: R
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Anjan
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Manisha
authors.initials: M
authors.lastname: Pandya
authors.forename: Pragya
authors.initials: P
authors.lastname: Bhateja
authors.forename: G
authors.initials: G
authors.lastname: Ramkumar
authors.forename: Biswajit
authors.initials: B
authors.lastname: Das
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D017291:Clarithromycin / Q000031:analogs & derivatives / Q000737:chemistry; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006193:Haemophilus influenzae / Q000378:metabolism; D006801:Humans; D048628:Ketolides / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D017291:Clarithromycin; C106791:telithromycin; D009584:Nitrogen