title: Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae.
abstract: A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N'-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N'-(β-cyanoethyl)-N'-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N'-(β-cyanoethyl)-N'-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3). Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. mirjana.bukvic@gmail.com
authors.forename: Mirjana
authors.initials: M
authors.lastname: Bukvić Krajačić
authors.forename: Miljenko
authors.initials: M
authors.lastname: Dumić
authors.forename: Predrag
authors.initials: P
authors.lastname: Novak
authors.forename: Mario
authors.initials: M
authors.lastname: Cindrić
authors.forename: Sanja
authors.initials: S
authors.lastname: Koštrun
authors.forename: Andrea
authors.initials: A
authors.lastname: Fajdetić
authors.forename: Sulejman
authors.initials: S
authors.lastname: Alihodžić
authors.forename: Karmen
authors.initials: K
authors.lastname: Brajša
authors.forename: Nedjeljko
authors.initials: N
authors.lastname: Kujundžić
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011008:Pneumococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013890:Thiourea / Q000737:chemistry* / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014508:Urea; D013890:Thiourea