GlaxoSmithKline Research Centre Zagreb, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia.
Bioorg Med Chem Lett. 2011 Jan 15;21(2):853-6. doi: 10.1016/j.bmcl.2010.11.079. Epub 2010 Nov 21.
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.
一系列新型的 3-去甲糖基-3-羟基 15 元氮杂内酯的脲和硫脲被发现、结构表征和生物评估。它们对选定的革兰氏阳性和革兰氏阴性细菌菌株表现出良好的抗菌活性。其中包括 N″取代的 9a-(N'-氨甲酰基-γ-氨基丙基)- (6a,c)、9a-(N'-硫代氨甲酰基-γ-氨基丙基)- (7a,e)、9a-[N'-(β-氰乙基)-N'-(氨甲酰基-γ-氨基丙基)]- (9a-c、9g)和 9a-[N'-(β-氰乙基)-N'-(硫代氨甲酰基-γ-氨基丙基)]-衍生物 (10d-f) 的 5-O-去氨基-9-脱氧-9-二氢-9a-氮杂-9a-同型红霉素 A (3)。在合成的化合物中，硫脲 7a 和脲 9b 的活性显著提高，与阿奇霉素 (1)相当，并且比 3-去甲糖基-阿奇霉素 (2)和母体 3-去甲糖基类似物对流出介导的耐药性肺炎链球菌的活性更好。
