111321-02-9Relevant articles and documents
Hybrids of macrolides and nucleobases or nucleosides
Costa, Anna M.,Vilarrasa, Jaume
, p. 3371 - 3375 (2000)
A few examples of hybrids/conjugates/chimeras of erythromycin A derivatives and nucleobases (uracil and thymine) or thymidine-derived nucleosides are reported. Linkers and reaction conditions have been investigated to avoid the degradation of the macrolide moiety (glycoside hydrolysis, ring cleavage, dehydration, etc.). (C) 2000 Elsevier Science Ltd.
Using chemical probes to investigate the sub-inhibitory effects of azithromycin
Glansdorp, Freija G.,Spandl, Richard J.,Swatton, Jane E.,Loiseleur, Olivier,Welch, Martin,Spring, David R.
, p. 4120 - 4124 (2008)
The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported. Furthermore, the synthesis of immobilized and biotin-tagged azithromycin analogues is described. These chemical probes were used in pull-down assays in an effort to identify azithromycin's binding partners in vivo. Results from these assays revealed, as expected, mainly ribosomal-related protein binding partners, suggesting that this is the primary target of the drug. This was further confirmed by studies using a P. aeruginosa strain containing plasmid-encoded ermC, which expresses a protein that modifies 23S rRNA and so blocks macrolide entry to the ribosome. In this strain, no biofilm inhibition was observed. This work supports the hypothesis that the sub-inhibitory effects of azithromycin are mediated through the ribosome. Moreover, the synthesis of these chemical probes, and proof of their utility, is of value in global target identification in P. aeruginosa and other species.
Roxithromycin intermediate preparation method
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Paragraph 0057-0060; 0061-0064; 0065-0068; 0069-0076, (2017/10/05)
The invention discloses a preparation method of a roxithromycin intermediate. The method comprises the following steps: (i) mixing and reacting a compound, triethylamine and hydroxylamine hydrochloride, the structures of which are shown in a formula II, to obtain the compound the structure of which is shown in a formula III; (ii) mixing the compound the structure of which is shown in the formula III, with methanol or ethanol, alkalinizing and mixing with water, to obtain a compound the structure of which is shown in the formula I.
Chemistry and biology of macrolide antiparasitic agents
Lee, Younjoo,Choi, Jun Yong,Fu, Hong,Harvey, Colin,Ravindran, Sandeep,Roush, William R.,Boothroyd, John C.,Khosla, Chaitan
experimental part, p. 2792 - 2804 (2011/06/24)
Macrolide antibacterial agents inhibit parasite proliferation by targeting the apicoplast ribosome. Motivated by the long-term goal of identifying antiparasitic macrolides that lack antibacterial activity, we have systematically analyzed the structure-activity relationships among erythromycin analogues and have also investigated the mechanism of action of selected compounds. Two lead compounds, N-benzylazithromycin (11) and N-phenylpropylazithromycin (30), were identified with significantly higher antiparasitic activity and lower antibacterial activity than erythromycin or azithromycin. Molecular modeling based on the cocrystal structure of azithromycin bound to the bacterial ribosome suggested that a substituent at the N-9 position of desmethylazithromycin could improve selectivity because of species-specific interactions with the ribosomal L22 protein. Like other macrolides, these lead compounds display a strong "delayed death phenotype"; however, their early effects on T. gondii replication are more pronounced.
