Bioorganic & Medicinal Chemistry Letters 2009-09-15

Water-soluble phosphate prodrugs of pleuromutilin analogues with potent in vivo antibacterial activity against Gram-positive pathogens.

Liqiang Fu, Zhiteng Jiang, Zhan Cai, Xin Liu, Huili He, Yushe Yang

Index: Bioorg. Med. Chem. Lett. 19(18) , 5407-10, (2009)

Full Text: HTML

Abstract

A phosphate prodrug strategy was investigated to address the problem of poor aqueous solubility of pleuromutilin analogues. Water-soluble phosphate prodrugs 6a, 6b and 6c of pleuromutilin analogues were designed and synthesized. Three compounds all exhibited excellent aqueous solubility (>50mg/mL) at near-neutral pH and sufficient stability in buffer solution. In particular, the phenol pleuromutilin prodrug 6c displayed favourable pharmacokinetic profiles and comparable potency with vancomycin against MSSA and MRSA strains in vivo.

Related Compounds

  • Pleuromutilin

Related Articles:

Novel ABC transporter gene, vga(C), located on a multiresistance plasmid from a porcine methicillin-resistant Staphylococcus aureus ST398 strain.

2009-08-01

[Antimicrob. Agents Chemother. 53 , 3589-91, (2009)]

Design, synthesis, and antibacterial activity of novel pleuromutilin derivatives bearing an amino thiazolyl ring.

2012-08-01

[Arch. Pharm. (Weinheim) 345(8) , 638-46, (2012)]

Single 23S rRNA mutations at the ribosomal peptidyl transferase centre confer resistance to valnemulin and other antibiotics in Mycobacterium smegmatis by perturbation of the drug binding pocket.

2009-03-01

[Mol. Microbiol. 71(5) , 1218-27, (2009)]

Pleuromutilin and its derivatives-the lead compounds for novel antibiotics.

2012-01-01

[Mini Rev. Med. Chem. 12(1) , 53-61, (2012)]

Mutilins derivatives: from veterinary to human-used antibiotics.

2009-10-01

[Mini Rev. Med. Chem. 9(12) , 1397-406, (2009)]

More Articles...