Pleuromutilin derivatives having a purine ring. Part 2: influence of the central spacer on the antibacterial activity against Gram-positive pathogens

Yoshimi Hirokawa; Hironori Kinoshita; Tomoyuki Tanaka; Takanori Nakamura; Koichi Fujimoto; Shigeki Kashimoto; Tsuyoshi Kojima; Shiro Kato

doi:10.1016/j.bmcl.2008.10.123

Pleuromutilin derivatives having a purine ring. Part 2: influence of the central spacer on the antibacterial activity against Gram-positive pathogens

Bioorg Med Chem Lett. 2009 Jan 1;19(1):170-4. doi: 10.1016/j.bmcl.2008.10.123. Epub 2008 Nov 5.

Authors

Yoshimi Hirokawa¹, Hironori Kinoshita, Tomoyuki Tanaka, Takanori Nakamura, Koichi Fujimoto, Shigeki Kashimoto, Tsuyoshi Kojima, Shiro Kato

Affiliation

¹ Chemistry Research Laboratories, Dainippon Sumitomo Pharma Co, Ltd, Enoki, Suita, Japan.

PMID: 19028096
DOI: 10.1016/j.bmcl.2008.10.123

Abstract

Structural modification of the 4-piperidinethio moiety, as a spacer of the first pleuromutilin analogues 2A and 2B having a purine ring, led to discovery of the novel pleuromutilin derivatives 14B and 17B. These compounds with good solubility in water showed promising in vitro antibacterial activity against various Gram-positive bacteria including MRSA, PRSP, and VRE and have potent in vivo efficacy.

MeSH terms

Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology
Diterpenes / chemistry
Gram-Positive Bacteria / drug effects*
Microbial Sensitivity Tests
Pleuromutilins
Polycyclic Compounds
Purines / chemistry*
Solubility
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Diterpenes
Polycyclic Compounds
Purines
purine