title: Pleuromutilin derivatives having a purine ring. Part 3: synthesis and antibacterial activity of novel compounds possessing a piperazine ring spacer.
abstract: SAR studies on the water-soluble thioether pleuromutilin analogue 6, which has excellent in vitro and in vivo antibacterial activities, led to discovery of the novel pleuromutilin derivatives having a piperazine ring spacer. These derivatives displayed potent and well-balanced in vitro antibacterial activity against various drug-susceptible and -resistant Gram-positive bacteria. In particular, the promising pleuromutilin analogues 37 and 40 were found to exhibit strong in vivo efficacy against Staphylococcus aureus Smith.
authors.affiliation: Chemistry Research Laboratories, Dainippon Sumitomo Pharma Co, Ltd, Enoki, Suita, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Hirokawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takanori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kashimoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kojima
authors.forename: Shiro
authors.initials: S
authors.lastname: Kato
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry; D004351:Drug Resistance; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D011083:Polycyclic Compounds; D011687:Purines / Q000737:chemistry*; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D000097567:Pleuromutilins
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D000077489:Piperazine; D010879:Piperazines; D011083:Polycyclic Compounds; D011687:Purines; D000097567:Pleuromutilins; C030985:purine