Pleuromutilin derivatives having a purine ring. Part 3: synthesis and antibacterial activity of novel compounds possessing a piperazine ring spacer.
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.
Hirokawa
Yoshimi
Y
Chemistry Research Laboratories, Dainippon Sumitomo Pharma Co, Ltd, Enoki, Suita, Japan.
Kinoshita
Hironori
H
Tanaka
Tomoyuki
T
Nakamura
Takanori
T
Fujimoto
Koichi
K
Kashimoto
Shigeki
S
Kojima
Tsuyoshi
T
Kato
Shiro
S
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
D000900:Anti-Bacterial Agents; D004224:Diterpenes; D000077489:Piperazine; D010879:Piperazines; D011083:Polycyclic Compounds; D011687:Purines; D000097567:Pleuromutilins; C030985:purine