Synthesis and biological evaluation of platensimycin analogs.
Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.
Shen
Hong C
HC
Departments of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA.
Ding
Fa-Xiang
FX
Singh
Sheo B
SB
Parthasarathy
Gopalakrishnan
G
Soisson
Stephen M
SM
Ha
Sookhee N
SN
Chen
Xun
X
Kodali
Srinivas
S
Wang
Jun
J
Dorso
Karen
K
Tata
James R
JR
Hammond
Milton L
ML
Maccoss
Malcolm
M
Colletti
Steven L
SL
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000218:Adamantane / Q000138:chemical synthesis* / Q000494:pharmacology; D062365:Aminobenzoates / Q000138:chemical synthesis* / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004352:Drug Resistance, Microbial; D013293:Enterococcus faecalis / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D015394:Molecular Structure; D013302:Streptomyces / Q000378:metabolism; D013329:Structure-Activity Relationship
D062365:Aminobenzoates; D000813:Anilides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; C490370:FabF protein, Enterococcus faecalis; D000218:Adamantane; C510909:platensimycin; D008712:Methicillin