Discovery and SAR of benzyl phenyl ethers as inhibitors of bacterial phenylalanyl-tRNA synthetase.
A series of benzyl phenyl ethers (BPEs) is described that displays potent inhibition of bacterial phenylalanyl-tRNA synthetase. The synthesis, SAR, and select ADMET data are provided.
Montgomery
Justin I
JI
Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor Campus, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. justin.montgomery@pfizer.com
Toogood
Peter L
PL
Hutchings
Kim M
KM
Liu
Jia
J
Narasimhan
Lakshmi
L
Braden
Timothy
T
Dermyer
Michael R
MR
Kulynych
Angela D
AD
Smith
Yvonne D
YD
Warmus
Joseph S
JS
Taylor
Clarke
C
D000255:Adenosine Triphosphate / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000201:enzymology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010647:Phenyl Ethers / Q000737:chemistry*; D010652:Phenylalanine-tRNA Ligase / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010647:Phenyl Ethers; D000255:Adenosine Triphosphate; D010652:Phenylalanine-tRNA Ligase