Exploring 9-benzyl purines as inhibitors of glutamate racemase (MurI) in Gram-positive bacteria.
An early SAR study of a screening hit series has generated a series of 9-benzyl purines as inhibitors of bacterial glutamate racemase (MurI) with micromolar enzyme potency and improved physical properties. X-ray co-crystal EI structures were obtained.
Geng
Bolin
B
AstraZeneca R&D Boston, Infection Discovery, 35 Gatehouse Drive, Waltham, MA 02451, USA. bolin.geng@astrazeneca.com
Breault
Gloria
G
Comita-Prevoir
Janelle
J
Petrichko
Randy
R
Eyermann
Charles
C
Lundqvist
Tomas
T
Doig
Peter
P
Gorseth
Elise
E
Noonan
Brian
B
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D013293:Enterococcus faecalis / Q000187:drug effects / Q000235:genetics; D016984:Enterococcus faecium / Q000187:drug effects / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics; D008968:Molecular Conformation; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D011687:Purines; D000591:Amino Acid Isomerases; C062292:glutamate racemase