Fine Tuning of physico-chemical parameters to optimise a new series of novobiocin analogues.
A novel series of novobiocin analogues has been synthesised by removing the lipophilic aryl chain in novobiocin and introducing an amino substituent. The structural modifications have been dictated by the control of lipophilicity and the dissociation constant of the resulting compounds. Antibacterial activity of the new coumarin derivatives could be correlated with the amount of uncharged form in physiological conditions.
Schio
L
L
Medicinal Chemistry, Aventis Pharma, 102 route de Noisy, F-93235 Cedex, Romainville, France. laurent.schio@aventis.com
Chatreaux
F
F
Loyau
V
V
Murer
M
M
Ferreira
A
A
Mauvais
P
P
Bonnefoy
A
A
Klich
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003374:Coumarins / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009675:Novobiocin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D003374:Coumarins; D009675:Novobiocin; C006260:clorobiocin; C030123:coumarin