Synthesis and structure-activity relationships of novel fungal chitin synthase inhibitors.
A novel Candida albicans chitin synthase 1 (CaChs1) inhibitor, RO-41-0986 (1) was discovered by random screening. Systematic modification led to the identification of a highly potent CaChs1 inhibitor, RO-09-3024 (2), having strong antifungal activity against Candida spp. in vitro.
Masubuchi
K
K
Department of Chemistry, Nippon Roche Research Center, Kamakura, Kanagawa, Japan.
Taniguchi
M
M
Umeda
I
I
Hattori
K
K
Suda
H
H
Kohchi
Y
Y
Isshiki
Y
Y
Sakai
T
T
Kohchi
M
M
Shirai
M
M
Okabe
H
H
Sudoh
M
M
Yamazaki
T
T
Shimma
N
N
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000201:enzymology; D001577:Benzophenones / Q000138:chemical synthesis*; D002175:Candida / Q000201:enzymology*; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D003454:Cryptococcus / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001577:Benzophenones; D004791:Enzyme Inhibitors; C415226:RO-09-3024; D002687:Chitin Synthase