CHALLIS, Gregory Leonard,GRIFFITHS, Daniel John,MASSCHELEIN, Joleen Solange Liesbet
申请号:
GBGB2017/051124
公开号:
WO2017/182828A1
申请日:
2017.04.21
申请国别(地区):
GB
年份:
2017
代理人:
摘要:
The invention provides novel compounds of formula (I) and their pharmaceutically acceptable salts, metabolites, isomers (e.g. stereoisomers) and prodrugs. Such compounds are effective in the treatment of infections caused by Gram-negative bacteria such as Acinetobacter baumannii. In formula (I), X is O, NR (where R is either H or C1-3 alkyl, e.g. CH3), or CH2; R3 is H, F, CI, Br, I, or CH3; R4 is H, or OH; R5 and R6 are independently selected from H and OH, or R5 and R6 together are =O; R7 is H, F, CI, Br, I, or CH3; R8 is H, OH, or -OC(O)NR'2 (where each R' is independently H or C1-3 alkyl, e.g. CH3), preferably R8 is H, OH or -OC(O)NH2; R9 is a 5- or 6-membered, saturated or unsaturated, carbocyclic ring optionally substituted by one or more substituents, or R9 is an optionally substituted straight-chained or branched C1-6 alkyl group (e.g. C1-3 alkyl group); R10 is a straight-chained or branched C1-8 alkyl group (e.g. C1-6 alkyl group), a C4-6 cycloalkyl group, or an optionally substituted aryl or heteroaryl group; and each --- independently represents an optional bond (i.e. each of C2-C3, C4-C5, C6-C7, C8-C9, C10-C11 and C18-C19 are independently either C-C (single) or C=C (double) bonds).L'invention concerne de nouveaux composés de formule (I) et leurs sels pharmaceutiquement acceptables, métabolites, isomères (par exemple, stéréo-isomères) et promédicaments. De tels composés sont efficaces dans le traitement d'infections causées par des bactéries à Gram négatif telles que Acinetobacter baumannii. Dans la formule (I), X est O, NR (où R est soit H soit C1-3 alkyle, par exemple CH3), ou CH2; R3 est H, F, Cl, Br, I, ou CH3; R4 est H, ou OH; R5 et R6 sont choisis indépendamment parmi H et OH, ou R5 et R6 sont conjointement =O; R7 est H, F, Cl, Br, I, ou CH3; R8 est H, OH, ou -OC(O)NR'2 (où chaque R' est indépendamment H ou C1-3alkyle, par exemple CH3), de préférence R8 est H, OH ou -OC(O)NH2; R9 est un cycle carbocyclique, saturé ou insaturé, de 5 ou 6 membres, éve