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    • 1. 发明申请
    • ANTIMICROBIAL AGENTS
    • WO2018193273A1
    • 2018-10-25
    • PCT/GB2018/051058
    • 2018-04-23
    • THE UNIVERSITY OF WARWICK
    • CHALLIS, Gregory LeonardJIAN, XinyunHOBSON, ChristianMASSCHELEIN, Joleen Solange Liesbet
    • C07C69/732C07C235/28A61K31/232A61P31/00C12N1/00C07D309/10
    • The invention provides novel analogues of enacyloxin Ha 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 . Compounds in accordance with the invention include those of formula (A), and their pharmaceutically acceptable salts, metabolites, isomers (e.g. stereoisomers) and prodrugs: In formula (A): X is 0 or NR x (where R* is either H or C 1-3 alkyl, e.g. CH 3 ); R 1 is a 5- or 6-membered, saturated or unsaturated, carbocyclic ring optionally substituted by one or more substituents, or R 1 is an optionally substituted straight-chained or branched C- 1-6 alkyl group (e.g. C 1-3 alkyl group); R 2 is H, F, CI, Br, I or CH 3 ; R 3 is H or OH; R 8 is a straight-chained or branched C 1-8 alkyl group (e.g. a C 1-6 aikyl group); Y is one of the following groups: (wherein each * denotes the point of attachment of the group to the remainder of the molecule; R 9 is H, F, CI, Br or I; R 4 and R 5 are independently selected from H and OH, or R 4 and R 5 together are =0, preferably R 4 is H and R 5 is OH; R 6 is H, F, CI, Br, I or CH 3 ; R 7 is H and R 7' is OH, or R 7 and R 7' together are =0, preferably R7 is H and R7' is OH); and each— independently represents an optional bond (i.e. each of C 2 -C 3 , C 4 -C 5 , C 6 -C 7 , C 8 -C 9 and C 10 -C 11 are independently either C-C (single) or C=C (double) bonds).