Kings College London;The Secretary of State for Health
发明人:
申请号：
EP16813021.9
公开号：
EP3386985A1
申请日:
2016.12.09
申请国别(地区):
EP
年份:
2018
代理人:
摘要：
The invention relates to pyrrolobenzodiazepines compounds (PBDs) and to pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular, to treat bacterial infections. The PBDs are compounds of formula (I): and salts and solvates thereof； wherein: dotted lines indicates the optional presence of a double bond； X, X1, X2, X3 and X4 are connecting functional groups； L is C1-12 alkylene； R4, R5 and R6 are independently selected from phenylene, cyclopentanylene, cyclohexanylene, 5 - to 9 -membered heteroarylene and 5 - to 6-membered hetereocyclylene groups, and these groups are optionally substituted with up to three optional substituent groups； R7 is selected from N(C1- 6 alkyl)(C1-6alkyl), 5 - to 6-membered nitrogen-containing hetereocyclyl groups, a monosaccharide moiety and an amino monosaccharide moiety wherein these groups are optionally substituted； and R8 and R9 either together form a double bond, or are selected from H and OR14, or R8 is a prodrug moiety and R9 is OR14； m is 0 or 1； with the proviso that when X4 is C(O)NH then the up to three optional substituents of R7 are not selected from (CH2)k -CO2R12； with the proviso that when X4 is (CH2)tO then R4 is not phenylene, m is 1 and R6 is not a 5 - to 9 -membered heteroarylene； and with the proviso that when X4 is C(O)NH or NHC(O) that R4 and/or R6 is not 5 - to 9 -membered heteroarylene.L'invention concerne des composés de type pyrrolobenzodiazépine (PBD) et des sels pharmaceutiquement acceptables correspondants, qui sont utiles comme médicaments, en particulier, pour traiter des infections bactériennes. Les PBD selon l'invention sont des composés de formule (I) : et des sels et des solvates correspondants ； dans laquelle : les lignes en pointillés indiquent la présence éventuelle d'une double liaison ； X, X1, X2, X3 et X4 sont des groupes fonctionnels de liaison ； L représente C1-12-alkylène ； R4, R5 et R6 sont choisis, indépendamment, parmi les groupes phénylène, cyclopentanylène, c
