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    • 4. 发明申请
    • PBD ANTIBACTERIAL AGENTS
    • PBD抗菌剂
    • WO2017098257A1
    • 2017-06-15
    • PCT/GB2016/053882
    • 2016-12-09
    • KING'S COLLEGE LONDONTHE SECRETARY OF STATE FOR HEALTH
    • RAHMAN, Khondaker MirazurSUTTON, John MarkPICCONI, Pietro
    • C07D487/04A61K31/5517A61P31/04
    • C07D487/04
    • 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, X 1 , X 2 , X 3 and X 4 are connecting functional groups; L is C 1 - 12 alkylene; R 4 , R 5 and R 6 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; R 7 is selected from N(C 1- 6 alkyl)(C 1-6 alkyl), 5 - to 6-membered nitrogen-containing hetereocyclyl groups, a monosaccharide moiety and an amino monosaccharide moiety wherein these groups are optionally substituted; and R 8 and R 9 either together form a double bond, or are selected from H and OR 14 , or R 8 is a prodrug moiety and R 9 is OR 14 ; m is 0 or 1; with the proviso that when X 4 is C(O)NH then the up to three optional substituents of R 7 are not selected from (CH2) k -CO 2 R 12 ; with the proviso that when X 4 is (CH 2 ) t O then R 4 is not phenylene, m is 1 and R 6 is not a 5 - to 9 -membered heteroarylene; and with the proviso that when X 4 is C(O)NH or NHC(O) that R 4 and/or R 6 is not 5 - to 9 -membered heteroarylene.
    • 本发明涉及吡咯并苯并二氮杂类化合物(PBD)及其药学上可接受的盐,其可用作药物,特别是用于治疗细菌感染。 PBD是式(I)的化合物:及其盐和溶剂化物; 其中:虚线表示任选存在双键; X,X 1,X 2,X 3和X 4连接官能团; L为C 1 -C 12亚烷基; R 5,R 5和R 6独立地选自亚苯基,环戊烯基,环己烯基,5至9元杂亚芳基和5至 6元杂环亚苯基,并且这些基团任选被至多三个任选取代基取代; R 7选自N(C 1-6 - 烷基)(C 1-6烷基),5(C 1 -C 6烷基) - 至6元含氮杂环基团,单糖部分和氨基单糖部分,其中这些基团任选被取代; 并且R 8和R 9或者一起形成双键,或者选自H和OR 14或R 8, 是前药部分,并且R 9是OR 14; m是0或1; 条件是当X 4是C(O)NH时,R 7的高达三个任选取代基不是从(CH 2)k - -CO 2 R 12;以及 - 条件是当X 4 =(CH 2)t O时,则R 4不是亚苯基,m 是1且R 6不是5至9元杂亚芳基; 并且附带条件是当X 4是C(O)NH或NHC(O)时,R 4和/或R 6不是 5至9元亚杂芳基。