THURSTON DAVID EDWIN,TAYLOR PETER WILLIAM,HOWARD PHILIP WILSON,RAHMAN KHONDAKER MIRAZUR
申请号：
NZ70147813
公开号：
NZ701478A
申请日:
2013.04.30
申请国别(地区):
NZ
年份:
2016
代理人:
摘要：
The present invention relates to pyrrolobenzodiazepines (PBDs). The inventors have found that PBD conjugates of the prior art may be modified in order to achieve improved properties, particularly antibacterial properties. In particular, the present invention relates to the incorporation of an amino acid residue containing a 5-membered heterocyclic group in combination with an arylene based amino acid residue in a PBD conjugate which results in highly effective compounds. The present invention therefore provides a PBD compound of formula I, a pharmaceutical composition comprising a compound of formula I and a use of a compound of formula I in the treatment of bacterial infections or a salt or solvate thereof, wherein: the dotted double bond indicates the presence of a single or double bond between C2 and C3； R2 is selected from -H, -OH, =O, =CH2, -CN, -R, OR, halo, dihalo, =CHR, =CHRR&rsquo；, -O-SO2-R, CO2R and COR； R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR&rsquo；, nitro, Me3Sn and halo； where R and R&rsquo； are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups； R10 and R11 either together form a double bond, or are selected from H and QRQ respectively, where Q is selected from O, S and NH and RQ is H or C1-7 alkyl or H and SOxM, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation； A is selected from A1, A2, A3, A4 or A5 where X1 and Y1 are selected from: CH and NH； CH and NMe； N and NMe； CH and S； N and S； N and O； and CH and O, respectively； X2 and Y2 are selected from: CH and NH； CH and NMe； N and NMe； CH and S； N and S； N and O； and CH and O, respectively； Z1 is selected from O and S； Z2 is selected from CH and N； F is selected from a single bond and &ndash；(E-F1)m-； each E is independently selected from a single bond, and &ndash；C(=O)-NH-； each F1 is independently a C3-20 heteroarylene group； m is 1, 2 or 3； G is selected from hydrogen, C1-4alkyl, C(=O) O C1-4alkyl, (CH2)
