PYRROLOBENZODIAZEPINES

摘要

A compound of formula (I) 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′, —O—SO2—R, CO2R and COR; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo; where R and R′ 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 -(E-F1)m-; each E is independently selected from a single bond, and —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)n—C3-20 heterocycloalkyl, and —O—(CH2)n—C3-20 heterocycloalkyl group; each n is 0-4; provided that A2 is not A2′, where X1 and Y1 of A2′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and provided that A3 is not A3′, where X2 and Y2 of A3′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; B is either a single bond or (B1), where X and Y of B1 are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and R1 is C1-4 alkyl.

主权项

1. A compound of formula I: 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′, —O—SO2—R, CO2R and COR; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo; where R and R′ 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 -(E-F1)m-; each E is independently selected from a single bond, and —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)n—C3-20 heterocycloalkyl, and —O—(CH2)n—C3-20 heterocycloalkyl group; each n is 0-4; provided that A2 is not A2′: where X1 and Y1 of A2′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and provided that A3 is not A3′: where X2 and Y2 of A3′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; B is either a single bond or: where X and Y of B1 are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and R1 is C1-4 alkyl.