| 摘要 |
The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof:;
wherein the bicyclic group:
;
is selected from the structures C1, C5 and C6:
;
wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or
;
Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims.
;The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity. |
| 主权项 |
1. A compound having the formula (VIII): wherein Q1 is a bond or a group CH2; R1 is hydroxy or O—Rz and R2a is hydroxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, the C1-25 hydrocarbyl group being optionally substituted by hydroxy, amino, mono- or di-C1-6 alkylamino, C1-6 acylamino, halogen or C1-4 alkoxy or C1-4 alkyl groups wherein the C1-4 alkoxy or C1-4 alkyl groups are each optionally substituted by two or more fluorine atoms; and wherein up to 3 non-terminal carbon atoms in the C1-25 hydrocarbyl group may optionally be replaced by oxygen, and up to one pair of adjacent non-terminal carbon atoms may optionally be replaced by C(═O)O or O(C═O); provided that Rp1 is not hydrogen when Lp is C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and Rp2 and Rp3 are the same or different and each is a group Rp1. |
