Benzamide derivatives and their use as HSP90 inhibtors

摘要

The invention provides a compound which is (a) a phenylamide derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate, prodrug or solvate thereof: wherein R1, R2, R3, R4, R5, R6 and R7 are as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90.;

主权项

1. A compound which is (a) a phenylamide of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide or hydrate thereof:wherein:
R1 and R3 are hydroxy; R2, R4 and R5 are the same or different and represent hydrogen, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, hydroxy, cyano, nitro or —NR′R″ wherein R′ and R″ are the same or different and represent hydrogen or unsubstituted C1-4 alkyl, and with the proviso that no more than two of R2, R4 and R5 are cyano or nitro; either:
(i) R6 represents —CH3, R7 represents —CR8R9-A wherein R8 and R9 are the same or different and represent a hydrogen, halogen, an unsubstituted C1-4 alkyl or C1-4 alkoxy group, and A represents a phenyl ring substituted with a group W; or(ii) R6 and R7, together with the nitrogen atom to which they are bonded, form a pyrrolidinyl, piperidinyl or isoindolinyl group which is substituted with a group W and is optionally further substituted with 1 or 2 groups which are the same or different and are selected from halogen, unsubstituted C1-4 alkyl, C1-4 alkoxy, hydroxyl, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 hydroxyalkyl, cyano, nitro, —SR′ and —NR′R″ where R′ and R″ are the same or different and represent hydrogen or unsubstituted C1-2, alkyl; W represents a group -Alk1—R; Alk1 represents a bond, a C1-4 alkylene group or a group —(C1-4alkylene)—NR′—(C1-4 alkylene)- wherein R′ represents hydrogen or C1-4alkyl; R represents a group of formula (X) R10 represents a hydrogen atom or a C1-4 alkyl group; Alk2 represents a group of , formula —C(R12)(R13)— wherein one of R12 and R13 is hydrogen or unsubstituted C1-2 alkyl and the other of R12 and R13 is an unsubstituted group selected from C1-4 alkyl, C3-7 carbocyclyl, phenyl, -hydroxy—(C1-4)alkyl, —(C1-4)alkoxy—(C1-4)alkyl, —(C1-2)alkyl-phenyl or —(C1-2)alkyl—(C3-7)carbocyclyl; and R11 is an ester group —COOR20 wherein R20 represents unsubstituted C1-4 alkyl or C3-7 carbocyclyl;
and wherein, unless otherwise stated:the alkyl, alkenyl and alkynyl groups and moieties in R2, R4, R5and Alk1, are unsubstituted or substituted with 1, 2 or 3 unsubstituted substituents which are the same or different and are selected from halogen, C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C2-4 alkenyloxy, C1-4 haloalkyl, C2-4 haloalkenyl, C1-4 haloalkoxy, C2-4 haloalkenyloxy, hydroxyl, —SR′, cyano, nitro, C1-4 hydroxyalkyl and —NR′R″ where R′ and R″ are the same or different and represent hydrogen or unsubstituted C1-2 alkyl.