Hydroxybenzamide derivatives and their use as inhibitors of Hsp90
The invention provides compounds of the general formula (I) which have activity as Hsp90 inhibitors.
1. A compound having the formula:
wherein
R 3 is C 1-5 hydrocarbyl;
R 10b is selected from the group consisting of halogen, OH, NH 2 , CH 2 OH, CH 2 NH 2 , O—C 1-6 -alkyl, NH—C 1-6 alkyl, aryl, heteroaryl, C 3-7 cycloalkyl, heterocyclyl, O-heteroaryl, O—C 3-7 cycloalkyl, O-heterocycloalkyl, C(═O)C 1-6 alkyl, C(═O)OC 1-6 alkyl, C(═O)NH 2 , C(═O)NHC 1-6 alkyl, C(═O)N(C 1-6 alkyl) 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , NC(═O)C 1-6 alkyl, C 6 aryl, OC 6 aryl, C(═O)C 6 aryl, C(═O)OC 6 aryl, C(═O)NH 2 , C(═O)NHC 6 aryl, C(═O)N(C 6 aryl) 2 , NH(C 6 aryl), N(C 6 aryl) 2 , NC(═O)C 6 aryl, C 5-6 heterocyclyl, OC 5-6 heterocyclyl, C(═O)C 5-6 heterocyclyl, C(═O)OC 5-6 heterocyclyl, C(═O)NHC 5-6 heterocyclyl, C(═O)N(C 5-6 heterocyclyl) 2 , NH(C 5-6 heterocyclyl), N(C 5-6 heterocyclyl) 2 , NC(═O)C 5-6 heterocyclyl, C(═O)NHC 1-6 alkyl, C 5-6 aryl, S(═O)C 1-6 alkyl, S(═O)N—C 1-6 alkyl and SO 2 N—C 1-6 alkyl; and a group [sol], CH 2 [sol] or OCH 2 CH 2 [sol] where [sol] is selected from the following groups
wherein n is 0, 1, 2 or 3;
or a hydrate, salt, tautomer or N-oxide thereof.
2. A compound, hydrate, salt, tautomer or N-oxide according to claim 1 wherein R 3 is selected from cyclopropyl and branched C 3-5 alkyl.
3. A compound, hydrate, salt, tautomer or N-oxide according to claim 2 wherein R 3 is isopropyl or tert-butyl.
4. A compound, hydrate, salt, tautomer or N-oxide according to claim 3 wherein R 3 is isopropyl.
5. A compound, hydrate, salt, tautomer or N-oxide according to any one of claims 1 - 4 wherein n is 1 or 2 and R 10b is selected from the group consisting of: heterocyclyl, NH(C 5-6 heterocyclyl); and a group [sol], CH 2 [sol] or OCH 2 CH 2 [sol] where [sol] is selected from the following groups:
6. A compound, hydrate, salt, tautomer or N-oxide according to claim 5 wherein n is one.
7. A pharmaceutical composition comprising a compound, hydrate, salt, tautomer or N-oxide according to claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition according to claim 7 wherein said pharmaceutically acceptable carrier is a carrier for intravenous administration.
9. A compound, hydrate, salt, tautomer or N-oxide according to any one of claims 1 to 4 wherein n is 1 or 2 and R 10b is selected from the group consisting of halogen, O—C 1-6 -alkyl, aryl, heterocyclyl, C(═O)OC 1-6 alkyl, C(═O)C 5-6 heterocyclyl, NH(C 5-6 heterocyclyl), and a group [sol], CH 2 [sol] or OCH 2 CH 2 [sol] where [sol] is selected from the following groups
10. A compound according claim 1 wherein the compound is a salt.