Benzamide derivatives useful as histone deacetylase inhibitors

• US 8,247,562 B2
• Filed: 09/10/2010
• Issued: 08/21/2012
• Est. Priority Date: 04/05/2002
• Status: Expired due to Fees

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Stokes, Elaine Sophie Elizabeth, Roberts, Craig Anthony, Waring, Michael James
• Primary Examiner(s): Balasubramanian, Venkataraman
• Application Number:
  US12/879,367
• Publication Number:
  US 20100331329A1
• Time in Patent Office: 711 Days
• Field of Search: 546/192, 546/196, 514/317, 514/320
• US Class Current: 546/192
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 211/34 with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 213/56 Amides
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 215/12 with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 237/08 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/26 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/42 One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 241/20 Nitrogen atoms nitro radicals C07D241/16
• CPC Class Codes: C07D 251/18 with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
• CPC Class Codes: C07D 277/24 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 277/30 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 295/155 with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 307/54 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems

Abstract

The invention concerns a compound of the formula (I)

wherein Ring A is heterocyclyl; m is 0-4 and each R¹ is a group such as hydroxy, halo, trifluoromethyl and cyano; R² is halo and n is 0-2; and each R⁴ is a group such as hydroxy, halo, trifluoromethyl and cyano; p is 0-4; and R³ is amino or hydroxy;
or pharmaceutically-acceptable salts or in-vivo-hydrolysable ester or amide thereof;
processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by histone deacetylase.

Claims

1. A compound of the formula (I):

2. A compound of the formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 wherein R³ is amino.

3. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof, according to claim 1, which process comprises:

(a) reacting a compound of the formula (II)

4. A pharmaceutical composition which comprises a compound of the formula (I), or a pharmaceutically acceptable salt thereof, according to any one of claim 1 or 2 in association with a pharmaceutically-acceptable diluent or carrier.

5. A compound selected from any one of the following:

N-(2-Aminophenyl)-4-(1-methylpiperidin-4-yl)benzamide;

N-(2-Aminophenyl)-4-piperidin-4-ylbenzamide;

N-(2-aminophenyl)-4-piperidin-3-ylbenzamide;

4-(1-acetylpiperidin-4-yl)-N-(2-aminophenyl)benzamide;

N-(2-aminophenyl)-4-[1-(4-bromobenzoyl)piperidin-4-yl]benzamide;

or a pharmaceutically acceptable salt thereof.