Aminophenyl derivatives as novel inhibitors of histone deacetylase

• US 8,119,650 B2
• Filed: 01/16/2007
• Issued: 02/21/2012
• Est. Priority Date: 01/19/2006
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Angibaud, Patrick René, Pilatte, Isabelle Noëlle Constance, Roux, Bruno, Arts, Janine
• Primary Examiner(s): RAO, DEEPAK R
• Application Number:
  US12/160,140
• Publication Number:
  US 20090018152A1
• Time in Patent Office: 1,862 Days
• Field of Search: 544/331, 514/275
• US Class Current: 514/275
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/14 containing three or more hetero rings

Abstract

This invention comprises the novel compounds of formula (I)

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, X and Y have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

Claims

1. A compound of formula (I)

2. A compound according to claim 1 wherein:

a) n is 0 or 1;

b) m is 1 or 2;

c) X is N or CH;

d) Y is NR⁸ wherein R⁸ is hydrogen, C_1-6alkyl, C_3-6cycloalkyl or C_3-6cycloalkylmethyl;

e) R¹ is hydrogen, C_1-6alkyl, hydroxyC_1-6alkyl, C_1-6alkylcarbonyl or C_1-6alkylsulphonyl;

f) R² is hydrogen or halo;

g) R³ is amino;

h) R⁴ is hydrogen or thienyl; and

i) R⁵, R⁶ and R⁷ are each hydrogen.

3. A compound according to claim 1 wherein:

a) n is 1;

b) m is 1;

c) X is N;

d) Y is NR⁸ wherein R⁸ is methyl;

e) R¹ is hydrogen;

f) R² is hydrogen or halo;

g) R³ is amino;

h) R⁴ is hydrogen or 2-thienyl; and

i) R⁵, R⁶ and R⁷ are each hydrogen.

5. A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound as claimed in claim 1.

6. A method of treating ovarian cancer in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

7. A combination of an anti-cancer agent and a compound of claim 1.

8. A process for preparing a compound according to claim 1, said process comprising:

reacting an intermediate of formula (II) wherein M represents hydrogen or an alkali metal, with a compound of formula (III), in the presence of a base;

9. A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound as claimed in claim 2.

10. A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound as claimed in claim 3.

4. A compound that is Compound No. 2:

11. A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound as claimed in claim 4.