Heterocyclic compounds as autotaxin inhibitors

• US 8,841,324 B2
• Filed: 03/03/2010
• Issued: 09/23/2014
• Est. Priority Date: 04/02/2009
• Status: Active Grant

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Staehle, Wolfgang, Schiemann, Kai, Schultz, Melanie
• Primary Examiner(s): JEAN-LOUIS, SAMIRA JM
• Application Number:
  US13/259,464
• Publication Number:
  US 20120015959A1
• Time in Patent Office: 1,665 Days
• Field of Search: 514/322, 514/414, 514/415, 514/394, 544/366, 544/373, 546/199, 546/220
• US Class Current: 514/322
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 231/56 Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 249/18 Benzotriazoles
• CPC Class Codes: C07D 263/58 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

Compounds of the formula (I), in which Het, R, X, Y, R¹ and p have the meanings indicated in claim 1, are autotaxin inhibitors and can be employed for the treatment of tumors.

Claims

1. A compound of formula I

2. A compound according to claim 1, in which

R¹ denotes Hal,

or a pharmaceutically acceptable salt or stereoisomer thereof.

3. A compound according to claim 1, in which

X denotes O or CH₂,

or a pharmaceutically acceptable salt or stereoisomer thereof.

4. A compound according to claim 1, in which

Y denotes CH₂ or CH₂O,

or a pharmaceutically acceptable salt or stereoisomer thereof.

5. A compound according to claim 1, in which

A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7H atoms are optionally replaced F and/or Cl,

or a pharmaceutically acceptable salt or stereoisomer thereof.

6. A compound according to claim 1, in which

p denotes 1, 2 or 3,

or a pharmaceutically acceptable salt or stereoisomer thereof.

7. A compound according to claim 1, in which

R¹ denotes Hal,

X denotes O or CH₂,

Y denotes CH₂ or CH₂O,

A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7H atoms are optionally replaced F and/or Cl, and

p denotes 1, 2 or 3,

or a pharmaceutically acceptable salt or stereoisomer thereof.

9. A process for preparing a compound of formula I according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, comprising

a) for the preparation of a compound of formula I in which

R denotes

10. A pharmaceutical composition comprising at least one compound of formula I according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, and one or more pharmaceutically acceptable excipients and/or adjuvants.

11. A method for inhibiting autotaxin, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.

13. A method for inhibiting autotaxin, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 7.

14. A method for inhibiting autotaxin, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 2.

17. A compound according to claim 1, in which R denotes

18. A compound according to claim 1, in which

R denotes

19. A compound according to claim 1, in which

R denotes

20. A method for inhibiting autotaxin, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 19.

8. A compound, which is one of the following compounds

12. A method for inhibiting autotaxin, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 8.

15. A compound, which is

16. A method for inhibiting autotaxin, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 15.