Benzene sulfonamide thiazole and oxazole compounds

• US 8,415,345 B2
• Filed: 05/04/2009
• Issued: 04/09/2013
• Est. Priority Date: 05/06/2008
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: GlaxoSmithKline LLC (GlaxoSmithKline PLC)
• Inventors: Adjabeng, George, Adams, Jerry Leroy, Dickerson, Scott Howard, Hornberger, Keith, Johnson, Neil W., Kuntz, Kevin, Petrov, Kimberly, Ralph, Jeffrey M., Rheault, Tara Renae, Schaaf, Gregory, Stellwagen, John, Tian, Xinrong, Uehling, David E., Waterson, Alex G., Wilson, Brian
• Primary Examiner(s): RAO, DEEPAK R
• Application Number:
  US12/991,004
• Publication Number:
  US 20110172215A1
• Time in Patent Office: 1,436 Days
• Field of Search: 544/60, 544/122, 544/295, 544/331, 514/227.8, 514/235.8, 514/252.14, 514/275
• US Class Current: 514/227.8
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.

Claims

1. A compound of formula (I)

2. The compound according to claim 1, wherein each R¹ is the same or different and is independently selected from halo, alkyl, haloalkyl, and —

OR⁶.

3. The compound according to claim 1, wherein Ring A is phenyl, 5-6 membered heterocycle or 5-6 membered heteroaryl.

4. The compound according to claim 1, wherein each of Q¹, Q², Q³, and Q⁴ is CH or C—

R², wherein at least two of Q¹, Q², Q³, and Q⁴ are CH.

5. The compound according to claim 1, wherein each R² is the same or different and is independently halo or C_1-3alkyl.

6. The compound according to claim 1 wherein each of Q¹, Q², and Q³ is CH and Q⁴ is C—

F or C—

Cl.

10. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

11. A method for treating melanoma in a human in need thereof, said method comprising administering to the human a therapeutically effective amount of a compound according to claim 1.

12. A process for preparing a compound according to claim 1, said process comprising reacting a compound of formula (VIII):

13. A process for preparing a compound according to claim 1 comprising reacting a compound of formula (XVIII):

14. The method according to claim 11, wherein said melanoma is metastatic melanoma having a mutation encoding a V600E amino acid substitution.

7. A compound of formula (I):

8. The compound according to claim 7, wherein the compound of formula (I) is a compound of formula (I-iii-a):

9. The compound according to claim 7, wherein the compound of formula (I) is a compound of formula (I-iii-b):