Benzene Sulfonamide Thiazole and Oxazole Compounds

• US 20140080851A1
• Filed: 11/25/2013
• Published: 03/20/2014
• 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
• Granted Patent: US 9,233,956 B2
• Time in Patent Office: Days
• US Class Current: 514/275
• 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. (canceled)

5. The method of claim 1, wherein said neoplasm is selected from breast cancer, cholanglocarcinoma, colorectal cancer, melanoma, non-small cell lung cancer, ovarian cancer, and thyroid cancer.

6. The method of claim 5, wherein said neoplasm is melanoma.

7. The method of claim 6, wherein said neoplasm is metastatic melanoma.

2. A method for treating a susceptible neoplasm in a mammal in need thereof comprising the steps of:

(a) analyzing a sample from said neoplasm to determine whether an activating mutation is present in the coding sequence for B-Raf in cells of said neoplasm;

(b) selecting a mammal having said neoplasm with an activating mutation in the coding sequence for B-Raf; and

(c) administering a therapeutically effective amount the compound of formula

3. The method of claim 2, wherein the activating mutation present in the coding sequence for BRAF results in a BRAF having an amino acid substitution selected from the group consisting of R462I, I463S, G464V, G464E, G466A, G466E, G466V, G469A, G469E, D594V, F595L, G596R, L597V, L597R, T599I, V600E, V600D, V600K, V600R, T119S, and K601E.

4. The method of claim 3, wherein the activating mutation present in the coding sequence for BRAF results in a BRAF having a V600E amino acid substitution.

8. The method of claim 2, wherein the activating mutation present in the coding sequence for BRAF results in the coding sequence of BRAF having a substitution of T1799A.

9. The method of claim 2, wherein said mammal is a human.