Compositions and methods for inhibition of cathepsins

• US 9,458,103 B2
• Filed: 10/02/2014
• Issued: 10/04/2016
• Est. Priority Date: 03/23/2012
• Status: Active Grant

• Current Assignee: Baylor University, Mateon Therapeutics, Inc.
• Original Assignee: Baylor University, Mateon Therapeutics, Inc.
• Inventors: Chaplin, David J., Gaddale Devanna, Kishore Kumar, Parker, Erica, Pinney, Kevin G., Song, Jiangli, Trawick, Mary L.
• Primary Examiner(s): Zucker, Paul A
• Assistant Examiner(s): LUDERER, MARK R
• Application Number:
  US14/505,165
• Publication Number:
  US 20150031915A1
• Time in Patent Office: 733 Days
• US Class Current: 1/1
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• 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: C07C 337/08 the other nitrogen atom being further doubly-bound to a carbon atom, e.g. thiosemicarbazones
• CPC Class Codes: C07C 49/786 Benzophenone

Abstract

This invention is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin K or cathepsin L, will be therapeutically useful.

Claims

1. A compound of formula I:

2. The compound of claim 1, wherein the compound is 3-benzoyl benzophenone thiosemicarbazone (3) having the formula:

3. The compound of claim 1, wherein n=1, m=0, and p=1.

4. The compound of claim 3, wherein R³ and R⁵ are fluoro.

5. The compound of claim 4, wherein the compound is 1,3-bis-(4-fluorobenzoyl) benzene thiosemicarbazone (13) having the formula:

6. The compound of claim 1, wherein n=0, m=1, and p=0.

7. The compound of claim 6, wherein R⁴ is benzoyl.

8. The compound of claim 7, wherein the compound is 1,3,5-Tribenzoyl benzene thiosemicarbazone (25) having the formula: