Proteasome inhibitors

• US 7,838,673 B2
• Filed: 10/16/2007
• Issued: 11/23/2010
• Est. Priority Date: 10/16/2007
• Status: Active Grant

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Olhava, Edward J., Danca, Mihaela Diana
• Primary Examiner(s): Kumar; Shailendra
• Application Number:
  US11/974,758
• Publication Number:
  US 20090099132A1
• Time in Patent Office: 1,134 Days
• Field of Search: 564/155, 549/32, 514/616, 514/464
• US Class Current: 544/229
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

Claims

1. A compound of formula (I):

2. The compound of claim 1, wherein P is R^d—

C(O)—

.

3. The compound of claim 1, wherein R^A is substituted or unsubstituted phenyl.

4. The compound of claim 1, wherein R^a and R^b, taken together with the carbon atom to which they are attached, form a cyclopropyl or cyclobutyl ring, either of which is substituted with 0-2 substituents —

R^B;

each R^B independently is a C_1-4 aliphatic, C_1-4 fluoroaliphatic, —

R^1b, -T-R^1b;

T² is C_1-4 alkylene; and

R^1b is a substituted or unsubstituted aromatic or cycloaliphatic group.

5. The compound of claim 3, wherein R^1b is substituted or unsubstituted phenyl.

6. The compound of claim 1, wherein R^a and R^b are each —

CH₃.

7. The compound of claim 1, wherein R^c has the formula —

(CH₂)_m—

R^c, m is 1 or 2, and R^c is substituted or unsubstituted phenyl.

8. The compound of claim 1, wherein R^c is C_1-4 aliphatic.

9. The compound of claim 8, wherein R^c is isobutyl.

10. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.