Substituted tricyclic compounds as protein kinase inhibitors

• US 7,312,226 B2
• Filed: 03/29/2005
• Issued: 12/25/2007
• Est. Priority Date: 10/14/2003
• Status: Expired due to Fees

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Montigen Pharmaceuticals, Inc. (Otsuka Holdings Company Limited), Arizona Board of Regents (University of Arizona)
• Inventors: Mahadevan, Daruka, Hurley, Laurence H., Warner, Steven L., Bearss, David J., Bashyam, Sridevi, Vankayalapati, Hariprasad
• Primary Examiner(s): Coleman, Brenda L.
• Assistant Examiner(s): Moore, Susanna
• Application Number:
  US11/092,168
• Publication Number:
  US 20050277658A1
• Time in Patent Office: 1,001 Days
• Field of Search: 544/250, 514/267
• US Class Current: 514/267
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 239/94 Nitrogen atoms
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/048 the oxygen-containing ring being five-membered
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/14 Ortho-condensed systems

Abstract

Protein kinase inhibitors are disclosed having utility in the treatment of protein kinase-mediated diseases and conditions, such as cancer. The compounds of this invention have the following structure:

including steroisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein A is a ring moiety selected from:

and wherein R1, R2, R3, X, Z, L1, Cycl1, L2 and Cycl2 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

Claims

1. A compound having the following structure:

2. The compound of claim 1, wherein L₂ is —

C(═

S)NHCH₂—

.

3. The compound of claim 1, wherein R₁ and R₂ are selected from hydrogen, —

OCH₃, —

OH, —

Cl, —

CF₃, or —

OC(═

O)CH₃, and R₃ is selected from hydrogen or —

NH₂.

4. The compound of claim 1, wherein R₁, R₂, and R₃ are hydrogen.

10. A composition comprising a compound of any one of claims 1, 5 and 9 in combination with a pharmaceutically acceptable excipient.

11. The compound of any one of claims 1 to 9, wherein the compound is a hydrochloride salt.

5. A compound having the following structure:

6. The compound of claim 5, wherein L₂ is —

C(═

S)NHCH₂—

.

7. The compound of claim 5, wherein R₁ and R₂ are selected from hydrogen, —

OCH₃, —

OH, —

Cl, —

CF₃, or —

OC(═

O)CH₃, and R₃ is selected from hydrogen or —

NH₂.

8. The compound of claim 5, wherein R₁, R₂, and R₃ are hydrogen.

9. A compound having the following structure: