Pyrimidine derivatives used as PI-3-kinase inhibitors

• US 8,217,035 B2
• Filed: 01/22/2007
• Issued: 07/10/2012
• Est. Priority Date: 01/20/2006
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Burger, Matthew, Ni, Zhi-Jie, Pecchi, Sabina, Atallah, Gordana, Bartulis, Sarah, Frazier, Kelly, Smith, Aaron, Verhagen, Joelle, Zhang, Yanchen, Wagman, Allan, Ng, Simon, Pfister, Keith, Poon, Daniel, Louie, Alicia, Pick, Teresa, Barsanti, Paul, Iwanowicz, Edwin, Fantl, Wendy, Hendrickson, Thomas, Knapp, Mark, Merritt, Hanne, Voliva, Charles, Wiesmann, Marion, Xin, Xiaohua
• Primary Examiner(s): ANDERSON, REBECCA L
• Application Number:
  US12/161,537
• Publication Number:
  US 20100249126A1
• Time in Patent Office: 1,996 Days
• Field of Search: 544/122, 514/232.2
• US Class Current: 514/232.2
• 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: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 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 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Phosphatidylinositol (PI) 3-kinase inhibitor compounds (I), their pharmaceutically acceptable salts, and prodrugs thereof; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.

Claims

1. The compound 4-(trifluoromethyl)-5-(2,6-dimorpholinopyrimidin-4-yl)pyridin-2-amine, of structure:

2. A composition, comprising a pharmaceutically acceptable carrier and an amount of a compound of claim 1 effective to inhibit PI3-K activity in a human or animal subject when administered thereto.

3. The composition of claim 2 further comprising at least one agent for the treatment of cancer.

4. The composition of claim 3, wherein the at least one agent for the treatment of cancer is vatalanib, imatinib, erlotinib, lapatinib, pertuzumab, trastuzumab, capecitabine, gemcitabine, irinotecan, paclitaxel, cisplatin, carboplatin, fulvestrant, dexamethasone, bevacizumab, docetaxel or gefitinib.

5. A method for treating ovarian cancer in a human or animal subject having ovarian cancer, comprising administering to the human or animal subject a composition comprising an amount of a compound of claim 1 effective to inhibit PI3-K activity in the human or animal subject.

6. The method of claim 5 further comprising administering to the human or animal subject at least one agent for the treatment of cancer.

7. The method of claim 6, wherein the at least one agent for the treatment of cancer is vatalanib, imatinib, erlotinib, lapatinib, pertuzumab, trastuzumab, capecitabine, gemcitabine, irinotecan, paclitaxel, cisplatin, carboplatin, fulvestrant, dexamethasone, bevacizumab, docetaxel or gefitinib.