The synthesis and SAR of 2-amino-pyrrolo[2,3-d]pyrimidines: a new class of Aurora-A kinase inhibitors.

Abstract

A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This study culminates in compound 30, an inhibitor with potent activity against Aurora A (IC50=0.008 microM), anti-proliferative activity against several tumor cell lines and induces polyploidy in H460 cells.

• Authors: Kevin J Moriarty, Holly K Koblish, Thomas Garrabrant, Jahanvi Maisuria, Ehab Khalil, Farah Ali, Ioanna P Petrounia, Carl S Crysler, Anna C Maroney, Dana L Johnson, Robert A Galemmo Jr
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 22 Pg. 5778-83 (Nov 15 2006) ISSN: 0960-894X [Print] England
• PMID: 16949284 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Pyrimidines
• Pyrroles
• Aurora Kinases
• Protein Serine-Threonine Kinases

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Aurora Kinases
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Humans
• Inhibitory Concentration 50
• Polyploidy
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Pyrimidines (chemical synthesis, pharmacology)
• Pyrroles (chemical synthesis, pharmacology)
• Structure-Activity Relationship