Details

Autor(en) / Beteiligte

• Fraley, Mark E.
• Rubino, Robert S.
• Hoffman, William F.
• Hambaugh, Scott R.
• Arrington, Kenneth L.
• Hungate, Randall W.
• Bilodeau, Mark T.
• Tebben, Andrew J.
• Rutledge, Ruth Z.
• Kendall, Richard L.
• McFall, Rosemary C.
• Huckle, William R.
• Coll, Kathleen E.
• Thomas, Kenneth A.

Titel

Optimization of a pyrazolo[1,5- a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2002-12, Vol.12 (24), p.3537-3541

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2002

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5- a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described. Graphic