Novel and efficient access to phenylamino-pyrimidine type protein kinase C inhibitors utilizing a Negishi cross-coupling strategy

Peter Stanetty; Gregor Hattinger; Michael Schnürch; Marko D Mihovilovic

doi:10.1021/jo0505223

Novel and efficient access to phenylamino-pyrimidine type protein kinase C inhibitors utilizing a Negishi cross-coupling strategy

J Org Chem. 2005 Jun 24;70(13):5215-20. doi: 10.1021/jo0505223.

Authors

Peter Stanetty¹, Gregor Hattinger, Michael Schnürch, Marko D Mihovilovic

Affiliation

¹ Vienna University of Technology, Institute of Applied Synthetic Chemistry, Getreidemarkt 9/163, A-1060 Vienna, Austria. peter.stanetty@tuwien.ac.at

PMID: 15960526
DOI: 10.1021/jo0505223

Abstract

A novel, short, and efficient synthetic pathway to 3-{4-[2-(3-chlorophenylamino)-pyrimidin-4-yl]-pyridin-2-ylamino}-propanol (CGP 60474) and a series of analogues was developed. The synthetic sequence consisted of a Negishi-type cross-coupling reaction in the key step followed by two subsequent nucleophilic substitution reactions. This strategy represents a versatile and robust protocol to access diverse analogues of the title compound for subsequent SAR studies as potential phenylamino-pyrimidine type protein kinase C inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Combinatorial Chemistry Techniques*
Molecular Structure
Protein Kinase C / antagonists & inhibitors*
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology
Structure-Activity Relationship

Substances

3-(4-(2-(3-chlorophenylamino)pyrimidin-4-yl)pyridin-2-ylamino)propanol
Protein Kinase Inhibitors
Pyrimidines
Protein Kinase C