Novel and efficient access to phenylamino-pyrimidine type protein kinase C inhibitors utilizing a Negishi cross-coupling strategy.
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.
Stanetty
Peter
P
Vienna University of Technology, Institute of Applied Synthetic Chemistry, Getreidemarkt 9/163, A-1060 Vienna, Austria. peter.stanetty@tuwien.ac.at
Hattinger
Gregor
G
Schnürch
Michael
M
Mihovilovic
Marko D
MD
D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C502153:3-(4-(2-(3-chlorophenylamino)pyrimidin-4-yl)pyridin-2-ylamino)propanol; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011493:Protein Kinase C