A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors.
Two new series of 2-amido- and 2-aminocarbonylpurines have been synthesized using a Pd catalyst cross-coupling reaction either with amides or amines in the presence of CO. Moderate in vitro inhibitory activity against CDK1 and CDK5 was observed with IC(50) of 0.9muM for the most active compound (18c).
Vandromme
Lucie
L
UMR 176, Institut Curie, Bât. 110-112, Centre Universitaire, 91405 Orsay, France.
Legraverend
Michel
M
Kreimerman
Sergio
S
Lozach
Olivier
O
Meijer
Laurent
L
Grierson
David S
DS
D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D002384:Catalysis; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C517083:9-isopropyl-6-(4-methoxy-benzylamino)-9H-purine-2-carboxylic acid isopropylamide; D000577:Amides; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D011687:Purines; D015075:2-Aminopurine; D010165:Palladium; D051360:Cyclin-Dependent Kinase 5; D016203:CDC2 Protein Kinase