Synthesis and CHK1 inhibitory potency of Hymenialdisine analogues.
A series of thieno[3,2-b]pyrroloazepinones derivatives related to Hymenialdisine were prepared and tested for CHK1 inhibitory activity. Nanomolar inhibitions were achieved when electron-withdrawing substituents were introduced at position 3 of the thiophene ring.
Parmentier
Jean-Gilles
JG
Medicinal Chemistry Division D, Institut de Recherche Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
Portevin
Bernard
B
Golsteyn
Roy M
RM
Pierré
Alain
A
Hickman
John
J
Gloanec
Philippe
P
De Nanteuil
Guillaume
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D000071877:Checkpoint Kinase 1; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004583:Electrons; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011494:Protein Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry
D000970:Antineoplastic Agents; D001381:Azepines; D011758:Pyrroles; D013876:Thiophenes; C107079:hymenialdisine; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1