3-Aryl beta-carbolin-1-ones as a new class of potent inhibitors of tumor cell proliferation: synthesis and biological evaluation.
A novel three-step synthesis of 3-aryl beta-carbolin-1-ones from non-indole starting materials has been developed. The two nitrogen atoms in beta-carbolin-1-one were introduced efficiently by Michael addition of ethyl acetamidocyanoacetate to chalcone. The desired pyridone and indole rings were assembled by an intramolecular ketone-nitrile annulation mediated by aqueous HCl-HOAc and a Cu(I)-catalyzed intramolecular N-arylation of the amide, respectively. The target compounds were found to possess significant activity against tumor cell proliferation.
Wang
Shaozhong
S
Department of Chemistry, Tsinghua University, Beijing, 100084, P R China.
Dong
Yanmei
Y
Wang
Xinyan
X
Hu
Xiaoyi
X
Liu
Jun O
JO
Hu
Yuefei
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry
D000970:Antineoplastic Agents; D002243:Carbolines; D007659:Ketones; D009570:Nitriles; C042514:cuprous ion; D003300:Copper