Τίτλος:
Design and synthesis of two cytotoxic analogs of the novel pyrrolo[1′,2′:1,2][1,4]diazepin [7,6-b]indol-5(6h)-one nucleus
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The design and synthesis of the two cytotoxic derivatives 15 and 16 of the novel pyrrolo[1′,2′:1,2][1,4]diazepin[7,6-b]indol-5(6H)-one nucleus is described. Readily available methyl 2-indolecarboxylates 5 and 6 are nitrosated with NaNO2 in AcOH to give the analogs 7 and 8, which are then oxidized with KMnO4 in aq. NaOH to provide the 3-NO2 acids 9 and 10. These, in turn, are subjected to amidation with (2S)-pyrrolidine-2-carboxaldehyde diethyl thioacetal in the presence of EDCI and HOBt and then to a 7-exo-trig cyclization reaction to give the target molecules 15 and 16. The new analogs were evaluated in the human leukemic K 562 cell line and were shown to have micromolar potency.
Συγγραφείς:
Tsotinis, A.
Vlachou, M.
Kiakos, K.
Hartley, J.A.
Thurston, D.E.
Περιοδικό:
Chemistry Letters
Εκδότης:
Chemical Society of Japan
Λέξεις-κλειδιά:
acetal derivative; actinium; carboxylic acid derivative; cytotoxic agent; drug analog; hydroxide; manganese derivative; methyl group; nitric acid; potassium derivative; proline derivative; pyrrolo[1',2':1,2][1,4]diazepin[7,6 b]indol 5(6h) one; sodium hydroxide; sodium nitrite; unclassified drug, amidation; article; cyclization; drug design; drug potency; drug screening; drug synthesis; human; human cell; leukemia cell; molecule; nitrosation; oxidation
