Matrix compare analysis discriminates subtle structural differences in a family of novel antiproliferative agents, diaryl-3-hydroxy-2,3,3a,10a-tetrahydrobenzo[b]cycylopenta[e]azepine-4,10(1H,5H)-diones.
A diastereoselective synthesis of diaryl-3-hydroxy-2,3,3a,10a-tetrahydrobenzo[b]cycylopenta[e]azepine-4,10(1H,5H)-diones is described employing a tandem Michael-aldol addition as key step. The novel compounds exhibit antiproliferative activity in a panel of in vitro cultivated cancer cell lines. The bioinformatic tool COMPARE was able to discriminate between two closely related subgroups of the title compounds, namely 1,3- and 2,3-disubstituted derivatives.
Kunick
Conrad
C
Technische Universität Braunschweig, Institut für Pharmazeutische Chemie, Beethovenstrasse 55, D-38106 Braunschweig, Germany. c.kunick@tu.bs.de
Bleeker
Carola
C
Prühs
Christian
C
Totzke
Frank
F
Schächtele
Christoph
C
Kubbutat
Michael H G
MH
Link
Andreas
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001552:Benzazepines / Q000138:chemical synthesis / Q000494:pharmacology; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001552:Benzazepines; D003517:Cyclopentanes