Rigid analogs of camptothecin as DNA topoisomerase I inhibitors.
Substituted 8-ethyl-2-(2-oxo-1,2-dihydroindol-3-ylidene)-8-hydroxy-2,3,5,8- tetrahydro-6-oxa-3a-azacyclopenta[b]naphthalene-1,4,7-triones were synthesized and evaluated as topoisomerase I inhibitors in an in vitro cleavable complex assay. The activity of these compounds may be attributed to their rigid, planar geometry, and an attempt was made to correlate the SAR in this series to known attributes of camptothecin.
Lackey
K
K
Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
Besterman
J M
JM
Fletcher
W
W
Leitner
P
P
Morton
B
B
Sternbach
D D
DD
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives*; D004247:DNA / Q000378:metabolism; D007536:Isomerism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000470:Alkaloids; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D004247:DNA; D002166:Camptothecin