Antitumor agents. 207. Design, synthesis, and biological testing of 4 beta-anilino-2-fluoro-4 '-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents

Authors
VanVliet, DS Tachibana, Y Bastow, KF Huang, ES Lee, KH
Citation
Ds. Vanvliet et al., Antitumor agents. 207. Design, synthesis, and biological testing of 4 beta-anilino-2-fluoro-4 '-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents, J MED CHEM, 44(9), 2001, pp. 1422-1428
Citations number
38
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
00222623 → ACNP
Volume
44
Issue
9
Year of publication
2001
Pages
1422 - 1428
Database
ISI
SICI code
0022-2623(20010426)44:9<1422:AA2DSA>2.0.ZU;2-Q
Abstract
2-Fluoropodophyllotoxin (11) and several 4 beta -anilino-2-fluoro-4 ' -O-de methyl analogues were synthesized and evaluated in both antineoplastic and antiviral assays. These compounds were moderately active against some cance r cell lines, but they were less active than the corresponding nonfluorinat ed analogues. Compound 11 exhibited the best activity against KB carcinoma with a GI(50) Of approximately 30 nM. Most compounds exhibited moderate act ivity against HCMV with ID50 and ID90 values in the range of 1 muM and 4 mu M, respectively. Both 9 and 11 showed an unusual 10-fold selectivity for HS V-2 compared to HSV-1.