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Preparation and antitumor activity of 2''-O-, 3''-O- and 2'',3''-di-O-substituted derivatives of etoposide.
- Source :
-
Chemical & pharmaceutical bulletin [Chem Pharm Bull (Tokyo)] 1992 Jul; Vol. 40 (7), pp. 1783-8. - Publication Year :
- 1992
-
Abstract
- The 2''-O-, 3''-O- and 2'',3''-di-O-substituted derivatives (4a--p) of etoposide were prepared by nucleophilic substitution of 4'-O-benzyloxycarbonyletoposide (2) followed by deprotection. Controlled reaction (a limited amount of reagents and low temperature) was required for preparing the mono-O-substituted derivatives. In terms of ED125 values, doses which show 125% of T/C against P388 leukemia in mice, both the 2''-O-acetate (4a, ED125 = 0.18 mg/kg) and 3''-O-acetate (4b, 0.23 mg/kg) were nearly as active as etoposide (1, 0.19 mg/kg), while the 2'',3''-di-O-acetate (4c, 1.9 mg/kg) was somewhat less potent. In the replacement with other substituents, antitumor activity of the 2''-O-substituted derivatives was affected much more by the difference of the substituents as compared with that of the corresponding 3''-O-substituted derivatives. In the 2'',3''-di-O-substituted derivatives, the activity was decreased additively on the substituents.
Details
- Language :
- English
- ISSN :
- 0009-2363
- Volume :
- 40
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Chemical & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 1394693
- Full Text :
- https://doi.org/10.1248/cpb.40.1783