Synthesis and evaluation of water-soluble non-prodrug analogs of docetaxel bearing sec-aminoethyl group at the C-10 position.

Abstract

To develop non-prodrugs of taxoids with satisfactory stability in vivo, high water-solubility, and potent antitumor activity, we prepared several 10-O-sec-aminoethyl docetaxel analogs (3) and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines, microtubule disassembly-inhibitory activity, and water-solubility. These analogs were synthesized from the 10-O-allyl baccatin derivatives (5a-c) using the beta-lactam synthon method. Among these analogs, the 10-O-(2-morpholinoethyl) (18, 21) and 10-O-(2-thiomorpholinoethyl) (19, 24) analogs exhibited cytotoxicity comparable or superior to that of docetaxel (2). In addition, the methanesulfonic acid salt (18a) had a high water-solubility.

• Authors: K Uoto, H Takenoshita, T Yoshino, Y Hirota, S Ando, I Mitsui, H Terasawa, T Soga
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 46 Issue 5 Pg. 770-6 (May 1998) ISSN: 0009-2363 [Print] Japan
• PMID: 9621410 (Publication Type: Journal Article)

Chemical References

• 10-O-sec-aminoethyl docetaxel
• Antineoplastic Agents, Phytogenic
• Taxoids
• Tubulin
• Docetaxel
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemical synthesis, pharmacology)
• Chemical Phenomena
• Chemistry, Physical
• Docetaxel
• Drug Screening Assays, Antitumor
• Humans
• Microtubules (drug effects, metabolism)
• Paclitaxel (analogs & derivatives, chemical synthesis, pharmacology)
• Solubility
• Swine
• Taxoids
• Tubulin (chemistry, isolation & purification)