Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2003-03-24
2004-11-23
Desai, Rita (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S083000
Reexamination Certificate
active
06821982
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for the preparation of camptothecin and camptothecin-like compounds and to novel intermediates used in this preparation.
BACKGROUND OF THE INVENTION
Camptothecin and many camptothecin-like compounds, i.e., derivatives have been found to have potent cytotoxicity, and hence, are potent antitumor agents. The camptothecin moiety common to these compounds has a chiral center at the 20 position. The configuration about this position appears to be important to the antitumor activity of camptothecin and its derivatives now in clinical trials.
Camptothecin and its derivatives can be produced using several processes taught in the art such as those described in U.S. Pat. Nos. 4,894,456; 4,399,282, 4,399,276; 4,943,579; European Patent Application 0 321 122 A2 published Jun. 21, 1989; U.S. Pat. No. 4,473,692, European Patent application No. 0 325 247 A2 published Jul. 26, 1989; European Patent application 0 556 585 A2 published Aug. 25, 1993; U.S. Pat. Nos. 4,981,968; 5,049,668; 5,162,532; 5,180,722; and European Patent application 0 540 099 A1 published May 5, 1993.
SUMMARY OF THE INVENTION
One aspect of the present invention is the preparation of the camptothecin derivative of formula (I′)
known by the chemical name “7-(4-methylpiperazino-methylene)-10,11-ethylenedioxy-20(R,S)-camptothecin,” which comprises cyclising the compound of formula (II″)
wherein X is halogen, particularly chloro, bromo, or iodo.
A particular aspect the invention provides a process for preparing a compound of formula (I) as shown in Scheme 1 wherein the configuration about the 20 position is (S)
Further aspects of the present invention provide the intermediate of formula (II′), particularly of formula (II), and novel intermediates used in the synthesis of the compounds of formula (II′) and (II) taught herein.
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Comins Daniel L.
Fang Francis Gerard
Huie Edward McDonald
Xie Shiping
Cooper & Dunham LLP
OSI Pharmaceuticals, Inc.
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