.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,232,477

« Back to Dashboard

Details for Patent: 6,232,477

Title: Methods of preparing new taxoids and pharmaceutical compositions containing them
Abstract:Methods of preparing new taxoids of general formula (I) are presented: ##STR1## in which: R.sub.4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 6 carbon atoms in an unbranched or branched chain, this radical unsubstituted or substituted with one or more halogen atoms, an alkoxy radical containing 1 to 4 carbon atoms, or alternatively R.sub.4 represents a cycloalkanoyloxy radical in which the cycloalkanoyl portion contains 4 to 8 carbon atoms, or alternatively R.sub.4 represents a benzoyloxy radical; R.sub.5 represents an alkoxy radical containing 1 to 4 carbon atoms, substituted by an alkylthio radical containing 1 to 4 carbon atoms; and Z represents a hydrogen atom or a radical of general formula: ##STR2##
Inventor(s): Bouchard; Herve (Thiais, FR), Bourzat; Jean-Dominique (Vincennes, FR), Commer.cedilla.on; Alain (Vitry-sur-Seine, FR)
Assignee: Aventis Pharma S.A. (Antony, FR)
Filing Date:Mar 17, 2000
Application Number:09/528,448
Claims:1. A method of preparing a taxoid of general formula: ##STR36##

in which:

Z represents a hydrogen atom or a radical of general formula: ##STR37##

in which:

R.sub.1 represents a benzoyl radical unsubstituted or substituted with one or more identical or different atoms or radicals selected from halogen atoms, and alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms or trifluoromethyl radicals, a thenoyl radical, a furoyl radical, and a radical R.sub.2 --O--C(.dbd.O)--, in which

R.sub.2 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms, a phenyl atoms, alkyl radicals containing 1 to 4 carbon atoms, and alkoxy radicals containing 1 to 4 carbon atoms), cyano radicals, carboxyl radicals, and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms;

R.sub.3 represents a phenyl radical;

R.sub.4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 6 carbon atoms in an unbranched or branched chain; and

R.sub.5 represents an alkoxy radical containing 1 to 4 carbon atoms in an unbranched or branched chain, substituted by an alkylthio radical containing 1 to 4 carbon atoms, comprising:

silylating a baccatin of formula (IX) ##STR38##

to obtain a silylated baccatin, where the silylation occurs at position 7;

acetylating said silylated baccatin to obtain a protected baccatin, wherein said acetylation occurs at position 10;

coupling the protected baccatin with an oxazolidine ring optionally monosubstituted or gem-disubstituted at position 2 to produce a coupled ester;

deprotecting said coupled ester with an acid to produce a desilylated taxoid;

reacting said desilylated taxoid in a Pummerer reaction to produce a methylthiomethylether derivative; and

deprotecting said methylthiomethylether derivative with an acid to produce the desired taxoid.

2. The method for preparing a taxoid according to claim 1 in which Z represents a radical of general formula (II), in which

R.sub.1 represents a benzoyl radical or a radical R.sub.2 --O--C(.dbd.O)-- in which R.sub.2 represents a tert-butyl radical;

R.sub.3 represents a phenyl radical;

R.sub.4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 4 carbon atoms; and

R.sub.5 represents an alkoxy radical containing 1 to 4 carbon atoms substituted by a methylthio radical.

3. The method for preparing a taxoid according to claim 1 for which Z represents a hydrogen atom or a radical of general formula (II) in which R.sub.1 represents a benzoyl radical or a radical R.sub.2 --O--C(.dbd.O)-- in which

R.sub.2 represents a tert-butyl radical;

R.sub.3 represents a phenyl radical;

R.sub.4 represents an acetoxy or methoxyacetoxy radical; and

R.sub.5 represents a methylthiomethoxy radical.

4. The method of preparing a taxoid of claim 1, wherein R.sub.4 is acetoxy.

5. The method of claim 1 wherein the taxoid (2R,3S)-3-benzoyl-2-hydroxy-3-phenyl propionate of 4,10.beta.-diacetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1,13.alpha.-dihy droxy-7.beta.-methylthiomethyloxy-9-oxo-tax-11-ene (XXXIV) ##STR39##

is prepared.

6. The method of claim 1 wherein the taxoid (2R,4S,5R) -3-benzoyl-2-(4-methoxyphenyl)-4-phenyloxazolidine-5-carboxylate of 4,10.beta.-diacetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1,13.alpha.-dihy droxy-7.beta.-methylthiomethyloxy-9-oxo-tax-11-ene (XXXIII) ##STR40##

is prepared.

7. A method of preparing a pharmaceutical composition, comprising preparing least one taxoid by the method of claim 1, in which Z represents a radical of general formula (II), and combining said at least one taxoid with one or more pharmaceutically acceptable carriers.

8. A method of preparing a pharmaceutical composition, comprising preparing at least one taxoid by the method of claim 5 or claim 6, and combining said at least one taxoid with one or more pharmaceutically acceptable carriers.

9. The method of claim 8, wherein the pharmaceutically acceptable carrier is a diluent or adjuvant.

10. The method of claim 8, further comprising another pharmacologically active compound.

11. The method of claim 9, further comprising another pharmacologically active compound.

12. A method of preparing a taxoid of general formula (XIV) ##STR41##

comprising:

silylating the baccatin of formula (IX) ##STR42##

to obtain a silylated baccatin wherein said silylation occurs at position 7;

acetylating said silylated baccatin to obtain a protected baccatin of formula (XXX), wherein said acetylation occurs at position 10;

coupling the protected baccatin of formula (XXX) ##STR43##

with a compound of formula (XXXa) ##STR44##

to produce a coupled ester of formula (XXXI); ##STR45##

deprotecting said coupled ester with an acid to produce a desilylated taxoid of formula (XXXII); ##STR46##

reacting said desilylated taxoid in a Pummerer reaction to produce a methylthiomethylether derivative of formula (XXXIII); ##STR47##

and

deprotecting said methylthiomethylether derivative with an acid to produce a compound of formula (XXXIV).
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc