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EP0505047A1 Expired / Lapsed EP ⏱️ 0.0 years remaining

Rearranged taxol compounds and method of using in testing of in vivo activity

Assignee: Virginia Tech Intellectual Properties Inc
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Filing: 1992-02-27
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Granted: —
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Expires: 2012-02-27
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Abstract

Abstract In a preferred embodiment, taxol is treated with mesyl chloride to prepare a taxol derivative with a contracted A-ring, which has comparable activity to taxol in a tubulin depolymerization assay, and which shows cytotoxicity against KB cells in a cell culture assay. In an alternate preferred embodiment, taxol is treated with triethyloxonium tetrafluoroborate (Meerwein's reagent) to produce a taxol derivative with an opened oxetane ring. In another alternate preferred embodiment, reaction of taxol with acetyl chloride yields a taxol derivative in which the oxetane ring is opened and the A-ring is contracted. All of the aforementioned products show in vivo activity in KB cell culture assays. Further, the preferred compounds have different in vivo activities, which makes them ideal to form a range of standards for use in biological testing of other compounds.

Inventors

  • 👤 David G.I. Kingston
  • 👤 Gamini Samaranyake

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-08 14:18
CPC Classifications
C; C07; C07D; C07D305/00; C07D305/14; A; A61; A61P; A61P35/00; C07D317/00; C07D317/08; C07D317/44; C07D317/70

Claims Analysis

Total Claims: 15
Claim 1
Independent Claim 23 words
A rearranged taxol compound having the following structure: wherein R1 is C(O)CH₃, R2 is H or Si(CH₂CH₃)₃, and R3 is H or Si(CH₂CH₃)₃.
Claim 2
Dependent Claim 25 words
A taxol compound having the following structure: wherein R1 is C(O)CH₃, R2 is H or OSi(CH₂CH₃)₃, R3 is OSO₂CH₃, and R4 is H or Si(CH₂CH₃)₃.
Claim 3
Dependent Claim 19 words
A rearranged taxol compound having the following structure: wherein R1 is H or C(O)CH₃, R2 is H or C(O)CH₃.
Claim 4
Dependent Claim 33 words
A process for producing taxol compounds with an A-ring contracted to five members, comprising the steps of: (a) protecting hydroxylated positions on taxol; and (b) reacting said protected taxol with a mesyl halide.
Claim 5
Dependent Claim 18 words
A process according to claim 4, further comprising the step of deprotecting said protected taxol to form A-Nor-taxol.
Claim 6
Dependent Claim 40 words
A process for producing taxol compounds with an A-ring contracted to five members, comprising the steps of: (a) reacting taxol with a trialkylsilyl halide to form a taxol silyl ether; and (b) reacting taxol silyl ether with a mesyl halide.
Claim 7
Dependent Claim 26 words
A process according to claim 6, further comprising the step of: (c) following step (b) removing silyl groups on said taxol silyl ether to yield A-Nor-taxol.
Claim 8
Dependent Claim 19 words
The process of claim 7, wherein step (c) is carried out by reacting said silylated A-Nor-taxol with pyridinium hydrofluoride.
Claim 9
Dependent Claim 20 words
The process of claim 6, 7 or 8, wherein said steps (a) and (b) are carried out in basic conditions.
Claim 10
Dependent Claim 24 words
The process of any one of claims 6, to 9, wherein said trialkylsiyl halide is triethylsilyl chloride, and said mesyl halide is mesyl chloride.
Claim 11
Dependent Claim 44 words
A process for producing rearranged taxol compounds comprising the reaction of taxol with an oxonium compound to form a taxol compound with an opened oxetane ring; and reacting said taxol compound with an opened oxetane ring with dimethoxypropane in the presence or p-toluenesulfonic acid.
Claim 12
Dependent Claim 12 words
The process of claim 11, wherein said oxonium compound is triethyloxonium tetrafluoroborate.
Claim 13
Dependent Claim 64 words
A process for determining the bioactivity of a compound,comprising treatment of an unknown compound in a bioactivity test and treatment under the same conditions of at least one of the compounds selected from the group comprised of A-Nor-taxol, a taxol compound with an opened oxetane ring, and a taxol compound with an opened oxetane ring and a five member A-ring fused to the B-ring.
Claim 14
Dependent Claim 14 words
A cytotoxic agent comprising a taxol compound having an A-ring contracted to five members.
Claim 15
Dependent Claim 15 words
The cytotoxic agent of claim 14, wherein said taxol compound has an intact oxetane D-ring.

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