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Furyl and thienyl substituted taxanes and pharmaceutical compositions containing them

Assignee: Florida State University
•
Filing: 1992-04-03
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Granted: 1993-07-13
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Expires: 2012-04-03
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Abstract

Abstract A taxane derivative of the formula ##STR1## wherein ##STR2## Z is --OT 1 , T 1 is hydrogen, hydroxyl protecting group, or --COT 2 , T 2 is H, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl or monocylic aryl, R 3 is benzoyl, substituted benzoyl or C 1 -C 6 alkoxycarbonyl, Ac is acetyl, and E 1 and E 2 are independently selected from hydrogen and functional groups which increase the water solubility of the taxane derivative are useful as antitumor agents.

Inventors

  • 👤 Robert A. Holton
  • 👤 Hossain Nadizadeh
  • 👤 Ronald J. Beidiger

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-28 22:05
CPC Classifications
C; C07; C07D; C07D407/00; C07D407/02; C07D407/12; A; A61; A61P; A61P35/00; C07D305/00; C07D305/14; C07D409/00; C07D409/02; C07D409/12; C07F; C07F7/00; C07F7/003; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55

Claims Analysis

Total Claims: 13
Claim 1
Independent Claim 276 words
A taxane derivative of the formula ##STR22## wherein ##STR23## Z is --OT 1 , T 1 is hydrogen, hydroxyl protecting group, or --COT 2 , T 2 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl, R 3 is benzoyl, substituted benzoyl or C 1 -C 6 alkoxycarbonyl wherein the substitution is on the para-position of the benzoyl group and the substituent is selected from the group consisting of Cl, Br, F, NO 2 -- and CH 3 O--, Ac is acetyl, E 1 and E 2 are independently hydrogen or --COGCOR 1 G is ethylene, propylene, CH═CH, 1,2-cyclohexane, or 1,2-phenylene, R 1 =OH base, NR 2 R 3 , OR 3 , SR 3 , OCH 2 CONR 4 R 5 , OH R 2 =hydrogen, methyl R 3 =(CH 2 ) n NR 6 R 7 ; (CH 2 ) n N.sup.⊕ R 6 R 7 R 8 X.sup.⊖ n=1 to 3 R 4 =hydrogen, lower alkyl containing 1 to 4 carbons R 5 =hydrogen, lower alkyl containing 1 to 4 carbons, benzyl, hydroxyethyl, CH 2 CO 2 H, dimethylaminoethyl R 6 R 7 =lower alkyl containing 1 to 2 carbons, benzyl or R 6 and R 7 together with the nitrogen atom of NR 6 R 7 form the following rings ##STR24## R 8 =lower alkyl containing 1 to 2 carbons, benzyl X.sup.⊖ =halide and base=NH 3 , (HOC 2 H 4 ) 3 N, N(CH 3 ) 3 , CH 3 N(C 2 H 4 OH) 2 , NH 2 (CH 2 ) 6 NH 2 , N-methylglucamine, NaOH, or KOH.
Claim 2
Dependent Claim 276 words
A taxane derivative of the formula ##STR22## wherein ##STR23## Z is --OT 1 , T 1 is hydrogen, hydroxyl protecting group, or --COT 2 , T 2 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl, R 3 is benzoyl, substituted benzoyl or C 1 -C 6 alkoxycarbonyl wherein the substitution is on the para-position of the benzoyl group and the substituent is selected from the group consisting of Cl, Br, F, NO 2 -- and CH 3 O--, Ac is acetyl, E 1 and E 2 are independently hydrogen or --COGCOR 1 G is ethylene, propylene, CH═CH, 1,2-cyclohexane, or 1,2-phenylene, R 1 =OH base, NR 2 R 3 , OR 3 , SR 3 , OCH 2 CONR 4 R 5 , OH R 2 =hydrogen, methyl R 3 =(CH 2 ) n NR 6 R 7 ; (CH 2 ) n N.sup.⊕ R 6 R 7 R 8 X.sup.⊖ n=1 to 3 R 4 =hydrogen, lower alkyl containing 1 to 4 carbons R 5 =hydrogen, lower alkyl containing 1 to 4 carbons, benzyl, hydroxyethyl, CH 2 CO 2 H, dimethylaminoethyl R 6 R 7 =lower alkyl containing 1 to 2 carbons, benzyl or R 6 and R 7 together with the nitrogen atom of NR 6 R 7 form the following rings ##STR24## R 8 =lower alkyl containing 1 to 2 carbons, benzyl X.sup.⊖ =halide and base=NH 3 , (HOC 2 H 4 ) 3 N, N(CH 3 ) 3 , CH 3 N(C 2 H 4 OH) 2 , NH 2 (CH 2 ) 6 NH 2 , N-methylglucamine, NaOH, or KOH.
Claim 3
Dependent Claim 101 words
A taxane derivative of the formula ##STR25## wherein ##STR26## Z is --OT 1 , T 1 is hydrogen, hydroxyl protecting group, or --COT 2 , T 2 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl, R 3 is benzoyl, substituted benzoyl or C 1 -C 6 alkoxycarbonyl wherein the substitution is on the para-position of the benzoyl group and the substituent is selected from the group consisting of Cl, Br, F, NO 2 -- and CH 3 O--, Ac is acetyl, and E 1 and E 2 are hydrogen.
Claim 4
Dependent Claim 101 words
A taxane derivative of the formula ##STR25## wherein ##STR26## Z is --OT 1 , T 1 is hydrogen, hydroxyl protecting group, or --COT 2 , T 2 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl, R 3 is benzoyl, substituted benzoyl or C 1 -C 6 alkoxycarbonyl wherein the substitution is on the para-position of the benzoyl group and the substituent is selected from the group consisting of Cl, Br, F, NO 2 -- and CH 3 O--, Ac is acetyl, and E 1 and E 2 are hydrogen.
Claim 5
Dependent Claim 10 words
The taxane of claim 2 wherein R 1 is ##STR27##
Claim 6
Dependent Claim 18 words
The taxane of claim 2 wherein R 1 is ##STR28## and the taxane has the 2'R, 3'S configuration.
Claim 7
Dependent Claim 10 words
The taxane of claim 2 wherein R 1 is ##STR29##
Claim 8
Dependent Claim 18 words
The taxane of claim 2 wherein R 1 is ##STR30## and the taxane has the 2'R, 3'S configuration.
Claim 9
Dependent Claim 23 words
A pharmaceutical composition which contains the taxane of claim 1 and one or more pharmacologically acceptable, inert or physiologically active diluents or adjuvants.
Claim 10
Dependent Claim 10 words
The composition of claim 7 wherein R 1 is ##STR31##
Claim 11
Dependent Claim 18 words
The composition of claim 7 wherein R 1 is ##STR32## and the taxane has the 2'R, 3'S configuration.
Claim 12
Dependent Claim 10 words
The composition of claim 7 wherein R 1 is ##STR33##
Claim 13
Dependent Claim 18 words
The composition of claim 7 wherein R 1 is ##STR34## and the taxane has the 2'R, 3'S configuration.

References Cited (Backward Citations)

EP0253739A1 Cited
US4814470A Cited
US4857653A Cited
EP0253738B1 Cited
US4942184A Cited
EP0336841A1 Cited
EP0336840A1 Cited
US4924012A Cited
US4924011A Cited
US5015744A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1996-07-12 1997-01-11 1997-07-13 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2000-07-12 2001-01-11 2001-07-13 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2004-07-12 2005-01-11 2005-07-13 $7700.00 Window Closed / Lapsed

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