Certain alkoxy substituted taxanes and pharmaceutical compositions containing them

Claim 2

A taxane derivative of the formula ##STR15## wherein R 1 is phenyl, R 3 is CH 3 O-- or CH 3 CH 2 O--, Z is --OCOT 2 , T 2 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocylic aryl, and Ac is acetyl.

Claim 3

The taxane derivative of claim 1 wherein R 1 is phenyl and R 3 is CH 3 O--.

Claim 4

The taxane derivative of claim 1 wherein, R 3 is CH 3 CH 2 O--, Z is --OCOCH 3 , and the taxane derivative has the 2'R, 3'S configuration.

Claim 5

The taxane derivative of claim 1 wherein R 3 is CH 3 CH 2 O--.

Claim 6

The taxane derivative of claim 2 wherein Z is --OCOCH 3 .

Claim 7

The taxane derivative of claim 1 wherein R 3 is CH 3 CH 2 O--, Z is --OCOCH 3 , and the taxane derivative has the 2'R, 3'S configuration.

Claim 8

A pharmaceutical composition which contains the taxane derivative of claim 1 and one or more pharmacologically acceptable, inert or physiologically active diluents or adjuvants.

Claim 9

The composition of claim 7 wherein R 3 is CH 3 O--.

Claim 10

The composition of claim 7 wherein Z is --OCOCH 3 .

Claim 11

The composition of claim 7 wherein R 3 is CH 3 O--, Z is --OCOCH 3 , and the taxane derivative has the 2'R, 3'S configuration.

Claim 12

The composition of claim 7 wherein R 3 is CH 3 CH 2 O--.

Claim 13

The composition of claim 7 wherein R 3 is CH 3 CH 2 O--, Z is --OCOCH 3 , and the taxane derivative has the 2'R, 3'S configuration.

Claim 14

A taxane derivative of the formula ##STR16## wherein R 1 is phenyl, R 3 is CH 3 O--, or CH 3 CH 2 O--, 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, Ac is acetyl, and E 1 and E 2 are independently selected from functional groups which increase the water solubility of the taxane derivative, the functional groups having the formula --COGCOR.sup.1 wherein 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 or OH, R 2 =hydrogen or methyl, R 3 =(CH 2 ) n NR 6 R 7 or (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, or R 5 =hydrogen, lower alkyl containing 1 to 4 carbons, benzyl, hydroxyethyl, CH 2 CO 2 H, dimethylaminoethyl, or R 6 R 7 =lower alkyl containing 1 or 2 carbons, benzyl or R 6 and R 7 together with the nitrogen atom of NR 6 R 7 form the following rings ##STR17## R 8 =lower alkyl containing 1 or 2 carbons, or 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, CaOH, or KOH.

Claim 15

A taxane derivative of the formula ##STR16## wherein R 1 is phenyl, R 3 is CH 3 O--, or CH 3 CH 2 O--, 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, Ac is acetyl, and E 1 and E 2 are independently selected from functional groups which increase the water solubility of the taxane derivative, the functional groups having the formula --COGCOR.sup.1 wherein 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 or OH, R 2 =hydrogen or methyl, R 3 =(CH 2 ) n NR 6 R 7 or (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, or R 5 =hydrogen, lower alkyl containing 1 to 4 carbons, benzyl, hydroxyethyl, CH 2 CO 2 H, dimethylaminoethyl, or R 6 R 7 =lower alkyl containing 1 or 2 carbons, benzyl or R 6 and R 7 together with the nitrogen atom of NR 6 R 7 form the following rings ##STR17## R 8 =lower alkyl containing 1 or 2 carbons, or 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, CaOH, or KOH.

Claim 16

The taxane derivative of claim 13 wherein R 3 is CH 3 O--.

Claim 17

The taxane derivative of claim 13 wherein R 3 is CH 3 O-- and Z is --OCOCH 3 .

Claim 18

The taxane derivative of claim 13 wherein R 3 is CH 3 CH 2 O--.

Claim 19

The taxane derivative of claim 13 wherein R 3 is CH 3 CH 2 O-- and Z is --OCOCH 3 .

Claim 20

A taxane derivative of the formula ##STR18## wherein R 1 is phenyl, R 3 is CH 3 O--, 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, and Ac is acetyl.

Claim 21

A taxane derivative of the formula ##STR18## wherein R 1 is phenyl, R 3 is CH 3 O--, 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, and Ac is acetyl.