Certain substituted taxanes and pharmaceutical compositions containing them

Claim 2

A taxane derivative of the formula ##STR51## wherein R 1 and R 3 are independently selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR52## provided, however, R 1 and R 3 are not both phenyl; Q is CH 3 --, (CH 3 ) 3 C--, Cl, Br, F, or NO 2 , 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 3

The taxane derivative of claim 1 wherein R 1 is ##STR53## and Q is as defined in claim 1.

Claim 4

The taxane derivative of claim 2 wherein R 3 is phenyl or ##STR54## and Q is as defined in claim 1.

Claim 5

The taxane derivative of claim 1 wherein R 3 is ##STR55## and Q is as defined in claim 1.

Claim 6

The taxane derivative of claim 4 wherein R 1 is phenyl or ##STR56## and Q is as defined in claim 1.

Claim 7

The taxane derivative of claim 1 wherein Z is --OH or --OCOCH 3 .

Claim 8

The taxane derivative of claim 1 wherein R 1 or R 3 is phenyl and Z is --OH or --OCOCH 3 .

Claim 9

The taxane derivative of claim 4 wherein R 1 is phenyl and Z is --OCOCH 3 .

Claim 10

The taxane derivative of claim 3 wherein R 3 is phenyl and Z is --OCOCH 3 .

Claim 11

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

Claim 12

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

Claim 13

The composition of claim 11 wherein R 1 or R 3 is phenyl and Z is --OH or --OCOCH 3 .

Claim 14

The composition of claim 11 wherein R 1 or R 3 is phenyl, Z is --OCOCH 3 , and the taxane has the 2'R, 3'S configuration.

Claim 15

A taxane derivative having the formula: ##STR57## wherein R 1 and R 3 are independently selected from the group consisting of phenyl, naphthyl, C 6 H 5 CHCH--, ##STR58## provided, however, R 1 and R 3 are not both phenyl; Q is CH 3 --, (CH 3 ) 3 C--, CH 3 O--, Cl, Br, F, or NO 2 --, 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 hydrogen and functional groups which increase the water solubility of the taxane derivative, the functional groups having the formula --COGCOR 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 ##STR59## 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, NaOH, or KOH.

Claim 16

A taxane derivative having the formula: ##STR57## wherein R 1 and R 3 are independently selected from the group consisting of phenyl, naphthyl, C 6 H 5 CHCH--, ##STR58## provided, however, R 1 and R 3 are not both phenyl; Q is CH 3 --, (CH 3 ) 3 C--, CH 3 O--, Cl, Br, F, or NO 2 --, 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 hydrogen and functional groups which increase the water solubility of the taxane derivative, the functional groups having the formula --COGCOR 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 ##STR59## 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, NaOH, or KOH.

Claim 17

The taxane derivative of claim 14 wherein R 1 is ##STR60## and Q is as defined in claim 25.

Claim 18

The taxane derivative of claim 14 wherein R 3 is ##STR61## and Q is as defined in claim 25.

Claim 19

The taxane derivative of claim 14 wherein Z is --OH or --OCOCH 3 .

Claim 20

A taxane derivative of the formula ##STR62## wherein R 1 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR63## R 3 is selected from the group comprising naphthyl, C 6 H 5 CHCH--, and ##STR64## Q is CH 3 --, (CH 3 ) 3 C--, CH 3 --, Cl, Br, F, or NO 2 , 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 ##STR62## wherein R 1 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR63## R 3 is selected from the group comprising naphthyl, C 6 H 5 CHCH--, and ##STR64## Q is CH 3 --, (CH 3 ) 3 C--, CH 3 --, Cl, Br, F, or NO 2 , 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 22

A taxane derivative of the formula ##STR65## wherein R 1 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR66## R 3 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR67## provided, however, R 1 and R 3 are not both phenyl, Q is CH 3 --, (CH 3 ) 3 C--, CH 3 O--, Cl, Br, F, or NO 2 , 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 monocyclic aryl, and Ac is acetyl.

Claim 23

A taxane derivative of the formula ##STR65## wherein R 1 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR66## R 3 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR67## provided, however, R 1 and R 3 are not both phenyl, Q is CH 3 --, (CH 3 ) 3 C--, CH 3 O--, Cl, Br, F, or NO 2 , 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 monocyclic aryl, and Ac is acetyl.

Claim 24

A taxane derivative of the formula ##STR68## wherein R 1 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR69## R 3 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR70## Q is CH 3 --, (CH 3 ) 3 C--, CH 3 O--, Cl, Br, F, or NO 2 , Z is --OCOT 2 , T 2 is C 2 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocyclic aryl, and Ac is acetyl.

Claim 25

A taxane derivative of the formula ##STR68## wherein R 1 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR69## R 3 is selected from the group comprising phenyl, naphthyl, C 6 H 5 CHCH--, and ##STR70## Q is CH 3 --, (CH 3 ) 3 C--, CH 3 O--, Cl, Br, F, or NO 2 , Z is --OCOT 2 , T 2 is C 2 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or monocyclic aryl, and Ac is acetyl.