DEUTERATED AND/OR FLUORINATED TAXANE DERIVATIVES
The invention relates to (among other things) deuterated and/or fluorinated docetaxel and cabazitaxel and derivatives thereof, as well as compositions comprising each of the foregoing.
1 . A compound selected from the group consisting of a deuterated cabazitaxel and a deuterated docetaxel.
2 . A compound selected from the group consisting of a fluorinated cabazitaxel and a fluorinated docetaxel.
3 . A compound having a structure encompassed by the following formula:
wherein:
R 10 is selected from the group consisting of OH, OC 1-6 organic radical, and a deuterated/fluorinated OC 1-6 organic radical;
R 7 is selected from the group consisting of OH, a OC 1-6 organic radical, and a deuterated/fluorinated OC 1-6 organic radical;
D 7 is selected from the group consisting of H, D and F;
D 8 is selected from the group consisting of H, D and F;
D 9 is selected from the group consisting of H, D and F;
D 10 is selected from the group consisting of H, D and F;
D 11 is selected from the group consisting of H, D and F;
D 12 is selected from the group consisting of H, D and F;
D 13 is selected from the group consisting of H, D and F;
D 14 is selected from the group consisting of H, D and F; and
D 15 is selected from the group consisting of H, D and F,
and further wherein at least one atom in the compound is either D or F,
and pharmaceutically acceptable salts thereof.
4 . The compound of claim 3 , wherein R 10 is a deuterated/fluorinated OC 1-6 organic radical.
5 . The compound of claim 4 , wherein the deuterated/fluorinated OC 1-6 organic radical is
wherein D 4 is selected from the group consisting of H, D, F and CF 3 , D 5 is selected from the group consisting of H, D, F and CF 3 , and D 6 is selected from the group consisting of H, D, F and CF 3 .
6 . The compound of claim 1 , wherein R 7 is a deuterated/fluorinated OC 1-6 organic radical.
7 . The compound of claim 6 , wherein the deuterated/fluorinated OC 1-6 organic radical is
wherein D 1 is selected from the group consisting of H, D, F and CF 3 , D 2 is selected from the group consisting of H, D, F and CF 3 , and D 3 is selected from the group consisting of H, D, F and CF 3 .
8 . The compound of claim 3 , wherein each of R 10 and R 7 are H.
9 . The compound of claim 3 , wherein each of R 10 and R 7 are CH 3 .
10 . The compound of claim 3 , wherein each of R 10 is CH 3 and R 7 is H.
11 . The compound of claim 3 , wherein each of R 10 is H and R 7 is CH 3 .
12 . The compound of claim 3 , having a structure encompassed by the following formula:
wherein:
D 1 is selected from the group consisting of H, D, F and CF 3 ;
D 2 is selected from the group consisting of H, D, F and CF 3 ;
D 3 is selected from the group consisting of H, D, F and CF 3 ;
D 4 is selected from the group consisting of H, D, F and CF 3 ;
D 5 is selected from the group consisting of H, D, F and CF 3 ;
D 6 is selected from the group consisting of H, D, F and CF 3 ;
D 7 is selected from the group consisting of H, D and F;
D 8 is selected from the group consisting of H, D and F;
D 9 is selected from the group consisting of H, D and F;
D 10 is selected from the group consisting of H, D and F;
D″ is selected from the group consisting of H, D and F;
D 12 is selected from the group consisting of H, D and F;
D 13 is selected from the group consisting of H, D and F;
D 14 is selected from the group consisting of H, D and F; and
D 15 is selected from the group consisting of H, D and F,
and further wherein at least one of D 1 , D 2 , D 3 , D 4 , D 5 , D 6 , D 7 , D 8 , D 9 , D 10 , D 11 , D 12 , D 13 , D 14 and D 15 is not H, and pharmaceutically acceptable salts thereof.
13 . The compound of claim 3 , selected from the group consisting of
14 . The compound of claim 3 , having a structure corresponding to:
15 . The compound of claim 3 , having a structure corresponding to:
16 . The compound of claim 3 , having a structure corresponding to:
17 . The compound of claim 3 , having a structure corresponding to:
18 . A composition comprising a compound of claim 1 and an optional pharmaceutically acceptable excipient.
19 . A dosage form comprising a compound of claim 1 .
20 . A method comprising deuterating a taxane.
21 . A method comprising fluorinating a taxane.
22 . A method comprising administering a compound of claim 1 to a mammal in need thereof.
23 . A compound having a structure encompassed by the following formula:
wherein PG is H or an amine protecting group, and R is selected from the group consisting of H, lower alkyl or arylakyl.
24 . A compound having a structure encompassed by the following formula:
wherein PG is H or an amine protecting group, R is H or lower alkyl, and m is an integer of from 1 to 8, inclusive.