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US 5,703,117 AGranted
Hydrolysis-promoting hydrophobic taxane derivatives
AssigneeThe Liposome Company, Inc.
InventorsEric Mayhew, Shaukat Ali, Andrew S. Janoff
Life of this patent
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Abstract
Provided herein is a taxane having a hydrocarbon attached at the 2' and/or 7 positions, the hydrocarbon's alpha position being occupied by a "hydrolysis-promoting group" ("HPG"). Substitution of an HPG for the methylene unit ordinarily occupying the alpha position allows for enhanced in vivo hydrolysis of the hydrocarbon-taxane bond, and hence, for enhanced taxane therapeutic activity. Also provided herein are taxane-containing compositions, and methods of administering taxanes to animals, including those afflicted with cancers.
Claims25
A taxane having the formula:
- ##STR5## wherein:
- A.sup.1 is H or a group having the formula Z--C(O)NHCH(C.sub.6 H.sub.5)CH(OR)--C(O)--, A.sup.2 is H or CH.sub.3 C(O)-- and;
- Z is C.sub.6 H.sub.5 --, C.sub.6 H.sub.5 CH.sub.2 --O--, C(CH.sub.3).sub.3 --O-- or CH(CH.sub.3).dbd.C(CH.sub.3)--;
- each of R and R.sup.1 is H or a group having the formula Y.sup.1 Y.sup.2, provided that at least one of R and R.sup.1 is not H and provided that when A.sup.3 is H, R.sup.1 is not H;
- y.sup.1 is --O(O)OHX.sup.1 (CH.sub.2).sub.n1 (CH.dbd.CH).sub.n2 (CH.sub.2).sub.n3 (CH.dbd.CH).sub.n4 (CH.sub.2).sub.n5 (CH.dbd.CH).sub.n6 (CH.sub.2).sub.n7 (CH.dbd.CH).sub.n8 (CH.sub.2).sub.n9 --;
- the sum of n1+2n2+n3+2n4+n5+2n6+n7+2n8+n9 is an integer of from 1 to 21, each of n2, n4, n6 and n8 is independently zero or 1, n1 is zero or an integer of from 1 to 21, n3 is zero or an integer of from 1 to 18, n5 is zero or an integer of from 1 to 15, n7 is zero or an integer of from 1 to 12, n9 is zero or an integer of from 1 to 9 and each of n1 to n9 can be the same or different at each occurrence;
- X.sup.1 is an hydrolysis-promoting group;
- and
- y.sup.2 is --CH.sub.3, --CO.sub.2 H or --CH.sub.2 OH.
6 more elements
Dependencies are inferred from the claim text.