9, 10-α, α-OH-taxane analogs and methods for production thereof

摘要

Provided herein are compounds, compositions containing the compounds, and methods for the treatment of cancer in a cancer patient. In particular, the compounds are made by a process comprising treating a first compound represented by either Formula G′ or Formula M′:;
with a second compound of generalized formula R8R9C(OCH3)2 and an acid selected from the group consisting of camphor sulfonic acid (CSA), p-toluene sulfonic acid (PTSA), hydrochloric acid (HCl) and acetic acid (AcOH), wherein R1 and R2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group; R7 is an alkyl group, an olefinic group, or an aromatic group; P1 is a hydroxyl protecting group; P5 is H or an acid labile protecting group at the 7-O position; R8 is H, alkyl group, olefinic or aromatic group; and R9 is: H, alkyl group, olefinic or aromatic or is as defined in the specification.

主权项

1. A pharmaceutical formulation comprising a first taxane compound in a concentration sufficient to inhibit growth of cancer cells that have developed multi-drug resistance (MDR); and a pharmaceutically acceptable carrier, the first taxane compound being produced by treating a second taxane compound represented by either Formula G′ or Formula M′ with a third compound of generalized formula R8R9C(OCH3)2 and an acid selected from the group consisting of camphor sulfonic acid (CSA), p-toluene sulfonic acid (PTSA), hydrochloric acid (HCl) and acetic acid (AcOH):wherein: R1 and R2 are each selected from H, an alkyl group, an olefinic group, an aromatic group, an O-alkyl group, an O-olefinic group, or an O-aromatic group;
R7 is: P1 is a hydroxyl protecting group; P5 is H or an acid labile protecting group at the 7-O position; R8 is: H, alkyl group, olefinic or aromatic group; R9 is: H, alkyl group, olefinic or aromatic or is:and a pharmaceutically acceptable carrier.