Deacetoxytaxol derivatives

Details Deacetoxytaxol derivatives Deacetoxytaxol derivatives

1996-12-06

1998-06-16

Trinh, Ba K.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549511, C07D30514

Patent

active

057672962

DESCRIPTION:

BRIEF SUMMARY
This is a 371 application of PCT/JP95/01163 filed on Jun. 9, 1995.


TECHNICAL FIELD

The present invention relates to novel taxol derivatives having an antitumor activity.


BACKGROUND ART

Taxol is a natural substance represented by the following chemical formula (i) and is obtainable in a small quantity from the bark of the Pacific yew tree, Taxus breviofolia, Taxaceae. ##STR2##
Taxol has been known to have an antitumor activity, and the unique mechanism of its action is based on an inhibitory activity on the disassembly of microtubules in cytokinesis. Thus, clinical application of taxol is expected as a new type of antitumor agent different from conventional antitumor agents.
Hitherto, only a very small quantity of taxol has been obtained from a natural source. However, in recent years, semi-synthesized taxol derivatives using, as a starting material, 10-O-deacetylbaccatin III represented by the following formula (ii) as a taxol precursor which is obtained relatively in a large quantity from needles of the Pacific yew tree have been reported (JP-A-03-505725). (The term "JP-A" as used herein means an unexamined published Japanese patent application.) ##STR3##
In particular, an attention has been drawn to Taxotere.RTM. having the following formula (iii) in view of its antitumor activity which is equal to or higher than that of taxol, and at present development of Taxotere.RTM. as an antitumor agent is in progress. ##STR4##
However, although taxol or derivatives represented by the above formula (iii), are potent as antitumor agents, it has been revealed that their effectiveness on cancers of digestive tracts, in particular, the cancer of large intestine, is weak, and hence derivatives having a strong antitumor activity have been desired.


DISCLOSURE OF INVENTION

Hitherto, taxol derivatives substituted at the 10-position with an acetoxy group or a hydroxy group, and those in which the hydroxy group is further substituted with an acyl group have been reported. Also an alkylaminocarbonyloxy group have been reported (EP-A-524093). Further, derivatives having only hydrogen atoms at the 10-position are also known (Tetrahedron Lett., 34, 4921 (1993)). As a result of extensive studies, the present inventors found that taxol derivatives in which an alkyl group has been introduced into the 10-position thereof exhibit a strong antitumor activity and completed the present invention.
The present invention relates to a compound represented by the general formula (I) ##STR5## wherein R.sup.1 represents an alkyl group, an alkenyl group or an alkynyl group (wherein these alkyl, alkenyl and alkynyl groups may have one or more substituents selected from the group consisting of a carboxyl group, an alkoxyl group, an aryloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a cyano group, a hydroxy group, an amino group, an alkylamino group, an acyl group, an acylamino group, an acyloxy group, an alkoxycarbonylamino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group and a 3- to 8-membered nitrogen containing saturated or unsaturated heterocyclic substituent (in which the heterocyclic substituent may have one or more alkyl groups on the carbon atom which is a constituent atom of the ring) represented by the formula: ##STR6## (wherein X represents an oxygen atom, a sulfur atom, CH.sub.2 CH--Y, NH or N--Y wherein Y represents an alkyl group); alkyl group; alkyl group; cycloalkyl group, an aryl group or a heterocyclic group (wherein these alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclic groups may have one or more substituent selected from the group consisting of a halogen atom, a hydroxy group, a carboxyl group, an alkyl group, an alkoxyl group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group); (wherein these alkyl, aryl and alkoxyl groups may have, one or more substituents selected from the group consisting of a halogen atom, a hy

Affiliated with

Also associated with

Rating

Deacetoxytaxol derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Deacetoxytaxol derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Deacetoxytaxol derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1727276