Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
2000-03-16
2000-10-24
Lambkin, Deborah C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514320, 544374, 544365, 544379, 546196, A61K 31495, A61K 31445, C07D40500, C07D40100, C07D40900
Patent
active
061368083
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to taxane derivatives having excellent solubility in water, and also to drugs containing the same.
BACKGROUND ART
Taxol (registered trademark) (i) represented by the following formula (i): ##STR2## is a diterpenoid available by extraction from the bark of the Pacific yew tree, Taxus brevifolia, and was isolated and determined in structure for the first time in 1971 by Wall, et al. (J. Am. Chem. Soc., 93, 2325, 1971). It has been reported to exhibit high efficacy against ovarian cancer and breast cancer (Ann. int. Med. 111, 273, 1989).
Formulation of Taxol into an injection however requires a special solvent, as it is a compound sparingly soluble in water. Taxol is therefore accompanied by problems in that the production of an injection is difficult and side effects may be induced by a solvent.
A great deal of work has therefore been conducted in recent years with a view to developing a water-soluble derivative of Taxol (Nicolaou, et al., Nature, 364, 464, 1993). Under the current circumstances, however, no derivatives have been found yet to be equipped with satisfactory properties.
Accordingly, an object of the present invention is to provide a novel Taxol derivative having improved water solubility and high antitumor activities.
DISCLOSURE OF THE INVENTION
With the foregoing circumstances in view, the present inventors have proceeded with extensive research. As a result, it has been found that a derivative of taxane (general name of the Taxol skeleton) represented by the below-described formula (1) has water solubility and antitumor activities, each extremely higher than Taxol and is hence useful as a drug, leading to the completion of the present invention.
The present invention therefore provides a taxane derivative represented by the following formula (1): ##STR3## [wherein, A represents a group ##STR4## (in which R.sup.1 represents a hydrogen atom, a substituted or unsubstituted alkyl group or a benzyloxycarbonyl group) or a group ##STR5## (in which R.sup.2 represents an amino group, a mono- or di-alkylamino group or a cyclic amino group), X represents an alkyl group, a pyridyl group, a thienyl group, a furyl group, a cycloalkyloxy group, an isopropyloxy group, a neopentyloxy group or a tert-amyloxy group, Y represents a hydrogen atom or a trialkylsilyl group, Ac represents an acetyl group, Bz represents a benzoyl group, and Ph represents a phenyl group] or a salt thereof.
Further, the present invention also provides a drug comprising the taxane derivative represented by the formula (1) or the salt thereof as an active ingredient.
Still further, the present invention also provides an antitumor agent comprising the taxane derivative represented by the formula (1) or the salt thereof as an active ingredient.
Still further, the present invention also provides a drug composition comprising the taxane derivative represented by the formula (1) or the salt thereof and a pharmaceutically acceptable carrier.
Still further, the present invention also provides use of the taxane derivative represented by the formula (1) or the salt thereof as a drug.
Still further, the present invention also provides use of the taxane derivative represented by the formula (1) or the salt thereof as an antitumor agent.
Still further, the present invention also provides a method for the treatment of a tumor, which comprises administering, to a patient suffering from the tumor, an effective amount of the taxane derivative represented by the formula (1) or the salt thereof.
BEST MODES FOR CARRYING OUT THE INVENTION
The taxane derivative according to the present invention is represented by the formula (1). The alkyl group represented by R.sup.1 as a substituent on the piperazino group among the groups represented by A may be an alkyl group having 1 to 10 carbon atoms, examples of which can include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-nonyl and n-decyl. Of these alkyl groups, those having 1 to 6 carbon atoms, especiall
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J. Kant, et al., Tetrahedron Letters, vol. 35, No. 1, pp. 5543-5546, "A Chemoselective Approach to Functionalize C-10 Position of 10-Deacetylbaccatin III. Synthesis and Biological Properties of Novel C-10 Taxol.RTM. Analogues," 1994.
Abe Atsuhiro
Nagata Hiroshi
Ogawa Takanori
Sawada Seigo
Shimizu Hideaki
Kabushiki Kaisha Yakul't Honsha
Lambkin Deborah C.
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