Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1988-02-09
1991-09-10
Brown, Johnnie R.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 26, C07H 1900
Patent
active
050475215
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to novel 5-fluorouracil derivatives.
BACKGROUND ART
The 5-fluorouracil derivatives of the present invention are novel compounds undisclosed in literature.
We carried out extensive research in an attempt to improve the antitumor action of known 5-fluorouracils and 2'-deoxy-5-fluorouridines and to render them less toxic, and succeeded in synthesizing a class of novel 2'-deoxy-5-fluorouridines which are substituted at the 3'- and/or 5'-position with a phenyl-lower alkyl group having a specific substituent, heterocyclic lower alkyl group optionally having a specific substituent or unsaturated heterocyclic group optionally having a specific substituent; and a class of novel 5-fluorouracils which are substituted at the 1-position with a lower alkyl group having a specific substituent and which have a specific acyl group introduced into the 3-position. We have found that these novel compounds are outstanding in anticancer action, absorption, long lasting effect and therapeutic index, low in toxicity, and therefore very useful as antitumor agents.
We have also successfully synthesized novel compounds which are usable as intermediates for synthesis of said novel compounds useful as antitumor agents.
DISCLOSURE OF INVENTION
The present invention provides a 5-fluorouracil derivative represented by the formula ##STR3## wherein R.sup.y is a hydrogen atom or acyl group, Z is a phenyl-lower alkoxy-lower alkyl group, thienyl-lower alkyl group optionally substituted with halogen atom on the thienyl ring , or a group ##STR4## wherein R.sup.1 and R.sup.2 are each a hydrogen atom, acyl group, phenyl-lower alkyl group having a group R.sup.x OCO-- on the phenyl ring, or a group --(A).sub.n B, the acyl group represented by R.sup.y, R.sup.1 and R.sup.2 being lower alkanoyl group, benzoyl group optionally having 1 to 3 substituents selected from halogen atom, lower alkyl group and lower alkoxy group, phenoxycarbonyl group or a group R.sup.x OCOYCO--, R.sup.x in the group R.sup.x OCO-- and the group R.sup.x OCOYCO-- being a pyridyl group optionally having 1 to 4 substituents selected from the group consisting of hydroxyl group, oxo group, halogen atom, amino group, carboxyl group, cyano group, nitro group, carbamoyl group, lower alkylcarbamoyl group, carboxy-lower alkylcarbamoyl group, lower alkoxycarbonyl-lower alkylcarbamoyl group, phenylcarbamoyl group optionally having on the phenyl ring 1 to 3 substituents selected from halogen atom, lower alkyl group and lower alkoxy group, lower alkyl group, lower alkenyl group, lower alkoxycarbonyl group, tetrahydrofuranyl group, tetrahydropyranyl group, lower alkoxy-lower alkyl group, phenyl-lower alkoxy-lower alkyl group, lower alkylthio-lower alkyl group, lower alkanoyloxy group, benzoyloxy group optionally having 1 to 3 substituents selected from halogen atom, lower alkyl group and lower alkoxy group, and phenoxycarbonyloxy group, Y in the group R.sup.x OCOYCO-- being an arylene group, A in the group --(A).sub.n B being a lower alkylene group, n in said group being 0 or 1 and B in said group being a 5- or 6-membered unsaturated heterocyclic group having 1 to 4 hetero-atoms selected from nitrogen, oxygen and sulfur and optionally having a benzene ring, naphthalene ring or pyridine ring condensed therewith, the heterocyclic ring optionally having 1 to 3 substituents attached thereon, the substituents being selected from the group consisting of hydroxyl group, cyano group, halogen atom, lower alkyl group, lower alkoxy group, phenyl group, lower alkoxy group having 1 or 2 phenyl groups optionally substituted with lower alkoxy group or halogen atom on the phenyl ring, phenoxy group optionally substituted with halogen atom or lower alkoxy group on the phenyl ring, nitro group, oxo group, benzoyloxy group, lower alkoxycarbonyl group, lower alkanoyloxy group, phenyl-lower alkylthio group and a group R.sup.x OCO-- (wherein R.sup.x is as defined above), with the proviso that when R.sup.1 is a hydrogen atom or acyl group, R.sup.2 is not a hydrogen atom
REFERENCES:
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Chemical Abstracts, vol. 101, 1984, p. 657, Abstract 55478 y published in Columbus, Ohio, U.S.A., on Feb. 16, 1984.
Fujii Setsuro
Hirohashi Mitsuru
Kojima Yutaka
Yamamoto Yoshihito
Brown Johnnie R.
Otsuka Pharmaceutical Co. Ltd.
Wilson James O.
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