WO1982001370A1 - N-phthalidyl-5-fluorouracil derivatives - Google Patents

N-phthalidyl-5-fluorouracil derivatives Download PDF

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Publication number
WO1982001370A1
WO1982001370A1 PCT/JP1981/000260 JP8100260W WO8201370A1 WO 1982001370 A1 WO1982001370 A1 WO 1982001370A1 JP 8100260 W JP8100260 W JP 8100260W WO 8201370 A1 WO8201370 A1 WO 8201370A1
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WO
WIPO (PCT)
Prior art keywords
group
compound
phthalidyl
water
hydrogen atom
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP1981/000260
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English (en)
French (fr)
Japanese (ja)
Inventor
Pharma Co Ltd Grelan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aska Pharmaceutical Co Ltd
Original Assignee
Grelan Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Grelan Pharmaceutical Co Ltd filed Critical Grelan Pharmaceutical Co Ltd
Priority to HU813269A priority Critical patent/HU188152B/hu
Priority to BR8108842A priority patent/BR8108842A/pt
Priority to AT81902732T priority patent/ATE13764T1/de
Priority to DE8181902732T priority patent/DE3170942D1/de
Publication of WO1982001370A1 publication Critical patent/WO1982001370A1/ja
Priority to DK256982A priority patent/DK151630B/da
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • N-phthalyl-5-phenylamine derivatives especially formula (I)
  • R 2 is a phthalidyl group (a hydrogen atom, a halogen atom, an alkoxy group)
  • an alkyl group is a hydrogen atom, an acyl group or a cyclic ether group
  • Phthalyl — 5 This is a phenolic derivative, and its purpose is to have an excellent antitumor effect. And to provide a substance that can be used as an anticancer drug.
  • Honkiaki has no such shortcomings of the so-called 5-hydroxyphenol derivative, is less toxic, and is stable in oily state. It is melted and absorbed into the body.
  • the purpose is to provide useful compounds
  • the present invention relates to a compound represented by the formula (I): 3 ′ ⁇
  • the compounds provided by the formula (I) of the present invention are, for example,
  • substitution position of 5 is not particularly limited, and 1 or more may be substituted at the 4 , 5, 5 or 7 positions of the group, respectively, and is used throughout the present specification.
  • alkyl group means a straight-chain or branched alkyl group having about 5 to about 5 carbon atoms, such as methyl, Echinore, F. Mouth pinole, butenole, amino, and hexinole groups: These are straight-chain or branched alquinone groups, respectively.
  • Alkoxy group means the above-mentioned alkyl group-substituted alkoxy group.
  • the water content of the compound in which R 4 is an acyl group in ( ⁇ ) is water, methanol, ethanol, isobronol, etc. This is done by alcohol.
  • the sensitizing medium there may be used, for example, salt, sulfur or the like. Yes, such as bions, may be added.
  • the corresponding 10 general formulas ( ⁇ , ( ⁇ )) Is performed by acylating a compound of a hydrogen atom, or equivalent to one or more of N 3 —Asynole 5—Fluoro port
  • the reaction is carried out by reacting the sil compound with an ⁇ -genated phthalide compound of the general formula (IV), in which case the acylation is carried out.
  • the reaction may be carried out by reacting the corresponding acyl halide or anhydride with such a compound.
  • acetyl chloride, sulfide, or the like may be used.
  • one phthalate loop 5 fluoroplastic induction force; manufactured; ⁇ ,-, misaligned
  • the compounds also have antitumor activity and are useful compounds as! J cancers.
  • C SK / He mice were inoculated subcutaneously into the flank of BaI'D mice, and a sample suspended or dissolved in a 0.3% CMC aqueous solution twice a day from the day after inoculation. Oral administration for 20 days and inoculation
  • mice for comparison ⁇ - (2-tetrahydrofuranyl-5.—full-year-old. The same was done.
  • mice from S to 7 weeks of age were grouped into 10 mice, each sample was orally administered, and the presence or absence of death over 3 weeks was observed, and the LDso value was determined.
  • the result is as follows.
  • Compound 1 Blood concentration> 2,500 nig / kg>
  • N 1—phthalyl 5—fluorouracil ( ⁇ ) and ⁇ , N 3 -diphthalidine 5 1.30 g of full-year-old uracilil were added to 10 ml of D 2 F (dissolved in water, stirred under ice-cooling, and hydrogenated sodium (content 60%) 0.80 g was added. Then, a solution of 4.59 g of 3-bromophthalide dissolved in 5 ml of DI F was added dropwise, and after 15 minutes under ice-cooling, further at room temperature for 3 hours. Stirring Add water 10 O mi and extract with crumb porch.Cloth porch layer is dried with water, water. Was added twice with 50 ml of ⁇ -hexane, and 20 ml of chloroform was added. The precipitated crystals 5 were removed. Ni-phthalyl-5-fluoropropyl Shinore
  • N 3 diphthalene 1-5 — ⁇ ⁇ . That is, the first diastereomer was obtained from the first ⁇ ⁇ -form eluate, and this was recrystallized from the vinegar and the melting point was 25. 5 to 2 5 8. To obtain 0.23 g (6%) of colorless granular crystals.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Thin Film Transistor (AREA)
PCT/JP1981/000260 1980-10-09 1981-09-30 N-phthalidyl-5-fluorouracil derivatives Ceased WO1982001370A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
HU813269A HU188152B (en) 1981-09-30 1981-09-30 Process for the preparation of anticancer n-phthalidyl-5-fluoro-uracile derivatives
BR8108842A BR8108842A (pt) 1980-10-09 1981-09-30 Derivados da n-ftalidil-5-fluoruracila
AT81902732T ATE13764T1 (de) 1980-10-09 1981-09-30 N-phthalidyl-5-fluor-uracil-abkoemmlinge.
DE8181902732T DE3170942D1 (en) 1980-10-09 1981-09-30 N-phthalidyl-5-fluorouracil derivatives
DK256982A DK151630B (da) 1980-10-09 1982-06-08 Analogifremgangsmaade til fremstilling af n-phthalidyl-5-fluoruracilderivater

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP55140509A JPS5767578A (en) 1980-10-09 1980-10-09 N-phthtalidy-5-fluorouracil derivative
JP80/140509801009 1980-10-09

Publications (1)

Publication Number Publication Date
WO1982001370A1 true WO1982001370A1 (en) 1982-04-29

Family

ID=15270296

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1981/000260 Ceased WO1982001370A1 (en) 1980-10-09 1981-09-30 N-phthalidyl-5-fluorouracil derivatives

Country Status (10)

Country Link
US (1) US4528372A (https=)
EP (1) EP0062068B1 (https=)
JP (1) JPS5767578A (https=)
AT (1) ATE13764T1 (https=)
AU (1) AU543835B2 (https=)
BR (1) BR8108842A (https=)
DE (1) DE3170942D1 (https=)
DK (1) DK151630B (https=)
SU (1) SU1258325A3 (https=)
WO (1) WO1982001370A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018080161A1 (ko) * 2016-10-25 2018-05-03 경북대학교 산학협력단 항병원성 활성 및 바이오필름 형성 억제 효과를 나타내는 화합물의 신규한 용도

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5993075A (ja) * 1982-11-18 1984-05-29 Shionogi & Co Ltd １−フタリジル−５−フルオロウラシル誘導体の製造法
US4864021A (en) * 1984-10-30 1989-09-05 Otsuka Pharmaceutical Co., Ltd. 5-fluorouracil derivatives

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2997481A (en) * 1958-09-02 1961-08-22 Dow Chemical Co Phthalides
JPS5324952B2 (https=) * 1973-11-28 1978-07-24
GB1518391A (en) * 1976-01-07 1978-07-19 Taiho Pharmaceutical Co Ltd Anti-tumour composition
US4196202A (en) * 1977-12-20 1980-04-01 Taiji Okada Carcinostatic composition containing 3-N-o-toluyl-5-fluorouracil producing the same
JPS5716881A (en) * 1980-07-04 1982-01-28 Shionogi & Co Ltd 5-fluorouracil derivative
JPS5732270A (en) * 1980-08-05 1982-02-20 Shionogi & Co Ltd Preparation of 3-substituted-5-halogenated uracil
JPS5732271A (en) * 1980-08-05 1982-02-20 Shionogi & Co Ltd Preparation of 1-substituted-5-halogenated uracil

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
No relevant documents have been disclosed *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018080161A1 (ko) * 2016-10-25 2018-05-03 경북대학교 산학협력단 항병원성 활성 및 바이오필름 형성 억제 효과를 나타내는 화합물의 신규한 용도

Also Published As

Publication number Publication date
DE3170942D1 (en) 1985-07-18
DK151630B (da) 1987-12-21
JPS5767578A (en) 1982-04-24
AU543835B2 (en) 1985-05-02
EP0062068A1 (en) 1982-10-13
AU7641181A (en) 1982-05-11
US4528372A (en) 1985-07-09
ATE13764T1 (de) 1985-06-15
JPS6348273B2 (https=) 1988-09-28
DK256982A (da) 1982-06-08
SU1258325A3 (ru) 1986-09-15
BR8108842A (pt) 1982-09-21
EP0062068B1 (en) 1985-06-12
EP0062068A4 (en) 1983-02-09

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