JP2631227B2 - 5'-benzyl-5-fluorouridine derivatives and intermediates thereof - Google Patents
5'-benzyl-5-fluorouridine derivatives and intermediates thereofInfo
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- JP2631227B2 JP2631227B2 JP63173062A JP17306288A JP2631227B2 JP 2631227 B2 JP2631227 B2 JP 2631227B2 JP 63173062 A JP63173062 A JP 63173062A JP 17306288 A JP17306288 A JP 17306288A JP 2631227 B2 JP2631227 B2 JP 2631227B2
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- fluorouridine
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- benzyl
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Description
【発明の詳細な説明】 産業上の利用分野 本発明は、新規な5′−ベンジル−5−フルオロウリ
ジン誘導体及び該誘導体を製造するための中間体に関す
る。該5′−ベンジル−5−フルオロウリジン誘導体は
優れた制癌作用及び抗ウイルス作用を有し、抗腫瘍剤及
び抗ウイルス剤として有用である。Description: TECHNICAL FIELD The present invention relates to a novel 5′-benzyl-5-fluorouridine derivative and an intermediate for producing the derivative. The 5'-benzyl-5-fluorouridine derivative has an excellent anticancer effect and antiviral effect, and is useful as an antitumor agent and an antiviral agent.
従来技術及びその問題点 5−フルオロウリジン(以下、FURとする)は、1959
年に最初に合成され、その優れた抗悪性腫瘍作用も既に
知られている(米国特許第2885398号)。しかしなが
ら、毒性が高いため、臨床で使用するには問題がある。Prior art and its problems 5-fluorouridine (hereinafter referred to as FUR) is 1959
It was first synthesized in 2000 and its excellent antineoplastic activity is already known (US Patent No. 2885398). However, it is problematic for clinical use due to its high toxicity.
従来、FURを種々の誘導体に変換することにより、上
記の問題を解決しようとする試みが数多く行われている
が、有用な誘導体は未だ得られていない(特開昭50−64
280、同51−52183、同57−91997、同61−246196)。Conventionally, many attempts have been made to solve the above problem by converting FUR into various derivatives, but useful derivatives have not yet been obtained (Japanese Patent Laid-Open No. 50-64).
280, 51-52183, 57-91997, 61-246196).
問題を解決するための手段 本発明者らは、かかる状況に鑑みて、臨床上有用なFU
Rの誘導体について検討した結果、上記の目的を達成し
うる本発明の5′−ベンジル−5−フルオロウリジン誘
導体及び該誘導体を製造する為の有用な中間体を見出だ
し、本発明を完成するに至った。Means for Solving the Problem In view of such circumstances, the present inventors have considered that clinically useful FU
As a result of studying the derivative of R, a 5'-benzyl-5-fluorouridine derivative of the present invention which can achieve the above object and a useful intermediate for producing the derivative were found, and the present invention was completed. Reached.
本発明は、下記一般式(I) 〔式中、R1はハロゲン原子、低級アルコキシ基又は低級
アルキル基を示し、nは0〜3の整数を示す。〕で表さ
れる5′−ベンジル−5−フルオロウリジン誘導体及び
下記一般式(II) 〔式中、R1及びnは前記に同じであり、R2及びR3は同一
又は相異なって低級アルキル基を示す。〕で表される中
間体を提供するものである。The present invention relates to the following general formula (I) [In the formula, R 1 represents a halogen atom, a lower alkoxy group or a lower alkyl group, and n represents an integer of 0 to 3. 5'-benzyl-5-fluorouridine derivative represented by the following general formula (II): [Wherein, R 1 and n are the same as above, and R 2 and R 3 are the same or different and represent a lower alkyl group. ] Is provided.
本発明の化合物(I)は、FURに比べ、毒性が低く、
強力な抗腫瘍作用及び抗ウイルス作用を有し、医薬とし
て有用である。又、化合物(II)は、化合物(I)を製
造するための中間体として有用である。The compound (I) of the present invention has lower toxicity than FUR,
It has strong antitumor and antiviral effects, and is useful as a medicine. Compound (II) is useful as an intermediate for producing compound (I).
上記一般式(I)及び(II)において、ハロゲン原子
として、フッ素、塩素、臭素、ヨウ素等が挙げられる。
低級アルコキシ基として、メトキシ、エトキシ、プロポ
キシ、ブトキシ、tert−ブトキシ、ペンチルオキシ、ヘ
キシルオキシ基等の炭素数1−6の直鎖又は分枝状のア
ルコキシ基が挙げられる。低級アルキル基として、メチ
ル、エチル、プロピル、イソプロピル、ブチル、sec−
ブチル、tert−ブチル、ペンチル、ヘキシル基等の炭素
数1−6の直鎖又は分枝状のアルキル基が挙げられる。In the general formulas (I) and (II), examples of the halogen atom include fluorine, chlorine, bromine, and iodine.
Examples of the lower alkoxy group include a linear or branched alkoxy group having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy groups. As lower alkyl groups, methyl, ethyl, propyl, isopropyl, butyl, sec-
Examples thereof include a linear or branched alkyl group having 1 to 6 carbon atoms such as butyl, tert-butyl, pentyl and hexyl groups.
本発明の化合物は、下記の方法によって製造される。 The compound of the present invention is produced by the following method.
一般式 〔式中、R2及びR3は前記に同じである。〕で表される化
合物(ジャーナル オブ メジカル ケミストリー(J.
Med.Chem.),24,893−897,(1981))を一般式 〔式中、R1及びnは前記と同じ。Xは臭素原子又はヨウ
素原子を示す。〕で表される置換ベンジルハライド化合
物と適当な溶媒中、塩基の存在下に反応させ、本発明の
中間体(II)を得、次いで、該中間体(II)の2′,3′
位のイソアルキリデン基を脱保護することにより本発明
の化合物(I)が得られる。General formula Wherein R 2 and R 3 are the same as above. ] (Journal of Medical Chemistry (J.
Med.Chem.), 24 , 893-897, (1981)) Wherein R 1 and n are the same as above. X represents a bromine atom or an iodine atom. With a substituted benzyl halide compound represented by the formula (I) in the presence of a base in a suitable solvent to obtain the intermediate (II) of the present invention,
The compound (I) of the present invention can be obtained by deprotecting the isoalkylidene group at the 2-position.
中間体(II)を得るための上記反応は有機溶媒中で行
われる。ここで用いられる溶媒としては、上記の反応に
悪影響を与えないものであれば、特に限定されず、例え
ば、ベンゼン、トルエン、キシレン等の芳香族炭化水素
類、ジエチルエーテル、テトラヒドロフラン、ジオキサ
ン等のエーテル類、アセトニトリル、ピリジン、ジメチ
ルホルムアミド、ジメチルスルホキシド等の非プロトン
性極性溶媒等の従来公知のものを単独であるいは複数混
合して用いることができる。The above reaction for obtaining the intermediate (II) is performed in an organic solvent. The solvent used here is not particularly limited as long as it does not adversely affect the above reaction.Examples include aromatic hydrocarbons such as benzene, toluene, and xylene, diethyl ether, tetrahydrofuran, and ethers such as dioxane. , Aprotic polar solvents such as acetonitrile, pyridine, dimethylformamide, dimethylsulfoxide and the like can be used singly or as a mixture of two or more.
塩基としては、この種の反応で通常用いられる種々の
塩基を使用でき、例えば、水素化ナトリウム、水素化カ
リウム等のアルカリ金属水素化物、水酸化リチウム、水
酸化ナトリウム、水酸化カリウム等のアルカリ金属水酸
化物、ナトリウムメトキシド、ナトリウムエトキシド、
カリウムtert−ブトキシド等のアルカリ金属アルコキサ
イド、ブチルリチウム、メチルリチウム、カリウムジシ
ラジド等の有機アルカリ金属、酸化銀、硝酸銀等が好適
に用いられる。As the base, various bases usually used in this type of reaction can be used, and examples thereof include alkali metal hydrides such as sodium hydride and potassium hydride, and alkali metal hydrides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide. Hydroxide, sodium methoxide, sodium ethoxide,
Alkali metal alkoxides such as potassium tert-butoxide, organic alkali metals such as butyl lithium, methyl lithium and potassium disilazide, silver oxide, silver nitrate and the like are preferably used.
塩基の使用量は、一般式(III)の化合物1モルに対
し、通常1〜10モル程度、好ましくは2〜4モル程度で
ある。置換ベンジルハロゲン化合物(IV)の使用量は、
化合物(III)1モルに対し、通常1〜10モル程度、好
ましくは1〜4モル程度である。The amount of the base to be used is generally about 1-10 mol, preferably about 2-4 mol, per 1 mol of compound of general formula (III). The amount of the substituted benzyl halide compound (IV) used is
It is generally about 1-10 mol, preferably about 1-4 mol, per 1 mol of compound (III).
反応温度は、特に限定されるものではないが、通常0
〜100℃程度、好ましくは室温から60℃程度が反応の進
行に有利である。Although the reaction temperature is not particularly limited, it is usually 0.
-100 ° C, preferably from room temperature to about 60 ° C, is advantageous for the progress of the reaction.
反応時間は、使用する溶媒、塩基の種類により異なる
が、一般に0.5〜24時間程度である。The reaction time varies depending on the type of solvent and base used, but is generally about 0.5 to 24 hours.
上記脱保護反応は、酸を用いる加水分解によって、適
当な溶媒中にて容易に実施される。ここで用いられる溶
媒としては、上記の反応に悪影響を及ぼさないものであ
れば、特に限定されるものではなく、例えば、ジエチル
エーテル、テトラヒドロフラン、ジオキサン等のエーテ
ル類、メタノール、エタノール、プロパノール、ブタノ
ール等のアルコール類、ジクロルメタン、クロロホル
ム、四塩化炭素、ジクロルエタン等のハロゲン化炭化水
素類、水等の従来公知のものを、単独であるいは複数混
合して用いることができる。The above deprotection reaction is easily carried out in a suitable solvent by hydrolysis using an acid. The solvent used here is not particularly limited as long as it does not adversely affect the above reaction, and examples thereof include diethyl ether, tetrahydrofuran, ethers such as dioxane, methanol, ethanol, propanol, and butanol. , Alcohols, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane and the like, and water, etc., can be used alone or in combination.
酸としては、この種の反応に用いられる種々の酸を使
用でき、例えば、塩酸、硫酸等の鉱酸、トリフルオロ酢
酸、酢酸、ギ酸、トシル酸等の有機酸、Dowex−50W
(H+)(ダウケミカルズ)、CK−08P(H+)(三菱化
成)等の強酸性陽イオン交換樹脂等が好適に用いられ
る。As the acid, various acids used in this type of reaction can be used.For example, mineral acids such as hydrochloric acid and sulfuric acid, trifluoroacetic acid, acetic acid, formic acid, organic acids such as tosylic acid, Dowex-50W
Strongly acidic cation exchange resins such as (H + ) (Dow Chemicals) and CK-08P (H + ) (Mitsubishi Kasei) are preferably used.
酸の使用量は、化合物(II)1モルに対し、通常0.01
〜10モル程度、好ましくは0.1〜5モル程度である。The amount of the acid to be used is generally 0.01 mol per 1 mol of compound (II).
About 10 mol, preferably about 0.1 to 5 mol.
上記の方法で得られる本発明の化合物(I)及び(I
I)は、再結晶、シリカゲルカラムクロマトグラフィー
等の通常の分離精製手段により、単離精製することがで
きる。The compounds (I) and (I) of the present invention obtained by the above method
I) can be isolated and purified by ordinary separation and purification means such as recrystallization and silica gel column chromatography.
実施例 下記に、本発明の実施例を示すが、本発明はこれに限
定されるものではない。Examples Examples of the present invention will be described below, but the present invention is not limited thereto.
実施例 1 5′−m−クロルベンジル−5−フルオロウリジン(I
−1)の製造 2′,3′−イソプロピリデン−5−フルオロウリジン
1.0g(3.3mM)を無水テトラヒドロフラン6mlに溶解し
た。上記溶液に60%水素化ナトリウム264mg(6.6mM)を
加え、60℃で、2時間撹拌した。室温に戻した後、m−
クロルベンジルクロライド532mg(3.3mM)を無水テトラ
ヒドロフラン1mlに溶解させた溶液を滴下し、続いてヨ
ウ化ナトリウム248mg(1.65mM)を加え、室温で19時間
反応させた。反応液を無水テトラヒドロフラン20mlで希
釈した後、イオン交換樹脂(WK−11、三菱化成社製)で
中和し、濾過した。濾液を減圧下に濃縮し、得られた残
渣をシリカゲルカラムクロマトグラフィー30gに付し、
クロロホルム−メタノール(50:1)で溶出し、1141mgの
2′,3′−イソプロピリデン−5′−m−クロロベンジ
ル−5−フルオロウリジン(V−1)を得た(収率81
%)。Example 1 5'-m-chlorobenzyl-5-fluorouridine (I
Preparation of -1) 2 ', 3'-isopropylidene-5-fluorouridine
1.0 g (3.3 mM) was dissolved in 6 ml of anhydrous tetrahydrofuran. 264 mg (6.6 mM) of 60% sodium hydride was added to the above solution, and the mixture was stirred at 60 ° C for 2 hours. After returning to room temperature, m-
A solution of 532 mg (3.3 mM) of chlorobenzyl chloride in 1 ml of anhydrous tetrahydrofuran was added dropwise, followed by 248 mg (1.65 mM) of sodium iodide and reacted at room temperature for 19 hours. The reaction solution was diluted with 20 ml of anhydrous tetrahydrofuran, neutralized with an ion exchange resin (WK-11, manufactured by Mitsubishi Kasei Co., Ltd.), and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography 30 g,
Elution with chloroform-methanol (50: 1) gave 1141 mg of 2 ', 3'-isopropylidene-5'-m-chlorobenzyl-5-fluorouridine (V-1) (yield 81).
%).
得られた化合物(V−1)の内1130mg(2.65mM)をク
ロロホルム5mlに溶解し、90%−トリフルオロ酢酸1mlを
加え、室温で24時間反応させた。反応液を減圧下に濃縮
し、得られた残渣をシリカゲルカラムクロマトグラフィ
ー20gに付し、クロロホルム−メタノール(20:1)によ
る溶出部分を減圧濃縮し、残渣をエーテルで再結晶さ
せ、濾集して、892mgの5′−m−クロルベンジル−5
−フルオロウリジン(I−1)を得た(収率87%)。1130 mg (2.65 mM) of the obtained compound (V-1) was dissolved in 5 ml of chloroform, 1 ml of 90% -trifluoroacetic acid was added, and the mixture was reacted at room temperature for 24 hours. The reaction solution was concentrated under reduced pressure, the obtained residue was subjected to silica gel column chromatography (20 g), the portion eluted with chloroform-methanol (20: 1) was concentrated under reduced pressure, the residue was recrystallized from ether, and collected by filtration. 892 mg of 5'-m-chlorobenzyl-5
-Fluorouridine (I-1) was obtained (yield 87%).
化合物(V−1)の1H−NMR(溶媒DMSO、内部標準TM
S)のδ(ppm)値及び収率(%)を第I表に、化合物
(I−1)の1H−NMR(溶媒DMSO、内部標準TMS)のδ
(ppm)値、収率(%)及び融点(℃)を第II表に各々
示す。 1 H-NMR of compound (V-1) (solvent DMSO, internal standard TM
Table 1 shows the δ (ppm) value and yield (%) of S), and the δ of 1 H-NMR (solvent DMSO, internal standard TMS) of compound (I-1).
Table II shows the (ppm) value, the yield (%) and the melting point (° C.).
実施例 2 5′−p−メトキシベンジル−5−フルオロウリジン
(I−10)の製造 2′,3′−イソプロピリデン−5−フルオロウリジン
1.0g(3.3mM)を無水テトラヒドロフラン6mlに溶解し
た。上記溶液に60%水素化ナトリウム264mg(6.6mM)を
加え、60℃で、2時間撹拌した。室温に戻した後、p−
メトキシベンジルブロマイド663mg(3.3mM)を無水テト
ラヒドロフラン1mlに溶解させた溶液を滴下し、続いて
ヨウ化ナトリウム248mg(1.65mM)を加え、室温で16時
間反応させた。反応液を無水テトラヒドロフラン20mlで
希釈した後、イオン交換樹脂(WK−11、三菱化成社製)
で中和し、濾過した。濾液を減圧下に濃縮し、得られた
残渣をシリカゲルカラムクロマトグラフィー30gに付
し、クロロホルム−メタノール(50:1)で溶出し、1197
mgの2′,3′−イソプロピリデン−5′−p−メトキシ
ベンジル−5−フルオロウリジン(V−10)を得た(収
率86%)。Example 2 Preparation of 5'-p-methoxybenzyl-5-fluorouridine (I-10) 2 ', 3'-isopropylidene-5-fluorouridine
1.0 g (3.3 mM) was dissolved in 6 ml of anhydrous tetrahydrofuran. 264 mg (6.6 mM) of 60% sodium hydride was added to the above solution, and the mixture was stirred at 60 ° C for 2 hours. After returning to room temperature, p-
A solution in which 663 mg (3.3 mM) of methoxybenzyl bromide was dissolved in 1 ml of anhydrous tetrahydrofuran was added dropwise, followed by addition of 248 mg (1.65 mM) of sodium iodide, followed by a reaction at room temperature for 16 hours. After diluting the reaction solution with 20 ml of anhydrous tetrahydrofuran, an ion exchange resin (WK-11, manufactured by Mitsubishi Kasei)
And filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (30 g), and eluted with chloroform-methanol (50: 1) to give 1197
mg of 2 ', 3'-isopropylidene-5'-p-methoxybenzyl-5-fluorouridine (V-10) was obtained (86% yield).
得られた化合物(V−10)の内1180mg(2.79mM)をテ
トラヒドロフラン3mlに溶解し、1N塩酸−テトラヒドロ
フラン(1:1)3mlを加え、室温で15時間反応させた。反
応液を減圧下に濃縮し、得られた残渣をシリカゲルカラ
ムクロマトグラフィー20gに付し、クロロホルム−メタ
ノール(20:1)による溶出部分を減圧濃縮し、残渣をエ
ーテルで再結晶させ、濾集して、886mgの5′−p−メ
トキシベンジル−5−フルオロウリジン(I−10)を得
た(収率83%)。1180 mg (2.79 mM) of the obtained compound (V-10) was dissolved in 3 ml of tetrahydrofuran, 3 ml of 1N hydrochloric acid-tetrahydrofuran (1: 1) was added, and the mixture was reacted at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure, the obtained residue was subjected to silica gel column chromatography (20 g), the portion eluted with chloroform-methanol (20: 1) was concentrated under reduced pressure, the residue was recrystallized from ether, and collected by filtration. Thus, 886 mg of 5'-p-methoxybenzyl-5-fluorouridine (I-10) was obtained (83% yield).
化合物(V−10)の1H−NMR(溶媒DMSO、内部標準TM
S)のδ(ppm)値及び収率(%)を第I表に、化合物
(I−10)の1H−NMR(溶媒DMSO、内部標準TMS)のδ
(ppm)値、収率(%)及び融点(℃)を第II表に各々
示す。 1 H-NMR of compound (V-10) (solvent DMSO, internal standard TM
Table 1 shows the δ (ppm) value and yield (%) of S), and the δ of 1 H-NMR (solvent DMSO, internal standard TMS) of compound (I-10).
Table II shows the (ppm) value, the yield (%) and the melting point (° C.).
以下、同様にして化合物(V−2)〜(V−9)、
(V−11)〜(V−12)及び化合物(I−2)〜(I−
9)、(I−11)〜(I−12)を製造し、これらの同定
値を第I表及び第II表に各々示す。Hereinafter, similarly, compounds (V-2) to (V-9),
(V-11) to (V-12) and compounds (I-2) to (I-
9), (I-11) to (I-12) were prepared, and their identification values are shown in Tables I and II, respectively.
薬理試験 マウス可移植性腫瘍ザルコーマ180細胞5×106個を雄
性ICR/JCLマウス(体重27〜30g)の背部皮下に移植し
た。検体を0.1%ツイーン80を含有する生理食塩水に溶
解または懸濁し、これを1群を7匹としたマウスに0.1m
l/10gマウス体重の用量で、腫瘍移植日後1日目、5日
目及び9日目に計3回腹腔内投与した。 Pharmacological Test 5 × 10 6 mouse transplantable tumor sarcoma 180 cells were implanted subcutaneously on the back of male ICR / JCL mice (body weight 27-30 g). A sample was dissolved or suspended in a physiological saline solution containing 0.1% Tween 80, and this was added to a group of 7 mice.
A dose of 1/10 g of the mouse body weight was administered intraperitoneally three times in total on the first, fifth and ninth days after the tumor implantation.
また、対照群には検体を含まない上記溶液を同様の方
法にて投与した。The above-mentioned solution containing no specimen was administered to the control group in the same manner.
移植後12日目に各検体投与群について、各々の投与量
での平均腫瘍重量を測定し、これらを対照群における平
均腫瘍重量と対比し、各投与量での対照群に対する腫瘍
増殖抑制率を求めた。On day 12 after transplantation, for each sample administration group, the average tumor weight at each dose was measured, these were compared with the average tumor weight in the control group, and the tumor growth inhibition rate for the control group at each dose was determined. I asked.
得られた結果を第III表に示す。 The results obtained are shown in Table III.
フロントページの続き (72)発明者 内田 淳二 徳島県徳島市川内町加賀須野463―10 (72)発明者 ヴィエジバ.コンスタンチ 徳島県板野郡北島町北村字新川屋41―2 (72)発明者 山田 雄次 徳島県徳島市住吉4―2―8 (56)参考文献 特開 昭61−246196(JP,A) 特開 昭57−91997(JP,A) 特開 昭61−109720(JP,A) 特開 昭61−134397(JP,A) 実開 昭57−142998(JP,U) 実開 昭57−91994(JP,U)Continuation of the front page (72) Inventor Junji Uchida 463-10 Kagasuno, Kawauchi-machi, Tokushima City, Tokushima Prefecture (72) Inventor Viegiba. Konstanti 41-2 Shinkawaya, Kitajima-cho, Kitajima-cho, Itano-gun, Tokushima Prefecture (72) Inventor Yuji Yamada 4-2-8, Sumiyoshi, Tokushima-shi, Tokushima Prefecture (56) References JP-A-61-246196 (JP, A) 57-91997 (JP, A) JP-A-61-109720 (JP, A) JP-A-61-134397 (JP, A) Japanese Utility Model Application No. 57-142998 (JP, U) Japanese Utility Model Application No. 57-91994 (JP, A) U)
Claims (1)
アルキル基を示し、nは0〜3の整数を示す。〕で表さ
れる5′−ベンジル−5−フルオロウリジン誘導体。(1) General formula [In the formula, R 1 represents a halogen atom, a lower alkoxy group or a lower alkyl group, and n represents an integer of 0 to 3. 5'-benzyl-5-fluorouridine derivative represented by the formula:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63173062A JP2631227B2 (en) | 1988-07-11 | 1988-07-11 | 5'-benzyl-5-fluorouridine derivatives and intermediates thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63173062A JP2631227B2 (en) | 1988-07-11 | 1988-07-11 | 5'-benzyl-5-fluorouridine derivatives and intermediates thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH0222291A JPH0222291A (en) | 1990-01-25 |
JP2631227B2 true JP2631227B2 (en) | 1997-07-16 |
Family
ID=15953508
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP63173062A Expired - Lifetime JP2631227B2 (en) | 1988-07-11 | 1988-07-11 | 5'-benzyl-5-fluorouridine derivatives and intermediates thereof |
Country Status (1)
Country | Link |
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JP (1) | JP2631227B2 (en) |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5791994A (en) * | 1980-11-26 | 1982-06-08 | Fuji Kagaku Kogyo Kk | 5'-o-(n-alkylcarbamoylalanyl)-5-fluorouridine and its preparation |
JPS57142998A (en) * | 1981-02-27 | 1982-09-03 | Fuji Kagaku Kogyo Kk | Novel 5-fluorouridine derivative and its preparation |
JPS61109720A (en) * | 1984-10-31 | 1986-05-28 | Otsuka Pharmaceut Co Ltd | Antitumor agent |
JPS61134397A (en) * | 1984-12-01 | 1986-06-21 | Fuji Kagaku Kogyo Kk | 5'-o-oligopeptidyl-5-fluorouridine and production thereof |
JPS61246196A (en) * | 1985-04-22 | 1986-11-01 | Fuji Kagaku Kogyo Kk | 5'-o-acyl-5-fluorouridine and production thereof |
-
1988
- 1988-07-11 JP JP63173062A patent/JP2631227B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
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JPH0222291A (en) | 1990-01-25 |
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