JPS6335639B2 - - Google Patents
Info
- Publication number
- JPS6335639B2 JPS6335639B2 JP11468086A JP11468086A JPS6335639B2 JP S6335639 B2 JPS6335639 B2 JP S6335639B2 JP 11468086 A JP11468086 A JP 11468086A JP 11468086 A JP11468086 A JP 11468086A JP S6335639 B2 JPS6335639 B2 JP S6335639B2
- Authority
- JP
- Japan
- Prior art keywords
- alacitidine
- stearyl phosphate
- sodium salt
- water
- stearyl
- 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.)
- Expired
Links
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 229910019142 PO4 Inorganic materials 0.000 claims description 13
- 239000010452 phosphate Substances 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 159000000000 sodium salts Chemical class 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UHGIMQLJWRAPLT-UHFFFAOYSA-N octadecyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCCCOP(O)(O)=O UHGIMQLJWRAPLT-UHFFFAOYSA-N 0.000 claims description 3
- QSNURPAXNFOIOV-FKLBCBSKSA-N 4-azanyl-1-[(2r,3s,4s,5r)-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1.O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 QSNURPAXNFOIOV-FKLBCBSKSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000009876 antimalignant effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- -1 concentrated Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- MVFPQYVAVMINHP-UHFFFAOYSA-L disodium;octadecyl phosphate Chemical compound [Na+].[Na+].CCCCCCCCCCCCCCCCCCOP([O-])([O-])=O MVFPQYVAVMINHP-UHFFFAOYSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Description
〔産業上の利用分野〕
本発明は抗悪性腫瘍剤として有用な1―β―D
―アラビノフラノシルシトシン―5′―ステアリル
りん酸ナトリウム塩(以下アラシチジン―5′―ス
テアリルりん酸ナトリウム塩と略す)の新規製造
法に関するものである。
〔従来の技術〕
アラシチジン―5′―ステアリルりん酸ナトリウ
ム塩の製造方法は特公昭55―49588号に開示され
ている。すなわち、アラシチジン―5′―ステアリ
ルりん酸(遊離酸)を水中でPH7.0に調整した後
濃縮し、エタノールを加えて沈澱を析出させ、ア
ラシチジン―5′―ステアリルりん酸ナトリウム塩
を得ている。
〔本発明が解決しようとしている問題点〕
特公昭55―49588号に開示された方法によつて
得られたアラシチジン―5′―ステアリルりん酸ナ
トリウム塩について、安定性を検討した結果、25
℃相対湿度76%の条件下では14カ月後含量が93.7
%に低下し、50℃相対湿度74%の条件下では3カ
月後含量が58.6%と著しく低下し、分解物として
1―β―D―アラビノフラノシルウラシル―5′―
ステアリルりん酸ナトリウム塩が生成することを
見い出した。
このような不安定な性質を有するため、本化合
物を医薬品として開発する場合、製剤調製時の取
り扱いが制約されるばかりでなく、薬剤の有効期
限が非常に短いものとなり、事実上医薬品として
市場に供し得ない。
〔問題点を解決するための処理手段〕
そこで、本発明者等は安定なアラシチジン―
5′―ステアリルりん酸ナトリウム塩の製造法につ
いて鋭意検討した結果、アラシチジン―5′―ステ
アリルりん酸含有水性溶液を水酸化ナトリウム
で、PH10〜13に調整した後該ステアリルりん酸の
ナトリウム塩を取得することにより安定なアラシ
チジン―5′―ステアリルりん酸ナトリウム塩が得
られることを見い出し本発明を完成した。
本発明におけるアラシチジン―5′―ステアリル
りん酸含有水性溶液としてはアラシチジン―5′―
ステアリルりん酸を水性溶媒に溶解もしくは懸濁
させたものの他、アラシチジン―5′―ステアリル
りん酸を含むアラシチジン―5′―ステアリルりん
酸ナトリウムを水性溶媒に溶解したものなどアラ
シチジン―5′―ステアリルりん酸を含む水性溶液
ならばすべて使用することができる。
水酸化ナトリウムで調整するPHの範囲は約PH10
〜13の範囲内であればよいが好ましくはPH10.3〜
12.0程度であり、より好ましくはPH10.5〜11.5程
度である。
また、水酸化ナトリウムは結晶のままでも水溶
液でも使用できるが、PHの調整が容易な水溶液を
使用するのが好ましい。
水性溶媒としては、水または水と混和する有機
溶媒と水との混合溶媒が挙げられる。水と混和す
る有機溶媒としては、メタノール、エタノール、
プロパノールのような低級アルコール類、アセト
ン、メチルエチルケトンのようなケトン類、テト
ラヒドロフラン、ジオキサンのような環状エーテ
ル類等が挙げられる。
水性溶媒中の水の量は、アラシチジン―5′―ス
テアリルりん酸1部に対して2〜99部、好ましく
は3〜10部である。
PH調整の温度は、特に制限はないが、30℃以下
で行うのが好ましい。PH調整によるナトリウム塩
の形成は中和反応のため瞬時に終了する。
本発明の化合物であるアラシチジン―5′―ステ
アリルりん酸ナトリウム塩の単離は常法により行
うことができる。例えば反応液をそのまま濃縮乾
固させるか、濃縮液を冷却して析出させるか、ま
たは水と混和する有機溶媒を水に対して大過剰、
好ましくは水に対して3〜5倍量になるように加
え、析出した結晶を取し、乾燥することによつ
て行われる。
このようにして得られた該ナトリウム塩の融点
は約219℃〜約223℃(分解)であつた。
〔発明の作用、効果〕
本発明によつて得られるアラシチジン―5′―ス
テアリルりん酸ナトリウム塩が安定性に優れてい
ることを以下の実験によつて説明する。
1 試 料
A 本発明品:実施例1で得られたアラシチジ
ン―5′―ステアリルりん酸ナトリウム塩
B 本発明品:実施例2で得られたアラシチジ
ン―5′―ステアリルりん酸ナトリウム塩
C 対照品:特公昭55―49588号の方法により
製造されたアラシチジン―5′―ステアリ
ルりん酸ナトリウム塩
2 試験方法:本発明品(試料A,B)及び対照
品(試料C)おのおの1gを秤量ビンに
取り飽和食塩溶液を入れたデジケーター
上で25℃(相対湿度76%)14カ月及び50
℃(相対湿度74%)3カ月保存し、前後
のアラシチジン―5′―ステアリルりん酸
及び分解物含量を測定した。
3 結 果:保存開始前及び保存後の測定結果を
表1に示す。
[Industrial Application Field] The present invention provides 1-β-D useful as an anti-malignant tumor agent.
This invention relates to a new method for producing arabinofuranosylcytosine-5'-stearyl phosphate sodium salt (hereinafter abbreviated as aracytidine-5'-stearyl phosphate sodium salt). [Prior Art] A method for producing alacitidine-5'-stearyl phosphate sodium salt is disclosed in Japanese Patent Publication No. 49588/1988. That is, alacitidine-5'-stearyl phosphate (free acid) was adjusted to pH 7.0 in water, concentrated, and ethanol was added to precipitate it to obtain alacitidine-5'-stearyl phosphate sodium salt. . [Problems to be solved by the present invention] As a result of examining the stability of alacitidine-5'-stearyl phosphate sodium salt obtained by the method disclosed in Japanese Patent Publication No. 55-49588, 25
After 14 months, the content is 93.7 at 76% relative humidity.
%, and under conditions of 50°C and relative humidity of 74%, the content significantly decreased to 58.6% after 3 months, and 1-β-D-arabinofuranosyluracil-5'-
It was discovered that stearyl phosphate sodium salt was produced. Due to this unstable property, when this compound is developed as a drug, it not only has restrictions on its handling during formulation preparation, but also has a very short expiration date, making it virtually impossible for it to be marketed as a drug. I can't offer it. [Treatment means for solving the problem] Therefore, the present inventors developed a stable alacitidine-
As a result of intensive research on the manufacturing method of 5'-stearyl phosphate sodium salt, we obtained the sodium salt of stearyl phosphate after adjusting the pH of an alacitidine-5'-stearyl phosphate-containing aqueous solution to 10-13 with sodium hydroxide. They found that stable alacitidine-5'-stearyl phosphate sodium salt could be obtained by doing this, and completed the present invention. As the aqueous solution containing alacitidine-5'-stearyl phosphate in the present invention, alacitidine-5'-
In addition to those in which stearyl phosphate is dissolved or suspended in an aqueous solvent, alacitidine-5'-stearyl phosphoric acid, such as those in which sodium alacitidine-5'-stearyl phosphate containing alacitidine-5'-stearyl phosphate is dissolved in an aqueous solvent, etc. Any aqueous solution containing an acid can be used. The pH range adjusted with sodium hydroxide is approximately PH10
It is sufficient if it is within the range of ~13, but preferably PH10.3 ~
The pH is about 12.0, more preferably about 10.5 to 11.5. Although sodium hydroxide can be used in its crystalline form or as an aqueous solution, it is preferable to use an aqueous solution whose pH can be easily adjusted. Examples of the aqueous solvent include water or a mixed solvent of water and an organic solvent that is miscible with water. Organic solvents that are miscible with water include methanol, ethanol,
Examples include lower alcohols such as propanol, ketones such as acetone and methyl ethyl ketone, and cyclic ethers such as tetrahydrofuran and dioxane. The amount of water in the aqueous solvent is from 2 to 99 parts, preferably from 3 to 10 parts, per part of aracytidine-5'-stearyl phosphate. The temperature for pH adjustment is not particularly limited, but it is preferably performed at 30°C or lower. The formation of sodium salt by pH adjustment ends instantly due to the neutralization reaction. The compound of the present invention, alacitidine-5'-stearyl phosphate sodium salt, can be isolated by conventional methods. For example, the reaction solution is directly concentrated to dryness, the concentrated solution is cooled and precipitated, or a water-miscible organic solvent is used in large excess relative to the water.
Preferably, it is added in an amount of 3 to 5 times the amount of water, and the precipitated crystals are collected and dried. The melting point of the sodium salt thus obtained was about 219°C to about 223°C (decomposed). [Operations and Effects of the Invention] The excellent stability of alacitidine-5'-stearyl phosphate sodium salt obtained by the present invention will be explained by the following experiment. 1 Sample A Product of the present invention: Sodium salt of alacitidine-5'-stearyl phosphate obtained in Example 1 B Product of the present invention: Sodium salt of alacitidine-5'-stearyl phosphate obtained in Example 2 C Control product : Alacitidine-5'-stearyl phosphate sodium salt 2 produced by the method of Japanese Patent Publication No. 55-49588 Test method: Place 1 g of each of the products of the present invention (Samples A and B) and the control product (Sample C) in a weighing bottle. 14 months and 50 years at 25°C (76% relative humidity) on a desiccator containing saturated saline solution.
C. (relative humidity 74%) for 3 months, and the contents of alacitidine-5'-stearyl phosphate and decomposition products before and after were measured. 3 Results: Table 1 shows the measurement results before and after storage.
実施例 1 アラシチジン―5′―ステアリルりん
酸500gに水1.5を加え、撹拌しながら水酸化
ナトリウムでPHを10.8に調整した後エタノール
6を加えて16時間放冷後沈澱を遠心過し、
30℃で減圧乾燥してアラシチジン―5′―ステア
リルりん酸ナトリウム塩332gを得た。本品の
融点は223℃(分解)、液体クロマトグラフイー
純度99.5%E1%
1cm(273nm,0.1NNaOH)
152.3であつた。
実施例 2 実施例1と同様の方法で得たアラシ
チジン―5′―ステアリルりん酸(乾燥物)2.40
gに水6mlを加え、更に1N水酸化ナトリウム
水溶液でPHを12.0に調整した後、エタノール30
mlを加え、55℃で3時間撹拌後、16時間放冷す
る。析出した沈澱を別し、30℃で10時間減圧
乾燥し、アラシチジン―5′―ステアリルりん酸
ナトリウム塩1.83gを得た。
本品の融点220℃(分解)、液体クロマトグラ
フイー純度99.5%、E1%
1cm(273nm,
0.1NNaOH)150.9であつた。
実施例 3 アラシチジン―5′―ステアリルりん
酸2.40gに水10mlを加え、撹拌しながら水酸化
ナトリウムでPH10.0に調整した後、溶液を減圧
乾固し、アラシチジン―5′―ステアリルりん酸
ナトリウム塩2.30gを得た。
本品の融点は、219.8℃(分解)、液体クロマ
トグラフイー純度99.1%、E1%
1cm(273nm,
0.1NNaOH)152.6であつた。
実施例 4 N4,O2′,O3′―トリアセチルアラ
シチジン―5′―リン酸(トリ―n―ブチルアン
モニウム)塩6.4g(10mmol)にステリルアル
コール5g、ピリジン30mlおよびp―トシルク
ロライド8gを加え、3時間反応させる。反応
後水及びクロロホルム50mlを加えて抽出し、ク
ロロホルム溶液にアンモニア水20ml及びエタノ
ールを加えて脱アセチル化し、水を加えて抽出
する。水層を分取し、濃塩酸を加えてPH2.5に
調整し、析出したアラシチジン―5′―ステアリ
ルりん酸を取した。未乾燥結晶に水20mlを加
え、1N水酸化ナトリウム水溶液でPHを10.5に
調整後、エタノール80mlを加えて結晶を析出さ
せ、アラシチジン―5′―ステアリルりん酸ナト
リウム塩4.20gを得た。
本品の液体クロマトグラフイー純度は99.62
%、融点221℃(分解)E1%
1cm(273nm,
0.1NNaOH)151.4であつた。
Example 1 Add 1.5 g of water to 500 g of alacitidine-5'-stearyl phosphoric acid, adjust the pH to 10.8 with sodium hydroxide while stirring, add 6 ethanol, and after cooling for 16 hours, the precipitate was centrifuged.
It was dried under reduced pressure at 30°C to obtain 332 g of alacitidine-5'-stearyl phosphate sodium salt. The melting point of this product is 223℃ (decomposition), liquid chromatography purity 99.5% E1% 1cm (273nm, 0.1NNaOH)
It was 152.3. Example 2 Aracytidine-5'-stearyl phosphoric acid (dry product) obtained in the same manner as Example 1 2.40
Add 6 ml of water to g, adjust the pH to 12.0 with 1N aqueous sodium hydroxide solution, and add 30 ml of ethanol.
ml, stirred at 55°C for 3 hours, and then allowed to cool for 16 hours. The deposited precipitate was separated and dried under reduced pressure at 30°C for 10 hours to obtain 1.83 g of alacitidine-5'-stearyl phosphate sodium salt. Melting point of this product: 220℃ (decomposed), liquid chromatography purity: 99.5%, E1%: 1cm (273nm,
0.1NNaOH) was 150.9. Example 3 Add 10 ml of water to 2.40 g of alacitidine-5'-stearyl phosphate, adjust the pH to 10.0 with sodium hydroxide while stirring, and dry the solution under reduced pressure to obtain sodium alacitidine-5'-stearyl phosphate. 2.30 g of salt was obtained. The melting point of this product is 219.8℃ (decomposition), liquid chromatography purity 99.1%, E1% 1cm (273nm,
0.1NNaOH) was 152.6. Example 4 6.4 g (10 mmol) of N 4 , O 2 ′, O 3 ′-triacetylaracytidine-5′-phosphoric acid (tri-n-butylammonium) salt, 5 g of steryl alcohol, 30 ml of pyridine, and p-tosyl Add 8 g of chloride and react for 3 hours. After the reaction, water and 50 ml of chloroform are added for extraction, 20 ml of aqueous ammonia and ethanol are added to the chloroform solution for deacetylation, and water is added for extraction. The aqueous layer was separated, concentrated hydrochloric acid was added to adjust the pH to 2.5, and the precipitated aracytidine-5'-stearyl phosphate was collected. After adding 20 ml of water to the undried crystals and adjusting the pH to 10.5 with a 1N aqueous sodium hydroxide solution, 80 ml of ethanol was added to precipitate the crystals to obtain 4.20 g of alacitidine-5'-stearyl phosphate sodium salt. The liquid chromatography purity of this product is 99.62.
%, melting point 221℃ (decomposition) E1% 1cm (273nm,
0.1NNaOH) was 151.4.
Claims (1)
5′―ステアリルりん酸含有水性溶液を水酸化ナト
リウムで、PH10〜13に調整した後、該ステアリル
りん酸のナトリウム塩を取得することを特徴とす
る1―β―D―アラビノフラノシルシトシン―
5′―ステアリルりん酸ナトリウム塩の製造法。1 1-β-D-arabinofuranosylcytosine-
1-β-D-arabinofuranosylcytosine, which is characterized in that the sodium salt of stearyl phosphate is obtained by adjusting an aqueous solution containing 5'-stearyl phosphate to pH 10 to 13 with sodium hydroxide.
Method for producing 5′-stearyl phosphate sodium salt.
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP61114680A JPS62273993A (en) | 1986-05-21 | 1986-05-21 | Novel production of sodium 1-beta-d-arabinofuranosylcytosine-5'-stearyl phosphate |
EP87104071A EP0239015B1 (en) | 1986-03-24 | 1987-03-19 | Process for producing 1-beta-d-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt and monohydrate thereof, and pharmaceutical composition containing the latter |
DE8787104071T DE3773716D1 (en) | 1986-03-24 | 1987-03-19 | METHOD FOR PRODUCING MONOSODIUM SALTS AND THEIR MONOHYDRATE OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE-5'STEARYLPHOSPHATE AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM. |
ES198787104071T ES2031462T3 (en) | 1986-03-24 | 1987-03-19 | PROCEDURE TO PRODUCE 1-B-D-ARABINOFURANOSILCITOSINA-5'-STERARILFOSFATO MONOSODICO AND MONOHIDRATO OF THE SAME, AND PHARMACEUTICAL COMPOUND THAT CONTAINS THIS LAST. |
HU871247A HU196429B (en) | 1986-03-24 | 1987-03-20 | Process for preparing monosodium salts of 1-beta-d-arabinofuranozylcytozine-5'-stearyl phosphate and the monohydrate of this salt |
AU70475/87A AU592165B2 (en) | 1986-03-24 | 1987-03-20 | Process for producing 1-beta-D-arabinofuranosylcytosine-5- stearylphosphate monosodium salt and monohydrate thereof |
CA000532597A CA1270820A (en) | 1986-03-24 | 1987-03-20 | PROCESS FOR PRODUCING 1-.beta.-D- ARABINOFURANOSYLCYTOSINE-5'-STEARYLPHOSPHATE MONOSODIUM SALT AND MONOHYDRATE THEREOF |
US07/028,951 US4812560A (en) | 1986-03-24 | 1987-03-23 | Process for producing 1-β-D-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt and monohydrate thereof |
KR1019870002697A KR910008801B1 (en) | 1986-03-24 | 1987-03-23 | Process for producing 1-beta-arabino-furanosylcytosine-5-stearylphosphate monosodium salt and monohydrate thereof |
US07/399,303 US5049663A (en) | 1986-03-24 | 1989-08-25 | Process for producing 1-β-D-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt and monohydrate thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP61114680A JPS62273993A (en) | 1986-05-21 | 1986-05-21 | Novel production of sodium 1-beta-d-arabinofuranosylcytosine-5'-stearyl phosphate |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS62273993A JPS62273993A (en) | 1987-11-28 |
JPS6335639B2 true JPS6335639B2 (en) | 1988-07-15 |
Family
ID=14643944
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP61114680A Granted JPS62273993A (en) | 1986-03-24 | 1986-05-21 | Novel production of sodium 1-beta-d-arabinofuranosylcytosine-5'-stearyl phosphate |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS62273993A (en) |
-
1986
- 1986-05-21 JP JP61114680A patent/JPS62273993A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS62273993A (en) | 1987-11-28 |
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