JPH04270281A - 2',3'-dideoxy-(6-methyl)selenopurine nucleoside derivative, its production and application to antiviral agent - Google Patents
2',3'-dideoxy-(6-methyl)selenopurine nucleoside derivative, its production and application to antiviral agentInfo
- Publication number
- JPH04270281A JPH04270281A JP16227091A JP16227091A JPH04270281A JP H04270281 A JPH04270281 A JP H04270281A JP 16227091 A JP16227091 A JP 16227091A JP 16227091 A JP16227091 A JP 16227091A JP H04270281 A JPH04270281 A JP H04270281A
- Authority
- JP
- Japan
- Prior art keywords
- dideoxyribofuranoside
- selenopurine
- general formula
- derivative
- formula
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 239000003443 antiviral agent Substances 0.000 title description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 150000004678 hydrides Chemical class 0.000 claims abstract description 6
- 208000030507 AIDS Diseases 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims abstract description 3
- 230000003612 virological effect Effects 0.000 claims abstract description 3
- 125000003277 amino group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 claims description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 125000003748 selenium group Chemical group *[Se]* 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 43
- 230000000840 anti-viral effect Effects 0.000 abstract description 11
- 239000012299 nitrogen atmosphere Substances 0.000 abstract description 9
- 239000011541 reaction mixture Substances 0.000 abstract description 5
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052711 selenium Inorganic materials 0.000 abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- -1 mercaptopyrimidine nucleoside derivatives Chemical class 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 241000700605 Viruses Species 0.000 description 3
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 3
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 3
- 229940124411 anti-hiv antiviral agent Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229910052798 chalcogen Inorganic materials 0.000 description 2
- 150000001787 chalcogens Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000002508 compound effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 239000011669 selenium Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229960000523 zalcitabine Drugs 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- GAJOUJZKZWZVPT-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(2-amino-6-$l^{1}-selanylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C12=NC(N)=NC([Se])=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O GAJOUJZKZWZVPT-UUOKFMHZSA-N 0.000 description 1
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 description 1
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 1
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 1
- HAPFLHFSIIJLAI-UHFFFAOYSA-N 6-methylselanyl-7h-purin-2-amine Chemical compound C[Se]C1=NC(N)=NC2=C1NC=N2 HAPFLHFSIIJLAI-UHFFFAOYSA-N 0.000 description 1
- 229940124321 AIDS medicine Drugs 0.000 description 1
- 241000819038 Chichester Species 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108010043277 recombinant soluble CD4 Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は、抗ウイルス効果を有す
る新規な２’，３’−ジデオキシ−６− （メチル）セ
レノプリンヌクレオシド類およびそれを含有する抗ウイ
ルス剤に関するものである。FIELD OF THE INVENTION The present invention relates to novel 2',3'-dideoxy-6-(methyl)selenopurine nucleosides having antiviral effects and antiviral agents containing the same.
【０００２】0002
【従来の技術】近年、種々の抗ウイルス剤の開発が盛ん
になっている。その中でも特に抗エイズウイルス剤（抗
ＨＩＶ剤）の開発が注目されている。これまでアジドチ
ミジン（ＡＺＴ）、ジデオキシシチジン（ＤＤＣ）、ジ
デオキシイノシン（ＤＤＩ）などのジデオキシヌクレオ
シド類及び硫酸デキストラン、可溶性ＣＤ４、ホスホノ
ホルメート、リバビジン、スラミンなどが知られている
。BACKGROUND OF THE INVENTION In recent years, various antiviral agents have been actively developed. Among these, the development of anti-AIDS virus agents (anti-HIV agents) is attracting particular attention. So far, dideoxynucleosides such as azidothymidine (AZT), dideoxycytidine (DDC), and dideoxyinosine (DDI), as well as dextran sulfate, soluble CD4, phosphonoformate, ribavidin, and suramin have been known.
【０００３】ＡＺＴ，ＤＤＣ，ＤＤＩなどはその構造か
ら２’，３’−ジデオキシヌクレオシド類という化合物
群に属し、３’位に水酸基を持たないため、ＤＮＡチェ
ーン・ターミネーターとして働き、エイズウイルスのＤ
ＮＡ合成を停止させることが知られている。ＡＺＴは現
在のところ唯一の抗エイズ認可薬であり、ＤＤＣ，ＤＤ
Ｉも高い抗ＨＩＶ活性を示すことから２’，３’−ジデ
オキシヌクレオシド類にはさらなる有効な抗ＨＩＶ剤の
出現が期待できる。AZT, DDC, DDI, etc. belong to the group of compounds called 2',3'-dideoxynucleosides because of their structure, and because they do not have a hydroxyl group at the 3' position, they function as DNA chain terminators, and they act as DNA chain terminators.
It is known to stop NA synthesis. AZT is currently the only approved anti-AIDS drug, and DDC, DD
Since 2',3'-dideoxynucleosides also exhibit high anti-HIV activity, it is expected that more effective anti-HIV agents will emerge from 2',3'-dideoxynucleosides.
【０００４】一方、２’，３’−ジデオキシヌクレオシ
ド類にカルコゲン元素である硫黄を導入した例としては
、２’，３’−ジデオキシ−６− メルカプトプリンヌ
クレオシド誘導体、２’，３’−ジデオキシ−４− メ
ルカプトピリミジンヌクレオシド誘導体があり、ある程
度抗ウイルス効果を示すことが知られている（特願平２
−４６１８３ 号、特願平１−７７６２７号）。On the other hand, examples of introducing sulfur, a chalcogen element, into 2',3'-dideoxy nucleosides include 2',3'-dideoxy-6-mercaptopurine nucleoside derivatives, 2',3'-dideoxy- 4- There are mercaptopyrimidine nucleoside derivatives, which are known to exhibit some degree of antiviral effect (Patent Application No. 2003).
-46183, Japanese Patent Application No. 1-77627).
【０００５】しかし、カルコゲン元素のなかでもセレン
原子を２’，３’−ジデオキシヌクレオシド類に導入し
た例はなく、リボヌクレオシド化合物あるいは ２’−
デオキシヌクレオシド化合物にセレン原子を導入した例
がいくつか知られているのみである。例えば、６−セレ
ノグアノシンは幾つかの腫瘍に対して効果がある（Ｂｉ
ｏｃｈｅｍ．Ｐｈａｒｍａｃ．２２，１４１（１９７３
））。However, among chalcogen elements, there is no example of introducing selenium atoms into 2',3'-dideoxynucleosides, and ribonucleoside compounds or 2'-
There are only a few known examples of introducing selenium atoms into deoxynucleoside compounds. For example, 6-selenoguanosine is effective against several tumors (Bi
ochem. Pharmac. 22, 141 (1973
)).
【０００６】[0006]
【発明が解決しようとする課題】上述した公知の抗エイ
ズウイルス剤（抗ＨＩＶ剤）はエイズウイルス（ＨＩＶ
）に対する活性や、細胞に対する毒性、及び、生体への
吸収性などの点で、まだ十分に満足すべきものは得られ
ていない。[Problems to be Solved by the Invention] The above-mentioned known anti-AIDS virus agents (anti-HIV agents) are effective against the AIDS virus (HIV).
), toxicity to cells, absorbability into living bodies, etc., have not yet been obtained that are fully satisfactory.
【０００７】本発明は、これらの問題点を解決した抗ウ
イルス剤を提供することを目的とするものである。The object of the present invention is to provide an antiviral agent that solves these problems.
【０００８】[0008]
【課題を解決するための手段】本発明は、２’，３’−
ジデオキシ−６−（メチル）セレノプリンヌクレオシド
誘導体が高い抗ウイルス活性を有することに基づいてい
る。[Means for Solving the Problems] The present invention provides 2', 3'-
It is based on the fact that dideoxy-6-(methyl)selenopurine nucleoside derivatives have high antiviral activity.
【０００９】本発明に掛る、下記一般式［Ｉ］で表され
る２’，３’−ジデオキシ−６− セレノプリンヌクレ
オシド誘導体は以下のようにして合成することができる
。The 2',3'-dideoxy-6-selenopurine nucleoside derivative represented by the following general formula [I] according to the present invention can be synthesized as follows.
【００１０】すなわち、一般式［Ｉ］で表される化合物
中の２−アミノ−６− セレノプリン−９−β−Ｄ−２
’，３’−ジデオキシリボフラノシドは、窒素雰囲気下
、一般式［ＩＩ］で表される化合物中の２−アミノ−６
− クロロプリン−９−β−Ｄ−２’，３’−ジデオキ
シリボフラノシドを２当モル量の水素化セレノナトリウ
ムエタノール溶液に滴下し、加熱、還流することによっ
て有利に得ることができる。
（式中Ｒは水素あるいはアミノ基を示す。）（式中Ｒは
水素あるいはアミノ基を示す。）That is, 2-amino-6-selenopurine-9-β-D-2 in the compound represented by general formula [I]
',3'-dideoxyribofuranoside is 2-amino-6 in the compound represented by the general formula [II] under a nitrogen atmosphere.
- It can be advantageously obtained by adding chloropurine-9-β-D-2',3'-dideoxyribofuranoside dropwise to a 2-equimolar seleno-sodium hydride ethanol solution and heating and refluxing. (In the formula, R represents hydrogen or an amino group.) (In the formula, R represents hydrogen or an amino group.)
【００１１】上記原料
の２−アミノ−６− クロロプリン−９−β−Ｄ−２’
，３’−ジデオキシリボフラノシドは、２’，３’−ジ
デオキシウリジンと２−アミノ−６− クロロプリンを
原料として、これらを微生物の作用により塩基交換反応
させることにより、容易にかつ収率よく得ることができ
る（特願平１−４６１８３ 号）。[0011] The above raw material 2-amino-6-chloropurine-9-β-D-2'
, 3'-dideoxyribofuranoside is produced easily and in high yield by using 2',3'-dideoxyuridine and 2-amino-6-chloropurine as raw materials and subjecting them to a base exchange reaction through the action of microorganisms. (Japanese Patent Application No. 1-46183).
【００１２】また、一般式［Ｉ］で表される化合物中の
６−セレノプリン−９−β−Ｄ−２’，３’−ジデオキ
シリボフラノシドは、窒素雰囲気下、一般式［ＩＩ］で
表される化合物中の６−クロロプリン−９−β−Ｄ−２
’，３’−ジデオキシリボフラノシドを７当モル量の水
素化セレノナトリウムエタノール溶液に滴下し、加熱還
流することによって有利に得ることができる。Further, 6-selenopurine-9-β-D-2',3'-dideoxyribofuranoside in the compound represented by the general formula [I] can be converted into a compound represented by the general formula [II] under a nitrogen atmosphere. 6-chloropurine-9-β-D-2 in the compound
It can be advantageously obtained by adding ',3'-dideoxyribofuranoside dropwise to a 7 equivalent molar amount of selenosodium hydride ethanol solution and heating to reflux.
【００１３】上記原料の６−クロロプリン−９−β−Ｄ
−２’，３’−ジデオキシリボフラノシドは、２’，３
’−ジデオキシウリジンと６−クロロプリンを原料とし
て、これらを微生物の作用により塩基交換反応させるこ
とにより、容易にかつ収率よく得ることができる。The above raw material 6-chloropurine-9-β-D
-2',3'-dideoxyribofuranoside is 2',3
It can be easily obtained with good yield by using '-dideoxyuridine and 6-chloropurine as raw materials and subjecting them to a base exchange reaction through the action of microorganisms.
【００１４】一方本発明に係る、一般式 ［ＩＩＩ］で
表される２’，３’−ジデオキシ−６− メチルセレノ
プリンヌクレオシド誘導体は以下のようにして合成する
ことができる。On the other hand, the 2',3'-dideoxy-6-methylselenopurine nucleoside derivative represented by the general formula [III] according to the present invention can be synthesized as follows.
【００１５】すなわち、２−アミノ−６− メチルセレ
ノプリン−９−β−Ｄ−２’，３’−ジデオキシリボフ
ラノジドは、一般式［Ｉ］で表される２−アミノ−６−
セレノプリン−９−β−Ｄ−２’，３’−ジデオキシ
リボフラノシドをアルカリ条件下、エタノール溶液中、
１．５当モル量のヨードメタンと反応させることによ
って得ることができる。
（式中Ｒは水素あるいはアミノ基を示す。）That is, 2-amino-6-methylselenopurine-9-β-D-2',3'-dideoxyribofuranodide is a 2-amino-6-methylselenopurine represented by the general formula [I].
Selenopurine-9-β-D-2',3'-dideoxyribofuranoside in an ethanol solution under alkaline conditions,
It can be obtained by reaction with 1.5 equivalents of iodomethane. (In the formula, R represents hydrogen or an amino group.)
【００１６
】原料となる上記一般式［Ｉ］で表される２−アミノ−
６− セレノプリン−９−β−Ｄ−２’，３’−ジデオ
キシリボフラノシドは、窒素雰囲気下、一般式［ＩＩ］
で表される２−アミノ−６− クロロプリン−９−β−
Ｄ−２’，３’−ジデオシキリボフラノシドを２当モル
量の水素化セレノナトリウムエタノール溶液に滴下し、
加熱、還流することによって得ることができる。
（式中Ｒは水素あるいはアミノ基を示す。）0016
] 2-Amino- represented by the above general formula [I] as a raw material
6-Selenopurine-9-β-D-2',3'-dideoxyribofuranoside is synthesized by the general formula [II] under a nitrogen atmosphere.
2-Amino-6-chloropurine-9-β-
D-2′,3′-dideoxyribofuranoside was added dropwise to a 2-equimolar amount of selenosodium hydride ethanol solution,
It can be obtained by heating and refluxing. (In the formula, R represents hydrogen or an amino group.)
【００１７
】通常、一般式 ［ＩＩＩ］で表される６−メチルセレ
ノプリン−９−β−Ｄ−２’，３’−ジデオキシリボフ
ラノジドは、一般式［Ｉ］で表される６−セレノプリン
−９−β−Ｄ−２’，３’−ジデオキシリボフラノシド
をエタノール溶液中、 １．５当モル量のヨードメタン
と反応させることによって得ることができる。0017
] Usually, 6-methylselenopurine-9-β-D-2',3'-dideoxyribofuranodide represented by the general formula [III] is 6-selenopurine-9 represented by the general formula [I] -β-D-2',3'-dideoxyribofuranoside can be obtained by reacting with 1.5 equivalents of iodomethane in an ethanol solution.
【００１８】原料の６−セレノプリン−９−β−Ｄ−２
’，３’−ジデオキシリボフラノシドは、窒素雰囲気下
、一般式［ＩＩ］で表される６−クロロプリン−９−β
−Ｄ−２’，３’−ジデオシキリボフラノシドを７当モ
ル量の水素化セレノナトリウムエタノール溶液に滴下し
、加熱、還流することによって得ることができる。Raw material 6-selenopurine-9-β-D-2
',3'-dideoxyribofuranoside is 6-chloropurine-9-β represented by the general formula [II] under a nitrogen atmosphere.
It can be obtained by adding -D-2',3'-dideoxyribofuranoside dropwise to a 7 equivalent molar amount of selenosodium hydride ethanol solution and heating and refluxing.
【００１９】このように合成した本発明の化合物は通常
の精製法、例えばカラムクロマト法あるいは再結晶法あ
るいはこれらの組合せにより容易に精製することができ
る。The compound of the present invention thus synthesized can be easily purified by conventional purification methods, such as column chromatography, recrystallization, or a combination thereof.
【００２０】[0020]
【実施例】以下の実施例に従い、本発明をさらに詳細に
説明する。EXAMPLES The present invention will be explained in more detail with reference to the following examples.
【００２１】（１）製造例１
２−アミノ−６− セレノプリン−９−β−Ｄ−２’，
３’−ジデオキシリボフラノシドの合成(1) Production Example 1 2-amino-6-selenopurine-9-β-D-2',
Synthesis of 3'-dideoxyribofuranoside
【００２２】還流管、滴下ロートを備えた ３００ｍｌ
三口フラスコを窒素雰囲気下に置き、三口フラスコに粉
末セレン １．６ｇ（２０ｍｍｏｌ）、エタノール３０
ｍｌを、滴下ロートに水素化ホウ素ナトリウム １．０
ｇ（２６ｍｍｏｌ）、エタノール３０ｍｌを夫々加え、
氷浴で冷やしながら水素化ホウ素ナトリウムのエタノー
ル溶液をゆっくり三口フラスコ中に滴下した。始めの活
発な泡立ちが終わった後、氷浴を取り除いた。ほとんど
無色の水素化セレノナトリウム（２０ｍｍｏｌ）のエタ
ノール溶液を調製した（Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ，
９５，１９７（１９７３））。300ml equipped with reflux tube and dropping funnel
Place the three-neck flask under a nitrogen atmosphere, and add 1.6 g (20 mmol) of powdered selenium and 30 ethanol to the three-neck flask.
Add 1.0 ml of sodium borohydride to the dropping funnel.
g (26 mmol) and 30 ml of ethanol were added,
The ethanol solution of sodium borohydride was slowly dropped into the three-necked flask while cooling in an ice bath. After the initial vigorous bubbling ceased, the ice bath was removed. An almost colorless ethanol solution of selenosodium hydride (20 mmol) was prepared (J. Am. Chem. Soc,
95, 197 (1973)).
【００２３】また別に、 ２００ｍｌフラスコを窒素雰
囲気下に置き、２−アミノ−６− クロロプリン−９−
β−Ｄ−２’，３’−ジデオキシリボフラノシド ２．
８ｇ（１０ｍｍｏｌ）とエタノール１４０ｍｌを加えよ
く攪拌しておいた。Separately, a 200 ml flask was placed under a nitrogen atmosphere, and 2-amino-6-chloropurine-9-
β-D-2',3'-dideoxyribofuranoside 2.
8 g (10 mmol) and 140 ml of ethanol were added and stirred thoroughly.
【００２４】この２−アミノ−６− クロロプリン−９
−β−Ｄ−２’，３’−ジデオキシリボフラノシドのエ
タノール溶液をブリッジを用いて、三口フラスコの水素
化セレノナトリウムのエタノール溶液に加えた。３時間
加熱、還流し、１晩放置した。反応混合物をビーカーに
あけて、ドラフト内でよく攪拌した（Ｄｒ．ＬＥＲＯＹ
Ｂ．ＴＯ−ＷＮＳＥＮＤ， “ＮＵＣＬＥＩＣ ＡＣ
ＩＤ ＣＨＥＭＩＳＴＲＹ”ＪＯＨＮＷＩＬＥＹ ＆
ＳＯＮＳ，Ｎｅｗ Ｙｏｒｋ ・Ｃｈｉｃｈｅｓｔｅｒ
・Ｂｒｉｓｂａｎｃ・Ｔｏｒｏｎｔｏ （１９７８）ｐ
．５９１ ）。This 2-amino-6-chloropurine-9
The ethanol solution of -β-D-2',3'-dideoxyribofuranoside was added to the ethanol solution of seleno sodium hydride in the three-necked flask using a bridge. The mixture was heated to reflux for 3 hours and left overnight. The reaction mixture was poured into a beaker and stirred thoroughly in a fume hood (Dr. LEROY
B. TO-WNSEND, “NUCLEIC AC
ID CHEMISTRY” JOHNWILEY &
SONS, New York/Chichester
・Brisbanc・Toronto (1978) p.
．． 591).
【００２５】懸濁液を、グラスウールを通して吸引ろ過
し、黄色透明の液体を得た。この溶液を８０ｍｌまで濃
縮し、１０％酢酸−エタノール溶液を加えｐＨ７に調整
した。
この溶液を冷却して淡黄色の粉末０．７２ｇ（２．３ｍ
ｍｏｌ），２３％を得た。The suspension was suction filtered through glass wool to obtain a yellow transparent liquid. This solution was concentrated to 80 ml and adjusted to pH 7 by adding 10% acetic acid-ethanol solution. This solution was cooled and 0.72 g (2.3 m
mol), 23%.
【００２６】
ＮＭＲスペクトル（ＤＭＳＯ−ｄ６）；δδ１．８０〜
２．６０ （４Ｈ，ｍ，Ｃ２′，Ｃ３′，−Ｈ）δ３
．５０〜３．６０ （２Ｈ，ｍ，Ｃ５′，−Ｈ）δ３
．９０〜４．４０ （１Ｈ，ｍ，Ｃ４′，−Ｈ）δ６
．００ （１Ｈ，ｔ，Ｃ１′，−Ｈ）δ
６．７０ （２Ｈ，ｓ，ＮＨ２，−Ｈ）
δ８．２０ （１Ｈ，ｓ，Ｃ８，−Ｈ）
マススペクトル（ＦＡＢＭＳ）ＭＡＴＲＩＸ；グリセロ
ール ＤＭＳＯ溶解
ＭＨ＋ ＝ｃａｌ． ３１６．０３１２ｆｏｕｎｄ．
３１６．０３２５NMR spectrum (DMSO-d6); δδ1.80~
2.60 (4H, m, C2', C3', -H) δ3
．． 50-3.60 (2H, m, C5', -H) δ3
．． 90-4.40 (1H, m, C4', -H) δ6
．． 00 (1H, t, C1', -H)δ
6.70 (2H,s,NH2,-H)
δ8.20 (1H, s, C8, -H)
Mass spectrum (FABMS) MATRIX; glycerol dissolved in DMSO MH+ = cal. 316.0312found.
316.0325
【００２７】（２）製造例２
６−セレノプリン−９−β−Ｄ−２’，３’−ジデオキ
シリボフラノシドの合成(2) Production Example 2 Synthesis of 6-selenopurine-9-β-D-2',3'-dideoxyribofuranoside
【００２８】還流管、滴下ロートを備えた １００ｍｌ
三口フラスコを窒素雰囲気下に置き、三口フラスコに粉
末セレン ７９６ｍｇ（１０ｍｍｏｌ）、エタノール６
ｍｌを、滴下ロートに水素化ホウ素ナトリウム ５００
ｍｇ（１３ｍｍｏｌ）、エタノール１５ｍｌを夫々加え
、氷浴で冷やしながら水素化ホウ素ナトリウムのエタノ
ール溶液を三口フラスコ中にゆっくり滴下した。始めの
活発な泡立ちが終わった後、氷浴を取り除いた。ほとん
ど無色の水素化セレノナトリウム（１０ｍｍｏｌ）のエ
タノール溶液を調製した（Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ
，９５，１９７（１９７３））。100ml equipped with reflux tube and dropping funnel
Place the three-neck flask under a nitrogen atmosphere, and add 796 mg (10 mmol) of powdered selenium and 6 ethanol to the three-neck flask.
Add 500 ml of sodium borohydride to the dropping funnel.
mg (13 mmol) and 15 ml of ethanol were added thereto, and the ethanol solution of sodium borohydride was slowly dropped into the three-necked flask while cooling in an ice bath. After the initial vigorous bubbling ceased, the ice bath was removed. An almost colorless ethanol solution of selenosodium hydride (10 mmol) was prepared (J. Am. Chem. Soc.
, 95, 197 (1973)).
【００２９】また別に、５０ｍｌフラスコを窒素雰囲気
下に置き、６−クロロプリン−９−β−Ｄ−２’，３’
−ジデオキシリボフラノシド３５８ｍｇ（１．４ｍｍｏ
ｌ）とエタノール１０ｍｌを加えよく攪拌しておいた。Separately, a 50 ml flask was placed under a nitrogen atmosphere, and 6-chloropurine-9-β-D-2',3'
-dideoxyribofuranoside 358 mg (1.4 mmo
1) and 10 ml of ethanol were added and stirred well.
【００３０】６−クロロプリン−９−β−Ｄ−２’，３
’−ジデオキシリボフラノシドのエタノール溶液をブリ
ッジを用いて、三口フラスコの水素化セレノナトリウム
のエタノール溶液に加えた。２時間加熱、還流し、１晩
放置した。
反応混合物をビーカーにあけて、ドラフト内でよく攪拌
した（ＮＵＣＬＥＩＣ ＡＣＩＤＣＨＥＭＩＳＴＲＹ
５９１（１９７８） ）。6-chloropurine-9-β-D-2',3
The ethanol solution of '-dideoxyribofuranoside was added to the ethanol solution of selenosodium hydride in the three-necked flask using a bridge. The mixture was heated to reflux for 2 hours and left overnight. The reaction mixture was poured into a beaker and stirred well in a fume hood (NUCLEIC ACID CHEMISTRY
591 (1978)).
【００３１】赤色の懸濁液を、セライトを通して吸引ろ
過し、黄色透明の液体を得た。この溶液を２０ｍｌまで
濃縮し、１０％酢酸−エタノール溶液を加えてｐＨ ７
．４に調整した。この溶液を冷却して淡黄色の粉末 １
９２ｍｇ（０．６４ｍｍｏｌ），４６％を得た。The red suspension was suction filtered through Celite to obtain a yellow transparent liquid. This solution was concentrated to 20 ml, and a 10% acetic acid-ethanol solution was added to adjust the pH to 7.
．． Adjusted to 4. Cool this solution and turn it into a pale yellow powder 1
92 mg (0.64 mmol), 46% was obtained.
【００３２】
ＮＭＲスペクトル（ＤＭＳＯ−ｄ６）；δδ１．８０〜
２．６０ （４Ｈ，ｍ，Ｃ２′，Ｃ３′，−Ｈ）δ３
．５０〜３．６０ （２Ｈ，ｍ，Ｃ５′，−Ｈ）δ３
．９０〜４．４０ （１Ｈ，ｍ，Ｃ４′，−Ｈ）δ６
．２０ （１Ｈ，ｔ，Ｃ１′，−Ｈ）δ
８．３０ （１Ｈ，ｓ，Ｃ２，−Ｈ）δ
８．７０ （１Ｈ，ｓ，Ｃ８，−Ｈ）マ
ススペクトル（ＦＡＢＭＳ）ＭＡＴＲＩＸ；グリセロー
ル ＤＭＳＯ溶解
ＭＨ＋ ＝ｃａｌ． ３０１．０２０３ｆｏｕｎｄ．
３０１．０２００NMR spectrum (DMSO-d6); δδ1.80~
2.60 (4H, m, C2', C3', -H) δ3
．． 50-3.60 (2H, m, C5', -H) δ3
．． 90-4.40 (1H, m, C4', -H) δ6
．． 20 (1H,t,C1',-H)δ
8.30 (1H,s,C2,-H)δ
8.70 (1H, s, C8, -H) mass spectrum (FABMS) MATRIX; Glycerol DMSO dissolved MH+ = cal. 301.0203found.
301.0200
【００３３】（３）抗ウイルス試験
試験ウイルスは、レトロウイルスの一種であるラウス肉
腫ウイルス（ＲＳＶ）を用いて行った。(3) Antiviral test The test virus was Rous sarcoma virus (RSV), which is a type of retrovirus.
【００３４】抗ウイルス試験は、初代培養細胞（ＣＨＩ
ＣＫ ＥＭＢＲＹＯ ＦＩＢＲＯＢＬＡＳＴ ）を用い
て、約３０分間ＲＳＶ感染させた。そして段階的に、希
釈した試料を添加して、４〜７日後にＲＳＶ感染による
細胞の形質転換がどの段階において抑制されたかを検鏡
により判定した。結果を次に示す。[0034] The antiviral test was carried out using primary cultured cells (CHI
RSV infection was carried out for about 30 minutes using CK EMBRYO FIBROBLAST). Then, diluted samples were added stepwise, and 4 to 7 days later, it was determined by microscopy at which stage the transformation of cells due to RSV infection was suppressed. The results are shown below.
【００３５】抗ウイルス活性：
化 合 物 効果（μｇ／ｍｌ）［
Ｉ，Ｒ＝Ｈ］ ８［Ｉ，Ｒ
＝ＮＨ２ ］ ４〜８Antiviral activity: Compound effect (μg/ml) [
I,R=H] 8[I,R
=NH2] 4-8
【００３６】（４
）製造例３
２−アミノ−６− メチルセレノプリン−９−β−Ｄ−
２’，３’−ジデオキシリボフラノシドの合成(4)
) Production Example 3 2-amino-6-methylselenopurine-9-β-D-
Synthesis of 2',3'-dideoxyribofuranoside
【００３７】水酸化ナトリウム ０．６ｇを水２ｍｌに
溶かし、エタノール３０ｍｌを加えた。２−アミノ−６
− セレノプリン−９−β−Ｄ−２’，３’−ジデオキ
シリボフラノシド ２００ｍｇ（０．６３７ｍｍｏｌ）
を溶液に溶かし、ヨードメタン５４μｌ（１２３ｍｇ
０．８６ｍｍｏｌ）と室温中、反応させた。反応混合物
は３０％酢酸水溶液を用いてｐＨ７に調整し、エタノー
ルを留去した後、酢酸エチルで抽出し、硫酸マグネシウ
ムで乾燥し、濃縮した後、シリカゲルクロマトグラフィ
ー（ワコーゲル Ｃ−２００ 酢酸エチル）で分離し
た。５４ｍｇ（０．１６ｍｍｏｌ）２５．８％[0037] 0.6 g of sodium hydroxide was dissolved in 2 ml of water, and 30 ml of ethanol was added. 2-amino-6
- Selenopurine-9-β-D-2',3'-dideoxyribofuranoside 200 mg (0.637 mmol)
Dissolve in the solution, add 54μl of iodomethane (123mg
0.86 mmol) at room temperature. The reaction mixture was adjusted to pH 7 using a 30% acetic acid aqueous solution, ethanol was distilled off, extracted with ethyl acetate, dried over magnesium sulfate, concentrated, and then subjected to silica gel chromatography (Wakogel C-200 ethyl acetate). separated. 54mg (0.16mmol) 25.8%
【００３８】
ＮＭＲスペクトル（ＤＭＳＯ−ｄ６）；δδ２．００〜
２．９０ （４Ｈ，ｍ，Ｃ２′，Ｃ３′，−Ｈ）δ２
．５０ （３Ｈ，ｓ，ＳｅＣＨ３）δ３
．８９ （２Ｈ，ｍ，Ｃ５′，−Ｈ）δ
４．２９ （１Ｈ，ｍ，Ｃ４′，−Ｈ）
δ５．９７ （１Ｈ，ｔ，Ｃ１′，−Ｈ
）δ５．０６ （２Ｈ，ｓ，ＮＨ２，−
Ｈ）δ７．７３ （１Ｈ，ｓ，Ｃ８，−
Ｈ）マススペクトル（ＦＡＢＭＳ）ＭＡＴＲＩＸ；グリ
セロール メタノール溶解
ＭＨ＋ ＝ｃａｌ． ３３０．０４６９１２ｆｏｕｎ
ｄ．３３０．０４７４５NMR spectrum (DMSO-d6); δδ2.00~
2.90 (4H, m, C2', C3', -H) δ2
．． 50 (3H,s,SeCH3)δ3
．． 89 (2H,m,C5',-H)δ
4.29 (1H, m, C4', -H)
δ5.97 (1H, t, C1', -H
) δ5.06 (2H,s,NH2,-
H) δ7.73 (1H,s,C8,-
H) Mass spectrum (FABMS) MATRIX; glycerol dissolved in methanol MH+ = cal. 330.046912foun
d. 330.04745
【００３９】（５）製造例４
６−メチルセレノプリン−９−β−Ｄ−２’，３’−ジ
デオキシリボフラノシドの合成(5) Production Example 4 Synthesis of 6-methylselenopurine-9-β-D-2',3'-dideoxyribofuranoside
【００４０】水酸化ナトリウム ０．６ｇを水２ｍｌに
溶かし、エタノール３０ｍｌを加えた。６−セレノプリ
ン−９−β−Ｄ−２’，３’−ジデオキシリボフラノシ
ド ２００ｍｇ（０．６６８ ｍｍｏｌ）を溶液に溶か
し、ヨードメタン５４μｌ（１２３ｍｇ ０．８６ｍｍ
ｏｌ）と室温中、反応させた。[0040] 0.6 g of sodium hydroxide was dissolved in 2 ml of water, and 30 ml of ethanol was added. Dissolve 200 mg (0.668 mmol) of 6-selenopurine-9-β-D-2',3'-dideoxyribofuranoside in a solution and add 54 μl (123 mg 0.86 mmol) of iodomethane.
ol) at room temperature.
【００４１】反応混合物は３０％酢酸水溶液を用いてｐ
Ｈ７に調整し、エタノールを留去した後、酢酸エチルで
抽出し、硫酸マグネシウムで乾燥し、濃縮した後、シリ
カゲルクロマトグラフィー（ワコーゲル Ｃ−２００
酢酸エチル）で分離した。３６ｍｇ（０．１２ｍｍｏ
ｌ）１７．２％飴状の生成物はメタノールから再結晶し
白色の針状晶を得た。
７．５ｍｇ（０．０２４ ｍｍｏｌ） ３．６％The reaction mixture was purified using 30% acetic acid aqueous solution.
After adjusting to H7 and distilling off ethanol, extraction with ethyl acetate, drying with magnesium sulfate, concentration, and silica gel chromatography (Wakogel C-200
Ethyl acetate). 36 mg (0.12 mmo
l) The 17.2% candy-like product was recrystallized from methanol to obtain white needle-like crystals. 7.5mg (0.024 mmol) 3.6%
【００
４２】ＮＭＲスペクトル（ＤＭＳＯ−ｄ６）；δδ２．
１９〜３．０７ （４Ｈ，ｍ，Ｃ２′，Ｃ３′，−Ｈ
）δ２．６２ （３Ｈ，ｓ，ＳｅＣＨ３
）δ３．９７ （２Ｈ，ｍ，Ｃ５′，−
Ｈ）δ４．３８ （１Ｈ，ｍ，Ｃ４′，
−Ｈ）δ６．２１ （１Ｈ，ｔ，Ｃ１′
，−Ｈ）δ８．６９ （１Ｈ，ｓ，Ｃ２
，−Ｈ）δ８．１７ （１Ｈ，ｓ，Ｃ８
，−Ｈ）マススペクトル（ＦＡＢＭＳ）ＭＡＴＲＩＸ；
グリセロール ＤＭＳＯ溶解
ＭＨ＋ ＝ｃａｌ． ３１５．０３６０１３ｆｏｕｎ
ｄ．３１５．０３６８１０00
42] NMR spectrum (DMSO-d6); δδ2.
19-3.07 (4H, m, C2', C3', -H
) δ2.62 (3H,s,SeCH3
) δ3.97 (2H, m, C5', -
H) δ4.38 (1H, m, C4',
-H) δ6.21 (1H, t, C1'
, -H) δ8.69 (1H,s,C2
, -H) δ8.17 (1H,s,C8
,-H) Mass spectrum (FABMS) MATRIX;
Glycerol DMSO dissolved MH+ = cal. 315.036013foun
d. 315.036810
【００４３】（６）抗ウイルス試験 上記の （３）抗ウイルス試験と同様に行った。(6) Antiviral test It was conducted in the same manner as in (3) antiviral test above.
【００４４】抗ウイルス活性：
化 合 物 効果（μｇ／ｍｌ）［
ＩＩＩ，Ｒ＝Ｈ］ ４［Ｉ
ＩＩ，Ｒ＝ＮＨ２ ］ ４Antiviral activity: Compound effect (μg/ml) [
III, R=H] 4[I
II, R=NH2 ] 4
【００４
５】004
5]
【発明の効果】以上示したように、この発明によれば、
２’，３’−ジデオキシヌクレオシドにセレン原子を導
入した、新規化合物が提供される。この化合物は抗ウイ
ルス作用に優れており、例えばエイズ等のウイルス病治
療薬として有効である。[Effects of the Invention] As shown above, according to this invention,
A novel compound is provided in which a selenium atom is introduced into a 2',3'-dideoxynucleoside. This compound has excellent antiviral activity and is effective as a therapeutic agent for viral diseases such as AIDS.
Claims (1)
６−セレノプリン−９−β−Ｄ−２’，３’−ジデオキ
シリボフラノシド誘導体。 【請求項２】 一般式 ［ＩＩＩ］ （式中Ｒは水素あるいはアミノ基を示す。）で表される
６−メチルセレノプリン−９−β−Ｄ−２’，３’−ジ
デオキシリボフラノシド誘導体。 【請求項３】 水素化ホウ素ナトリウムとセレン原子
から発生した水素化セレノナトリウムと下記一般式［Ｉ
Ｉ］で表される６−クロロプリン−９−β−Ｄ−２’，
３’− ジデオキシリボフラノシド誘導体を反応し、請
求項１記載の一般式［Ｉ］で表される化合物６−セレノ
プリン−９−β−Ｄ−２’，３’−ジデオキシリボフラ
ノシド誘導体を合成することを特徴とする製造方法。 （式中Ｒは水素あるいはアミノ基を示す。）【請求項４
】 ヨードメタンと請求項１記載の一般式［Ｉ］で表
される６−セレノプリン−９−β−Ｄ−２’，３’−ジ
デオキシリボフラノシド誘導体を反応し、請求項２記載
の一般式 ［ＩＩＩ］で表される化合物６−メチルセレ
ノプリン−９−β−Ｄ−２’，３’−ジデオキシリボフ
ラノシド誘導体を合成することを特徴とする製造方法。 【請求項５】 請求項１及び２記載の一般式［Ｉ］及
び ［ＩＩＩ］で表される化合物を有効成分とするエイ
ズ等のウイルス病治療方法及び治療薬。[Scope of Claims] [Claim 1] 6-selenopurine-9-β-D-2',3'-di- Deoxyribofuranoside derivative. 2. 6-methylselenopurine-9-β-D-2',3'-dideoxyribofuranoside derivative represented by the general formula [III] (wherein R represents hydrogen or an amino group) . [Claim 3] Sodium borohydride and selenosodium hydride generated from selenium atoms and the following general formula [I
6-chloropurine-9-β-D-2',
3'-dideoxyribofuranoside derivative is reacted to synthesize a compound 6-selenopurine-9-β-D-2',3'-dideoxyribofuranoside derivative represented by the general formula [I] according to claim 1. A manufacturing method characterized by: (In the formula, R represents hydrogen or an amino group.) [Claim 4
] Iodomethane and the 6-selenopurine-9-β-D-2',3'-dideoxyribofuranoside derivative represented by the general formula [I] according to claim 1 are reacted to obtain the general formula [I] according to claim 2. A manufacturing method characterized by synthesizing a compound 6-methylselenopurine-9-β-D-2',3'-dideoxyribofuranoside derivative represented by [III]. 5. A method and drug for treating viral diseases such as AIDS, which contain the compounds represented by formulas [I] and [III] according to claims 1 and 2 as active ingredients.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16227091A JPH0786107B2 (en) | 1991-01-11 | 1991-06-06 | 2 ', 3'-dideoxy-6- (methyl) selenopurine nucleoside derivative, production method thereof and antiviral agent using the same |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3-56204 | 1991-01-11 | ||
| JP5620491 | 1991-01-11 | ||
| JP16227091A JPH0786107B2 (en) | 1991-01-11 | 1991-06-06 | 2 ', 3'-dideoxy-6- (methyl) selenopurine nucleoside derivative, production method thereof and antiviral agent using the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04270281A true JPH04270281A (en) | 1992-09-25 |
| JPH0786107B2 JPH0786107B2 (en) | 1995-09-20 |
Family
ID=26397146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16227091A Expired - Lifetime JPH0786107B2 (en) | 1991-01-11 | 1991-06-06 | 2 ', 3'-dideoxy-6- (methyl) selenopurine nucleoside derivative, production method thereof and antiviral agent using the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0786107B2 (en) |
-
1991
- 1991-06-06 JP JP16227091A patent/JPH0786107B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0786107B2 (en) | 1995-09-20 |
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