JPH04173787A - New antiviral agent and its production - Google Patents
New antiviral agent and its productionInfo
- Publication number
- JPH04173787A JPH04173787A JP29804790A JP29804790A JPH04173787A JP H04173787 A JPH04173787 A JP H04173787A JP 29804790 A JP29804790 A JP 29804790A JP 29804790 A JP29804790 A JP 29804790A JP H04173787 A JPH04173787 A JP H04173787A
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- group
- represented
- formulas
- dideoxypurine
- 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
- 239000003443 antiviral agent Substances 0.000 title claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 7
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- 239000002342 ribonucleoside Substances 0.000 claims abstract 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 239000002777 nucleoside Substances 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000003835 nucleoside group Chemical group 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 108020004707 nucleic acids Proteins 0.000 claims description 5
- 150000007523 nucleic acids Chemical class 0.000 claims description 5
- 102000039446 nucleic acids Human genes 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- -1 purine compound Chemical class 0.000 claims 2
- 229940124522 antiretrovirals Drugs 0.000 claims 1
- 239000003903 antiretrovirus agent Substances 0.000 claims 1
- 238000007664 blowing Methods 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound 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 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 230000002195 synergetic effect Effects 0.000 abstract description 3
- 230000002860 competitive effect Effects 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 230000000840 anti-viral effect Effects 0.000 description 12
- 208000030507 AIDS Diseases 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 241000700605 Viruses Species 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
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- 244000005700 microbiome Species 0.000 description 4
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- 238000003786 synthesis reaction Methods 0.000 description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical group OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 3
- 241000700721 Hepatitis B virus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000006957 competitive inhibition Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 2
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 108020005202 Viral DNA Proteins 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- AFVLVVWMAFSXCK-VMPITWQZSA-N alpha-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 AFVLVVWMAFSXCK-VMPITWQZSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 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
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- JEZBOWZXUFLSEV-HIJFXMFQSA-N 2-amino-6-chloro-9-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-3H-purin-6-ol Chemical compound OC1(Cl)NC(N)=NC2=C1N=CN2[C@H]1CC[C@@H](CO)O1 JEZBOWZXUFLSEV-HIJFXMFQSA-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
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000701027 Human herpesvirus 6 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- CBCQWVQNMGNYEO-UHFFFAOYSA-N N(6)-hydroxyadenine Chemical compound ONC1=NC=NC2=C1NC=N2 CBCQWVQNMGNYEO-UHFFFAOYSA-N 0.000 description 1
- 244000292604 Salvia columbariae Species 0.000 description 1
- 235000012377 Salvia columbariae var. columbariae Nutrition 0.000 description 1
- 235000001498 Salvia hispanica Nutrition 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 235000002597 Solanum melongena Nutrition 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
- 230000037237 body shape Effects 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 235000014167 chia Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
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- 150000003212 purines Chemical class 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明の目的は、一般式[I]で示される新規な抗ウィ
ルス剤およびその製造法にある。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The object of the present invention is a novel antiviral agent represented by the general formula [I] and a method for producing the same.
(式中Xは水素原子あるいはアミン基のいずれかであり
、Rは水素原子、または薬理的に許容しうるエステル形
成基、好ましくはアセチル基、プロピオニル基、ベンゾ
イル基、その他のC2Qまでのアシル基のいずれかであ
る。)〔従来の技術〕
一般式[I]に示されるような、プリン塩基部にヒドロ
キシアミノ基(−NHOH)を持つ、2′,3′−ジデ
オキシプリンヌクレオシド類及びその合成に関する報告
は知られていない。(In the formula, X is either a hydrogen atom or an amine group, and R is a hydrogen atom or a pharmacologically acceptable ester-forming group, preferably an acetyl group, a propionyl group, a benzoyl group, or another acyl group up to C2Q) ) [Prior art] 2',3'-dideoxypurine nucleosides having a hydroxyamino group (-NHOH) in the purine base moiety as shown in general formula [I] and their synthesis There are no known reports regarding this.
また、抗ウイルス効果に関する報告も知られていない。Furthermore, there are no known reports regarding antiviral effects.
HBV (B型肝炎ウィルス)、CM■(サイトメガロ
ウィルス)、H8V(単純ヘルペスウイルス)などのウ
ィルスは、人に感染して時として重篤な疾病を引き起す
。また、毎年のように大流行をする、インフルエンザも
ウィルスによる病気であり、今やウィルス性疾患は、現
代人にとって大きな社会問題となっている。Viruses such as HBV (hepatitis B virus), CM■ (cytomegalovirus), and H8V (herpes simplex virus) infect humans and sometimes cause serious illnesses. In addition, influenza is a disease caused by a virus, which is prevalent every year, and viral diseases have now become a major social problem for modern people.
現在までに知られているウィルス病の中で、最も問題化
しているのが、HIV (エイズウィルス)によって引
き起されるAIDS(後天性免疫不全症候群)である。Among the viral diseases known to date, the most problematic is AIDS (Acquired Immune Deficiency Syndrome) caused by HIV (AIDS virus).
AIDSは、その治療方法が未だ確立されていないのと
、高い死亡率を持つことから、今や、人類に最も恐れら
れている病の一つである。AIDS is currently one of the diseases most feared by humanity because no treatment method has yet been established and it has a high mortality rate.
HIVに感染した患者の中には、HB■やCMVおよび
HHV−6(ヘルペスウィルスの一種でAIDS発病の
関連が指摘されている)に重感染している患者の例も知
られており、この意味からも、AIDSは深刻な病であ
る。It is known that some patients infected with HIV are co-infected with HB■, CMV, and HHV-6 (a type of herpesvirus that has been linked to the onset of AIDS); In this sense, AIDS is a serious disease.
AIDSの完全な治療法はまだ知られていないが、キャ
リアの人々の発症を予防したり、病気進行を遅らせてA
IDS患者の延命効果をもたらす薬剤は知られている。There is still no known complete cure for AIDS, but it is possible to prevent the onset of AIDS in carriers or slow the progression of the disease.
Medications are known that prolong the survival of IDS patients.
A Z T (P+oc、 Na11. ^cad
、 Sci、 υS^82゜7θ96(1985)
)は、この様な効果を示す、抗HIV剤の一つである。A Z T (P+oc, Na11. ^cad
, Sci, υS^82゜7θ96 (1985)
) is one of the anti-HIV agents that exhibits such effects.
AZTは現在唯一の認可薬であり、世界中で多く使用さ
れているが、骨髄毒性(N、 Eng、 IMcd
、 317. 192(1987))などの副作用が
知られている。さらに、AZTを長期に使用すると、H
IVのAZT耐性株が出現することがわかっており(S
cience 243. 1711f19H) ) 、
この面からもAZTに変わる次の抗HIV剤が待たれて
いる。AZT is currently the only approved drug and is widely used around the world, but it is associated with bone marrow toxicity (N, Eng, IMcd).
, 317. 192 (1987)) and other side effects are known. Furthermore, when using AZT for a long time, H
It is known that AZT-resistant strains of IV appear (S
science 243. 1711f19H) ),
From this point of view as well, we are eagerly awaiting the next anti-HIV drug that will replace AZT.
本発明の目的は、既存の薬剤に見られる以上のような種
々の欠点を克服する新しい抗ウィルス剤と、その合成方
法を提供することにある。An object of the present invention is to provide a new antiviral agent that overcomes the various drawbacks of existing drugs, and a method for synthesizing the same.
本発明は、−綴代[I]
(式中Xは水素原子あるいはアミノ基、Rは水素原子、
またはアセチル基、プロピオニル基。The present invention has the following advantages: -Tsujiro [I] (wherein X is a hydrogen atom or an amino group, R is a hydrogen atom,
Or acetyl group, propionyl group.
ベンゾイル基、その他のC2Qまでのアシル基のいずれ
かである。)
で示される新規な核酸誘導体が、抗ウィルス作用を有す
ることを見出したことに基づいている。It is either a benzoyl group or other acyl groups up to C2Q. This is based on the discovery that a novel nucleic acid derivative shown in ) has antiviral activity.
本発明は、上記の一般式[I]で表される、2′,3′
−ジデオキシプリンヌクレオシド類のうち、少なくとも
一種類を有効成分として含有することを特徴とする、新
規な抗ウィルス剤及びその製造方法に関するものである
。The present invention provides 2',3' represented by the above general formula [I]
- A novel antiviral agent characterized by containing at least one type of dideoxypurine nucleosides as an active ingredient, and a method for producing the same.
本発明において、出発物質として用いられる一般式[n
]で表されるプリン誘導体は、微生物による塩基交換反
応を用いて容易に得ることができる(特願平01−46
183号)。In the present invention, the general formula [n
] The purine derivative represented by
No. 183).
また、固定化した微生物を用いれば、工業的に安価に得
ることができる(特願平l1l−181885号)。Furthermore, if immobilized microorganisms are used, it can be obtained industrially at low cost (Japanese Patent Application No. 111-181885).
以下に、本発明の新規抗ウィルス剤、すなわち、6−ヒ
ドロキシアミノプリン−2′,3′−ジデオキシリボフ
ラノシド類の抗ウィルス作用について説明する。The antiviral action of the novel antiviral agent of the present invention, ie, 6-hydroxyaminopurine-2',3'-dideoxyribofuranosides, will be explained below.
本発明の新規抗ウィルス剤の持つ抗ウイルス効果は、拮
抗阻害効果とDNAチェーン・ターミネーション効果と
の相乗効果である。The antiviral effect of the novel antiviral agent of the present invention is a synergistic effect of a competitive inhibitory effect and a DNA chain termination effect.
これらの効果は、本発明の新規抗ウィルス剤が、2′,
3′−ジデオキシプリンリボフラノシド骨格という特殊
な構造をしていることに由来する。These effects are due to the fact that the novel antiviral agent of the present invention has 2′,
It originates from its unique structure of 3'-dideoxypurine ribofuranoside skeleton.
すなわち、本発明の新規抗ウィルス剤は、その構造がD
NAの成分であるヌクレオシド(特に、2′−デオキシ
アデノシン、2′−デオキシグアノシンなど)に非常に
似ている。That is, the novel antiviral agent of the present invention has the structure D
It is very similar to nucleosides (especially 2'-deoxyadenosine, 2'-deoxyguanosine, etc.) that are components of NA.
このため、ライスル由来の酵素に対する親和性が良く、
ライスルの酵素は本来の基質であるDNA構成核酸(2
′−デオキシアデノシン、2′−デオキシグアノシンな
ど)とまちがって本発明の新規抗ウィルス剤を取込み、
結果的に、ライスルDNAの合成を妨げて(拮抗阻害)
、第1の抗ウイルス効果を示す。For this reason, it has good affinity for enzymes derived from Lysul,
Lysl's enzyme uses its original substrate, DNA-constituent nucleic acid (2
'-deoxyadenosine, 2'-deoxyguanosine, etc.) and incorporate the novel antiviral agent of the present invention,
As a result, it prevents the synthesis of Lysul DNA (competitive inhibition).
, showing the first antiviral effect.
また、本発明の新規抗ウィルス剤は、3′の位置に水酸
基が存在しない構造をとっている。このため、−度ウイ
ルスDNA内に取込まれると、次の核酸が連結すること
ができず、ウィルスのDNA鎖はここで終結してしまう
。したがって、ウィルスはそれ以上増殖することができ
ずに、死滅してしまう。Furthermore, the novel antiviral agent of the present invention has a structure in which no hydroxyl group is present at the 3' position. Therefore, once it is incorporated into viral DNA, the next nucleic acid cannot be linked to it, and the viral DNA chain ends here. Therefore, the virus cannot reproduce any more and dies.
このようにして、本発明の新規抗ウィルス剤は、DNA
チェーン・ターミネータ−として働き、第2の抗ウイル
ス効果を示す。In this way, the novel antiviral agent of the present invention
It acts as a chain terminator and exhibits a second antiviral effect.
幸いなことに、人体の持つ酵素は、ウィルス由来の酵素
よりも格段に高度であるので、人体DNAやRNAの合
成において、拮抗阻害やチェーン・ターミネーションを
受けない。すなわち、本発明の抗ウィルス剤は人体の酵
素に対しては、基質特異性が非常に弱く、相互作用しな
い。Fortunately, the human body's enzymes are much more sophisticated than virus-derived enzymes, so they are not subject to competitive inhibition or chain termination during the synthesis of human DNA and RNA. That is, the antiviral agent of the present invention has very weak substrate specificity and does not interact with human enzymes.
現在、既にAIDS治療薬として認可されているAZT
や、臨床薬であるddIなどの抗ウイルス効果も、同様
に拮抗阻害とDNAチェーン・ターミネーションの相乗
効果によるとされているが、本発明の新規抗ウィルス剤
(すなわち6−ヒドロキシアミノプリン−2′,3′−
ジデオキシリボフラノシド類)は、以下に述べるように
、従来知られている薬(AZT、ddIなど)が持ち合
せていない特性と利点を持っている。AZT, which is currently approved as an AIDS treatment drug
The antiviral effect of the clinical drug ddI is also said to be due to the synergistic effect of competitive inhibition and DNA chain termination. ,3'-
Dideoxyribofuranosides) have properties and advantages that conventionally known drugs (AZT, ddI, etc.) do not have, as described below.
その特性とは、本発明の新規抗ウィルス剤が4種類の互
変異性体に変化できることによる。This property is due to the fact that the novel antiviral agent of the present invention can change into four types of tautomers.
簡単のために、−綴代[I]
(式中Xは水素原子あるいはアミノ基のいずれかであり
、Rは水素原子、またはアセチル基。For the sake of simplicity, -Tsujiro [I] (wherein X is either a hydrogen atom or an amino group, and R is a hydrogen atom or an acetyl group.
プロピオニル基、ベンゾイル基、その他のC20までの
アシル基のいずれかである。)で示される化合物のうち
、6−ヒドロキシアミノプリン−2′,3′−ジデオキ
シリボフラノシド の場合を例にとって説明する。It is a propionyl group, a benzoyl group, or any other acyl group up to C20. Among the compounds shown in ), the case of 6-hydroxyaminopurine-2',3'-dideoxyribofuranoside will be explained as an example.
下記に示すように、式(1)で表される、6−ヒドロキ
シアミノプリン−2′,3′−ジデオキシリボフラノシ
ドは、式(2)〜式(5)で表される4種の異性体の形
を安定構造として取り得る(互変異性)。As shown below, 6-hydroxyaminopurine-2',3'-dideoxyribofuranoside represented by formula (1) has four isomerisms represented by formulas (2) to (5). The body shape can be taken as a stable structure (tautomerism).
すなわち、本発明の新規抗ウィルス剤は、この性質のた
めに、抗ウィルス剤として有利となる以下の3つの効果
を持つことができる。That is, because of this property, the novel antiviral agent of the present invention can have the following three effects that are advantageous as an antiviral agent.
つまり、一種類の薬剤の投与で四種類の薬剤を投与した
のと同じ効果が期待できる。In other words, administering one type of drug can be expected to have the same effect as administering four types of drugs.
■ 酵素の代謝経路は、一般に一つの基質に対して、G
ne passWa7が基本である。■ Enzyme metabolic pathways generally require G for one substrate.
ne passWa7 is the basic.
例えば、アデノシン、イノシン、グアノシンのリン酸化
代謝は、それぞれ異なった酵素によって行われる。しか
し、本発明の新規抗ウィルス剤は、その互変異性効果に
よりいくつもの酵素に対して基質と成り得る。For example, the phosphorylation metabolism of adenosine, inosine, and guanosine is carried out by different enzymes. However, the novel antiviral agent of the present invention can serve as a substrate for several enzymes due to its tautomeric effect.
■ 4種類の互変異性体は瞬時に変化するの来にくい。■ It is difficult for the four types of tautomers to change instantly.
以上述べてきたように、本発明の新規抗ウィルス剤は、
分子内に6−ヒドロキシアミノプリンという特殊な構造
を有するために素早く互変異性ができ、ウィルスの酵素
親和性やウィルス耐性株耐性に優れるという、新しい特
性を持つ抗ウィルス剤である。As described above, the novel antiviral agent of the present invention is
It is an antiviral agent with new properties: it has a special structure called 6-hydroxyaminopurine in its molecule, which allows it to quickly become tautomerized, and it has excellent affinity for viral enzymes and resistance to virus-resistant strains.
本発明の新規抗ウィルス剤は、その部分構造に、2′,
3′−ジデオキシリボフラノシド骨格を有するため、特
にHIV(エイズウィルス)やR3V Oり肉腫ウィル
ス)などのレトロウィルスに対して有効であるが、他の
ウィルス、例えばB型肝炎ウィルスやヘルペスウィルス
に対しても、有効に作用する。The novel antiviral agent of the present invention has 2',
Because it has a 3'-dideoxyribofuranoside skeleton, it is particularly effective against retroviruses such as HIV (AIDS virus) and R3VO sarcoma virus), but it is effective against other viruses such as hepatitis B virus and herpes virus. It also works effectively against.
本発明において出発物質として用いられる、6位にハロ
ゲンを有する2′,3′−ジデオキシプリンヌクレオシ
ドは、前出のように微生物による塩基交換反応を用いて
容易に得ることができる(特願平01−46183号)
。例えば、6−クロログアニンとジデオキシウリジンと
を原料とした場合には、微生物(例えばEscheri
chia coli)を用いて塩基交換反応を行うと、
反応生成物である2′,3′−ジデオキシ−6−クロロ
グアノシンが良好な収率で得られる。また、固定化した
微生物を用いれば、さらに簡単に得ることができる(特
願平01−181885号)。The 2',3'-dideoxypurine nucleoside having a halogen at the 6-position, which is used as a starting material in the present invention, can be easily obtained using a base exchange reaction using a microorganism as described above (Japanese Patent Application No. -46183)
. For example, when 6-chloroguanine and dideoxyuridine are used as raw materials, microorganisms (such as Escheri
When a base exchange reaction is performed using chia coli),
The reaction product 2',3'-dideoxy-6-chloroguanosine is obtained in good yield. Moreover, it can be obtained even more easily by using immobilized microorganisms (Japanese Patent Application No. 181885/1999).
以上のようにして合成した、6位にハロゲンを有する2
′,3′−ジデオキシプリンヌクレオシドと、適当な有
機溶媒(例えばエタノール)とモノヒドロキシルアミン
とを用いて、本発明の新規抗ウィルス剤は容易に合成す
ることができる。2 having a halogen at the 6th position synthesized as above
The novel antiviral agent of the present invention can be easily synthesized using a ',3'-dideoxypurine nucleoside, a suitable organic solvent (eg, ethanol), and monohydroxylamine.
例えば、6−クロロ−2′,3′−ジデオキシプリンリ
ボフラノシドを、モノヒドロキシルアミンを溶解させた
エタノール中に加え、還流条件下に数時間撹拌すると、
6位の塩素とモノヒドロキシルアミンが反応して、目的
物である6−ヒドロキシアミノプリン−2′,3′−ジ
デオキシリボフラノシドが生成してくる。反応終了後、
反応溶液を室温までもどし、反応溶液と同量以上のエチ
ルエーテル中にブローすると、目的物の白色沈澱が得ら
れる。For example, when 6-chloro-2',3'-dideoxypurine ribofuranoside is added to ethanol in which monohydroxylamine is dissolved and stirred for several hours under reflux conditions,
The 6-position chlorine reacts with monohydroxylamine to produce the target product, 6-hydroxyaminopurine-2',3'-dideoxyribofuranoside. After the reaction is complete,
When the reaction solution is cooled to room temperature and blown into ethyl ether in an amount equal to or more than that of the reaction solution, a white precipitate of the desired product is obtained.
以上述べてきたように、本発明の合成方法によれば、容
易に入手可能な原料から簡単な手法によって、本発明に
係わる抗ウィルス剤を合成することができる。As described above, according to the synthesis method of the present invention, the antiviral agent according to the present invention can be synthesized by a simple method from readily available raw materials.
以下に実施例に従い、本発明をさらに詳細に説明する。 The present invention will be explained in more detail below with reference to Examples.
ただし、下記の実施例は説明のためにのみ示すものであ
って、如何なることがあっても本発明の範囲を制限する
意図は無い。However, the following examples are provided for illustrative purposes only and are not intended to limit the scope of the present invention in any way.
(1)製造例
製造例1
300 mlのナス型フラスコに、モノヒドロキシアミ
ンの塩酸塩12.0g (173mmol) 、水酸化
カリウムI1.2 g (20mmo I) 、無水エ
タノール200 mlを加え、2時間還流する。室温ま
で冷却後、沈澱したK(lをン濾過により除去し、炉液
を別の300 mlのナス型フラスコに移す。(1) Production Example Production Example 1 12.0 g (173 mmol) of monohydroxyamine hydrochloride, 1.2 g (20 mmol) of potassium hydroxide I, and 200 ml of absolute ethanol were added to a 300 ml eggplant-shaped flask for 2 hours. Reflux. After cooling to room temperature, the precipitated K(l) was removed by filtration, and the filtrate was transferred to another 300 ml eggplant-shaped flask.
これに、6−クロロプリン−2’−3’−ジデオキシリ
ボフラノシド1.45 g (5,7mmall を加
え、10時間還流する。その後室温まで戻し、2時間撹
拌を続ける。To this, 1.45 g (5.7 mmall) of 6-chloropurine-2'-3'-dideoxyribofuranoside is added and refluxed for 10 hours.Then, the temperature is returned to room temperature and stirring is continued for 2 hours.
反応終了後、エタノールを溜去した後、残渣をエチルエ
ーテル300m1中で撹拌すると、白い固形分が得られ
てくる。これを減圧過により集め、カラム処理(移動溶
媒
CHCl 3 :Me 0H=9 : 1)を行い、
UV吸収のあるフラクションを集め濃縮すると、無色の
薄片状結晶が得られてくる。この結晶を減圧乾燥(50
℃、 0. lmmHg 、 l0h)して、無色薄
片状結晶の6−ヒドロキシアミノプリン−2′,3′−
ジデオキシリボフラノシドを得た。収率86%。After the reaction was completed, the ethanol was distilled off and the residue was stirred in 300 ml of ethyl ether to obtain a white solid. This was collected by vacuum filtration and subjected to column treatment (mobile solvent CHCl 3 :Me 0H=9:1).
When the UV-absorbing fractions are collected and concentrated, colorless flaky crystals are obtained. The crystals were dried under reduced pressure (50
°C, 0. lmmHg, l0h), colorless flaky crystals of 6-hydroxyaminopurine-2',3'-
Dideoxyribofuranoside was obtained. Yield 86%.
無色薄片状結晶 融点112°C
NMRスペクトル(DMSO−δ6);δ1.66〜2
.60 (4H,m、 C2’ and C3’−H)
3、15〜3.80 (2H,m、 C5’−H)3
.80〜4.37 (IH,m、 C4’−H)6.
11 (III、 l、 CI’−H)7、
H(IIL s、 C1l −H)8.13
(IH,s、 C2−H)6.25〜8.95 (
3H,broad s、 C5’−OHandC6
−NHOH)
MSスペクトル(FAB−MS ; m/x)M+1
252
(C+。HI303 N、+1として)R1値(Sil
ica Get HF 254)0、 l 6 [CH
Cl 3 / M e OH= 9 / 1 ]0.
44 [CHCA! 3 Me 0H=4/1コ製
造例2
合成
300 mlのナス型フラスコに、モノヒドロキシアミ
ンの塩酸塩12.0 g (173mmol) 、水酸
化カリウムI 1.2 g (20mmo l) 、無
水エタノール200 mlを加え、2時間還流する。室
温まで冷却後、沈澱したKCIをン濾過により除去し、
炉液を別の300 mlのナス型フラスコに移す。Colorless flaky crystals Melting point 112°C NMR spectrum (DMSO-δ6); δ1.66-2
.. 60 (4H, m, C2' and C3'-H)
3, 15-3.80 (2H, m, C5'-H)3
.. 80-4.37 (IH, m, C4'-H)6.
11 (III, l, CI'-H)7,
H(IILs, C1l-H)8.13
(IH, s, C2-H) 6.25-8.95 (
3H, broads, C5'-OHandC6
-NHOH) MS spectrum (FAB-MS; m/x) M+1
252 (C+.HI303 N, +1) R1 value (Sil
ica Get HF 254) 0, l 6 [CH
Cl3/MeOH=9/1]0.
44 [CHCA! 3 Me 0H = 4/1 Co Production Example 2 Synthesis In a 300 ml eggplant-shaped flask, 12.0 g (173 mmol) of monohydroxyamine hydrochloride, 1.2 g (20 mmol) of potassium hydroxide I, and 200 g of absolute ethanol were added. ml and reflux for 2 hours. After cooling to room temperature, precipitated KCI was removed by filtration,
Transfer the furnace liquid to another 300 ml eggplant flask.
これに、2−アミノ−6−クロロプリン−2’ −3’
−ジデオキシリボフラノシド2.69 g (10m
mol)を加え、10時間還流する。その後室温まで戻
し、2時間撹拌を続ける。反応終了後、反応液をエチル
エーテル300m1中にブローすると、白い沈澱が得ら
れてくる。これを減圧 過により集め、エーテルで良く
洗浄し、これを減圧乾燥(50℃、 0.lmmHg
、 l0h) L、て、白色粉末状の2−アミノ6−
ヒドロキシアミノプリン−2′,3′−ジデオキシリボ
フラノシドを得た。To this, 2-amino-6-chloropurine-2'-3'
-dideoxyribofuranoside 2.69 g (10 m
mol) and reflux for 10 hours. Thereafter, the temperature is returned to room temperature and stirring is continued for 2 hours. After the reaction is completed, the reaction solution is blown into 300 ml of ethyl ether to obtain a white precipitate. This was collected by filtration under reduced pressure, washed well with ether, and dried under reduced pressure (50°C, 0.1 mmHg).
, l0h) L, te, white powdery 2-amino 6-
Hydroxyaminopurine-2',3'-dideoxyribofuranoside was obtained.
収率91%。 白色微結晶 融点156℃NMRスペク
トル(DMSO−δ6);δ1.72〜2.63 (4
H,m、 C2’ and C3’−H)3.32〜3
.80 (2H,m、 C5’−H)3.80〜4.3
0 (IH,m、 C4’−H)5.97 (IH
,t、 cl’−H)6.63 (2H,g、 C
6−NH2)7.87 (I)I、 s、 C
1l −H)5.0〜8.5 (3H,broad
s、 C5’−OHandC6−Nl−10H)
MSスペクトル(FAB −M S ; m#)M+1
267
(C+oH+、+03N6+lとして)R1値(Sil
ica Gel HF 254)0.09 [CHCl
3 /Me 0H=9/1]OJ2 [CHCA 、
Me 0H=4/1](2)抗ウイルス性試験
本発明による代表的化合物の抗ウイルスデータを以下に
示す。化合物番号は、本発明の実施例で製法を例示して
いる前記の実例の番号で示している。Yield 91%. White microcrystals Melting point 156℃ NMR spectrum (DMSO-δ6); δ1.72-2.63 (4
H, m, C2' and C3'-H) 3.32~3
.. 80 (2H, m, C5'-H) 3.80-4.3
0 (IH, m, C4'-H)5.97 (IH
,t, cl'-H)6.63 (2H,g, C
6-NH2)7.87 (I)I, s, C
1l -H)5.0~8.5 (3H, broad
s, C5'-OHandC6-Nl-10H) MS spectrum (FAB-MS; m#) M+1
267 (as C+oH+, +03N6+l) R1 value (Sil
ica Gel HF 254) 0.09 [CHCl
3/Me 0H=9/1]OJ2 [CHCA,
Me 0H=4/1] (2) Antiviral test Antiviral data of representative compounds according to the present invention are shown below. The compound number is indicated by the number of the above-mentioned example illustrating the preparation method in the Examples of the present invention.
試験例1
本発明の、−綴代[I]で表される化合物の抗ウィルス
作用を、ラウス肉腫ウィルス(RS V)を用いて試験
した。Test Example 1 The antiviral effect of the compound represented by -Tsukuriyo [I] of the present invention was tested using Rous sarcoma virus (RSV).
初代培養細胞(Chich Emb7o Fib+of
ast )を用いて、約30分間R3V感染させた。そ
して段階的に希釈した試料を添加し、4〜70後にR3
V感染による細胞の形質転換がどの段階において制御さ
れたかを検鏡により判定した。結果を表1に示した。Primary cultured cells (Cich Emb7o Fib+of
ast) for about 30 minutes. Then, stepwise diluted samples were added, and R3 was added after 4 to 70 minutes.
The stage at which cell transformation by V infection was controlled was determined by microscopy. The results are shown in Table 1.
表1 本発明の2′,3′−ジデオキシプリンリボフラ
ノシドの抗R3V活性
化合物番号 略 称 I D50 (μ
M) ED5o (μM)1 6−NHOH−d
dP 4 >5002 6−
NHOH−ddG 2 >250
ED5o : 50%細胞毒性濃度
表1に示されるとおり、本発明化合物は優れた抗ウイル
ス効果を示しており、また水に対する溶解性が非常に良
いため、本発明化合物がエイズやB型肝炎などのウィル
ス病治療薬として有効であることは明らかである。Table 1 Anti-R3V active compound number of 2',3'-dideoxypurine ribofuranoside of the present invention Abbreviation I D50 (μ
M) ED5o (μM)1 6-NHOH-d
dP4 >5002 6-
NHOH-ddG2 >250
ED5o: 50% cytotoxic concentration As shown in Table 1, the compound of the present invention exhibits an excellent antiviral effect, and has very good solubility in water, so the compound of the present invention is effective against diseases such as AIDS and hepatitis B. It is clear that it is effective as a therapeutic agent for viral diseases.
以上説明したように、この発明によれば、新規で抗ウィ
ルス作用の優れた化合物が提供される。例えば、エイズ
やB型肝炎およびヘルペス等のウィルス病治療薬とて極
めて有効である。As explained above, according to the present invention, a novel compound with excellent antiviral activity is provided. For example, it is extremely effective as a therapeutic agent for viral diseases such as AIDS, hepatitis B, and herpes.
Claims (1)
、Rは水素原子、またはアセチル基、プロピオニル基、
ベンゾイル基、その他の C20までのアシル基のいずれかである。)で示される
2′,3′−ジデオキシプリンリボヌクレオシド類。 (2)2−アミノ−6−ヒドロキシアミノプリン−9−
β−D−2′,3′−ジデオキシリボフラノシドである
請求項第(1)記載の化合物。 (3)6−ヒドロキシアミノプリン−9−β−D−2′
,3′−ジデオキシリボフラノシドである請求項(1)
記載の化合物。 (4)下記の式(2)〜式(5)で表される4種の互変
異性の形を安定構造としてとりうる請求項(3)記載の
化合物。 ▲数式、化学式、表等があります▼(2)▲数式、化学
式、表等があります▼(3) ▲数式、化学式、表等があります▼(4)▲数式、化学
式、表等があります▼(5) (5)一般式[II] ▲数式、化学式、表等があります▼[II] (式中Xは水素原子あるいはアミノ基のいずれかであり
、Yはハロゲン原子であり、Rは水素原子、またはアセ
チル基、プロピオニル基、ベンゾイル基、その他のC2
0までのアシル基のいずれかである。) に示すプリン化合物を、有機溶媒中、モノヒドロキシル
アミンで処理することにより、一般式[ I ]に示す2
′,3′−ジデオキシプリンリボヌクレオシド類を生成
させることを特徴とする核酸誘導体の製造法。 ▲数式、化学式、表等があります▼[ I ] (式中Xは水素原子あるいはアミノ基のいずれかであり
、Rは水素原子、またはアセチル基、プロピオニル基、
ベンゾイル基、その他のC20までのアシル基のいずれ
かである。) (6)請求項(5)記載の反応に用いる有機溶媒として
、一般式[II]に示すプリン化合物を完全に溶解でき、
かつ、反応に支障をきたさないメタノール、エタノール
などのアルコール系その他の溶媒を用いることを特徴と
する、一般式[ I ]で表される2′,3′−ジデオキ
シプリンヌクレオシド類の製造法。 (7)請求項(5)記載の反応を行う際に、反応生成物
である一般式[ I ]に示す2′,3′−ジデオキシプ
リンヌクレオシド類が溶解しにくい液体ベンゼン、エチ
ルエーテルその他の液体に、反応終了後の反応液を直接
ブローし、一般式[ I ]に示す2′,3′−ジデオキ
シプリンヌクレオシド類を析出させることを特徴とする
核酸誘導体の製造法。(8)請求項1記載の一般式[
I ]で表される2′,3′−ジデオキシプリンヌクレオ
シド類のうち、少なくとも一種を有効成分とする抗ウィ
ルス剤。 (9)請求項1記載の一般式[ I ]で表される2′,
3′−ジデオキシプリンヌクレオシド類のうち、少なく
とも一種を有効成分とする抗レトロウイルス剤。 (10)請求項1記載の一般式[ I ]で表される2′
,3′−ジデオキシプリンヌクレオシド類のうち、少な
くとも一種を有効成分とする後天性免疫不全症候群(A
IDS)の治療薬及び予防薬。 (11)請求項1記載の一般式[ I ]で表される2′
,3′−ジデオキシプリンヌクレオシド類のうち、少な
くとも一種を有効成分として含む、遺伝子工学上用いら
れる実験用医薬および実験用試薬。[Claims] (1) General formula [I] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [I] (In the formula, X is either a hydrogen atom or an amino group, and R is a hydrogen atom or an acetyl group, propionyl group,
It is either a benzoyl group or other acyl group up to C20. ) 2',3'-dideoxypurine ribonucleosides. (2) 2-amino-6-hydroxyaminopurine-9-
The compound according to claim 1, which is β-D-2',3'-dideoxyribofuranoside. (3) 6-hydroxyaminopurine-9-β-D-2'
, 3'-dideoxyribofuranoside. Claim (1)
Compounds described. (4) The compound according to claim (3), which can have four types of tautomeric forms represented by the following formulas (2) to (5) as stable structures. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (2) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (3) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( 5) (5) General formula [II] ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ [II] (In the formula, X is either a hydrogen atom or an amino group, Y is a halogen atom, and R is a hydrogen atom , or acetyl group, propionyl group, benzoyl group, or other C2
Any of up to 0 acyl groups. ) by treating the purine compound shown in formula [I] with monohydroxylamine in an organic solvent.
1. A method for producing a nucleic acid derivative, which comprises producing ',3'-dideoxypurine ribonucleosides. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] (In the formula, X is either a hydrogen atom or an amino group, and R is a hydrogen atom, or an acetyl group, a propionyl group,
It is either a benzoyl group or other acyl group up to C20. ) (6) The organic solvent used in the reaction according to claim (5) can completely dissolve the purine compound represented by the general formula [II],
A method for producing 2',3'-dideoxypurine nucleosides represented by the general formula [I], which is characterized in that an alcohol-based or other solvent such as methanol or ethanol that does not interfere with the reaction is used. (7) When carrying out the reaction described in claim (5), liquids such as benzene, ethyl ether, and other liquids in which the 2',3'-dideoxypurine nucleosides represented by the general formula [I], which are reaction products, are difficult to dissolve. A method for producing a nucleic acid derivative, which comprises directly blowing the reaction solution after completion of the reaction to precipitate 2',3'-dideoxypurine nucleosides represented by the general formula [I]. (8) General formula according to claim 1 [
An antiviral agent containing at least one kind of 2',3'-dideoxypurine nucleosides represented by [I] as an active ingredient. (9) 2' represented by the general formula [I] according to claim 1,
An antiretroviral agent containing at least one type of 3'-dideoxypurine nucleosides as an active ingredient. (10) 2′ represented by the general formula [I] according to claim 1
, 3'-dideoxypurine nucleosides as an active ingredient.
IDS) therapeutic and preventive drugs. (11) 2′ represented by the general formula [I] according to claim 1
, 3'-dideoxypurine nucleosides as an active ingredient.
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JP2298047A JP3059479B2 (en) | 1990-11-02 | 1990-11-02 | Novel antiviral agent and method for producing the same |
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JP2298047A JP3059479B2 (en) | 1990-11-02 | 1990-11-02 | Novel antiviral agent and method for producing the same |
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JPH04173787A true JPH04173787A (en) | 1992-06-22 |
JP3059479B2 JP3059479B2 (en) | 2000-07-04 |
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1990
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