JPS63243093A - Glycyrrhizin derivative - Google Patents
Glycyrrhizin derivativeInfo
- Publication number
- JPS63243093A JPS63243093A JP7636887A JP7636887A JPS63243093A JP S63243093 A JPS63243093 A JP S63243093A JP 7636887 A JP7636887 A JP 7636887A JP 7636887 A JP7636887 A JP 7636887A JP S63243093 A JPS63243093 A JP S63243093A
- Authority
- JP
- Japan
- Prior art keywords
- glycyrrhizin
- formula
- inhibitory effect
- effect
- gls
- 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
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical class O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 title claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 4
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 3
- -1 NH_4 Inorganic materials 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 16
- 239000004378 Glycyrrhizin Substances 0.000 abstract description 15
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 abstract description 15
- 229960004949 glycyrrhizic acid Drugs 0.000 abstract description 15
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 abstract description 15
- 235000019410 glycyrrhizin Nutrition 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 13
- 150000001875 compounds Chemical class 0.000 abstract description 11
- 102100034343 Integrase Human genes 0.000 abstract description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 8
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 abstract description 8
- 230000000840 anti-viral effect Effects 0.000 abstract description 5
- 231100000053 low toxicity Toxicity 0.000 abstract description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 abstract description 3
- 230000003449 preventive effect Effects 0.000 abstract description 3
- 241001430294 unidentified retrovirus Species 0.000 abstract description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 abstract description 2
- 208000030507 AIDS Diseases 0.000 abstract description 2
- CCVBWELWFSRMOR-UHFFFAOYSA-N [NH4+].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+] Chemical compound [NH4+].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+].[NH4+] CCVBWELWFSRMOR-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003443 antiviral agent Substances 0.000 abstract description 2
- 238000005670 sulfation reaction Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 241000700605 Viruses Species 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 208000037887 cell injury Diseases 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000005779 cell damage Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 108010088860 aralin Proteins 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 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
- 230000004083 survival effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は抗ウィルス活性を有する一般式（ｒ）で表わさ
れるグリチルリチン誘導体及びその薬理的に許容される
塩に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a glycyrrhizin derivative represented by the general formula (r) having antiviral activity and a pharmacologically acceptable salt thereof.
（式中Ｒは、ＳＯ３Ｍを表わし、ＭはＨ，ＮＩ＋、、ア
ルカリ金属原子を表わす。）
〔従来の技術〕
従来、抗ウイルス効果をもつ化合物が多数報告されてい
る。特に、近年世界的に広がりはじめた後天性免疫不全
症候群（ＡＩＤＳ）の病原ウィルス（Ｈｕｍａｎ Ｉ
ｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ Ｖｉｒｕｓ、 ＨＩ
Ｖ）に対して抗ウイルス効果を示す化合物の探索が活発
に行われている。それらの例としてポリアクリル酸・デ
キストランザルフェートなど（ＤｅＳｏｍｅｒ、 Ｐ、
ら； Ｊ、 Ｖｉｒｏｌ、 １９６８． ２．８７
８ ；同誌１９６８． ２．８８６）、スラミン（Ｄ
ｅ Ｃ１ｅｒｃｑ、 Ｅ、；Ｃａｎｃｅｒ Ｌｅｔｔ、
１９７９＋ ８ ＋ ９； Ｍｉｔｓｕｙａ、 Ｈ，
ら；Ｓｃｉｅｎｃｅ（Ｗａｓｈｉｎｇｔｏｎ、 Ｄ、Ｃ
，）１９８４，２２６．１７２）エバンス・ブルー（Ｂ
ａｌｚａｒｉｎｉ、 Ｊ、ら； Ｉｎｔ、 Ｊ。(In the formula, R represents SO3M, and M represents H, NI+, or an alkali metal atom.) [Prior Art] Many compounds having antiviral effects have been reported in the past. In particular, the pathogenic virus (Human I
immunodeficiency Virus, HI
The search for compounds that exhibit antiviral effects against V) is actively underway. Examples of these include polyacrylic acid and dextran sulfate (DeSomer, P.
et al; J, Virol, 1968. 2.87
8; same magazine 1968. 2.886), suramin (D
e C1ercq, E, ;Cancer Lett,
1979+8+9; Mitsuya, H.
Science (Washington, D, C
,) 1984, 226.172) Evans Blue (B
alzarini, J. et al; Int, J.
Ｃａｎｃｅｒ １９８６，３７．４５１）、アラリンカ
ルボン酸（Ｂａｌｚａｒｉｎｉ、Ｊ、 ら； Ｂ’＋
ｏｃｈｅｍ、 Ｂｉｏｐｈｙｓ、 Ｒｅｓ。Cancer 1986, 37.451), aralin carboxylic acid (Balzarini, J, et al.; B'+
ochem, Biophys, Res.
Ｃｏｍｍｕｎ、 １９Ｂ６．１３６ 、６４）、 ３’
−アジド−２’、３’−ジデオキシチミジン（八ＺＴ）
（Ｍｉｔｓｕｙａ。Commun, 19B6.136, 64), 3'
-Azide-2',3'-dideoxythymidine (8ZT)
(Mitsuya.
Ｈ，ら； Ｐｒｏｃ、 Ｎａｔｌ、 Ａｃａｄ、 Ｓｃ
ｉ、 ＩＪ、Ｓ、Δ、 １９８５゜玖、 ７０９６）、
２’、３’−ジデオキシヌクレオシド（Ｍｉｔｓｕｙａ
、 Ｈ，ら； Ｐｒｏｃ、 Ｎａｔｌ、 八ｃ
ａｄ、 Ｓｃｉ。H, et al; Proc, Natl, Acad, Sc
i, IJ, S, Δ, 1985゜ku, 7096),
2',3'-dideoxynucleoside (Mitsuya
, H, et al; Proc, Natl, 8c
ad, Sci.
Ｕ、Ｓ、八、 １９８６．服、１９１１）、グリデルリ
チン（伊藤正彦ら；第３４回日本ウィルス学会総会講演
要旨集１９８６． ｐ７０）などが報告されている。U, S, 8, 1986. Glyderritin (Masahiko Ito et al.; Abstracts of the 34th Annual Meeting of the Japanese Society for Virology, 1986. p. 70), etc. have been reported.
ウィルス、特に１（ＩＶに対してｉｎ ｖｉｔｒｏのみ
ならず臨床的に最も有効な化合物として／ＩＺＴが知ら
れているが、これとてもＡＩＤＳ患者の延命効果は認め
られるものの、治療薬あるいは予防薬とはなり得ておら
ず、また副作用にも問題があるため、早急に治療・予防
に有効な他の化合物を開発することが望まれていた。IZT is known as the most effective compound not only in vitro but also clinically against viruses, especially IV (IV), but although it has been shown to be effective in prolonging the survival of AIDS patients, it is not a therapeutic or preventive drug. However, there are problems with side effects, so there has been an urgent need to develop other compounds that are effective for treatment and prevention.
また、これらの薬剤は、−殻に、長期間連続的に投与す
る必要があるため、毒性、副作用が極力低いことが強く
望まれていた。Furthermore, since these drugs need to be administered continuously over a long period of time, it is strongly desired that their toxicity and side effects be as low as possible.
本発明はこのような問題点を解決するだめのものであっ
て、一般式ＣＩ）を有するグリチルリチンペンクサルフ
ェートが、この目的とする作用を有するものであること
を見出してなされたものである。The present invention is aimed at solving these problems, and was made based on the discovery that glycyrrhizin penxulfate having the general formula CI) has the desired effect.
本発明の一般式〔ＩＪで表わされる化合物を製造するに
は、グリチルリチンを常法によりサルフェート化すれば
よく、その−例を反応式で示せば次の通りである。In order to produce the compound represented by the general formula [IJ] of the present invention, glycyrrhizin may be converted into sulfate by a conventional method, and an example thereof is shown in the following reaction formula.
すなわち、ピリジン中でグリチルリチンに過剰量のクロ
ルスルホン酸を低温下に加えてサルフェート化反応を行
わせる。サルフェート化剤としてサルファトリオキサイ
ド−♂リジン（Ｓ０３・Ｃｓ１ｌＳＮ： Ｂａｕｍｇａ
ｌｔｅｎ、 Ｐ、 ； Ｂｅｒ、５９１１６０（１，９
２６））を用いてもよい。反応液から一般式（１）の化
合物を単離するには、通常使用される手段、たとえば≧
宿出、イオン交換クロマトグラフィー、薄層クロマトグ
ラフィー、再結晶等の方法を単独または組合わせて使用
すればよい。That is, an excess amount of chlorosulfonic acid is added to glycyrrhizin in pyridine at low temperature to cause a sulfation reaction. Sulfatrioxide-♂lysine (S03・Cs1lSN: Baumga
Ber, 591160 (1,9
26)) may be used. To isolate the compound of general formula (1) from the reaction solution, commonly used means, for example ≧
Methods such as emulation, ion exchange chromatography, thin layer chromatography, and recrystallization may be used alone or in combination.
本発明の一般式［１）の化合物は、必要に応じて薬理的
に許容し得る塩に変えることができる。塩としては、カ
リウム、ナトリウム等のアルカリ金属塩、アンモニウム
塩をあげることができ、これらの塩は常法によって容易
に製造することができる。The compound of general formula [1) of the present invention can be converted into a pharmacologically acceptable salt if necessary. Examples of the salt include alkali metal salts such as potassium and sodium salts, and ammonium salts, and these salts can be easily produced by conventional methods.
本発明の一般式ＣＩ）の化合物は、ウィルス、特にレト
ロウィルスに対して強い抗ウイルス効果を示すだけでな
く、有効濃度幅が広く、毒性も低く、逆転写酵素活性阻
害効果を示すため、Δ■ＤＳの治療薬および予防薬とし
て有用である。The compound of general formula CI) of the present invention not only exhibits a strong antiviral effect against viruses, especially retroviruses, but also has a wide effective concentration range, low toxicity, and exhibits a reverse transcriptase activity inhibitory effect. ■It is useful as a therapeutic and preventive drug for DS.
実施例Ｉ （グリチルリチンペンタサルフェート・アン
モニウム塩）
グリチルリチン８．２ｇをピリジン１００ｍｆｆに溶解
し、０℃にてクロルスルホン酸５．３ｍＡを滴下した。Example I (Glycyrrhizin pentasulfate ammonium salt) 8.2 g of glycyrrhizin was dissolved in 100 mff of pyridine, and 5.3 mA of chlorsulfonic acid was added dropwise at 0°C.
室温にて一晩攪拌した後ピリジンを留去し、油状の残留
物シリカゲル・クロマト（クロロホルム：メタノール５
：１）にて精製し、目的物（１）を含むフラクションに
アンモニア水を加えてｐＨを８とし、析出した結晶を濾
集後酢酸エチルで洗浄し、結晶５．Ｏｇを得た。After stirring overnight at room temperature, pyridine was distilled off and the oily residue was chromatographed on silica gel (chloroform: methanol 5
Ammonia water was added to the fraction containing the target product (1) to adjust the pH to 8, and the precipitated crystals were collected by filtration and washed with ethyl acetate to obtain crystals 5. Obtained Og.
融点＝１７５°Ｃ（分解）
Ｒｆ ： ０．４２ （ｎ−ブタノール：酢酸：水 ２
：１：１）〔α） ［１： ＋ ４２．６ （ｃ ＝
１ 、水）元素分析値（Ｃ４゜ＨｅｂＮａＯｓ＋Ｓ５と
して）実測値： Ｃ３７，５０Ｈ６，７８Ｎ ７．９７
５１１．６０計算値： Ｃ３７，１１Ｈ６，３７Ｎ
８．２４ Ｓ Ｉｌ、’ｒ８〔作 用〕
■ ＩＩＴＶ感染による細胞障害に対する抑制効ＭＴ−
４細胞に旧Ｖを感染させた後、所定の濃度になるように
実施例１の化合物（ＧＬＳ）を添加し、６日間培養した
。６日後に生存細胞数を観察することにより、旧Ｖ感染
による細胞障害がどの程度抑制されるかを測定した。対
照薬としてはグリチルリチン（ＧＬ）を用いた。その結
果を第１図に示した。口はＭＴ−４細胞に対する。また
、■はＨＩＶを感染させた細胞に対する効果を示す。Melting point = 175°C (decomposition) Rf: 0.42 (n-butanol:acetic acid:water 2
:1:1) [α) [1: + 42.6 (c =
1, Water) Elemental analysis value (as C4°HebNaOs+S5) Actual value: C37,50H6,78N 7.97
511.60 Calculated value: C37,11H6,37N
8.24 SIl,'r8 [Effect] ■ Suppressive effect on cell damage caused by IITV infection MT-
After infecting 4 cells with old V, the compound of Example 1 (GLS) was added to a predetermined concentration and cultured for 6 days. By observing the number of viable cells after 6 days, the extent to which cell damage caused by old V infection was suppressed was determined. Glycyrrhizin (GL) was used as a control drug. The results are shown in Figure 1. mouth to MT-4 cells. In addition, ■ indicates the effect on cells infected with HIV.
対照のＧＬが１．２５■／ｍｅで旧νの細胞障害抑制効
果が認められたのに対し、ＧＬＳでは０．２５〜２．５
ｍｇ／ ＋ｎｊ！ （ＧＬの１１５〜゛２倍）の広い濃
度範囲で抑制効果を示した。ＧＬＳは低濃度でも抑制効
果をもち、しかも細胞への毒性も低いため、有効濃度幅
が広いことが判る。The cytotoxicity suppressing effect of old ν was observed for the control GL at 1.25 μ/me, whereas for GLS it was 0.25 to 2.5
mg/+nj! It showed an inhibitory effect over a wide concentration range (115 to 2 times that of GL). Since GLS has an inhibitory effect even at low concentrations and has low toxicity to cells, it can be seen that it has a wide range of effective concentrations.
なおこの実験は、Ｈａｒａｃｌａ、Ｓら； ５ｃｉｅｎ
ｃｅ、１９８５゜２２９ 、５６３−５６６に記載され
た方法に従って行った。以下の実験も同様である。This experiment was performed by Haracla, S et al.
ce, 1985°229, 563-566. The same applies to the following experiments.
■ ＨＩＶ感染細胞の旧Ｖ抗原陽性化抑制効果ＭＴ−４
細胞に旧Ｖを感染させ、所定濃度のＧＬＳまたは対照薬
としてのＧＬを添加して培養し、一定時間後に間接螢光
抗体法（ＩＦ法）で旧Ｖ抗原陽性となった細胞を測定し
た。その結果を第２図に示した。■ Effect of suppressing old V antigen positivity in HIV-infected cells MT-4
Cells were infected with old V, cultured with the addition of a predetermined concentration of GLS or GL as a control drug, and after a certain period of time, cells that became positive for old V antigen were measured by indirect fluorescent antibody method (IF method). The results are shown in Figure 2.
・はＧＬＳまたはＧＬ無添加
○は 〃〃０．１２５ ｍｇ／ｍ Ｅ添加■は ／／
／１０．２５ １１口は ／／ ／１０
．５ ／／ムは ／／ ／／ １
△は 〃〃２
の場合を示す。- GLS or GL-free ○ is 〃〃0.125 mg/m E-added ■ is //
/10.25 11 shares are // /10
．． 5 //mu is // // 1 △ indicates the case of 〃〃2.
薬剤無添加では培養３日目で抗原陽性化率８２％、６日
目で１００％であったものが、ＧＬＳを０．２５〜０．
５ ｍｇ／ ｍＲ添加すると抗原陽性細胞の出現は３％
以下となり、有意に抑制されたことがわかる。ＧＬの場
合には、１〜２■／ｍＡ添加しないと抑制効果は現われ
ない。When no drug was added, the antigen positivity rate was 82% on the 3rd day of culture and 100% on the 6th day, but the GLS was 0.25-0.
When adding 5 mg/mR, the appearance of antigen-positive cells was 3%.
It can be seen that it was significantly suppressed. In the case of GL, no inhibitory effect appears unless it is added at 1 to 2 .mu./mA.
■ ＨＩＶおよびトリ骨髄性白血病ウィルス（八ｖｉａ
ｎ Ｍｙｅｌｏｂｌａｓｔｏｓｉｓ Ｖ １ｒｕｓ；
八ＭＶ）の逆転写酵素活性に対する阻害効果を第３図に
示した。■ HIV and avian myeloid leukemia virus (8via
n Myeloblastosis V 1rus;
The inhibitory effect of 8MV) on reverse transcriptase activity is shown in FIG.
Ｏは旧Ｖの、また、・はＡＭＶの逆転写酵素活性に対す
るＧＬＳの阻害効果を示す。O indicates the inhibitory effect of GLS on old V reverse transcriptase activity, and . indicates the inhibitory effect of GLS on AMV reverse transcriptase activity.
ＧＬには逆転写酵素阻害効果がないのに対してＧＬＳに
は阻害効果が認められた。GL had no reverse transcriptase inhibitory effect, whereas GLS had an inhibitory effect.
本発明の一般式（１）の化合物は、ウィルス感染による
細胞障害に対する抑Ｈｄｌ効果、感染細胞のウィルス抗
原陽性化抑制効果、レトロウィルスの逆転写酵素に対す
る阻害効果等を奏し、また毒性が弱いため、抗ウィルス
剤、ウィルス疾患の治療、予防に有用な薬剤となり得る
ものである。The compound of general formula (1) of the present invention has an Hdl inhibitory effect on cell damage caused by viral infection, an inhibitory effect on virus antigen positivity of infected cells, an inhibitory effect on retrovirus reverse transcriptase, etc., and has low toxicity. , an antiviral agent, and a drug useful in the treatment and prevention of viral diseases.
第１図は旧Ｖ感染による細胞障害に対するＧＬＳまたは
ＧＬの抑制効果を示したものであり、第２図はＨ１ν感
染細胞の旧Ｖ抗原陽性化に対するＧＬＳまたはＧＬの抑
制効果を示したものであり、第３図は旧ＶおよびＡＭＶ
の逆転写酵素活性に対するＧＬＳの阻害効果を示すもの
である。Figure 1 shows the inhibitory effect of GLS or GL on cell damage caused by old V infection, and Figure 2 shows the inhibitory effect of GLS or GL on the old V antigen positivity of H1ν-infected cells. , Figure 3 shows the old V and AMV
2 shows the inhibitory effect of GLS on the reverse transcriptase activity of .
Claims (1)
Ｒは−ＳＯ＿３Ｍを表わし、ＭはＨ、ＮＨ＿４、アルカ
リ金属原子を表わす。）。[Claims] Glycyrrhizin derivatives and salts thereof (in the formula,
R represents -SO_3M, and M represents H, NH_4, or an alkali metal atom. ).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62076368A JP2520252B2 (en) | 1987-03-31 | 1987-03-31 | Glycyrrhizin derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62076368A JP2520252B2 (en) | 1987-03-31 | 1987-03-31 | Glycyrrhizin derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63243093A true JPS63243093A (en) | 1988-10-07 |
| JP2520252B2 JP2520252B2 (en) | 1996-07-31 |
Family
ID=13603402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62076368A Expired - Fee Related JP2520252B2 (en) | 1987-03-31 | 1987-03-31 | Glycyrrhizin derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2520252B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0587374A2 (en) * | 1992-09-02 | 1994-03-16 | Virostat (Na) Nv | Sulfated sterol glycosides and their use against viral infections. |
| US5356880A (en) * | 1991-05-30 | 1994-10-18 | Sanwa Kagaku Kenkyusho Co., Ltd. | Glycyrrhetinic acid derivatives |
| US5624909A (en) * | 1992-09-10 | 1997-04-29 | Glycomed Incorporated | Derivatives of triterpenoid acids as inhibitors of cell-adhesion molecules ELAM-1 (e-selectin) and LECAM-1 (l-selectin) |
| JP2013028541A (en) * | 2011-06-20 | 2013-02-07 | Foundation For Biomedical Research & Innovation | Alpha-klotho/fgf23 complex formation-inhibiting compound |
-
1987
- 1987-03-31 JP JP62076368A patent/JP2520252B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5356880A (en) * | 1991-05-30 | 1994-10-18 | Sanwa Kagaku Kenkyusho Co., Ltd. | Glycyrrhetinic acid derivatives |
| EP0587374A2 (en) * | 1992-09-02 | 1994-03-16 | Virostat (Na) Nv | Sulfated sterol glycosides and their use against viral infections. |
| EP0587374A3 (en) * | 1992-09-02 | 1996-05-29 | Virostat Na Nv | Sulfated sterol glycosides and their use against viral infections |
| US5624909A (en) * | 1992-09-10 | 1997-04-29 | Glycomed Incorporated | Derivatives of triterpenoid acids as inhibitors of cell-adhesion molecules ELAM-1 (e-selectin) and LECAM-1 (l-selectin) |
| JP2013028541A (en) * | 2011-06-20 | 2013-02-07 | Foundation For Biomedical Research & Innovation | Alpha-klotho/fgf23 complex formation-inhibiting compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2520252B2 (en) | 1996-07-31 |
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