JP3598168B2 - Antiviral agent - Google Patents
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- JP3598168B2 JP3598168B2 JP06068196A JP6068196A JP3598168B2 JP 3598168 B2 JP3598168 B2 JP 3598168B2 JP 06068196 A JP06068196 A JP 06068196A JP 6068196 A JP6068196 A JP 6068196A JP 3598168 B2 JP3598168 B2 JP 3598168B2
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Description
【発明の属する技術分野】
この発明は、抗ウイルス剤に関するものである。さらに詳しくは、この発明は、優れた活性を有するフラノナフトキノン誘導体を有効成分とする新規な抗ウイルス剤に関するものである。
【0002】
【従来の技術とその課題】
RNAウイルスの感染によって起こる疾患には、日本脳炎、デング熱、麻疹、流行性耳下腺炎、風疹、インフルエンザ、A型肝炎、C型肝炎、黄熱病、出血熱、髄膜炎、小児性下痢症、狂犬病、エボラ出血熱、ラッサ熱、ポリオ、セントルイス脳炎、成人T細胞白血病、エイズ等があり、さらにRNAウイルス感染が原因と推定されている難治性疾患としては、慢性関節リウマチ、全身性エリテマトーデス、多発性硬化症、亜急性硬化性全脳炎、アルツハイマー病、潰瘍性大腸炎、クローン病、川崎病、糖尿病等があることが知られている。しかしながら、現状においては、RNAウイルス感染病に対して有効な化学治療薬はほとんど見出されていない。
実際にも、たとえば日本脳炎、インフルエンザ、麻疹、風疹、流行性耳下腺炎、ポリオ等の関連ウイルスが特定されているものについては、不活化ワクチンや生ワクチンを用いる予防治療がなされるのみであり(狂犬病は血清療法)、発症した場合の治療効果は低いのが実情である。また、非特異的な生体内抵抗物質であるインターフェロン(IFN)が現在最も有効な抗ウイルス剤として知られているが、このものは宿主細胞に対する毒性があり、発熱、全身倦怠感、頭痛、食欲不振、白血球血小板減少、中枢神経障害等の副作用が大きいという問題がある。
さらに、抗RNAウイルス化学療法剤としてはリバビリン、アマンタジンが知られているが、その効果は低く、細胞毒性に伴う不眠、神経過敏等の副作用が強い。このため、RNAウイルス感染病に対して優れた抗ウイルス活性を有し、しかも、細胞、生体組織に対する副作用の少ない有効な治療薬の出現が待たれている状況にある。
【課題を解決するための手段】
この発明は、上記のとおりの課題を解決するものとして、次式(I)
【0007】
【化2】
(式中のR1は水素原子、メチル基、または1−ヒドロキシエチル基であり、R2およびR3は、水素原子またはヒドロキシル基である)で表されるフラノナフトキノン誘導体を有効活性成分として含有することを特徴とする抗ウイルス剤を提供する。
【発明の実施の形態】
上記のとおりのフラノナフトキノン誘導体を有効活性成分とするこの発明の抗ウイルス剤および抗菌剤については、広範囲のフラノナフトキノン誘導体が用いられることになる。
これらを例示すると、たとえば、2−メチルナフト〔2,3−b〕フラン−4,9−ジオン、2−アセチルナフト〔2,3−b〕フラン−4,9−ジオン、2−(1−ヒドロキシエチル)ナフト〔2,3−b〕フラン−4,9−ジオン、ナフト〔2,3−b〕フラン−4,9−ジオン、5(または8)−ヒドロキシ−2−(1−ヒドロキシエチル)ナフト〔2,3−b〕フラン−4,9−ジオン、5(または8)−ヒドロキシナフト〔2,3−b〕フラン−4,9−ジオン、2−メチル−5(または8)−ヒドロキシ−2−メチルナフト〔2,3−b〕フラン−4,9−ジオン、1,3−ジメチルイソフラノナフトキノン、2−(アセチルエチレンアセタール)ナフト〔2,3−b〕フラン−4,9−ジオン、8−ヒドロキシ−7−メトキシナフト〔2,3−b〕フラン−4,9−ジオン、3−アセチル−5,8−ジメトキシ−2−メチルナフト〔2,3−b〕フラン−4,9−ジオン等々が挙げられる。もちろん、これら例示に何ら限定されることなく、前記の式により表わされる様々な態様がこの発明には可能である。そして、前記式におけるアルキル基、ヒドロキシアルキル基、アルコキシアルキル基については、活性を阻害しない限り、他の任意の置換基、たとえばアルケニル基、シクロアルキル基、シクロアルケニル基、アリール基、ハロゲン原子、アミノ基、ニトロ基、シアノ基、チオール基、チオエーテル基、カルボキシル基、エステル基、アミド基、スルホニル基、ハロホルミル基、複素環基等々が結合されていてもよい。
これらの各種の化合物は、これまで公知の様々な化学的合成の手法、あるいは天然物としての樹皮等からのフラノナフトキノン類の抽出等によって製造することができる。
そして、この発明の抗ウイルス剤は、たとえば、RNAウイルス全般を対象とすることができ、たとえば、適用し得る疾患としては、日本脳炎、デング熱、麻疹、流行性耳下腺炎、風疹、インフルエンザ、A型肝炎、C型肝炎、黄熱病、出血熱、髄膜炎、小児性下痢症、狂犬病、エボラ出血熱、ラッサ熱、ポリオ、セントルイス脳炎、成人T細胞白血病、エイズ等のRNAウイルスが原因となる疾患及びRNAウイルス感染が原因と推定されている慢性関節リウマチ、全身性エリテマトーデス、多発性硬化症、亜急性硬化性全脳炎、アルツハイマー病、潰瘍性大腸炎、クローン病、川崎病、糖尿病等の難治性疾患等が例示される。
このようなこの発明の抗ウイルス剤は、液剤、固形剤等の様々な剤形において、経口、皮下、静脈、外用等の各種の方法によって処方することができる。当然、その際には、従来公知の配合成分を添加し、塩、エステル等の保護剤をはじめ各種の態様として薬剤組成を構成することができる。
そこで、以下、実施例を示し、この実施例に沿ってさらに詳しくこの発明について説明する。
【実施例】
実施例1
(2−(1−ヒドロキシエチル)ナフト〔2,3−b〕フラン−4,9−ジオンの製造)
sec−BuLiを用いたメタレーション反応により合成した。すなわち、N,N−ジエチルベンズアミドに、エーテル中(又はTHF中)、−78℃でsec−BuLi(1eq.)とTMEDA(1eq.)を1時間反応させる。次に−78℃で5−(1−ヒドロキシエチル)−3−フルアルデヒド誘導体(1eq.)を滴下し、さらにsec−BuLi(4eq.)を加え徐々に室温にもどし、1晩攪拌を続ける。水を加えクロロホルム抽出し、クロロホルム層を飽和NaCl水で洗った後、乾燥留去する。残渣をPTLC(クロロホルム:アセトン=100:1)により分離精製し、保護基を除去し、次式の化合物の黄色結晶を得た。
【化3】
実施例2
(2−メチルナフト〔2,3−b〕フラン−4,9−ジオンの製造)
2−ヒドロキシ−1,4−ナフトキノンとプロピオンアルデヒドから合成した2−ヒドロキシ−3−(2−プロペニル)−1,4−ナフトキノン(150mg)とDDQ(200mg)をベンゼン(20ml)中攪拌、還流する。2〜3時間後、冷却し、濾過して濾液を留去する。残渣をカラムクロマトグラフィー(シリカゲル30g、ベンゼン)にかけ、最初の黄色分画より目的の次式化合物を黄色結晶として得た(35%)。
【化4】
【表1】
実施例3
(A)8−ヒドロキシナフト〔2,3−b〕フラン−4,9−ジオン、および(B)8−ヒドロキシ−2−メチルナフト〔2,3−b〕フラン−4,9−ジオンの製造)
塩化アルミニウム(2.5g)と無水3−ヒドロキシフタル酸(1g)をニトロベンゼン(5ml)に加え、アセチルフラン(0.7g)または2−アセチル−5−メチルフランを滴下し100℃で一晩加熱する。その後、クロロホルム抽出しニトロベンゼンを減圧留去した後カラムクロマトグラフィー(シリカゲル50g、ベンゼン)にかけ、精製し、次式化合物の黄色結晶を得た(〜5%)。
【化5】
【表2】
【化6】
【表3】
実施例4
(5−ヒドロキシ−2−(1−ヒドロキシエチル)ナフト〔2,3−b〕フラン−4,9−ジオンの製造)
Tecomaipe 乾燥樹皮(ブラジル産)10kgを純メタノール10l宛で30分3回加温還流下に抽出し、溶媒を減圧留去した。抽出物(1.45kg)をクロロホルム4l宛で3回冷浸し、クロロホルム層を水洗後、硫酸マグネシウムで乾燥し、溶媒を留去して抽出物10gを得た。これをトルエン・酢酸エチルエステル(4:1)を展開溶媒としてシリカゲル60F254 を用いて分離薄層クロマトグラフィーを反復して行い、Rf=0.24のスポットを抽出、クロロホルム−メタノール(9:1)で抽出し計8mgの次式化合物を得た(融点181℃)。
【化7】
実施例5
(抗ウイルス剤)
<A>試験材料
ウイルス:日本脳炎ウイルス(JEV)JaGAr−01株を用いた。
細胞:ウイルス感染用細胞として、サル腎臓細胞株Vero細胞を用い、5%牛胎仔血清を含むDMEM培地で37℃、5%CO2 存在下に培養した。
<B>試験方法
ウイルス感染とフラノナフトキノン誘導体による阻害:単層培養のVero細胞にJEVを10m.o.j.のウイルス量で感染させ、培養した。フラノナフトキノン誘導体はウイルス感染直後に添加し、ウイルス増殖を示す培養液中への放出ウイルス量に対する影響を調べた。
ウイルス量の測定:増殖したウイルス力価はBHK細胞を用いたプラーク法にて測定し、プラーク形成単位(PFU)で表わした。
細胞変性効果:ウイルスに感染した細胞が特異な円形顆粒状を呈することを利用して、ウイルス感染性を示す細胞変性効果(CPE)を測定した。
<C>試験結果
培養液中に放出されたJEVを感染24時間後に採取し、その力価を測定することによって、ウイルス増殖の阻害を調べた。前記実施例2の化合物による各種濃度での結果を示したものが表4である。
この表4のとおり、JEV増殖は濃度依存性に阻害され、50%増殖を阻害する濃度(IC50)は0.04μg/mlであった。3.3μg/mlでJEVの増殖は約90%阻害され、10μg/mlで98%阻害された。このような高い濃度でも宿主のVero細胞に対する細胞毒性は観察されず、また、ウイルス感染によって生じるCPEも認められなかった。
【表4】
実施例1、2、および3の化合物を用いた場合の3.3μg/ml濃度付近での結果を示したものが表5である。75%〜94%のJEV増殖阻害効果を示した。さらに実施例1および2の化合物については薬剤による細胞毒性が観察されなかった。
【表5】
なお、参考のためにインターフェロン(IFN)をポジティブコントロールとして用いた場合の結果を示したものが表6である。IFNは濃度依存性にJEVの増殖を阻害した。
また、抗菌剤OFLXの抗ウイルス活性をJEV増殖系でネガティブコントロールとして調査したが、宿主細胞に対する細胞毒性が生じる高濃度(100μg/ml)においても、顕著なJEV増殖阻害活性は認められなかった。
【表6】
JEVはフラビウイルス科に属するRNAウイルスであり、現在不活化ワクチンを用いた予防法のみがある。しかし近縁ウイルスだけに限ってみても、依然として猛威をふるっているデングウイルスには有効なワクチンはなく、C型肝炎ウイルスの場合はその世界的な広がりからみてさらに深刻である。
このような状況において、たとえば実施例2の化合物をはじめとするこの発明のフラノナフトキノン誘導体は、以上の結果からも、宿主細胞に対する細胞毒性なしにJEVに強い抗ウイルス活性を示し、RNAウイルスに対する有効な抗ウイルス剤であることが確認された。
【発明の効果】
以上詳しく説明したとおり、この発明により、抗ウイルス活性に優れ、しかも副作用の少ないフラノナフトキノン誘導体からなる抗ウイルス剤が提供される。TECHNICAL FIELD OF THE INVENTION
The present invention relates to anti-viral agents. More particularly, this invention relates to a novel antiviral agent comprising as an active ingredient Furano naphthoquinone derivative having superior activity.
[0002]
[Prior art and its problems]
Diseases caused by RNA virus infection include Japanese encephalitis, dengue, measles, mumps, rubella, influenza, hepatitis A, hepatitis C, yellow fever, hemorrhagic fever, meningitis, pediatric diarrhea , Rabies, Ebola hemorrhagic fever, Lassa fever, polio, St. Louis encephalitis, adult T-cell leukemia, AIDS, and the like. Intractable diseases that are presumed to be caused by RNA virus infection include rheumatoid arthritis, systemic lupus erythematosus, and multiple It is known that there are sclerosis, subacute sclerosing panencephalitis, Alzheimer's disease, ulcerative colitis, Crohn's disease, Kawasaki disease, diabetes and the like. However, at present, few chemotherapeutic agents effective against RNA virus infectious diseases have been found.
In fact, for cases where related viruses such as Japanese encephalitis, influenza, measles, rubella, mumps, polio, etc. have been identified, prophylactic treatment using inactivated vaccines or live vaccines is only performed. Yes (serum therapy for rabies), and the treatment effect is low when it occurs. In addition, interferon (IFN), a nonspecific bioresistance substance, is currently known as the most effective antiviral agent, but it is toxic to host cells, and produces fever, general malaise, headache, appetite. There is a problem that side effects such as poor performance, decreased white blood cell platelets, and central nervous system disorders are large.
Furthermore, ribavirin and amantadine are known as anti-RNA virus chemotherapeutic agents, but their effects are low and they have strong side effects such as insomnia and nervousness due to cytotoxicity. Therefore, there is a need for an effective therapeutic agent that has excellent antiviral activity against RNA virus infectious diseases and has few side effects on cells and living tissues.
[Means for Solving the Problems]
The present invention solves the above-mentioned problems by providing the following formula (I)
[0007]
Embedded image
(Wherein R 1 is a hydrogen atom, a methyl group, or a 1-hydroxyethyl group, and R 2 and R 3 are a hydrogen atom or a hydroxyl group) as the active ingredient. An antiviral agent is provided.
BEST MODE FOR CARRYING OUT THE INVENTION
A wide range of furanonaphthoquinone derivatives will be used for the antiviral and antibacterial agents of the present invention containing the furanonaphthoquinone derivative as an active ingredient as described above.
When these are illustrated, for example, 2-methylnaphtho [2,3-b] furan-4,9-dione, 2-acetylnaphtho [2,3-b] furan-4,9-dione, 2- (1-hydroxy Ethyl) naphtho [2,3-b] furan-4,9-dione, naphtho [2,3-b] furan-4,9-dione, 5 (or 8) -hydroxy-2- (1-hydroxyethyl) Naphtho [2,3-b] furan-4,9-dione, 5 (or 8) -hydroxynaphtho [2,3-b] furan-4,9-dione, 2-methyl-5 (or 8) -hydroxy -2-Methylnaphtho [2,3-b] furan-4,9-dione, 1,3-dimethylisofuranonaphthoquinone, 2- (acetylethyleneacetal) naphtho [2,3-b] furan-4,9-dione , 8-hydroxy-7-methoxy Shift [2,3-b] furan-4,9-dione, 3-acetyl-5,8-dimethoxy-2-methylnaphtho [2,3-b] furan-4,9-dione, etc. are exemplified. Of course, without being limited to these exemplifications, various embodiments represented by the above formulas are possible in the present invention. As for the alkyl group, hydroxyalkyl group and alkoxyalkyl group in the above formula, other arbitrary substituents such as alkenyl group, cycloalkyl group, cycloalkenyl group, aryl group, halogen atom, amino Groups, nitro groups, cyano groups, thiol groups, thioether groups, carboxyl groups, ester groups, amide groups, sulfonyl groups, haloformyl groups, heterocyclic groups and the like may be bonded.
These various compounds can be produced by various known chemical synthesis techniques, or by extracting furanonaphthoquinones from bark or the like as a natural product.
The antiviral agent of the present invention can be applied to, for example, RNA viruses in general. For example, applicable diseases include Japanese encephalitis, dengue fever, measles, mumps, rubella, influenza, Diseases caused by RNA viruses such as hepatitis A, hepatitis C, yellow fever, hemorrhagic fever, meningitis, pediatric diarrhea, rabies, Ebola, fever, polio, St. Louis encephalitis, adult T-cell leukemia, AIDS, etc. And refractory diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, subacute sclerosing panencephalitis, Alzheimer's disease, ulcerative colitis, Crohn's disease, Kawasaki disease, and diabetes that are presumed to be caused by RNA virus infection Diseases and the like are exemplified.
Such an antiviral agent of the present invention can be formulated in various dosage forms such as a liquid preparation and a solid preparation by various methods such as oral, subcutaneous, intravenous, and external use. Naturally, in that case, a conventionally well-known compounding component can be added, and a pharmaceutical composition can be constituted in various modes including a protective agent such as a salt and an ester.
Therefore, the present invention will be described below in more detail with reference to examples.
【Example】
Example 1
(Production of 2- (1-hydroxyethyl) naphtho [2,3-b] furan-4,9-dione)
It was synthesized by a metallation reaction using sec-BuLi. That is, sec-BuLi (1 eq.) And TMEDA (1 eq.) Are reacted with N, N-diethylbenzamide in ether (or in THF) at −78 ° C. for 1 hour. Next, a 5- (1-hydroxyethyl) -3-furaldehyde derivative (1 eq.) Is added dropwise at −78 ° C., sec-BuLi (4 eq.) Is further added, the temperature is gradually returned to room temperature, and stirring is continued overnight. After adding water and extracting with chloroform, the chloroform layer is washed with saturated NaCl water, and then dried and distilled off. The residue was separated and purified by PTLC (chloroform: acetone = 100: 1) to remove the protecting group, thereby obtaining a yellow crystal of the following compound.
Embedded image
Example 2
(Production of 2-methylnaphtho [2,3-b] furan-4,9-dione)
2-Hydroxy-3- (2-propenyl) -1,4-naphthoquinone (150 mg) synthesized from 2-hydroxy-1,4-naphthoquinone and propionaldehyde and DDQ (200 mg) are stirred and refluxed in benzene (20 ml). . After 2-3 hours, cool, filter and evaporate the filtrate. The residue was subjected to column chromatography (silica gel 30 g, benzene) to obtain the target compound of the following formula as yellow crystals from the first yellow fraction (35%).
Embedded image
[Table 1]
Example 3
(A) Production of 8-hydroxynaphtho [2,3-b] furan-4,9-dione and (B) 8-hydroxy-2-methylnaphtho [2,3-b] furan-4,9-dione)
Aluminum chloride (2.5 g) and 3-hydroxyphthalic anhydride (1 g) were added to nitrobenzene (5 ml), acetylfuran (0.7 g) or 2-acetyl-5-methylfuran was added dropwise, and the mixture was heated at 100 ° C. overnight. I do. Thereafter, extraction with chloroform was performed, and nitrobenzene was distilled off under reduced pressure, and the residue was purified by column chromatography (50 g of silica gel, benzene) to obtain yellow crystals of the following compound (化合物 5%).
Embedded image
[Table 2]
Embedded image
[Table 3]
Example 4
(Production of 5-hydroxy-2- (1-hydroxyethyl) naphtho [2,3-b] furan-4,9-dione)
Tecomaipe 10 kg of dried bark (produced in Brazil) was extracted three times for 30 minutes with 10 l of pure methanol under heating and reflux, and the solvent was distilled off under reduced pressure. The extract (1.45 kg) was cold-soaked three times with 4 l of chloroform, the chloroform layer was washed with water, dried over magnesium sulfate, and the solvent was distilled off to obtain 10 g of the extract. This was repeated by separation and thin-layer chromatography using silica gel 60F254 using toluene / acetic acid ethyl ester (4: 1) as a developing solvent to extract a spot with Rf = 0.24, chloroform-methanol (9: 1). To give a total of 8 mg of the following compound (melting point: 181 ° C.).
Embedded image
Example 5
(Antiviral agent)
<A> Test material virus: Japanese encephalitis virus (JEV) JaGAr-01 strain was used.
Cells: Monkey kidney cell line Vero cells were used as cells for virus infection, and cultured in DMEM medium containing 5% fetal calf serum at 37 ° C. in the presence of 5% CO 2.
<B> Test method Virus infection and inhibition by furanonaphthoquinone derivative: JEV was added to Vero cells in monolayer culture at 10 m. o. j. , And cultured. The furanonaphthoquinone derivative was added immediately after virus infection, and the effect on the amount of virus released into the culture medium showing virus growth was examined.
Measurement of the amount of virus: The titer of the proliferated virus was measured by a plaque method using BHK cells, and expressed in plaque forming units (PFU).
Cytopathic effect: Cytopathic effect (CPE) showing virus infectivity was measured by utilizing the fact that cells infected with a virus had a specific round granular shape.
<C> Test Results JEV released into the culture solution was collected 24 hours after infection, and its titer was measured to examine the inhibition of virus growth. Table 4 shows the results of the compound of Example 2 at various concentrations.
As shown in Table 4, JEV proliferation was inhibited in a concentration-dependent manner, and the concentration (IC50) at which 50% growth was inhibited was 0.04 μg / ml. At 3.3 μg / ml, the proliferation of JEV was inhibited by about 90% and at 10 μg / ml, 98%. No cytotoxicity to host Vero cells was observed even at such a high concentration, and no CPE caused by viral infection was observed.
[Table 4]
Table 5 shows the results near the concentration of 3.3 μg / ml when the compounds of Examples 1, 2, and 3 were used. It showed a 75% to 94% JEV growth inhibitory effect. Furthermore, the compounds of Examples 1 and 2 did not show cytotoxicity due to the drug.
[Table 5]
Table 6 shows the results when interferon (IFN) was used as a positive control for reference. IFN inhibited the growth of JEV in a concentration-dependent manner.
Further, the antiviral activity of the antibacterial agent OFLX was examined as a negative control in the JEV growth system, but no remarkable JEV growth inhibitory activity was observed even at a high concentration (100 μg / ml) at which cytotoxicity to host cells occurs.
[Table 6]
JEV is an RNA virus belonging to the Flaviviridae family, and there is currently only a prophylactic method using an inactivated vaccine. However, the dengue virus, which is still on the rise, has no effective vaccine, and the hepatitis C virus is even more serious in view of its worldwide spread.
Under these circumstances, the furanonaphthoquinone derivatives of the present invention, including the compound of Example 2, for example, show a strong antiviral activity against JEV without cytotoxicity against host cells from the above results, and are effective against RNA viruses. It was confirmed that it was an effective antiviral agent .
【The invention's effect】
As described above in detail, the present invention is excellent in antiviral activity, antiviral agent is provided moreover comprising a small Furano naphthoquinone derivative side effects.
Claims (1)
で表されるフラノナフトキノン誘導体を有効活性成分として含有することを特徴とする抗ウイルス剤。The following formula (I)
An antiviral agent comprising a furanonaphthoquinone derivative represented by the formula (1) as an active ingredient.
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JP06068196A JP3598168B2 (en) | 1996-03-18 | 1996-03-18 | Antiviral agent |
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JP06068196A JP3598168B2 (en) | 1996-03-18 | 1996-03-18 | Antiviral agent |
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Cited By (2)
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US7538234B2 (en) | 2007-05-31 | 2009-05-26 | Taheebo Japan Co., Ltd. | Preparation of Optically active 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4, 9-diones having anticancer activities |
US7910752B2 (en) | 2005-03-16 | 2011-03-22 | Taheebo Japan Co., Ltd. | Anticancer compound, intermediate therefor, and processes for producing these |
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WO2000054792A1 (en) * | 1999-03-17 | 2000-09-21 | Morinaga & Co., Ltd. | Drugs, foods, drinks and feeds containing cocoa component |
JP2001097860A (en) | 1999-09-29 | 2001-04-10 | Japan Science & Technology Corp | Anti-drug-resistant bacterium agent and anti-chlamydia agent |
EP2200431B1 (en) | 2007-09-10 | 2016-07-20 | Boston Biomedical, Inc. | Novel compositions and methods for cancer treatment |
US20160030384A1 (en) | 2013-04-09 | 2016-02-04 | Boston Biomedical, Inc. | 2-acetylnaphtho[2,3-b]furan -4,9-dione for use on treating cancer |
CA3045306A1 (en) | 2016-11-29 | 2018-06-07 | Boston Biomedical, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
US10646464B2 (en) | 2017-05-17 | 2020-05-12 | Boston Biomedical, Inc. | Methods for treating cancer |
WO2020161959A1 (en) * | 2019-02-06 | 2020-08-13 | タヒボジャパン株式会社 | Naphthoquinone compound having antibacterial and antiviral activities and pharmaceutical use thereof |
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Cited By (2)
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US7910752B2 (en) | 2005-03-16 | 2011-03-22 | Taheebo Japan Co., Ltd. | Anticancer compound, intermediate therefor, and processes for producing these |
US7538234B2 (en) | 2007-05-31 | 2009-05-26 | Taheebo Japan Co., Ltd. | Preparation of Optically active 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4, 9-diones having anticancer activities |
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