WO1996033712A1 - Remede pour lutter contre le syndrome de l'immunodeficience acquise - Google Patents

Remede pour lutter contre le syndrome de l'immunodeficience acquise Download PDF

Info

Publication number
WO1996033712A1
WO1996033712A1 PCT/JP1996/001106 JP9601106W WO9633712A1 WO 1996033712 A1 WO1996033712 A1 WO 1996033712A1 JP 9601106 W JP9601106 W JP 9601106W WO 9633712 A1 WO9633712 A1 WO 9633712A1
Authority
WO
WIPO (PCT)
Prior art keywords
hiv
phenyl
salt
therapeutic agent
aids
Prior art date
Application number
PCT/JP1996/001106
Other languages
English (en)
Japanese (ja)
Inventor
Masanori Baba
Ikuro Muruyama
Hiroyuki Masayasu
Original Assignee
Daiichi Pharmaceutical Co., Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Daiichi Pharmaceutical Co., Ltd. filed Critical Daiichi Pharmaceutical Co., Ltd.
Priority to AU55137/96A priority Critical patent/AU5513796A/en
Publication of WO1996033712A1 publication Critical patent/WO1996033712A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D293/00—Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms
    • C07D293/10—Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms condensed with carbocyclic rings or ring systems

Definitions

  • the present invention relates to a therapeutic agent for acquired immunodeficiency syndrome (AIDS) and a therapeutic agent for HIV infection, which have excellent anti-HIV effects in both acute and persistent HIV infection systems.
  • AIDS acquired immunodeficiency syndrome
  • HIV infection HIV infection
  • AIDS is a disease caused by HIV infection, the number of which has increased rapidly since its discovery in the United States in 1983 and is now widespread worldwide.
  • HIV the virus that causes AIDS, includes type 1 (HIV-1) and type 2
  • HIV-1 HIV-2
  • HIV-1 often has its gene mutated during viral replication, which makes it difficult to develop an effective vaccine, and inhibits reverse transcriptase, which is currently used as an anti-HIV-1 agent
  • the emergence of drug-resistant viruses also hinders effective chemotherapy for drugs and protease inhibitors under development. Recent studies indicate that virus turnover in infected individuals
  • N-acetyl-L-cysteine has been reported to have an inhibitory effect on the growth of HIV-1 [Ro ederer, M., Staa1, FJT, Raju, PAeta 1 .: Proc. Na USA, 87: 4884-4888 (1990)). Clinically tested as a therapeutic agent for AIDS.
  • NAC was weak in activity, required large-dose administration, and had a problem with increased side effects.
  • an object of the present invention is to provide a therapeutic agent for AIDS which has a high activity and effectively suppresses the proliferation of HIV-1 even at a low concentration. Disclosure of the invention
  • the present invention provides an AIDS therapeutic agent comprising 2-phenyl-1,2-benzisoselenazole-3 (2H) -one or a salt thereof as an active ingredient.
  • the present invention also provides a therapeutic agent for HIV infection, comprising 2-phenyl-1,2-benbuisoselenazole-3 (2H) one (1) or a salt thereof as an active ingredient.
  • the present invention provides the use of 2-phenyl-1,2-benbuisoselenabul-13 (2H) -one or a salt thereof for producing an AIDS therapeutic agent.
  • the present invention provides the use of 2-phenyl-1,2-benzisoselenazoluru 3 (2H) -one or a salt thereof for the manufacture of a therapeutic agent for HIV infection.
  • the present invention further provides a method for treating AIDS, which comprises administering to a patient an effective amount of 2-phenyl-1,2-benbuisoselenabul-3 (2H) one or a salt thereof.
  • the present invention provides a method for treating HIV infection, which comprises administering to a patient an effective amount of 2-phenyl-1,2-benzoisoselenabul-3 (2H) one or a salt thereof. It provides a method.
  • the 2-phenyl-1,2-benzoisoselenabul-13 (2H) one used in the present invention is a known compound, and has already been used as an antirheumatic agent (JP-A-57-56427), Agents (JP-A-57-67568), therapeutic agents for diseases caused by oxidative stress (JP-A-62-294613), therapeutic agents for liver diseases (JP-A-63-27431), malignant tumors Therapeutic agent (Japanese Patent Application Laid-Open No. 63-183528), renal disease therapeutic agent (Japanese Patent Application Laid-Open No. 64-56615), -1 311 13), Heart disease therapeutic agent (Japanese Patent Application Laid-Open No.
  • Gastrointestinal disease therapeutic agent Japanese Patent Application Laid-Open No. 1132522
  • radiation injury treatment Japanese Patent Application Laid-Open (JP-A) No. 113577-18
  • an agent for infectious diseases Japanese Patent Application Laid-Open No. 11-82025
  • an agent for suppressing restenosis after percutaneous coronary angioplasty Japanese Patent Application Laid-open No. No. 5,255,084.
  • nothing is known about its effects on HIV.
  • the 2-phenyl-1,2-benzoisoselenazol-3 (2H) -one may be used as its salt or may be a hydrate.
  • Ebselen or a salt thereof strongly suppresses cell death due to acute HIV infection, as shown in the test examples below. It also strongly suppresses HIV proliferation caused by TNF-stimulation in HIV persistently infected cells. Therefore, it is considered to be effective as a therapeutic agent for AIDS because it suppresses infection and onset of HIV.
  • the therapeutic agent for AIDS and the therapeutic agent for HIV infection of the present invention may be prepared by adding excipients, binders, lubricants, disintegrants, coating agents, emulsifiers, suspending agents, solvents, and solvents to ebselen or a salt thereof as necessary.
  • Pharmaceutical carriers such as auxiliaries, absorption aids, and softening bases are added as appropriate, or riboforming is performed, and manufactured according to standard methods for oral administration, injection, rectal administration, etc. It can be obtained by making the agent.
  • Formulations for oral administration include granules, tablets, dragees, capsules, soft carbs, pills, solutions, emulsions, suspensions, etc.
  • Formulations for injection administration include intravenous injection, muscle Suppositories, capsules, and the like are preferable as preparations for intrarectal administration, such as for intravenous injection, subcutaneous injection, and intravenous injection.
  • the dosage varies depending on the route of administration, age of the patient, symptoms, etc., but in general, for oral administration per adult daily, 100 to 2.0 mg of ebselen or a salt thereof, particularly 200 to 1 mg , 100 mg is preferable, and it is administered once or in several divided doses.
  • MTT dye by the method of S. et al., CPauwe ls, R, Balza rini, J., ⁇ aba, M. eta 1 .: J. Virol. Methods, 20: 309-321 (1988)] This was performed using
  • HIV-1 infected cells were denatured and killed by more than 75% of uninfected cells due to the growth of the virus.
  • the number of viable cells increased as the concentration of DNA was increased, and virus growth was suppressed.
  • uninfected cells a slight decrease in the number of viable cells was observed at concentrations of 10 M or more. Force Observed under a microscope at 20 ⁇ M (Ebselen did not show any obvious cytotoxicity. Based on the above results, this drug has an inhibitory effect on the growth of HIV-1. I understand.
  • HIV-1 After infecting cells, HIV-1 is incorporated into the host DNA, and for some reason (site force, heat, ultraviolet light, etc.), transcription from the DNA occurs and multiplies. Whether ebselen has such an inhibitory effect on the proliferation of HIV-1 was determined by determining whether OM10.1 cells, which are persistently infected with HIV-1 cells and usually do not show virus proliferation, [Bu tera, ST, Perez, VL, Wu, B. — Y.eta 1 .: J. Virol., 65: 464 5-4653 (1991)].
  • OM1 0. 1 cells 5 X 1 0 4 ce 1 1 Then, after preincubation for 24 hours in the presence of various concentrations of ebselen, TNF—, a kind of cytokin, was added to a concentration of 10 UZm. After further culturing for 3 days, the amount of p24 antigen (proportional to the amount of virus) in the supernatant was measured using an ELISA kit. Table 3 shows the results.
  • the therapeutic agent for AIDS and the therapeutic agent for HIV infection of the present invention are excellent in the inhibitory effect on HIV-1 infection and the inhibitory effect on HIV-1 proliferation by cytokines such as TNF-H in HIV-1 persistently infected cell lines, Because of its high safety, it is useful for treating AIDS.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Un remède s'appliquant au SIDA et aux infections dues au VIH comprend 2-phényl-1,2-benzizosélénazol-3(2H)-one ou son sel, utilisé comme principe actif. Ce médicament est excellent pour combattre l'infection due au VIH et empêcher la prolifération du VIH-1 dans une lignée cellulaire infectée en permanence par le VIH-1 à l'aide d'une cytokine telle que TNF-α. Ce médicament présente également une excellente innocuité et peut donc être utilisé dans le traitement du SIDA.
PCT/JP1996/001106 1995-04-25 1996-04-24 Remede pour lutter contre le syndrome de l'immunodeficience acquise WO1996033712A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU55137/96A AU5513796A (en) 1995-04-25 1996-04-24 Remedy for acquired immunodeficiency syndrome

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP9927395 1995-04-25
JP7/99273 1995-04-25

Publications (1)

Publication Number Publication Date
WO1996033712A1 true WO1996033712A1 (fr) 1996-10-31

Family

ID=14243078

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1996/001106 WO1996033712A1 (fr) 1995-04-25 1996-04-24 Remede pour lutter contre le syndrome de l'immunodeficience acquise

Country Status (2)

Country Link
AU (1) AU5513796A (fr)
WO (1) WO1996033712A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1174423A1 (fr) * 1999-03-31 2002-01-23 Daiichi Pharmaceutical Co., Ltd. Substrats pour thioredoxine reductase
US10058542B1 (en) 2014-09-12 2018-08-28 Thioredoxin Systems Ab Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5756427A (en) * 1980-07-17 1982-04-05 Nattermann A & Cie Medicine containing 2-phenyl-1,2-benzisoselenazole- 3(2h)-one
JPS5767568A (en) * 1980-07-17 1982-04-24 Nattermann A & Cie Benzisoselenazolone compound
JPS62294613A (ja) * 1986-05-20 1987-12-22 ア−．ナタ−マン　ウント　コンパニ−　ゲゼルシヤフト　ミツト　ベシユレンクテル　ハフツング 酸化ストレスが原因の病気の治療のための薬剤
JPS63183528A (ja) * 1986-11-08 1988-07-28 アー．ナターマン　ウント　コンパニー　ゲゼルシャフト　ミット　ベシュレンクテル　ハフツング 悪性腫瘍治療剤
JPS6456615A (en) * 1987-08-27 1989-03-03 Daiichi Seiyaku Co Remedy for nephropathy
JPH01131114A (ja) * 1987-08-28 1989-05-24 Dai Ichi Seiyaku Co Ltd 心臓疾患治療剤
JPH01131113A (ja) * 1987-08-27 1989-05-24 Dai Ichi Seiyaku Co Ltd 脳障害治療剤
JPH01132522A (ja) * 1987-11-18 1989-05-25 Dai Ichi Seiyaku Co Ltd 消化管疾患治療剤
JPH01135718A (ja) * 1987-11-18 1989-05-29 A Nattermann & Cie Gmbh 放射線障害治療剤
JPH01180825A (ja) * 1988-01-06 1989-07-18 Dai Ichi Seiyaku Co Ltd 感染症用剤
JPH05255084A (ja) * 1992-01-17 1993-10-05 Dai Ichi Seiyaku Co Ltd 経皮的冠動脈形成術後の再狭窄抑制剤

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5756427A (en) * 1980-07-17 1982-04-05 Nattermann A & Cie Medicine containing 2-phenyl-1,2-benzisoselenazole- 3(2h)-one
JPS5767568A (en) * 1980-07-17 1982-04-24 Nattermann A & Cie Benzisoselenazolone compound
JPS62294613A (ja) * 1986-05-20 1987-12-22 ア−．ナタ−マン　ウント　コンパニ−　ゲゼルシヤフト　ミツト　ベシユレンクテル　ハフツング 酸化ストレスが原因の病気の治療のための薬剤
JPS63183528A (ja) * 1986-11-08 1988-07-28 アー．ナターマン　ウント　コンパニー　ゲゼルシャフト　ミット　ベシュレンクテル　ハフツング 悪性腫瘍治療剤
JPS6456615A (en) * 1987-08-27 1989-03-03 Daiichi Seiyaku Co Remedy for nephropathy
JPH01131113A (ja) * 1987-08-27 1989-05-24 Dai Ichi Seiyaku Co Ltd 脳障害治療剤
JPH01131114A (ja) * 1987-08-28 1989-05-24 Dai Ichi Seiyaku Co Ltd 心臓疾患治療剤
JPH01132522A (ja) * 1987-11-18 1989-05-25 Dai Ichi Seiyaku Co Ltd 消化管疾患治療剤
JPH01135718A (ja) * 1987-11-18 1989-05-29 A Nattermann & Cie Gmbh 放射線障害治療剤
JPH01180825A (ja) * 1988-01-06 1989-07-18 Dai Ichi Seiyaku Co Ltd 感染症用剤
JPH05255084A (ja) * 1992-01-17 1993-10-05 Dai Ichi Seiyaku Co Ltd 経皮的冠動脈形成術後の再狭窄抑制剤

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1174423A1 (fr) * 1999-03-31 2002-01-23 Daiichi Pharmaceutical Co., Ltd. Substrats pour thioredoxine reductase
EP1174423A4 (fr) * 1999-03-31 2008-03-19 Arne Holmgren Substrats pour thioredoxine reductase
US7671211B1 (en) 1999-03-31 2010-03-02 Arne Holmgren Substrates for thioredoxin reductase
US10058542B1 (en) 2014-09-12 2018-08-28 Thioredoxin Systems Ab Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith
US11013730B1 (en) 2014-09-12 2021-05-25 Thioredoxin Systems Ab Composition comprising selenazol or thiazalone derivatives and silver and method of treatment therewith

Also Published As

Publication number Publication date
AU5513796A (en) 1996-11-18

Similar Documents

Publication Publication Date Title
JP5769762B2 (ja) 治療組成物およびその使用
US6093702A (en) Mixtures of dideoxy-nucleosides and hydroxycarbamide for inhibiting retroviral spread
US5736527A (en) Method of treating HIV in humans by administration of ddI and hydroxycarbamide
WO2011088561A1 (fr) Composés antiviraux et compositions
Higashi-Kuwata et al. Identification of a novel long-acting 4’-modified nucleoside reverse transcriptase inhibitor against HBV
Ichimura et al. Polymerase substrate depletion: a novel strategy for inhibiting the replication of the human immunodeficiency virus
KR20050044587A (ko) Ｂ형 간염 바이러스 감염 치료용 포스포네이트뉴클레오타이드 유사체의 용도
JP2720169B2 (ja) 抗レトロウイルス活性をもつ糖タンパク処理抑制剤
WO2023142318A1 (fr) Composition pharmaceutique pour le traitement de l'hépatite virale
WO2023142317A1 (fr) Composition pharmaceutique pour le traitement de l'hépatite virale
JP2001072585A (ja) ウイルス性心筋炎の予防または治療薬剤
JPH0232093A (ja) 抗レトロウィルスジフルオロ化ヌクレオシド類
KR940010441B1 (ko) B형감염의 항비루스제
Jacobson et al. Approaches to the treatment of cytomegalovirus retinitis: ganciclovir and foscarnet
WO1996033712A1 (fr) Remede pour lutter contre le syndrome de l'immunodeficience acquise
EP0384532A1 (fr) Polymères vinyliques sulfatés dans des compositions pour traiter les infections rétrovirales
EP3600332B1 (fr) Prophylaxie du vih post-exposition
Mitsuya et al. Antiviral therapy against HIV infection
JPH02207021A (ja) グアニジノ安息香酸誘導体を有効成分として含有する抗レトロウイルス剤
CN114099482A (zh) β-石竹烯在预防和治疗病毒感染中的应用
JPH03227925A (ja) エイズ原因ウィルスに対する抗ウイルス剤
WO1995017875A2 (fr) MELANGES DE DIDESOXY-NUCLEOSIDES ET DE β-HYDROXAMATE DE L'ACIDE D-ASPARTIQUE UTILISE DANS L'INHIBITION DE LA PROPAGATION D'UN RETROVIRUS
SINGH et al. Novel Role of Combination Therapy of Lamivudine and Zidovudine Antiretroviral Drugs in Elevating The Efficiency
Hladik A new hypothesis on HIV cure [version 1; referees: 2 approved]
Hladik A new hypothesis on HIV cure [v1; ref status: indexed, http://f1000r. es/3qj]

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AU BB BG BR CA CN CZ EE GE HU IS JP KG KR LK LR LT LV MD MG MK MN MX NO NZ PL RO SG SI SK TR TT UA US UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA