AR020065A1 - USE OF CISTEINE PROTEASE INHIBITORS FOR THE MANUFACTURE OF A PHARMACEUTICAL MEDICINAL COMPOSITION AND COMPOSITION - Google Patents

USE OF CISTEINE PROTEASE INHIBITORS FOR THE MANUFACTURE OF A PHARMACEUTICAL MEDICINAL COMPOSITION AND COMPOSITION

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Publication number
AR020065A1
AR020065A1 ARP990101578A ARP990101578A AR020065A1 AR 020065 A1 AR020065 A1 AR 020065A1 AR P990101578 A ARP990101578 A AR P990101578A AR P990101578 A ARP990101578 A AR P990101578A AR 020065 A1 AR020065 A1 AR 020065A1
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AR
Argentina
Prior art keywords
ylcarbonyl
thiazol
leucinyl
hydrazide
amino
Prior art date
Application number
ARP990101578A
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Spanish (es)
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Smithkline Beecham Corp
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Publication date
Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp
Publication of AR020065A1 publication Critical patent/AR020065A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/99—Enzyme inactivation by chemical treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
    • C07C281/06—Compounds containing any of the groups, e.g. semicarbazides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/56—Amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/22—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

Se refiere a composicion farmacéuticas que inhiben proteasas, tales como las proteasas de cisteína. En particular, se refiere al uso de inhibidores deproteasas de cisteína para la fabricacion de un medicamento para inhibir las proteasas de cisteína,que comprende un compuesto elegido entre el grupo formadopor 2-[N-(N-benciloxicarbonilglicinil)]-2-[N-benciloxicarbonil-L-leucinil)]carbohidrazida; (3RS)-1-(N-benciloxilocarbonil-L-leucinil)-3-[N(4-fenoxibenzoil)amino]pirrolidin-4-ona; (1S)-N-[2-[1-(N-benciloxicarbonilamino)-3-metilbutil]-tiazol-4-ilcarbonil]]-N-[N-(2-piridinilmetoxicarbonil)-L-leucinil]hidrazida; 1-(N-benciloxicarbonil-L-leucinilamino)-3-(2-benciloxifenilsulfonil)amino-propan-2-ona; N-[2-(2-benciloxifenil)tiazol-4-ilcarbonil]-N-[N-(3-piridinilmetoxi-carbonil)-L-leucinil]hidrazida; (1S)-N-[2-[1-(N-benciloxicarbonilamino)-3-metilbutil]-tiazol-4-ilcarbonil-N-[N(3-piridinilmetoxicarbonil)-L-leucinil]]hidrazida; 1-[N-(4-morfolinocarbamoil)-L-leucinilamino]-3-(4-fenoxifenilsulfonil)amino-propan-2-ona; N-[2-(1-naftil)tiazol-4-ilcarbonil]-N-[N-(4-piridinil-metoxicarbonil)-L-leucinil]hidrazida; N-[2-(2-benciloxifenil)tiazol-4-ilcarbonil]-N-(N-pirazinacarbonil-L-leucinil)hidrazida; N-[N-(1-bencil-5-metilimidazol-4-ilcarbonil)-L-leucinil]-N-[2-(1-naftil)tiazol-4-ilcarbonil]hidrazida; (3RS)-3-[N-(-benciloxibenzoil)-L-leucinilamino]tetrahidrofuran-4-ona; N-[2-[N-ciclopropil-N-(2-metilpropil)amino]tiazol-4-il-carbonil]-N-[N-(5-metil-2-feniloxazol-4-ilcarbonil)-L-leucinil]hidrazida; 1-[3-(2-piridinil)fenilacetamilano]-3-[N-(2-tiofenocarbonil)-L-leucinilamino]propan-2-ona; (3S)-3-[N-(benzotiazol-6-ilcrbonil)-L-leucinilamino]-1-[3-(2-piridinil)fenilacetilamino]butan-2-ona; N-[2-[N-ciclopropil-N-(2-metilpropil)amino]tiazol-4-il-carbonil]-N-[N-(7-metoxibenzofuran-2-ilcarbonil)-L-beta-ciclopropilalanil]hidrazida; 1-[N-(benzoxazol-5-ilcarbonil)-L-leucinilamino]-3-[3-2-piridinil)fenilacetilamino]propan-2-ona; 1-[N-[4-[2-(N,N-dimetilamino)etoxi]benzoil]-L-leucinilamino]-3-[3-(2-piridinil)fenilacetilamino]propan-2-ona; y N-[2-[N-ciclopropil-N-(2-metilpropil)amino)tiazol-4-il-carbonil]-N-[N-[5[2-(N,N-dimetilamino)etoxi]benzofuran-2-ilcarbonil]-It refers to pharmaceutical compositions that inhibit proteases, such as cysteine proteases. In particular, it refers to the use of cysteine deprotease inhibitors for the manufacture of a medicament for inhibiting cysteine proteases, which comprises a compound chosen from the group consisting of 2- [N- (N-benzyloxycarbonylglycinyl)] - 2- [N -benzyloxycarbonyl-L-leucinyl)] carbohydrazide; (3RS) -1- (N-benzyloxylocarbonyl-L-leuccinyl) -3- [N (4-phenoxybenzoyl) amino] pyrrolidin-4-one; (1S) -N- [2- [1- (N-Benzyloxycarbonylamino) -3-methylbutyl] -thiazol-4-ylcarbonyl]] - N- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; 1- (N-benzyloxycarbonyl-L-leuccinylamino) -3- (2-benzyloxyphenylsulfonyl) amino-propan-2-one; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; (1S) -N- [2- [1- (N-Benzyloxycarbonylamino) -3-methylbutyl] -thiazol-4-ylcarbonyl-N- [N (3-pyridinylmethoxycarbonyl) -L-leucinyl]] hydrazide; 1- [N- (4-morpholinocarbamoyl) -L-leucinylamino] -3- (4-phenoxyphenylsulfonyl) amino-propan-2-one; N- [2- (1-Naphthyl) thiazol-4-ylcarbonyl] -N- [N- (4-pyridinyl-methoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N- (N-pyrazinecarbonyl-L-leucinyl) hydrazide; N- [N- (1-benzyl-5-methylimidazol-4-ylcarbonyl) -L-leucinyl] -N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; (3RS) -3- [N - (- benzyloxybenzoyl) -L-leucinylamino] tetrahydrofuran-4-one; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-yl-carbonyl] -N- [N- (5-methyl-2-phenyloxazol-4-ylcarbonyl) -L-leucinyl ] hydrazide; 1- [3- (2-Pyridinyl) phenylacetamine] -3- [N- (2-thiophenecarbonyl) -L-leuccinylamino] propan-2-one; (3S) -3- [N- (benzothiazol-6-ylcrbonyl) -L-leucinylamino] -1- [3- (2-pyridinyl) phenylacetylamino] butan-2-one; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-yl-carbonyl] -N- [N- (7-methoxybenzofuran-2-ylcarbonyl) -L-beta-cyclopropylalanyl] hydrazide ; 1- [N- (benzoxazol-5-ylcarbonyl) -L-leucinylamino] -3- [3-2-pyridinyl) phenylacetylamino] propan-2-one; 1- [N- [4- [2- (N, N-dimethylamino) ethoxy] benzoyl] -L-leucinylamino] -3- [3- (2-pyridinyl) phenylacetylamino] propan-2-one; and N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino) thiazol-4-yl-carbonyl] -N- [N- [5 [2- (N, N-dimethylamino) ethoxy] benzofuran- 2-ilcarbonyl] -

ARP990101578A 1998-04-09 1999-04-07 USE OF CISTEINE PROTEASE INHIBITORS FOR THE MANUFACTURE OF A PHARMACEUTICAL MEDICINAL COMPOSITION AND COMPOSITION AR020065A1 (en)

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US8122198P 1998-04-09 1998-04-09

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Country Status (17)

Country Link
EP (1) EP1068304A4 (en)
JP (1) JP2002511491A (en)
KR (1) KR20010042535A (en)
CN (1) CN1304447A (en)
AR (1) AR020065A1 (en)
AU (1) AU3482099A (en)
CA (1) CA2327282A1 (en)
CO (1) CO5080800A1 (en)
DZ (1) DZ2752A1 (en)
HU (1) HUP0101513A2 (en)
IL (1) IL138628A0 (en)
MA (1) MA26618A1 (en)
NO (1) NO20005032L (en)
PE (1) PE20000421A1 (en)
PL (1) PL343373A1 (en)
TR (1) TR200002940T2 (en)
WO (1) WO1999053039A1 (en)

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US7132449B2 (en) 2001-01-17 2006-11-07 Amura Therapeutics Limited Inhibitors of cruzipain and other cysteine proteases
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WO2005034949A1 (en) 2003-09-09 2005-04-21 University Of Florida Desferrithiocin derivatives and their use as iron chelators
TR201910900T4 (en) 2005-04-04 2019-08-21 Univ Florida Desferritiokine polyether analogs.
WO2007012180A1 (en) * 2005-07-26 2007-02-01 Merck Frosst Canada Ltd. Papain family cysteine protease inhibitors for the treatment of parasitic diseases
NZ579994A (en) 2007-03-15 2011-09-30 Univ Florida Desferrithiocin polyether analogues useful in the treatment of pathological conditions responsive to chelation or sequestration of trivalent metal
EP2225196B1 (en) 2007-11-29 2015-01-28 Merck Canada Inc. Cysteine protease inhibitors for the treatment of parasitic diseases
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EP2633855A1 (en) 2012-03-01 2013-09-04 Veterinärmedizinische Universität Wien Protease inhibitors for treating Trichomonas gallinae infections
JP6838966B2 (en) 2013-11-22 2021-03-03 ユニバーシティー オブ フロリダ リサーチ ファンデーション， インク． Desfericiosin analogs and their use
KR20170140306A (en) 2015-04-27 2017-12-20 유니버시티 오브 플로리다 리서치 파운데이션, 인코포레이티드 Metabolically programmed metal chelating agents and uses thereof

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CA2327282A1 (en) 1999-10-21
NO20005032D0 (en) 2000-10-06
EP1068304A1 (en) 2001-01-17
IL138628A0 (en) 2001-10-31
JP2002511491A (en) 2002-04-16
CO5080800A1 (en) 2001-09-25
MA26618A1 (en) 2004-12-20
HUP0101513A2 (en) 2001-08-28
NO20005032L (en) 2000-11-16
EP1068304A4 (en) 2001-05-09
PL343373A1 (en) 2001-08-13
AU3482099A (en) 1999-11-01
CN1304447A (en) 2001-07-18
TR200002940T2 (en) 2001-02-21
DZ2752A1 (en) 2003-09-15
PE20000421A1 (en) 2000-05-21
KR20010042535A (en) 2001-05-25
WO1999053039A1 (en) 1999-10-21

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