WO2001002424A3 - Peptide boronic acid inhibitors of hepatitis c virus protease - Google Patents

Peptide boronic acid inhibitors of hepatitis c virus protease Download PDF

Info

Publication number
WO2001002424A3
WO2001002424A3 PCT/US2000/018655 US0018655W WO0102424A3 WO 2001002424 A3 WO2001002424 A3 WO 2001002424A3 US 0018655 W US0018655 W US 0018655W WO 0102424 A3 WO0102424 A3 WO 0102424A3
Authority
WO
WIPO (PCT)
Prior art keywords
hepatitis
boronic acid
acid inhibitors
virus protease
peptide boronic
Prior art date
Application number
PCT/US2000/018655
Other languages
French (fr)
Other versions
WO2001002424A2 (en
Inventor
Charles A Kettner
Sharada Jagannathan
Timothy Patrick Forsyth
Original Assignee
Du Pont Pharm Co
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 Du Pont Pharm Co filed Critical Du Pont Pharm Co
Priority to AU57888/00A priority Critical patent/AU5788800A/en
Priority to CA002376965A priority patent/CA2376965A1/en
Priority to EP00943413A priority patent/EP1196436A2/en
Publication of WO2001002424A2 publication Critical patent/WO2001002424A2/en
Publication of WO2001002424A3 publication Critical patent/WO2001002424A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/69—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1027—Tetrapeptides containing heteroatoms different from O, S, or N
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/503—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses
    • C12N9/506—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses derived from RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Virology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Communicable Diseases (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

The present invention relates generally to novel α-aminoboronic acids and corresponding peptide analogs represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R?1, R2, R3, Y1, Y2¿, and A are described herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of hepatitis C viral infections. The compounds of the invention are inhibitors of hepatitis C viral protease.
PCT/US2000/018655 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease WO2001002424A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU57888/00A AU5788800A (en) 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease
CA002376965A CA2376965A1 (en) 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease
EP00943413A EP1196436A2 (en) 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14256199P 1999-07-07 1999-07-07
US60/142,561 1999-07-07

Publications (2)

Publication Number Publication Date
WO2001002424A2 WO2001002424A2 (en) 2001-01-11
WO2001002424A3 true WO2001002424A3 (en) 2001-07-19

Family

ID=22500325

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2000/018655 WO2001002424A2 (en) 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease
PCT/US2000/018590 WO2001002601A2 (en) 1999-07-07 2000-07-07 Cell-based assay systems for examining hcv ns3 protease activity

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2000/018590 WO2001002601A2 (en) 1999-07-07 2000-07-07 Cell-based assay systems for examining hcv ns3 protease activity

Country Status (4)

Country Link
EP (1) EP1196436A2 (en)
AU (2) AU5920400A (en)
CA (1) CA2376965A1 (en)
WO (2) WO2001002424A2 (en)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002230763A1 (en) * 2000-12-13 2008-01-03 Bristol-Myers Squibb Pharma Company Inhibitors of hepatitis c virus ns3 protease
US6653295B2 (en) 2000-12-13 2003-11-25 Bristol-Myers Squibb Company Inhibitors of hepatitis C virus NS3 protease
AU2002243508A1 (en) 2001-01-10 2002-07-24 Bristol-Myers Squibb Company Patent Department Alpha-aminoboronic acids prepared by novel synthetic methods
CA2435146C (en) 2001-01-25 2011-03-29 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Formulation of boronic acid compounds
US7119072B2 (en) 2002-01-30 2006-10-10 Boehringer Ingelheim (Canada) Ltd. Macrocyclic peptides active against the hepatitis C virus
US6642204B2 (en) 2002-02-01 2003-11-04 Boehringer Ingelheim International Gmbh Hepatitis C inhibitor tri-peptides
US7091184B2 (en) 2002-02-01 2006-08-15 Boehringer Ingelheim International Gmbh Hepatitis C inhibitor tri-peptides
PT1396270E (en) 2002-09-09 2006-08-31 Trigen Ltd PROCESS FOR THE PREPARATION OF UTEISNCOMO INTERMEDIATE COMPOUNDS.
US7371729B2 (en) 2002-09-09 2008-05-13 Trigen Limited Boronic acid salts useful in parenteral formulations
US20050075279A1 (en) 2002-10-25 2005-04-07 Boehringer Ingelheim International Gmbh Macrocyclic peptides active against the hepatitis C virus
ATE547412T1 (en) 2003-04-11 2012-03-15 Vertex Pharma INHIBITORS OF SERINE PROTEASES, IN PARTICULAR HCV NS3-NS4A PROTEASE
AU2011203054B2 (en) * 2003-04-11 2012-04-26 Vertex Pharmaceuticals, Incorporated Inhibitors of Serine Proteases, Particularly HCV NS3-NS4A Protease
US7405210B2 (en) 2003-05-21 2008-07-29 Osi Pharmaceuticals, Inc. Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase
UY28323A1 (en) 2003-05-21 2004-12-31 Boehringer Ingelheim Int INHIBITING COMPOUNDS OF HEPATITIS C
US20050136394A1 (en) * 2003-06-23 2005-06-23 Hong Fang Cell-based assay for identifying peptidase inhibitors
US7223745B2 (en) 2003-08-14 2007-05-29 Cephalon, Inc. Proteasome inhibitors and methods of using the same
US7576206B2 (en) 2003-08-14 2009-08-18 Cephalon, Inc. Proteasome inhibitors and methods of using the same
MY148123A (en) 2003-09-05 2013-02-28 Vertex Pharma Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
PE20050431A1 (en) 2003-09-22 2005-07-19 Boehringer Ingelheim Int MACROCYCLIC PEPTIDES ACTIVE AGAINST HEPATITIS C VIRUS
ES2358333T3 (en) 2004-01-21 2011-05-09 Boehringer Ingelheim International Gmbh MACROCYCLIC PEPTIDES WITH ACTION AGAINST THE VIRUS OF HEPATITIS C.
EP1725555B1 (en) 2004-03-08 2010-10-06 Prosidion Ltd. Pyrrolopyridine-2-carboxylic acid hydrazides as inhibitors of glycogen phosphorylase
PT1765360E (en) 2004-06-14 2009-12-24 Anacor Pharmaceuticals Inc Anti-viral uses of borinic acid complexes
WO2006007708A1 (en) 2004-07-20 2006-01-26 Boehringer Engelheim International Gmbh Hepatitis c inhibitor peptide analogs
UY29016A1 (en) 2004-07-20 2006-02-24 Boehringer Ingelheim Int ANALOGS OF INHIBITING DIPEPTIDES OF HEPATITIS C
WO2006059164A2 (en) 2004-12-02 2006-06-08 Prosidion Limited Pyrrolopyridine-2-carboxylic acid amides
US7468383B2 (en) 2005-02-11 2008-12-23 Cephalon, Inc. Proteasome inhibitors and methods of using the same
EP1863804A1 (en) * 2005-04-01 2007-12-12 Methylgene, Inc. Inhibitors of histone deacetylase
US20090325889A1 (en) * 2005-08-01 2009-12-31 David Alan Campbell Hepatitis c serine protease inhibitors and uses therefor
KR101069051B1 (en) 2006-05-23 2011-09-29 아이알엠 엘엘씨 Compounds and compositions as channel activating protease inhibitors
EP1886685A1 (en) 2006-08-11 2008-02-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods, uses and compositions for modulating replication of hcv through the farnesoid x receptor (fxr) activation or inhibition
WO2008070733A2 (en) * 2006-12-06 2008-06-12 Phenomix Corporation Macrocyclic hepatitis c serine protease inhibitors and uses therefor
BRPI0807483A2 (en) 2007-02-09 2014-05-13 Irm Llc COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATE PROTEASE INHIBITORS
US7442830B1 (en) 2007-08-06 2008-10-28 Millenium Pharmaceuticals, Inc. Proteasome inhibitors
US7838673B2 (en) 2007-10-16 2010-11-23 Millennium Pharmaceuticals, Inc. Proteasome inhibitors
KR101690571B1 (en) 2008-06-17 2016-12-28 밀레니엄 파머슈티컬스 인코퍼레이티드 Boronate ester compounds and pharmaceutical compositions thereof
AR075090A1 (en) 2008-09-29 2011-03-09 Millennium Pharm Inc ACID DERIVATIVES 1-AMINO-2-CYCLLOBUTILETILBORONICO PROTEOSOMA INHIBITORS, USEFUL AS ANTI-BANKER AGENTS, AND PHARMACEUTICAL COMPOSITIONS THAT UNDERSTAND THEM.
AU2010341530B2 (en) 2009-12-22 2016-03-10 Cephalon, Inc. Proteasome inhibitors and processes for their preparation, purification and use
AR080185A1 (en) * 2010-02-19 2012-03-21 Glaxo Group Ltd DERIVATIVES OF BORONIC AND BENZOFURAN ACID, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND USE OF THE SAME IN THE TREATMENT AND / OR PREVENTION OF VIRAL INFECTIONS, IN PARTICULAR BY HEPATITIS C (HCV) VIRUSES.
CN102892291A (en) 2010-03-31 2013-01-23 米伦纽姆医药公司 Derivatives of 1-amino-2-cyclopropylethylboronic acid
AU2011329485A1 (en) * 2010-11-18 2013-04-18 Glaxo Group Limited Compounds
WO2012107589A1 (en) 2011-02-11 2012-08-16 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment and prevention of hcv infections
CN103929965B (en) * 2011-08-17 2016-08-17 葛兰素史克有限责任公司 Therapeutic Method
JP6367712B2 (en) * 2011-08-19 2018-08-01 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Benzofuran compounds for the treatment of hepatitis C virus infection
US10092574B2 (en) 2012-09-26 2018-10-09 Valorisation-Recherche, Limited Partnership Inhibitors of polynucleotide repeat-associated RNA foci and uses thereof
KR102481856B1 (en) 2014-05-20 2022-12-26 밀레니엄 파머슈티컬스 인코퍼레이티드 Boron-containing proteasome inhibitors for use after primary cancer therapy
BR112017006349A2 (en) * 2014-10-01 2017-12-12 Merck Patent Gmbh boronic acid derivatives
EP3201207B1 (en) * 2014-10-01 2021-02-24 Merck Patent GmbH Boronic acid derivatives
JP6662865B2 (en) * 2014-10-01 2020-03-11 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ Boronic acid derivatives
JP7164521B2 (en) 2016-06-21 2022-11-01 オリオン・オフサルモロジー・エルエルシー carbocyclic prolinamide derivatives
CN114685453A (en) 2016-06-21 2022-07-01 奥瑞恩眼科有限责任公司 Heterocyclic prolinamide derivatives
BR112023018321A2 (en) 2021-03-15 2024-01-02 Maze Therapeutics Inc GLYCOGEN SYNTHASE 1 (GYS1) INHIBITORS AND METHODS OF USE THEREOF

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998017679A1 (en) * 1996-10-18 1998-04-30 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease
WO1998022496A2 (en) * 1996-11-18 1998-05-28 F. Hoffmann-La Roche Ag Antiviral peptide derivatives
WO1999007733A2 (en) * 1997-08-11 1999-02-18 Boehringer Ingelheim (Canada) Ltd. Hepatitis c inhibitor peptides

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5599906A (en) * 1990-04-13 1997-02-04 Schering Corporation Protease assays
IT1272179B (en) * 1994-02-23 1997-06-16 Angeletti P Ist Richerche Bio METHODOLOGY TO REPRODUCE IN VITRO THE PROTEOLITHIC ACTIVITY OF THE NS3 PROTEASE OF THE VIRUS HCV.
US5861267A (en) * 1995-05-01 1999-01-19 Vertex Pharmaceuticals Incorporated Methods, nucleotide sequences and host cells for assaying exogenous and endogenous protease activity
KR100209095B1 (en) * 1996-06-28 1999-07-15 성재갑 Substitution hepatitis c virus which can be used for detecting the activity of the hcv protease, and recombinant gene and use
WO1998037180A2 (en) * 1997-02-22 1998-08-27 Abbott Laboratories Hcv fusion protease and polynucleotide encoding same
US6280940B1 (en) * 1998-08-05 2001-08-28 Agouron Pharmaceuticals, Inc. Reporter gene system for use in cell-based assessment of inhibitors of the Hepatitis C virus protease
MXPA01011045A (en) * 1999-05-04 2002-07-22 Boehringer Ingelheim Ltd Surrogate cell-based system and method for assaying the activity of hepatitis c virus ns3 protease.

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998017679A1 (en) * 1996-10-18 1998-04-30 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease
WO1998022496A2 (en) * 1996-11-18 1998-05-28 F. Hoffmann-La Roche Ag Antiviral peptide derivatives
WO1999007733A2 (en) * 1997-08-11 1999-02-18 Boehringer Ingelheim (Canada) Ltd. Hepatitis c inhibitor peptides

Also Published As

Publication number Publication date
AU5920400A (en) 2001-01-22
CA2376965A1 (en) 2001-01-11
WO2001002424A2 (en) 2001-01-11
AU5788800A (en) 2001-01-22
WO2001002601A2 (en) 2001-01-11
WO2001002601A3 (en) 2001-07-26
EP1196436A2 (en) 2002-04-17

Similar Documents

Publication Publication Date Title
WO2001002424A3 (en) Peptide boronic acid inhibitors of hepatitis c virus protease
WO2005007681A3 (en) Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
CA2173328A1 (en) HIV Protease Inhibitors
WO2004113365A3 (en) Hepatitis c serine protease tri-peptide inhibitors
WO2004072243A3 (en) Macrocyclic hepatitis c serine protease inhibitors
WO2005037860A3 (en) Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
TW200510391A (en) Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
HUP0100100A2 (en) Hepatitis c inhibitor peptide analogues, pharmaceutical compositions comprising thereof and their use
FI923619A (en) CYCLIC PEPTIDER OCH DERAS ANVAENDNING
DE602004023924D1 (en) Ease-hemmer
CA2411754A1 (en) 4-[(4-chloro-2-hydroxybenzoyl)amino]butanoic acid and compositions for delivering active agents
BG106439A (en) Pharmaceutical composition of improved solubility and oral absorptivity, containing benzamide derivative
YU42503A (en) Arylated furane and thiophene carboxylic acid amides with potassium channel blocking effect
IT1255222B (en) CYCLIC OLIGONUCLEOTIDES PHOSPHOROTIDATES
DE69518840D1 (en) N-(3-amino-2-hydroxybutyl)sulfonamid-derivate as hiv-protease-inhibitoren
WO2001032691A8 (en) Hcv ns3 protease inhibitors
RU2002100058A (en) 1-Methylcarbapenem Crystal Derivatives
RS50046B (en) PHARMACEUTICAL COMPOSITIONS OF TIZOXANIDE AND NITAZOXANIDE
WO2001078648A3 (en) 6-methylnicotinamide derivatives as antiviral agents
WO1993014767A3 (en) Pharmaceutical preparation based on rhamnolipid against dermatological diseases, e.g. papilloma virus infections
WO2002000166A3 (en) New compounds useful as antibacterial agents
EP0647616A4 (en) Zinc tranexamate compound.
RU2003102629A (en) PHARMACEUTICAL COMPONENT BASED ON HUMAN PARTIREOID HORMONE AND CONTAINING ITS PHARMACEUTICAL COMPOSITION FOR INTRASASAL USE
ATE253938T1 (en) PHARMACEUTICAL COMBINATION OF ANTIVIRAL ACTIVE INGREDIENTS
EP1149832A4 (en) Benzamide derivatives and drugs containing the same

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AU BR CA CN CZ EE HU IL IN JP KR LT LV MX NO NZ PL RO SG SI SK TR UA VN ZA

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AU BR CA CN CZ EE HU IL IN JP KR LT LV MX NO NZ PL RO SG SI SK TR UA VN ZA

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

WWE Wipo information: entry into national phase

Ref document number: 2376965

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2000943413

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 2000943413

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2000943413

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP