PE71599A1 - PROTEASE INHIBITORS - Google Patents

PROTEASE INHIBITORS

Info

Publication number
PE71599A1
PE71599A1 PE1998000336A PE00033698A PE71599A1 PE 71599 A1 PE71599 A1 PE 71599A1 PE 1998000336 A PE1998000336 A PE 1998000336A PE 00033698 A PE00033698 A PE 00033698A PE 71599 A1 PE71599 A1 PE 71599A1
Authority
PE
Peru
Prior art keywords
alkyl
alkyll
ccero
alkylll
amino
Prior art date
Application number
PE1998000336A
Other languages
Spanish (es)
Inventor
Robert W Marquis
Daniel F Veber
Andrew D Gribble
Jason Witherington
Ashley Edward Fenwick
Original Assignee
Smithkline Beecham Plc
Smithkline Beecham Corp
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 Smithkline Beecham Plc, Smithkline Beecham Corp filed Critical Smithkline Beecham Plc
Publication of PE71599A1 publication Critical patent/PE71599A1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/99Enzyme inactivation by chemical treatment
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings 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
    • C07D307/32Oxygen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06Anabolic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04Heterocyclic 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
    • C07D307/18Heterocyclic 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
    • C07D307/22Nitrogen atoms not forming part of a nitro radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
    • C07D307/83Oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/86Benzo [b] furans; Hydrogenated benzo [b] furans with an oxygen atom directly attached in position 7
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D309/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
    • C07D309/30Oxygen atoms, e.g. delta-lactones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D407/00Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Pyrane Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

SE REFIERE A UN COMPUESTO DE FORMULA (I) O SU SAL, DONDE: R1 ES R", R"C(O), R"R`NC(O), ENTRE OTROS; R2 Y R4 SON H, ALQUILO C1-C6, ALQUENILO C2-C6, Ar-ALQUILO Ccero-C6, Het-ALQUILO Ccero-C6; R3 ES H, ALQUILO C1-C6, ALQUENILO C2-C6, ALQUINILO C2-C6, ENTRE OTROS; R5 ES H, ALQUILO C1-C6, ALQUENILO C2-C6, ENTRE OTROS; R6 ES H, ALQUILO C1-C6, ALQUENILO C2-C6, ENTRE OTROS; R' ES H, ALQUILO C1-C6, ALQUENILO C2-C6, ENTRE OTROS; R" ES ALQUILO C1-C6, Ar-ALQUILO C CERO-C6, ENTRE OTROS; X ES O o S; n ES 1-3. SON COMPUESTOS PREFERIDOS 4-(R,S)-AMINO-N-[(3,4-METILENDIOXIBENZOIL)-S-LEUCINA]-TETRAHIDROFURAN-3-ONA, TRANS-4-(R,S)-AMINO-N-[BENCILOXICARBONIL)-S-LEUCINA]-3-HIDROXITETRAHIDROFURANO, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. EL COMPUESTO (I) INHIBE LA ENZIMA CISTEINA PROTEASA EN PARTICULAR LA CATEPSINA K, POR LO QUE PUEDE SER UTIL PARA INHIBIR PERDIDA OSEA, OSTEOPOROSIS, ENFERMEDAD GINGIVAL O PERIODONTAL; TRATAR UNA ENFERMEDAD CARACTERIZADA POR UNA DEGRADACION EXCESIVA DE CARTILAGO O MATRIZ COMO LA OSTEOARTRITIS O ARTRITIS REUMATOIDEREFERS TO A COMPOUND OF FORMULA (I) OR ITS SALT, WHERE: R1 IS R ", R" C (O), R "R`NC (O), AMONG OTHERS; R2 AND R4 ARE H, RENT C1-C6 , C2-C6 ALKYYL, Ar-Ccero-C6 ALKYL, Het-Ccero-C6 ALKYL; R3 ES H, C1-C6 ALKYL, C2-C6 ALKYLL, AMONG OTHERS; R5 IS H, C1-C6 ALKYL , C2-C6 ALKYLLL, AMONG OTHERS; R6 IS H, C1-C6 ALKYLL, C2-C6 ALKYLL, AMONG OTHERS; R 'ES H, C1-C6 ALKYLL, C2-C6 ALKYLLL, R1 IS C1- C6, Ar-ALKYL C ZERO-C6, AMONG OTHERS; X IS O or S; n IS 1-3. THEY ARE PREFERRED COMPOUNDS 4- (R, S) -AMINO-N - [(3,4-METHYLENDIOXIBENZOIL) -S-LEUCINE] -TETRAHYDROFURAN-3-ONA, TRANS-4- (R, S) -AMINO-N- [ BENCILOXICARBONIL) -S-LEUCINA] -3-HIDROXITETRAHIDROFURANO, AMONG OTHERS. IT ALSO REFERS TO A PROCEDURE FOR PREPARATION. COMPOUND (I) INHIBITS THE CYSTEINE ENZYME PROTEASE IN PARTICULAR CATEPSIN K, SO IT MAY BE USEFUL TO INHIBIT LOSS OF OSEA, OSTEOPOROSIS, GINGIVAL OR PERIODONTAL DISEASE; TREAT A DISEASE CHARACTERIZED BY EXCESSIVE DEGRADATION OF CARTILAGO OR MATRIX LIKE OSTEOARTHRITIS OR RHEUMATOID ARTHRITIS

PE1998000336A 1997-05-06 1998-05-05 PROTEASE INHIBITORS PE71599A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US4575897P 1997-05-06 1997-05-06

Publications (1)

Publication Number Publication Date
PE71599A1 true PE71599A1 (en) 1999-09-15

Family

ID=21939723

Family Applications (1)

Application Number Title Priority Date Filing Date
PE1998000336A PE71599A1 (en) 1997-05-06 1998-05-05 PROTEASE INHIBITORS

Country Status (19)

Country Link
EP (1) EP1003846A4 (en)
JP (1) JP2001525804A (en)
KR (1) KR20010012256A (en)
CN (1) CN1255161A (en)
AR (1) AR013079A1 (en)
AU (1) AU7562598A (en)
BR (1) BR9809306A (en)
CA (1) CA2288868A1 (en)
CO (1) CO4950618A1 (en)
HU (1) HUP0002247A3 (en)
IL (1) IL132088A0 (en)
NO (1) NO995434D0 (en)
NZ (1) NZ337889A (en)
PE (1) PE71599A1 (en)
PL (1) PL336856A1 (en)
TR (1) TR199902766T2 (en)
UY (1) UY25143A1 (en)
WO (1) WO1998050533A1 (en)
ZA (1) ZA983762B (en)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CO5150165A1 (en) * 1998-11-13 2002-04-29 Smithkline Beecham Plc PROTEASE INHIBITORS: KATEPSIN K TYPE
DZ3083A1 (en) * 1999-02-19 2004-06-02 Smithkline Beecham Corp New protease inhibitor compounds, process for their preparation and pharmaceutical compositions containing them
GB9911417D0 (en) * 1999-05-18 1999-07-14 Peptide Therapeutics Ltd Furanone derivatives as inhibitors of cathepsin s
WO2001034599A1 (en) * 1999-11-10 2001-05-17 Smithkline Beecham Corporation Protease inhibitors
US20040024000A1 (en) * 2000-10-19 2004-02-05 Rajeshwar Singh Dihydropyrimidine derivatives as cysteine protease inhibitors
JP2004513942A (en) * 2000-11-17 2004-05-13 メディヴァー ユーケイ リミテッド Cysteine protease inhibitor
JP2004520439A (en) * 2000-11-17 2004-07-08 メディヴィル・アクチボラグ Cysteine protease inhibitor
JP2004522738A (en) * 2001-01-17 2004-07-29 アミュラ テラピューティクス リミテッド Cyclic 2-carbonylaminoketones as inhibitors of cruzipaine and other cysteine proteases
US7132449B2 (en) 2001-01-17 2006-11-07 Amura Therapeutics Limited Inhibitors of cruzipain and other cysteine proteases
AU2002219397B2 (en) * 2001-01-17 2008-02-14 Grünenthal GmbH Inhibitors of cruzipain and other cysteine proteases
NZ526912A (en) * 2001-01-17 2005-02-25 Amura Therapeutics Ltd Inhibitors of cruzipain and other cysteine proteases
WO2003037892A1 (en) * 2001-10-29 2003-05-08 Boehringer Ingelheim Pharmaceuticals, Inc. Compounds useful as reversible inhibitors of cysteine proteases
NZ537853A (en) * 2002-07-16 2007-02-23 Amura Therapeutics Ltd Inhibitors of cathepsin K and related cysteine protesases of the CA clan
KR100962972B1 (en) 2002-07-26 2010-06-09 주식회사유한양행 1-phenylpiperidin-3-one derivatives and processes for the preparation thereof
BRPI0413324A (en) 2003-08-06 2006-10-10 Senomyx Inc t1r hetero-oligomeric taste receptors, cell lines expressing said receptors, and taste compounds
AU2016206281B2 (en) * 2003-08-06 2017-11-30 Senomyx, Inc. Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof
DE602005019971D1 (en) * 2004-01-08 2010-04-29 Medivir Ab INHIBITORS OF CYSTONE PROTEASE
CA2619706A1 (en) * 2005-08-17 2007-02-22 Schering Corporation Novel high affinity quinoline-based kinase ligands
GB0614042D0 (en) 2006-07-14 2006-08-23 Amura Therapeutics Ltd Compounds
MX2009012847A (en) * 2007-06-13 2009-12-08 Bristol Myers Squibb Co Dipeptide analogs as coagulation factor inhibitors.
US7893067B2 (en) 2007-06-27 2011-02-22 Medivir Ab Cysteine protease inhibitors
EP2240491B1 (en) 2008-01-09 2015-07-15 Amura Therapeutics Limited TETRAHYDROFURO(2,3-b)PYRROL-3-ONE DERIVATIVES AS INHIBITORS OF CYSTEINE PROTEINASES
GB0817424D0 (en) * 2008-09-24 2008-10-29 Medivir Ab Protease inhibitors

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3190431B2 (en) * 1991-07-01 2001-07-23 三菱化学株式会社 Ketone derivatives
JPH05140063A (en) * 1991-11-19 1993-06-08 Suntory Ltd Dipeptide derivative and medicine for preventing and improving osteopathy, containing the same compound as active component
CA2111930A1 (en) * 1992-12-25 1994-06-26 Ryoichi Ando Aminoketone derivatives
JP2848232B2 (en) * 1993-02-19 1999-01-20 武田薬品工業株式会社 Aldehyde derivatives
JP3599287B2 (en) * 1993-04-28 2004-12-08 三菱化学株式会社 Sulfonamide derivative
US5403952A (en) * 1993-10-08 1995-04-04 Merck & Co., Inc. Substituted cyclic derivatives as novel antidegenerative agents
SK88997A3 (en) * 1995-10-30 1998-05-06 Smithkline Beecham Corp Method of inhibiting cathepsin k
TW448172B (en) * 1996-03-08 2001-08-01 Pharmacia & Upjohn Co Llc Novel hydroxamic acid derivatives useful for the treatment of diseases related to connective tissue degradation
WO1998004539A1 (en) * 1996-07-29 1998-02-05 Mitsubishi Chemical Corporation Oxygenic heterocyclic derivatives

Also Published As

Publication number Publication date
NO995434L (en) 1999-11-05
KR20010012256A (en) 2001-02-15
TR199902766T2 (en) 2000-02-21
CA2288868A1 (en) 1998-11-12
EP1003846A1 (en) 2000-05-31
WO1998050533A1 (en) 1998-11-12
NO995434D0 (en) 1999-11-05
PL336856A1 (en) 2000-07-17
UY25143A1 (en) 1998-11-27
CO4950618A1 (en) 2000-09-01
JP2001525804A (en) 2001-12-11
IL132088A0 (en) 2001-03-19
AR013079A1 (en) 2000-12-13
AU7562598A (en) 1998-11-27
CN1255161A (en) 2000-05-31
HUP0002247A3 (en) 2003-01-28
HUP0002247A2 (en) 2001-05-28
BR9809306A (en) 2000-07-04
EP1003846A4 (en) 2002-11-13
NZ337889A (en) 2001-09-28
ZA983762B (en) 1998-11-06

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