UY25143A1 - PROCEDURE FOR THE PREPARATION OF PROTEASE INHIBITORS. - Google Patents

PROCEDURE FOR THE PREPARATION OF PROTEASE INHIBITORS.

Info

Publication number
UY25143A1
UY25143A1 UY25143A UY25143A UY25143A1 UY 25143 A1 UY25143 A1 UY 25143A1 UY 25143 A UY25143 A UY 25143A UY 25143 A UY25143 A UY 25143A UY 25143 A1 UY25143 A1 UY 25143A1
Authority
UY
Uruguay
Prior art keywords
alkyl
het
alkenyl
cysteine proteases
inhibitors
Prior art date
Application number
UY25143A
Other languages
Spanish (es)
Inventor
F Veber Daniel
D Gribble Andrew
Witherington J
E Fenwick Ashley
Robert Marquis
Original Assignee
Smithkline Beecham Corp Y Smithkline Beecham P L C
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 Corp Y Smithkline Beecham P L C filed Critical Smithkline Beecham Corp Y Smithkline Beecham P L C
Publication of UY25143A1 publication Critical patent/UY25143A1/en

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Classifications

    • 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
    • C07D307/26—Heterocyclic 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
    • C07D307/30—Heterocyclic 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
    • C07D307/32—Oxygen 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06—Anabolic agents
    • 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
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic 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
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [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
    • C07D307/83—Oxygen atoms
    • 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
    • C07D307/77—Heterocyclic 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
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/86—Benzo [b] furans; Hydrogenated benzo [b] furans with an oxygen atom directly attached in position 7
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic 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
    • C07D309/28—Heterocyclic 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
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/12—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic 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
    • C07D407/02—Heterocyclic 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
    • C07D407/12—Heterocyclic 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
    • 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

Landscapes

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

Abstract

Procedimiento para preparar compuestos derivados n-sustituidos de 4-amino-tetrahidrofuran-3-ona, 4-aminotetrahidropiran-3-ona y 4-aminotetrahidrotiofen-3-ona utilizados como inhibidores de cisteína proteasas, particularmente catepsina k. Son útiles en el tratamiento de enfermedades caracterizadas por la pérdida excesiva de hueso o cartílago, por ejemplo osteoporosis, periodontitis y artritis, en las que están implicadas cisteína proteasas. Es un compuesto de fórmula l en que: R1 es R'', R''C(O), R''C(S), R''OC(O), CH(R6)C(O); R2 es H, alquilo, alquenilo, Ar-alquilo, o Het-alquilo; R3 es H, alquilo, alquenilo, alquinilo, cicloalquil, Het-alquilo; R4 es H, alquilo, alquenilo, Ar-alquilo, Het-alquilo; R5 en cada caso, es independientemente H, alquilo, alquenilo, Ar-alquilo, Het-alquilo; X es O o S; y nes 1,2 o 3; o una sal farmacéuticamente aceptables, que son inhibidores de cisteína proteasas. Ejemplo de un compuesto de fórmula l sería: 4-(R, S)-Amino-N-[(3,4-diclorobenzoil)-S-leucina]-tetrahidrofuran-3-ona.Process for preparing n-substituted derivative compounds of 4-amino-tetrahydrofuran-3-one, 4-aminotetrahydropyran-3-one and 4-aminotetrahydrothiophen-3-one used as inhibitors of cysteine proteases, particularly cathepsin k. They are useful in the treatment of diseases characterized by excessive loss of bone or cartilage, for example osteoporosis, periodontitis and arthritis, in which cysteine proteases are involved. It is a compound of formula I in which: R1 is R ", R" C (O), R "C (S), R" OC (O), CH (R6) C (O); R2 is H, alkyl, alkenyl, Ar-alkyl, or Het-alkyl; R3 is H, alkyl, alkenyl, alkynyl, cycloalkyl, Het-alkyl; R4 is H, alkyl, alkenyl, Ar-alkyl, Het-alkyl; R5 at each occurrence is independently H, alkyl, alkenyl, Ar-alkyl, Het-alkyl; X is O or S; and nes 1,2 or 3; or a pharmaceutically acceptable salt, which are inhibitors of cysteine proteases. Example of a compound of formula I would be: 4- (R, S) -Amino-N - [(3,4-dichlorobenzoyl) -S-leucine] -tetrahydrofuran-3-one.

UY25143A 1997-05-06 1998-08-17 PROCEDURE FOR THE PREPARATION OF PROTEASE INHIBITORS. UY25143A1 (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
UY25143A1 true UY25143A1 (en) 1998-11-27

Family

ID=21939723

Family Applications (1)

Application Number Title Priority Date Filing Date
UY25143A UY25143A1 (en) 1997-05-06 1998-08-17 PROCEDURE FOR THE PREPARATION OF 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
WO2002032879A1 (en) * 2000-10-19 2002-04-25 Naeja Pharmaceutical Inc. Dihydropyrimidine derivatives as cysteine protease inhibitors
DE60118793T2 (en) * 2000-11-17 2007-04-26 Medivir Ab CYSTEIN PROTEASE INHIBITORS
IL155961A0 (en) * 2000-11-17 2003-12-23 Medivir Uk Ltd Cysteine protease inhibitors
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
WO2002057246A2 (en) * 2001-01-17 2002-07-25 Amura Therapeutics Limited Inhibitors of cruzipain and other cysteine proteases
CN1269822C (en) * 2001-01-17 2006-08-16 阿姆拉医疗有限公司 Inhibitors of cruzipain and other cysteine proteases
US7132449B2 (en) 2001-01-17 2006-11-07 Amura Therapeutics Limited Inhibitors of cruzipain and other cysteine proteases
US6841571B2 (en) * 2001-10-29 2005-01-11 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
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
RU2419602C2 (en) 2003-08-06 2011-05-27 Синомикс Инк. Novel aromatising substances, taste modifiers, flavouring compounds, taste boosters, umami or sweet taste endowing compounds, and/or boosters and use thereof
WO2005066180A1 (en) 2004-01-08 2005-07-21 Medivir Ab Cysteine protease inhibitors
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
JP5318094B2 (en) * 2007-06-13 2013-10-16 ブリストル−マイヤーズ スクイブ カンパニー Dipeptide analogs as clotting factor inhibitors
US7893067B2 (en) 2007-06-27 2011-02-22 Medivir Ab Cysteine protease inhibitors
WO2009087379A2 (en) 2008-01-09 2009-07-16 Amura Therapeutics Limited Tetrahydrofuro (3, 2 -b) pyrrol- 3 -one derivatives as inhibitors of cysteine proteinases
GB0817424D0 (en) 2008-09-24 2008-10-29 Medivir Ab Protease inhibitors

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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
NZ324921A (en) * 1995-10-30 2000-07-28 Smithkline Beecham Corp Cathepsin K crystal structure and methods of identifying inhibitors of this protease
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
NZ337889A (en) 2001-09-28
JP2001525804A (en) 2001-12-11
BR9809306A (en) 2000-07-04
AR013079A1 (en) 2000-12-13
ZA983762B (en) 1998-11-06
KR20010012256A (en) 2001-02-15
PL336856A1 (en) 2000-07-17
NO995434L (en) 1999-11-05
TR199902766T2 (en) 2000-02-21
CA2288868A1 (en) 1998-11-12
CN1255161A (en) 2000-05-31
HUP0002247A3 (en) 2003-01-28
HUP0002247A2 (en) 2001-05-28
AU7562598A (en) 1998-11-27
PE71599A1 (en) 1999-09-15
EP1003846A4 (en) 2002-11-13
EP1003846A1 (en) 2000-05-31
IL132088A0 (en) 2001-03-19
CO4950618A1 (en) 2000-09-01
WO1998050533A1 (en) 1998-11-12
NO995434D0 (en) 1999-11-05

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Legal Events

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ABAN Application deemed to be withdrawn (no publication fee paid)

Effective date: 20001213