IL175106A0 - Novel keto-oxadiazole derivatives as cathepsin inhibitors - Google Patents

Novel keto-oxadiazole derivatives as cathepsin inhibitors

Info

Publication number
IL175106A0
IL175106A0 IL175106A IL17510606A IL175106A0 IL 175106 A0 IL175106 A0 IL 175106A0 IL 175106 A IL175106 A IL 175106A IL 17510606 A IL17510606 A IL 17510606A IL 175106 A0 IL175106 A0 IL 175106A0
Authority
IL
Israel
Prior art keywords
oxadiazole derivatives
cathepsin inhibitors
novel keto
keto
novel
Prior art date
Application number
IL175106A
Other languages
English (en)
Original Assignee
Aventis Pharma Inc
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 Aventis Pharma Inc filed Critical Aventis Pharma Inc
Publication of IL175106A0 publication Critical patent/IL175106A0/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D261/00Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon 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
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P1/14Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P11/06Antiasthmatics
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
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    • AHUMAN NECESSITIES
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    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
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    • A61P21/04Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
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    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/14Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A61P5/16Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D267/00Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/02Seven-membered rings
    • C07D267/08Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D267/10Seven-membered rings having the hetero atoms in positions 1 and 4 not condensed with other rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D271/00Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/061,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D271/00Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/101,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D271/00Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/101,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • C07D271/1071,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with two aryl or substituted aryl radicals attached in positions 2 and 5
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic 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
    • C07D295/16Heterocyclic 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
    • C07D295/18Heterocyclic 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 carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/195Radicals derived from nitrogen analogues of carboxylic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic 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
    • C07D295/16Heterocyclic 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
    • C07D295/20Heterocyclic 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
    • C07D295/215Radicals derived from nitrogen analogues of carbonic acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06191Dipeptides containing heteroatoms different from O, S, or N
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Pain & Pain Management (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Vascular Medicine (AREA)
IL175106A 2003-10-24 2006-04-23 Novel keto-oxadiazole derivatives as cathepsin inhibitors IL175106A0 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US51437303P 2003-10-24 2003-10-24
PCT/US2004/035282 WO2005040142A1 (en) 2003-10-24 2004-10-22 Novel keto-oxadiazole derivatives as cathepsin inhibitors

Publications (1)

Publication Number Publication Date
IL175106A0 true IL175106A0 (en) 2006-09-05

Family

ID=34520197

Family Applications (1)

Application Number Title Priority Date Filing Date
IL175106A IL175106A0 (en) 2003-10-24 2006-04-23 Novel keto-oxadiazole derivatives as cathepsin inhibitors

Country Status (18)

Country Link
US (1) US7482448B2 (enExample)
EP (1) EP1682524A1 (enExample)
JP (1) JP4769192B2 (enExample)
KR (1) KR20070008517A (enExample)
CN (1) CN100543017C (enExample)
AU (1) AU2004284089B2 (enExample)
BR (1) BRPI0415826A (enExample)
CA (1) CA2547591C (enExample)
IL (1) IL175106A0 (enExample)
MA (1) MA28170A1 (enExample)
ME (1) MEP39608A (enExample)
MX (1) MXPA06004422A (enExample)
NO (1) NO20062150L (enExample)
NZ (1) NZ546504A (enExample)
RS (1) RS20060280A (enExample)
RU (1) RU2346943C2 (enExample)
WO (1) WO2005040142A1 (enExample)
ZA (1) ZA200603183B (enExample)

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JP5215167B2 (ja) 2005-03-22 2013-06-19 ビロベイ,インコーポレイティド システインプロテアーゼ阻害剤としてのスルホニル基含有化合物
WO2007137738A1 (de) * 2006-06-01 2007-12-06 Sanofi-Aventis Spiro-cyclische nitrile als protease-inhibitoren
US7893112B2 (en) 2006-10-04 2011-02-22 Virobay, Inc. Di-fluoro containing compounds as cysteine protease inhibitors
CA2664878A1 (en) * 2006-10-04 2008-04-10 Virobay, Inc. Di-fluoro containing compounds as cysteine protease inhibitors
MY162041A (en) 2007-02-28 2017-05-31 Sanofi Aventis Imaging probes
BRPI0822420A2 (pt) * 2008-04-01 2014-10-07 Virobay Inc Composto, composição farmaceutica, e, métodos para tratar uma doença em uma animal e para tratar um paciente que passa por uma tarepia.
US7741327B2 (en) 2008-04-16 2010-06-22 Hoffmann-La Roche Inc. Pyrrolidinone glucokinase activators
CN102264710B (zh) * 2008-12-19 2014-11-05 美迪维尔英国有限公司 半胱氨酸蛋白酶抑制剂
US7893099B2 (en) * 2009-06-11 2011-02-22 Hoffman-La Roche Inc. Cyclopentane derivatives
US20110021570A1 (en) 2009-07-23 2011-01-27 Nancy-Ellen Haynes Pyridone glucokinase activators
US8324417B2 (en) * 2009-08-19 2012-12-04 Virobay, Inc. Process for the preparation of (S)-2-amino-5-cyclopropyl-4,4-difluoropentanoic acid and alkyl esters and acid salts thereof
US8895497B2 (en) 2009-12-04 2014-11-25 Dcb-Usa, Llc Cathepsin S inhibitors
US8500766B2 (en) * 2009-12-18 2013-08-06 Colgate-Palmolive Company Oral care implement multiple soft tissue cleaner components
US8178689B2 (en) 2010-06-17 2012-05-15 Hoffman-La Roche Inc. Tricyclic compounds
AU2013305759C1 (en) 2012-08-23 2018-01-18 Janssen Biopharma, Inc. Compounds for the treatment of paramoxyvirus viral infections
WO2020201572A1 (en) 2019-04-05 2020-10-08 Université De Bretagne Occidentale Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning

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CA2547591A1 (en) 2005-05-06
CA2547591C (en) 2010-08-17
AU2004284089B2 (en) 2009-11-26
NO20062150L (no) 2006-05-12
NZ546504A (en) 2009-01-31
AU2004284089A1 (en) 2005-05-06
WO2005040142A1 (en) 2005-05-06
RU2006117788A (ru) 2007-11-27
US7482448B2 (en) 2009-01-27
RS20060280A (sr) 2008-08-07
HK1101871A1 (zh) 2007-10-26
ZA200603183B (en) 2007-09-26
BRPI0415826A (pt) 2007-01-02
WO2005040142B1 (en) 2005-07-14
MA28170A1 (fr) 2006-09-01
US20060189657A1 (en) 2006-08-24
MXPA06004422A (es) 2006-07-03
WO2005040142A9 (en) 2005-06-09
JP2007509175A (ja) 2007-04-12
JP4769192B2 (ja) 2011-09-07
CN1898219A (zh) 2007-01-17
KR20070008517A (ko) 2007-01-17
CN100543017C (zh) 2009-09-23
EP1682524A1 (en) 2006-07-26
RU2346943C2 (ru) 2009-02-20
MEP39608A (en) 2011-02-10

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