EP0931045A1 - Inhibiteurs de metalloproteinases matricielles et leurs utilisations pharmaceutiques - Google Patents

Inhibiteurs de metalloproteinases matricielles et leurs utilisations pharmaceutiques

Info

Publication number
EP0931045A1
EP0931045A1 EP97939527A EP97939527A EP0931045A1 EP 0931045 A1 EP0931045 A1 EP 0931045A1 EP 97939527 A EP97939527 A EP 97939527A EP 97939527 A EP97939527 A EP 97939527A EP 0931045 A1 EP0931045 A1 EP 0931045A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
sulfonylamino
patient
compound
dibenzofuran
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP97939527A
Other languages
German (de)
English (en)
Inventor
Patrick Michael O'brien
Joseph Armand Picard
Drago Robert Sliskovic
Andrew David White
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Warner Lambert Co LLC
Original Assignee
Warner Lambert Co LLC
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 Warner Lambert Co LLC filed Critical Warner Lambert Co LLC
Publication of EP0931045A1 publication Critical patent/EP0931045A1/fr
Withdrawn legal-status Critical Current

Links

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
    • C07D307/77—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
    • C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • 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
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/76—Dibenzothiophenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Definitions

  • the present invention relates to a method of inhibiting matrix metalloprotemases using compounds that are dibenzofuran sulfonamide derivatives. More particularly, the present invention relates to a method of treating diseases in which matrix metalloproteinases are involved such as multiple sclerosis, atherosclerotic plaque rupture, restenosis, aortic aneurism, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthritis, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leukocytes.
  • diseases in which matrix metalloproteinases are involved such as multiple sclerosis, atherosclerotic plaque rupture, restenosis, aortic aneurism, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthritis, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leuk
  • the compounds of the present invention are inhibitors of matrix metalloproteinases, e.g., stromelysin-1 and gelatinase A (72 kDa gelatinase).
  • matrix metalloproteinases e.g., stromelysin-1 and gelatinase A (72 kDa gelatinase).
  • Stromelysin-1 and gelatinase A are members of the matrix metalloproteinases (MMP). Other members include fibroblast collagenase, neutrophil collagenase, gelatinase B (92 kDa gelatinase), stromelysin-2, stromelysin-3, matrilysin, collagenase 3, and the newly discovered membrane- associated matrix metalloproteinases (Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., and Seiki M., Nature, 1994;370:61-65). Stromelysin-1 is also known as MMP03 and gelatinase A is known as
  • the ability of the matrix metalloproteinases to degrade various components of connective tissue makes them potential targets for controlling pathological processes.
  • the rupture of atherosclerotic plaques is the most common event initiating coronary thrombosis.
  • Destabilization and degradation of the extracellular matrix surrounding these plaques by MMPs has been proposed as a cause of plaque fissuring.
  • the shoulders and regions of foam cell accumulation in human atherosclerotic plaques show locally increased expression of gelatinase B, stromelysin-1, and interstitial collagenase.
  • Inhibitors of matrix metalloproteinases will have utility in treating degenerative aortic disease associated with thinning of the medial aortic wall. Increased levels of the proteolytic activities of MMPs have been identified in patients with aortic aneurisms and aortic stenosis (Vine N. and Powell J.T.. "Metalloproteinases in degenerative aortic diseases,” Clin. Sci., 1991;81 :233-239).
  • Heart failure arises from a variety of diverse etiologies, but a common characteristic is cardiac dilation which has been identified as an independent risk factor for mortality (Lee T.H., Hamilton M.A., Stevenson L.W., Moriguchi J.D., Fonarow G.C., Child J.S., Laks H., and Walden J.A., "Impact of left ventricular size on the survival in advanced heart failure," Am. J. Cardiol., 1993;72:672-676).
  • vascular smooth muscle cells vascular smooth muscle cells
  • Stromelysin is produced by basal keratinocytes in a variety of chronic ulcers (Saarialho-Kere U.K., Ulpu K., Pentland A.P., Birkedal-Hansen H., Parks W.C, Welgus H.G., "Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds," J. Clin. Invest.,
  • a peptide of the conserved MMP propeptide sequence was a weak inhibitor of gelatinase A and inhibited human tumor cell invasion through a layer of reconstituted basement membrane (Melchiori A., Albili A., Ray J.M., and Stetler- Stevenson W.G., Cancer Res.,
  • Inhibitors of MMPs have shown activity in models of tumor angiogenesis (Taraboletti G., Garofalo A., Belotti D., Drudis T., Borsotti P., Scanziani E., Brown P.D., and Giavazzi R., Journal of the National Cancer
  • TIMP-1 and TIMP-2 prevented the formation of collagen fragments, but not proteoglycan fragments, from the degradation of both the bovine nasal and pig articular cartilage models for arthritis, while a synthetic peptide hydroxamate could prevent the formation of both fragments
  • M is a natural (L) alpha amino acid derivative having the structure
  • X is O, S, S(O) n , CH 2 , CO, or NRQ;
  • R is hydrogen, C ⁇ -Cg alkyl, or -Ci -Cg alkyl-phenyl;
  • R is a side chain of a natural alpha amino acid;
  • R2 and R are independently hydrogen, -C1-C5 alkyl, phenyl -NO2, halogen, -OR 5 , -CN, -CO R 5 , -SO3R 5 , -CHO, -COR 5 , -CONR 5 R 6 , -(CH 2 ) n NR 5 R 6 , -CF3, or -NHCOR 5 ; each R 5 and R ⁇ are independently hydrogen or C1-C5 alkyl; and n is 0 to 2, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.
  • X is O. In another embodiment of the invention of Formula I, X is S. In another embodiment of the invention of Formula I, X is CH 2 .
  • R ⁇ - is hydroxy, C1-C5 alkoxy, -NHOH, or -NHObenzyl.
  • R is the side chain of the natural alpha amino acid glycine, alanine, valine, leucine, isoleucine, cysteine, aspartic acid, or phenylalanine.
  • the present invention provides a method of inhibiting a matrix metalloproteinase in a patient in need of matrix metalloproteinase inhibition, the method comprising administering to the patient a therapeutically effective amount of a compound of Formula II
  • Z is a natural (L) amino acid derivative having the structure
  • R" 3 is a side chain of a natural alpha amino acid; and R c is hydrogen, C1-C5 alkyl, or -CH 2 phenyl; and n is 0 to 2, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof. Also provided is a method of inhibiting a matrix metalloproteinase in a patient in need of matrix metalloproteinase inhibition, the method comprising administering to the patient a therapeutically effective amount of a compound of Formula IV.
  • each R 5 and R ⁇ are independently hydrogen or C]-C5 alkyl;
  • R a is C1-C5 alkoxy, hydroxy, or -NHOR c ;
  • R c is hydrogen, C1-C5 alkyl, or -CH 2 phenyl; and n is 0 to 2, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
  • R" is a side chain of a natural alpha amino acid; and R c is hydrogen, C1-C5 alkyl, or -CH 2 phenyl; and n is 0 to 2, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
  • R a is C1-C5 alkoxy, hydroxy, or -NHOR c ; n is 0 to 2;
  • Z is a natural (L) amino acid derivative having the structure
  • R ⁇ and R4 are independently hydrogen, -C1-C5 alkyl, phenyl -NO 2 , halogen, -OR 5 , -CN, -CO 2 R 5 , -SO3R 5 , -CHO, -COR 5 , -CONR R ⁇ , -(CH 2 ) n NR 5 R 6 , -CF3, or -NHCOR 5 ; each R 5 and R ⁇ are independently hydrogen or C ⁇ -C5 alkyl;
  • R c is hydrogen, C1-C5 alkyl, or -CH 2 phenyl; and n is 0 to 2, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
  • Also provided by the present invention is a method of treating atherosclerotic plaque rupture, the method comprising administering to a patient having an atherosclerotic plaque at risk for rupture a therapeutically effective amount of a compound of Formula I-VIII.
  • Also provided by the present invention is a method of treating or preventing restenosis, the method comprising administering to a patient having restenosis or at risk of having restenosis a therapeutically effective amount of a compound of Formula I-VIII. Also provided by the present invention is a method of treating aortic aneurism, the method comprising administering to a patient having aortic aneurism a therapeutically effective amount of a compound of Formula I-VIII.
  • Also provided by the present invention is a method of treating periodontal disease, the method comprising administering to a patient having periodontal disease a therapeutically effective amount of a compound of Formula I-VIII. Also provided by the present invention is a method of treating comeal ulceration, the method comprising administering to a patient having comeal ulceration a therapeutically effective amount of a compound of Formula I-VIII. Also provided by the present invention is a method of treating burns, the method comprising administering to a patient having bums a therapeutically effective amount of a compound of Formula I-VIII.
  • Also provided by the present invention is a method of treating cancer metastasis, the method comprising administering to a patient having cancer metastasis a therapeutically effective amount of a compound of Formula I-VIII.
  • R2 and R ⁇ are independently hydrogen, -Ci -C5 alkyl, phenyl -NO 2 , halogen,
  • a “therapeutically effective amount” is an amount of a compound of Formula I-VIII that when administered to a patient having a disease that can be treated with a compound of Formula I-VIII ameliorates a symptom of the disease.
  • Full-length enzymes are assayed in 50 mM HEPES, 10 mM CaCl 2 , pH 7.0; SCD in 50 mM MES, 10 mM CaCl 2 , pH 6.0; and GaCD in 50 mM MOPS, 10 mM

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention porte sur un procédé d'inhibition de métalloprotéinases matricielles mettant en oeuvre des composés qui sont des dérivés de dibenzofurane sulfonamide ayant la formule (I). L'invention porte plus particulièrement sur un procédé de traitement de pathologies dans lesquelles interviennent les métalloprotéinases matricielles, pathologies telles que sclérose en plaques, rupture de la plaque d'athérosclérose, resténose, anévrisme de l'aorte, insuffisance cardiaque, paradontolyse, ulcération de la cornée, brûlures, ulcères de décubitus, lésions ou ulcères chroniques, métastase cancéreuse, angiogénie tumorale, arthrite ou autre maladies autoimmunes ou inflammatoires selon l'invasion des tissus par les leucocytes.
EP97939527A 1996-09-04 1997-08-22 Inhibiteurs de metalloproteinases matricielles et leurs utilisations pharmaceutiques Withdrawn EP0931045A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US2506296P 1996-09-04 1996-09-04
US25062P 1996-09-04
US5571397P 1997-08-07 1997-08-07
US55713P 1997-08-07
PCT/US1997/014859 WO1998009934A1 (fr) 1996-09-04 1997-08-22 Inhibiteurs de metalloproteinases matricielles et leurs utilisations pharmaceutiques

Publications (1)

Publication Number Publication Date
EP0931045A1 true EP0931045A1 (fr) 1999-07-28

Family

ID=26699216

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97939527A Withdrawn EP0931045A1 (fr) 1996-09-04 1997-08-22 Inhibiteurs de metalloproteinases matricielles et leurs utilisations pharmaceutiques

Country Status (8)

Country Link
EP (1) EP0931045A1 (fr)
JP (1) JP2000517341A (fr)
KR (1) KR20000068414A (fr)
AU (1) AU735013B2 (fr)
BR (1) BR9711988A (fr)
CA (1) CA2256716A1 (fr)
NZ (1) NZ333063A (fr)
WO (1) WO1998009934A1 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20000068415A (ko) 1996-09-04 2000-11-25 로즈 암스트롱, 크리스틴 에이. 트러트웨인 매트릭스 메탈로프로테이나제 억제용 화합물 및 방법
NZ334897A (en) * 1996-12-09 2001-02-23 Warner Lambert Co Medicaments for treating and preventing heart failure and ventricular dilatation
GB9706255D0 (en) 1997-03-26 1997-05-14 Smithkline Beecham Plc Novel compounds
PL346011A1 (en) * 1998-07-21 2002-01-14 Warner Lambert Co Coadministration of acat and mmp inhibitors for the treatment of atherosclerotic lesions
AU758619B2 (en) 1998-07-30 2003-03-27 Warner-Lambert Company Tricyclic sulfonamides and their derivatives as inhibitors of matrix metalloproteinases
WO2000006560A1 (fr) * 1998-07-30 2000-02-10 Warner-Lambert Company Composes heteroaromatiques tricycliques et leurs derives utilises comme inhibiteurs des metalloproteinases matricielles
AU5647099A (en) * 1998-09-11 2000-04-03 Shionogi & Co., Ltd. Remedal or preventive agent for congestive heart failure
DE60120881T2 (de) * 2000-04-07 2007-01-18 Samsung Electronics Co., Ltd., Suwon Sulfonamide als matrix-metalloproteinase inhibitoren
MXPA01013172A (es) 2001-02-14 2002-08-21 Warner Lambert Co Inhibidores sulfonamida de metaloproteinasa de matriz.
AR035455A1 (es) * 2001-04-23 2004-05-26 Hoffmann La Roche Derivados triciclicos de alquilhidroxamato , procesos para su elaboracion, composiciones farmaceuticas que los contienen, y el uso de dichos compuestos en la preparacion de medicamentos
ATE380185T1 (de) 2002-10-23 2007-12-15 Glenmark Pharmaceuticals Ltd Tricyclische verbindungen zur behandlung von entzündlichen- und allergischen erkrankungen: verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen
EP1620429B1 (fr) 2003-04-11 2009-04-01 Glenmark Pharmaceuticals S.A. Nouveaux composes heterocycliques pour le traitement des affections inflammatoires et allergiques, leur procede de preparation et compositions pharmaceutiques les contenant
WO2004111044A1 (fr) * 2003-06-17 2004-12-23 Glenmark Pharmaceuticals Ltd. Composes tricycliques efficaces dans le traitement des affections inflammatoires et allergiques : leur procede de preparation
BRPI0516341A (pt) 2004-10-13 2008-09-02 Glenmark Pharmaceuticals Sa método para preparação de intermediários de n-(3,5-dicloropirid-4-il)-4-difluorometoxi-8-metanoss ulfonamido-dibenzo [b,d] furano-1-carboxamida, método para a preparação de compostos intermediários de n-(3,5-dicloropirid-4-il)-4-difluorometoxi-8-metanoss ulfonamido-dibenzo [b,d] furano-1-carboxamida, n-(3,5-dicloropirid-4-il)-4-difluorometoxi-8-metanoss ulfonamido-dibenzeno [b,d] furano-1-carboxamida, método para a sìntese de n-(3,5-dicloropirid-4-il)-4-difluorometoxi-8-metanoss ulfonamido-dibenzo [b,d] furano-1-carboxamida e seu sal sódico de n-(3,5-dicloropirid-4-il)-4-difluorometoxi-8-metanoss ulfonamido-dibenzo [b,d] furano-1-carboxamida
SI1831227T1 (sl) 2004-12-17 2013-09-30 Glenmark Pharmaceuticals S.A. Nove heterociklične spojine uporabne za zdravljenje vnetnih in alergijskih motenj
PL1831227T3 (pl) 2004-12-17 2013-10-31 Glenmark Pharmaceuticals Sa Nowe związki heterocykliczne użyteczne w leczeniu stanów zapalnych i dolegliwości alergicznych
WO2008057254A2 (fr) * 2006-10-27 2008-05-15 Wyeth Composés tricycliques servant d'inhibiteurs des métalloprotéases matricielles
AR066412A1 (es) * 2007-05-04 2009-08-19 Wyeth Corp Derivados de dibenzofurano y dibenzotiofeno, composiciones farmaceuticas que los contienen y usos en patologias tales como trastornos oseos, crecimiento de tumores, diabetes y obesidad.
CN105906665B (zh) * 2016-05-16 2017-11-28 中国医学科学院医药生物技术研究所 咔唑磺酰胺衍生物前药或其可药用盐及其制备方法和应用
WO2021147882A1 (fr) * 2020-01-21 2021-07-29 深圳信立泰药业股份有限公司 Inhibiteur de la cathepsine k dérivé du dibenzofurane, son procédé de préparation et son utilisation médicale

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2065966C3 (de) * 1969-09-06 1978-11-16 Ajinomoto Co., Inc., Tokio N-Fluorenyl-sulfonyl-aminocarbonsäuren sowie diese enthaltende Mittel
NL7013043A (fr) * 1969-09-06 1971-03-09
US3845097A (en) * 1969-09-06 1974-10-29 Ajinomoto Kk N-substituted amino acids and novel ester
US4097472A (en) * 1974-11-08 1978-06-27 Mitsubishi Chemical Industries Limited N2 -arylsulfonyl-l-argininamides and the pharmaceutically acceptable salts thereof
DE3577700D1 (de) * 1984-11-30 1990-06-21 Shosuke Okamoto Lysinderivat und proteinase-inhibitor.
US5455258A (en) * 1993-01-06 1995-10-03 Ciba-Geigy Corporation Arylsulfonamido-substituted hydroxamic acids
PT828726E (pt) * 1995-06-02 2002-03-28 Warner Lambert Co Inibidores triciclicos de metaloproteinases de matriz
PL326700A1 (en) * 1995-11-17 1998-10-26 Warner Lambert Co Sulphonamide-based inhibitors of intercellular substance metaloproteinases
SK282995B6 (sk) * 1996-01-23 2003-01-09 Shionogi And Co., Ltd. Zlúčenina na inhibíciu metaloproteázy a prostriedok s jej obsahom

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9809934A1 *

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AU735013B2 (en) 2001-06-28
KR20000068414A (ko) 2000-11-25
BR9711988A (pt) 1999-08-24
AU4159597A (en) 1998-03-26
CA2256716A1 (fr) 1998-03-12
NZ333063A (en) 2000-12-22
WO1998009934A1 (fr) 1998-03-12
JP2000517341A (ja) 2000-12-26

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