WO2000018748A1 - Derives de rhodanine utiles pour le traitement et la prevention de troubles metaboliques des os - Google Patents

Derives de rhodanine utiles pour le traitement et la prevention de troubles metaboliques des os Download PDF

Info

Publication number
WO2000018748A1
WO2000018748A1 PCT/EP1999/007250 EP9907250W WO0018748A1 WO 2000018748 A1 WO2000018748 A1 WO 2000018748A1 EP 9907250 W EP9907250 W EP 9907250W WO 0018748 A1 WO0018748 A1 WO 0018748A1
Authority
WO
WIPO (PCT)
Prior art keywords
signifies
thiazolidin
thioxo
phenyl
benzylidene
Prior art date
Application number
PCT/EP1999/007250
Other languages
English (en)
Inventor
Angelika Esswein
Wolfgang Schaefer
Christos Tsaklakidis
Konrad Honold
Klaus Kaluza
Eike Hoffmann
Original Assignee
Roche Diagnostics Gmbh
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 Roche Diagnostics Gmbh filed Critical Roche Diagnostics Gmbh
Priority to AU63309/99A priority Critical patent/AU6330999A/en
Publication of WO2000018748A1 publication Critical patent/WO2000018748A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
    • C07D277/34—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
    • C07D277/36—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Definitions

  • Rhodanine derivatives for the treatment and prevention of metabolic bone disorders
  • the present invention is concerned with rhodanine derivatives for the treatment and prevention of metabolic bone disorders, a process for their manufacture as well as medicaments which contain these compounds.
  • bone resorption inhibitors such as oestrogens, calcitonin and biphosphonates have primarily been used for the treatment of metabolic bone disorders.
  • the use of these substances is, however, limited and also does not show the desired effect in all cases.
  • Compounds which have a stimulating activity on bone synthesis and in addition contribute to an increase in an already reduced bone mass are accordingly of especial significance for the treatment of metabolic bone disorders.
  • Compounds having the rhodanine structural element are known as antidiabetics, cytostatics, inflammation inhibitors and for the treatment of cardiovascular illnesses, e.g. WO9305039, WO 9705875, EP 677517.
  • the parathyroid hormone (PTH) is the natural ligand of the receptor and an important regulator for the maintenance of the calcium level in the body.
  • PTH can stimulate bone formation or bone resorption. In this, it acts as a regulatory hormone on a series of enzymes, inter alia, on adenylate cyclase (cAMP synthesis) and on ornithine decarboxylase.
  • cAMP synthesis adenylate cyclase
  • PTH mobilizes calcium from bones in the case of calcium deficiency, reduces calcium excretion from the kidneys and simultaneously improves the resorption of calcium from the intestine by an increased synthesis of l,25-(OH) 2 D 3 .
  • a normalization of the calcium level is achieved by the action on these target organs.
  • rhodanine derivatives of the present invention stimulate the PTH receptor- mediated cAMP formation.
  • Compounds of the present invention are accordingly suitable for the broad treatment of metabolic bone disorders. They can be used primarily to good effect where the bone synthesis is disturbed, i.e. they are especially suitable for the treatment of osteopenic disorders of the skeletal system such as e.g. osteoporosis, inter alia, osteogenesis imperfecta as well as for the local assistance in bone regeneration and osteoinduction such as e.g. in orthopedic and maxillary medical indications, in fracture healing, osteosyntheses, pseudoarthroses and for the healing in of bone implants.
  • osteopenic disorders of the skeletal system such as e.g. osteoporosis, inter alia, osteogenesis imperfecta as well as for the local assistance in bone regeneration and osteoinduction
  • fracture healing, osteosyntheses, pseudoarthroses e.g. in orthopedic and maxillary medical indications, in fracture healing, osteosyntheses, pseudoarthroses and
  • rhodanine derivatives of the present invention as active substances furthermore form a basis for the local and systemic treatment of rheumatoid arthritis, osteoarthritis and degenerative arthrosis.
  • the object of the present invention are compounds of general formula (I),
  • m signifies a number between 0 and 8
  • q signifies a number between 0 and 8
  • A signifies a single bond and m signifies 0 when X signifies CH 2
  • A signifies a single or double bond
  • R 3 signifies hydrogen or lower alkyl
  • Z signifies oxygen, sulphur
  • W signifies an optionally mono- or polysubstituted saturated or unsaturated mono- (sic), bi- or tricycle which can contain one or more hetero atoms,
  • lower alkyl signifies linear or branched alkyl residues with one to six carbon atoms, preferably methyl, ethyl, propyl, i-propyl, butyl, t-butyl, pentyl, hexyl, particularly methyl.
  • Alkoxy groups signify a combination of a C ⁇ -C 10 -alkyl group in accordance with the above definition with an oxygen atom, e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy and pentoxy groups.
  • Substituents are preferably lower alkyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, hydroxy, benzyl, benzyloxy, phenyl, dioxymethylene, cyanobenzoxymethyl, pyrrolidine, alkoxyhydroxy, carboxyl, dialkylamino, styryl and halogen.
  • this is preferably a residue such as the naphthyl, tetrahydronaphthyl, decalinyl, quinolinyl, chromane, chromene, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolyl, benzimidazolyl, indazolyl, oxindolyl, benzofuranyl, benzothiophenyl, benzothiazolyl, benzoxazolyl or purinyl residue, especially the indolyl, naphthyl, benzimidazolyl, quinolinyl, tetrahydroquinolinyl, benzothiophenyl and benzofuranyl residue, which optionally can be mono- or polysubstituted.
  • Substituents are preferably lower alkyl, Ci-C ⁇ -alkoxy, alkoxycarbonyl, alkylcarbonyl, hydroxy, benzyl, benzyloxy, phenyl, dioxymethylene, cyanobenzoxymethyl, pyrrolidine, alkoxyhydroxy, carboxyl, dialkylamino, styryl and halogen.
  • Tricycle signifies anthracene, fluorene, dibenzofuran, dibenzooxepine or carbazole.
  • m signifies a number between 0 and 8
  • A signifies a single bond and m signifies 0 when X signifies CH 2
  • A signifies a single or double bond
  • Ri R 2 signify hydrogen or lower alkyl, whereby Ri and R 2 can be the same or different and, when m signifies 2-8, Ri and R 2 in the group can have various significances within the following sequence
  • R 3 signifies hydrogen or lower alkyl
  • Z signifies oxygen, sulphur
  • W signifies an optionally mono- or polysubstituted saturated or unsaturated mono- (sic), bi- or tricycle which can contain one or more hetero atoms,
  • W is not 4-(2.5-di-tert. butyl-phenyl), if X is methylene, as well as their physiologically compatible salts, esters, optically active forms, racemates, tautomers, as well as derivatives which can be metabolized in vivo to compounds of general formula (I), as well as the use of these compounds for the production of medicaments.
  • Preferred are compounds of general formula I in which X signifies C S, Z signifies oxygen, A signifies a double bond, m signifies a number from 0 to 2, q signifies 0 or 1, Ri and R 2 respectively signify hydrogen or methyl, R 3 signifies hydrogen or methyl and W signifies a phenyl, naphthyl, thiophenyl, benzothiophenyl, furanyl, phenyl, pyridyl, cyclohexenyl, dibenzooxepinyl, pyrryl or imidazolyl residue, which optionally can be mono- or polysubstituted by halogen, hydroxy, methoxy, ethoxy, benzyloxy, butoxycarbnyl, methyl, i-propyl, t-butyl, dioxymethylenee, cyanobenzoxymethyl or benzyl.
  • ⁇ -halocarboxylic acids and aldehydes used as starting materials are either commercially available, known or can be prepared analogously to the generally known processes.
  • Compounds of formula (I) can be administered (sic) in liquid, solid or aerosol form orally, enterally, parenterally, topically, nasally, pulmonary or rectally in all usual non- toxic pharmaceutically acceptable carrier materials, adjuvants and additives.
  • the compounds of formula (I) can also be applied locally to/in the bones (optionally with surgical intervention).
  • parenteral embraces subcutaneous, intravenous and intramuscular delivery or infusions.
  • Oral administration forms can be e.g. tablets, capsules, dragees, syrups, solutions, suspensions, emulsions, elixirs etc., which can contain one or more additives from the following groups, such as flavourings, sweeteners, colouring agents and preservatives.
  • Oral administration forms contain the active ingredient together with non-toxic, pharmaceutically acceptable carrier materials which are suitable for the production of tablets, capsules, dragees etc., such as e.g. calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; starch, mannitol, methylcellulose, talc, highly dispersible silicic acids, high molecular fatty acids (such as stearic acid), groundnut oil, olive oil, paraffin, miglyol, gelatine, agar-agar, magnesium stearate, beeswax, cetyl alcohol, lecithin, gl cerol, animal and vegetable fats, solid high molecular polymers (such as polyethylene glycol).
  • carrier materials which are suitable for the production of tablets, capsules, dragees etc., such as e.g. calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; starch, mannitol, methylcellulose,
  • Tablets, capsules, dragees etc. can be provided with an appropriate coating, e.g. glyceryl mono- stearate or glyceryl distearate, in order to prevent undesired side effects in the gastrointestinal tract or to give a longer duration of action by the delayed absorption in the gastrointestinal tract.
  • an appropriate coating e.g. glyceryl mono- stearate or glyceryl distearate
  • sterile injectable aqueous or oily solutions or suspensions which contain the usual additives such as stabilizers and solubilizers.
  • additives can be e.g. water, isotonic saline, 1,3- butanediol, fatty acids (such as oleic acid), mono- and diglycerides or miglyol.
  • non-irritating additives which are solid at normal temperatures and liquid at rectal temperatures, such as e.g. cocoa butter and polyethylene glycol.
  • Pharmaceutically usual carrier media are used for application as aerosols. Creams, tinctures, gels, solutions or suspensions etc. with the pharmaceutically usual additives are used for external application.
  • the dosage can depend n a variety of factors such as mode of administration, species, age and/or individual condition.
  • the doses to be administered daily or at intervals lie at 1- 1000 mg/individual, preferably at 10-250 mg/individual, and can be taken at one time or divided over several times.
  • the compounds of formula (I) can also be applied locally to/in the bones (optionally with surgical intervention).
  • the application directly to/in the bones (optionally with surgical intervention) can be effected locally or carrier-bonded either in solution or suspension, conveniently by infusion or injection.
  • Carrier-bonded compounds of formula (I) can be administered, for example, as gels, pastes, solids or as a coating on implants.
  • Biocompatible and preferably biodegradable materials are used as the carrier. Preferably, the materials themselves also induce wound healing or osteogenesis.
  • the compounds of formula (I) are imbedded in polymer gels or films in order to immobilize them and to apply these preparations directly on the site of the bone to be treated.
  • polymer-based gels or films consist, for example, of glycerine, methylcellulose, hyaluronic acid, polyethylene oxides and/or poloxamers.
  • collagen, gelatines and alginates are described, for example, in WO 93/00050 and WO 93/20859.
  • Further polymers are polylactic acid (PLA) and copolymers of lactic acid and glycolic acid (PLPG) (Hollinger el al., J. Biomed. Mater. Res.
  • DBM Decorated Bone Matrix
  • polymers as are used, for example, for the adsorption of TGF ⁇ and which are described in EP-A 0 616 814 and EP-A-0 567 391 and synthetic bone matrices in accordance with WO 91/18558.
  • suitable as carriers for the compounds of formula (I) are materials which are usually used for the implantation of bone substitutes or otherwise of therapeutically active substances. Such carriers are based, for example, on calcium sulphate, tricalcium phosphate, hydroxylapatite (sic) and its biodegradable derivatives and polyanhydrides. Apart from these biodegradable carriers there are also suitable carriers which are not biodegradable, but which are biocompatible. Such carriers are, for example, sintered hydroxylapatite, bioglass, aluminates or other ceramic materials (e.g. calcium aluminium phosphate). These materials are preferably used in combination with the biodegradable materials, such as especially polylactic acid, hydroxylapatite, collagen or tricalcium phosphate. Further non-degradable carriers are described, for example, in US Patent 4,164,560.
  • a carrier which liberates the compounds of formula (I) continuously at the target site is especially preferred.
  • a carrier which liberates the compounds of formula (I) continuously at the target site are especially suitable for this.
  • Preferred in the scope of the present invention are, apart form the compounds named in the Examples and compounds derivable by a combination of all of the significances of the substituents set forth in the claims, the following derivatives as well as their physiologically compatible salts, esters, optically active forms, racemates, tautomers as well as derivatives which can be metabolized in vivo to compounds of general formula (I), as well as the use of these compounds for the production of medicaments, Preferred Compounds (PC):
  • rhodanine derivative (Example 1) is dissolved in 40 ml of dioxan, treated with 1 mmol of P 2 S 5 and heated at reflux. After 2 to 10 hours the mixture is treated with active charcoal and filtered. The dioxan is removed under a vacuum and the residue is crystallized with ethanol. For purification, it is treated with cold dimethylformamide, treated with active charcoal and precipitated with water.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des composés représentés par la formule générale (I), dans laquelle m est un nombre compris entre 0 et 8; q est un nombre compris entre 0 et 8; X est le groupe CH2 ou C=S, A étant une liaison simple et m est 0 si X est CH2; A est une liaison simple ou double; R1 et R2 sont hydrogène ou alkyle inférieur, R1 et R2 pouvant être identiques ou différents, et, si m est compris entre 2 et 8, R1 et R2 dans le groupe CR1=CR2 peuvent avoir diverses notations dans la séquence suivante; R3 est hydrogène ou alkyle inférieur; Z est oxygène, soufre; W est un composé monocyclique, bicyclique ou tricyclique saturé ou insaturé comportant éventuellement une ou plusieurs substitutions, qui peut contenir un ou plusieurs hétéroatomes. L'invention concerne également les sels physiologiquement compatibles de ces composés, leurs esters, leurs formes optiquement actives, leurs racémates, leurs tautomères, ainsi que des dérivés pouvant être métabolisés in vivo pour obtenir des composés représentés par la formule générale (I), et l'utilisation de ces composés en vue de produire des médicaments utiles pour prévenir ou traiter des troubles métaboliques des os.
PCT/EP1999/007250 1998-09-30 1999-09-30 Derives de rhodanine utiles pour le traitement et la prevention de troubles metaboliques des os WO2000018748A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63309/99A AU6330999A (en) 1998-09-30 1999-09-30 Rhodanine derivatives for the treatment and prevention of metabolic bone disorders

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP98118538.2 1998-09-30
EP98118538 1998-09-30

Publications (1)

Publication Number Publication Date
WO2000018748A1 true WO2000018748A1 (fr) 2000-04-06

Family

ID=8232726

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/007250 WO2000018748A1 (fr) 1998-09-30 1999-09-30 Derives de rhodanine utiles pour le traitement et la prevention de troubles metaboliques des os

Country Status (2)

Country Link
AU (1) AU6330999A (fr)
WO (1) WO2000018748A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001016123A1 (fr) * 1999-08-31 2001-03-08 Maxia Pharmaceuticals, Inc. Benzylidene-thiazolidinediones et analogues et leur utilisation pour le traitement de l'inflammation
WO2003097621A1 (fr) * 2002-05-17 2003-11-27 Qlt Inc. Procedes d'utilisation de derives de thiazolidinedithione
WO2004043955A1 (fr) * 2002-11-13 2004-05-27 Rigel Pharmaceuticals, Inc. Derives de rhodanine et compositions pharmaceutiques les contenant
JP2005538188A (ja) * 2002-07-10 2005-12-15 アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ アゾリジノン−ビニル縮合−ベンゼン誘導体
WO2006024699A1 (fr) * 2004-08-30 2006-03-09 Karyon-Ctt Ltd Composes de thioxothiazolidinone utilises comme produits pharmaceutiques
US7071218B2 (en) 2001-11-15 2006-07-04 Incyte San Diego Incorporated N-substituted heterocycles for the treatment of hypercholesteremia, dyslipidemia and other metabolic disorders; cancer, and other diseases
US7102000B2 (en) 2002-03-08 2006-09-05 Incyte San Diego Inc. Heterocyclic amide derivatives for the treatment of diabetes and other diseases
WO2006119736A2 (fr) * 2005-05-09 2006-11-16 Combinature Biopharm Ag Modulateurs du domaine pdz
US7153875B2 (en) 2001-03-07 2006-12-26 Incyte San Diego Heterocyclic derivatives for the treatment of cancer and other proliferative diseases
US7196108B2 (en) 2002-03-08 2007-03-27 Incyte San Diego Inc. Bicyclic heterocycles for the treatment of diabetes and other diseases
US7265139B2 (en) 2001-03-08 2007-09-04 Incyte San Diego Inc. RXR activating molecules
US7674792B2 (en) 2005-06-08 2010-03-09 Glaxosmithkline Llc 5(Z)-5-(6-quinoxalinylmethylidene)-2-[2,6-dichlorophenyl)amino]-1,3-thiazol-4(5H)-one
US7767701B2 (en) 2002-11-22 2010-08-03 Glaxosmithkline Llc Chemical compounds
CN107382996A (zh) * 2017-06-30 2017-11-24 中国农业大学 一种特异性抑制植物质膜H+‑ATPase的化合物及其制备方法和应用

Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2196797A1 (en) * 1972-08-25 1974-03-22 Aries Robert Parasiticidal 5-styryl rhodanines - prepd. by condensation of a subst ben-aldehyde and a 5-methyl rhodanine
EP0211670A2 (fr) * 1985-08-09 1987-02-25 Eli Lilly And Company Composés de di-t-butylphénol
EP0237138A1 (fr) * 1986-01-07 1987-09-16 Yamanouchi Pharmaceutical Co., Ltd. Composés hétérocycliques, leur préparation et compositions pharmaceutiques les contenant
EP0316790A1 (fr) * 1987-11-13 1989-05-24 Nisshin Flour Milling Co., Ltd. Dérivés de rhodanine, procédé de préparation, leur utilisation et les compositions pharmaceutiques les contenant
EP0343643A2 (fr) * 1988-05-25 1989-11-29 Warner-Lambert Company Dérivés arylméthyléniques, sélectionnés de thiazolidinones, d'imidazolidinones et d'oxazolidinones utiles comme agents anti-allergiques et comme agents anti-inflammatoires
EP0391644A2 (fr) * 1989-04-07 1990-10-10 Eli Lilly And Company Dérivés de rhodanine arylsubstitués
EP0398179A1 (fr) * 1989-05-19 1990-11-22 Nisshin Flour Milling Co., Ltd. Dérivés de rhodanine et composés pharmaceutiques
EP0434394A2 (fr) * 1989-12-21 1991-06-26 Eli Lilly And Company Composés pour le traitement d'inflammations intestinales
JPH05306224A (ja) * 1992-04-24 1993-11-19 Wakamoto Pharmaceut Co Ltd ドーパミン β−ヒドロキシラーゼ阻害剤
EP0587377A2 (fr) * 1992-09-10 1994-03-16 Eli Lilly And Company Thiazolidinones comme agents hypoglycemiants et pour le traitement de la maladie d'Alzheimer
EP0604983A1 (fr) * 1992-12-28 1994-07-06 Mitsubishi Chemical Corporation Dérivés du naphtalène
EP0677517A1 (fr) * 1994-03-16 1995-10-18 Eli Lilly And Company Traitement de la maladie d'Alzheimer employant des inhibiteurs de cathepsin
EP0691129A2 (fr) * 1994-07-06 1996-01-10 Eli Lilly And Company Composés thiazolidinones et pyrrolidinones pour inhiber la perte osseuse
WO1996026207A1 (fr) * 1995-02-23 1996-08-29 Nissan Chemical Industries, Ltd. Composes de thiazolidine et d'oxazolidine de type indoles avec action hypoglycemique
EP0783888A1 (fr) * 1995-12-26 1997-07-16 Sankyo Company Limited Utilisation de la troglitazone et de thiazolidinediones apparentées dans la fabrication d'un médicament destiné au traitement et la prévention de l'ostéoporose
WO1998001445A1 (fr) * 1996-07-09 1998-01-15 Smithkline Beecham S.P.A. Derives d'indole pour le traitement de l'osteoporose

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2196797A1 (en) * 1972-08-25 1974-03-22 Aries Robert Parasiticidal 5-styryl rhodanines - prepd. by condensation of a subst ben-aldehyde and a 5-methyl rhodanine
EP0211670A2 (fr) * 1985-08-09 1987-02-25 Eli Lilly And Company Composés de di-t-butylphénol
EP0237138A1 (fr) * 1986-01-07 1987-09-16 Yamanouchi Pharmaceutical Co., Ltd. Composés hétérocycliques, leur préparation et compositions pharmaceutiques les contenant
EP0316790A1 (fr) * 1987-11-13 1989-05-24 Nisshin Flour Milling Co., Ltd. Dérivés de rhodanine, procédé de préparation, leur utilisation et les compositions pharmaceutiques les contenant
EP0343643A2 (fr) * 1988-05-25 1989-11-29 Warner-Lambert Company Dérivés arylméthyléniques, sélectionnés de thiazolidinones, d'imidazolidinones et d'oxazolidinones utiles comme agents anti-allergiques et comme agents anti-inflammatoires
EP0391644A2 (fr) * 1989-04-07 1990-10-10 Eli Lilly And Company Dérivés de rhodanine arylsubstitués
EP0398179A1 (fr) * 1989-05-19 1990-11-22 Nisshin Flour Milling Co., Ltd. Dérivés de rhodanine et composés pharmaceutiques
EP0434394A2 (fr) * 1989-12-21 1991-06-26 Eli Lilly And Company Composés pour le traitement d'inflammations intestinales
JPH05306224A (ja) * 1992-04-24 1993-11-19 Wakamoto Pharmaceut Co Ltd ドーパミン β−ヒドロキシラーゼ阻害剤
EP0587377A2 (fr) * 1992-09-10 1994-03-16 Eli Lilly And Company Thiazolidinones comme agents hypoglycemiants et pour le traitement de la maladie d'Alzheimer
EP0604983A1 (fr) * 1992-12-28 1994-07-06 Mitsubishi Chemical Corporation Dérivés du naphtalène
EP0677517A1 (fr) * 1994-03-16 1995-10-18 Eli Lilly And Company Traitement de la maladie d'Alzheimer employant des inhibiteurs de cathepsin
US5747517A (en) * 1994-03-16 1998-05-05 Eli Lilly And Company Benzylidene rhodanines
EP0691129A2 (fr) * 1994-07-06 1996-01-10 Eli Lilly And Company Composés thiazolidinones et pyrrolidinones pour inhiber la perte osseuse
WO1996026207A1 (fr) * 1995-02-23 1996-08-29 Nissan Chemical Industries, Ltd. Composes de thiazolidine et d'oxazolidine de type indoles avec action hypoglycemique
EP0783888A1 (fr) * 1995-12-26 1997-07-16 Sankyo Company Limited Utilisation de la troglitazone et de thiazolidinediones apparentées dans la fabrication d'un médicament destiné au traitement et la prévention de l'ostéoporose
WO1998001445A1 (fr) * 1996-07-09 1998-01-15 Smithkline Beecham S.P.A. Derives d'indole pour le traitement de l'osteoporose

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 120, no. 17, 25 April 1994, Columbus, Ohio, US; abstract no. 208602b, YASUHIRO O page 101; XP002093303 *
HANS BEHRINGER ET AL: "Substituierte 5-methylen-rhodanine aus 5-chlormethylen-rhodaninen", CHEMISCHE BERICHTE., vol. 91, 1958, WEINHEIM DE, pages 2773 - 2782, XP002093301 *
P.M. CHAKRABARTI ET AL: "An improved synthesis of substituted benzo[b]thiophen-2-carboxylic acids and related acids", TETRAHEDRON., vol. 25, 1969, OXFORD GB, pages 2781 - 2785, XP002093302 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7226940B2 (en) 1999-08-31 2007-06-05 Incyte San Diego, Inc. Substituted heterocycles for the treatment of diabetes and other diseases
US6765013B2 (en) 1999-08-31 2004-07-20 Incyte San Diego Thiazolidinedione derivatives for the treatment of diabetes and other diseases
US6974826B2 (en) 1999-08-31 2005-12-13 Incyte San Diego Inc. Imidazolidinedione derivatives for the treatment of diabetes and other diseases
WO2001016123A1 (fr) * 1999-08-31 2001-03-08 Maxia Pharmaceuticals, Inc. Benzylidene-thiazolidinediones et analogues et leur utilisation pour le traitement de l'inflammation
US7153875B2 (en) 2001-03-07 2006-12-26 Incyte San Diego Heterocyclic derivatives for the treatment of cancer and other proliferative diseases
US7265139B2 (en) 2001-03-08 2007-09-04 Incyte San Diego Inc. RXR activating molecules
US7071218B2 (en) 2001-11-15 2006-07-04 Incyte San Diego Incorporated N-substituted heterocycles for the treatment of hypercholesteremia, dyslipidemia and other metabolic disorders; cancer, and other diseases
US7196108B2 (en) 2002-03-08 2007-03-27 Incyte San Diego Inc. Bicyclic heterocycles for the treatment of diabetes and other diseases
US7102000B2 (en) 2002-03-08 2006-09-05 Incyte San Diego Inc. Heterocyclic amide derivatives for the treatment of diabetes and other diseases
JP2005535593A (ja) * 2002-05-17 2005-11-24 キューエルティー インコーポレーティッド チアゾリジンジチオン誘導体の使用方法
WO2003097621A1 (fr) * 2002-05-17 2003-11-27 Qlt Inc. Procedes d'utilisation de derives de thiazolidinedithione
JP2005538188A (ja) * 2002-07-10 2005-12-15 アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ アゾリジノン−ビニル縮合−ベンゼン誘導体
JP4782564B2 (ja) * 2002-07-10 2011-09-28 メルク セローノ ソシエテ アノニム アゾリジノン−ビニル縮合−ベンゼン誘導体
WO2004043955A1 (fr) * 2002-11-13 2004-05-27 Rigel Pharmaceuticals, Inc. Derives de rhodanine et compositions pharmaceutiques les contenant
US7767701B2 (en) 2002-11-22 2010-08-03 Glaxosmithkline Llc Chemical compounds
WO2006024699A1 (fr) * 2004-08-30 2006-03-09 Karyon-Ctt Ltd Composes de thioxothiazolidinone utilises comme produits pharmaceutiques
WO2006119736A2 (fr) * 2005-05-09 2006-11-16 Combinature Biopharm Ag Modulateurs du domaine pdz
WO2006119736A3 (fr) * 2005-05-09 2007-09-20 Combinature Biopharm Ag Modulateurs du domaine pdz
US7674792B2 (en) 2005-06-08 2010-03-09 Glaxosmithkline Llc 5(Z)-5-(6-quinoxalinylmethylidene)-2-[2,6-dichlorophenyl)amino]-1,3-thiazol-4(5H)-one
CN107382996A (zh) * 2017-06-30 2017-11-24 中国农业大学 一种特异性抑制植物质膜H+‑ATPase的化合物及其制备方法和应用
CN107382996B (zh) * 2017-06-30 2020-11-06 中国农业大学 一种特异性抑制植物质膜H+-ATPase的化合物及其制备方法和应用

Also Published As

Publication number Publication date
AU6330999A (en) 2000-04-17

Similar Documents

Publication Publication Date Title
EP0513379B1 (fr) Derive de 2-arylthiazole et composition pharmaceutique contenant ce derive
US6673816B1 (en) Rhodanine carboxylic acid derivatives for the treatment and prevention of metabolic bone disorders
WO2000018748A1 (fr) Derives de rhodanine utiles pour le traitement et la prevention de troubles metaboliques des os
US4376777A (en) Thiazolidine derivatives use
WO1997012615A1 (fr) Derives benzimidazole actifs comme inhibiteurs de la 15-lo
HU203228B (en) Process for producing new thiazole derivatives and leukotriene-antagonist pharmaceutical compositions comprising same as active ingredient
EP0526598B1 (fr) Nouveaux derives de pyrocatechine a activite pharmacologique
IE83426B1 (en) New pharmacologically active catechol derivatives
KR20000016412A (ko) 신규한 치환 2,4-티아졸리디네디온 유도체, 이의제조 방법 및이를 함유하는 약제학적 조성물
JP4285723B2 (ja) 新規な２−（ｎ−シアノイミノ）チアゾリジン−４−オン誘導体
HU217116B (hu) Tiazolidin-2,4-dion-származékok, sóik, valamint eljárás a vegyületek és az ezeket tartalmazó gyógyászati készítmények előállítására
JP3105545B2 (ja) ４―オキソブタン酸を含有する医薬組成物
KR850001933B1 (ko) 2-치환된-페닐티아졸 유도체의 제조방법
WO2000018746A1 (fr) Derives de thiazolidine utiles pour le traitement et la prevention de troubles metaboliques des os
US6476059B1 (en) Use of polycyclic 2-aminothiazole systems for the treatment of obesity
AU763111B2 (en) Polycyclic 2-amino-thiazole systems, method for the production thereof and medicament containing said compounds
ES2382312T3 (es) Derivados de ácidos arilalcanoicos sustituidos como agonistas de PAN-PPAR con potente actividad antihiperglucémica y antihiperlipidémica
US4576940A (en) Anti-allergic 3-indolecarboxamides
JP2948076B2 (ja) 新規チアゾリジンジオン化合物
EP0718290A1 (fr) Dérivés carboxyalcoyle hétérocycliques
WO2000018745A1 (fr) Derives d'oxazolidine utiles pour le traitement et la prevention de troubles metaboliques des os
AU621479B2 (en) New benzothiazolinone derivatives, process for manufacturing them, and pharmaceutical compositions which contain them
US5468761A (en) 4-methyl-5-substituted-1,3-oxazoles having anti-inflammatory activity
HU191265B (en) Process for preparing 5-/2-alkoxy-phenyl/-thiazolidine-diones
JP2005320250A (ja) ビスラクトン誘導体及びその医薬組成物としての使用

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref country code: AU

Ref document number: 1999 63309

Kind code of ref document: A

Format of ref document f/p: F

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW 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 BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

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

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase