WO2000018745A1 - Derives d'oxazolidine utiles pour le traitement et la prevention de troubles metaboliques des os - Google Patents

Derives d'oxazolidine utiles pour le traitement et la prevention de troubles metaboliques des os Download PDF

Info

Publication number
WO2000018745A1
WO2000018745A1 PCT/EP1999/007253 EP9907253W WO0018745A1 WO 2000018745 A1 WO2000018745 A1 WO 2000018745A1 EP 9907253 W EP9907253 W EP 9907253W WO 0018745 A1 WO0018745 A1 WO 0018745A1
Authority
WO
WIPO (PCT)
Prior art keywords
signifies
oxazolidin
thioxo
oxazolidine
dione
Prior art date
Application number
PCT/EP1999/007253
Other languages
English (en)
Inventor
Angelika Esswein
Wolfgang Schaefer
Christos Tsaklakidis
Konrad Honold
Klaus Kaluza
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 AU63311/99A priority Critical patent/AU6331199A/en
Publication of WO2000018745A1 publication Critical patent/WO2000018745A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic 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
    • C07D263/34—Heterocyclic 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 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
    • C07D263/44—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic 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
    • C07D263/34—Heterocyclic 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 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
    • C07D263/46—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention is concerned with oxazolidine 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.
  • antidiabetics Compounds having the oxazolidine structural element are known as antidiabetics, cytostatics inflammation inhibitors and for the treatment of cardiovascular illnesses and bacterial infections, with the treatment of osteoporosis in addition to an antidiabetic activity also being described in Applications EP 708098 and EP-A-676398.
  • 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.
  • oxazolidine 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.
  • A signifies a single or double bond
  • R signifies hydroxyl, lower alkoxyl or the NR ⁇ R 2 residue, whereby Ri and R 2 can be the same or different
  • R 5 signifies hydrogen or methyl
  • X signifies oxygen or sulphur
  • W signifies an optionally mono- or polysubstituted saturated or unsaturated mono-, 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 Ci-Cio-alkyl group in accordance with the above definition with an oxygen atom, e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy and pentoxy groups.
  • phenyl phenyl ether diphenylmethane and bipheny
  • substituents there come into consideration primarily lower alkyl, alkoxy, amino, dialkylamino, dioxymethylene, benzonitrile, benzyl, benzyloxy, carboxyl, hydroxy, mercaptoalkyl, styryl, phenoxy, and halogen.
  • this is preferably a residue such as the naphthyl, tetrahydronaphthyl, decalinyl, quinolinyl, chromane, chromene, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolyl, benzimidazolyl, indazolyl, oxindolyl, benzofiiranyl, benzothiophenyl, benzothiazolyl, benzoxazolyl or purinyl residue, especially the indolyl, naphthyl, benzimidazolyl, quinolinyl, tetrahydroquinolinyl benzothiophenyl and benzofiiranyl residue, which optionally can be mono- or polysubstituted.
  • this is preferably a residue such as the anthracene, dibenzooxepine, phenanthrene, fluorene, dibenzofuran or carbazole residue.
  • A signifies a single or double bond
  • R 4 signifies hydroxyl, lower alkoxyl or the NR.R 2 residue, whereby Rj and R 2 can be the same or different
  • R 5 signifies hydrogen or methyl X signifies oxygen or sulphur
  • W signifies an optionally mono- or polysubstituted saturated or unsaturated mono-, bi- or tricycle which can contain one or more hetero atoms
  • W is not phenol or 2-hydroxypyridine or its bicyclic derivatives, if m equals 0 and g unequal 0,
  • W is not phenol and benzofuran, if A is a single bond, X is oxygen and g is 1 or 2,
  • W is not phenyl, benzofuran, benzoxazol, if m and g together equal 0,
  • m signifies a number between 0 and 2
  • q signifies the number 0 or 1
  • A signifies a double bond
  • Ri signifies hydrogen
  • R 2 /R 3 signify hydrogen or methyl
  • R 5 signifies hydrogen or methyl
  • X signifies sulphur
  • W signifies an optionally mono- or polysubstituted phenyl, phenanthrene, benzofuran, benzothiophene, biphenyl, cyclohexenyl or naphthalene residue.
  • ⁇ -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, glycerol, 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 appUcation 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, conveniendy 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 Demineralized Bone Matrix
  • 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,

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (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 compris entre 0 et 8; A est une liaison simple ou double; R1 est hydrogène ou CH2)a-COR4, a étant compris entre 0 et 6, de préférence entre 1 et 3; R2, R3 sont hydrogène ou alkyle inférieur, R2 et R3 pouvant être identiques ou différents, et, si m est compris entre 2 et 8, R2 et R3 dans le groupe CR2=CR3 peuvent avoir diverses notations dans la séquence suivante; R4 est hydroxyle, alcoxy inférieur ou le résidu NR1R2, R1 et R2 pouvant être identiques ou différents; R5 est hydrogène ou méthyle; X est oxygène ou 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 leurs 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/EP1999/007253 1998-09-30 1999-09-30 Derives d'oxazolidine utiles pour le traitement et la prevention de troubles metaboliques des os WO2000018745A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63311/99A AU6331199A (en) 1998-09-30 1999-09-30 Oxazolidine derivatives for the treatment and prevention of metabolic bone disorders

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP98118522.6 1998-09-30
EP98118522 1998-09-30

Publications (1)

Publication Number Publication Date
WO2000018745A1 true WO2000018745A1 (fr) 2000-04-06

Family

ID=8232724

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/007253 WO2000018745A1 (fr) 1998-09-30 1999-09-30 Derives d'oxazolidine utiles pour le traitement et la prevention de troubles metaboliques des os

Country Status (2)

Country Link
AU (1) AU6331199A (fr)
WO (1) WO2000018745A1 (fr)

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2169334A1 (en) * 1972-01-26 1973-09-07 Boehringer Sohn Ingelheim Biaxially stretched injection mouldings - esp hollow articles such as bottles
GB2083810A (en) * 1980-07-28 1982-03-31 Pfizer Hypoglycemic 5-substituted oxazolidine-2,4-diones
EP0097453A2 (fr) * 1982-06-23 1984-01-04 Pfizer Inc. Oxazolidines-2, 4-dione contenant un substituant alicyclique à activité hypoglycémique
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
EP0428312A2 (fr) * 1989-11-13 1991-05-22 Pfizer Inc. Oxazolidinedione comme agents hypoglycémiques
WO1992002520A1 (fr) * 1990-08-06 1992-02-20 Beecham Group P.L.C. Derives d'oxazolidine dione
EP0612743A1 (fr) * 1993-02-26 1994-08-31 Takeda Chemical Industries, Ltd. Dérivés de l'oxazolidinedione, leurs production et leurs utilisation pour réduire les niveaux de sucres et lipides dans le sang
EP0643050A1 (fr) * 1993-09-14 1995-03-15 Takeda Chemical Industries, Ltd. Dérivés d'oxazolidinedione et leur utilisation comme agents hypoglycémiques
US5468762A (en) * 1994-05-18 1995-11-21 American Home Products Corporation Azolidinediones as antihyperglycemic agents
US5498621A (en) * 1992-05-01 1996-03-12 Pfizer Inc. Oxazolidinedione hypoglycemic agents
WO1997000249A1 (fr) * 1995-06-16 1997-01-03 Takeda Chemical Industries, Ltd. Composes heterocycliques et production et utilisation de ces derniers
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 (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2169334A1 (en) * 1972-01-26 1973-09-07 Boehringer Sohn Ingelheim Biaxially stretched injection mouldings - esp hollow articles such as bottles
GB2083810A (en) * 1980-07-28 1982-03-31 Pfizer Hypoglycemic 5-substituted oxazolidine-2,4-diones
EP0097453A2 (fr) * 1982-06-23 1984-01-04 Pfizer Inc. Oxazolidines-2, 4-dione contenant un substituant alicyclique à activité hypoglycémique
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
EP0428312A2 (fr) * 1989-11-13 1991-05-22 Pfizer Inc. Oxazolidinedione comme agents hypoglycémiques
WO1992002520A1 (fr) * 1990-08-06 1992-02-20 Beecham Group P.L.C. Derives d'oxazolidine dione
US5498621A (en) * 1992-05-01 1996-03-12 Pfizer Inc. Oxazolidinedione hypoglycemic agents
EP0612743A1 (fr) * 1993-02-26 1994-08-31 Takeda Chemical Industries, Ltd. Dérivés de l'oxazolidinedione, leurs production et leurs utilisation pour réduire les niveaux de sucres et lipides dans le sang
EP0643050A1 (fr) * 1993-09-14 1995-03-15 Takeda Chemical Industries, Ltd. Dérivés d'oxazolidinedione et leur utilisation comme agents hypoglycémiques
US5468762A (en) * 1994-05-18 1995-11-21 American Home Products Corporation Azolidinediones as antihyperglycemic agents
WO1997000249A1 (fr) * 1995-06-16 1997-01-03 Takeda Chemical Industries, Ltd. Composes heterocycliques et production et utilisation de ces derniers
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 (13)

* Cited by examiner, † Cited by third party
Title
AKITO NAGATSU ET AL: "Novel antioxidants from roasted perilla sees", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 43, no. 5, 1995, TOKYO JP, pages 887 - 889, XP002093527 *
BARRIE C.C. CANTELLO ET AL: "[[Omega-(heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents", JOURNAL OF MEDICINAL CHEMISTRY., vol. 37, no. 23, 1994, AMERICAN CHEMICAL SOCIETY. WASHINGTON., US, pages 3977 - 3985, XP002127022, ISSN: 0022-2623 *
CHEMICAL ABSTRACTS, vol. 111, no. 17, 23 October 1989, Columbus, Ohio, US; abstract no. 153681h, N.A.SHENBERG ET AL: "5-arylidene-2-thio-4-oxazolidinones in hydroxy and aminomethylation reactions" page 710; XP002093532 *
CHEMICAL ABSTRACTS, vol. 48, no. 19, 10 October 1954, Columbus, Ohio, US; abstract no. 11391b, N.K.USHENKO ET AL: "Substitution in the azolidine ring. V. Preparation of 2-thiono-4-oxazolidinone and its transformations" XP002093531 *
CHEMICAL ABSTRACTS, vol. 89, no. 13, 25 September 1978, Columbus, Ohio, US; abstract no. 109198j, N.A.SHENBERG ET AL: "Study of the reactivity and tautomerism of azolidines.XXIII. Alkylation of salts of 5-benzylidene-2-thiooxazolidin-4-ones" page 894; XP002093533 *
FRIEDRICH WEYGAND ET AL: "Über die Umsetzung von alpha-chlor-alpha-äthylmercapto-ketonen mit Kaliumrhodanid.Ein neuer Weg zu Oxazolthionen", CHEMISCHE BERICHTE., vol. 91, 1958, WEINHEIM DE, pages 2537 - 2542, XP002093528 *
KHIM.GERETEROTSIKL.SOEDIN, no. 1, 1989, pages 106 - 108 *
PAUL C. UNANGST ET AL: "Synthesis and biological evaluation of 5-[[3,5-Bis(1,1dimethylethyl)-4-hydroxyphenyl]methylene]oxazoles,-thiazoles,and -imidazoles: Novel dual 5-lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity", JOURNAL OF MEDICINAL CHEMISTRY., vol. 37, no. 2, 1994, AMERICAN CHEMICAL SOCIETY. WASHINGTON., US, pages 322 - 328, XP002127023, ISSN: 0022-2623 *
ROBERT L.DOW ET AL: "Benzyloxazolidine-2,4-diones as potent hypoglycemic agents", JOURNAL OF MEDICINAL CHEMISTRY., vol. 34, no. 5, 1991, WASHINGTON US, pages 1538 - 1544, XP002093529 *
TAKASHI SOHDA ET AL: "Studies on antidiabetic agents.I. Synthesis of 5-[4-(2-methyl-2-phenylpropoxy)-benzyl]thiazolidine-2,4-dione (AL-321) and related compou nds.", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 30, no. 10, 1982, TOKYO JP, pages 3563 - 3573, XP002093530 *
THOMAS R. HERRIN ET AL: "Antimalarial.Synthesis and antimalarial activity of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine and derivatives", JOURNAL OF MEDICINAL CHEMISTRY., vol. 18, no. 12, 1975, AMERICAN CHEMICAL SOCIETY. WASHINGTON., US, pages 1216 - 1223, XP002127021, ISSN: 0022-2623 *
UKRAIN.KHIM.ZHUR., vol. 16, 1950, pages 545 - 551 *
ZH.ORG.KHIM., vol. 14, no. 6, 1978, pages 1323 - 1327 *

Also Published As

Publication number Publication date
AU6331199A (en) 2000-04-17

Similar Documents

Publication Publication Date Title
US6673816B1 (en) Rhodanine carboxylic acid derivatives for the treatment and prevention of metabolic bone disorders
US3912748A (en) Benzoxazole derivatives
TW400330B (en) Novel thiazolidine-2, 4-dione, substitute, the manufacture method and the pharmaceutical compositions therefof
WO2000018748A1 (fr) Derives de rhodanine utiles pour le traitement et la prevention de troubles metaboliques des os
JP4703563B2 (ja) 代謝障害を治療するための化合物
SK19152001A3 (sk) Substituované fenoxyoctové kyseliny
US5510376A (en) Aminocycloalkanobenzodioxoles as beta-3 selective adrenergic agents
HU217116B (hu) Tiazolidin-2,4-dion-származékok, sóik, valamint eljárás a vegyületek és az ezeket tartalmazó gyógyászati készítmények előállítására
US3962452A (en) Benzoxazole derivatives as therapeutics
DE60130031T2 (de) Dihydronaphthalinderivat verbindungen und arzneimittel, die diese verbindungen als wirkstoff enthalten
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
WO2000018746A1 (fr) Derives de thiazolidine utiles pour le traitement et la prevention de troubles metaboliques des os
US5482971A (en) Beta3 -adrenergic agents and their use in pharmaceutical compositions
ES2382312T3 (es) Derivados de ácidos arilalcanoicos sustituidos como agonistas de PAN-PPAR con potente actividad antihiperglucémica y antihiperlipidémica
WO2000018745A1 (fr) Derives d'oxazolidine utiles pour le traitement et la prevention de troubles metaboliques des os
WO2014180544A1 (fr) Dérivés d'hydantoïne comme inhibiteurs de cd38
JPS61286359A (ja) Ｎ−〔〔５−（トリフルオロメチル）−６−メトキシ−１−ナフタレニル〕チオキソメチルまたはカルボニル〕−ｎ−メチルグリシンアミド
AU2441600A (en) Polycyclic thiazole systems and their utilization as anorectics
KR870001267B1 (ko) 5-(2-알콕시페닐)티아졸 리딘디온의 제조방법
JP5496913B2 (ja) 代謝異常の治療のための化合物
USRE29608E (en) Benzoxazole derivatives
JPS63310821A (ja) ５−リポキシゲナーゼの阻害剤としてのフエノール性チオエーテル、スルホキサイドおよびジスルフアイド
JPH07309852A (ja) 新規チアゾリジンジオン化合物
US4021440A (en) Cyanomethyl substituted benzoxazoles

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref country code: AU

Ref document number: 1999 63311

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