WO1995003293A1 - Derives de l'isoflavone - Google Patents

Derives de l'isoflavone Download PDF

Info

Publication number
WO1995003293A1
WO1995003293A1 PCT/HU1994/000028 HU9400028W WO9503293A1 WO 1995003293 A1 WO1995003293 A1 WO 1995003293A1 HU 9400028 W HU9400028 W HU 9400028W WO 9503293 A1 WO9503293 A1 WO 9503293A1
Authority
WO
WIPO (PCT)
Prior art keywords
general formula
alkyl
group
compounds
isoflavone
Prior art date
Application number
PCT/HU1994/000028
Other languages
English (en)
Inventor
Mihály NÓGRÁDI
Ágnes GOTTSEGEN
Sándor ANTUS
János STRELISKY
Borbála VERMES
András WOLFNER
Ádám MAJOR
Tamás Szüts
Istvánné BENDEFFY
Tamásné Mármarosi
Original Assignee
Chinoin Ltd.
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 Chinoin Ltd. filed Critical Chinoin Ltd.
Priority to EP94921776A priority Critical patent/EP0710234A1/fr
Priority to AU72367/94A priority patent/AU7236794A/en
Publication of WO1995003293A1 publication Critical patent/WO1995003293A1/fr
Priority to KR1019960700364A priority patent/KR960703888A/ko

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/38—2,3-Dihydro derivatives, e.g. isoflavanones

Definitions

  • the present invention relates to isoflavone, isoflavan-4-one and isoflavane derivatives of the general formula (I),
  • R 1 represents C ⁇ galkyl substituted by alkylcarbonyl, carboxy, sulfonic acid, hydroxy, phenoxy, piperidino, morpholino or piridino or by a
  • R 1 represents C 1 -. 18 alkyl optionally substituted by alkyl-carbonyl, alkoxycarbonyl, carboxy, sulfonic acid, hydroxy, phenoxy, piperidino, morpholino or piridino or by a (C 1 _. 4 al yl) 2 N-(CH 2 ) m CO(CH 2 )p- group; or stands for C 3 .
  • R 1 represents C ⁇ galkyl optionally substituted by alkyl-carbonyl, alkoxycarbonyl, carboxy, sulfonic acid, hydroxy, alkoxy, phenyl optionally substituted by a halo atom, phenoxy, piperidino, morpholino or piridino or by a (C 1 - 4 alkyl) 2 N-(CH 2 ) m CO(CH 2 )p- group; or stands for C 3 .
  • R stands for C-*_ 8 alkyl, halogen, C ⁇ alkoxymethyl, C 2 . 5 -acyloxymethyl, or hydroxymethyl;
  • R 4 stands for hydrogen or C ⁇ alkyl;
  • R 2 and R 3 stand for hydrogen or C galkoxy
  • R 5 and R 6 together stand for an oxo group or separately stand for hydrogen; the dotted line means a double bond being optionally present; n is 0 or 1; m is an integer from 1 to 4; and p is an integer from 1 to 4.
  • the compounds of the general formula (I) can be used for the prevention and treatment of osteoporosis.
  • the compounds of the general formula (IA) can be prepared by reacting ketones of the general formula
  • R, n, R 1 , R 2 and R 3 are as defined for the general formula (I), a) with alkyl orthoformate in the presence of a basic catalyst, or b) with hydrogen cyanide and/or cyanic salts in the presence of hydrohalides; or c) with alkyl formiate in the presence of an alkali metal; or d) with alkyloxalylhalide, and the isoflavone ester thus obtained is, if desired, saponified and/or decarboxylated; or e) with organic carboxylic anhydride; or f) with N,N-dialkyl acid amide in the presence of phosphorous chloride; or g) by dehydrating 2-hydroxy-isoflavanone derivatives of the general formula (I), a) with alkyl orthoformate in the presence of a basic catalyst, or b) with hydrogen cyanide and/or cyanic salts in the presence of hydrohalides; or c) with alkyl formiate in the presence
  • a suitably substituted ketone is reacted with alkyl orthoformiate, preferably ethyl ester, in an aprotic solvent having a high boiling point.
  • a solvent pyrrolidine, dimethyl formamide or diethylene glycol dimethyl ether is used.
  • a basic catalyst preferably " piperidine, morpholine, pyrrolidine and other secondary amines may be used.
  • the ketones are reacted with hydrogen cyanide in an aprotic solvent in the presence of dry gaseous hydrochloric acid or other hydrohalogenic acids or Lewis acids.
  • Non-basic aprotic solvents may also be used in the reaction, preferably diethyl ether or other dialkyl ethers.
  • catalyst zinc chloride or other Lewis acids may be used.
  • the reaction is carried out with hydrogen cyanide or an appropriate salt thereof, preferably with zinc cyanide.
  • the mixture may be saturated with dry gaseous hydrochloric acid and the substituted ⁇ -fo ⁇ nimino-2-hydroxyphenylben2yl-ketone chlorohydrates thus obtained are decomposed with aqueous treatment.
  • the ketones of the formula (IH) are reacted with alkyl formiates in the presence of an alkali metal.
  • a 2-alkoxycarbonyl-isoflavone derivative is obtained, which is, if desired, converted into an isoflavone derivative unsubstituted in position 2 by hydrolyzing the ester group and by subsequent decarboxylation.
  • This process variant can preferably be carried out with methyl- or ethyl oxalyl chloride in the presence of a basic acid binding agent in an appropriate aprotic solvent, preferably pyridine or another tertiary amine.
  • the suitably substituted 2-hydroxy-phenyl benzyl ketone is reacted with organic acid anhydrides in the presence of a basic catalyst.
  • a basic catalyst suitably an alkali salt of the acid component of the acid anhydride, or in the presence of tertiary amines, without solvent or in an aprotic solvent having high boiling point, such as pyridine or dimethyl formamide.
  • the ketone is reacted with N,N-dialkyl acid amides in the presence of phosphorus oxychloride, preferably by heating the suitably substituted 2-hydroxy-phenyl benzyl ketone with N,N-dialkyl acid amid (e.g. dimethyl formamide or dimethyl acetamide) and phosphorous oxychloride, using as solvent the N,N-dialkyl acid amide itself.
  • N,N-dialkyl acid amid e.g. dimethyl formamide or dimethyl acetamide
  • phosphorous oxychloride e.g. dimethyl formamide or dimethyl acetamide
  • 2-hydroxy-isoflavones of the formula (IV) are dehydrated by heating or by warming in an acidic medium in polar solvent.
  • such derivatives may be obtained from the compounds of the formula (HI) or (TV) in which R 1 stands for hydrogen or it is not the R 1 group which is required in the target product.
  • the R 1 group is introduced into the place of the hydrogen atom or, respectively, an R 1 group is converted into another R 1 group.
  • This step can be carried out by the partial or total alkylation of the mono- or polyhydroxy-isoflavones, which alkylation can preferably be carried out by reacting with alkyl halides or substituted alkyl halides, alkyl sulfonic lactones, alkyl sulfates, olefines or epoxydes, preferably by heating the alkylating agent in a suitable solvent, e.g. ketones, dimethyl formamide or ethers containing a higher number of carbon atoms with the isoflavones to be alkylated.
  • a suitable solvent e.g. ketones, dimethyl formamide or ethers containing a higher number of carbon atoms with the isoflavones to be alkylated.
  • an acid binding agent such as alkali carbonate
  • alkyl bromides and alkyl chlorides
  • This step can be carried out by the partial or total desacylation or the partial and total desalkylation of acyloxy and polyacyloxy, alkyloxy and polyalkyloxy isoflavones.
  • Acyloxy or polyacyloxy isoflavones are formed when process variant e) is carried out with di- or polyhydroxy phenyl benzyl ketones containing a hydroxy group in position 2.
  • the desacylation is preferably carried out in an acidic or basic medium in the presence of a polar solvent.
  • This step can also be carried out by decarboxylating isoflavone-2-carboxylic acids. Isoflavone-2- carboxylic acids are formed during process variant d) and their decarboxylation is preferably carried out by heating with or without the presence of a catalyst, such as copper dust.
  • the compounds of the general formula (IB), wherein R, n, R 1 , R 2 , R 3 and R 4 are as defined for general formula (I) are prepared by the reduction of the compounds of the general formula (IA), wherein R, n, R 1 , R 2 , R 3 and R 4 are as defined for general formula (I).
  • the reduction is carried out by catalytic hydrogenation or by using metal hydrides.
  • a nobel metal catalyst preferably a palladium on charcoal catalyst is used and the reduction is carried out in an organic solvent, preferably in acetone.
  • a complex metal hydride preferably diisobutyl aluminum hydride is used and the reduction is carried out at a low temperature (-70 °C).
  • the compounds of the general formula (IC), wherein R, n, R 1 , R 2 , R 3 and R 4 are as defined for general formula (I) are prepared aby the catalytic hydrogenation of the compounds of the general formula (IB), wherein R, n, R 1 , R 2 , R 3 and R 4 are as defined for general formula (I), in the presence of a noble metal or nickel catalyst.
  • the reduction is preferably carried out in a polar solvent, preferably acetic acid or ethyl acetate.
  • R 1 stands for alkyl substituted by carboxy
  • the hydrolysis is preferably carried out in an acidic medium, preferably with lower organic acids in the presence of a strong acid catalyst.
  • the compounds of the general formula (IA) containing a methyl group in position 6 are prepared by the reduction of halomethyl isoflavones obtained from the compounds of the general formula (IA) containing a hydrogen atom in position by halomethylation.
  • the reduction is carried out preferably in the presence of metals, preferably zinc.
  • the compounds of the general formula (I) containing an alkoxy or hydroxymethyl group in position 6 are prepared either by replacing the halo atom of the halomethyl isoflavones prepared as described above with an alkoxy group by the aid of alcohols or by replacing said halo atom with an 0-acetyl group by the aid of sodium acetate and by subsequently converting the acetoxy group into an OH group.
  • Ipriflavone (7-Isopropoxy-isoflavone) is able to inhibit bone resorption either in vitro or in vivo (Notoya, K. et al. Inhibitory effect of Ipriflavone on pit formation in mouse unfractionated bone cells, Calcif. Tissue Int. 51, (Supl. 1) 53-56 (1992); Notoya, K. et al. Inhibitory effect of Ipriflavone on osteoclast-mediated bone resorption and new osteoclast formation in long-term cultures of mouse unfractionated bone cells, Calcif Tissue Int. 50, 314-319 (1992).
  • Ipriflavone also could increase the mineralization of the extracellular matrix of human bone cell cultures (Ref. Ecsedi, G.G. Model for in vitro investigation of bone mineralization, Agents and Actions 41, 84-85 (1994.)
  • the compounds of the general formula (I) may be utilized in the therapy in the form of preparations containing the active ingredient together with inert, non-toxic, pharmaceutically acceptable solid or liquid diluents or carriers.
  • the preparations can contain biologically active known substances such as vitamins, amino acids, choline chloride, salts of mineral acids, trace elements etc.
  • talc, gelatine, calcium carbonate, magnesium stearate, starch, water, polyalkylene glycols etc. may be used.
  • the compositions may be formulated as solid (e.g. tablets, dragees, capsules, suppositories etc.) or liquid (e.g. solution, suspension or emulsion) preparations.
  • 7-(l-ethoxycarbonyl-l-decyloxy)-isoflavone FL 279), m.p.: 97-99 °C are prepared in a similar way from 7-hydroxy-isoflavone and the corresponding alkyl halide or substituted alkyl halide.
  • 7-(3-methyl-l-butyloxy)-isoflavone FL 191), m.p.: 107-108 °C, is prepared from 7-hydroxy-3',4'-dimethoxy-isoflavone by using 3-methyl-l-butylbromid.
  • a mixture of 16 g of 6-n-hexyl-7-hydroxy-isoflavone, 14 ml of isopropylbromide and 70 ml of dimethylformamide are stirred for 4 hours at a temperature of 90 °C in the presence of 16 g of potassium carbonate.
  • reaction mixture is poured into 500 ml of water, the product is separated, then recrystallized from 80% aqueous methanol. 15 g of 6-n-hexyl-7-(l-methylethoxy)- -isoflavone are obtained, m.p. 37-39 °C.
  • 6-n-hexyl-7-ethoxy-isoflavone FL 319, m.p.: 57-59 °C, and 6-n-hexyl-7-
  • 7-ethoxy-5-methyl-isoflavan-4-one (FL 299), m.p.: 97-98 °C, is prepared in a similar way from 7-ethoxy-5-methyl-isoflavone.
  • 7-cyclohexyl-isoflavan-4-one (FL 312), m.p.: 119-120 °C, is prepared from 7-(l-cyclohex-2-enyloxy)-isoflavone (FL 286) by hydrogenation until a hydrogen ptake of 2.2 equimolar amount.
  • 7-cyclohexyl-isoflavane m.p.: 90-92 °C
  • 7-(l- -cyclohex-2-enyloxy)-isoflavone is prepared from 7-(l- -cyclohex-2-enyloxy)-isoflavone by hydrogenation until a hydrogen uptake of 4 equimolar amount.
  • Example 9 36.2 g of 2-hydroxy-4-(3-phenoxy-l-propyloxy)-phenylbenzyl-ketone, 22 g of ethyl orthofo ⁇ niate and 5 g of morpholine are boiled in 200 ml of dimethyl formamide for 8 hours. The ethanol formed during the reaction is removed through a fractionating attachment, then a great part of the solvent is evaporated in vacuo and the residue is diluted with diluted aqueous hydrochloric acid. The raw product is filtered off and recrystallized from acetone to obtain 32 g of 7-(3-phenoxy-l-propyloxy)-isoflavone (FL 230), m.p.: 123-125 °C.
  • Example 13 2.0 g of 7-(carbethoxymethoxy)-isoflavone are dissolved in 10 ml of diethylamino ethanol, 2.0 g of potassium carbonate are added to the solution and the mixture is boiled for 5 hours under stirring, then poured into a mixture of ice and 2% hydrochloric acid. The product is separated by suction and recrystallized from a mixture of methanol and acetone. 7-(N,N-chethyla ⁇ unoethoxy- -carbonylmethoxy)-isoflavone (FL 105) is obtained in an amount of 1.5 g, m.p.: 227-228 °C.
  • 8-acetoxymethyl-7-(2-propyloxy)-isoflavone (FL 521), m.p.: 107-109 °C, is prepared from 8-chloromethyl-7-(2-propyloxy)-isoflavone in a similar way.

Abstract

La présente invention se rapporte à l'isoflavone, isoflavan-4-one et à des dérivés d'isoflavane de la formule générale (I), à leurs sels, à des compositions pharmaceutiques contenant les composés de la formule générale (I), et à un procédé de préparation de ceux-ci. Dans la formule générale (I), si n vaut 0, R5 et R6 réunis représentent un groupe oxo et la ligne en pointillés à pour signification une liaison double, R1 représente alkyle C¿1-18? substitué par alkylcarbonyle, carboxy, l'acide sulfonique, hydroxy, phénoxy, pipéridino, morpholino ou piridino ou par un groupe (alkylC1-4)2N-(CH2)mCO(CH2)p- ou un groupe (alkylC1-4)2N-(CH2)mOCO(CH2)p-; ou représente cycloalcényle ou cycloalkyle C3-6; ou si n vaut 1, R?5 et R6¿ réunis représentent un groupe oxo et la ligne en pointillés représente une liaison double, R1 représente alkyle C¿1-18? éventuellement substitué par alkyl-carbonyle, alcoxycarbonyle, carboxy, l'acide sulfonique, hydroxy, phénoxy, pipéridino, morpholino ou piridino ou par un groupe (alkylC1-4)2N-(CH2)mCO(CH2)p-; ou représente cycloalcényle ou cycloalkyle C3-6 ou alcényle C2-6; ou si n vaut 0 ou 1, R?5 et R6¿ réunis représentent un groupe oxo ou représentent séparément hydrogène, et la ligne en pointillés ne représente pas une liaison chimique, R1 représente alkyle C¿1-18? éventuellement substitué par alkyl-carbonyle, alcoxycarbonyle, carboxy, l'acide sulfonique, hydroxy, alcoxy, phényle éventuellement substitué par un atome halo, phénoxy, pipéridino, morpholino ou piridino ou par un groupe (alkylC1-4)2N-(CH2)mCO(CH2)p-; ou représente cycloalkyle C3-6 ou alcényle C2-6; ou R représente alkyle C1-8, halogène, alcoxyméthyle C1-4 acyloxyméthyle-C2-5, ou hydroxyméthyle; R?4¿ remplace hydrogène ou alkyle C¿1-4?; R?2 et R3¿ représentent hydrogène ou alcoxy C?1-6; R5 et R6¿ réunis représentent un groupe oxo ou séparément représentent hydrogène; la ligne en pointillés représente une liaison double qui est éventuellement présente; n vaut 0 ou 1; m est un nombre entier de 1 à 4; et p est un nombre entier de 1 à 4. Les composés de la formule générale (I) peuvent être utilisés dans la prévention et le traitement de l'ostéoporose. Ils sont préparés par des procédés bien connus en chimie organique.
PCT/HU1994/000028 1993-07-20 1994-07-19 Derives de l'isoflavone WO1995003293A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP94921776A EP0710234A1 (fr) 1993-07-20 1994-07-19 Derives de l'isoflavone
AU72367/94A AU7236794A (en) 1993-07-20 1994-07-19 Isoflavone derivatives
KR1019960700364A KR960703888A (ko) 1993-07-20 1996-01-19 이소플라본 유도체 (isoflavone derivatives)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU2083/93 1993-07-20
HU9302083A HUT68558A (en) 1993-07-20 1993-07-20 Method for preparing isoflavon derivatives

Publications (1)

Publication Number Publication Date
WO1995003293A1 true WO1995003293A1 (fr) 1995-02-02

Family

ID=10983803

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1994/000028 WO1995003293A1 (fr) 1993-07-20 1994-07-19 Derives de l'isoflavone

Country Status (7)

Country Link
EP (1) EP0710234A1 (fr)
KR (1) KR960703888A (fr)
CN (1) CN1129445A (fr)
AU (1) AU7236794A (fr)
CA (2) CA2167597A1 (fr)
HU (1) HUT68558A (fr)
WO (1) WO1995003293A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998029403A1 (fr) * 1997-01-03 1998-07-09 Chiesi Farmaceutici S.P.A. Derives de l'isoflavone, procedes pour les preparer et compositions pharmaceutiques les contenant__________________________________________________________________________________________________
WO1999065893A1 (fr) * 1998-06-13 1999-12-23 C & C Research Laboratories Derives de benzopyran ou de thiobenzopyran
US6087366A (en) * 1996-03-07 2000-07-11 The Trustees Of Columbia University In The City Of New York Use of flavopiridol or a pharmaceutically acceptable salt thereof for inhibiting cell damage or cell death
EP1153020A1 (fr) * 1999-02-15 2001-11-14 Novogen Research Pty. Ltd. Preparation de derives d'isoflavone
WO2002017909A1 (fr) * 2000-08-14 2002-03-07 Korea Institute Of Oriental Medicine Agent therapeutique contre l'osteoporose comprenant comme principe actif des derives de quercetine
WO2004014886A1 (fr) * 2002-08-07 2004-02-19 University Of Mississippi Agents anti-giardiase et leur utilisation
WO2005121116A1 (fr) * 2004-06-08 2005-12-22 Novartis Ag Derives de chromone utiles en tant qu'antagonistes de vanilloide
US7033621B1 (en) 1997-04-28 2006-04-25 Novogen, Inc. Isoflavone compositions produced from legumes
US7312344B2 (en) 2001-03-08 2007-12-25 Novogen Research Pty Limited Dimeric isoflavones
US7488494B2 (en) 1999-09-06 2009-02-10 Novogen Research Pty Ltd. Compositions and therapeutic methods involving isoflavones and analogues thereof
JP2009536610A (ja) * 2006-02-28 2009-10-15 カウンシル オブ サイエンティフィク アンド インダストリアル リサーチ 骨疾患の予防／治療のための医薬組成物及びその調製方法
US7618998B2 (en) 2008-02-26 2009-11-17 Kaosiung Medical University Isoflavone derivatives and pharmaceutical compositions comprising the same
US7960399B2 (en) 2004-06-08 2011-06-14 Novartis Ag Quinazolinone derivatives useful as vanilloid antagonists

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102964322A (zh) * 2012-12-12 2013-03-13 中国药科大学 异黄酮或类黄酮脂肪醚类衍生物、其制备方法和医药用途
CN108264506B (zh) * 2018-01-17 2021-01-26 中国药科大学 异黄酮衍生物、其制备方法和医药用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0136569A2 (fr) * 1983-09-05 1985-04-10 Takeda Chemical Industries, Ltd. Dérivés d'isoflavone, leur préparation et leur utilisation
WO1991015483A1 (fr) * 1990-04-06 1991-10-17 Chinoin Gyógyszer És Vegyészeti Termékek Gyára Rt Procede ameliore de preparation de derives substitues d'isoflavone

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0136569A2 (fr) * 1983-09-05 1985-04-10 Takeda Chemical Industries, Ltd. Dérivés d'isoflavone, leur préparation et leur utilisation
WO1991015483A1 (fr) * 1990-04-06 1991-10-17 Chinoin Gyógyszer És Vegyészeti Termékek Gyára Rt Procede ameliore de preparation de derives substitues d'isoflavone

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 104, No. 17, issued 28 April 1986, (Columbus, Ohio, USA), MATSUDA, Y. et al.: "Isoflavone derivatives", page 548, column 2, abstract no. 147 153b; & JP,A,60 199 396, 08-10-95. *
CHEMICAL ABSTRACTS, Vol. 108. No. 1, issued 04 January 1988, (Columbus, Ohio, USA), WATANABE, S. et al.: "Use of isoflavone derivatives as immunosuppressants", page 53, column 2, abstract no. 622c; & JP,A,62 106 016, 16-05-87. *
CHEMICAL ABSTRACTS, Vol. 87, No. 3, issued 18 July 1977, (Columbus, Ohio, USA), NORO, T. et al.: "Synthesis of isoflavone derivatives. II. Synthesis of 6-hydroxy-2'-methoxy-5'-nitroisoflavone", page 623, column 2, abstract no. 22 970q; & YAKUGAKU ZASSHI 1977, 97 (2), 215-17. *

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6087366A (en) * 1996-03-07 2000-07-11 The Trustees Of Columbia University In The City Of New York Use of flavopiridol or a pharmaceutically acceptable salt thereof for inhibiting cell damage or cell death
WO1998029403A1 (fr) * 1997-01-03 1998-07-09 Chiesi Farmaceutici S.P.A. Derives de l'isoflavone, procedes pour les preparer et compositions pharmaceutiques les contenant__________________________________________________________________________________________________
US7033621B1 (en) 1997-04-28 2006-04-25 Novogen, Inc. Isoflavone compositions produced from legumes
US6645951B1 (en) 1998-06-13 2003-11-11 Chugai Seiyaku Kabushiki Kaisha Benzopyran or thiobenzopyran derivatives
WO1999065893A1 (fr) * 1998-06-13 1999-12-23 C & C Research Laboratories Derives de benzopyran ou de thiobenzopyran
US7074819B2 (en) 1998-06-13 2006-07-11 Chugai Seiyaku Kabushiki Kaisha Benzopyran or thiobenzopyran derivatives
EP1153020A4 (fr) * 1999-02-15 2002-08-21 Novogen Res Pty Ltd Preparation de derives d'isoflavone
EP1153020A1 (fr) * 1999-02-15 2001-11-14 Novogen Research Pty. Ltd. Preparation de derives d'isoflavone
JP2002537295A (ja) * 1999-02-15 2002-11-05 ノボゲン リサーチ ピーティーワイ リミテッド イソフラボン誘導体の製造方法
US7488494B2 (en) 1999-09-06 2009-02-10 Novogen Research Pty Ltd. Compositions and therapeutic methods involving isoflavones and analogues thereof
WO2002017909A1 (fr) * 2000-08-14 2002-03-07 Korea Institute Of Oriental Medicine Agent therapeutique contre l'osteoporose comprenant comme principe actif des derives de quercetine
US7312344B2 (en) 2001-03-08 2007-12-25 Novogen Research Pty Limited Dimeric isoflavones
US7468445B2 (en) 2002-08-07 2008-12-23 University Of Mississippi Antigiardial agents and use thereof
WO2004014886A1 (fr) * 2002-08-07 2004-02-19 University Of Mississippi Agents anti-giardiase et leur utilisation
KR100903713B1 (ko) * 2004-06-08 2009-06-19 노파르티스 아게 바닐로이드 길항제로서 유용한 크로몬 유도체
JP2008501762A (ja) * 2004-06-08 2008-01-24 ノバルティス アクチエンゲゼルシャフト バニロイドアンタゴニストとして有用なクロモン誘導体
WO2005121116A1 (fr) * 2004-06-08 2005-12-22 Novartis Ag Derives de chromone utiles en tant qu'antagonistes de vanilloide
US7960399B2 (en) 2004-06-08 2011-06-14 Novartis Ag Quinazolinone derivatives useful as vanilloid antagonists
US8211902B2 (en) 2004-06-08 2012-07-03 Novartis Ag Quinazolinone derivatives useful as vanilloid antagonists
US8809528B2 (en) 2004-06-08 2014-08-19 Novartis Ag Quinazolinone derivatives useful as vanilloid antagonists
US9102653B2 (en) 2004-06-08 2015-08-11 Novartis Ag Substituted quinazolinones as vanilloid antagonists
JP2009536610A (ja) * 2006-02-28 2009-10-15 カウンシル オブ サイエンティフィク アンド インダストリアル リサーチ 骨疾患の予防／治療のための医薬組成物及びその調製方法
US7618998B2 (en) 2008-02-26 2009-11-17 Kaosiung Medical University Isoflavone derivatives and pharmaceutical compositions comprising the same

Also Published As

Publication number Publication date
AU7236794A (en) 1995-02-20
HUT68558A (en) 1995-06-28
CA2167597A1 (fr) 1995-02-02
CA2167714A1 (fr) 1995-02-02
EP0710234A1 (fr) 1996-05-08
KR960703888A (ko) 1996-08-31
CN1129445A (zh) 1996-08-21
HU9302083D0 (en) 1993-10-28

Similar Documents

Publication Publication Date Title
WO1995003293A1 (fr) Derives de l'isoflavone
CA1286299C (fr) Derives de 3,4-dihydrobenzopyran et leurs usages en medecine
RU1836344C (ru) Способ получени птеридин-4(3Н)-онов или их фармацевтически приемлемых солей с щелочными металлами
US4621089A (en) Pyrazolopyridine derivatives and their use in treating inflammation and allergic conditions
AU2005251920A1 (en) Chromone derivatives useful as vanilloid antagonists
Agui et al. Studies on quinoline derivatives and related compounds. 1. A new synthesis of 1‐alkyl‐1, 4‐dihydro‐4‐oxo‐3‐quinolinecarboxylic acids
US4705782A (en) Indene and naphthalene derivatives
SU634673A3 (ru) Способ получени имидазо (4,5- )пиридинов или их солей
NO137899B (no) Analogifremgangsm}te for fremstilling av terapeutisk aktive n (1h-tetrazol-5-yl)-kinaldamider
EP0055068B1 (fr) Dérivés de la quinoléinone et leur application comme médicaments
EP0350990A1 (fr) Dérivés de pyridazinone
CN104804003A (zh) 5-芳基-1H-吡唑并[4,3-d]嘧啶-7(6H)-酮的合成工艺
CA2391654A1 (fr) Aryloxy-propanolamines destinees a ameliorer la production de betail
SU1579459A3 (ru) Способ получени производных 1-метиламинохино-линкарбоновой кислоты или их солей присоединени фармацевтически приемлемых кислот
FI71733B (fi) Foerfarande foer framstaellning av farmaceutiskt aktiva 3,6-substituerade 2-vinyl-kromoner
CS240967B2 (en) Preparation method of carbazic acid derivatives
US3449403A (en) Novel acrylates
CA1110249A (fr) Indolopyrones ayant des proprietes antiallergiques
Mosti et al. Synthesis and cardiotonic activity of esters of 2-substituted 5-acetyl-1, 6-dihydro-6-oxo-3-pyridinecarboxylic acids
PL124296B1 (en) Process for preparing novel derivatives of aurone
WO2018125548A1 (fr) Procédés de préparation de 6-aminoisoquinoline
Shinde et al. Sulfamic acid catalysed one-pot three-component condensation for the synthesis of 1, 4-dihydropyrano [2, 3-c] pyrazoles
CA1138868A (fr) Derives de la quinoxaline-di-n-oxyde
Göker et al. Synthesis and antiaggregator activity of some new derivatives of 4H-1-benzopyran-4-one
DK157025B (da) Analogifremgangsmaade til fremstilling af 4h-furo(3,2-b)indoler eller farmaceutisk acceptable salte deraf

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 94193107.2

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR BY CA CH CN CZ DE DK ES FI GB HU JP KP KR KZ LK LT LU LV MG MN MW NL NO NZ PL PT RO RU SD SE SI SK UA US UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN 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
WWE Wipo information: entry into national phase

Ref document number: 2167714

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1994921776

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 1996 586778

Country of ref document: US

Date of ref document: 19960305

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 1994921776

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1994921776

Country of ref document: EP