CA2167597A1 - Pharmaceutical compositions containing as active agent isoflavone derivatives or salts thereof - Google Patents
Pharmaceutical compositions containing as active agent isoflavone derivatives or salts thereofInfo
- Publication number
- CA2167597A1 CA2167597A1 CA002167597A CA2167597A CA2167597A1 CA 2167597 A1 CA2167597 A1 CA 2167597A1 CA 002167597 A CA002167597 A CA 002167597A CA 2167597 A CA2167597 A CA 2167597A CA 2167597 A1 CA2167597 A1 CA 2167597A1
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen
- stands
- stand
- general formula
- pharmaceutical compositions
- 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.)
- Abandoned
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
Abstract
The present invention relates to pharmaceutical compositions containing as active agent isoflavone derivatives of general formula (I), wherein R1 represents a C2-C18alkyl optionally substituted by C1-6alkoxy, hydroxyl, C1-6carbalkoxy, phenyl, benzoyl or a halo atom;
phenylalkyl containing a C1-3alkyl chain optionally substituted by a halo atom or a nitro group or C2-6alkenyl; R2 and R3 stand for hydrogen or C1-6alkoxy; R4 stands for hydrogen, C1-6alkyl or carboxyl; R5 stands for hydrogen or C1-4alkyl; R6 stands for hydrogen or, if R5 stands for hydrogen, R6 may also stand for methyl or hydroxymethyl, with the proviso that if R2, R3, R4, R5 and R6 stand for hydrogen, R1 is other than isopropyl, or salt thereof. The pharmaceutical compositions according to the invention are prepared by known methods and are suitable for the treatment of osteoporosis.
phenylalkyl containing a C1-3alkyl chain optionally substituted by a halo atom or a nitro group or C2-6alkenyl; R2 and R3 stand for hydrogen or C1-6alkoxy; R4 stands for hydrogen, C1-6alkyl or carboxyl; R5 stands for hydrogen or C1-4alkyl; R6 stands for hydrogen or, if R5 stands for hydrogen, R6 may also stand for methyl or hydroxymethyl, with the proviso that if R2, R3, R4, R5 and R6 stand for hydrogen, R1 is other than isopropyl, or salt thereof. The pharmaceutical compositions according to the invention are prepared by known methods and are suitable for the treatment of osteoporosis.
Description
~1~7~7 .
PlIARlUA( ~;U llCAL COl~OSITION~ CONTA~NING AS ACTIVE
AGENT ISOFLAVONE DE~IV~TIVES OR SALTS T~EREOF
The present invention relates to ph~ceutical compositions cont~ining as active agent isoflavone derivatives of the general formula R
~ R (I), R10 ~ ~ R4 wherein Rl represents a C2 l8alkyl op~onally substihlte~l by Cl 6alkoxy, hydroxyl, Cl 6carbalkoxy, phenyl, benzoyl or a halo atom; phenylaLkyl co,~ .g a Cl 3aLkyl chain optionally substituted by a halo atom or a nitro group or C2 6aL'cenyl;
R2 and R3 stand for hydrogen or Cl 6aLkoxy;
R4 stands for hydrogen, Cl~alkyl or carboxyl;
Rs stands for hydrogen or Cl 4aLkyl;
20 R6 stands for hydrogen or, if ~5 stands for hydrogen, R6 may also stand for methyl or hydroxymethyl, with the proviso that if R2, R3, R4, R5 and R6 stand for hydrogen, Rl is other than isopropyl, or salt thereof. The composition can be ~l~ared by ~lmixing an isoflavone denvative of the general formula (I), wherein Rl, R2, R3, R4 and R5 are as defined 25 above, ~l~ed in a known m~nner, with filling, tlilnting and other ~ ry sllbst~nces generally used in the ph~rm~ceutical industry and formlll~tinp~
ph~rm~celltical compositions. The compositions are suitable for the tre~tment ofosteoporosis.
The compounds of the general formula (I) cont~ining a hydrogen atom in the place30 of R6 are ~r~ared by a) reacting ketones of the general formula t R5 0 ~ C CH2 ~ R (III), R o 0H
Wo 95/03040 216 7 ~S ~ 7 2 PCT/HU94/00027 wherein Rs, Rl, R2 and R3 are as defined above, with alkyl orthoformiate in the presence of a basic catalyst, or b~ reacting ketones of the general formula 1 ~ C --R O OH
wherein R5, Rl, R2 and R3 as defined above, with hydrogen cyanide and/or cyanic salts in the presence of a hydrohalogenic acid, or c~ reacting ketones of the general formula (III), wherein R5, Rl, R2 and R3 as defined above, with alkyl formiate in the presence of an alkali metal, or d) reacting ketones of the general formula (m~, wherein R5, Rl, R2 and R3 as ~l~fine~l above, with aLkyloxalkyl halide and, if desired, saponifying and/ordecarboxyIating the isoflavone ester thus obtained, or e) reacting ketonec ofthe general formula (m), wherein R5, Rl, R2 and R3 as define~l above, with organic carboxylic acid anhydride, or i~) re~clmg ketones of the general formula (II~, wherein R5, Rl, R2 and R3 as 1efine~1 above, with N,N-diaLIcyl acid amide in the presence of phosporous chloride, or g~ dehydrating 2-hydroxy isoflavone derivatives of the general formula ~ R3 (IV), Rlo ~ H
OH
wherein ~5, Rl, R2 and R3 as defined above, and optionally introducing into a compound of the general formula (I), wherein Rl is hydrogen, an Rl group other than hydrogen, if desired, co~v~llhlg an another Rl group into another Rl group and, if desired, conver~ng a compound of the ~çner~ formula (I) thus obtained 35 into its salt or set~ng it free from its salt.
(~lm~~ri~n Patent Specific~ion No. 162,377) wo 95/03040 3 ~ ~ 6 ~ ~ 9 7 PCT/HUg4/00027 ~t .
compounds of the general forrnuIa (I) cont~in;n~ a hydrogen atom in position 6 by halomethylation. The retl~l~.fion is preferably calried out in the presence of metals, ~r~rel~bly zinc.
S The compounds of the general forrnula (I) Cont~inin~ an alkoxy or hydroxymethyl group in position 6 are plepalcd either by replacing the halo atom of the halornethyl isoflavones ~lep~es as described above by an alkoxy group by the aidof alcohols or by replacing said halo atom by an 0-acetyl group by the aid of sodium acetate and by subsequently converting the acetoxy group into a hydroxy 10 group.
The active agents of the compositions according to the invention can be preparedin a known manner. The term "kno-vn manner" comprises all the methods which could be leamed from the lil~laLu~e until the date of priority.
According to the ~nn~ n Patent Specification No. 162,377 the compounds of the general form~ (T) and salts thereof exert a cholesterol level decreasing effect in the blood and they inflnenee the metabolism, thus, the majority of these compounds show an anabolitic, while the others show a catabolitic effect.
It is lmown that osteoporosis is a disease which manifests itself frequently with women being in the menopause.
Oestrogenic ~ alions, c~lçitcnine, vitamin D and other c~lci~lm-co..~
~fe~ions are used for the tre~tment of osteoporosis. However, none of these 25 ~r~al~lions proved to be s~lfficiPntly effective ~ nct this disease.
We'have found that the compounds of the general fi rmlll~ and salts thereof can effectively be used for the prophylaxis and tre~tment of osteoporosis.
It is known that Ipriflavone (7-Isopropoxy-isoflavone) is able to inhibit bone 30 resorption either in vitro or in vivo (Notoya, K. et al. Inhibitory effect ofIpriflavone on pit form~1ion in mouse unfractionated bone cells, Calcif.Tissue Int.
51, (Supl. 1) 53-56 (1992); Notoya, K. et al. Inhibitory effect of Ipriflavone on osteoclast-me~ te~l bone resorption and new osteoclast formation in longterm cultures of mouse unfr~ction~fetl bone cells, Calcif Tissue Int. 50, 314-319 (1992).
35 On the other hand, it is known that Ipriflavone also could increase the mineralization of the ex~cellnl~r matrix of human bone cell cultures (Ref. Ecsedi, G.G. Model for in vitro inves1;~tion of bone mineralization, Agents and Actions 41, 8~85 (1994.) -wo 95/03040 2 1~ 7 5 9 7 4 PCT/~IU94/00027 To estim~te the effectiveness of the compounds of the general ~ormula (I) on bone rO, .,1~l ion an in vitro mineralization model was developed. Under certain circl-m~t~nces cultures of par~ally selected (osteoblast-enriched) human bone cells ori~in~ted from either nasal bone of adults or foetus femur produce Type I
S coll~ene, bone specific proteins (e.g. osteocalcin), prostanoides (PGE2, PGF2a, PGI2, etc. and aCcl~m~ te c~lci-lm into the synthesized matrix (Re: Ecsedi, G.G., Characterization of cells of human nasal bone cell cultures, 4th Int. Symposium on Osteoporosis, 27 March- 2 April, 1993 Hong Kong; Abstr. no. 534~.
Method, Cells of subcultures 8-12 (usually 8th or 9th) were drop-inoculated at adensity of 2*10'`4 cells per well 96-well plates. On the day 3 the tre~tments were started with the compound of ~e Formula I at two conce~ aLions~
l()A-8 and 10^-10 M. Because ethanolic 10^-5 and 10^-7 M stock solutions of the compounds were used in the tre~tment~ all culture media cont~ined 0.1 % ethanol insluAing the Controls. Media were changed on each 2-3 day. The tre~tment~ were finished on the day 21, the total calcium (Ca) and DNA content of lhe 6-parallelsamples were measured by Bo~krin.~er Test Combination (MPR3) and the spectrofluorometric 3,5~ minobenzoic acid (DABA) method, respectively, 1hen the ratios, Ca/DNA were c~1c~
In tihe table of ~he compounds of Formula I below, data are given in percentages co~ ~ed to the average of the Con~rol value (100%) Name of Conc~;"LI alion Ca DNA Ca/DNA
Compound ~-log Ml % % %
Ipriflavone 8 121 100 121 (7-isopropoxy- 10 111 108 103 isoflavone) (7-n-nonyloxy- 10 108 103 104 -isoflavone) covered by ~e general Formula (I) (7-n-propoxy- 10 180 106 168 -isoflavone) covered by ~e ~ener~l Formula (I) ~7~7 .
In the tre~ nt ~e compounds of ~e general formula (I) can ~le~l~bly be used in the form of capsules, tablets or tablets with prolonged effect. These ph~ ceutical preparation can be made by methods krlown per se.
S The invention is elucidated in detail by the following non-limitinf~ examples. The following compositions are prepared in a known m~nner:
Example 1 Capsules 1~ A compolmd of ~e general formula (I)200 mg colloidal silicic acid 20 mg talc 20 mg magnesium ~lea,~Le 20 mg lactose 80 mg Example 2 Tablets A compound of the general fo~mula (I)200 mg m~gnecil-m sLea~le 4mg ~lc 7 mg polyvinyl-pyrrolidone 13 mg lactose 60 mg potato sta~ch 36 mg Esmaspreny (forrnaldehyde c~çine) 60 mg
PlIARlUA( ~;U llCAL COl~OSITION~ CONTA~NING AS ACTIVE
AGENT ISOFLAVONE DE~IV~TIVES OR SALTS T~EREOF
The present invention relates to ph~ceutical compositions cont~ining as active agent isoflavone derivatives of the general formula R
~ R (I), R10 ~ ~ R4 wherein Rl represents a C2 l8alkyl op~onally substihlte~l by Cl 6alkoxy, hydroxyl, Cl 6carbalkoxy, phenyl, benzoyl or a halo atom; phenylaLkyl co,~ .g a Cl 3aLkyl chain optionally substituted by a halo atom or a nitro group or C2 6aL'cenyl;
R2 and R3 stand for hydrogen or Cl 6aLkoxy;
R4 stands for hydrogen, Cl~alkyl or carboxyl;
Rs stands for hydrogen or Cl 4aLkyl;
20 R6 stands for hydrogen or, if ~5 stands for hydrogen, R6 may also stand for methyl or hydroxymethyl, with the proviso that if R2, R3, R4, R5 and R6 stand for hydrogen, Rl is other than isopropyl, or salt thereof. The composition can be ~l~ared by ~lmixing an isoflavone denvative of the general formula (I), wherein Rl, R2, R3, R4 and R5 are as defined 25 above, ~l~ed in a known m~nner, with filling, tlilnting and other ~ ry sllbst~nces generally used in the ph~rm~ceutical industry and formlll~tinp~
ph~rm~celltical compositions. The compositions are suitable for the tre~tment ofosteoporosis.
The compounds of the general formula (I) cont~ining a hydrogen atom in the place30 of R6 are ~r~ared by a) reacting ketones of the general formula t R5 0 ~ C CH2 ~ R (III), R o 0H
Wo 95/03040 216 7 ~S ~ 7 2 PCT/HU94/00027 wherein Rs, Rl, R2 and R3 are as defined above, with alkyl orthoformiate in the presence of a basic catalyst, or b~ reacting ketones of the general formula 1 ~ C --R O OH
wherein R5, Rl, R2 and R3 as defined above, with hydrogen cyanide and/or cyanic salts in the presence of a hydrohalogenic acid, or c~ reacting ketones of the general formula (III), wherein R5, Rl, R2 and R3 as defined above, with alkyl formiate in the presence of an alkali metal, or d) reacting ketones of the general formula (m~, wherein R5, Rl, R2 and R3 as ~l~fine~l above, with aLkyloxalkyl halide and, if desired, saponifying and/ordecarboxyIating the isoflavone ester thus obtained, or e) reacting ketonec ofthe general formula (m), wherein R5, Rl, R2 and R3 as define~l above, with organic carboxylic acid anhydride, or i~) re~clmg ketones of the general formula (II~, wherein R5, Rl, R2 and R3 as 1efine~1 above, with N,N-diaLIcyl acid amide in the presence of phosporous chloride, or g~ dehydrating 2-hydroxy isoflavone derivatives of the general formula ~ R3 (IV), Rlo ~ H
OH
wherein ~5, Rl, R2 and R3 as defined above, and optionally introducing into a compound of the general formula (I), wherein Rl is hydrogen, an Rl group other than hydrogen, if desired, co~v~llhlg an another Rl group into another Rl group and, if desired, conver~ng a compound of the ~çner~ formula (I) thus obtained 35 into its salt or set~ng it free from its salt.
(~lm~~ri~n Patent Specific~ion No. 162,377) wo 95/03040 3 ~ ~ 6 ~ ~ 9 7 PCT/HUg4/00027 ~t .
compounds of the general forrnuIa (I) cont~in;n~ a hydrogen atom in position 6 by halomethylation. The retl~l~.fion is preferably calried out in the presence of metals, ~r~rel~bly zinc.
S The compounds of the general forrnula (I) Cont~inin~ an alkoxy or hydroxymethyl group in position 6 are plepalcd either by replacing the halo atom of the halornethyl isoflavones ~lep~es as described above by an alkoxy group by the aidof alcohols or by replacing said halo atom by an 0-acetyl group by the aid of sodium acetate and by subsequently converting the acetoxy group into a hydroxy 10 group.
The active agents of the compositions according to the invention can be preparedin a known manner. The term "kno-vn manner" comprises all the methods which could be leamed from the lil~laLu~e until the date of priority.
According to the ~nn~ n Patent Specification No. 162,377 the compounds of the general form~ (T) and salts thereof exert a cholesterol level decreasing effect in the blood and they inflnenee the metabolism, thus, the majority of these compounds show an anabolitic, while the others show a catabolitic effect.
It is lmown that osteoporosis is a disease which manifests itself frequently with women being in the menopause.
Oestrogenic ~ alions, c~lçitcnine, vitamin D and other c~lci~lm-co..~
~fe~ions are used for the tre~tment of osteoporosis. However, none of these 25 ~r~al~lions proved to be s~lfficiPntly effective ~ nct this disease.
We'have found that the compounds of the general fi rmlll~ and salts thereof can effectively be used for the prophylaxis and tre~tment of osteoporosis.
It is known that Ipriflavone (7-Isopropoxy-isoflavone) is able to inhibit bone 30 resorption either in vitro or in vivo (Notoya, K. et al. Inhibitory effect ofIpriflavone on pit form~1ion in mouse unfractionated bone cells, Calcif.Tissue Int.
51, (Supl. 1) 53-56 (1992); Notoya, K. et al. Inhibitory effect of Ipriflavone on osteoclast-me~ te~l bone resorption and new osteoclast formation in longterm cultures of mouse unfr~ction~fetl bone cells, Calcif Tissue Int. 50, 314-319 (1992).
35 On the other hand, it is known that Ipriflavone also could increase the mineralization of the ex~cellnl~r matrix of human bone cell cultures (Ref. Ecsedi, G.G. Model for in vitro inves1;~tion of bone mineralization, Agents and Actions 41, 8~85 (1994.) -wo 95/03040 2 1~ 7 5 9 7 4 PCT/~IU94/00027 To estim~te the effectiveness of the compounds of the general ~ormula (I) on bone rO, .,1~l ion an in vitro mineralization model was developed. Under certain circl-m~t~nces cultures of par~ally selected (osteoblast-enriched) human bone cells ori~in~ted from either nasal bone of adults or foetus femur produce Type I
S coll~ene, bone specific proteins (e.g. osteocalcin), prostanoides (PGE2, PGF2a, PGI2, etc. and aCcl~m~ te c~lci-lm into the synthesized matrix (Re: Ecsedi, G.G., Characterization of cells of human nasal bone cell cultures, 4th Int. Symposium on Osteoporosis, 27 March- 2 April, 1993 Hong Kong; Abstr. no. 534~.
Method, Cells of subcultures 8-12 (usually 8th or 9th) were drop-inoculated at adensity of 2*10'`4 cells per well 96-well plates. On the day 3 the tre~tments were started with the compound of ~e Formula I at two conce~ aLions~
l()A-8 and 10^-10 M. Because ethanolic 10^-5 and 10^-7 M stock solutions of the compounds were used in the tre~tment~ all culture media cont~ined 0.1 % ethanol insluAing the Controls. Media were changed on each 2-3 day. The tre~tment~ were finished on the day 21, the total calcium (Ca) and DNA content of lhe 6-parallelsamples were measured by Bo~krin.~er Test Combination (MPR3) and the spectrofluorometric 3,5~ minobenzoic acid (DABA) method, respectively, 1hen the ratios, Ca/DNA were c~1c~
In tihe table of ~he compounds of Formula I below, data are given in percentages co~ ~ed to the average of the Con~rol value (100%) Name of Conc~;"LI alion Ca DNA Ca/DNA
Compound ~-log Ml % % %
Ipriflavone 8 121 100 121 (7-isopropoxy- 10 111 108 103 isoflavone) (7-n-nonyloxy- 10 108 103 104 -isoflavone) covered by ~e general Formula (I) (7-n-propoxy- 10 180 106 168 -isoflavone) covered by ~e ~ener~l Formula (I) ~7~7 .
In the tre~ nt ~e compounds of ~e general formula (I) can ~le~l~bly be used in the form of capsules, tablets or tablets with prolonged effect. These ph~ ceutical preparation can be made by methods krlown per se.
S The invention is elucidated in detail by the following non-limitinf~ examples. The following compositions are prepared in a known m~nner:
Example 1 Capsules 1~ A compolmd of ~e general formula (I)200 mg colloidal silicic acid 20 mg talc 20 mg magnesium ~lea,~Le 20 mg lactose 80 mg Example 2 Tablets A compound of the general fo~mula (I)200 mg m~gnecil-m sLea~le 4mg ~lc 7 mg polyvinyl-pyrrolidone 13 mg lactose 60 mg potato sta~ch 36 mg Esmaspreny (forrnaldehyde c~çine) 60 mg
Claims (3)
1. A pharmaceutical composition for the treatment of osteoporosis, which comprises as active ingredient a therapeutically active amount of a compound of the general formula (I), wherein R1 represents a C2-18alkyl optionally substituted by C1-6alkoxy, hydroxyl, C1-6carbalkoxy, phenyl, benzoyl or a halo atom; phenylalkyl containing a C1-3alkyl chain optionally substituted by a halo atom or a nitro group or C2-6alkenyl;
R2 and R3 stand for hydrogen or C1-6alkoxy;
R4 stands for hydrogen, C1-6alkyl or carboxyl;
R5 stands for hydrogen or C1-4alkyl;
R6 stands for hydrogen or, if R5 stands for hydrogen, R6 may also stand for methyl or hydroxymethyl, with the proviso that if R2, R3, R4, R5 and R6 stand for hydrogen, R1 is other than isopropyl, in admixture with suitable inert, solid or liquid carriers and optionally with usual therapeutical additives and auxiliary agent.
R2 and R3 stand for hydrogen or C1-6alkoxy;
R4 stands for hydrogen, C1-6alkyl or carboxyl;
R5 stands for hydrogen or C1-4alkyl;
R6 stands for hydrogen or, if R5 stands for hydrogen, R6 may also stand for methyl or hydroxymethyl, with the proviso that if R2, R3, R4, R5 and R6 stand for hydrogen, R1 is other than isopropyl, in admixture with suitable inert, solid or liquid carriers and optionally with usual therapeutical additives and auxiliary agent.
2. Use of compounds of the general formula (I), wherein R1, R2, R3, R4 and R5 are as defined in claim 1, for formulating pharmaceutical compositions for the treatment of osteoporosis.
3. Method of treatment of osteoporosis of an affected human or animal subject, which comprises the step of administering in an effective amount a compound of the general formula (I), wherein R1, R2, R3, R4 and R5 are as defined in claim 1, in admixture with suitable inert, solid or liquid carriers and optionally with usual therapeutical additives and auxiliary agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9302083A HUT68558A (en) | 1993-07-20 | 1993-07-20 | Method for preparing isoflavon derivatives |
| HU2082/93 | 1993-07-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2167597A1 true CA2167597A1 (en) | 1995-02-02 |
Family
ID=10983803
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002167597A Abandoned CA2167597A1 (en) | 1993-07-20 | 1994-07-18 | Pharmaceutical compositions containing as active agent isoflavone derivatives or salts thereof |
| CA002167714A Abandoned CA2167714A1 (en) | 1993-07-20 | 1994-07-19 | Isoflavone derivatives |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002167714A Abandoned CA2167714A1 (en) | 1993-07-20 | 1994-07-19 | Isoflavone derivatives |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0710234A1 (en) |
| KR (1) | KR960703888A (en) |
| CN (1) | CN1129445A (en) |
| AU (1) | AU7236794A (en) |
| CA (2) | CA2167597A1 (en) |
| HU (1) | HUT68558A (en) |
| WO (1) | WO1995003293A1 (en) |
Families Citing this family (15)
| 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 |
| IT1289154B1 (en) * | 1997-01-03 | 1998-09-29 | Chiesi Farma Spa | ISOFLAVONE DERIVATIVES THEIR PREPARATION AND THEIR THERAPEUTIC USE |
| US6146668A (en) | 1997-04-28 | 2000-11-14 | Novogen, Inc. | Preparation of isoflavones from legumes |
| KR20000001793A (en) * | 1998-06-13 | 2000-01-15 | 이경하 | Novel benzopyran or thiobenzopyran derivatives |
| AUPP868599A0 (en) * | 1999-02-15 | 1999-03-11 | Novogen Research Pty Ltd | Production of isoflavone derivatives |
| AUPQ266199A0 (en) | 1999-09-06 | 1999-09-30 | Novogen Research Pty Ltd | Compositions and therapeutic methods involving isoflavones and analogues thereof |
| KR100408231B1 (en) * | 2000-08-14 | 2003-12-01 | 한국 한의학 연구원 | Flavonoid derivateives for prevention and treatment of osteoporosis |
| AUPR363301A0 (en) | 2001-03-08 | 2001-04-05 | Novogen Research Pty Ltd | Dimeric isoflavones |
| AU2003255232A1 (en) | 2002-08-07 | 2004-02-25 | University Of Mississippi | Antigiardial agents and use thereof |
| GB0412768D0 (en) * | 2004-06-08 | 2004-07-07 | Novartis Ag | Organic compounds |
| GB0412769D0 (en) | 2004-06-08 | 2004-07-07 | Novartis Ag | Organic compounds |
| JP2009536610A (en) * | 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 | Pharmaceutical composition for the prevention / treatment of bone disease and preparation method thereof |
| TWI324514B (en) | 2008-02-26 | 2010-05-11 | Univ Kaohsiung Medical | Isoflavone derivatives and pharmaceutical compositions comprising the same |
| CN102964322A (en) * | 2012-12-12 | 2013-03-13 | 中国药科大学 | Isoflavone or flavonoid aliphatic ether derivates, preparation method and medical application thereof |
| CN108264506B (en) * | 2018-01-17 | 2021-01-26 | 中国药科大学 | Isoflavone derivative, preparation method and medical application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6054379A (en) * | 1983-09-05 | 1985-03-28 | Takeda Chem Ind Ltd | Novel 4h-1-benzopyran-4-one derivative, its preparation and its use |
| AU631860B2 (en) * | 1990-04-06 | 1992-12-10 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara | An improved process for the preparation of substituted isoflavone derivatives |
-
1993
- 1993-07-20 HU HU9302083A patent/HUT68558A/en unknown
-
1994
- 1994-07-18 CA CA002167597A patent/CA2167597A1/en not_active Abandoned
- 1994-07-19 AU AU72367/94A patent/AU7236794A/en not_active Abandoned
- 1994-07-19 WO PCT/HU1994/000028 patent/WO1995003293A1/en not_active Application Discontinuation
- 1994-07-19 CN CN94193107A patent/CN1129445A/en active Pending
- 1994-07-19 CA CA002167714A patent/CA2167714A1/en not_active Abandoned
- 1994-07-19 EP EP94921776A patent/EP0710234A1/en not_active Withdrawn
-
1996
- 1996-01-19 KR KR1019960700364A patent/KR960703888A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU7236794A (en) | 1995-02-20 |
| HUT68558A (en) | 1995-06-28 |
| WO1995003293A1 (en) | 1995-02-02 |
| CA2167714A1 (en) | 1995-02-02 |
| EP0710234A1 (en) | 1996-05-08 |
| KR960703888A (en) | 1996-08-31 |
| CN1129445A (en) | 1996-08-21 |
| HU9302083D0 (en) | 1993-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2167597A1 (en) | Pharmaceutical compositions containing as active agent isoflavone derivatives or salts thereof | |
| US5716995A (en) | Anti-osteopathic composition | |
| JP4550417B2 (en) | Polyazolidinone compounds as ligands for prostaglandin EP2 and / or EP4 receptors | |
| AU773081B2 (en) | Bioavailable composition of natural and synthetic HCA | |
| AU2267395A (en) | Benzofuran derivatives useful as inhibitors of bone resorption | |
| US4898870A (en) | Pyrroloquinoline quinone compounds useful as an enzyme inhibitor | |
| IL133585A0 (en) | Soluble prodrugs of paclitaxel | |
| PT1213296E (en) | DERIVATIVES OF GLUCOPIRANOSILOXIPIRAZOLE MEDICAL COMPOSITIONS THAT CONTAIN THEM AND INTERMEDIARIES IN THEIR PRODUCTION | |
| FR2722098A1 (en) | NOVEL MEDICINES BASED ON METRO-NIDAZOLE OR A SYNERGETIC MIXTURE OF METRONIDAZOLE AND CLINDAMYCIN | |
| LV12766A (en) | Composition of l-dopa esters | |
| EP0577356B1 (en) | Topical composition for preventing or treating acne vulgaris | |
| WO1991013898A1 (en) | O6-benzylated guanine, guanosine and 2'-deoxyguanosine compounds possessing o6-alkylguanine-dna alkyltransferase depleting activity | |
| De Haan et al. | The risk of sensibilization and contact urticaria upon topical application of fumaric acid derivatives | |
| US5389646A (en) | Methods for treatment and prevention of bone loss using 2,3-benzopyrans | |
| Hudgins et al. | Cytostatic activity of phenylacetate and derivatives against tumor cells: Correlation with lipophilicity and inhibition of protein prenylation | |
| US5519054A (en) | Pharmaceutical compositions containing N-acetyl-cysteine derivatives useful for the treatment of cataract | |
| CA2438509A1 (en) | Use of cyclohexenone derivatives for the manufacture of a medicament in the treatment of dysuria | |
| US4950686A (en) | Anti-mycoplasma agent | |
| JP2001516698A (en) | Fatty acids as dietary supplements | |
| US20030203974A1 (en) | Methods for treating subjects infected with herpes virus or Neisseria gonorrheae | |
| AU7236694A (en) | Pharmaceutical compositions containing as active agent isoflavone derivatives or salts thereof | |
| WO2001074753A1 (en) | Synthetic derivatives of lunularic acid, medicaments containing said compounds, method for producing the lunularic acid derivatives and the use thereof | |
| EP0526502B1 (en) | Phenolic amine depigmenting and antimelanoma agents | |
| ATE450602T1 (en) | STEM CELL DIFFERENTIATION-INDUCING PROMOTERS | |
| US4678810A (en) | Medical uses of halogenobenzohenone-oxime derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |