JPS62263146A - フアイブレ−トの製法 - Google Patents
フアイブレ−トの製法Info
- Publication number
- JPS62263146A JPS62263146A JP62106179A JP10617987A JPS62263146A JP S62263146 A JPS62263146 A JP S62263146A JP 62106179 A JP62106179 A JP 62106179A JP 10617987 A JP10617987 A JP 10617987A JP S62263146 A JPS62263146 A JP S62263146A
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- formula
- temperature
- group
- moles
- 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.)
- Granted
Links
- 229940125753 fibrate Drugs 0.000 title claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 title claims description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000002904 solvent Substances 0.000 claims abstract description 22
- -1 (4-chlorophenyl)hydroxymethyl Chemical group 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 9
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 229910052794 bromium Inorganic materials 0.000 claims abstract 2
- 229910052801 chlorine Inorganic materials 0.000 claims abstract 2
- 229910052731 fluorine Inorganic materials 0.000 claims abstract 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 239000012429 reaction media Substances 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 229960002297 fenofibrate Drugs 0.000 claims description 18
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 13
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 239000002244 precipitate Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 7
- 238000001556 precipitation Methods 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 150000002989 phenols Chemical class 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims 4
- 239000000126 substance Substances 0.000 claims 4
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- 239000000203 mixture Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- XXSPGBOGLXKMDU-UHFFFAOYSA-N 2-bromo-2-methylpropanoic acid Chemical compound CC(C)(Br)C(O)=O XXSPGBOGLXKMDU-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 235000015320 potassium carbonate Nutrition 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- RUETVLNXAGWCDS-UHFFFAOYSA-N (4-chlorophenyl)-(4-hydroxyphenyl)methanone Chemical compound C1=CC(O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 RUETVLNXAGWCDS-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- 238000006561 solvent free reaction Methods 0.000 description 4
- QRPUVEAHEMVOOG-UHFFFAOYSA-O (4-hydroxyphenyl)methanone Chemical compound OC1=CC=C([C+]=O)C=C1 QRPUVEAHEMVOOG-UHFFFAOYSA-O 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960001214 clofibrate Drugs 0.000 description 3
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229960000516 bezafibrate Drugs 0.000 description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- XAJAXMBTYZIQEV-UHFFFAOYSA-N 2-(3-phenoxyphenoxy)propanoic acid Chemical class OC(=O)C(C)OC1=CC=CC(OC=2C=CC=CC=2)=C1 XAJAXMBTYZIQEV-UHFFFAOYSA-N 0.000 description 1
- CDUYSGJRDZEJPK-UHFFFAOYSA-N 2-(4-acetylphenoxy)-2-methylpropanoic acid Chemical compound CC(=O)C1=CC=C(OC(C)(C)C(O)=O)C=C1 CDUYSGJRDZEJPK-UHFFFAOYSA-N 0.000 description 1
- PTTPXKJBFFKCEK-UHFFFAOYSA-N 2-Methyl-4-heptanone Chemical compound CC(C)CC(=O)CC(C)C PTTPXKJBFFKCEK-UHFFFAOYSA-N 0.000 description 1
- SXERGJJQSKIUIC-UHFFFAOYSA-N 2-Phenoxypropionic acid Chemical class OC(=O)C(C)OC1=CC=CC=C1 SXERGJJQSKIUIC-UHFFFAOYSA-N 0.000 description 1
- MONMFXREYOKQTI-UHFFFAOYSA-N 2-bromopropanoic acid Chemical class CC(Br)C(O)=O MONMFXREYOKQTI-UHFFFAOYSA-N 0.000 description 1
- BMAMWMHVCSHJBV-UHFFFAOYSA-N 2-chloro-5-(2,4-dichlorophenoxy)phenol Chemical compound C1=C(Cl)C(O)=CC(OC=2C(=CC(Cl)=CC=2)Cl)=C1 BMAMWMHVCSHJBV-UHFFFAOYSA-N 0.000 description 1
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- JARYNZCVPRATTB-UHFFFAOYSA-N ethyl 2-[4-(4-chlorobenzoyl)phenoxy]propanoate Chemical compound C1=CC(OC(C)C(=O)OCC)=CC=C1C(=O)C1=CC=C(Cl)C=C1 JARYNZCVPRATTB-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960000701 fenofibric acid Drugs 0.000 description 1
- MQOBSOSZFYZQOK-UHFFFAOYSA-N fenofibric acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MQOBSOSZFYZQOK-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 1
- KFOPKOFKGJJEBW-ZSSYTAEJSA-N methyl 2-[(1s,7r,8s,9s,10r,13r,14s,17r)-1,7-dihydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]acetate Chemical compound C([C@H]1O)C2=CC(=O)C[C@H](O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC(=O)OC)[C@@]1(C)CC2 KFOPKOFKGJJEBW-ZSSYTAEJSA-N 0.000 description 1
- ACEONLNNWKIPTM-UHFFFAOYSA-N methyl 2-bromopropanoate Chemical compound COC(=O)C(C)Br ACEONLNNWKIPTM-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical group COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/708—Ethers
- C07C69/712—Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Sampling And Sample Adjustment (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Drilling Tools (AREA)
- Polishing Bodies And Polishing Tools (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8606258A FR2598146B1 (fr) | 1986-04-30 | 1986-04-30 | Nouveau procede de preparation de fibrates. |
| FR8606258 | 1986-04-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62263146A true JPS62263146A (ja) | 1987-11-16 |
| JPH0529343B2 JPH0529343B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-04-30 |
Family
ID=9334781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62106179A Granted JPS62263146A (ja) | 1986-04-30 | 1987-04-28 | フアイブレ−トの製法 |
Country Status (9)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009513613A (ja) * | 2005-10-28 | 2009-04-02 | フルニエ ラボラトリーズ アイルランド リミテッド | 酸と第四級アンモニウムとの塩を調製するための新規な方法 |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0725725B2 (ja) * | 1987-07-23 | 1995-03-22 | 保土谷化学工業株式会社 | ベンズアミド誘導体 |
| GB2221681A (en) * | 1988-01-22 | 1990-02-14 | Kh Nii Endokrinolog I Khim | Undecylic ether n-chlorophenoxyisobutyric acid and a pharmaceutical preparation for treating hyperlipemia based on it |
| US5008439A (en) * | 1988-03-21 | 1991-04-16 | Hoechst Celanese Corporation | Synthesis of 2-(4-hydroxyphenoxy) alkanoic acid esters |
| IL102707A (en) * | 1992-08-02 | 1996-11-14 | Cherkez Stephen | Processes for the preparation of tyramine derivatives |
| EP0625504B1 (de) | 1993-05-12 | 1997-08-27 | HEUMANN PHARMA GmbH | Stabile und kristalline Form von Bezafibrat |
| US5412112A (en) * | 1994-06-14 | 1995-05-02 | Industrial Technology Research Institute | Derivatives and preparation of 2,2-dimethyl-5-substituted phenoxy-pentanoic acids |
| US6838091B2 (en) | 1998-12-18 | 2005-01-04 | Abbott Laboratories | Formulations comprising lipid-regulating agents |
| US6814977B1 (en) | 1998-12-18 | 2004-11-09 | Abbott Laboratories | Formulations comprising lipid-regulating agents |
| US7014864B1 (en) | 1998-12-18 | 2006-03-21 | Abbott Laboratories | Formulations comprising lipid-regulating agents |
| US6180138B1 (en) | 1999-01-29 | 2001-01-30 | Abbott Laboratories | Process for preparing solid formulations of lipid-regulating agents with enhanced dissolution and absorption |
| US6368622B2 (en) | 1999-01-29 | 2002-04-09 | Abbott Laboratories | Process for preparing solid formulations of lipid regulating agents with enhanced dissolution and absorption |
| US6383517B1 (en) | 1999-01-29 | 2002-05-07 | Abbott Laboratories | Process for preparing solid formulations of lipid-regulating agents with enhanced dissolution and absorption |
| US6719999B2 (en) | 1999-03-31 | 2004-04-13 | Abbott Laboratories | Formulations comprising lipid-regulating agents |
| US6372251B2 (en) | 1999-06-11 | 2002-04-16 | Abbott Laboratories | Formulations comprising lipid-regulating agents |
| US6982251B2 (en) * | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| BR0206644A (pt) * | 2001-01-26 | 2004-02-25 | Schering Corp | Combinações de inibidor(es) de absorção de esteróis com agente(s) cardiovascular(es) para o tratamento de condições vasculares |
| MXPA03006727A (es) * | 2001-01-26 | 2003-10-24 | Schering Corp | Combinaciones de acido nicotinico y derivados del mismo con inhibidor(es) de la absorcion de los esteroles, y tratamiento para indicaciones vasculares. |
| US20060287254A1 (en) * | 2001-01-26 | 2006-12-21 | Schering Corporation | Use of substituted azetidinone compounds for the treatment of sitosterolemia |
| US7071181B2 (en) * | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
| CA2434504A1 (en) * | 2001-01-26 | 2002-08-01 | Teddy Kosoglou | Combinations of sterol absorption inhibitor(s) with blood modifiers for treating vascular conditions |
| ES2290562T3 (es) * | 2001-01-26 | 2008-02-16 | Schering Corporation | Combinaciones del activador del receptor activado por el proliferador de los peroxisomas (ppar) fenofibrato con el inhibidor de la absorcion de esteroles ezetimiba para indicaciones vasculares. |
| ES2287250T3 (es) * | 2001-01-26 | 2007-12-16 | Schering Corporation | Combinaciones de secuestrante(s) de acidos biliares e inhibidor(es) de la absorcion de esteroles y tratamientos para indicaciones vasculares. |
| KR20070120617A (ko) * | 2001-01-26 | 2007-12-24 | 쉐링 코포레이션 | 치환된 아제티딘온 화합물을 포함하는 약제학적 조성물 |
| ITMI20010203A1 (it) * | 2001-02-02 | 2002-08-02 | Solchem Italiana Spa | Processo per la preparazione di fibrati |
| ITMI20010936A1 (it) * | 2001-05-08 | 2002-11-08 | Laboratorio Chimico Int Spa | Processo per la produzione di acidi 2-4-(2,2-dialociclopropil)fenossi|-alcanoici e loro esteri |
| WO2002096415A2 (en) * | 2001-05-25 | 2002-12-05 | Schering Corporation | Use of azetidinone substituted derivatives in the treatment of alzheimer's disease |
| US7053080B2 (en) * | 2001-09-21 | 2006-05-30 | Schering Corporation | Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors |
| ES2272776T3 (es) * | 2001-09-21 | 2007-05-01 | Schering Corporation | Tratamiento de xantomas con derivados de azetidinona como inhibidores de la absorcion de esterol. |
| US20030119808A1 (en) * | 2001-09-21 | 2003-06-26 | Schering Corporation | Methods of treating or preventing cardiovascular conditions while preventing or minimizing muscular degeneration side effects |
| US7056906B2 (en) * | 2001-09-21 | 2006-06-06 | Schering Corporation | Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women |
| BR0212907A (pt) * | 2001-09-21 | 2004-10-13 | Schering Corp | Métodos para tratamento ou prevenção de inflamação vascular usando inibidor(es) da absorção de esteróis |
| WO2004043456A1 (en) * | 2002-11-06 | 2004-05-27 | Schering Corporation | Cholesterol absorption inhibitors for the treatment of demyelination |
| US7208486B2 (en) * | 2003-03-07 | 2007-04-24 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| DE602004016123D1 (de) * | 2003-03-07 | 2008-10-09 | Schering Corp | Substituierte azetidinon-derivate, deren pharmazeutische formulierungen und deren verwendung zur behandlung von hypercholesterolemia |
| US7192944B2 (en) | 2003-03-07 | 2007-03-20 | Schering Corp. | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| US7459442B2 (en) * | 2003-03-07 | 2008-12-02 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| CA2544309A1 (en) * | 2003-11-05 | 2005-05-26 | Schering Corporation | Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions |
| US8062664B2 (en) * | 2003-11-12 | 2011-11-22 | Abbott Laboratories | Process for preparing formulations of lipid-regulating drugs |
| EP1837327A1 (en) * | 2006-03-23 | 2007-09-26 | SOLMAG S.p.A. | Method for preparing pure fenofibrate |
| KR20100062976A (ko) * | 2007-07-05 | 2010-06-10 | 피노르가 에스.에이. | 페노피브레이트의 제조방법 |
| CN103373921B (zh) | 2012-04-26 | 2016-08-10 | 浙江海正药业股份有限公司 | 4-((取代苯基)二氟甲基)苯氧基羧酸衍生物及其制备方法和医药用途 |
| US11427528B2 (en) | 2016-07-29 | 2022-08-30 | Hangzhou Solipharma Co., Ltd. | Fenofibrate crystalline form and manufacturing method thereof |
| CN107698422A (zh) * | 2017-08-21 | 2018-02-16 | 赵剑锋 | 一种2‑[4‑(4‑ 氯苯甲酰) 苯氧基]‑2‑ 甲基丙酸的合成工艺 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2060573A1 (de) * | 1969-12-18 | 1971-06-24 | Ciba Geigy Ag | Neue Carbonsaeuren und Verfahren zu ihrer Herstellung |
| US3795691A (en) * | 1971-06-23 | 1974-03-05 | American Home Prod | Cholesterol-lowering agents |
| US3759950A (en) * | 1971-09-20 | 1973-09-18 | American Home Prod | 2-phenoxyalkanoic acid esters |
| CH626318A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1977-03-08 | 1981-11-13 | Ciba Geigy Ag | |
| IT1141655B (it) * | 1980-02-12 | 1986-10-08 | Schiapparelli Spa | Nuovi derivati dell'acido propanoico ad attivita' ipolipidemica e ipocolesterolemica |
| DE3150233A1 (de) * | 1981-12-18 | 1983-06-30 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von 2-(hydroxiphenoxi)-carbonsaeureestern |
| US4661505A (en) * | 1982-11-03 | 1987-04-28 | Eli Lilly And Company | Leukotriene antagonists |
| IL71668A (en) * | 1983-05-13 | 1988-07-31 | Dow Chemical Co | Method of preparing esters of aryloxyphenoxy propanoic acid |
-
1986
- 1986-04-30 FR FR8606258A patent/FR2598146B1/fr not_active Expired
-
1987
- 1987-04-27 AT AT87400967T patent/ATE49195T1/de not_active IP Right Cessation
- 1987-04-27 ES ES87400967T patent/ES2005059B3/es not_active Expired - Lifetime
- 1987-04-27 EP EP87400967A patent/EP0245156B1/fr not_active Expired - Lifetime
- 1987-04-27 DE DE8787400967T patent/DE3761307D1/de not_active Expired - Lifetime
- 1987-04-27 US US07/043,184 patent/US4739101A/en not_active Expired - Lifetime
- 1987-04-27 CA CA000535685A patent/CA1282424C/en not_active Expired - Lifetime
- 1987-04-28 JP JP62106179A patent/JPS62263146A/ja active Granted
-
1990
- 1990-03-30 GR GR90400186T patent/GR3000418T3/el unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009513613A (ja) * | 2005-10-28 | 2009-04-02 | フルニエ ラボラトリーズ アイルランド リミテッド | 酸と第四級アンモニウムとの塩を調製するための新規な方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US4739101A (en) | 1988-04-19 |
| ES2005059B3 (es) | 1990-03-16 |
| EP0245156B1 (fr) | 1990-01-03 |
| FR2598146B1 (fr) | 1989-01-20 |
| ATE49195T1 (de) | 1990-01-15 |
| DE3761307D1 (de) | 1990-02-08 |
| ES2005059A4 (es) | 1989-03-01 |
| EP0245156A1 (fr) | 1987-11-11 |
| CA1282424C (en) | 1991-04-02 |
| JPH0529343B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-04-30 |
| FR2598146A1 (fr) | 1987-11-06 |
| GR3000418T3 (en) | 1991-06-28 |
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