WO2003104180A1 - Procede de preparation d'acide 4-(4-fluorobenzoyl) butyrique - Google Patents
Procede de preparation d'acide 4-(4-fluorobenzoyl) butyrique Download PDFInfo
- Publication number
- WO2003104180A1 WO2003104180A1 PCT/IN2003/000159 IN0300159W WO03104180A1 WO 2003104180 A1 WO2003104180 A1 WO 2003104180A1 IN 0300159 W IN0300159 W IN 0300159W WO 03104180 A1 WO03104180 A1 WO 03104180A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compound
- fluorobenzene
- preparation
- improved process
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- ZBQROUOOMAMCQW-UHFFFAOYSA-N 5-(4-fluorophenyl)-5-oxopentanoic acid Chemical compound OC(=O)CCCC(=O)C1=CC=C(F)C=C1 ZBQROUOOMAMCQW-UHFFFAOYSA-N 0.000 title abstract description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 54
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims abstract description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 57
- 150000001875 compounds Chemical class 0.000 claims description 37
- 239000002904 solvent Substances 0.000 claims description 24
- 239000011541 reaction mixture Substances 0.000 claims description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 14
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000003637 basic solution Substances 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 230000020477 pH reduction Effects 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 238000011084 recovery Methods 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 claims 1
- KDFQYGBJUYYWDJ-UHFFFAOYSA-N azane;sodium Chemical compound N.[Na] KDFQYGBJUYYWDJ-UHFFFAOYSA-N 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 9
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 abstract description 2
- 229960000815 ezetimibe Drugs 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- SHKWSBAVRQZYLE-UHFFFAOYSA-N 5-oxo-5-phenylpentanoic acid Chemical compound OC(=O)CCCC(=O)C1=CC=CC=C1 SHKWSBAVRQZYLE-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/083—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid anhydrides
Definitions
- the present invention relates to an improved process for the preparation of 4-(4- fluorobenzoyl)butyric acid.
- the 4-(4-fluorobenzoyl)butyric acid has the formula-I given below.
- the 4-(4-fluorobenzoyl)butyric acid has the formula-I is a key raw material for the synthesis of anti-hyperlipoproteinemetic drug ezetimibe (US 5767115, Schering).
- the main criticality in making the compound of formula-I lies in controlling the desfluoro analogue impurity (4-benzoylbutyric acid) at an acceptable level ( ⁇ 0.05% w/w by HPLC).
- the main objective of the present invention is, therefore, to provide an improved process for the preparation of compound of formula-I as defined above overcoming all the disadvantages present in the hitherto known processes.
- Another objective of the present invention is to provide an improved process for the preparation of compound of formula-I as defined above which is simple and economical.
- Another objective of the present invention is to provide an improved process for the preparation of compound of formula-I as defined above which does not have any mixing problem when the process is used on any scale of operation
- Another objective of the present invention is to provide an improved process for the preparation of compound of formula-I as defined above which does not have reaction quenching problem when the process is used on any scale of operation
- Still another objective of the present invention is to provide an improved process for the preparation of compound of formula-I as defined above which does not require high quality fluorobenzene
- Another objective of the present invention is to provide an improved process for the preparation of compound of formula-I as defined above which does not require fluorobenzene as solvent medium to carry out the Friedel-Crafts reaction SUMARY OF INVENTION
- the present invention provides an improved process for the preparation of compound (4-4(fluorobenzoyl)butyric acid) of the formula-I
- I which comprises: (a) Preparing a solution of normal quality fluorobenzene, glutaric anhydride and halogenated solvent, the amount of fluorobenzene used being in a molar ratio of 0.5 to 0.7 molar equivalent with regard to the amount of glutaric anhydride used. (b) Preparing a mixture of aluminum chloride, normal quality fluorobenzene and halogenated solvent, the amount of fluorobenzene used being in a molar ratio of 0.5 to 0.6 molar equivalent with regard to the amount of glutaric anhydride used and the amount of halogenated solvent used being at least 4-6 times (w/v) with regard to the amount of glutaric anhydride used.
- step (c) Adding the solution obtained in step (a) to the mixture obtained in step (b) at a • temperature in the range of 10 to 25°C.
- step (g) Filtering and washing the residue with the same halogenated solved used in step (b) above to obtain the compound of the formula-I.
- the normal quality of fluorobenzene used in step (a) refers to the impurity level of benzene.
- the benzene content in fluorobenzene may be between 300-700ppm.
- the halogenated solvent used in step (b) may be selected form methylene chloride, ethylene dichloride, 1,1,2,2-tetrachloroethane.
- the base used in step (h) may be selected from sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, and ammonia.
- the acid used in step (h) may be selected from hydrochloric acid, hydrobromic acid, sulfuric acid, acetic acid, and propionic acid.
- the solvent used for recrystallization in step (j) may be selected from acetone, methyl ethyl ketone, methyl isobutyl ketone, toluene, acetonitrile, methanol, ethanol, ethyl acetate, hexane or a mixture of these solvents.
- Tnto a 3L three-necked RB flnsk were charged 500ml of methylene chloride, 250 ⁇ r of aluminum chloride and 45gr of fluorobenzene (benzene content 700ppm) under nitrogen atmosphere.
- the reaction mixture was cooled to 10°C and a solution of lOOgr of glutaric anhydride, 45gr of fluorobenzene (benzene content 700ppm) and 500ml of methylene chloride was added slowly over a period of 3hrs between 10-15°C.
- the reaction mixture was maintained for another one hour at the same temperature.
- the reaction mixture was slowly poured onto a mixture of crushed ice (700gr) and cone. HC1 (300ml) below 10°C.
- the reaction mass temperature was allowed to reach 25°C and methylene chloride distilled off from the reaction mixture below 50°C. After cooling the reaction mixture to 20°C, solids were filtered off and washed with 500ml of water.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
La présente invention concerne un procédé amélioré de préparation d'acide 4-(4-fluorobenzoyl)butyrique, qu'on prépare à l'échelle commerciale au moyen de fluorobenzène de qualité standard (ayant une teneur en benzène comprise entre 300 et 700 ppm) et d'un niveau acceptable d'impureté d'analogue desfluoro (moins d'environ 0,1% par CLHP). L'acide 4-(4-fluorobenzoyl)butyrique représenté par la formule (I) est un matériau clé pour la synthèse d'un médicament à effet similaire à l'hyperlipoprotéinémie appelé l'ezetimibe. Formule (I)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003237593A AU2003237593A1 (en) | 2002-06-05 | 2003-04-16 | Process for the preparation of 4-(4-fluorobenzoyl) butyric acid |
| US10/516,770 US20050250961A1 (en) | 2002-06-05 | 2003-04-16 | Process for the preparation of 4-(4-fluorobenzoyl) butyric acid |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN427/MAS/2002 | 2002-06-05 | ||
| IN427CH2002 | 2002-06-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2003104180A1 true WO2003104180A1 (fr) | 2003-12-18 |
Family
ID=29727194
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2003/000159 WO2003104180A1 (fr) | 2002-06-05 | 2003-04-16 | Procede de preparation d'acide 4-(4-fluorobenzoyl) butyrique |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003237593A1 (fr) |
| WO (1) | WO2003104180A1 (fr) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020131807A1 (fr) * | 2018-12-17 | 2020-06-25 | Vertex Pharmaceuticals Incorporated | Inhibiteurs d'apol1 et leurs procédés d'utilisation |
| JP2023530276A (ja) * | 2020-06-12 | 2023-07-14 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｐｏｌ１阻害剤の固体形態及びその使用 |
| US11801234B2 (en) | 2020-03-06 | 2023-10-31 | Vertex Pharmaceuticals Incorporated | Methods of treating APOL-1 dependent focal segmental glomerulosclerosis |
| US11866446B2 (en) | 2020-08-26 | 2024-01-09 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| US12116343B2 (en) | 2020-01-29 | 2024-10-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| US12281102B2 (en) | 2020-06-12 | 2025-04-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| CN120136685A (zh) * | 2025-05-15 | 2025-06-13 | 奥瑞隆新材料(山东)有限公司 | 一种低成本环保生产1,4-二（4-氟苯甲酰基）苯的工艺 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000034240A1 (fr) * | 1998-12-07 | 2000-06-15 | Schering Corporation | Procede relatif a la synthese d'azetidinones |
| US6207822B1 (en) * | 1998-12-07 | 2001-03-27 | Schering Corporation | Process for the synthesis of azetidinones |
| WO2001038305A2 (fr) * | 1999-11-25 | 2001-05-31 | Fournier Industrie Et Sante | Nouveaux antagonistes des recepteurs de l'il-8 |
-
2003
- 2003-04-16 AU AU2003237593A patent/AU2003237593A1/en not_active Abandoned
- 2003-04-16 WO PCT/IN2003/000159 patent/WO2003104180A1/fr not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000034240A1 (fr) * | 1998-12-07 | 2000-06-15 | Schering Corporation | Procede relatif a la synthese d'azetidinones |
| US6207822B1 (en) * | 1998-12-07 | 2001-03-27 | Schering Corporation | Process for the synthesis of azetidinones |
| WO2001038305A2 (fr) * | 1999-11-25 | 2001-05-31 | Fournier Industrie Et Sante | Nouveaux antagonistes des recepteurs de l'il-8 |
Non-Patent Citations (1)
| Title |
|---|
| BAENS, NICOLE P. ET AL: "Synthesis of 2,5-substituted piperidines: transposition of 1,4-substitution pattern for the analgesic drug R6582", TETRAHEDRON (1993), 49(15), 3193-202, XP002022790 * |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12060346B2 (en) | 2018-12-17 | 2024-08-13 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| WO2020131807A1 (fr) * | 2018-12-17 | 2020-06-25 | Vertex Pharmaceuticals Incorporated | Inhibiteurs d'apol1 et leurs procédés d'utilisation |
| JP2022515369A (ja) * | 2018-12-17 | 2022-02-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｐｏｌ１の阻害剤及びその使用方法 |
| US11618746B2 (en) | 2018-12-17 | 2023-04-04 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| IL283592B1 (en) * | 2018-12-17 | 2025-04-01 | Vertex Pharma | APOL1 inhibitors and methods of using them |
| JP7573528B2 (ja) | 2018-12-17 | 2024-10-25 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｐｏｌ１の阻害剤及びその使用方法 |
| CN113453760A (zh) * | 2018-12-17 | 2021-09-28 | 弗特克斯药品有限公司 | Apol1抑制剂及其使用方法 |
| TWI848031B (zh) * | 2018-12-17 | 2024-07-11 | 美商維泰克斯製藥公司 | Apol1抑制劑及其使用方法 |
| CN113453760B (zh) * | 2018-12-17 | 2024-05-24 | 弗特克斯药品有限公司 | Apol1抑制剂及其使用方法 |
| US12116343B2 (en) | 2020-01-29 | 2024-10-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| US11801234B2 (en) | 2020-03-06 | 2023-10-31 | Vertex Pharmaceuticals Incorporated | Methods of treating APOL-1 dependent focal segmental glomerulosclerosis |
| JP2023530276A (ja) * | 2020-06-12 | 2023-07-14 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｐｏｌ１阻害剤の固体形態及びその使用 |
| US12281102B2 (en) | 2020-06-12 | 2025-04-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| US11866446B2 (en) | 2020-08-26 | 2024-01-09 | Vertex Pharmaceuticals Incorporated | Inhibitors of APOL1 and methods of using same |
| CN120136685A (zh) * | 2025-05-15 | 2025-06-13 | 奥瑞隆新材料(山东)有限公司 | 一种低成本环保生产1,4-二（4-氟苯甲酰基）苯的工艺 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003237593A1 (en) | 2003-12-22 |
| AU2003237593A8 (en) | 2003-12-22 |
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