JP5769627B2 - ボリノスタットの調製方法 - Google Patents
ボリノスタットの調製方法 Download PDFInfo
- Publication number
- JP5769627B2 JP5769627B2 JP2011531571A JP2011531571A JP5769627B2 JP 5769627 B2 JP5769627 B2 JP 5769627B2 JP 2011531571 A JP2011531571 A JP 2011531571A JP 2011531571 A JP2011531571 A JP 2011531571A JP 5769627 B2 JP5769627 B2 JP 5769627B2
- Authority
- JP
- Japan
- Prior art keywords
- coupling agent
- cdi
- dcc
- molar equivalents
- mixture
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims description 76
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 title claims description 71
- 229960000237 vorinostat Drugs 0.000 title claims description 68
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 78
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 claims description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 72
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 71
- 239000000203 mixture Substances 0.000 claims description 56
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
- 239000007822 coupling agent Substances 0.000 claims description 51
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 39
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 35
- 239000003960 organic solvent Substances 0.000 claims description 25
- PAXDAFSGJPGLGR-UHFFFAOYSA-N 8-anilino-8-oxooctanoic acid Chemical compound OC(=O)CCCCCCC(=O)NC1=CC=CC=C1 PAXDAFSGJPGLGR-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 17
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 17
- 239000012190 activator Substances 0.000 claims description 15
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 13
- YNBDVONJRSJFLP-UHFFFAOYSA-N 8-(hydroxyamino)-8-oxooctanoic acid Chemical compound ONC(=O)CCCCCCC(O)=O YNBDVONJRSJFLP-UHFFFAOYSA-N 0.000 claims description 7
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 claims description 5
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 5
- VMKJWLXVLHBJNK-UHFFFAOYSA-N cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 claims description 5
- -1 1-ethyl Chemical group 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 description 18
- 230000008569 process Effects 0.000 description 15
- 239000007787 solid Substances 0.000 description 13
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
- 201000005962 mycosis fungoides Diseases 0.000 description 11
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 10
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 10
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 208000000453 Skin Neoplasms Diseases 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 201000000849 skin cancer Diseases 0.000 description 5
- 0 *C(*C(Nc1ccccc1)=O)=O Chemical compound *C(*C(Nc1ccccc1)=O)=O 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 239000007806 chemical reaction intermediate Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- RMIBXGXWMDCYEK-UHFFFAOYSA-N oxonane-2,9-dione Chemical compound O=C1CCCCCCC(=O)O1 RMIBXGXWMDCYEK-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KIBVFIDMXQZCBS-UHFFFAOYSA-N 2-methyloctanedioic acid Chemical compound OC(=O)C(C)CCCCCC(O)=O KIBVFIDMXQZCBS-UHFFFAOYSA-N 0.000 description 1
- KOVPXZDUVJGGFU-UHFFFAOYSA-N 8-methoxy-8-oxooctanoic acid Chemical compound COC(=O)CCCCCCC(O)=O KOVPXZDUVJGGFU-UHFFFAOYSA-N 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- AEKHNNJSMVVESS-UHFFFAOYSA-N o-trimethylsilylhydroxylamine Chemical compound C[Si](C)(C)ON AEKHNNJSMVVESS-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 229940061261 zolinza Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1746/KOL/2008 | 2008-10-15 | ||
| IN1746KO2008 | 2008-10-15 | ||
| PCT/GB2009/051376 WO2010043904A2 (en) | 2008-10-15 | 2009-10-14 | Improved process |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012505872A JP2012505872A (ja) | 2012-03-08 |
| JP2012505872A5 JP2012505872A5 (enExample) | 2012-11-29 |
| JP5769627B2 true JP5769627B2 (ja) | 2015-08-26 |
Family
ID=41822438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011531571A Expired - Fee Related JP5769627B2 (ja) | 2008-10-15 | 2009-10-14 | ボリノスタットの調製方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8883851B2 (enExample) |
| EP (1) | EP2349985A2 (enExample) |
| JP (1) | JP5769627B2 (enExample) |
| CN (1) | CN102264694B (enExample) |
| AU (1) | AU2009305214B2 (enExample) |
| CA (1) | CA2740559C (enExample) |
| NZ (1) | NZ592686A (enExample) |
| WO (1) | WO2010043904A2 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1391812B1 (it) * | 2008-07-29 | 2012-01-27 | Maria Grazia Rimoli | Profarmaco galattosilato del ketorolac ad uso analgesico e antinfiammatorio con migliori caratteristiche farmacocinetiche e profilo tossicologico del farmaco di partenza |
| AU2009321384A1 (en) | 2008-11-26 | 2011-06-23 | Generics [Uk] Limited | Polymorphs |
| WO2011061545A1 (en) | 2009-11-23 | 2011-05-26 | Generics [Uk] Limited | Hplc method for analyzing vorinostat |
| US20110313044A1 (en) * | 2010-06-18 | 2011-12-22 | Urquima S.A. | Polymorphs of Suberoylanilide Hydroxamic Acid |
| CN103018346A (zh) * | 2011-09-20 | 2013-04-03 | 北京本草天源药物研究院 | 伏立诺他及其药物组合物中的杂质的高效液相色谱分析方法 |
| CN104693071A (zh) * | 2013-12-04 | 2015-06-10 | 山东新时代药业有限公司 | 一种n- 羟基-n’- 苯基辛二酰胺制备方法 |
| CN103922967B (zh) * | 2014-04-15 | 2016-06-01 | 北京化工大学 | 一种异羟肟酸类化合物及其在制备抑制癌细胞增殖和/或治疗癌症的药物中的应用 |
| CN104292133B (zh) * | 2014-09-29 | 2016-06-01 | 烟台市华文欣欣医药科技有限公司 | 一种抗癌药物伏立诺他的合成方法 |
| CN104649925A (zh) * | 2015-02-13 | 2015-05-27 | 山东新时代药业有限公司 | 一种伏立诺他中间体的制备方法 |
| CN105259261A (zh) * | 2015-10-09 | 2016-01-20 | 扬子江药业集团江苏海慈生物药业有限公司 | 一种药物中苯胺含量的测定方法 |
| CN106008267B (zh) * | 2016-06-27 | 2018-04-06 | 马腾 | 一种抗癌药物伏立诺他的制备方法 |
| CN106187818B (zh) * | 2016-06-27 | 2017-12-08 | 刘美新 | 一种制备抗癌药物伏立诺他的方法 |
| US11554123B2 (en) * | 2017-03-01 | 2023-01-17 | Saint Joseph's University | Compositions and methods for reactivating latent HIV-1 infections |
| TWI650139B (zh) | 2017-10-11 | 2019-02-11 | 行政院原子能委員會核能硏究所 | 含有放射性同位素氟的異羥肟酸類造影劑、其製備方法及其用途 |
| CN109134313B (zh) * | 2018-10-16 | 2021-05-25 | 新昌县勤勉生物医药科技有限公司 | 一种利用改性介孔材料催化制备伏立诺他的方法 |
| CN110283102B (zh) * | 2019-05-31 | 2022-09-27 | 宿州亿帆药业有限公司 | 一种伏林司他ⅰ晶型的制备方法 |
| CN113943232A (zh) * | 2021-11-25 | 2022-01-18 | 汤斌 | 一种从大鲵肽中提取伏立诺他的方法 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5369108A (en) * | 1991-10-04 | 1994-11-29 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and methods of use thereof |
| GB9504084D0 (en) * | 1995-03-01 | 1995-04-19 | British Biotech Pharm | Synthesis of carboxylic and hydroxamic acid derivatives |
| IT1283637B1 (it) * | 1996-05-14 | 1998-04-23 | Italfarmaco Spa | Composti ad attivita' antinfiammatoria ed immunosoppressiva |
| US6497820B1 (en) | 1998-02-03 | 2002-12-24 | Arqule, Inc. | Rapid method for separation of small molecules using reverse phase high performance liquid chromatography |
| US6541661B1 (en) * | 1999-11-23 | 2003-04-01 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7456219B2 (en) * | 2002-03-04 | 2008-11-25 | Merck Hdac Research, Llc | Polymorphs of suberoylanilide hydroxamic acid |
| EP2322160A1 (en) | 2002-03-04 | 2011-05-18 | Merck HDAC Research, LLC | Methods of inducing terminal differentiation |
| PT1663194E (pt) | 2003-08-26 | 2010-07-06 | Merck Hdac Res Llc | Utilizaão de saha para o tratamento de mesotelioma |
| CN1870985B (zh) * | 2003-08-26 | 2011-11-30 | 默克Hdac研究有限责任公司 | 用hdac抑制剂治疗癌症的方法 |
| EP1541549A1 (en) | 2003-12-12 | 2005-06-15 | Exonhit Therapeutics S.A. | Tricyclic hydroxamate and benzaminde derivatives, compositions and methods |
| RU2354362C2 (ru) | 2005-05-20 | 2009-05-10 | Мерк Энд Ко., Инк. | Композиции субероиланилид-гидроксаминовой кислоты и способы их получения |
| TWI415603B (zh) * | 2005-05-20 | 2013-11-21 | Merck Sharp & Dohme | １，８－辛二醯基苯胺羥胺酸（ｓｕｂｅｒｏｙｌａｎｉｌｉｄｅ ｈｙｄｒｏｘａｍｉｃ ａｃｉｄ）之調配物及其製配方法 |
| JP2010504969A (ja) | 2006-09-28 | 2010-02-18 | メルク エンド カムパニー インコーポレーテッド | Ｓａｈａのアミン塩基塩及びその多形 |
| MX2009003405A (es) | 2006-09-28 | 2009-04-09 | Merck & Co Inc | Composiciones farmaceuticas de inhibidores de la histona desacetilasa y compuestos quelantes de metal, y complejos de quelato de metal-inhibidor de histona desacetilasa. |
| US20110041589A1 (en) | 2007-12-14 | 2011-02-24 | Generics [Uk] Limited | New hpcl method |
| WO2009098515A1 (en) * | 2008-02-07 | 2009-08-13 | Generics [Uk] Limited | Novel process for the preparation of vorinostat |
| US20090223286A1 (en) | 2008-02-13 | 2009-09-10 | Vandana Singh | Analytical method for determination of related substances of imipenem and cilastatin |
| CZ2008167A3 (cs) | 2008-03-14 | 2010-02-24 | Zentiva, A. S. | Specifické necistoty montelukastu |
| AU2009321384A1 (en) | 2008-11-26 | 2011-06-23 | Generics [Uk] Limited | Polymorphs |
| US20110269838A1 (en) | 2008-11-26 | 2011-11-03 | Vinayak Gore | Novel processes and pure polymorphs |
-
2009
- 2009-10-14 AU AU2009305214A patent/AU2009305214B2/en not_active Ceased
- 2009-10-14 NZ NZ592686A patent/NZ592686A/xx not_active IP Right Cessation
- 2009-10-14 CA CA2740559A patent/CA2740559C/en not_active Expired - Fee Related
- 2009-10-14 EP EP09748455A patent/EP2349985A2/en not_active Withdrawn
- 2009-10-14 JP JP2011531571A patent/JP5769627B2/ja not_active Expired - Fee Related
- 2009-10-14 WO PCT/GB2009/051376 patent/WO2010043904A2/en not_active Ceased
- 2009-10-14 CN CN200980150218.2A patent/CN102264694B/zh not_active Expired - Fee Related
- 2009-10-14 US US13/124,337 patent/US8883851B2/en active Active
-
2014
- 2014-10-06 US US14/506,741 patent/US9162974B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| NZ592686A (en) | 2012-12-21 |
| JP2012505872A (ja) | 2012-03-08 |
| US9162974B2 (en) | 2015-10-20 |
| WO2010043904A3 (en) | 2010-09-16 |
| AU2009305214A1 (en) | 2010-04-22 |
| CN102264694A (zh) | 2011-11-30 |
| US20150018424A1 (en) | 2015-01-15 |
| CN102264694B (zh) | 2015-11-25 |
| EP2349985A2 (en) | 2011-08-03 |
| US20110263712A1 (en) | 2011-10-27 |
| CA2740559A1 (en) | 2010-04-22 |
| CA2740559C (en) | 2016-02-16 |
| WO2010043904A2 (en) | 2010-04-22 |
| US8883851B2 (en) | 2014-11-11 |
| AU2009305214B2 (en) | 2015-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5769627B2 (ja) | ボリノスタットの調製方法 | |
| CN100369894C (zh) | 氧化氮合酶抑制剂磷酸盐 | |
| CN103492361B (zh) | 取代的1-苄基环烷基羧酸及其用途 | |
| US20110039937A1 (en) | Novel process for the preparation of vorinostat | |
| US20110269838A1 (en) | Novel processes and pure polymorphs | |
| EP2450343A1 (en) | Method for producing threo-3-(3,4-dihydroxyphenyl)-l-serine | |
| CN104292133B (zh) | 一种抗癌药物伏立诺他的合成方法 | |
| JP2004284982A (ja) | ４−グアニジノ安息香酸またはその誘導体のエステル化方法 | |
| US8754129B2 (en) | Crystalline vorinostat form VI | |
| JP4463515B2 (ja) | Ｌ−アンセリンの合成法 | |
| US7425648B2 (en) | Process for the preparation of nateglinide, preferably in B-form | |
| EP1535900A1 (en) | Process for the preparation of nateglinide, preferably in b-form | |
| CA2570041C (en) | Process for the preparation of nateglinide | |
| CN120271527A (zh) | 一种萘普生衍生物及其制备方法和应用 | |
| JP2000515143A (ja) | ベンゾイルプロピオン酸エステル誘導体 | |
| HK1165787A (en) | Method for producing threo-3-(3,4-dihydroxyphenyl)-l-serine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121012 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121012 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20131121 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131126 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140220 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140227 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140523 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141216 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150316 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150526 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150623 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5769627 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |