MX2012009782A - Procesos para la sintesis de diariltiohidantoina y compuestos de diarilhidantoina. - Google Patents
Procesos para la sintesis de diariltiohidantoina y compuestos de diarilhidantoina.Info
- Publication number
- MX2012009782A MX2012009782A MX2012009782A MX2012009782A MX2012009782A MX 2012009782 A MX2012009782 A MX 2012009782A MX 2012009782 A MX2012009782 A MX 2012009782A MX 2012009782 A MX2012009782 A MX 2012009782A MX 2012009782 A MX2012009782 A MX 2012009782A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- formula
- reacting
- alkyl
- equivalents
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 317
- 238000000034 method Methods 0.000 title claims abstract description 100
- 230000008569 process Effects 0.000 title claims abstract description 77
- 230000015572 biosynthetic process Effects 0.000 title abstract description 21
- 238000003786 synthesis reaction Methods 0.000 title abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 69
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 239000011541 reaction mixture Substances 0.000 claims description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 31
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 230000007062 hydrolysis Effects 0.000 claims description 24
- 238000006460 hydrolysis reaction Methods 0.000 claims description 24
- 150000007529 inorganic bases Chemical class 0.000 claims description 23
- 229940126062 Compound A Drugs 0.000 claims description 22
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 22
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- OEKATORRSPXJHE-UHFFFAOYSA-N 2-acetylcyclohexan-1-one Chemical compound CC(=O)C1CCCCC1=O OEKATORRSPXJHE-UHFFFAOYSA-N 0.000 claims description 12
- 230000003197 catalytic effect Effects 0.000 claims description 12
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 11
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 11
- 230000032050 esterification Effects 0.000 claims description 9
- 238000005886 esterification reaction Methods 0.000 claims description 9
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 238000002955 isolation Methods 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000002152 alkylating effect Effects 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 abstract description 32
- 206010060862 Prostate cancer Diseases 0.000 abstract description 28
- 229940088597 hormone Drugs 0.000 abstract description 14
- 239000005556 hormone Substances 0.000 abstract description 14
- 229940126601 medicinal product Drugs 0.000 abstract 1
- 239000002798 polar solvent Substances 0.000 description 70
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- 239000000047 product Substances 0.000 description 54
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 52
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 44
- 229940011051 isopropyl acetate Drugs 0.000 description 44
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 44
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
- -1 K2C03 Chemical class 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 30
- 229910052757 nitrogen Inorganic materials 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000002425 crystallisation Methods 0.000 description 18
- 230000008025 crystallization Effects 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 238000010438 heat treatment Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 14
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 13
- 150000001721 carbon Chemical group 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 239000003960 organic solvent Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 108010080146 androgen receptors Proteins 0.000 description 12
- 102000001307 androgen receptors Human genes 0.000 description 12
- 150000001767 cationic compounds Chemical class 0.000 description 12
- 229910001411 inorganic cation Inorganic materials 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 239000003098 androgen Substances 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 10
- 235000015320 potassium carbonate Nutrition 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 229940030486 androgens Drugs 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 9
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- 239000003446 ligand Substances 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 6
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
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- 229910001414 potassium ion Inorganic materials 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 5
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- 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 4
- GVMQERXYJLHNIZ-UHFFFAOYSA-N 4-(2-carboxypropan-2-ylamino)-2-fluorobenzoic acid Chemical compound OC(=O)C(C)(C)NC1=CC=C(C(O)=O)C(F)=C1 GVMQERXYJLHNIZ-UHFFFAOYSA-N 0.000 description 4
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- BAJCFNRLEJHPTQ-UHFFFAOYSA-N 4-bromo-2-fluoro-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(Br)C=C1F BAJCFNRLEJHPTQ-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 238000007309 Fischer-Speier esterification reaction Methods 0.000 description 4
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- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
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- 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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30779610P | 2010-02-24 | 2010-02-24 | |
| PCT/US2011/026135 WO2011106570A1 (en) | 2010-02-24 | 2011-02-24 | Processes for the synthesis of diarylthiohydantoin and diarylhydantoin compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2012009782A true MX2012009782A (es) | 2012-11-29 |
Family
ID=44507217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2012009782A MX2012009782A (es) | 2010-02-24 | 2011-02-24 | Procesos para la sintesis de diariltiohidantoina y compuestos de diarilhidantoina. |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US9174943B2 (enExample) |
| EP (2) | EP3329775B1 (enExample) |
| JP (1) | JP5718372B2 (enExample) |
| KR (1) | KR101514659B1 (enExample) |
| CN (1) | CN103108549B (enExample) |
| BR (1) | BR112012021406B1 (enExample) |
| CA (1) | CA2790924C (enExample) |
| CY (2) | CY1120207T1 (enExample) |
| DK (2) | DK2538785T3 (enExample) |
| ES (2) | ES2671343T3 (enExample) |
| HU (2) | HUE038637T2 (enExample) |
| MX (1) | MX2012009782A (enExample) |
| PL (2) | PL3329775T3 (enExample) |
| PT (2) | PT2538785T (enExample) |
| RU (1) | RU2554081C2 (enExample) |
| SI (2) | SI2538785T1 (enExample) |
| WO (1) | WO2011106570A1 (enExample) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7709517B2 (en) * | 2005-05-13 | 2010-05-04 | The Regents Of The University Of California | Diarylhydantoin compounds |
| TWI469971B (zh) | 2007-10-26 | 2015-01-21 | Univ California | 二芳基乙內醯脲類化合物 |
| EP3124481B1 (en) * | 2010-02-16 | 2018-03-28 | Aragon Pharmaceuticals, Inc. | Androgen receptor modulators and uses thereof |
| WO2012119559A1 (en) | 2011-03-10 | 2012-09-13 | Suzhou Kintor Pharmaceuticals,Inc. | Androgen receptor antagonists and uses thereof |
| WO2013067151A1 (en) * | 2011-11-02 | 2013-05-10 | Medivation Prostate Therapeutics, Inc. | Treatment methods using diarylthiohydantoin derivatives |
| KR20150053963A (ko) * | 2012-09-11 | 2015-05-19 | 닥터 레디스 레보러터리즈 리미티드 | 엔잘루타마이드 다형태 및 그의 제조 |
| TWI673051B (zh) * | 2012-09-11 | 2019-10-01 | 美商梅維森前列腺療法有限責任公司 | 恩雜魯它脈（ｅｎｚａｌｕｔａｍｉｄｅ）之調和物 |
| WO2014052237A1 (en) | 2012-09-26 | 2014-04-03 | Aragon Pharmaceuticals, Inc. | Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer |
| EP2911666B1 (en) | 2012-10-26 | 2022-08-24 | Memorial Sloan-Kettering Cancer Center | Modulators of resistant androgen receptor |
| EP2945628B1 (en) | 2013-01-15 | 2020-04-15 | Aragon Pharmaceuticals, Inc. | Androgen receptor modulator in combination with abiraterone acetate and prednisone for treating prostate cancer |
| RU2520134C1 (ru) | 2013-02-27 | 2014-06-20 | Общество с ограниченной ответственностью "Авионко" (ООО "Авионко") | Замещенные (r)-3-(4-метилкарбамоил-3-фторфениламино)-тетрагидро-фуран-3-енкарбоновые кислоты и их эфиры, способ их получения и применения |
| WO2014167428A2 (en) * | 2013-04-10 | 2014-10-16 | Shilpa Medicare Limited | Amorphous 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-n-methylbenzamide |
| JP6346944B2 (ja) * | 2013-09-19 | 2018-06-20 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーＧｌａｘｏＳｍｉｔｈＫｌｉｎｅ ＬＬＣ | 組み合わせ薬物療法 |
| WO2015054804A1 (zh) * | 2013-10-14 | 2015-04-23 | 杭州普晒医药科技有限公司 | 恩杂鲁胺的固态形式及其制备方法和用途 |
| US20160251316A1 (en) | 2013-10-31 | 2016-09-01 | Sun Pharmaceutical Industries Limited | Process for the preparation of enzalutamide |
| US20160318875A1 (en) | 2013-12-16 | 2016-11-03 | Sun Pharmaceutical Industries Limited | Processes and intermediates for the preparation of enzalutamide |
| CN104803918B (zh) * | 2014-01-26 | 2017-11-10 | 上海医药工业研究院 | 恩杂鲁胺的制备方法 |
| CN104803919A (zh) * | 2014-01-26 | 2015-07-29 | 上海医药工业研究院 | 用于制备恩杂鲁胺中间体的方法 |
| US9611225B2 (en) * | 2014-01-27 | 2017-04-04 | Cadila Healthcare Limited | Process for preparation of androgen receptor antagonist |
| EP3105208A1 (en) | 2014-02-13 | 2016-12-21 | Ranbaxy Laboratories Limited | Process for the preparation of enzalutamide |
| CN104844521B (zh) * | 2014-02-13 | 2017-08-15 | 成都伊诺达博医药科技有限公司 | 抗前列腺癌药物恩杂鲁胺的合成方法 |
| CN104844520B (zh) * | 2014-02-13 | 2017-09-05 | 成都伊诺达博医药科技有限公司 | 一种合成恩杂鲁胺的方法 |
| CZ2014232A3 (cs) | 2014-04-07 | 2015-10-14 | Zentiva, K.S. | Způsob výroby enzalutamidu |
| CN103910679B (zh) * | 2014-04-23 | 2016-05-25 | 杭州新博思生物医药有限公司 | 一种恩杂鲁胺的制备方法 |
| CN103980141A (zh) * | 2014-04-25 | 2014-08-13 | 山东大学 | 恩泽特鲁的合成方法 |
| CN104016924B (zh) * | 2014-06-16 | 2016-04-13 | 上海鼎雅药物化学科技有限公司 | 一种“一锅法”合成恩杂鲁胺的方法 |
| RU2557235C1 (ru) * | 2014-07-08 | 2015-07-20 | Александр Васильевич Иващенко | Замещенные 2-тиоксо-имидазолидин-4-оны и их спироаналоги, противораковый активный компонент, фармацевтическая композиция, лекарственный препарат, способ лечения рака простаты |
| US20170190670A1 (en) * | 2014-07-11 | 2017-07-06 | Shilpa Medicare Limited | Improved process for the preparation of enzalutamide |
| CN105461633A (zh) * | 2014-07-31 | 2016-04-06 | 江苏豪森药业集团有限公司 | 恩杂鲁胺的制备方法 |
| CN105367441B (zh) * | 2014-08-18 | 2018-11-06 | 上海医药工业研究院 | 用于合成恩杂鲁胺的新化合物 |
| CN105461634A (zh) * | 2014-08-19 | 2016-04-06 | 江苏豪森药业集团有限公司 | 恩杂鲁胺的制备方法 |
| US10131636B2 (en) * | 2014-10-01 | 2018-11-20 | Laurus Labs Limited | Process for the preparation of Enzalutamide |
| CN104356068A (zh) * | 2014-10-30 | 2015-02-18 | 杭州新博思生物医药有限公司 | 恩杂鲁胺新晶型及其制备方法 |
| LT3233803T (lt) * | 2014-12-19 | 2019-04-10 | Aragon Pharmaceuticals, Inc. | Diariltiohidantoino junginio gamybos būdas |
| ITUB20151256A1 (it) | 2015-05-28 | 2016-11-28 | Olon Spa | Processo industriale per la preparazione di enzalutamide |
| ITUB20151311A1 (it) * | 2015-05-28 | 2016-11-28 | Olon Spa | Procedimento per la preparazione di enzalutamide |
| ITUB20151204A1 (it) | 2015-05-28 | 2016-11-28 | Olon Spa | Procedimento per la preparazione di enzalutamide |
| JP6753396B2 (ja) * | 2015-05-29 | 2020-09-09 | アステラス製薬株式会社 | エンザルタミド結晶形の製造方法 |
| TWI613194B (zh) * | 2015-06-10 | 2018-02-01 | 台灣神隆股份有限公司 | 用於製備恩雜魯胺的新穎方法 |
| CN105330560A (zh) * | 2015-10-13 | 2016-02-17 | 福格森（武汉）生物科技股份有限公司 | 一种恩杂鲁胺中间体的制备方法 |
| TWI726969B (zh) | 2016-01-11 | 2021-05-11 | 比利時商健生藥品公司 | 用作雄性激素受體拮抗劑之經取代之硫尿囊素衍生物 |
| CN107954936B (zh) * | 2016-10-17 | 2021-03-19 | 海创药业股份有限公司 | 一种制备氘代咪唑二酮类化合物的方法 |
| CN108069869B (zh) * | 2016-11-09 | 2022-03-01 | 上海医药工业研究院 | 一种Apalutamide的制备方法及其中间体 |
| TW201831461A (zh) * | 2017-01-18 | 2018-09-01 | 台灣神隆股份有限公司 | 製備阿帕魯醯胺的方法 |
| PL3616696T3 (pl) | 2017-04-28 | 2025-05-05 | Astellas Pharma Inc. | Kompozycja farmaceytczna do podawania doustnego zawierająca enzalutamid |
| CN107501237B (zh) * | 2017-08-17 | 2022-03-22 | 上海西浦医药科技有限公司 | 一种Apalutamide的合成方法 |
| KR20240096623A (ko) | 2017-10-16 | 2024-06-26 | 아라곤 파마슈티컬스, 인코포레이티드 | 비-전이성 거세-저항성 전립선암의 치료를 위한 항-안드로겐 |
| HUE064356T2 (hu) * | 2017-11-28 | 2024-03-28 | Aarti Pharmalabs Ltd | Eljárás enzalutamid elõállítására új intermedier felhasználásával |
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| CN109988077A (zh) * | 2017-12-29 | 2019-07-09 | 上海法默生物科技有限公司 | 一种阿帕鲁胺的合成方法及中间体 |
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