CA2297246A1 - Tamoxifen and analogues thereof - Google Patents
Tamoxifen and analogues thereof Download PDFInfo
- Publication number
- CA2297246A1 CA2297246A1 CA002297246A CA2297246A CA2297246A1 CA 2297246 A1 CA2297246 A1 CA 2297246A1 CA 002297246 A CA002297246 A CA 002297246A CA 2297246 A CA2297246 A CA 2297246A CA 2297246 A1 CA2297246 A1 CA 2297246A1
- Authority
- CA
- Canada
- Prior art keywords
- solvent
- tamoxifen
- isomer
- derivative
- precursor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 title claims abstract description 94
- 229960001603 tamoxifen Drugs 0.000 title claims abstract description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 49
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims description 82
- 239000000203 mixture Substances 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 15
- 239000002243 precursor Substances 0.000 claims description 14
- 238000001953 recrystallisation Methods 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 229910052698 phosphorus Inorganic materials 0.000 claims description 11
- 238000009835 boiling Methods 0.000 claims description 10
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 230000001833 anti-estrogenic effect Effects 0.000 claims description 7
- 239000000328 estrogen antagonist Substances 0.000 claims description 5
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000003495 polar organic solvent Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 125000000951 phenoxy group Chemical class [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- -1 2-chloroethoxy tamoxifen Chemical compound 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical class C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZUVNHKQPUCOXAA-UHFFFAOYSA-N 1-[4-(2-chloroethoxy)phenyl]-2-phenylbutan-1-one Chemical compound C=1C=CC=CC=1C(CC)C(=O)C1=CC=C(OCCCl)C=C1 ZUVNHKQPUCOXAA-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 101100515517 Arabidopsis thaliana XI-I gene Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000950314 Figura Species 0.000 description 1
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 1
- 101000642464 Homo sapiens Spermatogenesis-associated protein 2-like protein Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102100030254 Spermatogenesis-associated protein 2 Human genes 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- MKYQPGPNVYRMHI-UHFFFAOYSA-N Triphenylethylene Chemical group C=1C=CC=CC=1C=C(C=1C=CC=CC=1)C1=CC=CC=C1 MKYQPGPNVYRMHI-UHFFFAOYSA-N 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000001344 alkene derivatives Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical class 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical class 0.000 description 1
- 125000005157 alkyl carboxy group Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9715479.3 | 1997-07-23 | ||
| GBGB9715479.3A GB9715479D0 (en) | 1997-07-23 | 1997-07-23 | Tamoxifen and analogues thereof |
| PCT/GB1998/002171 WO1999005088A1 (en) | 1997-07-23 | 1998-07-21 | Tamoxifen and analogues thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2297246A1 true CA2297246A1 (en) | 1999-02-04 |
Family
ID=10816289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002297246A Abandoned CA2297246A1 (en) | 1997-07-23 | 1998-07-21 | Tamoxifen and analogues thereof |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0998447A1 (de) |
| JP (1) | JP2001510819A (de) |
| AU (1) | AU8452998A (de) |
| CA (1) | CA2297246A1 (de) |
| GB (2) | GB9715479D0 (de) |
| HU (1) | HUP0002807A3 (de) |
| NO (1) | NO316376B1 (de) |
| WO (1) | WO1999005088A1 (de) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE637389A (de) * | 1962-09-13 | |||
| EP0127128B1 (de) * | 1983-05-24 | 1987-02-25 | Bristol-Myers Company | Verfahren zur Umwandlung von 1,2-Diphenyl-1-[4-(2-dimethylamino-ethoxy)-phenyl]-1-buten-E-Isomeren zu Tamoxifen-Hydrochlorid |
| GB2160202B (en) * | 1984-06-12 | 1987-12-02 | Nat Res Dev | Preparation of tamoxifen |
| ATE80152T1 (de) * | 1987-04-21 | 1992-09-15 | Heumann Pharma Gmbh & Co | Stabile loesungsmitteladdukte von z-1-(p-betadimethylamino-ethoxyphenyl)-1-(p-hydroxyphenyl) 2-phenylbut-1-en. |
| DE3736682A1 (de) * | 1987-10-29 | 1989-05-11 | Klinge Co Chem Pharm Fab | Verfahren zur herstellung von trans-1,1,2-triphenyl-but-1-en-derivaten |
| CA2150230C (en) * | 1993-10-25 | 1998-10-27 | Fumihiko Shinozaki | Process for producing acid-addition salt of z-isomer of triphenylethylene compound |
| US5693863A (en) * | 1994-01-03 | 1997-12-02 | Klinge Pharma Gmbh | Method for the production of E-1- 4'- (2- Dimethylaminoethoxy) - Phenyl!-1-(3-Hydroxyphenyl) -2-Phenyl-1-Butene |
| GB9601167D0 (en) * | 1996-01-20 | 1996-03-20 | Univ Bradford | Tamoxifen and analogues thereof |
-
1997
- 1997-07-23 GB GBGB9715479.3A patent/GB9715479D0/en active Pending
-
1998
- 1998-07-21 HU HU0002807A patent/HUP0002807A3/hu unknown
- 1998-07-21 GB GB9815904A patent/GB2327673B/en not_active Expired - Fee Related
- 1998-07-21 WO PCT/GB1998/002171 patent/WO1999005088A1/en not_active Application Discontinuation
- 1998-07-21 CA CA002297246A patent/CA2297246A1/en not_active Abandoned
- 1998-07-21 AU AU84529/98A patent/AU8452998A/en not_active Abandoned
- 1998-07-21 JP JP2000504090A patent/JP2001510819A/ja not_active Withdrawn
- 1998-07-21 EP EP98935177A patent/EP0998447A1/de not_active Withdrawn
-
2000
- 2000-01-21 NO NO20000329A patent/NO316376B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999005088A1 (en) | 1999-02-04 |
| NO20000329L (no) | 2000-03-23 |
| HUP0002807A1 (hu) | 2001-11-28 |
| AU8452998A (en) | 1999-02-16 |
| JP2001510819A (ja) | 2001-08-07 |
| GB9715479D0 (en) | 1997-10-01 |
| GB2327673B (en) | 2002-03-27 |
| GB9815904D0 (en) | 1998-09-16 |
| HUP0002807A3 (en) | 2002-01-28 |
| GB2327673A (en) | 1999-02-03 |
| EP0998447A1 (de) | 2000-05-10 |
| NO316376B1 (no) | 2004-01-19 |
| NO20000329D0 (no) | 2000-01-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |