HU226326B1 - Benzothiophene compounds, intermediates, process for their production, their use and compositions containing them - Google Patents
Benzothiophene compounds, intermediates, process for their production, their use and compositions containing them Download PDFInfo
- Publication number
- HU226326B1 HU226326B1 HU9600476A HUP9600476A HU226326B1 HU 226326 B1 HU226326 B1 HU 226326B1 HU 9600476 A HU9600476 A HU 9600476A HU P9600476 A HUP9600476 A HU P9600476A HU 226326 B1 HU226326 B1 HU 226326B1
- Authority
- HU
- Hungary
- Prior art keywords
- benzo
- thiophene
- formula
- compound
- ethoxy
- Prior art date
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- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title claims description 337
- 238000000034 method Methods 0.000 title claims description 69
- 230000008569 process Effects 0.000 title claims description 24
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000000203 mixture Substances 0.000 title description 33
- 239000000543 intermediate Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 268
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 135
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 125
- -1 methyl-1-pyrrolidinyl Chemical group 0.000 claims description 124
- 125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 95
- 238000006243 chemical reaction Methods 0.000 claims description 82
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 79
- 125000006239 protecting group Chemical group 0.000 claims description 63
- 239000000262 estrogen Substances 0.000 claims description 46
- 229940011871 estrogen Drugs 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 44
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 20
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 201000010260 leiomyoma Diseases 0.000 claims description 15
- 206010027304 Menopausal symptoms Diseases 0.000 claims description 14
- 208000001132 Osteoporosis Diseases 0.000 claims description 13
- 201000009273 Endometriosis Diseases 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 239000000583 progesterone congener Substances 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 7
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 239000012038 nucleophile Substances 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 5
- 208000010579 uterine corpus leiomyoma Diseases 0.000 claims description 5
- 201000007954 uterine fibroid Diseases 0.000 claims description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229940088597 hormone Drugs 0.000 claims description 4
- 239000005556 hormone Substances 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 3
- 229940043279 diisopropylamine Drugs 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 206010029897 Obsessive thoughts Diseases 0.000 claims 1
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- 125000001841 imino group Chemical group [H]N=* 0.000 claims 1
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- 230000035755 proliferation Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 185
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 93
- 238000005160 1H NMR spectroscopy Methods 0.000 description 81
- 239000000243 solution Substances 0.000 description 74
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 64
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- 235000019439 ethyl acetate Nutrition 0.000 description 62
- 238000004458 analytical method Methods 0.000 description 61
- 238000001819 mass spectrum Methods 0.000 description 57
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- 238000002844 melting Methods 0.000 description 56
- 230000008018 melting Effects 0.000 description 56
- 239000007787 solid Substances 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 229910052757 nitrogen Inorganic materials 0.000 description 47
- 238000011282 treatment Methods 0.000 description 46
- 230000002829 reductive effect Effects 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 241001465754 Metazoa Species 0.000 description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 39
- OFHAGSNEHHNRSV-UHFFFAOYSA-N 1-benzothiophene;hydrochloride Chemical compound Cl.C1=CC=C2SC=CC2=C1 OFHAGSNEHHNRSV-UHFFFAOYSA-N 0.000 description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 210000001519 tissue Anatomy 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- 230000000694 effects Effects 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- 210000004291 uterus Anatomy 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 17
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 238000000921 elemental analysis Methods 0.000 description 15
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- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
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- 238000010998 test method Methods 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
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- 239000000706 filtrate Substances 0.000 description 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 10
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- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 10
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 9
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/396,401 US5510357A (en) | 1995-02-28 | 1995-02-28 | Benzothiophene compounds as anti-estrogenic agents |
| US55276095A | 1995-11-03 | 1995-11-03 | |
| US08/552,636 US5723474A (en) | 1995-02-28 | 1995-11-03 | Benzothiophene compounds, intermediates, compositions, and methods |
| US08/552,564 US5998441A (en) | 1995-02-28 | 1995-11-03 | Benzothiophene compounds, intermediates, compositions, and methods |
| US08/552,890 US5919800A (en) | 1995-02-28 | 1995-11-03 | Benzothiophene compounds, intermediates, compositions, and methods |
| US08/552,565 US5977093A (en) | 1995-02-28 | 1995-11-03 | Benzothiophene compounds, intermediates, compositions, and methods |
| US08/552,679 US5856339A (en) | 1995-02-28 | 1995-11-03 | Benzothiophene compounds, intermediates, compositions, and methods |
| US08/554,223 US5856340A (en) | 1995-02-28 | 1995-11-03 | Method of treating estrogen dependent cancers |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| HU9600476D0 HU9600476D0 (en) | 1996-04-29 |
| HUP9600476A2 HUP9600476A2 (hu) | 1999-06-28 |
| HUP9600476A3 HUP9600476A3 (en) | 1999-07-28 |
| HU226326B1 true HU226326B1 (en) | 2008-08-28 |
Family
ID=27575428
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9600476A HU226326B1 (en) | 1995-02-28 | 1996-02-27 | Benzothiophene compounds, intermediates, process for their production, their use and compositions containing them |
Country Status (8)
| Country | Link |
|---|---|
| CN (1) | CN1086700C (cs) |
| BR (1) | BR9600829A (cs) |
| CA (1) | CA2170479C (cs) |
| CZ (1) | CZ290200B6 (cs) |
| FI (1) | FI120345B (cs) |
| HU (1) | HU226326B1 (cs) |
| NO (1) | NO314229B1 (cs) |
| TR (1) | TR199600127A2 (cs) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE535691C2 (sv) * | 2011-03-08 | 2012-11-13 | Kat2Biz Ab | Reduktion av C-O-bindningar via katalytisk transfer hydrogenolys |
| CN102746290B (zh) * | 2012-06-21 | 2014-08-27 | 成都苑东药业有限公司 | 一种噻唑类化合物及其制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4117512A1 (de) * | 1991-05-25 | 1992-11-26 | Schering Ag | 2-phenylbenzo(b)furane und -thiophene, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
-
1996
- 1996-02-16 TR TR96/00127A patent/TR199600127A2/xx unknown
- 1996-02-27 CN CN96105752A patent/CN1086700C/zh not_active Expired - Fee Related
- 1996-02-27 CZ CZ1996588A patent/CZ290200B6/cs not_active IP Right Cessation
- 1996-02-27 CA CA 2170479 patent/CA2170479C/en not_active Expired - Fee Related
- 1996-02-27 HU HU9600476A patent/HU226326B1/hu not_active IP Right Cessation
- 1996-02-27 FI FI960909A patent/FI120345B/fi not_active IP Right Cessation
- 1996-02-27 BR BR9600829A patent/BR9600829A/pt not_active IP Right Cessation
- 1996-02-27 NO NO19960796A patent/NO314229B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO960796D0 (no) | 1996-02-27 |
| CN1086700C (zh) | 2002-06-26 |
| HUP9600476A2 (hu) | 1999-06-28 |
| CA2170479A1 (en) | 1996-08-29 |
| HU9600476D0 (en) | 1996-04-29 |
| CA2170479C (en) | 2009-04-14 |
| FI960909A (fi) | 1996-08-29 |
| FI960909A0 (fi) | 1996-02-27 |
| BR9600829A (pt) | 1997-12-30 |
| AU4579796A (en) | 1996-09-05 |
| CZ290200B6 (cs) | 2002-06-12 |
| AU699753B2 (en) | 1998-12-17 |
| FI120345B (fi) | 2009-09-30 |
| NO314229B1 (no) | 2003-02-17 |
| HUP9600476A3 (en) | 1999-07-28 |
| NO960796L (no) | 1996-08-29 |
| CN1159448A (zh) | 1997-09-17 |
| TR199600127A2 (tr) | 1996-10-21 |
| CZ58896A3 (en) | 1996-09-11 |
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