PT1025077E - Novas ariloxi-alquil-dialquilaminas - Google Patents
Novas ariloxi-alquil-dialquilaminas Download PDFInfo
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- PT1025077E PT1025077E PT98953459T PT98953459T PT1025077E PT 1025077 E PT1025077 E PT 1025077E PT 98953459 T PT98953459 T PT 98953459T PT 98953459 T PT98953459 T PT 98953459T PT 1025077 E PT1025077 E PT 1025077E
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- Prior art keywords
- alkyl
- formula
- compound
- halogen
- alcohol
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 121
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 46
- -1 C 1 -C 4 alkyl Chemical group 0.000 claims description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical group 0.000 claims description 26
- 150000001299 aldehydes Chemical class 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 239000012279 sodium borohydride Substances 0.000 claims description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- WZEOZJQLTRFNCU-UHFFFAOYSA-N trifluoro(trifluoromethoxy)methane Chemical class FC(F)(F)OC(F)(F)F WZEOZJQLTRFNCU-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 230000002152 alkylating effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 4
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 150000003457 sulfones Chemical class 0.000 claims description 3
- 150000003462 sulfoxides Chemical class 0.000 claims description 3
- 125000004951 trihalomethoxy group Chemical group 0.000 claims description 3
- 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 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 5
- 125000004423 acyloxy group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- COOWZQXURKSOKE-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol;hydrochloride Chemical compound Cl.C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 COOWZQXURKSOKE-UHFFFAOYSA-N 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 101150009274 nhr-1 gene Proteins 0.000 claims 1
- 239000000243 solution Substances 0.000 description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 239000011541 reaction mixture Substances 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 31
- 239000007787 solid Substances 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- 239000000047 product Substances 0.000 description 25
- 239000000758 substrate Substances 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 19
- 239000000262 estrogen Substances 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- 238000003556 assay Methods 0.000 description 18
- 229940011871 estrogen Drugs 0.000 description 18
- 229960005309 estradiol Drugs 0.000 description 17
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 235000002639 sodium chloride Nutrition 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 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 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 210000000988 bone and bone Anatomy 0.000 description 12
- VOXZDWNPVJITMN-UHFFFAOYSA-N 13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2C3CCC(C)(C(CC4)O)C4C3CCC2=C1 VOXZDWNPVJITMN-UHFFFAOYSA-N 0.000 description 11
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 11
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 102000029816 Collagenase Human genes 0.000 description 10
- 108060005980 Collagenase Proteins 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108010026132 Gelatinases Proteins 0.000 description 8
- 102000013382 Gelatinases Human genes 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000003610 charcoal Substances 0.000 description 8
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 7
- 239000007995 HEPES buffer Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 229960001603 tamoxifen Drugs 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- QBXGBNZCIAVBCA-UHFFFAOYSA-N [4-(2-piperidin-1-ylethoxy)phenyl]methanol Chemical compound C1=CC(CO)=CC=C1OCCN1CCCCC1 QBXGBNZCIAVBCA-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 230000001833 anti-estrogenic effect Effects 0.000 description 6
- 239000012131 assay buffer Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 229960002424 collagenase Drugs 0.000 description 6
- 229930182833 estradiol Natural products 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 6
- 229960004622 raloxifene Drugs 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 5
- 206010065687 Bone loss Diseases 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 229920002307 Dextran Polymers 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 206010014733 Endometrial cancer Diseases 0.000 description 5
- 206010014759 Endometrial neoplasm Diseases 0.000 description 5
- 229940073608 benzyl chloride Drugs 0.000 description 5
- 210000000172 cytosol Anatomy 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 239000000328 estrogen antagonist Substances 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000012417 linear regression Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 4
- KQXRJVROLOXPNS-UHFFFAOYSA-N 2-[4-[(2-phenylindol-1-yl)methyl]phenoxy]ethanamine Chemical class C1=CC(OCCN)=CC=C1CN1C2=CC=CC=C2C=C1C1=CC=CC=C1 KQXRJVROLOXPNS-UHFFFAOYSA-N 0.000 description 4
- KRIJKJMYOVWRSJ-UHFFFAOYSA-N 3-methyl-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)-1h-indole Chemical compound C1=C2C(C)=C(C=3C=CC(OCC=4C=CC=CC=4)=CC=3)NC2=CC=C1OCC1=CC=CC=C1 KRIJKJMYOVWRSJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 229910004809 Na2 SO4 Inorganic materials 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229940046836 anti-estrogen Drugs 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Substances OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 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 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
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- 239000011734 sodium Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
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- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 3
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 3
- JGLGVYACPZLMND-UHFFFAOYSA-N 1-[2-[4-(chloromethyl)phenoxy]ethyl]piperidine;hydrochloride Chemical compound Cl.C1=CC(CCl)=CC=C1OCCN1CCCCC1 JGLGVYACPZLMND-UHFFFAOYSA-N 0.000 description 3
- JICOGKJOQXTAIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 JICOGKJOQXTAIP-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940063238 premarin Drugs 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 1
- 229960002119 raloxifene hydrochloride Drugs 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- SMYMDRJWEFCCCI-UHFFFAOYSA-N trichloro(trichloromethoxy)methane Chemical compound ClC(Cl)(Cl)OC(Cl)(Cl)Cl SMYMDRJWEFCCCI-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000001836 utereotrophic effect Effects 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Gynecology & Obstetrics (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Pregnancy & Childbirth (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Detergent Compositions (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US95081897A | 1997-10-15 | 1997-10-15 | |
| US09/161,653 US6005102A (en) | 1997-10-15 | 1998-09-28 | Aryloxy-alkyl-dialkylamines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1025077E true PT1025077E (pt) | 2007-05-31 |
Family
ID=26858006
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT98953459T PT1025077E (pt) | 1997-10-15 | 1998-10-14 | Novas ariloxi-alquil-dialquilaminas |
Country Status (26)
| Country | Link |
|---|---|
| EP (2) | EP1777214A3 (https=) |
| JP (1) | JP2001519410A (https=) |
| KR (1) | KR100669836B1 (https=) |
| CN (1) | CN1231458C (https=) |
| AR (1) | AR015183A1 (https=) |
| AT (1) | ATE355264T1 (https=) |
| AU (1) | AU757630C (https=) |
| BR (1) | BR9813069A (https=) |
| CA (1) | CA2306343C (https=) |
| CY (1) | CY1106497T1 (https=) |
| DE (1) | DE69837210T2 (https=) |
| DK (1) | DK1025077T3 (https=) |
| EA (1) | EA003937B1 (https=) |
| EE (1) | EE200000225A (https=) |
| ES (1) | ES2281937T3 (https=) |
| HU (1) | HUP0004419A3 (https=) |
| ID (1) | ID24417A (https=) |
| IL (2) | IL135343A0 (https=) |
| NO (1) | NO20001938L (https=) |
| NZ (1) | NZ503793A (https=) |
| PL (1) | PL198443B1 (https=) |
| PT (1) | PT1025077E (https=) |
| SI (1) | SI1025077T1 (https=) |
| SK (1) | SK286460B6 (https=) |
| TR (1) | TR200001012T2 (https=) |
| WO (1) | WO1999019293A1 (https=) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA005932B1 (ru) * | 1998-05-15 | 2005-08-25 | Уайт | 2-фенил-1-[4-(2-аминоэтокси)бензил]индол в комбинации с эстрогенами |
| US6479535B1 (en) | 1998-05-15 | 2002-11-12 | Wyeth | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole and estrogen formulations |
| CA2382683A1 (en) * | 1999-09-13 | 2001-03-22 | American Home Products Corporation | Glucopyranosides conjugates of 2-(4-hydroxy-phenyl)-1-¬4-(2-amin-1-yl-ethoxy)-benzyl|-1h-indol-5-ols |
| US6455568B2 (en) | 2000-07-06 | 2002-09-24 | Wyeth | Combination therapy for inhibiting sphincter incontinence |
| AR029538A1 (es) | 2000-07-06 | 2003-07-02 | Wyeth Corp | Composiciones farmaceuticas de agentes estrogenicos |
| AU2001273144A1 (en) | 2000-07-06 | 2002-01-21 | Wyeth | Use of substituted indole compounds for treating neuropeptide y-related conditions |
| MXPA03000170A (es) | 2000-07-06 | 2003-05-27 | Wyeth Corp | Combinaciones de un inhibidor de recaptacion de serotonina selectivo y agentes estrogenicos. |
| AR029539A1 (es) | 2000-07-06 | 2003-07-02 | Wyeth Corp | Combinaciones de estatinas y agentes estrogenicos |
| EP1656938A1 (en) | 2000-07-06 | 2006-05-17 | Wyeth | Combinations of SSRI and estrogenic agents |
| WO2002003990A2 (en) | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted insole compounds for treating excessive intraocular pressure |
| US6376486B1 (en) | 2000-07-06 | 2002-04-23 | American Home Products Corporation | Methods of inhibiting sphincter incontinence |
| US6369051B1 (en) | 2000-07-06 | 2002-04-09 | American Home Products Corporation | Combinations of SSRI and estrogenic agents |
| JP2004532834A (ja) * | 2001-03-23 | 2004-10-28 | イーライ・リリー・アンド・カンパニー | ヒスタミンｈ３受容体アンタゴニストである非イミダゾール系アリールアルキルアミン化合物、その製造および治療的使用 |
| JP2004531559A (ja) | 2001-05-22 | 2004-10-14 | イーライ・リリー・アンド・カンパニー | エストロゲン欠乏または内因性エストロゲンに対する異常な生理反応に関連する疾患を抑制するためのテトラヒドロキノリン誘導体 |
| EP1395563B1 (en) | 2001-05-22 | 2006-03-29 | Eli Lilly And Company | 2-substituted 1,2,3,4-tetrahydroquinolines and derivatives thereof, compositions and methods |
| US7314937B2 (en) | 2002-03-21 | 2008-01-01 | Eli Lilly And Company | Non-imidazole aryl alkylamines compounds as histamine H3 receptor antagonists, preparation and therapeutic uses |
| US7098241B2 (en) | 2002-12-16 | 2006-08-29 | Hoffmann-La Roche Inc. | Thiophene hydroxamic acid derivatives |
| WO2005100316A1 (en) | 2004-04-07 | 2005-10-27 | Wyeth | Crystalline polymorph of a bazedoxifene acetate |
| JP2007532548A (ja) | 2004-04-07 | 2007-11-15 | ワイス | バゼドキシフェンアセテートの結晶質多形体 |
| MXPA06011686A (es) | 2004-04-08 | 2006-12-14 | Wyeth Corp | Ascorbato de bazedoxifeno como modulador del receptor de estrogeno selectivo. |
| JP2008509148A (ja) * | 2004-08-05 | 2008-03-27 | ワイス | 塩酸ピピンドキシフェン一水和物の結晶多形 |
| EP1836155A2 (en) * | 2005-01-13 | 2007-09-26 | Wyeth, A Corporation of the State of Delaware | Processes for the preparation of aminoethoxybenzyl alcohols |
| US20100087661A1 (en) * | 2007-02-12 | 2010-04-08 | Josef Jirman | Method for the preparation of 5-benzyloxy-2-(4-benzyloxphenyl)-3-methyl-1h-indole |
| WO2009102771A1 (en) * | 2008-02-11 | 2009-08-20 | Wyeth | Methods of converting polymorphic form b of bazedoxifene acetate to polymorphic form a of bazedoxifene acetate |
| CA2758109A1 (en) * | 2009-04-13 | 2010-10-21 | Sandoz Ag | Processes for the synthesis of bazedoxifene acetate and intermediates thereof |
| US8569483B2 (en) | 2011-06-21 | 2013-10-29 | Divi's Laboratories, Ltd. | Process for the preparation of bazedoxifene acetate and intermediates thereof |
| CN104151265B (zh) * | 2013-05-13 | 2016-10-05 | 上海医药工业研究院 | 醋酸巴多昔芬中间体的制备方法 |
| US9751835B2 (en) | 2013-05-15 | 2017-09-05 | Indiana University Research And Technology Corporation | Processes and intermediates for preparing indole pharmaceuticals |
| IT201800006562A1 (it) * | 2018-06-21 | 2019-12-21 | Procedimento e intermedi utili per la preparazione di indoli | |
| IT201900001923A1 (it) | 2019-02-11 | 2020-08-11 | Erregierre Spa | Sali di bazedoxifene utili per la preparazione di bazedoxifene acetato |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH448121A (de) | 1963-03-13 | 1967-12-15 | Hoffmann La Roche | Verfahren zur Herstellung substituierter Hydrazinverbindungen |
| WO1991007107A1 (en) * | 1989-11-13 | 1991-05-30 | Pfizer Inc. | Oxazolidinedione hypoglycemic agents |
| GB9326332D0 (en) | 1993-12-23 | 1994-02-23 | Karo Bio | Indole derivatives |
| CA2259487A1 (en) * | 1996-07-01 | 1998-01-08 | Margaret Mary Faul | Hypoglycemic and hypolipidemic compounds |
| YU40999A (sh) * | 1997-02-27 | 2002-06-19 | American Cyanamid Company | N-hidroksi-2-(alkil,aril ili heteroaril sulfanil,sulfinil ili sulfonil)-3-supstituisani alkil,aril ili heteroarilamidi, kao inhibitori za matrične metaloproteinaze |
| EP1011666A4 (en) * | 1997-04-30 | 2004-03-31 | Lilly Co Eli | ANTITHROMBOTIC AGENTS |
-
1998
- 1998-10-14 PT PT98953459T patent/PT1025077E/pt unknown
- 1998-10-14 ES ES98953459T patent/ES2281937T3/es not_active Expired - Lifetime
- 1998-10-14 ID IDW20000680A patent/ID24417A/id unknown
- 1998-10-14 AU AU10831/99A patent/AU757630C/en not_active Ceased
- 1998-10-14 HU HU0004419A patent/HUP0004419A3/hu unknown
- 1998-10-14 SK SK537-2000A patent/SK286460B6/sk not_active IP Right Cessation
- 1998-10-14 SI SI9830877T patent/SI1025077T1/sl unknown
- 1998-10-14 EE EEP200000225A patent/EE200000225A/xx unknown
- 1998-10-14 EP EP07003195A patent/EP1777214A3/en not_active Withdrawn
- 1998-10-14 EA EA200000416A patent/EA003937B1/ru not_active IP Right Cessation
- 1998-10-14 EP EP98953459A patent/EP1025077B1/en not_active Expired - Lifetime
- 1998-10-14 PL PL339908A patent/PL198443B1/pl not_active IP Right Cessation
- 1998-10-14 KR KR1020007004031A patent/KR100669836B1/ko not_active Expired - Fee Related
- 1998-10-14 AR ARP980105112A patent/AR015183A1/es unknown
- 1998-10-14 WO PCT/US1998/021609 patent/WO1999019293A1/en not_active Ceased
- 1998-10-14 NZ NZ503793A patent/NZ503793A/xx unknown
- 1998-10-14 DK DK98953459T patent/DK1025077T3/da active
- 1998-10-14 CN CNB988121492A patent/CN1231458C/zh not_active Expired - Fee Related
- 1998-10-14 JP JP2000515866A patent/JP2001519410A/ja active Pending
- 1998-10-14 IL IL13534398A patent/IL135343A0/xx active IP Right Grant
- 1998-10-14 AT AT98953459T patent/ATE355264T1/de not_active IP Right Cessation
- 1998-10-14 BR BR9813069-2A patent/BR9813069A/pt not_active Application Discontinuation
- 1998-10-14 DE DE69837210T patent/DE69837210T2/de not_active Expired - Lifetime
- 1998-10-14 TR TR2000/01012T patent/TR200001012T2/xx unknown
- 1998-10-14 CA CA2306343A patent/CA2306343C/en not_active Expired - Fee Related
-
2000
- 2000-03-29 IL IL135343A patent/IL135343A/en not_active IP Right Cessation
- 2000-04-13 NO NO20001938A patent/NO20001938L/no not_active Application Discontinuation
-
2007
- 2007-04-05 CY CY20071100491T patent/CY1106497T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
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