AU710149B2 - Estrogenic agents - Google Patents
Estrogenic agents Download PDFInfo
- Publication number
- AU710149B2 AU710149B2 AU18920/97A AU1892097A AU710149B2 AU 710149 B2 AU710149 B2 AU 710149B2 AU 18920/97 A AU18920/97 A AU 18920/97A AU 1892097 A AU1892097 A AU 1892097A AU 710149 B2 AU710149 B2 AU 710149B2
- Authority
- AU
- Australia
- Prior art keywords
- ethoxy
- methyl
- benzyl
- pharmaceutically acceptable
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired, expires
Links
- 239000000262 estrogen Substances 0.000 title claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 126
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 105
- 150000003839 salts Chemical class 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 85
- -1 C 1 -C 4 alkoxy Chemical group 0.000 claims description 51
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 44
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
- 239000000460 chlorine Substances 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 150000002475 indoles Chemical class 0.000 claims description 12
- 210000001519 tissue Anatomy 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 150000005215 alkyl ethers Chemical class 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004951 trihalomethoxy group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 206010065687 Bone loss Diseases 0.000 claims description 6
- 206010030247 Oestrogen deficiency Diseases 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
- 230000002357 endometrial effect Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229950010765 pivalate Drugs 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 159000000021 acetate salts Chemical class 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 238000011161 development Methods 0.000 claims description 3
- 230000035755 proliferation Effects 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- NPHFOFOYWYLBTF-UHFFFAOYSA-N 3-methyl-1h-indol-5-ol Chemical compound C1=C(O)C=C2C(C)=CNC2=C1 NPHFOFOYWYLBTF-UHFFFAOYSA-N 0.000 claims description 2
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 2
- CKPMAJHDNHAJOW-UHFFFAOYSA-N 1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C=1C=C(CN2C3=CC=CC=C3C=C2)C=CC=1OCCN1CCCCC1 CKPMAJHDNHAJOW-UHFFFAOYSA-N 0.000 claims 2
- LCBUPLPGMALPAB-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-methyl-2-phenylindol-5-ol Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=CC=C1 LCBUPLPGMALPAB-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- HLMMZYAZBSGGEA-UHFFFAOYSA-N 1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C1=CC2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 HLMMZYAZBSGGEA-UHFFFAOYSA-N 0.000 claims 1
- IOZPLJVUDWIYIN-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-3-methyl-5-phenylmethoxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C12=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C(C=2C=C3OCOC3=CC=2)N1CC(C=C1)=CC=C1OCCN1CCCCC1 IOZPLJVUDWIYIN-UHFFFAOYSA-N 0.000 claims 1
- GRNXCSPNKRKBIG-UHFFFAOYSA-N 2-(3-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=CC(O)=C1 GRNXCSPNKRKBIG-UHFFFAOYSA-N 0.000 claims 1
- UWLYKIFSJQWOHY-UHFFFAOYSA-N 3-methyl-2-(4-methylphenyl)-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(C)C=C1 UWLYKIFSJQWOHY-UHFFFAOYSA-N 0.000 claims 1
- DJMHECLYFXQQCT-UHFFFAOYSA-N 3-methyl-2-(4-methylphenyl)-5-phenylmethoxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C1=CC=C(C)C=C1 DJMHECLYFXQQCT-UHFFFAOYSA-N 0.000 claims 1
- BQYMNRMHTXRMGR-UHFFFAOYSA-N 3-methyl-2-phenyl-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=CC=C1 BQYMNRMHTXRMGR-UHFFFAOYSA-N 0.000 claims 1
- IPPCWZMRTPZJGB-UHFFFAOYSA-N 3-methyl-5-phenylmethoxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-2-(4-propan-2-yloxyphenyl)indole Chemical compound C1=CC(OC(C)C)=CC=C1C1=C(C)C2=CC(OCC=3C=CC=CC=3)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 IPPCWZMRTPZJGB-UHFFFAOYSA-N 0.000 claims 1
- ATXFFPXTECEUDK-UHFFFAOYSA-N 3-methyl-5-phenylmethoxy-2-(3-phenylmethoxyphenyl)-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 ATXFFPXTECEUDK-UHFFFAOYSA-N 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 348
- 238000005481 NMR spectroscopy Methods 0.000 description 147
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
- 238000006243 chemical reaction Methods 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 29
- 239000000047 product Substances 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 229960005309 estradiol Drugs 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- 229910001868 water Inorganic materials 0.000 description 23
- 241000700159 Rattus Species 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 19
- 229940011871 estrogen Drugs 0.000 description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 19
- 210000000988 bone and bone Anatomy 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical class C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 239000007858 starting material Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 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 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 238000003556 assay Methods 0.000 description 10
- 102000015694 estrogen receptors Human genes 0.000 description 10
- 108010038795 estrogen receptors Proteins 0.000 description 10
- 150000002431 hydrogen Chemical group 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 230000001833 anti-estrogenic effect Effects 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000000328 estrogen antagonist Substances 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 150000001412 amines Chemical class 0.000 description 8
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- UFZKWTITXBRSPK-UHFFFAOYSA-N (4-phenylmethoxyphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1OCC1=CC=CC=C1 UFZKWTITXBRSPK-UHFFFAOYSA-N 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 7
- 229940046836 anti-estrogen Drugs 0.000 description 7
- 239000003610 charcoal Substances 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 210000004291 uterus Anatomy 0.000 description 7
- 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 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
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- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- MKYMYZJJFMPDOA-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCC1=CC=CC=C1 MKYMYZJJFMPDOA-UHFFFAOYSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
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- MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical class BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 5
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- 210000000172 cytosol Anatomy 0.000 description 5
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 5
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- 229930182833 estradiol Natural products 0.000 description 5
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- 238000009472 formulation Methods 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 5
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- 239000002243 precursor Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- SMYMDRJWEFCCCI-UHFFFAOYSA-N trichloro(trichloromethoxy)methane Chemical compound ClC(Cl)(Cl)OC(Cl)(Cl)Cl SMYMDRJWEFCCCI-UHFFFAOYSA-N 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- MNSDXQDMZMYLNL-UHFFFAOYSA-N 1-(2-chloroethoxy)-4-(chloromethyl)benzene Chemical compound ClCCOC1=CC=C(CCl)C=C1 MNSDXQDMZMYLNL-UHFFFAOYSA-N 0.000 description 4
- CHIFTAQVXHNVRW-UHFFFAOYSA-N 1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=C1 CHIFTAQVXHNVRW-UHFFFAOYSA-N 0.000 description 4
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- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
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- WZEOZJQLTRFNCU-UHFFFAOYSA-N trifluoro(trifluoromethoxy)methane Chemical compound FC(F)(F)OC(F)(F)F WZEOZJQLTRFNCU-UHFFFAOYSA-N 0.000 description 4
- 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- GVSMQKKMAYLKMM-UHFFFAOYSA-N 3-chloro-1h-indole Chemical class C1=CC=C2C(Cl)=CNC2=C1 GVSMQKKMAYLKMM-UHFFFAOYSA-N 0.000 description 3
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 238000008940 Alkaline Phosphatase assay kit Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63397496A | 1996-04-19 | 1996-04-19 | |
| US633974 | 1996-04-19 | ||
| US08/833,271 US5998402A (en) | 1996-04-19 | 1997-04-04 | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents |
| US833271 | 1997-04-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1892097A AU1892097A (en) | 1997-10-23 |
| AU710149B2 true AU710149B2 (en) | 1999-09-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU18920/97A Expired AU710149B2 (en) | 1996-04-19 | 1997-04-17 | Estrogenic agents |
Country Status (26)
| Country | Link |
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| EP (1) | EP0802183B1 (en, 2012) |
| JP (1) | JP4093611B2 (en, 2012) |
| KR (1) | KR100480193B1 (en, 2012) |
| CN (1) | CN1106383C (en, 2012) |
| AR (1) | AR011503A1 (en, 2012) |
| AT (1) | ATE206701T1 (en, 2012) |
| AU (1) | AU710149B2 (en, 2012) |
| BR (1) | BRPI9715334B8 (en, 2012) |
| CO (1) | CO4900051A1 (en, 2012) |
| CY (2) | CY2325B1 (en, 2012) |
| CZ (1) | CZ291701B6 (en, 2012) |
| DE (2) | DE69707189T2 (en, 2012) |
| DK (1) | DK0802183T3 (en, 2012) |
| EA (1) | EA001448B1 (en, 2012) |
| ES (1) | ES2162198T3 (en, 2012) |
| FR (1) | FR09C0048I2 (en, 2012) |
| HU (1) | HU227077B1 (en, 2012) |
| IL (1) | IL120701A (en, 2012) |
| LU (1) | LU91608I2 (en, 2012) |
| MX (1) | MX9702865A (en, 2012) |
| NL (1) | NL300416I2 (en, 2012) |
| NO (2) | NO309564B1 (en, 2012) |
| NZ (1) | NZ314601A (en, 2012) |
| PT (1) | PT802183E (en, 2012) |
| SK (1) | SK281737B6 (en, 2012) |
| UA (1) | UA48148C2 (en, 2012) |
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| CA2287980A1 (en) | 1997-04-30 | 1998-11-05 | Daniel Jon Sall | Antithrombotic agents |
| DE69819539T2 (de) | 1997-05-01 | 2004-09-30 | Eli Lilly And Co., Indianapolis | Antithrombotische mittel |
| UA68365C2 (en) * | 1997-11-06 | 2004-08-16 | Wyeth Corp | Peroral contraception by combination of anti-estrogen and progestin |
| US6069153A (en) * | 1998-05-12 | 2000-05-30 | American Home Products Corporation | Indenoindoles and benzocarbazoles as estrogenic agents |
| EP1082319B1 (en) * | 1998-05-12 | 2006-09-13 | Wyeth | Benzocarbazole and indenoindole derived estrogenic agents |
| US6479535B1 (en) | 1998-05-15 | 2002-11-12 | Wyeth | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole and estrogen formulations |
| CA2331318A1 (en) * | 1998-05-15 | 1999-11-25 | James Harrison Pickar | Compositions comprising 2-phenyl-indole compounds and estrogen formulations |
| IL139130A (en) * | 1998-05-15 | 2005-11-20 | Wyeth Corp | 2-Phenyl-1 ä4-(2-aminoethoxy)-benzylü-indole in combination with estrogens |
| US6465445B1 (en) | 1998-06-11 | 2002-10-15 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| US7005428B1 (en) | 1998-06-11 | 2006-02-28 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| ATE258934T1 (de) | 1998-10-30 | 2004-02-15 | Lilly Co Eli | Azaindol derivate und ihre verwendung als antithrombotische wirkstoffe |
| TWI220898B (en) * | 1999-03-04 | 2004-09-11 | Wyeth Corp | N-substituted indolines as estrogenic agents |
| EP1159268A1 (en) * | 1999-03-04 | 2001-12-05 | American Home Products Corporation | N-SUBSTITUTED BENzOYL INDOLES AS ESTROGENIC AGENTS |
| US6380185B1 (en) | 1999-03-04 | 2002-04-30 | American Home Products Corporation | N-substituted benzoyl indoles as estrogenic agents |
| US6358943B1 (en) | 1999-03-04 | 2002-03-19 | American Home Products Corporation | N-substituted indolines as estrogenic agents |
| ATE316093T1 (de) * | 1999-09-13 | 2006-02-15 | Wyeth Corp | Glucopyranosid-konjugate von 2-(4-hydroxy-phenyl)-1-(4-(2-amin-1-yl-ethoxy)- enzyl)-1h-indol-5-olen |
| US6380166B1 (en) | 1999-09-13 | 2002-04-30 | American Home Products Corporation | Glucopyranosides conjugates of 2-(4-hydroxy-phenyl)-3-methyl-1-[4-(2-amin-1-yl-ethoxy)-benzyl]-1H-indol-5-ols |
| IL149990A0 (en) * | 2000-01-28 | 2002-12-01 | Endorech Inc | Selective estrogen receptor modulators in combination with estrogens |
| US20020013327A1 (en) * | 2000-04-18 | 2002-01-31 | Lee Andrew G. | Compositions and methods for treating female sexual dysfunction |
| US6358991B2 (en) * | 2000-07-06 | 2002-03-19 | American Home Products Corporation | Methods of treating neuropeptide Y-related conditions |
| AU2001271784A1 (en) * | 2000-07-06 | 2002-01-21 | Wyeth | Therapy for prosthesis-related bone degeneration |
| AU2001273074A1 (en) * | 2000-07-06 | 2002-01-21 | Wyeth | Combinations of ssri and estrogenic agents |
| US20020022617A1 (en) * | 2000-07-06 | 2002-02-21 | American Home Products Corporation | Methods for increasing nitric oxide synthase activity |
| AR030064A1 (es) * | 2000-07-06 | 2003-08-13 | Wyeth Corp | Metodos para inhibir los efectos uterotroficos de los agentes estrogenicos |
| AR029538A1 (es) * | 2000-07-06 | 2003-07-02 | Wyeth Corp | Composiciones farmaceuticas de agentes estrogenicos |
| AU2001271706A1 (en) * | 2000-07-06 | 2002-01-21 | American Home Products Corporation | Use of substituted indole compounds for treating breast disorders |
| WO2002003989A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for treating sphincter incontinence |
| AU2001271782A1 (en) | 2000-07-06 | 2002-01-21 | Wyeth | Use of substituted insole compounds for treating excessive intraocular pressure |
| EP1656938A1 (en) | 2000-07-06 | 2006-05-17 | Wyeth | Combinations of SSRI and estrogenic agents |
| EP1177787A3 (en) * | 2000-07-28 | 2003-09-10 | Pfizer Products Inc. | Use of an estrogen agonist/antagonist for treating cataracts |
| ATE321754T1 (de) | 2001-05-22 | 2006-04-15 | Lilly Co Eli | 2-substituierte 1,2,3,4-tetrahydrochinoline und derivate davon, zusammensetzungen und verfahren |
| 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 |
| UA85374C2 (en) * | 2002-06-13 | 2009-01-26 | Уайт | bazedoxifene treatment regimen |
| US7399867B2 (en) | 2002-07-22 | 2008-07-15 | Eli Lilly And Company | Selective estrogen receptor modulators containing a phenylsulfonyl group |
| WO2004058682A1 (ja) | 2002-12-26 | 2004-07-15 | Eisai Co., Ltd. | 選択的エストロゲン受容体モジュレーター |
| US7250440B2 (en) * | 2003-08-12 | 2007-07-31 | Wyeth | (Hydroxyphenyl)-1H-indole-3-carbaldehyde oxime derivatives as estrogenic agents |
| JP2007532560A (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多形 |
| RU2006132352A (ru) | 2004-04-07 | 2008-05-20 | Вайет (Us) | Кристаллическая полиморфная форма базедоксифен ацетата |
| BRPI0509385A (pt) | 2004-04-08 | 2007-09-18 | Wyeth Corp | composto, composição, métodos de preparar o sal, ea dispensão sólida, de tratar um mamìfero tendo uma doença ou sìndrome associadas com a deficiência de estrogênio ou excesso de estrogênio, uma doença ou distúrbio associados com a proliferação ou desenvolvimento anormal dos tecidos endometriais, de tratar cáncer de mama em um mamìfero, e uma mulher pós-menopáusica quanto a um ou mais distúrbios vasomotores, de reduzir colesterol, e de inibir perda óssea em um mamìfero, dispersão sólida, e, uso de um composto |
| EP1771169A1 (en) | 2004-07-14 | 2007-04-11 | PTC Therapeutics, Inc. | Methods for treating hepatitis c |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| MX2007000762A (es) | 2004-07-22 | 2007-04-02 | Ptc Therapeutics Inc | Tienopiridinas para tratamientode hepatitis c. |
| CA2575618A1 (en) * | 2004-08-05 | 2006-02-16 | Wyeth | Crystalline polymorph of pipindoxifene hydrochloride monohydrate |
| CN102406650A (zh) | 2004-10-20 | 2012-04-11 | 恩多研究公司 | 单独的性甾体前体或与选择性雌激素受体调节剂联合用于防治绝经后女性的阴道疾病和病症 |
| FR2880625B1 (fr) * | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| US20100087661A1 (en) * | 2007-02-12 | 2010-04-08 | Josef Jirman | Method for the preparation of 5-benzyloxy-2-(4-benzyloxphenyl)-3-methyl-1h-indole |
| US8268806B2 (en) | 2007-08-10 | 2012-09-18 | Endorecherche, Inc. | Pharmaceutical compositions |
| US8183367B2 (en) * | 2008-02-11 | 2012-05-22 | Wyeth Llc | Methods of preparing polymorphic form A of bazedoxifene acetate |
| JP5635493B2 (ja) | 2008-04-16 | 2014-12-03 | カロ バイオ アクチェブラーグ | 新規エストロゲン受容体リガンド |
| EP2419406A1 (en) * | 2009-04-13 | 2012-02-22 | Sandoz AG | Processes for the synthesis of bazedoxifene acetate and intermediates thereof |
| US20100317635A1 (en) | 2009-06-16 | 2010-12-16 | Endorecherche, Inc. | Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators |
| ITMI20091109A1 (it) | 2009-06-23 | 2010-12-24 | Wyeth Corp | Forma polimorfa d di bazedoxifene acetato e metodi per la sua preparazione |
| AU2011267798B2 (en) | 2010-06-16 | 2015-04-02 | Endorecherche, Inc. | Methods of treating or preventing estrogen-related diseases |
| US7968732B1 (en) | 2010-09-07 | 2011-06-28 | Divi's Laboratories, Ltd. | Process for the preparation of 5-benzyloxy-2-(4-benzyloxyphenyl)-3-methyl-1H-indole |
| WO2012037187A2 (en) | 2010-09-14 | 2012-03-22 | Dr. Reddy's Laboratories Ltd. | Preparation of crystalline bazedoxifene and its salts |
| US8569483B2 (en) | 2011-06-21 | 2013-10-29 | Divi's Laboratories, Ltd. | Process for the preparation of bazedoxifene acetate and intermediates thereof |
| CN102690225B (zh) * | 2012-04-11 | 2014-12-24 | 南京友杰医药科技有限公司 | 巴多昔芬的合成方法 |
| US9751835B2 (en) * | 2013-05-15 | 2017-09-05 | Indiana University Research And Technology Corporation | Processes and intermediates for preparing indole pharmaceuticals |
| US9744177B2 (en) | 2014-03-10 | 2017-08-29 | Endorecherche, Inc. | Treatment of male androgen deficiency symptoms or diseases with sex steroid precursor combined with SERM |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| US10420734B2 (en) | 2014-03-28 | 2019-09-24 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| WO2016097071A1 (en) * | 2014-12-18 | 2016-06-23 | F. Hoffmann-La Roche Ag | Estrogen receptor modulators and uses thereof |
| KR20190110400A (ko) | 2018-03-20 | 2019-09-30 | 엠에프씨 주식회사 | 새로운 중간체를 이용한 바제독시펜의 제조방법 |
| 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 |
| US11246874B1 (en) | 2021-04-20 | 2022-02-15 | Oxygen Biotech LLC | Treatment of COVID-19 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU373940A3 (en, 2012) * | 1970-01-21 | 1973-03-12 | ||
| DE2557342A1 (de) * | 1975-12-19 | 1977-06-30 | Hoechst Ag | Basisch substituierte indolderivate und verfahren zu ihrer herstellung |
| US4656187A (en) * | 1981-08-03 | 1987-04-07 | Eli Lilly And Company | Treatment of mammary cancer |
| DE3232968A1 (de) * | 1981-09-10 | 1983-06-09 | Degussa Ag, 6000 Frankfurt | Neue 2-(hydroxy-phenyl)-indole und verfahren zu deren herstellung |
| CA1241660A (en) * | 1984-06-25 | 1988-09-06 | Yvan Guindon | Indole-2-alkanoic acids |
| GB8707051D0 (en) * | 1986-04-15 | 1987-04-29 | Ici America Inc | Heterocyclic carboxamides |
| DE3821148A1 (de) * | 1988-06-23 | 1989-12-28 | Erwin Von Dr Angerer | Aminoalkylindole, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
| US5395842A (en) * | 1988-10-31 | 1995-03-07 | Endorecherche Inc. | Anti-estrogenic compounds and compositions |
| GB9004301D0 (en) * | 1990-02-26 | 1990-04-18 | Fujisawa Pharmaceutical Co | Indolebutyric acid derivatives and process for preparation thereof |
| US5051442A (en) * | 1990-04-25 | 1991-09-24 | Merrell Dow Pharmaceuticals Inc. | 3-indolyl thioacetate derivatives and NMDA receptor antagonistic use thereof |
| KR950701317A (ko) * | 1992-05-08 | 1995-03-23 | 오오쓰까 아끼히꼬 | 인돌 유도체(Indole Derivative) |
| DE69422450T2 (de) * | 1993-06-29 | 2000-06-08 | Takeda Chemical Industries, Ltd. | Chinoline oder Chinazolin-Derivate und deren Verwendung zur Herstellung eines Medikaments für die Behandlung von Osteoporose |
| GB9326332D0 (en) * | 1993-12-23 | 1994-02-23 | Karo Bio | Indole derivatives |
| DE4426625A1 (de) * | 1994-07-27 | 1996-03-14 | Schering Ag | 2-Phenylindole, Verfahren zu deren Herstellung, diese enthaltende pharmazeutische Präparate sowie deren Verwendung zur Herstellung von Arzneimitteln |
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