NZ314601A - 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole derivatives as estrogenic agents and pharmaceutical compositions - Google Patents
2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole derivatives as estrogenic agents and pharmaceutical compositionsInfo
- Publication number
- NZ314601A NZ314601A NZ314601A NZ31460197A NZ314601A NZ 314601 A NZ314601 A NZ 314601A NZ 314601 A NZ314601 A NZ 314601A NZ 31460197 A NZ31460197 A NZ 31460197A NZ 314601 A NZ314601 A NZ 314601A
- Authority
- NZ
- New Zealand
- Prior art keywords
- benzyl
- ethoxy
- methyl
- phenyl
- acceptable salt
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 239000000262 estrogen Substances 0.000 title description 23
- 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 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 125
- 150000003839 salts Chemical class 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 82
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- -1 tnhalomethyl Chemical group 0.000 claims description 29
- 150000002148 esters Chemical class 0.000 claims description 27
- 229960005309 estradiol Drugs 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- 125000004093 cyano group Chemical class *C#N 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 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
- 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 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 210000001519 tissue Anatomy 0.000 claims description 11
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical class 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 9
- 150000005215 alkyl ethers Chemical class 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 229910019142 PO4 Inorganic materials 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 206010065687 Bone loss Diseases 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 5
- 235000012000 cholesterol Nutrition 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 206010030247 Oestrogen deficiency Diseases 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 150000002170 ethers Chemical class 0.000 claims description 4
- 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 claims description 4
- 229960004622 raloxifene Drugs 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 230000002357 endometrial effect Effects 0.000 claims description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 229950010765 pivalate Drugs 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 208000037663 Best vitelliform macular dystrophy Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 230000037396 body weight Effects 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000011161 development Methods 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 210000002303 tibia Anatomy 0.000 claims description 2
- UMVQSSHQPMMTBP-UHFFFAOYSA-N 1-[[4-[2-(3,3-dimethylpiperidin-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CC(C)(C)CCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UMVQSSHQPMMTBP-UHFFFAOYSA-N 0.000 claims 1
- DNWWBBQJWGPFNQ-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]-3-methoxyphenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCCCCC2)C(OC)=CC=1CN(C1=CC=C(O)C=C1C=1C)C=1C1=CC=C(O)C=C1 DNWWBBQJWGPFNQ-UHFFFAOYSA-N 0.000 claims 1
- GLPVNLVSGIFUEL-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-methyl-2-phenyl-5-phenylmethoxyindole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C1=CC=CC=C1 GLPVNLVSGIFUEL-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- NPZACNAERPDSGY-UHFFFAOYSA-N 1-[[4-[2-(azocan-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 NPZACNAERPDSGY-UHFFFAOYSA-N 0.000 claims 1
- XIMOWWMQJVPDBJ-BGYRXZFFSA-N 1-[[4-[2-[(2R,6S)-2,6-dimethylpiperidin-1-yl]ethoxy]phenyl]methyl]indole Chemical compound C[C@@H]1N([C@@H](CCC1)C)CCOC1=CC=C(CN2C=CC3=CC=CC=C23)C=C1 XIMOWWMQJVPDBJ-BGYRXZFFSA-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
- CFBVBWXVYLXPJE-UHFFFAOYSA-N 2-(4-ethoxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C1=CC(OCC)=CC=C1C1=C(C)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 CFBVBWXVYLXPJE-UHFFFAOYSA-N 0.000 claims 1
- GZGPRSXNTFCESG-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-1-[[4-[2-(4-hydroxypiperidin-1-yl)ethoxy]phenyl]methyl]-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCC(O)CC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 GZGPRSXNTFCESG-UHFFFAOYSA-N 0.000 claims 1
- QFOMEAKDJGTPOK-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1-[[4-[2-(2-methylpiperidin-1-yl)ethoxy]phenyl]methyl]indol-5-ol Chemical compound CC1CCCCN1CCOC(C=C1)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 QFOMEAKDJGTPOK-UHFFFAOYSA-N 0.000 claims 1
- IRJAERPTWHZZOI-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1-[[4-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl]methyl]indol-5-ol Chemical compound C1CC(C)CCN1CCOC(C=C1)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 IRJAERPTWHZZOI-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
- WFLWMAKFIUHTIN-UHFFFAOYSA-N 5-hydroxy-2-(4-hydroxyphenyl)-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole-3-carbonitrile Chemical compound C1=CC(O)=CC=C1C1=C(C#N)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 WFLWMAKFIUHTIN-UHFFFAOYSA-N 0.000 claims 1
- 241000132446 Inula Species 0.000 claims 1
- UCJGJABZCDBEDK-UHFFFAOYSA-N bazedoxifene Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UCJGJABZCDBEDK-UHFFFAOYSA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 483
- 238000005481 NMR spectroscopy Methods 0.000 description 161
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 58
- 229910001868 water Inorganic materials 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 34
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- 239000007787 solid Substances 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 238000003786 synthesis reaction Methods 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 230000000694 effects Effects 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 19
- 229940011871 estrogen Drugs 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 210000000988 bone and bone Anatomy 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 150000002475 indoles Chemical class 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
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- 239000006260 foam Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 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 11
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- 102000015694 estrogen receptors Human genes 0.000 description 10
- 108010038795 estrogen receptors Proteins 0.000 description 10
- UFZKWTITXBRSPK-UHFFFAOYSA-N (4-phenylmethoxyphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1OCC1=CC=CC=C1 UFZKWTITXBRSPK-UHFFFAOYSA-N 0.000 description 9
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- 150000001412 amines Chemical class 0.000 description 9
- 230000001833 anti-estrogenic effect Effects 0.000 description 9
- 239000000328 estrogen antagonist Substances 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
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- 235000019341 magnesium sulphate Nutrition 0.000 description 8
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- 239000007858 starting material Substances 0.000 description 8
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- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 6
- GVSMQKKMAYLKMM-UHFFFAOYSA-N 3-chloro-1h-indole Chemical class C1=CC=C2C(Cl)=CNC2=C1 GVSMQKKMAYLKMM-UHFFFAOYSA-N 0.000 description 5
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- 239000002243 precursor Substances 0.000 description 5
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- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
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- 241001465754 Metazoa Species 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DFXWVJDNAQELDD-UHFFFAOYSA-N [4-(2-chloroethoxy)phenyl]methanol Chemical compound OCC1=CC=C(OCCCl)C=C1 DFXWVJDNAQELDD-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 4
- 150000007857 hydrazones Chemical class 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
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- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
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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
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- 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
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- 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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- 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
-
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63397496A | 1996-04-19 | 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ314601A true NZ314601A (en) | 1999-09-29 |
Family
ID=27092026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ314601A NZ314601A (en) | 1996-04-19 | 1997-04-15 | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole derivatives as estrogenic agents and pharmaceutical compositions |
Country Status (26)
Families Citing this family (68)
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| JP2001523254A (ja) | 1997-04-30 | 2001-11-20 | イーライ・リリー・アンド・カンパニー | 抗血栓剤 |
| ES2210747T3 (es) | 1997-05-01 | 2004-07-01 | Eli Lilly And Company | Agentes antitromboticos. |
| ID24568A (id) * | 1997-11-06 | 2000-07-27 | American Home Prod | Kontrasepsi oral yang mengandung anti-estrogen plus progestin |
| DE69933212D1 (de) * | 1998-05-12 | 2006-10-26 | Wyeth Corp | Benzocarbazol und indenoindole derivate als östrogene agentien |
| US6069153A (en) * | 1998-05-12 | 2000-05-30 | American Home Products Corporation | Indenoindoles and benzocarbazoles as estrogenic agents |
| US6479535B1 (en) | 1998-05-15 | 2002-11-12 | Wyeth | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole and estrogen formulations |
| EP1076558B1 (en) * | 1998-05-15 | 2003-07-16 | Wyeth | 2-phenyl-1-[-(2-aminoethoxy)-benzyl -indole in combination with estrogens |
| WO1999059969A1 (en) * | 1998-05-15 | 1999-11-25 | American Home Products Corporation | Compositions comprising 2-phenyl-indole compounds and estrogen formulations |
| US7005428B1 (en) | 1998-06-11 | 2006-02-28 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| US6465445B1 (en) | 1998-06-11 | 2002-10-15 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| DE69914563T2 (de) * | 1998-10-30 | 2004-12-16 | Eli Lilly And Co., Indianapolis | Azaindol derivate und ihre Verwendung als antithrombotische Wirkstoffe |
| TWI220898B (en) * | 1999-03-04 | 2004-09-11 | Wyeth Corp | N-substituted indolines as estrogenic agents |
| WO2000051983A1 (en) * | 1999-03-04 | 2000-09-08 | 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 |
| 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 |
| WO2001019839A1 (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 |
| SK9592002A3 (en) * | 2000-01-28 | 2003-12-02 | Endorech Inc | A method for reduction or elimination of the incidence of menopausal symptoms, method of treatment or decreasing the risk of an acquiring disease, a pharmaceutical composition and a kit |
| US20020013327A1 (en) * | 2000-04-18 | 2002-01-31 | Lee Andrew G. | Compositions and methods for treating female sexual dysfunction |
| AU2001273144A1 (en) * | 2000-07-06 | 2002-01-21 | Wyeth | Use of substituted indole compounds for treating neuropeptide y-related conditions |
| AR030064A1 (es) * | 2000-07-06 | 2003-08-13 | Wyeth Corp | Metodos para inhibir los efectos uterotroficos de los agentes estrogenicos |
| WO2002003989A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for treating sphincter incontinence |
| US20020016318A1 (en) * | 2000-07-06 | 2002-02-07 | American Home Products Corporation | Methods of treating breast disorders |
| CA2414111A1 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for increasing nitric oxide synthase activity |
| US6509332B2 (en) | 2000-07-06 | 2003-01-21 | Wyeth | Methods of treating excessive intraocular pressure |
| EP1311293A2 (en) * | 2000-07-06 | 2003-05-21 | Wyeth | Combinations of ssri and estrogenic agents |
| EP1656938A1 (en) | 2000-07-06 | 2006-05-17 | Wyeth | Combinations of SSRI and estrogenic agents |
| AR029538A1 (es) * | 2000-07-06 | 2003-07-02 | Wyeth Corp | Composiciones farmaceuticas de agentes estrogenicos |
| WO2002003992A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for treating prosthesis-related bone degeneration |
| EP1177787A3 (en) * | 2000-07-28 | 2003-09-10 | Pfizer Products Inc. | Use of an estrogen agonist/antagonist for treating cataracts |
| WO2002094788A1 (en) | 2001-05-22 | 2002-11-28 | Eli Lilly And Company | 2-substituted 1,2,3,4-tetrahydroquinolines and derivatives thereof, compositions and methods |
| ES2236536T3 (es) | 2001-05-22 | 2005-07-16 | Eli Lilly And Company | Derivados tetrahidroquinolino para la inhibicion de enfermedades asociadas con la privacion de estrogenos o con una respuesta fisiologica aberrante a estrogenos endogenos. |
| WO2003105834A1 (en) * | 2002-06-13 | 2003-12-24 | Wyeth | Bazedoxifene treatment regimens |
| BR0312675A (pt) | 2002-07-22 | 2005-05-03 | Lilly Co Eli | Composto ou um sal de adição de ácido farmacêutico do mesmo,m e, métodos para tratar endometriose, e para tratar leiomioma uterino |
| AU2003292625B2 (en) | 2002-12-26 | 2008-07-24 | Eisai R & D Management Co., Ltd. | Selective estrogen receptor modulators |
| 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 |
| TW200536845A (en) | 2004-04-07 | 2005-11-16 | Wyeth Corp | Crystalline polymorph of bazedoxifene acetate |
| 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 |
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| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
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| US20060030591A1 (en) * | 2004-08-05 | 2006-02-09 | Wyeth | Crystalline polymorph of pipindoxifene hydrochloride monohydrate |
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| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
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| CN107406424B (zh) * | 2014-12-18 | 2020-08-25 | 豪夫迈·罗氏有限公司 | 雌激素受体调节剂及其用途 |
| 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 |
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| SU373940A3 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 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 |
| CA2135160A1 (en) * | 1992-05-08 | 1993-11-25 | Masatoshi Inai | Indole derivative |
| ATE188377T1 (de) * | 1993-06-29 | 2000-01-15 | 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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1997
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