UA79504C2 - Indols for treating diseases associated with androgen receptors - Google Patents
Indols for treating diseases associated with androgen receptors Download PDFInfo
- Publication number
- UA79504C2 UA79504C2 UAA200503773A UA2005003773A UA79504C2 UA 79504 C2 UA79504 C2 UA 79504C2 UA A200503773 A UAA200503773 A UA A200503773A UA 2005003773 A UA2005003773 A UA 2005003773A UA 79504 C2 UA79504 C2 UA 79504C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- pyridin
- nitrophenyl
- indole
- hydroxy
- Prior art date
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- 102000001307 androgen receptors Human genes 0.000 title abstract description 22
- 108010080146 androgen receptors Proteins 0.000 title abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 17
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 16
- 201000010099 disease Diseases 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 134
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- -1 2-nitrophenyl Chemical group 0.000 claims abstract description 98
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 36
- 150000002367 halogens Chemical class 0.000 claims abstract description 31
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 29
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 18
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims abstract description 13
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 12
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 8
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000006574 non-aromatic ring group Chemical group 0.000 claims abstract description 5
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 15
- 125000005843 halogen group Chemical group 0.000 claims abstract 5
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 31
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- OTTXCOAOKOEENK-UHFFFAOYSA-N 2,2-difluoroethenone Chemical group FC(F)=C=O OTTXCOAOKOEENK-UHFFFAOYSA-N 0.000 claims description 8
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 5
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 11
- 230000003637 steroidlike Effects 0.000 abstract description 4
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 abstract 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- 239000000203 mixture Substances 0.000 description 65
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 239000012043 crude product Substances 0.000 description 22
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000012267 brine Substances 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 238000007429 general method Methods 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 208000035475 disorder Diseases 0.000 description 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000002475 indoles Chemical class 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 11
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- 239000003098 androgen Substances 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- NTNKNFHIAFDCSJ-UHFFFAOYSA-N (2-nitrophenyl) thiohypochlorite Chemical compound [O-][N+](=O)C1=CC=CC=C1SCl NTNKNFHIAFDCSJ-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 125000001041 indolyl group Chemical group 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 206010002261 Androgen deficiency Diseases 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- UPPZRAXFGLPSDA-UHFFFAOYSA-N 6-methoxy-3-(2-nitrophenyl)sulfanyl-1-(pyridin-2-ylmethyl)indole Chemical compound C=1N(CC=2N=CC=CC=2)C2=CC(OC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O UPPZRAXFGLPSDA-UHFFFAOYSA-N 0.000 description 5
- 230000001548 androgenic effect Effects 0.000 description 5
- 229940030486 androgens Drugs 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- KVSVNRFSKRFPIL-UHFFFAOYSA-N 1-(bromomethyl)-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(CBr)=C1 KVSVNRFSKRFPIL-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 230000002280 anti-androgenic effect Effects 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- ARXBGRULZDYQEF-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-6-methoxyindole Chemical compound C12=CC(OC)=CC=C2C=CN1CC1=CC(F)=CC(F)=C1 ARXBGRULZDYQEF-UHFFFAOYSA-N 0.000 description 3
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 3
- 150000001408 amides Chemical group 0.000 description 3
- 239000000051 antiandrogen Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
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- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 3
- 125000004492 methyl ester group Chemical group 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
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- 238000000746 purification Methods 0.000 description 3
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- 239000012265 solid product Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 2
- QNQVDTTWHQKRGP-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-6-methoxy-3-(2-nitrophenyl)sulfanylindole Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(OC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O QNQVDTTWHQKRGP-UHFFFAOYSA-N 0.000 description 2
- CWIPIYXFHAQWHN-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-6-nitroindole Chemical compound C12=CC([N+](=O)[O-])=CC=C2C=CN1CC1=CC(F)=CC(F)=C1 CWIPIYXFHAQWHN-UHFFFAOYSA-N 0.000 description 2
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- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 2
- UNLZMZRDMYJNPT-UHFFFAOYSA-N 6-methoxy-3-(2-nitrophenyl)sulfanyl-1h-indole Chemical compound C=1NC2=CC(OC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O UNLZMZRDMYJNPT-UHFFFAOYSA-N 0.000 description 2
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- 239000005711 Benzoic acid Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 101000775732 Homo sapiens Androgen receptor Proteins 0.000 description 2
- 101000928259 Homo sapiens NADPH:adrenodoxin oxidoreductase, mitochondrial Proteins 0.000 description 2
- 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 2
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- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
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- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42457902P | 2002-11-07 | 2002-11-07 | |
| EP02079648 | 2002-11-07 | ||
| PCT/EP2003/050783 WO2004041782A1 (en) | 2002-11-07 | 2003-11-03 | Indoles useful in the treatment of androgen-receptor related diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA79504C2 true UA79504C2 (en) | 2007-06-25 |
Family
ID=42635437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA200503773A UA79504C2 (en) | 2002-11-07 | 2003-03-11 | Indols for treating diseases associated with androgen receptors |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP1585727B1 (de) |
| JP (1) | JP4643989B2 (de) |
| CN (1) | CN100391944C (de) |
| AT (1) | ATE469128T1 (de) |
| AU (1) | AU2003301853B2 (de) |
| BR (1) | BR0316020A (de) |
| CA (1) | CA2504907C (de) |
| ES (1) | ES2344836T3 (de) |
| NZ (1) | NZ539657A (de) |
| PL (1) | PL376728A1 (de) |
| RS (1) | RS20050340A (de) |
| RU (1) | RU2328484C2 (de) |
| TW (1) | TWI310032B (de) |
| UA (1) | UA79504C2 (de) |
| WO (1) | WO2004041782A1 (de) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200602317A (en) | 2004-04-23 | 2006-01-16 | Akzo Nobel Nv | Novel androgens |
| DE102004047272A1 (de) * | 2004-09-24 | 2006-04-06 | Schering Ag | Inhibitoren der löslichen Adenylatzyklase |
| US7417066B2 (en) | 2005-06-08 | 2008-08-26 | Schering Ag | Inhibitors of soluble adenylate cyclase |
| DE102005027274A1 (de) * | 2005-06-08 | 2006-12-14 | Schering Ag | Inhibitoren der löslichen Adenylatzyklase |
| CN101203491A (zh) * | 2005-06-24 | 2008-06-18 | 伊莱利利公司 | 可用作雄激素受体调节剂的四氢咔唑衍生物（sarm） |
| WO2007073231A1 (en) * | 2005-12-23 | 2007-06-28 | Victor Lvovoch Limonov | Agent for treating tumoral diseases, a method for the production thereof and a method for treating tumoral diseases |
| DE102006014324B4 (de) * | 2006-03-23 | 2009-01-08 | Bayer Schering Pharma Aktiengesellschaft | Inhibitoren der löslichen Adenylatzyklase |
| ES2593379T3 (es) | 2006-03-27 | 2016-12-09 | The Regents Of The University Of California | Modulador del receptor de andrógenos para el tratamiento del cáncer de próstata y enfermedades asociadas con el receptor de andrógenos |
| ES2452343T3 (es) * | 2006-09-29 | 2014-04-01 | Glaxosmithkline Llc | Compuestos de indol sustituidos |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| JP5308458B2 (ja) | 2008-02-22 | 2013-10-09 | ラジウス ヘルス，インコーポレイテッド | 選択的アンドロゲン受容体調節物質 |
| RU2408592C2 (ru) * | 2008-12-31 | 2011-01-10 | Федеральное государственное образовательное учреждение высшего профессионального образования "ЮЖНЫЙ ФЕДЕРАЛЬНЫЙ УНИВЕРСИТЕТ" (ЮФУ) | Гидрогалогениды 3-[1-(2-гидрокси-3-пиперидин-1-ил-пропил)-1н-индол-3-ил]-1-фенил-пропенона, обладающие местноанестезирующей и антиаритмической активностью |
| US8987319B2 (en) | 2010-02-04 | 2015-03-24 | Radius Health, Inc. | Selective androgen receptor modulators |
| LT2568806T (lt) | 2010-05-12 | 2016-09-26 | Radius Health, Inc. | Terapiniai režimai |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| ES2550319T3 (es) | 2010-09-28 | 2015-11-06 | Radius Health, Inc | Moduladores selectivos del receptor de andrógenos |
| SG10201902568YA (en) | 2012-09-26 | 2019-04-29 | Aragon Pharmaceuticals Inc | Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer |
| RS64115B1 (sr) | 2014-03-28 | 2023-04-28 | Univ Duke | Lečenje kancera dojke upotrebom selektivnih modulatora receptora estrogena |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| EP4066827A1 (de) | 2016-06-22 | 2022-10-05 | Ellipses Pharma Ltd | Verfahren zur behandlung von ar+-brustkrebs |
| CN117417263A (zh) | 2017-01-05 | 2024-01-19 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
| CN113861186B (zh) * | 2021-09-10 | 2023-08-25 | 浙江师范大学 | 基于异恶唑取代苯甲酰胺类衍生物及抗前列腺癌药物应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ179580A (en) * | 1974-12-30 | 1978-04-03 | Mcneilab Inc | 2-or 3-(w-tertiaryaminoalkyl)-thioindoles and the corresponding sulfinyl and sulfonyl analogs |
| US4059583A (en) * | 1975-11-13 | 1977-11-22 | Mcneil Laboratories, Incorporated | Substituted indoles |
| GB9204365D0 (en) * | 1992-02-28 | 1992-04-08 | Pfizer Ltd | Indoles |
| ATE340792T1 (de) * | 2002-02-01 | 2006-10-15 | Hoffmann La Roche | Substituierte indole als alpha-1 agonisten |
| TW200401641A (en) * | 2002-07-18 | 2004-02-01 | Wyeth Corp | 1-Heterocyclylalkyl-3-sulfonylindole or-indazole derivatives as 5-hydroxytryptamine-6 ligands |
-
2003
- 2003-03-11 UA UAA200503773A patent/UA79504C2/uk unknown
- 2003-10-30 TW TW092130277A patent/TWI310032B/zh not_active IP Right Cessation
- 2003-11-03 AT AT03810458T patent/ATE469128T1/de not_active IP Right Cessation
- 2003-11-03 BR BR0316020-3A patent/BR0316020A/pt not_active IP Right Cessation
- 2003-11-03 ES ES03810458T patent/ES2344836T3/es not_active Expired - Lifetime
- 2003-11-03 CN CNB2003801039507A patent/CN100391944C/zh not_active Expired - Fee Related
- 2003-11-03 JP JP2004549180A patent/JP4643989B2/ja not_active Expired - Fee Related
- 2003-11-03 RS YUP-2005/0340A patent/RS20050340A/sr unknown
- 2003-11-03 NZ NZ539657A patent/NZ539657A/en not_active IP Right Cessation
- 2003-11-03 RU RU2005117374/04A patent/RU2328484C2/ru not_active IP Right Cessation
- 2003-11-03 EP EP03810458A patent/EP1585727B1/de not_active Expired - Lifetime
- 2003-11-03 PL PL376728A patent/PL376728A1/pl not_active Application Discontinuation
- 2003-11-03 AU AU2003301853A patent/AU2003301853B2/en not_active Ceased
- 2003-11-03 WO PCT/EP2003/050783 patent/WO2004041782A1/en not_active Ceased
- 2003-11-03 CA CA2504907A patent/CA2504907C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NZ539657A (en) | 2008-04-30 |
| ES2344836T3 (es) | 2010-09-08 |
| TW200418793A (en) | 2004-10-01 |
| RU2328484C2 (ru) | 2008-07-10 |
| CA2504907A1 (en) | 2004-05-21 |
| BR0316020A (pt) | 2005-09-20 |
| JP4643989B2 (ja) | 2011-03-02 |
| RS20050340A (sr) | 2007-06-04 |
| EP1585727A1 (de) | 2005-10-19 |
| WO2004041782A1 (en) | 2004-05-21 |
| CA2504907C (en) | 2011-10-11 |
| TWI310032B (en) | 2009-05-21 |
| PL376728A1 (pl) | 2006-01-09 |
| EP1585727B1 (de) | 2010-05-26 |
| CN1714078A (zh) | 2005-12-28 |
| CN100391944C (zh) | 2008-06-04 |
| AU2003301853B2 (en) | 2010-02-18 |
| JP2006507293A (ja) | 2006-03-02 |
| ATE469128T1 (de) | 2010-06-15 |
| RU2005117374A (ru) | 2006-01-20 |
| AU2003301853A1 (en) | 2004-06-07 |
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