IL178562A - History of androgenic indole, pharmaceutical preparations containing them, and their uses - Google Patents
History of androgenic indole, pharmaceutical preparations containing them, and their usesInfo
- Publication number
- IL178562A IL178562A IL178562A IL17856206A IL178562A IL 178562 A IL178562 A IL 178562A IL 178562 A IL178562 A IL 178562A IL 17856206 A IL17856206 A IL 17856206A IL 178562 A IL178562 A IL 178562A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- cyano
- optionally substituted
- compound according
- nitro
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 15
- 150000002475 indoles Chemical class 0.000 title description 6
- 230000001548 androgenic effect Effects 0.000 title description 5
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 158
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
- -1 cyano, formyl Chemical group 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 239000003098 androgen Substances 0.000 claims description 21
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 21
- 108010080146 androgen receptors Proteins 0.000 claims description 18
- 102000001307 androgen receptors Human genes 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 16
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 16
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 229940030486 androgens Drugs 0.000 claims description 11
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 4
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 3
- 239000002583 male contraceptive agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- HCFFYOWYOSJBMJ-UHFFFAOYSA-N 1-(furan-3-ylmethyl)-n-methyl-3-(2-nitrophenyl)sulfanylindol-6-amine Chemical compound C=1N(CC2=COC=C2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O HCFFYOWYOSJBMJ-UHFFFAOYSA-N 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 238
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 108
- 238000000034 method Methods 0.000 description 96
- 239000000047 product Substances 0.000 description 94
- 229940093499 ethyl acetate Drugs 0.000 description 79
- 235000019439 ethyl acetate Nutrition 0.000 description 79
- 238000004440 column chromatography Methods 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 44
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
- 239000000203 mixture Substances 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
- 229910052938 sodium sulfate Inorganic materials 0.000 description 34
- 235000011152 sodium sulphate Nutrition 0.000 description 34
- 239000012267 brine Substances 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 32
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000007864 aqueous solution Substances 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 229920006395 saturated elastomer Polymers 0.000 description 27
- 239000002253 acid Substances 0.000 description 26
- 239000002585 base Substances 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
- 235000017557 sodium bicarbonate Nutrition 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- 101150041968 CDC13 gene Proteins 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 101000632319 Homo sapiens Septin-7 Proteins 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 102100027981 Septin-7 Human genes 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 238000005804 alkylation reaction Methods 0.000 description 13
- 239000002168 alkylating agent Substances 0.000 description 12
- 229940100198 alkylating agent Drugs 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- 230000029936 alkylation Effects 0.000 description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- PSWCIARYGITEOY-UHFFFAOYSA-N 6-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2C=CNC2=C1 PSWCIARYGITEOY-UHFFFAOYSA-N 0.000 description 8
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 108700008625 Reporter Genes Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 230000036515 potency Effects 0.000 description 5
- 230000003637 steroidlike Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 238000007126 N-alkylation reaction Methods 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 4
- 238000002657 hormone replacement therapy Methods 0.000 description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000000583 progesterone congener Substances 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- NTNKNFHIAFDCSJ-UHFFFAOYSA-N (2-nitrophenyl) thiohypochlorite Chemical compound [O-][N+](=O)C1=CC=CC=C1SCl NTNKNFHIAFDCSJ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 101100232079 Arabidopsis thaliana HSR4 gene Proteins 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 201000003585 eunuchism Diseases 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 208000037106 male hypogonadism Diseases 0.000 description 3
- BAQGCWNPCFABAY-UHFFFAOYSA-N methyl 2-sulfanylbenzoate Chemical compound COC(=O)C1=CC=CC=C1S BAQGCWNPCFABAY-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 3
- CXBJCROZMWLGAU-UHFFFAOYSA-N (2-bromophenyl) thiohypochlorite Chemical compound ClSC1=CC=CC=C1Br CXBJCROZMWLGAU-UHFFFAOYSA-N 0.000 description 2
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 2
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 108700012941 GNRH1 Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010058359 Hypogonadism Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
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- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
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- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- 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
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- 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
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- 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
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US56504304P | 2004-04-23 | 2004-04-23 | |
| EP04101700 | 2004-04-23 | ||
| PCT/EP2005/051766 WO2005102998A1 (en) | 2004-04-23 | 2005-04-21 | Novel androgens |
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| IL178562A0 IL178562A0 (en) | 2007-02-11 |
| IL178562A true IL178562A (en) | 2011-05-31 |
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Families Citing this family (13)
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| HRP20050396A2 (en) | 2002-11-07 | 2005-06-30 | Akzo Nobel N.V. | Indoles useful in the treatment of androgen-receptor related diseases |
| BRPI0907844B8 (pt) | 2008-02-22 | 2021-05-25 | Radius Health Inc | compostos e método para modular um receptor de andrógeno, processos de preparação e composição farmacêutica dos mesmos e seus usos |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| US8987319B2 (en) | 2010-02-04 | 2015-03-24 | Radius Health, Inc. | Selective androgen receptor modulators |
| PT2568806T (pt) | 2010-05-12 | 2016-08-05 | Radius Health Inc | Regimes terapêuticos |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| WO2012047617A1 (en) | 2010-09-28 | 2012-04-12 | Radius Health, Inc. | Selective androgen receptor modulators |
| PL3122426T3 (pl) | 2014-03-28 | 2023-05-15 | Duke University | Leczenie raka sutka z zastosowaniem selektywnych modulatorów receptora estrogenowego |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| SMT202200199T1 (it) | 2016-06-22 | 2022-07-21 | Ellipses Pharma Ltd | Metodi di trattamento del cancro del seno ar+. |
| EP4374925A3 (en) | 2017-01-05 | 2025-01-15 | Radius Pharmaceuticals, Inc. | Polymorphic forms of rad1901-2hcl |
| CN112423844B (zh) | 2018-07-04 | 2024-08-13 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
| CN119390714A (zh) | 2019-02-12 | 2025-02-07 | 雷迪厄斯制药公司 | 方法和化合物 |
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| 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 |
| JPS63313770A (ja) | 1987-06-16 | 1988-12-21 | Sumitomo Chem Co Ltd | イサチン誘導体、その製造法およびそれを有効成分とする除草剤 |
| ES2054784T3 (es) | 1987-08-08 | 1994-08-16 | Akzo Nv | Un metodo para la fabricacion de un implante. |
| DE3924052A1 (de) | 1989-07-21 | 1991-01-24 | Bayer Ag | N- (indol-6-yl)-heterocyclen |
| FR2662713B1 (fr) * | 1990-05-29 | 1994-04-08 | Oreal | Procede de teinture de fibres keratiniques avec un aminoindole associe a un derive quinonique. |
| FR2675380A1 (fr) | 1991-04-18 | 1992-10-23 | Oreal | Procede de teinture des fibres keratiniques avec des aminoindoles, a ph basique, compositions mises en óoeuvre et nouveaux composes. |
| US5938792A (en) * | 1991-04-18 | 1999-08-17 | L'oreal | Process for dyeing keratinous fibers with aminoindoles and oxidation dye precursors at basic Ph's and dyeing agents |
| GB9204365D0 (en) | 1992-02-28 | 1992-04-08 | Pfizer Ltd | Indoles |
| US5482960A (en) | 1994-11-14 | 1996-01-09 | Warner-Lambert Company | Nonpeptide endothelin antagonists |
| JP3107290B2 (ja) * | 1996-05-20 | 2000-11-06 | 株式会社日立製作所 | 燃料装荷方法 |
| HUP9904215A3 (en) | 1996-11-25 | 2002-01-28 | Procter & Gamble | 2-imidazolinylaminoindole compounds useful as alpha-2 adrenoceptor agonists |
| TW358031B (en) | 1997-04-11 | 1999-05-11 | Akze Nobel N V | Drug delivery system for 2 or more active substances |
| US5969155A (en) * | 1997-04-11 | 1999-10-19 | The United States Of America As Represented By The Secretary Of The Army | Conversion of trinitrotoluene into high value compounds |
| HUP0100156A3 (en) | 1998-02-25 | 2002-12-28 | Genetics Inst Inc Cambridge | Indole derivatives as inhibitors of phospholipase a2 and use of them for producing pharmaceutical compositions |
| JP2002504539A (ja) | 1998-02-25 | 2002-02-12 | ジェネティックス・インスチチュート・インコーポレーテッド | ホスホリパーゼ酵素の阻害剤 |
| GB9819033D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds VI |
| US6645974B2 (en) | 2001-07-31 | 2003-11-11 | Merck & Co., Inc. | Androgen receptor modulators and methods for use thereof |
| US6933316B2 (en) * | 2001-12-13 | 2005-08-23 | National Health Research Institutes | Indole compounds |
| JP4316232B2 (ja) * | 2001-12-28 | 2009-08-19 | 武田薬品工業株式会社 | アンドロゲン受容体拮抗剤 |
| AU2002367424A1 (en) | 2001-12-28 | 2003-07-24 | Takeda Chemical Industries, Ltd. | Androgen receptor antagonists |
| PL373410A1 (en) * | 2002-02-01 | 2005-08-22 | F.Hoffman-La Roche Ag | Substituted indoles as alpha-1 agonists |
| UA79504C2 (en) * | 2002-11-07 | 2007-06-25 | Organon Nv | Indols for treating diseases associated with androgen receptors |
| HRP20050396A2 (en) * | 2002-11-07 | 2005-06-30 | Akzo Nobel N.V. | Indoles useful in the treatment of androgen-receptor related diseases |
| RU2313524C2 (ru) * | 2003-05-09 | 2007-12-27 | Ф.Хоффманн-Ля Рош Аг | МИТИЛИНДОЛЫ И МЕТИЛПИРРОЛОПИРИДИНЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ АКТИВНОСТЬЮ α-1-АДРЕНЕРГИЧЕСКИХ АГОНИСТОВ |
-
2005
- 2005-04-13 TW TW094111712A patent/TW200602317A/zh unknown
- 2005-04-21 PE PE2005000446A patent/PE20060196A1/es not_active Application Discontinuation
- 2005-04-21 JP JP2007508908A patent/JP4997101B2/ja not_active Expired - Fee Related
- 2005-04-21 US US11/587,192 patent/US7812036B2/en not_active Expired - Fee Related
- 2005-04-21 EP EP05737941A patent/EP1742912B1/en not_active Expired - Lifetime
- 2005-04-21 CN CN2005800164068A patent/CN1956954B/zh not_active Expired - Fee Related
- 2005-04-21 BR BRPI0510078-0A patent/BRPI0510078A/pt not_active IP Right Cessation
- 2005-04-21 MX MXPA06012201A patent/MXPA06012201A/es active IP Right Grant
- 2005-04-21 DE DE602005023145T patent/DE602005023145D1/de not_active Expired - Lifetime
- 2005-04-21 ES ES05737941T patent/ES2349754T3/es not_active Expired - Lifetime
- 2005-04-21 WO PCT/EP2005/051766 patent/WO2005102998A1/en not_active Ceased
- 2005-04-21 CA CA2562571A patent/CA2562571C/en not_active Expired - Fee Related
- 2005-04-21 AU AU2005235751A patent/AU2005235751B2/en not_active Ceased
- 2005-04-21 AT AT05737941T patent/ATE478844T1/de not_active IP Right Cessation
- 2005-04-22 MY MYPI20051785A patent/MY144304A/en unknown
- 2005-04-22 AR ARP050101602A patent/AR049885A1/es unknown
-
2006
- 2006-10-15 IL IL178562A patent/IL178562A/en not_active IP Right Cessation
-
2010
- 2010-09-22 US US12/887,607 patent/US20110009428A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AR049885A1 (es) | 2006-09-13 |
| CN1956954A (zh) | 2007-05-02 |
| CA2562571C (en) | 2013-01-08 |
| AU2005235751A1 (en) | 2005-11-03 |
| JP4997101B2 (ja) | 2012-08-08 |
| EP1742912B1 (en) | 2010-08-25 |
| MY144304A (en) | 2011-08-29 |
| PE20060196A1 (es) | 2006-04-01 |
| WO2005102998A1 (en) | 2005-11-03 |
| AU2005235751B2 (en) | 2011-03-24 |
| CA2562571A1 (en) | 2005-11-03 |
| US20070225352A1 (en) | 2007-09-27 |
| IL178562A0 (en) | 2007-02-11 |
| ES2349754T3 (es) | 2011-01-11 |
| DE602005023145D1 (de) | 2010-10-07 |
| BRPI0510078A (pt) | 2007-10-16 |
| US20110009428A1 (en) | 2011-01-13 |
| EP1742912A1 (en) | 2007-01-17 |
| ATE478844T1 (de) | 2010-09-15 |
| MXPA06012201A (es) | 2007-01-17 |
| JP2007533707A (ja) | 2007-11-22 |
| US7812036B2 (en) | 2010-10-12 |
| CN1956954B (zh) | 2011-05-04 |
| TW200602317A (en) | 2006-01-16 |
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