RU2722441C2 - Замещённые индольные соединения в качестве понижающих регуляторов рецепторов эстрогена - Google Patents
Замещённые индольные соединения в качестве понижающих регуляторов рецепторов эстрогена Download PDFInfo
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- RU2722441C2 RU2722441C2 RU2018135203A RU2018135203A RU2722441C2 RU 2722441 C2 RU2722441 C2 RU 2722441C2 RU 2018135203 A RU2018135203 A RU 2018135203A RU 2018135203 A RU2018135203 A RU 2018135203A RU 2722441 C2 RU2722441 C2 RU 2722441C2
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- 102000015694 estrogen receptors Human genes 0.000 title claims abstract description 41
- 108010038795 estrogen receptors Proteins 0.000 title claims abstract description 41
- 150000002475 indoles Chemical class 0.000 title abstract description 3
- 208000035327 Oestrogen receptor positive breast cancer Diseases 0.000 claims abstract description 10
- 201000007281 estrogen-receptor positive breast cancer Diseases 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 133
- 150000003839 salts Chemical class 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 229910052731 fluorine Inorganic materials 0.000 claims description 35
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- 229910052794 bromium Inorganic materials 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 26
- 229910052740 iodine Inorganic materials 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 3
- -1 indole compound Chemical class 0.000 abstract description 81
- 239000003814 drug Substances 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 11
- 239000000126 substance Substances 0.000 abstract description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 325
- 238000006243 chemical reaction Methods 0.000 description 268
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 266
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 188
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
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- 229910052757 nitrogen Inorganic materials 0.000 description 111
- 239000012043 crude product Substances 0.000 description 96
- 235000019439 ethyl acetate Nutrition 0.000 description 90
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 82
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 79
- 239000012074 organic phase Substances 0.000 description 78
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 74
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 67
- 239000000203 mixture Substances 0.000 description 66
- 239000000047 product Substances 0.000 description 66
- 238000005481 NMR spectroscopy Methods 0.000 description 59
- 235000019253 formic acid Nutrition 0.000 description 56
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 55
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 53
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 45
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000002953 preparative HPLC Methods 0.000 description 35
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 34
- 239000000460 chlorine Substances 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- 239000012299 nitrogen atmosphere Substances 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 29
- 239000012267 brine Substances 0.000 description 29
- 239000000706 filtrate Substances 0.000 description 29
- 235000011167 hydrochloric acid Nutrition 0.000 description 29
- 238000010898 silica gel chromatography Methods 0.000 description 28
- 239000007864 aqueous solution Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 25
- 125000005842 heteroatom Chemical group 0.000 description 25
- 125000001424 substituent group Chemical group 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 206010006187 Breast cancer Diseases 0.000 description 21
- 208000026310 Breast neoplasm Diseases 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 238000004237 preparative chromatography Methods 0.000 description 20
- 125000003118 aryl group Chemical group 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 18
- 125000004429 atom Chemical group 0.000 description 17
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 16
- 125000003410 quininyl group Chemical group 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 15
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 15
- 239000012046 mixed solvent Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 14
- 229940125797 compound 12 Drugs 0.000 description 14
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 239000012634 fragment Substances 0.000 description 13
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
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- 229910000024 caesium carbonate Inorganic materials 0.000 description 11
- 238000012746 preparative thin layer chromatography Methods 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- BURHGPHDEVGCEZ-KJGLQBJMSA-N (e)-3-[4-[(e)-2-(2-chloro-4-fluorophenyl)-1-(1h-indazol-5-yl)but-1-enyl]phenyl]prop-2-enoic acid Chemical compound C=1C=C(F)C=C(Cl)C=1C(/CC)=C(C=1C=C2C=NNC2=CC=1)\C1=CC=C(\C=C\C(O)=O)C=C1 BURHGPHDEVGCEZ-KJGLQBJMSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
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- 229910052760 oxygen Inorganic materials 0.000 description 9
- SYKXNRFLNZUGAJ-UHFFFAOYSA-N platinum;triphenylphosphane Chemical compound [Pt].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 SYKXNRFLNZUGAJ-UHFFFAOYSA-N 0.000 description 9
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 9
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- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
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- 125000001072 heteroaryl group Chemical group 0.000 description 8
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
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- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 7
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- 229910052796 boron Inorganic materials 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 7
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- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
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- 239000012298 atmosphere Substances 0.000 description 5
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- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 5
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
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- 125000003226 pyrazolyl group Chemical group 0.000 description 4
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 3
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Classifications
-
- 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
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/06—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 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
-
- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| CN201610180518.7 | 2016-03-25 | ||
| CN201610180518 | 2016-03-25 | ||
| CN201610867918.5 | 2016-09-29 | ||
| CN201610867918 | 2016-09-29 | ||
| PCT/CN2017/078139 WO2017162206A1 (zh) | 2016-03-25 | 2017-03-24 | 作为雌激素受体降解剂的吲哚并取代哌啶类化合物 |
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| CN111032627B (zh) * | 2017-09-25 | 2023-10-20 | 罗欣健康科技发展(北京)有限公司 | 一种雌激素受体抑制剂的晶型及其制备方法 |
| CN113490850B (zh) | 2018-08-17 | 2024-12-06 | 基因泰克公司 | 用于治疗乳腺癌的诊断和治疗方法 |
| KR102858291B1 (ko) * | 2018-11-28 | 2025-09-12 | 뤄신 파마슈티컬 (상하이) 컴퍼니 리미티드 | 에스트로겐 수용체 하향 조절제의 염 형태와 결정형, 및 이의 제조방법 |
| BR112021011728A8 (pt) * | 2018-12-17 | 2023-01-31 | Chia Tai Tianqing Pharmaceutical Group Co Ltd | Antagonista do receptor de estrogênio |
| CN116891461A (zh) * | 2022-03-30 | 2023-10-17 | 罗欣药业(上海)有限公司 | 一种serd中间体的合成方法 |
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| WO2015136017A1 (en) * | 2014-03-13 | 2015-09-17 | F. Hoffmann-La Roche Ag | Methods and compositions for modulating estrogen receptor mutants |
| WO2015136016A2 (en) * | 2014-03-13 | 2015-09-17 | F. Hoffmann-La Roche Ag | Therapeutic combinations with estrogen receptor modulators |
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| US20100317635A1 (en) * | 2009-06-16 | 2010-12-16 | Endorecherche, Inc. | Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators |
| GB0917571D0 (en) * | 2009-10-07 | 2009-11-25 | Karobio Ab | Novel estrogen receptor ligands |
| NZ630124A (en) | 2012-03-20 | 2016-01-29 | Seragon Pharmaceuticals Inc | Estrogen receptor modulators and uses thereof |
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- 2017-03-24 KR KR1020187030877A patent/KR102111792B1/ko active Active
- 2017-03-24 RU RU2018135203A patent/RU2722441C2/ru active
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- 2017-03-24 JP JP2019500726A patent/JP6790222B2/ja active Active
- 2017-03-24 WO PCT/CN2017/078139 patent/WO2017162206A1/zh not_active Ceased
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| EA000815B1 (ru) * | 1996-04-19 | 2000-04-24 | Американ Хоум Продактс Корпорейшн | Производные индола в качестве эстрогенных агентов |
| WO2012037411A2 (en) * | 2010-09-16 | 2012-03-22 | Aragon Pharmaceuticals, Inc. | Estrogen receptor modulators and uses thereof |
| WO2015136017A1 (en) * | 2014-03-13 | 2015-09-17 | F. Hoffmann-La Roche Ag | Methods and compositions for modulating estrogen receptor mutants |
| WO2015136016A2 (en) * | 2014-03-13 | 2015-09-17 | F. Hoffmann-La Roche Ag | Therapeutic combinations with estrogen receptor modulators |
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| CA3018801A1 (en) | 2017-09-28 |
| CN108884035A (zh) | 2018-11-23 |
| KR20180128456A (ko) | 2018-12-03 |
| ES2821407T3 (es) | 2021-04-26 |
| RU2018135203A (ru) | 2020-04-27 |
| HK1256936A1 (zh) | 2019-10-04 |
| US20190106414A1 (en) | 2019-04-11 |
| AU2017239348A1 (en) | 2018-11-15 |
| EP3434668B1 (en) | 2020-08-26 |
| KR102111792B1 (ko) | 2020-05-18 |
| EP3434668A1 (en) | 2019-01-30 |
| SG11201808363TA (en) | 2018-10-30 |
| CA3018801C (en) | 2020-06-23 |
| JP2019512550A (ja) | 2019-05-16 |
| WO2017162206A1 (zh) | 2017-09-28 |
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