CA2490580C - Selective estrogen receptor modulators containing a naphthalene group - Google Patents

Info

Publication number

CA2490580C

CA2490580C CA2490580A CA2490580A CA2490580C CA 2490580 C CA2490580 C CA 2490580C CA 2490580 A CA2490580 A CA 2490580A CA 2490580 A CA2490580 A CA 2490580A CA 2490580 C CA2490580 C CA 2490580C

Authority

CA

Canada

Prior art keywords

mmol

add

compound

phenyl

dry

Prior art date

2002-07-22

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• 229940095743 selective estrogen receptor modulator Drugs 0.000 title abstract description 11
• 239000000333 selective estrogen receptor modulator Substances 0.000 title abstract description 11
• 125000001624 naphthyl group Chemical group 0.000 title 1
• 150000003839 salts Chemical class 0.000 claims abstract description 43
• 239000002253 acid Substances 0.000 claims abstract description 39
• 201000009273 Endometriosis Diseases 0.000 claims abstract description 12
• 201000010260 leiomyoma Diseases 0.000 claims abstract description 11
• 206010046798 Uterine leiomyoma Diseases 0.000 claims abstract description 9
• 201000007954 uterine fibroid Diseases 0.000 claims abstract description 9
• 150000001875 compounds Chemical class 0.000 claims description 346
• -1 NR3R3a Chemical group 0.000 claims description 60
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 7
• 101150047265 COR2 gene Proteins 0.000 claims description 6
• 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
• 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 claims description 4
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 655
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 405
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 354
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 350
• 238000003756 stirring Methods 0.000 description 181
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 171
• 239000012141 concentrate Substances 0.000 description 151
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 150
• 235000008504 concentrate Nutrition 0.000 description 150
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 140
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 133
• 235000019439 ethyl acetate Nutrition 0.000 description 128
• 239000000243 solution Substances 0.000 description 123
• 239000012044 organic layer Substances 0.000 description 117
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 110
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 108
• 238000006243 chemical reaction Methods 0.000 description 104
• 229910001868 water Inorganic materials 0.000 description 103
• 239000000203 mixture Substances 0.000 description 96
• 229920006395 saturated elastomer Polymers 0.000 description 89
• 239000012267 brine Substances 0.000 description 87
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 87
• 239000007921 spray Substances 0.000 description 84
• 150000002500 ions Chemical class 0.000 description 83
• 238000001819 mass spectrum Methods 0.000 description 82
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
• 239000010410 layer Substances 0.000 description 79
• 229910052938 sodium sulfate Inorganic materials 0.000 description 79
• 235000011152 sodium sulphate Nutrition 0.000 description 79
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
• 239000000284 extract Substances 0.000 description 73
• 239000007787 solid Substances 0.000 description 71
• 238000002360 preparation method Methods 0.000 description 66
• 239000011541 reaction mixture Substances 0.000 description 66
• 239000000741 silica gel Substances 0.000 description 62
• 229910002027 silica gel Inorganic materials 0.000 description 62
• 229910052681 coesite Inorganic materials 0.000 description 61
• 229910052906 cristobalite Inorganic materials 0.000 description 61
• 235000017557 sodium bicarbonate Nutrition 0.000 description 61
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 61
• 229910052682 stishovite Inorganic materials 0.000 description 61
• 229910052905 tridymite Inorganic materials 0.000 description 61
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 55
• XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 54
• 235000019341 magnesium sulphate Nutrition 0.000 description 54
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 52
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 52
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 50
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
• 239000000047 product Substances 0.000 description 41
• 229910052757 nitrogen Inorganic materials 0.000 description 40
• 238000010992 reflux Methods 0.000 description 38
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 36
• 239000007832 Na2SO4 Substances 0.000 description 35
• 239000002904 solvent Substances 0.000 description 33
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 31
• 239000002002 slurry Substances 0.000 description 30
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 239000012458 free base Substances 0.000 description 27
• 239000000463 material Substances 0.000 description 27
• 238000010791 quenching Methods 0.000 description 27
• 239000000706 filtrate Substances 0.000 description 26
• 238000003818 flash chromatography Methods 0.000 description 26
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 239000000725 suspension Substances 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• 239000002244 precipitate Substances 0.000 description 22
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 21
• 241000700159 Rattus Species 0.000 description 21
• 239000000843 powder Substances 0.000 description 20
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 19
• 229910015845 BBr3 Inorganic materials 0.000 description 18
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• 238000003556 assay Methods 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• 239000012065 filter cake Substances 0.000 description 17
• 238000005192 partition Methods 0.000 description 17
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 238000000034 method Methods 0.000 description 14
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
• 239000000556 agonist Substances 0.000 description 13
• 235000011114 ammonium hydroxide Nutrition 0.000 description 13
• 210000004027 cell Anatomy 0.000 description 13
• 229940011871 estrogen Drugs 0.000 description 13
• 239000000262 estrogen Substances 0.000 description 13
• 238000010926 purge Methods 0.000 description 13
• 239000003826 tablet Substances 0.000 description 13
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• 239000005557 antagonist Substances 0.000 description 12
• 239000013058 crude material Substances 0.000 description 12
• 229960005309 estradiol Drugs 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• 235000019270 ammonium chloride Nutrition 0.000 description 10
• 239000012911 assay medium Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 229960000583 acetic acid Drugs 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 229910000029 sodium carbonate Inorganic materials 0.000 description 9
• 235000017550 sodium carbonate Nutrition 0.000 description 9
• 210000004291 uterus Anatomy 0.000 description 9
• 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 8
• MDNDJMCSXOXBFZ-UHFFFAOYSA-N 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane Chemical compound O1CC(C)(C)COB1B1OCC(C)(C)CO1 MDNDJMCSXOXBFZ-UHFFFAOYSA-N 0.000 description 8
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 8
• 229930182833 estradiol Natural products 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
• 238000011282 treatment Methods 0.000 description 8
• 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 8
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
• 206010067269 Uterine fibrosis Diseases 0.000 description 7
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 7
• 229910002092 carbon dioxide Inorganic materials 0.000 description 7
• 239000012091 fetal bovine serum Substances 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 235000011056 potassium acetate Nutrition 0.000 description 7
• 238000002953 preparative HPLC Methods 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
• 239000000908 ammonium hydroxide Substances 0.000 description 6
• GHQPBDDZGPAVJP-UHFFFAOYSA-N azanium;methanol;hydroxide Chemical compound N.O.OC GHQPBDDZGPAVJP-UHFFFAOYSA-N 0.000 description 6
• 210000000988 bone and bone Anatomy 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 238000001514 detection method Methods 0.000 description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
• 239000007884 disintegrant Substances 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 238000011534 incubation Methods 0.000 description 6
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 6
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
• 239000008194 pharmaceutical composition Substances 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• 230000000638 stimulation Effects 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• SERCRKYPSIZEAN-UHFFFAOYSA-N 1-[2-[4-[(2-bromo-6-phenylmethoxy-1-benzothiophen-3-yl)oxy]phenoxy]ethyl]piperidine Chemical compound C=1C=C2C(OC=3C=CC(OCCN4CCCCC4)=CC=3)=C(Br)SC2=CC=1OCC1=CC=CC=C1 SERCRKYPSIZEAN-UHFFFAOYSA-N 0.000 description 5
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
• DCQUVHFLDMCHML-UHFFFAOYSA-N 6-methoxy-2-(4-methylsulfanylphenyl)naphthalen-1-ol Chemical compound C1=CC2=CC(OC)=CC=C2C(O)=C1C1=CC=C(SC)C=C1 DCQUVHFLDMCHML-UHFFFAOYSA-N 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 239000006260 foam Substances 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 239000012362 glacial acetic acid Substances 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
• 230000002611 ovarian Effects 0.000 description 5
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
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