NO310617B1 - Steroidreseptormodulatorforbindelser, farmasöytiske sammensetninger inneholdende disse, samt anvendelse avforbindelsene eller sammensetningene for fremstilling avmedikamenter - Google Patents
Steroidreseptormodulatorforbindelser, farmasöytiske sammensetninger inneholdende disse, samt anvendelse avforbindelsene eller sammensetningene for fremstilling avmedikamenter Download PDFInfo
- Publication number
- NO310617B1 NO310617B1 NO19972591A NO972591A NO310617B1 NO 310617 B1 NO310617 B1 NO 310617B1 NO 19972591 A NO19972591 A NO 19972591A NO 972591 A NO972591 A NO 972591A NO 310617 B1 NO310617 B1 NO 310617B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- quinoline
- tetrahydro
- trifluoromethyl
- dihydro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 740
- 239000000203 mixture Substances 0.000 title claims abstract description 101
- 108010085012 Steroid Receptors Proteins 0.000 title claims abstract description 29
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 27
- 102000005969 steroid hormone receptors Human genes 0.000 title claims abstract 9
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 239000003814 drug Substances 0.000 title claims description 10
- 229940079593 drug Drugs 0.000 title claims description 8
- 229940075993 receptor modulator Drugs 0.000 title abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 53
- 230000008569 process Effects 0.000 claims abstract description 34
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 491
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 102
- 229910052739 hydrogen Inorganic materials 0.000 claims description 79
- 239000001257 hydrogen Substances 0.000 claims description 77
- 238000011282 treatment Methods 0.000 claims description 64
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 57
- 230000000694 effects Effects 0.000 claims description 35
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 24
- 125000005605 benzo group Chemical group 0.000 claims description 24
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 21
- 229940088597 hormone Drugs 0.000 claims description 20
- 239000005556 hormone Substances 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 108090000623 proteins and genes Proteins 0.000 claims description 18
- 230000037396 body weight Effects 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 11
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 11
- 206010000496 acne Diseases 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 201000010260 leiomyoma Diseases 0.000 claims description 11
- 201000009273 Endometriosis Diseases 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 9
- 230000035558 fertility Effects 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 201000004384 Alopecia Diseases 0.000 claims description 8
- 208000001132 Osteoporosis Diseases 0.000 claims description 8
- 206010060862 Prostate cancer Diseases 0.000 claims description 8
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 8
- 206010068168 androgenetic alopecia Diseases 0.000 claims description 8
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
- 230000023852 carbohydrate metabolic process Effects 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 7
- 239000003792 electrolyte Substances 0.000 claims description 7
- 230000037356 lipid metabolism Effects 0.000 claims description 7
- 230000022558 protein metabolic process Effects 0.000 claims description 7
- SCJNYBYSTCRPAO-LXBQGUBHSA-N CN(C)C\C=C\C(=O)NC1=CC=C(N=C1)C(=O)N[C@@]1(C)CCC[C@H](C1)NC1=NC(C2=CNC3=CC=CC=C23)=C(Cl)C=N1 Chemical compound CN(C)C\C=C\C(=O)NC1=CC=C(N=C1)C(=O)N[C@@]1(C)CCC[C@H](C1)NC1=NC(C2=CNC3=CC=CC=C23)=C(Cl)C=N1 SCJNYBYSTCRPAO-LXBQGUBHSA-N 0.000 claims description 6
- 206010014733 Endometrial cancer Diseases 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 6
- 210000002027 skeletal muscle Anatomy 0.000 claims description 6
- WHRLDGRNFSXOAE-UHFFFAOYSA-N 2,2,8-trimethyl-n-[(2-methylpropan-2-yl)oxy]-1h-quinoline-7-carboxamide Chemical compound N1C(C)(C)C=CC2=CC=C(C(=O)NOC(C)(C)C)C(C)=C21 WHRLDGRNFSXOAE-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000000829 suppository Substances 0.000 claims description 5
- YZSCPLGKKMSBMV-UHFFFAOYSA-N 5-fluoro-4-(8-fluoro-4-propan-2-yl-2,3-dihydro-1,4-benzoxazin-6-yl)-N-[5-(1-methylpiperidin-4-yl)pyridin-2-yl]pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)C1CCN(CC1)C)C1=CC2=C(OCCN2C(C)C)C(=C1)F YZSCPLGKKMSBMV-UHFFFAOYSA-N 0.000 claims description 4
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 claims description 4
- 206010027514 Metrorrhagia Diseases 0.000 claims description 4
- CLCTZVRHDOAUGJ-UHFFFAOYSA-N N-[4-(3-chloro-4-cyanophenoxy)cyclohexyl]-6-[4-[[4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindol-5-yl]piperazin-1-yl]methyl]piperidin-1-yl]pyridazine-3-carboxamide Chemical compound FC1=CC2=C(C=C1N1CCN(CC3CCN(CC3)C3=CC=C(N=N3)C(=O)NC3CCC(CC3)OC3=CC(Cl)=C(C=C3)C#N)CC1)C(=O)N(C1CCC(=O)NC1=O)C2=O CLCTZVRHDOAUGJ-UHFFFAOYSA-N 0.000 claims description 4
- 206010046788 Uterine haemorrhage Diseases 0.000 claims description 4
- OTKPPUXRIADSGD-PPRNARJGSA-N avoparcina Chemical compound O([C@@H]1C2=CC=C(C(=C2)Cl)OC=2C=C3C=C(C=2O[C@H]2C([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@@H]2O[C@@H](C)[C@H](O)[C@H](N)C2)OC2=CC=C(C=C2)[C@@H](O)[C@H](C(N[C@H](C(=O)N[C@H]3C(=O)N[C@H]2C(=O)N[C@@H]1C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)C=1C=CC(O)=CC=1)=O)NC(=O)[C@H](NC)C=1C=CC(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)=CC=1)[C@H]1C[C@@H](N)[C@@H](O)[C@H](C)O1 OTKPPUXRIADSGD-PPRNARJGSA-N 0.000 claims description 4
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- DFBKLUNHFCTMDC-GKRDHZSOSA-N endrin Chemical compound C([C@@H]1[C@H]2[C@@]3(Cl)C(Cl)=C([C@]([C@H]22)(Cl)C3(Cl)Cl)Cl)[C@@H]2[C@H]2[C@@H]1O2 DFBKLUNHFCTMDC-GKRDHZSOSA-N 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 238000012423 maintenance Methods 0.000 claims 1
- 210000000952 spleen Anatomy 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 12
- 229940119457 Steroid receptor agonist Drugs 0.000 abstract 1
- 229940044551 receptor antagonist Drugs 0.000 abstract 1
- 239000002464 receptor antagonist Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 489
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 292
- 235000019439 ethyl acetate Nutrition 0.000 description 204
- 239000000243 solution Substances 0.000 description 172
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 111
- 238000005481 NMR spectroscopy Methods 0.000 description 97
- 239000007787 solid Substances 0.000 description 93
- 239000000741 silica gel Substances 0.000 description 84
- 229910002027 silica gel Inorganic materials 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 80
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- 239000011541 reaction mixture Substances 0.000 description 49
- 239000003921 oil Substances 0.000 description 48
- 238000007429 general method Methods 0.000 description 47
- 238000003756 stirring Methods 0.000 description 47
- 239000000556 agonist Substances 0.000 description 46
- 239000005557 antagonist Substances 0.000 description 46
- 239000000460 chlorine Substances 0.000 description 46
- 239000011734 sodium Substances 0.000 description 46
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 44
- -1 steroid compounds Chemical class 0.000 description 43
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 42
- 238000003818 flash chromatography Methods 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
- BRBUBWGIXRYEFW-UHFFFAOYSA-N 2,2,4-trimethyl-n-[(2-methylpropan-2-yl)oxy]-1h-quinoline-7-carboxamide Chemical compound CC(C)(C)ONC(=O)C1=CC=C2C(C)=CC(C)(C)NC2=C1 BRBUBWGIXRYEFW-UHFFFAOYSA-N 0.000 description 37
- 108010080146 androgen receptors Proteins 0.000 description 34
- VOLMSPGWNYJHQQ-UHFFFAOYSA-N Pyranone Natural products CC1=C(O)C(=O)C(O)CO1 VOLMSPGWNYJHQQ-UHFFFAOYSA-N 0.000 description 33
- 102100032187 Androgen receptor Human genes 0.000 description 32
- 239000012267 brine Substances 0.000 description 32
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- GDXFUCLITVBASU-UHFFFAOYSA-N 2,2,4-trimethyl-1h-quinolin-7-ol Chemical compound OC1=CC=C2C(C)=CC(C)(C)NC2=C1 GDXFUCLITVBASU-UHFFFAOYSA-N 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- 229920006395 saturated elastomer Polymers 0.000 description 31
- 235000005074 zinc chloride Nutrition 0.000 description 31
- 239000011592 zinc chloride Substances 0.000 description 31
- 239000002904 solvent Substances 0.000 description 30
- 238000000746 purification Methods 0.000 description 29
- 230000002829 reductive effect Effects 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 27
- 238000004587 chromatography analysis Methods 0.000 description 27
- 229910000104 sodium hydride Inorganic materials 0.000 description 27
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 108091008582 intracellular receptors Proteins 0.000 description 23
- 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 23
- 229930040373 Paraformaldehyde Natural products 0.000 description 22
- 102000027411 intracellular receptors Human genes 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 239000000843 powder Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000012230 colorless oil Substances 0.000 description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 21
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
- 102000007451 Steroid Receptors Human genes 0.000 description 20
- 239000012298 atmosphere Substances 0.000 description 20
- 238000007363 ring formation reaction Methods 0.000 description 20
- 239000012312 sodium hydride Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- 102000003998 progesterone receptors Human genes 0.000 description 19
- 108090000468 progesterone receptors Proteins 0.000 description 19
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 18
- 239000007789 gas Substances 0.000 description 18
- 239000003446 ligand Substances 0.000 description 18
- 230000009467 reduction Effects 0.000 description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 17
- 238000003556 assay Methods 0.000 description 17
- OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 16
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000002168 alkylating agent Substances 0.000 description 16
- 229940100198 alkylating agent Drugs 0.000 description 16
- 239000003638 chemical reducing agent Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 14
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 14
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 14
- 229920002866 paraformaldehyde Polymers 0.000 description 14
- 150000003248 quinolines Chemical class 0.000 description 14
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 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 12
- 230000029936 alkylation Effects 0.000 description 12
- 238000005804 alkylation reaction Methods 0.000 description 12
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 11
- 108060001084 Luciferase Proteins 0.000 description 11
- 239000005089 Luciferase Substances 0.000 description 11
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 11
- 102100021316 Mineralocorticoid receptor Human genes 0.000 description 11
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 11
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 238000012761 co-transfection Methods 0.000 description 11
- 230000000875 corresponding effect Effects 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 11
- 238000010511 deprotection reaction Methods 0.000 description 11
- 102000015694 estrogen receptors Human genes 0.000 description 11
- 108010038795 estrogen receptors Proteins 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 11
- 229960001712 testosterone propionate Drugs 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 10
- 210000001625 seminal vesicle Anatomy 0.000 description 10
- WHMYYHLVLALUIU-UHFFFAOYSA-N tert-butyl 4-ethyl-7-methoxy-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC1=CC=C2C(CC)CCN(C(=O)OC(C)(C)C)C2=C1 WHMYYHLVLALUIU-UHFFFAOYSA-N 0.000 description 10
- 201000010653 vesiculitis Diseases 0.000 description 10
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 9
- 229960003473 androstanolone Drugs 0.000 description 9
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 9
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 9
- 230000009260 cross reactivity Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- LGZKLHWXHGCPIA-UHFFFAOYSA-N 2,2,4,8-tetramethyl-n-[(2-methylpropan-2-yl)oxy]-1h-quinoline-7-carboxamide Chemical compound CC(C)(C)ONC(=O)C1=CC=C2C(C)=CC(C)(C)NC2=C1C LGZKLHWXHGCPIA-UHFFFAOYSA-N 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 239000004031 partial agonist Substances 0.000 description 8
- 210000002307 prostate Anatomy 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- MSTZRUVWTJKSGP-UHFFFAOYSA-N tert-butyl 7-methoxy-4-oxo-2,3-dihydroquinoline-1-carboxylate Chemical compound O=C1CCN(C(=O)OC(C)(C)C)C2=CC(OC)=CC=C21 MSTZRUVWTJKSGP-UHFFFAOYSA-N 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- MAPBYCTYIMFIBU-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-7-amine Chemical compound C1CCNC2=CC(N)=CC=C21 MAPBYCTYIMFIBU-UHFFFAOYSA-N 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
- 101150041968 CDC13 gene Proteins 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- FBOFHVFMPNNIKN-UHFFFAOYSA-N dimethylquinoline Natural products C1=CC=C2N=C(C)C(C)=CC2=C1 FBOFHVFMPNNIKN-UHFFFAOYSA-N 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 229920000137 polyphosphoric acid Polymers 0.000 description 7
- 239000000186 progesterone Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 150000003431 steroids Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- MQTNSXZENRCZIY-UHFFFAOYSA-N 2,2,4-trimethyl-1h-quinolin-7-amine Chemical compound NC1=CC=C2C(C)=CC(C)(C)NC2=C1 MQTNSXZENRCZIY-UHFFFAOYSA-N 0.000 description 6
- BUWPZNOVIHAWHW-UHFFFAOYSA-N 2,3-dihydro-1h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CCNC2=C1 BUWPZNOVIHAWHW-UHFFFAOYSA-N 0.000 description 6
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000003098 androgen Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 230000005595 deprotonation Effects 0.000 description 6
- 238000010537 deprotonation reaction Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229960003387 progesterone Drugs 0.000 description 6
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 230000003637 steroidlike Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- KUMFMTLVOBDOIB-UHFFFAOYSA-N tert-butyl 2,2-dimethyl-4-oxo-3h-quinoline-1-carboxylate Chemical compound C1=CC=C2C(=O)CC(C)(C)N(C(=O)OC(C)(C)C)C2=C1 KUMFMTLVOBDOIB-UHFFFAOYSA-N 0.000 description 6
- OHBYOXMCVJKGFU-UHFFFAOYSA-N tert-butyl 2-methyl-4-oxo-2,3-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(C)CC(=O)C2=C1 OHBYOXMCVJKGFU-UHFFFAOYSA-N 0.000 description 6
- 229960003604 testosterone Drugs 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- FFQYYRYSKOPMBQ-UHFFFAOYSA-N (3-aminophenyl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CC=CC(N)=C1 FFQYYRYSKOPMBQ-UHFFFAOYSA-N 0.000 description 5
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 5
- GFPDGNNHUTZOGB-UHFFFAOYSA-N 2,2-dimethyl-n-[(2-methylpropan-2-yl)oxy]-1h-quinoline-7-carboxamide Chemical compound C1=CC(C)(C)NC2=CC(C(=O)NOC(C)(C)C)=CC=C21 GFPDGNNHUTZOGB-UHFFFAOYSA-N 0.000 description 5
- BAAUCXCLMDAZEL-UHFFFAOYSA-N 2-bromo-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1Br BAAUCXCLMDAZEL-UHFFFAOYSA-N 0.000 description 5
- OYRSWEMMJWLNTL-UHFFFAOYSA-N 3-amino-2-methyl-n-[(2-methylpropan-2-yl)oxy]benzamide Chemical compound CC1=C(N)C=CC=C1C(=O)NOC(C)(C)C OYRSWEMMJWLNTL-UHFFFAOYSA-N 0.000 description 5
- ARPQRBZUZNHUCJ-UHFFFAOYSA-N 3-amino-n-[(2-methylpropan-2-yl)oxy]benzamide Chemical compound CC(C)(C)ONC(=O)C1=CC=CC(N)=C1 ARPQRBZUZNHUCJ-UHFFFAOYSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000000051 antiandrogen Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 5
- 239000013058 crude material Substances 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
- 238000006396 nitration reaction Methods 0.000 description 5
- 229910017604 nitric acid Inorganic materials 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 125000001979 organolithium group Chemical group 0.000 description 5
- 125000002734 organomagnesium group Chemical group 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 238000012746 preparative thin layer chromatography Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- GDCIBEYCLNBFEO-UHFFFAOYSA-N tert-butyl 3-methyl-4-oxo-2,3-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2C(=O)C(C)CN(C(=O)OC(C)(C)C)C2=C1 GDCIBEYCLNBFEO-UHFFFAOYSA-N 0.000 description 5
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- SDFQKEYHIXNETB-UHFFFAOYSA-N (3-nitrophenyl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CC=CC([N+]([O-])=O)=C1 SDFQKEYHIXNETB-UHFFFAOYSA-N 0.000 description 4
- HOTOOVITDWCOQP-UHFFFAOYSA-N 2,2,4,8-tetramethyl-1h-quinolin-7-amine Chemical compound NC1=CC=C2C(C)=CC(C)(C)NC2=C1C HOTOOVITDWCOQP-UHFFFAOYSA-N 0.000 description 4
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 4
- UMXPKGQJQAQXLU-UHFFFAOYSA-N 2,3-dihydro-1h-indol-6-amine Chemical compound NC1=CC=C2CCNC2=C1 UMXPKGQJQAQXLU-UHFFFAOYSA-N 0.000 description 4
- DFTPIAYUXFRTRN-UHFFFAOYSA-N 2-methyl-n-[(2-methylpropan-2-yl)oxy]-3-nitrobenzamide Chemical compound CC1=C(C(=O)NOC(C)(C)C)C=CC=C1[N+]([O-])=O DFTPIAYUXFRTRN-UHFFFAOYSA-N 0.000 description 4
- HBSFTVGBQDJTAW-UHFFFAOYSA-N 2-methylbut-3-yn-2-yl acetate Chemical compound CC(=O)OC(C)(C)C#C HBSFTVGBQDJTAW-UHFFFAOYSA-N 0.000 description 4
- BIVHHDHXDURQMJ-UHFFFAOYSA-N 4-ethyl-1,2,3,4-tetrahydroquinolin-7-ol Chemical compound OC1=CC=C2C(CC)CCNC2=C1 BIVHHDHXDURQMJ-UHFFFAOYSA-N 0.000 description 4
- WSWMGHRLUYADNA-UHFFFAOYSA-N 7-nitro-1,2,3,4-tetrahydroquinoline Chemical compound C1CCNC2=CC([N+](=O)[O-])=CC=C21 WSWMGHRLUYADNA-UHFFFAOYSA-N 0.000 description 4
- 239000002841 Lewis acid Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 230000002280 anti-androgenic effect Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 238000002657 hormone replacement therapy Methods 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 150000007517 lewis acids Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- IOFGNSHEDOEPRZ-UHFFFAOYSA-N tert-butyl (3-aminophenyl)sulfanylformate Chemical compound CC(C)(C)OC(=O)SC1=CC=CC(N)=C1 IOFGNSHEDOEPRZ-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- PXGVLRMOLONCMQ-UHFFFAOYSA-N 2,2,8-trimethyl-3,4-dihydro-1h-quinolin-7-amine Chemical compound C1CC(C)(C)NC2=C1C=CC(N)=C2C PXGVLRMOLONCMQ-UHFFFAOYSA-N 0.000 description 3
- LNNIPFBSWGVRIX-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydro-1h-quinolin-7-amine Chemical compound C1=C(N)C=C2NC(C)(C)CCC2=C1 LNNIPFBSWGVRIX-UHFFFAOYSA-N 0.000 description 3
- JPRUARIRIAZJNY-UHFFFAOYSA-N 2-bromo-n-(2-methylprop-2-enyl)-5-nitroaniline Chemical compound CC(=C)CNC1=CC([N+]([O-])=O)=CC=C1Br JPRUARIRIAZJNY-UHFFFAOYSA-N 0.000 description 3
- OVSRQUPJJIAWID-UHFFFAOYSA-N 3,3-dimethyl-1,2-dihydroindol-6-amine Chemical compound NC1=CC=C2C(C)(C)CNC2=C1 OVSRQUPJJIAWID-UHFFFAOYSA-N 0.000 description 3
- OBRVKOVWGSBITQ-UHFFFAOYSA-N 3,3-dimethyl-6-nitro-1,2-dihydroindole Chemical compound [O-][N+](=O)C1=CC=C2C(C)(C)CNC2=C1 OBRVKOVWGSBITQ-UHFFFAOYSA-N 0.000 description 3
- ATHOUIIZDUZMNO-UHFFFAOYSA-N 3,3-dimethyl-7-nitro-2,4-dihydro-1h-quinoline Chemical compound [O-][N+](=O)C1=CC=C2CC(C)(C)CNC2=C1 ATHOUIIZDUZMNO-UHFFFAOYSA-N 0.000 description 3
- ATWZNUYMQQXKFL-UHFFFAOYSA-N 3-(4-benzylphenyl)-3-oxopropanenitrile Chemical compound C1=CC(C(CC#N)=O)=CC=C1CC1=CC=CC=C1 ATWZNUYMQQXKFL-UHFFFAOYSA-N 0.000 description 3
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 3
- YEPSVJBFTQLMSC-UHFFFAOYSA-N 3-methyl-7-nitro-1,2,3,4-tetrahydroquinoline Chemical compound [O-][N+](=O)C1=CC=C2CC(C)CNC2=C1 YEPSVJBFTQLMSC-UHFFFAOYSA-N 0.000 description 3
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 3
- RTZZCYNQPHTPPL-UHFFFAOYSA-N 3-nitrophenol Chemical compound OC1=CC=CC([N+]([O-])=O)=C1 RTZZCYNQPHTPPL-UHFFFAOYSA-N 0.000 description 3
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 3
- ZXVOEKDIKOZSJE-UHFFFAOYSA-N 4-ethyl-1,2,3,4-tetrahydroquinolin-7-amine Chemical compound NC1=CC=C2C(CC)CCNC2=C1 ZXVOEKDIKOZSJE-UHFFFAOYSA-N 0.000 description 3
- VWGKOUAMOLNBMK-UHFFFAOYSA-N 4-ethyl-1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2C(CC)CCNC2=C1 VWGKOUAMOLNBMK-UHFFFAOYSA-N 0.000 description 3
- SCUPVDCMBKLPEF-UHFFFAOYSA-N 4-ethyl-7-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound COC1=CC=C2C(CC)CCNC2=C1 SCUPVDCMBKLPEF-UHFFFAOYSA-N 0.000 description 3
- KHICVIXCBAIKLK-UHFFFAOYSA-N 4-methyl-7-nitro-1,2,3,4-tetrahydroquinoline Chemical compound [O-][N+](=O)C1=CC=C2C(C)CCNC2=C1 KHICVIXCBAIKLK-UHFFFAOYSA-N 0.000 description 3
- LTNYDSMDSLOMSM-UHFFFAOYSA-N 6-nitro-2,3-dihydro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2CCNC2=C1 LTNYDSMDSLOMSM-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229940123407 Androgen receptor antagonist Drugs 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108091027981 Response element Proteins 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 206010046798 Uterine leiomyoma Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 229940030486 androgens Drugs 0.000 description 3
- 230000002051 biphasic effect Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 229960002074 flutamide Drugs 0.000 description 3
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 3
- 210000004392 genitalia Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 3
- 229960003248 mifepristone Drugs 0.000 description 3
- UXSSDPITEOFAMK-UHFFFAOYSA-N n-(dithiophen-2-ylmethylidene)hydroxylamine Chemical compound C=1C=CSC=1C(=NO)C1=CC=CS1 UXSSDPITEOFAMK-UHFFFAOYSA-N 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 229930185107 quinolinone Natural products 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- YABZDOANPKVYLL-UHFFFAOYSA-N tert-butyl (2,2,4-trimethyl-1h-quinolin-7-yl)sulfanylformate Chemical compound CC(C)(C)OC(=O)SC1=CC=C2C(C)=CC(C)(C)NC2=C1 YABZDOANPKVYLL-UHFFFAOYSA-N 0.000 description 3
- PGMSSNZIUUOGBU-UHFFFAOYSA-N tert-butyl 3,3-dimethyl-2,4-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)CC(C)(C)CC2=C1 PGMSSNZIUUOGBU-UHFFFAOYSA-N 0.000 description 3
- GHSGVQKTCAMTDS-UHFFFAOYSA-N tert-butyl 3-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2CC(C)CN(C(=O)OC(C)(C)C)C2=C1 GHSGVQKTCAMTDS-UHFFFAOYSA-N 0.000 description 3
- CKAGGBQOSITTFK-UHFFFAOYSA-N tert-butyl 4-ethyl-4-hydroxy-2,3-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2C(CC)(O)CCN(C(=O)OC(C)(C)C)C2=C1 CKAGGBQOSITTFK-UHFFFAOYSA-N 0.000 description 3
- CYGRMFJNCYLVQM-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-methyl-2,3-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)CCC(C)(O)C2=C1 CYGRMFJNCYLVQM-UHFFFAOYSA-N 0.000 description 3
- DMYGKKLNCNOCLQ-UHFFFAOYSA-N tert-butyl 4-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2C(C)CCN(C(=O)OC(C)(C)C)C2=C1 DMYGKKLNCNOCLQ-UHFFFAOYSA-N 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
- VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 description 2
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 description 2
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- HJJRGZMJZDSMDB-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-7-ol Chemical compound C1CCNC2=CC(O)=CC=C21 HJJRGZMJZDSMDB-UHFFFAOYSA-N 0.000 description 2
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
- MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 description 2
- 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 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- ZBHHZYLYNZYQHB-UHFFFAOYSA-N 2,2,3-trimethyl-3,4-dihydro-1h-quinoline Chemical compound C1=CC=C2NC(C)(C)C(C)CC2=C1 ZBHHZYLYNZYQHB-UHFFFAOYSA-N 0.000 description 2
- IWLJISHMBSLRDL-UHFFFAOYSA-N 2,2,4,8-tetramethyl-n-[(2-methylpropan-2-yl)oxy]-3,4-dihydro-1h-quinoline-7-carboxamide Chemical compound CC(C)(C)ONC(=O)C1=CC=C2C(C)CC(C)(C)NC2=C1C IWLJISHMBSLRDL-UHFFFAOYSA-N 0.000 description 2
- KGZBBHQZCMBWRZ-UHFFFAOYSA-N 2,2,4-trimethyl-n-[(2-methylpropan-2-yl)oxy]-3,4-dihydro-1h-quinoline-7-carboxamide Chemical compound CC(C)(C)ONC(=O)C1=CC=C2C(C)CC(C)(C)NC2=C1 KGZBBHQZCMBWRZ-UHFFFAOYSA-N 0.000 description 2
- IJDHZLYEVDYFOY-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydro-1h-quinolin-7-ol Chemical compound C1=C(O)C=C2NC(C)(C)CCC2=C1 IJDHZLYEVDYFOY-UHFFFAOYSA-N 0.000 description 2
- AUAGMNMBRXUKON-UHFFFAOYSA-N 2,4,4a,5-tetrahydro-1h-quinolin-3-one Chemical compound C1=CCC2CC(=O)CNC2=C1 AUAGMNMBRXUKON-UHFFFAOYSA-N 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- NATPHGMSUDVTPH-UHFFFAOYSA-N 3,3-dimethyl-2,4-dihydro-1h-quinolin-7-amine Chemical compound NC1=CC=C2CC(C)(C)CNC2=C1 NATPHGMSUDVTPH-UHFFFAOYSA-N 0.000 description 2
- GIMAFCCXNRALND-UHFFFAOYSA-N 3,3-dimethyl-2,4-dihydro-1h-quinoline Chemical compound C1=CC=C2CC(C)(C)CNC2=C1 GIMAFCCXNRALND-UHFFFAOYSA-N 0.000 description 2
- BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 description 2
- LPBUNLNGOABTDH-UHFFFAOYSA-N 3-methyl-1,2,3,4-tetrahydroquinolin-7-amine Chemical compound NC1=CC=C2CC(C)CNC2=C1 LPBUNLNGOABTDH-UHFFFAOYSA-N 0.000 description 2
- BUZMGUAGCNSWQB-UHFFFAOYSA-N 3-methyl-1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CC(C)CNC2=C1 BUZMGUAGCNSWQB-UHFFFAOYSA-N 0.000 description 2
- IURCRCLIBTWMOM-UHFFFAOYSA-N 4-methyl-1,2,3,4-tetrahydroquinolin-7-amine Chemical compound NC1=CC=C2C(C)CCNC2=C1 IURCRCLIBTWMOM-UHFFFAOYSA-N 0.000 description 2
- JICYVEOGNFERHO-UHFFFAOYSA-N 4-propyl-1,2,3,4-tetrahydroquinolin-7-ol Chemical compound OC1=CC=C2C(CCC)CCNC2=C1 JICYVEOGNFERHO-UHFFFAOYSA-N 0.000 description 2
- CBWWWVHWYSZQDX-UHFFFAOYSA-N 4-propyl-1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2C(CCC)CCNC2=C1 CBWWWVHWYSZQDX-UHFFFAOYSA-N 0.000 description 2
- MNALUTYMBUBKNX-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(OC)=CC=C21 MNALUTYMBUBKNX-UHFFFAOYSA-N 0.000 description 2
- UNQYAAAWKOOBFQ-UHFFFAOYSA-N 7-[(4-chlorophenyl)methyl]-8-[4-chloro-3-(trifluoromethoxy)phenoxy]-1-(3-hydroxypropyl)-3-methylpurine-2,6-dione Chemical compound C=1C=C(Cl)C=CC=1CN1C=2C(=O)N(CCCO)C(=O)N(C)C=2N=C1OC1=CC=C(Cl)C(OC(F)(F)F)=C1 UNQYAAAWKOOBFQ-UHFFFAOYSA-N 0.000 description 2
- WDKNRIQDGSVRBO-UHFFFAOYSA-N 7-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound C1CCNC2=CC(OC)=CC=C21 WDKNRIQDGSVRBO-UHFFFAOYSA-N 0.000 description 2
- FXMJBPUDUVWRGI-UHFFFAOYSA-N 7-methoxy-2,3-dihydro-1h-quinolin-4-one Chemical compound O=C1CCNC2=CC(OC)=CC=C21 FXMJBPUDUVWRGI-UHFFFAOYSA-N 0.000 description 2
- NJAGLJSQFZHCAL-UHFFFAOYSA-N 7-methoxy-2-methyl-2,3-dihydro-1h-quinolin-4-one Chemical compound O=C1CC(C)NC2=CC(OC)=CC=C21 NJAGLJSQFZHCAL-UHFFFAOYSA-N 0.000 description 2
- AXXIBDJPCRUVDM-UHFFFAOYSA-N 7-methoxy-4-methyl-1,2,3,4-tetrahydroquinoline Chemical compound CC1CCNC2=CC(OC)=CC=C21 AXXIBDJPCRUVDM-UHFFFAOYSA-N 0.000 description 2
- MVGRRCWUYJUSBH-UHFFFAOYSA-N 7-methoxy-4-propyl-1,2,3,4-tetrahydroquinoline Chemical compound COC1=CC=C2C(CCC)CCNC2=C1 MVGRRCWUYJUSBH-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 2
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 240000004385 Centaurea cyanus Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 208000005171 Dysmenorrhea Diseases 0.000 description 2
- 206010013935 Dysmenorrhoea Diseases 0.000 description 2
- 108090000331 Firefly luciferases Proteins 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000928259 Homo sapiens NADPH:adrenodoxin oxidoreductase, mitochondrial Proteins 0.000 description 2
- 101000574060 Homo sapiens Progesterone receptor Proteins 0.000 description 2
- 206010060800 Hot flush Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 208000019022 Mood disease Diseases 0.000 description 2
- 241000713333 Mouse mammary tumor virus Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229960002478 aldosterone Drugs 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000012875 competitive assay Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 102000046818 human AR Human genes 0.000 description 2
- 238000006197 hydroboration reaction Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229960004400 levonorgestrel Drugs 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 229940090668 parachlorophenol Drugs 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000583 progesterone congener Substances 0.000 description 2
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 2
- RIZZXCJMFIGMON-UHFFFAOYSA-N prop-2-ynyl acetate Chemical compound CC(=O)OCC#C RIZZXCJMFIGMON-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- NEBHPNNWUHTYAH-UHFFFAOYSA-N tert-butyl 2,2-dimethylquinoline-1-carboxylate Chemical compound C1=CC=C2C=CC(C)(C)N(C(=O)OC(C)(C)C)C2=C1 NEBHPNNWUHTYAH-UHFFFAOYSA-N 0.000 description 2
- PJRVULCZGPIDOD-UHFFFAOYSA-N tert-butyl 4-ethyl-7-methoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC1=CC=C2C(CC)CC(C)N(C(=O)OC(C)(C)C)C2=C1 PJRVULCZGPIDOD-UHFFFAOYSA-N 0.000 description 2
- QHTWKXRLSZPMMB-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-propyl-2,3-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2C(CCC)(O)CCN(C(=O)OC(C)(C)C)C2=C1 QHTWKXRLSZPMMB-UHFFFAOYSA-N 0.000 description 2
- KXAMNYKYZHLDQC-UHFFFAOYSA-N tert-butyl 4-hydroxy-7-methoxy-4-methyl-2,3-dihydroquinoline-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)(C)C=2C1=CC(OC)=CC=2 KXAMNYKYZHLDQC-UHFFFAOYSA-N 0.000 description 2
- UIFOUBFGWSHWLM-UHFFFAOYSA-N tert-butyl 4-oxo-2,3-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)CCC(=O)C2=C1 UIFOUBFGWSHWLM-UHFFFAOYSA-N 0.000 description 2
- ANNLBDUCHGQRJO-UHFFFAOYSA-N tert-butyl 7-methoxy-2-methyl-4-oxo-2,3-dihydroquinoline-1-carboxylate Chemical compound O=C1CC(C)N(C(=O)OC(C)(C)C)C2=CC(OC)=CC=C21 ANNLBDUCHGQRJO-UHFFFAOYSA-N 0.000 description 2
- DLMBHUXWMLPMQN-UHFFFAOYSA-N tert-butyl 7-methoxy-4-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound CC1CCN(C(=O)OC(C)(C)C)C2=CC(OC)=CC=C21 DLMBHUXWMLPMQN-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- BCUWDJPRIHGCRN-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-3-ol Chemical compound C1=CC=C2CC(O)CNC2=C1 BCUWDJPRIHGCRN-UHFFFAOYSA-N 0.000 description 1
- RYPZGQVVZOCWGK-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-4-ol Chemical compound C1=CC=C2C(O)CCNC2=C1 RYPZGQVVZOCWGK-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KUKMUQNCOFLFOE-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxy]-3-phenylurea Chemical class CC(C)(C)ONC(=O)NC1=CC=CC=C1 KUKMUQNCOFLFOE-UHFFFAOYSA-N 0.000 description 1
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- SKYYXVRRINSHIN-UHFFFAOYSA-N 2,2,4,8-tetramethyl-3,4-dihydro-1h-quinolin-7-amine Chemical compound NC1=CC=C2C(C)CC(C)(C)NC2=C1C SKYYXVRRINSHIN-UHFFFAOYSA-N 0.000 description 1
- WGOKUZDQNGNKLX-UHFFFAOYSA-N 2,2,4-trimethyl-3,4-dihydro-1h-quinolin-7-amine Chemical compound NC1=CC=C2C(C)CC(C)(C)NC2=C1 WGOKUZDQNGNKLX-UHFFFAOYSA-N 0.000 description 1
- VQGOKEXBIOULBD-UHFFFAOYSA-N 2,2,8-trimethyl-n-[(2-methylpropan-2-yl)oxy]-3,4-dihydro-1h-quinoline-7-carboxamide Chemical compound N1C(C)(C)CCC2=CC=C(C(=O)NOC(C)(C)C)C(C)=C21 VQGOKEXBIOULBD-UHFFFAOYSA-N 0.000 description 1
- NOKKEYPRZXQLQA-UHFFFAOYSA-N 2,2-dimethyl-1h-quinolin-7-ol Chemical compound OC1=CC=C2C=CC(C)(C)NC2=C1 NOKKEYPRZXQLQA-UHFFFAOYSA-N 0.000 description 1
- JWSUYSBONRNZRW-UHFFFAOYSA-N 2,2-dimethyl-1h-quinoline Chemical compound C1=CC=C2C=CC(C)(C)NC2=C1 JWSUYSBONRNZRW-UHFFFAOYSA-N 0.000 description 1
- YUGBJANWDNEPPX-UHFFFAOYSA-N 2,2-dimethyl-n-[(2-methylpropan-2-yl)oxy]-3,4-dihydro-1h-quinoline-7-carboxamide Chemical compound C1CC(C)(C)NC2=CC(C(=O)NOC(C)(C)C)=CC=C21 YUGBJANWDNEPPX-UHFFFAOYSA-N 0.000 description 1
- JZICUKPOZUKZLL-UHFFFAOYSA-N 2-methyl-1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2NC(C)CCC2=C1 JZICUKPOZUKZLL-UHFFFAOYSA-N 0.000 description 1
- KTJXYZFZRRYVJJ-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1h-quinolin-4-one Chemical compound C1=CC=C2NC(C)CC(=O)C2=C1 KTJXYZFZRRYVJJ-UHFFFAOYSA-N 0.000 description 1
- HFCFJYRLBAANKN-UHFFFAOYSA-N 2-methyl-3-nitroaniline Chemical compound CC1=C(N)C=CC=C1[N+]([O-])=O HFCFJYRLBAANKN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- SRCCLYMWDRNUAF-UHFFFAOYSA-N 3,3-dimethyl-1,2-dihydroindole Chemical compound C1=CC=C2C(C)(C)CNC2=C1 SRCCLYMWDRNUAF-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- MLYRFAXZAQJEHP-RZNUTPGSSA-N 3-[(8r,9s,10r,13s,14s,17s)-7-acetylsulfanyl-17-hydroxy-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-17-yl]propanoic acid Chemical compound C1C[C@]2(C)[C@](CCC(O)=O)(O)CC[C@H]2[C@@H]2C(SC(=O)C)CC3=CC(=O)CC[C@]3(C)[C@H]21 MLYRFAXZAQJEHP-RZNUTPGSSA-N 0.000 description 1
- DCUQUNJESLMZPF-UHFFFAOYSA-N 3-amino-5h-phenanthridin-6-one Chemical compound C1=CC=C2C3=CC=C(N)C=C3NC(=O)C2=C1 DCUQUNJESLMZPF-UHFFFAOYSA-N 0.000 description 1
- DHAJHGGHYYPVTM-UHFFFAOYSA-N 3-amino-n-tert-butylbenzamide Chemical compound CC(C)(C)NC(=O)C1=CC=CC(N)=C1 DHAJHGGHYYPVTM-UHFFFAOYSA-N 0.000 description 1
- FXGNIWAMJJDYMZ-UHFFFAOYSA-N 3-anilinobutanoic acid Chemical compound OC(=O)CC(C)NC1=CC=CC=C1 FXGNIWAMJJDYMZ-UHFFFAOYSA-N 0.000 description 1
- USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-UHFFFAOYSA-N 0.000 description 1
- ISLOXRTUQJQYES-UHFFFAOYSA-N 3-nitro-5h-phenanthridin-6-one Chemical compound C1=CC=C2C3=CC=C([N+](=O)[O-])C=C3NC(=O)C2=C1 ISLOXRTUQJQYES-UHFFFAOYSA-N 0.000 description 1
- HBCSOCHVMJKLLO-UHFFFAOYSA-N 3-nitrobenzenethiol Chemical compound [O-][N+](=O)C1=CC=CC(S)=C1 HBCSOCHVMJKLLO-UHFFFAOYSA-N 0.000 description 1
- NXTNASSYJUXJDV-UHFFFAOYSA-N 3-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(C(Cl)=O)=C1 NXTNASSYJUXJDV-UHFFFAOYSA-N 0.000 description 1
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 description 1
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
- NSXWVWBHCINPIG-UHFFFAOYSA-N 4-methoxyphenylthionophosphine sulfide Chemical compound COC1=CC=C(P(=S)=S)C=C1 NSXWVWBHCINPIG-UHFFFAOYSA-N 0.000 description 1
- OXNZWCYNCDWCJA-UHFFFAOYSA-N 4-methyl-1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2C(C)CCNC2=C1 OXNZWCYNCDWCJA-UHFFFAOYSA-N 0.000 description 1
- OGFCYRNIJNJKBK-UHFFFAOYSA-N 4-methyl-7-nitrochromen-2-one Chemical compound C1=C([N+]([O-])=O)C=CC2=C1OC(=O)C=C2C OGFCYRNIJNJKBK-UHFFFAOYSA-N 0.000 description 1
- CWFCXNPEHZJDEM-UHFFFAOYSA-N 4-propyl-1,2,3,4-tetrahydroquinolin-7-amine Chemical compound NC1=CC=C2C(CCC)CCNC2=C1 CWFCXNPEHZJDEM-UHFFFAOYSA-N 0.000 description 1
- XESZUVZBAMCAEJ-UHFFFAOYSA-N 4-tert-butylcatechol Chemical compound CC(C)(C)C1=CC=C(O)C(O)=C1 XESZUVZBAMCAEJ-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- QZZLLHOMMCKWIQ-UHFFFAOYSA-N 7-amino-4-(methoxymethyl)chromen-2-one Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2COC QZZLLHOMMCKWIQ-UHFFFAOYSA-N 0.000 description 1
- JBNOVHJXQSHGRL-UHFFFAOYSA-N 7-amino-4-(trifluoromethyl)coumarin Chemical class FC(F)(F)C1=CC(=O)OC2=CC(N)=CC=C21 JBNOVHJXQSHGRL-UHFFFAOYSA-N 0.000 description 1
- MJXYFLJHTUSJGU-UHFFFAOYSA-N 7-amino-4-methyl-1h-quinolin-2-one Chemical compound NC1=CC=C2C(C)=CC(=O)NC2=C1 MJXYFLJHTUSJGU-UHFFFAOYSA-N 0.000 description 1
- CZXBVBATQPHSSL-UHFFFAOYSA-N 7-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=CC2=C1C(=O)CC2 CZXBVBATQPHSSL-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000005676 Adrenogenital syndrome Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000004746 Atrophic Vaginitis Diseases 0.000 description 1
- 206010003693 Atrophic vulvovaginitis Diseases 0.000 description 1
- 238000006237 Beckmann rearrangement reaction Methods 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 208000008448 Congenital adrenal hyperplasia Diseases 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 239000012988 Dithioester Chemical class 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 229940102550 Estrogen receptor antagonist Drugs 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 101000836540 Homo sapiens Aldo-keto reductase family 1 member B1 Proteins 0.000 description 1
- 101000809450 Homo sapiens Amphiregulin Proteins 0.000 description 1
- 101000775732 Homo sapiens Androgen receptor Proteins 0.000 description 1
- 101000882584 Homo sapiens Estrogen receptor Proteins 0.000 description 1
- 101000615613 Homo sapiens Mineralocorticoid receptor Proteins 0.000 description 1
- 101000738977 Homo sapiens Reverse transcriptase/ribonuclease H Proteins 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- BVVFOLSZMQVDKV-KXQIQQEYSA-N ICI-164384 Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2[C@H](CCCCCCCCCCC(=O)N(C)CCCC)CC3=CC(O)=CC=C3[C@H]21 BVVFOLSZMQVDKV-KXQIQQEYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 238000006945 Knorr synthesis reaction Methods 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 206010024434 Lichen sclerosus Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- 241001134446 Niveas Species 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- 239000004015 abortifacient agent Substances 0.000 description 1
- 231100000641 abortifacient agent Toxicity 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000010981 acute adrenal insufficiency Diseases 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001974 anti-anabolic effect Effects 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- TWYFZUKKZYDZDF-UHFFFAOYSA-N but-1-yn-1-amine Chemical compound CCC#CN TWYFZUKKZYDZDF-UHFFFAOYSA-N 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- 229940117916 cinnamic aldehyde Drugs 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000008294 cold cream Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 150000004775 coumarins Chemical class 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000005022 dithioester group Chemical class 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 150000002157 estra-4,9-dienes Chemical class 0.000 description 1
- 239000003687 estradiol congener Substances 0.000 description 1
- JKKFKPJIXZFSSB-CBZIJGRNSA-N estrone 3-sulfate Chemical compound OS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 JKKFKPJIXZFSSB-CBZIJGRNSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- OVPIQFGJQAQWAJ-UHFFFAOYSA-N ethyl 3-(furan-3-yl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C=1C=COC=1 OVPIQFGJQAQWAJ-UHFFFAOYSA-N 0.000 description 1
- XGIRWPYENXRJMZ-UHFFFAOYSA-N ethyl 4,4,4-trichloro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(Cl)(Cl)Cl XGIRWPYENXRJMZ-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 102000054091 human NR3C2 Human genes 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008311 hydrophilic ointment Substances 0.000 description 1
- YPQLFJODEKMJEF-UHFFFAOYSA-N hydroxyflutamide Chemical compound CC(C)(O)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 YPQLFJODEKMJEF-UHFFFAOYSA-N 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- IQZZFVDIZRWADY-UHFFFAOYSA-N isocumarine Natural products C1=CC=C2C(=O)OC=CC2=C1 IQZZFVDIZRWADY-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000000990 laser dye Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000002332 leydig cell Anatomy 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 210000000260 male genitalia Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- QGBPKJFJAVDUNC-UHFFFAOYSA-N methyl 4-methoxy-3-oxobutanoate Chemical compound COCC(=O)CC(=O)OC QGBPKJFJAVDUNC-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- REHYMUARMNSKGV-UHFFFAOYSA-N n-(2-methylbut-3-yn-2-yl)aniline Chemical compound C#CC(C)(C)NC1=CC=CC=C1 REHYMUARMNSKGV-UHFFFAOYSA-N 0.000 description 1
- OPDAAQUHXJMLHA-UHFFFAOYSA-N n-[(2-methylpropan-2-yl)oxy]-3-nitrobenzamide Chemical compound CC(C)(C)ONC(=O)C1=CC=CC([N+]([O-])=O)=C1 OPDAAQUHXJMLHA-UHFFFAOYSA-N 0.000 description 1
- KPZLTNGEMSLVQI-UHFFFAOYSA-N n-[(2-methylpropan-2-yl)oxy]-4-oxo-2,3-dihydroquinoline-1-carboxamide Chemical compound C1=CC=C2N(C(=O)NOC(C)(C)C)CCC(=O)C2=C1 KPZLTNGEMSLVQI-UHFFFAOYSA-N 0.000 description 1
- DOWVMJFBDGWVML-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide Chemical compound C1=NC(C=2C=[N+]([O-])C=CC=2)=CN1C(=O)N(C)C1CCCCC1 DOWVMJFBDGWVML-UHFFFAOYSA-N 0.000 description 1
- VBEGHXKAFSLLGE-UHFFFAOYSA-N n-phenylnitramide Chemical class [O-][N+](=O)NC1=CC=CC=C1 VBEGHXKAFSLLGE-UHFFFAOYSA-N 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 description 1
- 229960004719 nandrolone Drugs 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 229940053934 norethindrone Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 201000010808 postmenopausal atrophic vaginitis Diseases 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940063238 premarin Drugs 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 108090000765 processed proteins & peptides Chemical class 0.000 description 1
- 229940077150 progesterone and estrogen Drugs 0.000 description 1
- 239000000044 progesterone antagonist Substances 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 description 1
- RZAUIOKDXQWSQE-UHFFFAOYSA-N quinolin-7-amine Chemical compound C1=CC=NC2=CC(N)=CC=C21 RZAUIOKDXQWSQE-UHFFFAOYSA-N 0.000 description 1
- KDYVCOSVYOSHOL-UHFFFAOYSA-N quinolin-7-ylmethanamine Natural products C1=CC=NC2=CC(C)=CC=C21 KDYVCOSVYOSHOL-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- ZFHMZPCYWFLUKE-UHFFFAOYSA-N tert-butyl 2,2,3-trimethyl-3,4-dihydroquinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(C)(C)C(C)CC2=C1 ZFHMZPCYWFLUKE-UHFFFAOYSA-N 0.000 description 1
- UVIMEGQRBNTSHQ-UHFFFAOYSA-N tert-butyl 3,3-dimethyl-4-oxo-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)CC(C)(C)C(=O)C2=C1 UVIMEGQRBNTSHQ-UHFFFAOYSA-N 0.000 description 1
- MCURVBFIKIYYIS-UHFFFAOYSA-N tert-butyl 4-ethyl-4-hydroxy-7-methoxyquinoline-1-carboxylate Chemical compound COC1=CC=C2C(CC)(O)C=CN(C(=O)OC(C)(C)C)C2=C1 MCURVBFIKIYYIS-UHFFFAOYSA-N 0.000 description 1
- UAEPLUCRXAVIAV-UHFFFAOYSA-N tert-butyl 4-hydroxy-7-methoxy-4-propyl-2,3-dihydroquinoline-1-carboxylate Chemical compound COC1=CC=C2C(CCC)(O)CCN(C(=O)OC(C)(C)C)C2=C1 UAEPLUCRXAVIAV-UHFFFAOYSA-N 0.000 description 1
- ZVUFXBLYDJPJLT-UHFFFAOYSA-N tert-butyl 4-hydroxy-7-methoxy-4-propylquinoline-1-carboxylate Chemical compound COC1=CC=C2C(CCC)(O)C=CN(C(=O)OC(C)(C)C)C2=C1 ZVUFXBLYDJPJLT-UHFFFAOYSA-N 0.000 description 1
- XDYAFSCRKBRFDN-UHFFFAOYSA-N tert-butyl 7-methoxy-4-propyl-2h-quinoline-1-carboxylate Chemical compound COC1=CC=C2C(CCC)=CCN(C(=O)OC(C)(C)C)C2=C1 XDYAFSCRKBRFDN-UHFFFAOYSA-N 0.000 description 1
- BHGJDEWMNKNXGI-UHFFFAOYSA-N tert-butyl 7-methoxy-4-propyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC1=CC=C2C(CCC)CCN(C(=O)OC(C)(C)C)C2=C1 BHGJDEWMNKNXGI-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 208000008480 vulvar lichen sclerosus Diseases 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
-
- 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
- C07D413/02—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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D417/02—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 containing two hetero rings
- C07D417/04—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 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Liquid Crystal (AREA)
- Optical Modulation, Optical Deflection, Nonlinear Optics, Optical Demodulation, Optical Logic Elements (AREA)
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US36352994A | 1994-12-22 | 1994-12-22 | |
US08/464,360 US5693646A (en) | 1994-12-22 | 1995-06-05 | Steroid receptor modulator compounds and methods |
US08/465,556 US5696133A (en) | 1994-12-22 | 1995-06-05 | Steroid receptor modulator compounds and methods |
US08/462,643 US5696130A (en) | 1994-12-22 | 1995-06-05 | Tricyclic steroid receptor modulator compounds and methods |
US08/465,429 US5696127A (en) | 1994-12-22 | 1995-06-05 | Steroid receptor modulator compounds and methods |
US08/463,231 US5688808A (en) | 1994-12-22 | 1995-06-05 | Steroid receptor modulator compounds and methods |
US08/464,541 US5688810A (en) | 1994-12-22 | 1995-06-05 | Steroid receptor modulator compounds and methods |
US08/464,546 US5693647A (en) | 1994-12-22 | 1995-06-05 | Steroid receptor modulator compounds and methods |
PCT/US1995/016096 WO1996019458A2 (en) | 1994-12-22 | 1995-12-13 | Steroid receptor modulator compounds and methods |
Publications (3)
Publication Number | Publication Date |
---|---|
NO972591D0 NO972591D0 (no) | 1997-06-06 |
NO972591L NO972591L (no) | 1997-08-14 |
NO310617B1 true NO310617B1 (no) | 2001-07-30 |
Family
ID=27575415
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19972591A NO310617B1 (no) | 1994-12-22 | 1997-06-06 | Steroidreseptormodulatorforbindelser, farmasöytiske sammensetninger inneholdende disse, samt anvendelse avforbindelsene eller sammensetningene for fremstilling avmedikamenter |
NO20003534A NO312162B1 (no) | 1994-12-22 | 2000-07-07 | Progesteronreseptor-modulatorforbindelser, farmasöytiske sammensetninger inneholdende disse og anvendelsen av forbindelsene |
NO20003551A NO312098B1 (no) | 1994-12-22 | 2000-07-10 | Steroidreseptormodulatorforbindelser, farmasöytiske sammensetninger inneholdende disse samt anvendelse avforbindelsene |
NO20003550A NO20003550D0 (no) | 1994-12-22 | 2000-07-10 | Farmasøytiske sammensetninger og anvendelse herav |
NO20003552A NO313049B1 (no) | 1994-12-22 | 2000-07-10 | Progesteron-agonistforbindelser, farmasöytiske preparater inneholdende disse og anvendelsen av forbindelsen |
Family Applications After (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20003534A NO312162B1 (no) | 1994-12-22 | 2000-07-07 | Progesteronreseptor-modulatorforbindelser, farmasöytiske sammensetninger inneholdende disse og anvendelsen av forbindelsene |
NO20003551A NO312098B1 (no) | 1994-12-22 | 2000-07-10 | Steroidreseptormodulatorforbindelser, farmasöytiske sammensetninger inneholdende disse samt anvendelse avforbindelsene |
NO20003550A NO20003550D0 (no) | 1994-12-22 | 2000-07-10 | Farmasøytiske sammensetninger og anvendelse herav |
NO20003552A NO313049B1 (no) | 1994-12-22 | 2000-07-10 | Progesteron-agonistforbindelser, farmasöytiske preparater inneholdende disse og anvendelsen av forbindelsen |
Country Status (17)
Country | Link |
---|---|
EP (7) | EP1043326A1 (zh) |
JP (2) | JPH10510840A (zh) |
CN (2) | CN1626534A (zh) |
AT (2) | ATE252560T1 (zh) |
AU (1) | AU717251B2 (zh) |
BR (1) | BR9510486A (zh) |
CA (1) | CA2208347A1 (zh) |
CZ (1) | CZ176197A3 (zh) |
DE (2) | DE69531998T2 (zh) |
DK (1) | DK0800519T3 (zh) |
ES (1) | ES2208699T3 (zh) |
HU (1) | HUT78117A (zh) |
NO (5) | NO310617B1 (zh) |
NZ (1) | NZ300739A (zh) |
PT (1) | PT800519E (zh) |
RU (1) | RU2191774C2 (zh) |
WO (1) | WO1996019458A2 (zh) |
Families Citing this family (111)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000513362A (ja) * | 1996-06-27 | 2000-10-10 | リガンド・ファーマスーティカルス・インコーポレーテッド | アンドロゲン受容体モジュレーター化合物及び方法 |
US6017924A (en) | 1996-06-27 | 2000-01-25 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
AUPO427196A0 (en) * | 1996-12-19 | 1997-01-23 | University Of Sydney, The | A method for preventing or controlling cataract |
US5929058A (en) * | 1996-12-24 | 1999-07-27 | Zymogenetics, Inc. | Treatment agents and methods for treating type II diabetes and symptoms of type II diabetes |
US6291442B1 (en) | 1998-02-03 | 2001-09-18 | The General Hospital Corporation | Pharmacological modulators of voltage-gated potassium ion channels |
US6380207B2 (en) | 1998-02-13 | 2002-04-30 | Abbott Laboratories | Glucocortiocoid-selective antiinflammatory agents |
DK1053239T3 (da) * | 1998-02-13 | 2003-04-22 | Abbott Lab | Gluccocorticoid-selektive, anti-inflammatoriske midler |
US6506766B1 (en) * | 1998-02-13 | 2003-01-14 | Abbott Laboratories | Glucocortiocoid-selective antinflammatory agents |
US6001846A (en) * | 1998-02-17 | 1999-12-14 | Ligand Pharmaceuticals Incorporated | Process for the preparation of 1,2-dihydroquinolines |
US6093825A (en) * | 1998-05-27 | 2000-07-25 | American Home Products | Methods for preparation of 1,2-dihydroquinolines |
US6093826A (en) * | 1998-06-08 | 2000-07-25 | Ligand Pharmaceuticals Incorporated | Process for the preparation of C(5)-substituted 1,2-dihydro-5H-chromeno[3,4-f] quinolines |
EP1093362A1 (en) | 1998-06-12 | 2001-04-25 | Ligand Pharmaceuticals Incorporated | Treatment of anti-estrogen resistant breast cancer using rxr modulators |
US6417214B1 (en) | 1999-05-04 | 2002-07-09 | Wyeth | 3,3-substituted indoline derivatives |
CA2371273A1 (en) * | 1999-05-04 | 2000-11-09 | Andrew Fensome | Tetracyclic progesterone receptor modulator compounds and methods |
US6407101B1 (en) | 1999-05-04 | 2002-06-18 | American Home Products Corporation | Cyanopyrroles |
US6509334B1 (en) | 1999-05-04 | 2003-01-21 | American Home Products Corporation | Cyclocarbamate derivatives as progesterone receptor modulators |
US6498154B1 (en) | 1999-05-04 | 2002-12-24 | Wyeth | Cyclic regimens using quinazolinone and benzoxazine derivatives |
US6358948B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
US6399593B1 (en) | 1999-05-04 | 2002-06-04 | Wyeth | Cyclic regimens using cyclic urea and cyclic amide derivatives |
EP1175411B1 (en) * | 1999-05-04 | 2008-02-20 | Wyeth | Cyclothiocarbamate derivatives as progesterone receptor modulators |
US6444668B1 (en) | 1999-05-04 | 2002-09-03 | Wyeth | Combination regimens using progesterone receptor modulators |
US6319912B1 (en) | 1999-05-04 | 2001-11-20 | American Home Products Corporation | Cyclic regimens using 2,1-benzisothiazoline 2,2-dioxides |
US6462032B1 (en) | 1999-05-04 | 2002-10-08 | Wyeth | Cyclic regimens utilizing indoline derivatives |
MXPA01011286A (es) * | 1999-05-04 | 2003-07-14 | American Home Prod | Derivados de ciclocarbamato como moduladores de receptor de progesterona. |
US6380235B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Benzimidazolones and analogues |
US6391907B1 (en) | 1999-05-04 | 2002-05-21 | American Home Products Corporation | Indoline derivatives |
US6423699B1 (en) | 1999-05-04 | 2002-07-23 | American Home Products Corporation | Combination therapies using benzimidazolones |
US6369056B1 (en) | 1999-05-04 | 2002-04-09 | American Home Products Corporation | Cyclic urea and cyclic amide derivatives |
US6355648B1 (en) | 1999-05-04 | 2002-03-12 | American Home Products Corporation | Thio-oxindole derivatives |
US6339098B1 (en) * | 1999-05-04 | 2002-01-15 | American Home Products Corporation | 2,1-benzisothiazoline 2,2-dioxides |
US6380178B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Cyclic regimens using cyclocarbamate and cyclic amide derivatives |
US6329416B1 (en) | 1999-05-04 | 2001-12-11 | American Home Products Corporation | Combination regimens using 3,3-substituted indoline derivatives |
US6358947B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Tetracyclic progesterone receptor modulator compounds and methods |
WO2000066560A1 (en) * | 1999-05-04 | 2000-11-09 | American Home Products Corporation | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
US6306851B1 (en) | 1999-05-04 | 2001-10-23 | American Home Products Corporation | Cyclocarbamate and cyclic amide derivatives |
TR200200507T2 (tr) | 1999-08-27 | 2002-10-21 | Ligand Pharmaceuticals Inc | Androjen reseptörü modülatör bileşikleri ve metotları |
WO2001016133A2 (en) | 1999-08-27 | 2001-03-08 | Ligand Pharmaceuticals Incorporated | 8-substituted-6-trifluoromethyl-9-pyrido[3,2-g]quinoline compounds as androgen receptor modulators |
US6566372B1 (en) | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
BR0014161A (pt) * | 1999-08-31 | 2002-05-21 | Jenapharm Gmbh | Mesoprogestinas (moduladores de receptor de progesterona) no tratamento e prevenção de distúrbios ginecológicos dependentes de hormÈnio benigno |
WO2001019770A2 (en) | 1999-09-14 | 2001-03-22 | Ligand Pharmaceuticals Incorporated | Rxr modulators with improved pharmacologic profile |
US7037919B1 (en) | 1999-10-14 | 2006-05-02 | Kaken Pharmaceutical Co. Ltd. | Tetrahydroquinoline derivatives |
UA73119C2 (en) | 2000-04-19 | 2005-06-15 | American Home Products Corpoir | Derivatives of cyclic thiocarbamates, pharmaceutical composition including noted derivatives of cyclic thiocarbamates and active ingredients of medicines as modulators of progesterone receptors |
HUP0303165A3 (en) * | 2000-06-28 | 2006-05-29 | Bristol Myers Squibb Co | Fused cyclic compounds as modulators of nuclear hormone receptor function, process for their preparation and pharmaceutical compositions containing them |
ATE309208T1 (de) * | 2000-08-23 | 2005-11-15 | Akzo Nobel Nv | 10-aryl-11h-benzo(b)fluoren-derivate und analoga als östrogene mittel |
AU2001286243A1 (en) * | 2000-09-14 | 2002-03-26 | Kaken Pharmaceutical Co., Ltd. | Tetrahydroquinoline compounds |
CZ2003780A3 (cs) * | 2000-09-19 | 2004-01-14 | Bristol-Myers Squibb Company | Kondenzované heterocyklické sukcinimidové sloučeniny a jejich analogy, modulátory funkce receptorů hormonů jádra |
US7214690B2 (en) | 2001-02-23 | 2007-05-08 | Ligand Pharmaceuticals Incorporated | Tricyclic quinolinone and tricyclic quinoline androgen receptor modulator compounds and methods |
US7026484B2 (en) * | 2001-02-23 | 2006-04-11 | Ligand Pharmaceuticals Incorporated | Tricyclic androgen receptor modulator compounds and methods |
US6608216B2 (en) | 2001-06-29 | 2003-08-19 | Abbott Laboratories | Process for the preparation of chiral glucocorticoid receptor agents |
WO2003002548A1 (en) * | 2001-06-29 | 2003-01-09 | Abbott Laboratories | A process for the preparation of chiral glucocorticoid receptor agents |
SK286759B6 (sk) | 2001-07-02 | 2009-05-07 | N.V. Organon | Tetrahydrochinolínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
JP2003073374A (ja) * | 2001-08-31 | 2003-03-12 | Kaken Pharmaceut Co Ltd | 2環性芳香族アミン誘導体 |
TW200301107A (en) * | 2001-12-13 | 2003-07-01 | Wyeth Corp | Substituted 6H-dibenzo[c,h]chromenes as estrogenic agents |
ATE346058T1 (de) | 2002-01-14 | 2006-12-15 | Boehringer Ingelheim Pharma | Glucocorticoid mimetika, verfahren zu ihrer herstellung, pharmazeutische formulierungen sie enthaltend und verwendungen davon |
TW200304371A (en) | 2002-02-22 | 2003-10-01 | Akzo Nobel Nv | Substituted 10-ary1-11H-benzo [b] fluorenes and 7-ary1-5, 6-dihydro-benz [a] anthracenes for selective effects on estrogen receptors |
ES2528764T3 (es) | 2002-02-28 | 2015-02-12 | University Of Tennessee Research Foundation | Moduladores selectivos multisustituidos del receptor de andrógeno y métodos de uso de los mismos |
AU2003230581A1 (en) | 2002-03-15 | 2003-09-29 | Eli Lilly And Company | Dihydroindol-2-one derivatives as steroid hormone nuclear receptor modulators |
CA2477764A1 (en) | 2002-03-26 | 2003-10-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
MXPA04009329A (es) | 2002-03-26 | 2005-01-25 | Boehringer Ingelheim Pharma | Mimeticos de glucocorticoides, metodos para su preparacion, composiciones farmaceuticas y usos de los mismos. |
AU2003230869B2 (en) * | 2002-04-26 | 2010-02-25 | Ortho-Mcneil Pharmaceutical, Inc. | 2-(quinolonyl)-fused heterocycles as androgen receptor modulators |
US7405234B2 (en) | 2002-05-17 | 2008-07-29 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
US7186864B2 (en) | 2002-05-29 | 2007-03-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
US7074806B2 (en) | 2002-06-06 | 2006-07-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
DE60322713D1 (de) | 2002-08-21 | 2008-09-18 | Boehringer Ingelheim Pharma | Substituierte dihydrochinoline als glucocorticoid-mmimetika,verfahren zu deren herstellung, pharmazeutische zubereitungen und deren verwendung |
AU2003278744B2 (en) | 2002-08-28 | 2010-07-29 | Harbor Biosciences, Inc. | Therapeutic treatment methods |
DE20301728U1 (de) | 2002-10-11 | 2004-03-11 | Ligand Pharmaceuticals, Inc., San Diego | 5-substituierte 7,9-Difluor-5H-Chromeno(3,4-f) -Chinolin-Verbindungen als selektive Progesteronrezeptormodulator-Verbindungen |
AU2003258047A1 (en) | 2002-10-11 | 2004-05-04 | Ligand Pharmaceuticals Incorporated | 5-(1',1'-CYCLOALKYL/ALKENYL)METHYLIDENE 1,2-DIHYDRO-5H-CHROMENO(3,4-f)QUINOLINES AS SELECTIVE PROGESTERONE RECEPTOR MODULATOR COMPOUNDS |
CL2003001544A1 (es) | 2002-10-11 | 2005-01-07 | Ligand Pharm Inc | Compuestos derivados de 5-cicloalquenil-5h-cromeno[3,4-f]quinolina de formula i, moduladores selectivos del receptor de progesterona; composicion farmaceutica; y su uso en el tratamiento de sangrado uterino disfuncional, dismenorrea, endometriosis, l |
US7632858B2 (en) | 2002-11-15 | 2009-12-15 | Bristol-Myers Squibb Company | Open chain prolyl urea-related modulators of androgen receptor function |
TWI306855B (en) * | 2002-12-20 | 2009-03-01 | Organon Nv | Tetrahydroquinoline derivatives |
TWI322012B (en) * | 2002-12-20 | 2010-03-21 | Organon Nv | Tetrahydroquinoline derivatives |
JP4373926B2 (ja) | 2003-01-03 | 2009-11-25 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 1−プロパノール及び1−プロピルアミン誘導体ならびにグルココルチコイドリガンドとしての使用 |
AU2004224082A1 (en) * | 2003-03-28 | 2004-10-07 | Pfizer Products Inc. | 1,2,4-substitute 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydro-quinoxaline derivatives as CETP inhibitors for the treatment of atherosclerosis and obesity |
US7816372B2 (en) | 2003-08-22 | 2010-10-19 | Ligand Pharmaceuticals Incorporated | 6-cycloamino-2-quinolinone derivatives as androgen receptor modulator compounds |
UY28526A1 (es) | 2003-09-24 | 2005-04-29 | Boehringer Ingelheim Pharma | Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos |
US7507843B2 (en) | 2003-10-16 | 2009-03-24 | Boehringer Ingelheim Pharmaceuticals, Inc. | Stereoselective synthesis of certain trifluoromethyl-substituted alcohols |
US7256208B2 (en) | 2003-11-13 | 2007-08-14 | Bristol-Myers Squibb Company | Monocyclic N-Aryl hydantoin modulators of androgen receptor function |
US7820702B2 (en) | 2004-02-04 | 2010-10-26 | Bristol-Myers Squibb Company | Sulfonylpyrrolidine modulators of androgen receptor function and method |
US7696241B2 (en) | 2004-03-04 | 2010-04-13 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
US7625923B2 (en) | 2004-03-04 | 2009-12-01 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
US7388027B2 (en) | 2004-03-04 | 2008-06-17 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
WO2005090282A1 (en) | 2004-03-12 | 2005-09-29 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
US7795272B2 (en) | 2004-03-13 | 2010-09-14 | Boehringer Ingelheim Pharmaceutical, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof |
JP2008512458A (ja) * | 2004-09-07 | 2008-04-24 | ワイス | 6H−[1]ベンゾピラノ[4,3−b]キノリン及びエストロゲン様物質としてのそれらの使用 |
JP2008525525A (ja) | 2004-12-27 | 2008-07-17 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | グルココルチコイドミメティクス、その製法、医薬組成物及び使用 |
CN101137655A (zh) | 2005-06-17 | 2008-03-05 | 配体药物公司 | 雄激素受体调节剂化合物和方法 |
US7709516B2 (en) | 2005-06-17 | 2010-05-04 | Endorecherche, Inc. | Helix 12 directed non-steroidal antiandrogens |
KR101390094B1 (ko) * | 2005-09-14 | 2014-04-28 | 산텐 세이야꾸 가부시키가이샤 | 글루코코르티코이드 수용체 결합 활성을 갖는 신규1,2-디히드로퀴놀린 유도체 |
JP4825636B2 (ja) * | 2005-09-14 | 2011-11-30 | 参天製薬株式会社 | グルココルチコイド受容体結合活性を有する新規1,2−ジヒドロキノリン誘導体 |
WO2007075884A2 (en) * | 2005-12-21 | 2007-07-05 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
WO2008059866A1 (fr) | 2006-11-14 | 2008-05-22 | Santen Pharmaceutical Co., Ltd. | Nouveau dérivé 1,2-dihydroquinoline comprenant un groupe alkyle inférieur à substitution phénylamino et un groupe phényle dans lequel est introduit un ester en tant que substituants |
CN101547909A (zh) | 2006-12-06 | 2009-09-30 | 贝林格尔.英格海姆国际有限公司 | 糖皮质激素模拟物、其制备方法、药物组合物及其用途 |
TWI410422B (zh) * | 2007-01-15 | 2013-10-01 | Mitsubishi Tanabe Pharma Corp | 縮合四氫喹啉衍生物及其醫藥用途 |
JP2008255112A (ja) * | 2007-03-13 | 2008-10-23 | Santen Pharmaceut Co Ltd | 2,2,4−トリメチル−6−フェニル−1,2−ジヒドロキノリン誘導体からなるグルココルチコイド受容体アゴニスト |
US9284345B2 (en) | 2007-04-12 | 2016-03-15 | Endorecherche, Inc. | 17alpha-substituted steroids as systemic antiandrogens and selective androgen receptor modulators |
WO2009103007A2 (en) * | 2008-02-13 | 2009-08-20 | Ligand Pharmaceuticals Incorporated | Steroid hormone receptor modulator compounds and methods |
CA2724055C (en) * | 2008-05-12 | 2016-08-02 | Santen Pharmaceutical Co., Ltd. | Glucocorticoid receptor agonist comprising 2,2,4-trimethyl-6-phenyl-1,2 -dihydroquinoline derivatives having substituted oxy group |
EP2130831A1 (en) | 2008-06-06 | 2009-12-09 | InterMed Discovery GmbH | CDC25 inhibitors |
AU2009256289A1 (en) | 2008-06-06 | 2009-12-10 | Boehringer Ingelheim International Gmbh | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
CN102239149B (zh) * | 2008-10-06 | 2015-05-13 | 约翰·霍普金斯大学 | 喹啉化合物作为血管新生、人类甲硫氨酰氨肽酶、以及sirt1的抑制剂,以及治疗病症的方法 |
CN103613538B (zh) * | 2013-11-22 | 2015-05-20 | 山东斯递尔化工科技有限公司 | 一种2,2,4-三甲基-1,2-二氢化喹啉聚合体的催化合成工艺 |
US9682960B2 (en) | 2013-12-19 | 2017-06-20 | Endorecherche, Inc. | Non-steroidal antiandrogens and selective androgen receptor modulators with a pyridyl moiety |
EP3265127B1 (en) | 2015-03-02 | 2024-02-21 | Corcept Therapeutics, Inc. | Mifepristone and octreotide for use in the treatment of cushing's syndrome in a patient having an adrenocorticotropic hormone (acth)-secreting pancreatic neuroendocrine tumor |
MX2017011885A (es) | 2015-03-30 | 2018-02-19 | Corcept Therapeutics Inc | Uso de antagonistas de receptores de glucocorticoides en combinacion con glucocorticoides para tratar la insuficiencia adrenal. |
ES2865334T3 (es) | 2015-08-13 | 2021-10-15 | Corcept Therapeutics Inc | Método de diagnóstico diferencial de síndrome de Cushing dependiente de ACTH |
KR102197526B1 (ko) | 2016-01-19 | 2020-12-31 | 코어셉트 쎄라퓨틱스 인코포레이티드 | 이소성 쿠싱 증후군의 감별 진단 |
CN106397317B (zh) * | 2016-09-26 | 2019-03-22 | 天津师范大学 | 1,2,3,4-四氢喹啉化合物及其合成方法与应用 |
CA3065555A1 (en) | 2017-06-20 | 2018-12-27 | Corcept Therapeutics, Inc. | Methods of treating neuroepithelial tumors using selective glucocorticoid receptor modulators |
CN107805248A (zh) * | 2017-11-01 | 2018-03-16 | 长春海谱润斯科技有限公司 | 一种含有苯并咪唑结构的衍生物及其制备方法和有机电致发光器件 |
CN111499607B (zh) * | 2019-01-30 | 2022-04-19 | 哈尔滨工业大学(深圳) | 一种六元芳基内酯或六元芳基内酰胺化合物的制备方法 |
US20240269280A1 (en) | 2020-12-18 | 2024-08-15 | Instil Bio (Uk) Limited | Processing of tumor infiltrating lymphocytes |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3635941A (en) * | 1969-04-01 | 1972-01-18 | Eastman Kodak Co | Disperse mono azo dyes containing an acylamidotetrahydroquinoline group |
GB1379387A (en) * | 1970-12-11 | 1975-01-02 | Agfa Gevaert | Photoconductive recording materials |
US3907507A (en) * | 1971-04-26 | 1975-09-23 | Heliodoro Monroy Rivera | Novel apparatus for the obtention of substituted 1,2-dihydroquinolines |
NZ221729A (en) * | 1986-09-15 | 1989-07-27 | Janssen Pharmaceutica Nv | Imidazolyl methyl-substituted benzimidazole derivatives and pharmaceutical compositions |
DK0934937T3 (da) * | 1990-11-30 | 2002-04-02 | Otsuka Pharma Co Ltd | Azolderivater som superoxidradikalinhibitor |
JPH04316557A (ja) * | 1991-04-16 | 1992-11-06 | Kyorin Pharmaceut Co Ltd | 6−アリール環状アントラニル酸誘導体 |
-
1995
- 1995-12-13 AT AT95944089T patent/ATE252560T1/de not_active IP Right Cessation
- 1995-12-13 AU AU45977/96A patent/AU717251B2/en not_active Ceased
- 1995-12-13 CN CNA2004100740784A patent/CN1626534A/zh active Pending
- 1995-12-13 JP JP8519861A patent/JPH10510840A/ja not_active Ceased
- 1995-12-13 DK DK95944089T patent/DK0800519T3/da active
- 1995-12-13 EP EP00113830A patent/EP1043326A1/en not_active Withdrawn
- 1995-12-13 NZ NZ300739A patent/NZ300739A/xx unknown
- 1995-12-13 EP EP00113916A patent/EP1043315A1/en not_active Withdrawn
- 1995-12-13 EP EP00113915A patent/EP1041066A1/en not_active Withdrawn
- 1995-12-13 HU HU9702305A patent/HUT78117A/hu unknown
- 1995-12-13 CZ CZ971761A patent/CZ176197A3/cs unknown
- 1995-12-13 PT PT95944089T patent/PT800519E/pt unknown
- 1995-12-13 CN CNB951977024A patent/CN1172917C/zh not_active Expired - Fee Related
- 1995-12-13 ES ES95944089T patent/ES2208699T3/es not_active Expired - Lifetime
- 1995-12-13 DE DE69531998T patent/DE69531998T2/de not_active Expired - Fee Related
- 1995-12-13 EP EP95944089A patent/EP0800519B1/en not_active Expired - Lifetime
- 1995-12-13 RU RU97112141/04A patent/RU2191774C2/ru not_active IP Right Cessation
- 1995-12-13 WO PCT/US1995/016096 patent/WO1996019458A2/en not_active Application Discontinuation
- 1995-12-13 EP EP00113829A patent/EP1043325B1/en not_active Expired - Lifetime
- 1995-12-13 EP EP00113914A patent/EP1041071A1/en not_active Withdrawn
- 1995-12-13 BR BR9510486A patent/BR9510486A/pt not_active IP Right Cessation
- 1995-12-13 EP EP03023907A patent/EP1382597A3/en not_active Withdrawn
- 1995-12-13 DE DE69533180T patent/DE69533180T2/de not_active Expired - Fee Related
- 1995-12-13 AT AT00113829T patent/ATE269336T1/de not_active IP Right Cessation
- 1995-12-13 CA CA002208347A patent/CA2208347A1/en not_active Abandoned
-
1997
- 1997-06-06 NO NO19972591A patent/NO310617B1/no unknown
-
2000
- 2000-07-07 NO NO20003534A patent/NO312162B1/no unknown
- 2000-07-10 NO NO20003551A patent/NO312098B1/no unknown
- 2000-07-10 NO NO20003550A patent/NO20003550D0/no not_active Application Discontinuation
- 2000-07-10 NO NO20003552A patent/NO313049B1/no unknown
-
2007
- 2007-02-28 JP JP2007048504A patent/JP2007217418A/ja not_active Withdrawn
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO310617B1 (no) | Steroidreseptormodulatorforbindelser, farmasöytiske sammensetninger inneholdende disse, samt anvendelse avforbindelsene eller sammensetningene for fremstilling avmedikamenter | |
US6121450A (en) | Intermediates for preparation of steroid receptor modulator compounds | |
US6696459B1 (en) | Steroid receptor modulator compounds and methods | |
US6017924A (en) | Androgen receptor modulator compounds and methods | |
EP0918774B9 (en) | Androgen receptor modulator compounds and methods | |
WO2001016133A2 (en) | 8-substituted-6-trifluoromethyl-9-pyrido[3,2-g]quinoline compounds as androgen receptor modulators | |
AU762398B2 (en) | Steroid receptor modulator compounds and methods | |
HUT78121A (hu) | Androgén receptor modulátor kondenzált kinolin- és indolszármazékok, eljárás előállításukra, alkalmazásuk és az ezeket tartalmazó gyógyszerkészítmények | |
MXPA98010831A (en) | Compounds and modulators of androge receiver | |
AU2003248406A1 (en) | Steroid receptor modulator compounds and methods |