DE69726513T2 - Benzo[B]thiophenverbindungen,Zwischenprodukte,Verfahren,Zusammensetzungen und Methode - Google Patents
Benzo[B]thiophenverbindungen,Zwischenprodukte,Verfahren,Zusammensetzungen und Methode Download PDFInfo
- Publication number
- DE69726513T2 DE69726513T2 DE69726513T DE69726513T DE69726513T2 DE 69726513 T2 DE69726513 T2 DE 69726513T2 DE 69726513 T DE69726513 T DE 69726513T DE 69726513 T DE69726513 T DE 69726513T DE 69726513 T2 DE69726513 T2 DE 69726513T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- alkyl
- thiophene
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 process Substances 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title abstract description 38
- 239000000543 intermediate Substances 0.000 title abstract description 31
- 239000000203 mixture Substances 0.000 title abstract description 26
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title description 22
- 230000008569 process Effects 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 162
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 239000000262 estrogen Substances 0.000 claims description 36
- 229940011871 estrogen Drugs 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class 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 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 239000000583 progesterone congener Substances 0.000 claims description 12
- 208000024891 symptom Diseases 0.000 claims description 12
- 208000001132 Osteoporosis Diseases 0.000 claims description 10
- 206010027304 Menopausal symptoms Diseases 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 230000001575 pathological effect Effects 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 201000009273 Endometriosis Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 230000001419 dependent effect Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 150000003462 sulfoxides Chemical class 0.000 claims description 3
- XHSNXNMCXYVKIL-UHFFFAOYSA-N OCl[N+]([O-])=O Chemical compound OCl[N+]([O-])=O XHSNXNMCXYVKIL-UHFFFAOYSA-N 0.000 claims description 2
- 210000000709 aorta Anatomy 0.000 claims description 2
- 230000035755 proliferation Effects 0.000 claims description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims 4
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- 208000016599 Uterine disease Diseases 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 210000000038 chest Anatomy 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000010260 leiomyoma Diseases 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 abstract 3
- 229930192474 thiophene Natural products 0.000 abstract 1
- 150000003577 thiophenes Chemical class 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 210000000988 bone and bone Anatomy 0.000 description 17
- 238000009472 formulation Methods 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 14
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 238000010561 standard procedure Methods 0.000 description 7
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 6
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000011877 solvent mixture Substances 0.000 description 6
- 125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 102000003982 Parathyroid hormone Human genes 0.000 description 5
- 108090000445 Parathyroid hormone Proteins 0.000 description 5
- 238000006069 Suzuki reaction reaction Methods 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 238000009164 estrogen replacement therapy Methods 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000000199 parathyroid hormone Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 210000004291 uterus Anatomy 0.000 description 5
- KLNDEFDWKQKFCW-UHFFFAOYSA-N 2-(3-methoxyphenyl)-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 KLNDEFDWKQKFCW-UHFFFAOYSA-N 0.000 description 4
- VXMQTVRMGZVSKE-UHFFFAOYSA-N 4-[[2-(3-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenol Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(O)=CC=2)=C1 VXMQTVRMGZVSKE-UHFFFAOYSA-N 0.000 description 4
- 229940122361 Bisphosphonate Drugs 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000002140 halogenating effect Effects 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000009245 menopause Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229960001319 parathyroid hormone Drugs 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 150000001543 aryl boronic acids Chemical class 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 230000001076 estrogenic effect Effects 0.000 description 3
- 230000005283 ground state Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229940053934 norethindrone Drugs 0.000 description 3
- 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 3
- 230000007170 pathology Effects 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 0 *C1C=CC(c2c(*)c(ccc(I)c3)c3[s]2)=*C1* Chemical compound *C1C=CC(c2c(*)c(ccc(I)c3)c3[s]2)=*C1* 0.000 description 2
- OUODOIAYZKMYRN-UHFFFAOYSA-N 1-[2-[4-[[2-(3-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenoxy]ethyl]piperidine;hydrochloride Chemical compound Cl.COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 OUODOIAYZKMYRN-UHFFFAOYSA-N 0.000 description 2
- OFHAGSNEHHNRSV-UHFFFAOYSA-N 1-benzothiophene;hydrochloride Chemical compound Cl.C1=CC=C2SC=CC2=C1 OFHAGSNEHHNRSV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- UAEZGVKNQHEJAL-UHFFFAOYSA-N 2-(3-methoxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound COC1=CC=CC(C2=C(C3=CC=C(O)C=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 UAEZGVKNQHEJAL-UHFFFAOYSA-N 0.000 description 2
- XHGPQRBWXLCDNP-UHFFFAOYSA-N 2-iodo-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound IC=1SC2=CC=CC=C2C=1OC(C=C1)=CC=C1OCC1=CC=CC=C1 XHGPQRBWXLCDNP-UHFFFAOYSA-N 0.000 description 2
- UECUPGFJVNJNQA-UHFFFAOYSA-N 2-phenylbenzenethiol Chemical class SC1=CC=CC=C1C1=CC=CC=C1 UECUPGFJVNJNQA-UHFFFAOYSA-N 0.000 description 2
- UZTMOYFTZZOWFQ-UHFFFAOYSA-N 3-[3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]phenol;hydrochloride Chemical compound Cl.OC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 UZTMOYFTZZOWFQ-UHFFFAOYSA-N 0.000 description 2
- FGRCVTCAKNOSSL-UHFFFAOYSA-N 3-bromo-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)Br)=C1 FGRCVTCAKNOSSL-UHFFFAOYSA-N 0.000 description 2
- NXLZMGKLCBPRQU-UHFFFAOYSA-N 3-bromo-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene 1-oxide Chemical compound COC1=CC=CC(C=2S(C3=CC(OC)=CC=C3C=2Br)=O)=C1 NXLZMGKLCBPRQU-UHFFFAOYSA-N 0.000 description 2
- LSGAMPIEVKGIHI-UHFFFAOYSA-N 3-chloro-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)Cl)=C1 LSGAMPIEVKGIHI-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- AKLUWZVPOMDDLC-UHFFFAOYSA-N 4-[[6-methoxy-2-(3-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenol Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(O)=CC=2)=C1 AKLUWZVPOMDDLC-UHFFFAOYSA-N 0.000 description 2
- RXIRVUJXMZXAOI-UHFFFAOYSA-N 6-methoxy-2-(2-methoxyphenyl)-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCC1=CC=CC=C1 RXIRVUJXMZXAOI-UHFFFAOYSA-N 0.000 description 2
- SJERDHWNHQRVIF-UHFFFAOYSA-N 6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C=2SC3=CC(OC)=CC=C3C=2)=C1 SJERDHWNHQRVIF-UHFFFAOYSA-N 0.000 description 2
- HHVNUOQWPCGMHY-UHFFFAOYSA-N 6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene 1-oxide Chemical compound COC1=CC=CC(C=2S(C3=CC(OC)=CC=C3C=2)=O)=C1 HHVNUOQWPCGMHY-UHFFFAOYSA-N 0.000 description 2
- LUPWQLHJPYFJKN-UHFFFAOYSA-N 6-methoxy-2-(3-methoxyphenyl)-3-(4-methylphenyl)sulfonyl-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)S(=O)(=O)C=2C=CC(C)=CC=2)=C1 LUPWQLHJPYFJKN-UHFFFAOYSA-N 0.000 description 2
- CBPYDUSTYYVPGP-UHFFFAOYSA-N 6-methoxy-2-(3-methoxyphenyl)-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 CBPYDUSTYYVPGP-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010020100 Hip fracture Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 150000004663 bisphosphonates Chemical class 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000003245 coal Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 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 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229940063238 premarin Drugs 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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 1
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- UEOCICLWNYTZBO-UHFFFAOYSA-N (3-methoxyphenoxy)boronic acid Chemical compound COC1=CC=CC(OB(O)O)=C1 UEOCICLWNYTZBO-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-Me3C6H3 Natural products CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- WNRWEBKEQARBKV-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine Chemical compound ClCCN1CCCCC1 WNRWEBKEQARBKV-UHFFFAOYSA-N 0.000 description 1
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- GJDWXLOTBZOCFD-UHFFFAOYSA-N 1-[2-[4-[[2-(3,4-dimethoxyphenyl)-6-methoxy-1-benzothiophen-3-yl]oxy]phenoxy]ethyl]piperidine Chemical compound C=1C=C(OC)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 GJDWXLOTBZOCFD-UHFFFAOYSA-N 0.000 description 1
- VTAHJGIBKJBFSA-UHFFFAOYSA-N 1-[2-[4-[[2-(3-fluoro-4-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenoxy]ethyl]piperidine;hydrochloride Chemical compound Cl.C1=C(F)C(OC)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=CC=C2S1 VTAHJGIBKJBFSA-UHFFFAOYSA-N 0.000 description 1
- VXEMSWOVUXSYBS-UHFFFAOYSA-N 1-[2-[4-[[2-(3-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenoxy]ethyl]piperidine Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 VXEMSWOVUXSYBS-UHFFFAOYSA-N 0.000 description 1
- QRWASEOSILKNFO-UHFFFAOYSA-N 1-[3-[4-[[2-(3-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenoxy]propyl]piperidine Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCCN3CCCCC3)=CC=2)=C1 QRWASEOSILKNFO-UHFFFAOYSA-N 0.000 description 1
- RSXSFLQDFIPTCO-UHFFFAOYSA-N 1-benzothiophene;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound C1=CC=C2SC=CC2=C1.OC(=O)CC(O)(C(O)=O)CC(O)=O RSXSFLQDFIPTCO-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- SPXOTSHWBDUUMT-UHFFFAOYSA-N 138-42-1 Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- VYRNCUJHCHROFS-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound C1=C(OC)C(OC)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 VYRNCUJHCHROFS-UHFFFAOYSA-N 0.000 description 1
- MQKUPBWEUPTFFD-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound C=1C=C(O)C(Cl)=CC=1C=1SC2=CC(O)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 MQKUPBWEUPTFFD-UHFFFAOYSA-N 0.000 description 1
- QKRDIUBCVYIMSL-UHFFFAOYSA-N 2-(3-fluoro-4-methoxyphenyl)-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound C1=C(F)C(OC)=CC=C1C1=C(OC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C2=CC=CC=C2S1 QKRDIUBCVYIMSL-UHFFFAOYSA-N 0.000 description 1
- CWYNSQDRNDBNKE-UHFFFAOYSA-N 2-(3-hydroxy-2-methylphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound CC1=C(O)C=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 CWYNSQDRNDBNKE-UHFFFAOYSA-N 0.000 description 1
- QUVRCJHIKIUEOW-UHFFFAOYSA-N 2-(3-hydroxy-2-methylphenyl)-3-[4-(2-pyrrolidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound CC1=C(O)C=CC=C1C1=C(OC=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(O)C=C2S1 QUVRCJHIKIUEOW-UHFFFAOYSA-N 0.000 description 1
- YGGLCWOVQVVYKQ-UHFFFAOYSA-N 2-(3-hydroxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound OC1=CC=CC(C2=C(C3=CC=C(O)C=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 YGGLCWOVQVVYKQ-UHFFFAOYSA-N 0.000 description 1
- XWUPDHFTQCWMDN-UHFFFAOYSA-N 2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C=2SC3=CC=CC=C3C=2)=C1 XWUPDHFTQCWMDN-UHFFFAOYSA-N 0.000 description 1
- NZHISGHBPAPCJU-UHFFFAOYSA-N 2-(3-methoxyphenyl)-1-benzothiophene 1-oxide Chemical compound COC1=CC=CC(C=2S(C3=CC=CC=C3C=2)=O)=C1 NZHISGHBPAPCJU-UHFFFAOYSA-N 0.000 description 1
- VQINVOBWTKZQJK-UHFFFAOYSA-N 2-(3-methoxyphenyl)-3-(4-methylphenyl)sulfonyl-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)S(=O)(=O)C=2C=CC(C)=CC=2)=C1 VQINVOBWTKZQJK-UHFFFAOYSA-N 0.000 description 1
- GOQNIOFONRBQOF-UHFFFAOYSA-N 2-(3-methoxyphenyl)-3-[4-(2-pyrrolidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol;oxalic acid Chemical compound OC(=O)C(O)=O.COC1=CC=CC(C2=C(C3=CC=C(O)C=C3S2)OC=2C=CC(OCCN3CCCC3)=CC=2)=C1 GOQNIOFONRBQOF-UHFFFAOYSA-N 0.000 description 1
- ZFDLFRZURJFWAZ-UHFFFAOYSA-N 2-(3-methoxyphenyl)-3-[4-[2-(4-methylphenyl)sulfonylethoxy]phenoxy]-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCS(=O)(=O)C=3C=CC(C)=CC=3)=CC=2)=C1 ZFDLFRZURJFWAZ-UHFFFAOYSA-N 0.000 description 1
- NKCGSNLYNUPHGB-UHFFFAOYSA-N 2-(4-fluoro-3-hydroxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound C=1C=C(F)C(O)=CC=1C=1SC2=CC(O)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 NKCGSNLYNUPHGB-UHFFFAOYSA-N 0.000 description 1
- NDEJPNUNJGUMQB-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound C1=C(F)C(OC)=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 NDEJPNUNJGUMQB-UHFFFAOYSA-N 0.000 description 1
- SFIPEXFBEUBODA-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol Chemical compound C1=C(F)C(OC)=CC(C2=C(C3=CC=C(O)C=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 SFIPEXFBEUBODA-UHFFFAOYSA-N 0.000 description 1
- YYIJTKJGGNSKME-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C=C1C1=CC=C(F)C(OC)=C1 YYIJTKJGGNSKME-UHFFFAOYSA-N 0.000 description 1
- ATOQGLHEJBGQOG-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene 1-oxide Chemical compound O=S1C2=CC(OC)=CC=C2C=C1C1=CC=C(F)C(OC)=C1 ATOQGLHEJBGQOG-UHFFFAOYSA-N 0.000 description 1
- SUKKEMXXHXLING-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-6-methoxy-3-(4-methylphenyl)sulfonyl-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C(S(=O)(=O)C=2C=CC(C)=CC=2)=C1C1=CC=C(F)C(OC)=C1 SUKKEMXXHXLING-UHFFFAOYSA-N 0.000 description 1
- XNLDXUFUDNPRLY-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-6-methoxy-3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCC1=CC=CC=C1 XNLDXUFUDNPRLY-UHFFFAOYSA-N 0.000 description 1
- AIWSAZCHHATQFC-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-6-methoxy-3-[4-[2-(4-methylphenyl)sulfonylethoxy]phenoxy]-1-benzothiophene Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCCS(=O)(=O)C1=CC=C(C)C=C1 AIWSAZCHHATQFC-UHFFFAOYSA-N 0.000 description 1
- MNURPFVONZPVLA-UHFFFAOYSA-N 2-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1Cl MNURPFVONZPVLA-UHFFFAOYSA-N 0.000 description 1
- MUKKRRSMMDHDED-UHFFFAOYSA-N 2-fluoro-4-[3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]phenol;hydrochloride Chemical compound Cl.C1=C(F)C(O)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=CC=C2S1 MUKKRRSMMDHDED-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- HMGCGUWFPZVPEK-UHFFFAOYSA-N 2-naphthalen-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=C1 HMGCGUWFPZVPEK-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- ONJRTQUWKRDCTA-UHFFFAOYSA-N 2h-thiochromene Chemical compound C1=CC=C2C=CCSC2=C1 ONJRTQUWKRDCTA-UHFFFAOYSA-N 0.000 description 1
- YJKYBLAUEBDCSU-UHFFFAOYSA-N 3-(4-phenylmethoxyphenoxy)-1-benzothiophene Chemical compound C=1C=C(OC=2C3=CC=CC=C3SC=2)C=CC=1OCC1=CC=CC=C1 YJKYBLAUEBDCSU-UHFFFAOYSA-N 0.000 description 1
- MEGDDERINISWIY-UHFFFAOYSA-N 3-[3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]phenol Chemical compound OC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 MEGDDERINISWIY-UHFFFAOYSA-N 0.000 description 1
- SRQACPUSXOEQKU-UHFFFAOYSA-N 3-[4-(2-bromoethoxy)phenoxy]-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCBr)=CC=2)=C1 SRQACPUSXOEQKU-UHFFFAOYSA-N 0.000 description 1
- MTAPMJXMHJYEFU-UHFFFAOYSA-N 3-[4-(2-bromoethoxy)phenoxy]-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCCBr)C=C1 MTAPMJXMHJYEFU-UHFFFAOYSA-N 0.000 description 1
- ORGGYDIFWWTQDP-UHFFFAOYSA-N 3-[4-(2-bromoethoxy)phenoxy]-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCCBr)C=C1 ORGGYDIFWWTQDP-UHFFFAOYSA-N 0.000 description 1
- UEMSISPKNVYCFI-UHFFFAOYSA-N 3-[4-(2-bromoethoxy)phenoxy]-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(OCCBr)=CC=2)=C1 UEMSISPKNVYCFI-UHFFFAOYSA-N 0.000 description 1
- WREQYWAXOAHDAX-UHFFFAOYSA-N 3-[4-(2-bromopropoxy)phenoxy]-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCC(C)Br)=CC=2)=C1 WREQYWAXOAHDAX-UHFFFAOYSA-N 0.000 description 1
- ARXHRVZVMGITNA-UHFFFAOYSA-N 3-[4-(2-bromopropoxy)phenoxy]-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCC(C)Br)C=C1 ARXHRVZVMGITNA-UHFFFAOYSA-N 0.000 description 1
- KTLKGTJILRWKSM-UHFFFAOYSA-N 3-[4-(2-bromopropoxy)phenoxy]-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCC(C)Br)C=C1 KTLKGTJILRWKSM-UHFFFAOYSA-N 0.000 description 1
- WUSBBFKMBIHVBE-UHFFFAOYSA-N 3-[4-(2-bromopropoxy)phenoxy]-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(OCC(C)Br)=CC=2)=C1 WUSBBFKMBIHVBE-UHFFFAOYSA-N 0.000 description 1
- RMTNCZHHCXOZNB-UHFFFAOYSA-N 3-[4-(2-chloroethoxy)phenoxy]-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCCCl)=CC=2)=C1 RMTNCZHHCXOZNB-UHFFFAOYSA-N 0.000 description 1
- FBNNDPSTHHIPRT-UHFFFAOYSA-N 3-[4-(2-chloroethoxy)phenoxy]-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCCCl)C=C1 FBNNDPSTHHIPRT-UHFFFAOYSA-N 0.000 description 1
- GMOVVXKCSSBPSI-UHFFFAOYSA-N 3-[4-(2-chloroethoxy)phenoxy]-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCCCl)C=C1 GMOVVXKCSSBPSI-UHFFFAOYSA-N 0.000 description 1
- NGBPNGZCEUIWLB-UHFFFAOYSA-N 3-[4-(2-chloroethoxy)phenoxy]-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(OCCCl)=CC=2)=C1 NGBPNGZCEUIWLB-UHFFFAOYSA-N 0.000 description 1
- UEVCTYACHLNTTB-UHFFFAOYSA-N 3-[4-(2-chloropropoxy)phenoxy]-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(OCC(C)Cl)=CC=2)=C1 UEVCTYACHLNTTB-UHFFFAOYSA-N 0.000 description 1
- IUCIABJKWPVEGP-UHFFFAOYSA-N 3-[4-(2-chloropropoxy)phenoxy]-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCC(C)Cl)C=C1 IUCIABJKWPVEGP-UHFFFAOYSA-N 0.000 description 1
- HIDXGLQZVPGQHE-UHFFFAOYSA-N 3-[4-(2-chloropropoxy)phenoxy]-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(OCC(C)Cl)C=C1 HIDXGLQZVPGQHE-UHFFFAOYSA-N 0.000 description 1
- QJMCKSNOEVVLSV-UHFFFAOYSA-N 3-[4-(2-chloropropoxy)phenoxy]-6-methoxy-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(OCC(C)Cl)=CC=2)=C1 QJMCKSNOEVVLSV-UHFFFAOYSA-N 0.000 description 1
- KUYBKTDXFCHYBQ-UHFFFAOYSA-N 3-[6-hydroxy-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]benzene-1,2-diol Chemical compound C=1C=CC(O)=C(O)C=1C=1SC2=CC(O)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 KUYBKTDXFCHYBQ-UHFFFAOYSA-N 0.000 description 1
- BEBILKJSLIXGJP-UHFFFAOYSA-N 3-[6-methoxy-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]phenol Chemical compound C=1C=CC(O)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 BEBILKJSLIXGJP-UHFFFAOYSA-N 0.000 description 1
- SRWDQSRTOOMPMO-UHFFFAOYSA-N 3-bromo-1-benzothiophene Chemical compound C1=CC=C2C(Br)=CSC2=C1 SRWDQSRTOOMPMO-UHFFFAOYSA-N 0.000 description 1
- JSOQCODKQVLALE-UHFFFAOYSA-N 3-bromo-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)Br)=C1 JSOQCODKQVLALE-UHFFFAOYSA-N 0.000 description 1
- WSGWDSBRPJCISC-UHFFFAOYSA-N 3-bromo-2-(3-methoxyphenyl)-1-benzothiophene 1-oxide Chemical compound COC1=CC=CC(C=2S(C3=CC=CC=C3C=2Br)=O)=C1 WSGWDSBRPJCISC-UHFFFAOYSA-N 0.000 description 1
- DSCPTVTZYAQBIB-UHFFFAOYSA-N 3-bromo-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C(Br)=C1C1=CC=C(F)C(OC)=C1 DSCPTVTZYAQBIB-UHFFFAOYSA-N 0.000 description 1
- KNSCTANPMZEBCG-UHFFFAOYSA-N 3-bromo-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene 1-oxide Chemical compound O=S1C2=CC(OC)=CC=C2C(Br)=C1C1=CC=C(F)C(OC)=C1 KNSCTANPMZEBCG-UHFFFAOYSA-N 0.000 description 1
- DDEYMGADORHXJL-UHFFFAOYSA-N 3-bromo-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C(Br)=C1C1=CC=CC=C1OC DDEYMGADORHXJL-UHFFFAOYSA-N 0.000 description 1
- DKBFGGTXVOOWDL-UHFFFAOYSA-N 3-bromo-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene 1-oxide Chemical compound O=S1C2=CC(OC)=CC=C2C(Br)=C1C1=CC=CC=C1OC DKBFGGTXVOOWDL-UHFFFAOYSA-N 0.000 description 1
- HOKVCOSATCXNAR-UHFFFAOYSA-N 3-chloro-2-(3-methoxyphenyl)-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=CC=C3S2)Cl)=C1 HOKVCOSATCXNAR-UHFFFAOYSA-N 0.000 description 1
- PFDAJGNEFUSAPB-UHFFFAOYSA-N 3-chloro-2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C(Cl)=C1C1=CC=C(F)C(OC)=C1 PFDAJGNEFUSAPB-UHFFFAOYSA-N 0.000 description 1
- HCZNHEDKASIFDU-UHFFFAOYSA-N 3-chloro-6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C(Cl)=C1C1=CC=CC=C1OC HCZNHEDKASIFDU-UHFFFAOYSA-N 0.000 description 1
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
- BPVQJTJLWMFXBE-UHFFFAOYSA-N 4-[6-hydroxy-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]benzene-1,2-diol Chemical compound C=1C=C(O)C(O)=CC=1C=1SC2=CC(O)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 BPVQJTJLWMFXBE-UHFFFAOYSA-N 0.000 description 1
- DARZKKRTCPVSQC-UHFFFAOYSA-N 4-[6-methoxy-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-2-yl]benzene-1,2-diol Chemical compound C=1C=C(O)C(O)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 DARZKKRTCPVSQC-UHFFFAOYSA-N 0.000 description 1
- CAOKHXCVRWLVNC-UHFFFAOYSA-N 4-[[2-(2-chloro-3,4-dimethoxyphenyl)-6-methoxy-1-benzothiophen-3-yl]oxy]phenol Chemical compound C=1C=C(OC)C(OC)=C(Cl)C=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(O)C=C1 CAOKHXCVRWLVNC-UHFFFAOYSA-N 0.000 description 1
- ANKMTKJNJZHQLA-UHFFFAOYSA-N 4-[[2-(3-fluoro-4-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenol Chemical compound C1=C(F)C(OC)=CC=C1C1=C(OC=2C=CC(O)=CC=2)C2=CC=CC=C2S1 ANKMTKJNJZHQLA-UHFFFAOYSA-N 0.000 description 1
- PBMVNZIQLZPOFA-UHFFFAOYSA-N 4-[[2-(4-fluoro-3-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenol Chemical compound C1=C(F)C(OC)=CC(C2=C(C3=CC=CC=C3S2)OC=2C=CC(O)=CC=2)=C1 PBMVNZIQLZPOFA-UHFFFAOYSA-N 0.000 description 1
- UAUXAVIFUGKXIO-UHFFFAOYSA-N 4-[[2-(4-fluoro-3-methoxyphenyl)-6-methoxy-1-benzothiophen-3-yl]oxy]phenol Chemical compound C=1C=C(F)C(OC)=CC=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(O)C=C1 UAUXAVIFUGKXIO-UHFFFAOYSA-N 0.000 description 1
- RUVKCSPYQMSBRD-UHFFFAOYSA-N 4-[[6-methoxy-2-(2-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenol Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC1=CC=C(O)C=C1 RUVKCSPYQMSBRD-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- IWYVYUZADLIDEY-UHFFFAOYSA-M 4-methoxybenzenesulfonate Chemical compound COC1=CC=C(S([O-])(=O)=O)C=C1 IWYVYUZADLIDEY-UHFFFAOYSA-M 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 1
- JLQYGKWHOLNSKH-UHFFFAOYSA-N 6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C=C1C1=CC=CC=C1OC JLQYGKWHOLNSKH-UHFFFAOYSA-N 0.000 description 1
- OLKHKJIIIKPWHY-UHFFFAOYSA-N 6-methoxy-2-(2-methoxyphenyl)-1-benzothiophene 1-oxide Chemical compound O=S1C2=CC(OC)=CC=C2C=C1C1=CC=CC=C1OC OLKHKJIIIKPWHY-UHFFFAOYSA-N 0.000 description 1
- FHTZTENWKVNGOA-UHFFFAOYSA-N 6-methoxy-2-(2-methoxyphenyl)-3-(4-methylphenyl)sulfonyl-1-benzothiophene Chemical compound S1C2=CC(OC)=CC=C2C(S(=O)(=O)C=2C=CC(C)=CC=2)=C1C1=CC=CC=C1OC FHTZTENWKVNGOA-UHFFFAOYSA-N 0.000 description 1
- DVZSHHIUDIZIDY-UHFFFAOYSA-N 6-methoxy-2-(2-methoxyphenyl)-3-[4-[2-(4-methylphenyl)sulfonylethoxy]phenoxy]-1-benzothiophene Chemical compound C=1C=CC=C(OC)C=1C=1SC2=CC(OC)=CC=C2C=1OC(C=C1)=CC=C1OCCS(=O)(=O)C1=CC=C(C)C=C1 DVZSHHIUDIZIDY-UHFFFAOYSA-N 0.000 description 1
- ATYANUAEWCJDJQ-UHFFFAOYSA-N 6-methoxy-2-(3-methoxyphenyl)-3-[4-[2-(4-methylphenyl)sulfonylethoxy]phenoxy]-1-benzothiophene Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC)C=C3S2)OC=2C=CC(OCCS(=O)(=O)C=3C=CC(C)=CC=3)=CC=2)=C1 ATYANUAEWCJDJQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000004746 Atrophic Vaginitis Diseases 0.000 description 1
- 206010003693 Atrophic vulvovaginitis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- WKRLQDKEXYKHJB-UHFFFAOYSA-N Equilin Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3=CCC2=C1 WKRLQDKEXYKHJB-UHFFFAOYSA-N 0.000 description 1
- UOACKFBJUYNSLK-XRKIENNPSA-N Estradiol Cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H](C4=CC=C(O)C=C4CC3)CC[C@@]21C)C(=O)CCC1CCCC1 UOACKFBJUYNSLK-XRKIENNPSA-N 0.000 description 1
- RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
- QECVIPBZOPUTRD-UHFFFAOYSA-N N=S(=O)=O Chemical class N=S(=O)=O QECVIPBZOPUTRD-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- ICTXHFFSOAJUMG-SLHNCBLASA-N Norethynodrel Chemical compound C1CC(=O)CC2=C1[C@H]1CC[C@](C)([C@](CC3)(O)C#C)[C@@H]3[C@@H]1CC2 ICTXHFFSOAJUMG-SLHNCBLASA-N 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920000081 Polyestradiol phosphate Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- LCYXYLLJXMAEMT-SAXRGWBVSA-N Pyridinoline Chemical compound OC(=O)[C@@H](N)CCC1=C[N+](C[C@H](O)CC[C@H](N)C([O-])=O)=CC(O)=C1C[C@H](N)C(O)=O LCYXYLLJXMAEMT-SAXRGWBVSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010067269 Uterine fibrosis Diseases 0.000 description 1
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
- HHXRBPPDANGOIT-UHFFFAOYSA-N [2-(2,3-diacetyloxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-yl] acetate Chemical compound C=1C=CC(OC(C)=O)=C(OC(C)=O)C=1C=1SC2=CC(OC(=O)C)=CC=C2C=1OC(C=C1)=CC=C1OCCN1CCCCC1 HHXRBPPDANGOIT-UHFFFAOYSA-N 0.000 description 1
- JRSSNIFUCRGOOH-UHFFFAOYSA-N [2-(3-hydroxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-yl] benzoate Chemical compound OC1=CC=CC(C2=C(C3=CC=C(OC(=O)C=4C=CC=CC=4)C=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 JRSSNIFUCRGOOH-UHFFFAOYSA-N 0.000 description 1
- LITGQZLQXCTVNB-UHFFFAOYSA-N [2-(3-methoxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-yl] acetate Chemical compound COC1=CC=CC(C2=C(C3=CC=C(OC(C)=O)C=C3S2)OC=2C=CC(OCCN3CCCCC3)=CC=2)=C1 LITGQZLQXCTVNB-UHFFFAOYSA-N 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- YTIVTFGABIZHHX-UHFFFAOYSA-L acetylenedicarboxylate(2-) Chemical compound [O-]C(=O)C#CC([O-])=O YTIVTFGABIZHHX-UHFFFAOYSA-L 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000003150 biochemical marker Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 229960003608 clomifene Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- PDRGHUMCVRDZLQ-UHFFFAOYSA-N d-equilenin Natural products OC1=CC=C2C(CCC3(C4CCC3=O)C)=C4C=CC2=C1 PDRGHUMCVRDZLQ-UHFFFAOYSA-N 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- NFDFQCUYFHCNBW-SCGPFSFSSA-N dienestrol Chemical compound C=1C=C(O)C=CC=1\C(=C/C)\C(=C\C)\C1=CC=C(O)C=C1 NFDFQCUYFHCNBW-SCGPFSFSSA-N 0.000 description 1
- 229960003839 dienestrol Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000001278 effect on cholesterol Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- PDRGHUMCVRDZLQ-WMZOPIPTSA-N equilenin Chemical compound OC1=CC=C2C(CC[C@]3([C@H]4CCC3=O)C)=C4C=CC2=C1 PDRGHUMCVRDZLQ-WMZOPIPTSA-N 0.000 description 1
- WKRLQDKEXYKHJB-HFTRVMKXSA-N equilin Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 WKRLQDKEXYKHJB-HFTRVMKXSA-N 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960005416 estradiol cypionate Drugs 0.000 description 1
- 229960004766 estradiol valerate Drugs 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- HZEQBCVBILBTEP-ZFINNJDLSA-N estropipate Chemical compound C1CNCCN1.OS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 HZEQBCVBILBTEP-ZFINNJDLSA-N 0.000 description 1
- 229940081345 estropipate Drugs 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 208000020089 femoral neck fracture Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 229940001490 fosamax Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- KQDJZZWCYTXUDE-UHFFFAOYSA-N hydron;thiophene;chloride Chemical compound Cl.C=1C=CSC=1 KQDJZZWCYTXUDE-UHFFFAOYSA-N 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- TVZISJTYELEYPI-UHFFFAOYSA-N hypodiphosphoric acid Chemical compound OP(O)(=O)P(O)(O)=O TVZISJTYELEYPI-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229960004400 levonorgestrel Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004616 medroxyprogesterone Drugs 0.000 description 1
- FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 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
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003821 menstrual periods Effects 0.000 description 1
- IMSSROKUHAOUJS-MJCUULBUSA-N mestranol Chemical compound C1C[C@]2(C)[C@@](C#C)(O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 IMSSROKUHAOUJS-MJCUULBUSA-N 0.000 description 1
- 229960001390 mestranol Drugs 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- RBXVOQPAMPBADW-UHFFFAOYSA-N nitrous acid;phenol Chemical class ON=O.OC1=CC=CC=C1 RBXVOQPAMPBADW-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229960001858 norethynodrel Drugs 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- SJLOMQIUPFZJAN-UHFFFAOYSA-N oxorhodium Chemical compound [Rh]=O SJLOMQIUPFZJAN-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229960001298 polyestradiol phosphate Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 201000010808 postmenopausal atrophic vaginitis Diseases 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001072 progestational effect Effects 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- HNDXKIMMSFCCFW-UHFFFAOYSA-M propane-2-sulfonate Chemical compound CC(C)S([O-])(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-M 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940063222 provera Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910003450 rhodium oxide Inorganic materials 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 102000012498 secondary active transmembrane transporter activity proteins Human genes 0.000 description 1
- 108040003878 secondary active transmembrane transporter activity proteins Proteins 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical class O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 206010041569 spinal fracture Diseases 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
- WHLUQAYNVOGZST-UHFFFAOYSA-N tifenamil Chemical compound C=1C=CC=CC=1C(C(=O)SCCN(CC)CC)C1=CC=CC=C1 WHLUQAYNVOGZST-UHFFFAOYSA-N 0.000 description 1
- 229940019375 tiludronate Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 230000001836 utereotrophic effect Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/64—Oxygen atoms
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/56—Radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2512496P | 1996-08-29 | 1996-08-29 | |
| US25124P | 1996-08-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69726513D1 DE69726513D1 (de) | 2004-01-15 |
| DE69726513T2 true DE69726513T2 (de) | 2004-09-30 |
Family
ID=21824170
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69726513T Expired - Fee Related DE69726513T2 (de) | 1996-08-29 | 1997-08-27 | Benzo[B]thiophenverbindungen,Zwischenprodukte,Verfahren,Zusammensetzungen und Methode |
Country Status (7)
| Country | Link |
|---|---|
| US (4) | US5843965A (enExample) |
| EP (1) | EP0827959B1 (enExample) |
| JP (1) | JPH1095778A (enExample) |
| AT (1) | ATE255574T1 (enExample) |
| CA (1) | CA2214072C (enExample) |
| DE (1) | DE69726513T2 (enExample) |
| ES (1) | ES2212048T3 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2214072C (en) * | 1996-08-29 | 2006-11-14 | Eli Lilly And Company | Benzo [b] thiophene compounds, intermediates, processes, compositions, and methods |
| AU735703B2 (en) * | 1997-06-10 | 2001-07-12 | Karo Bio Ab | Estrogen receptor ligands |
| WO1999051587A1 (en) * | 1998-04-01 | 1999-10-14 | Ono Pharmaceutical Co., Ltd. | Fused thiophene derivatives and drugs containing the same as the active ingredient |
| PL343438A1 (en) * | 1998-04-08 | 2001-08-13 | Lilly Co Eli | Pulmonary and nasal delivery of raloxifene |
| US6087378A (en) * | 1998-10-13 | 2000-07-11 | Eli Lilly And Company | Pharmaceutical formulations and applications thereof for the treatment of estrogen deprivation syndrome |
| JP2004531559A (ja) * | 2001-05-22 | 2004-10-14 | イーライ・リリー・アンド・カンパニー | エストロゲン欠乏または内因性エストロゲンに対する異常な生理反応に関連する疾患を抑制するためのテトラヒドロキノリン誘導体 |
| WO2002094788A1 (en) * | 2001-05-22 | 2002-11-28 | Eli Lilly And Company | 2-substituted 1,2,3,4-tetrahydroquinolines and derivatives thereof, compositions and methods |
| EP3192795B1 (en) | 2012-10-24 | 2020-12-02 | The Board of Trustees of the University of Illionis | Compositions and methods for treating estrogen-related medical disorders |
| ES2774935T3 (es) | 2012-10-24 | 2020-07-23 | Univ Illinois | Composiciones y métodos para tratar trastornos médicos relacionados con estrógeno |
| CN114516853A (zh) * | 2022-02-24 | 2022-05-20 | 青岛科技大学 | 一种含药物分子的苯并噻吩衍生物的电催化制备方法 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1300575B (de) * | 1965-05-21 | 1969-08-07 | Bristol Myers Co | Benzo[b]thiophene |
| US3394125A (en) * | 1965-10-23 | 1968-07-23 | Bristol Myers Co | 2-phenyl-3-tertiary-aminoalkoxy phenyl-and corresponding tertiaryaminoalkyl thio benzfurans substituted in the benzo nucleus with an alkoxy or tertiaryamino alkoxy or alkylthio group |
| US4230862A (en) * | 1975-10-28 | 1980-10-28 | Eli Lilly And Company | Antifertility compounds |
| US4133814A (en) * | 1975-10-28 | 1979-01-09 | Eli Lilly And Company | 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents |
| US4380635A (en) * | 1981-04-03 | 1983-04-19 | Eli Lilly And Company | Synthesis of acylated benzothiophenes |
| US4418068A (en) * | 1981-04-03 | 1983-11-29 | Eli Lilly And Company | Antiestrogenic and antiandrugenic benzothiophenes |
| GB2097788B (en) * | 1981-04-03 | 1985-04-24 | Lilly Co Eli | Benzothiophene compounds and process for preparing them |
| US4358593A (en) * | 1981-04-03 | 1982-11-09 | Eli Lilly And Company | Process for preparing 3-(4-aminoethoxybenzoyl)benzo[b]thiophenes |
| JPH02501301A (ja) * | 1987-09-25 | 1990-05-10 | チバ‐ガイギー アクチェンゲゼルシャフト | ４‐（トリアルキルベンジル）‐ピペラジニル化合物のジアシル誘導体 |
| US5395842A (en) * | 1988-10-31 | 1995-03-07 | Endorecherche Inc. | Anti-estrogenic compounds and compositions |
| DE4117512A1 (de) * | 1991-05-25 | 1992-11-26 | Schering Ag | 2-phenylbenzo(b)furane und -thiophene, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
| JP3157882B2 (ja) * | 1991-11-15 | 2001-04-16 | 帝国臓器製薬株式会社 | 新規なベンゾチオフエン誘導体 |
| TW366342B (en) * | 1992-07-28 | 1999-08-11 | Lilly Co Eli | The use of 2-phenyl-3-aroylbenzothiophenes in inhibiting bone loss |
| TW383306B (en) * | 1992-12-22 | 2000-03-01 | Lilly Co Eli | New use of 2-phenyl-3-aroylbenzothiophenes in lowering serum cholesterol |
| US5482949A (en) * | 1993-03-19 | 1996-01-09 | Eli Lilly And Company | Sulfonate derivatives of 3-aroylbenzo[b]thiophenes |
| US6756388B1 (en) * | 1993-10-12 | 2004-06-29 | Pfizer Inc. | Benzothiophenes and related compounds as estrogen agonists |
| US5461065A (en) * | 1993-10-15 | 1995-10-24 | Eli Lilly And Company | Methods for inhibiting endometriosis |
| US5492921A (en) * | 1994-09-20 | 1996-02-20 | Eli Lilly And Company | Benzothiophene compounds, compositions, and methods for inhibiting aortal smooth muscle proliferation |
| IL132952A (en) * | 1995-02-28 | 2002-02-10 | Lilly Co Eli | Benzothiophene derivatives |
| US5510357A (en) * | 1995-02-28 | 1996-04-23 | Eli Lilly And Company | Benzothiophene compounds as anti-estrogenic agents |
| US6395755B1 (en) * | 1995-03-10 | 2002-05-28 | Eli Lilly And Company | Benzothiophene pharmaceutical compounds |
| US5728724A (en) * | 1995-08-17 | 1998-03-17 | Eli Lilly And Company | Benzothiophene compounds |
| CA2214072C (en) * | 1996-08-29 | 2006-11-14 | Eli Lilly And Company | Benzo [b] thiophene compounds, intermediates, processes, compositions, and methods |
-
1997
- 1997-08-25 CA CA002214072A patent/CA2214072C/en not_active Expired - Fee Related
- 1997-08-27 ES ES97306546T patent/ES2212048T3/es not_active Expired - Lifetime
- 1997-08-27 US US08/924,772 patent/US5843965A/en not_active Expired - Fee Related
- 1997-08-27 AT AT97306546T patent/ATE255574T1/de not_active IP Right Cessation
- 1997-08-27 DE DE69726513T patent/DE69726513T2/de not_active Expired - Fee Related
- 1997-08-27 EP EP97306546A patent/EP0827959B1/en not_active Expired - Lifetime
- 1997-08-28 JP JP9232472A patent/JPH1095778A/ja not_active Ceased
-
1998
- 1998-06-30 US US09/107,593 patent/US5977382A/en not_active Expired - Fee Related
- 1998-06-30 US US09/107,344 patent/US5977098A/en not_active Expired - Fee Related
- 1998-06-30 US US09/107,831 patent/US5952513A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE255574T1 (de) | 2003-12-15 |
| CA2214072A1 (en) | 1998-02-28 |
| DE69726513D1 (de) | 2004-01-15 |
| US5952513A (en) | 1999-09-14 |
| EP0827959A2 (en) | 1998-03-11 |
| EP0827959A3 (en) | 1998-03-18 |
| US5843965A (en) | 1998-12-01 |
| US5977098A (en) | 1999-11-02 |
| ES2212048T3 (es) | 2004-07-16 |
| JPH1095778A (ja) | 1998-04-14 |
| EP0827959B1 (en) | 2003-12-03 |
| CA2214072C (en) | 2006-11-14 |
| US5977382A (en) | 1999-11-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69525699T2 (de) | Naphthyl-Derivate, Zwischenprodukte, Verfahren, Zusammensetzungen, die sie enthalten | |
| DE69526550T2 (de) | 2-(4-Hydroxyphenyl)-benzothiophen-Derivate, Zubereitungen und Methoden zur Milderung der Symptome des post-menopausalen Syndroms | |
| DE69602638T2 (de) | Naphthylverbindungen, Zwischenprodukte, Zusammensetzungen und Methoden | |
| DE69726541T2 (de) | 1-Aryloxy-2-arylnaphthylverbindungen, Zwischenprodukte, Zusammensetzungen und Verfahren | |
| DE69616396T2 (de) | Benzothiophen-Verbindungen, Zwischenprodukte, Zusammensetzungen und Verfahren | |
| DE69611015T2 (de) | Pentazyklische Verbindungen, Zwischenprodukte, Verfahren, Zubereitungen und Methode | |
| DE69629624T2 (de) | Verbindungen mit stickstoffenthaltenden nichtbasischen Seitenketten und diese enthaltende Zubereitungen | |
| DE69628246T2 (de) | Naphthyl- und Dihydronaphthylverbindungen als Arzneimittel | |
| DE69532079T2 (de) | Benzofuranverbindungen, präparate und verfahren | |
| DE69724733T2 (de) | Substituierte Benzo(b)thiophene als selektive Östrogenrezeptormodulatoren | |
| DE69611452T2 (de) | Benzothiophenderivate | |
| DE69726513T2 (de) | Benzo[B]thiophenverbindungen,Zwischenprodukte,Verfahren,Zusammensetzungen und Methode | |
| DE69707611T2 (de) | Dihydronaphthalen- und Naphthalenderivate, Zwischenverbindungen, Zusammensetzungen und deren Herstellungsverfahren | |
| DE69731043T2 (de) | Benzo[B]thiophen-Verbindungen, Zwischenprodukte, Verfahren und Zusammensetzungen | |
| MXPA98000800A (en) | Compounds, intermediates of naftilo and dihidronaftilo, compositions and meto | |
| DE69635852T2 (de) | Verbindungen mit Stickstoff enthaltenden, nichtbasischen Seitenketten und diese enthaltende Zubereitungen | |
| DE69708418T2 (de) | Naphthylverbindungen und Zusammensetzungen | |
| DE69706386T2 (de) | 2-Aryl-3-Aminoaryloxynaphthylverbindungen, Zwischenverbindungen, Zusammensetzungen und Verfahren | |
| DE69730796T2 (de) | Naphthylverbindungen, Zusammensetzungen und Verfahren | |
| DE69724062T2 (de) | Benzothiophenderivate, Zwischenprodukte, Verfahren, Zubereitungen und Methoden | |
| DE69600709T2 (de) | Verbindungen mit N-Acyliertem Piperidin in der Seitenkette und Zusammensetzungen | |
| DE69629500T2 (de) | Benzothiophene Verbindungen als Pharmazeutika | |
| DE60210283T2 (de) | 2-substituierte 1,2,3,4-tetrahydrochinoline und derivate davon, zusammensetzungen und verfahren | |
| DE69724548T2 (de) | Substituierte 2,3-Aryl-Benzothiophene und ihre östrogene Aktivität | |
| DE69711527T2 (de) | Benzofluorenverbindungen, Zwischenverbindungen, Zusammensetzungen und Verfahren |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |