CA2203078C - 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]indoles en tant qu'agents oestrogeniques - Google Patents

Info

Publication number

CA2203078C

CA2203078C CA 2203078 CA2203078A CA2203078C CA 2203078 C CA2203078 C CA 2203078C CA 2203078 CA2203078 CA 2203078 CA 2203078 A CA2203078 A CA 2203078A CA 2203078 C CA2203078 C CA 2203078C

Authority

CA

Canada

Prior art keywords

nmr

dmso

methyl

indole

indol

Prior art date

1997-04-04

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

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• 239000000262 estrogen Substances 0.000 title abstract description 23
• KQXRJVROLOXPNS-UHFFFAOYSA-N 2-[4-[(2-phenylindol-1-yl)methyl]phenoxy]ethanamine Chemical class C1=CC(OCCN)=CC=C1CN1C2=CC=CC=C2C=C1C1=CC=CC=C1 KQXRJVROLOXPNS-UHFFFAOYSA-N 0.000 title abstract description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 109
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
• 150000003839 salts Chemical class 0.000 claims description 26
• 241000124008 Mammalia Species 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 210000001519 tissue Anatomy 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 11
• 206010065687 Bone loss Diseases 0.000 claims description 7
• 206010030247 Oestrogen deficiency Diseases 0.000 claims description 7
• 230000009471 action Effects 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 6
• 230000002357 endometrial effect Effects 0.000 claims description 5
• 230000035755 proliferation Effects 0.000 claims description 5
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 230000002159 abnormal effect Effects 0.000 claims description 4
• 238000011161 development Methods 0.000 claims description 4
• 208000011580 syndromic disease Diseases 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• UCJGJABZCDBEDK-UHFFFAOYSA-N bazedoxifene Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UCJGJABZCDBEDK-UHFFFAOYSA-N 0.000 claims 2
• 238000000034 method Methods 0.000 abstract description 74
• 238000011282 treatment Methods 0.000 abstract description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 486
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
• 238000005160 1H NMR spectroscopy Methods 0.000 description 87
• 238000005481 NMR spectroscopy Methods 0.000 description 77
• 229910001868 water Inorganic materials 0.000 description 67
• 238000006243 chemical reaction Methods 0.000 description 60
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 59
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
• 239000000243 solution Substances 0.000 description 40
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
• 235000019439 ethyl acetate Nutrition 0.000 description 34
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 31
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 31
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• 239000007787 solid Substances 0.000 description 29
• 229960005309 estradiol Drugs 0.000 description 28
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
• 239000000047 product Substances 0.000 description 28
• 230000015572 biosynthetic process Effects 0.000 description 27
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 230000000694 effects Effects 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• 238000003786 synthesis reaction Methods 0.000 description 21
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 20
• 241000700159 Rattus Species 0.000 description 19
• 229940011871 estrogen Drugs 0.000 description 19
• 239000003921 oil Substances 0.000 description 19
• 235000019198 oils Nutrition 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 18
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
• 210000000988 bone and bone Anatomy 0.000 description 16
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
• 229910000104 sodium hydride Inorganic materials 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 125000004093 cyano group Chemical group *C#N 0.000 description 14
• 239000006260 foam Substances 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• -1 -C02H- Chemical group 0.000 description 13
• ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical class C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 239000012267 brine Substances 0.000 description 12
• 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 12
• 239000007858 starting material Substances 0.000 description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 11
• 125000003282 alkyl amino group Chemical group 0.000 description 11
• 150000002475 indoles Chemical class 0.000 description 11
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 10
• 102000015694 estrogen receptors Human genes 0.000 description 10
• 108010038795 estrogen receptors Proteins 0.000 description 10
• 229910052736 halogen Inorganic materials 0.000 description 10
• 150000002367 halogens Chemical class 0.000 description 10
• 235000019341 magnesium sulphate Nutrition 0.000 description 10
• 239000000741 silica gel Substances 0.000 description 10
• 229910002027 silica gel Inorganic materials 0.000 description 10
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 230000001833 anti-estrogenic effect Effects 0.000 description 9
• 239000000328 estrogen antagonist Substances 0.000 description 9
• 229910052739 hydrogen Inorganic materials 0.000 description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 238000003556 assay Methods 0.000 description 8
• 239000003610 charcoal Substances 0.000 description 8
• 239000001257 hydrogen Substances 0.000 description 8
• 150000002431 hydrogen Chemical group 0.000 description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
• 239000000203 mixture Substances 0.000 description 8
• 210000004291 uterus Anatomy 0.000 description 8
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 229940046836 anti-estrogen Drugs 0.000 description 7
• 125000001309 chloro group Chemical group Cl* 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 7
• 125000004953 trihalomethyl group Chemical group 0.000 description 7
• 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 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 125000005843 halogen group Chemical group 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• 125000004951 trihalomethoxy group Chemical group 0.000 description 6
• UFZKWTITXBRSPK-UHFFFAOYSA-N (4-phenylmethoxyphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1OCC1=CC=CC=C1 UFZKWTITXBRSPK-UHFFFAOYSA-N 0.000 description 5
• GVSMQKKMAYLKMM-UHFFFAOYSA-N 3-chloro-1h-indole Chemical class C1=CC=C2C(Cl)=CNC2=C1 GVSMQKKMAYLKMM-UHFFFAOYSA-N 0.000 description 5
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
• 108060001084 Luciferase Proteins 0.000 description 5
• 125000004414 alkyl thio group Chemical group 0.000 description 5
• MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical class BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 5
• 235000012000 cholesterol Nutrition 0.000 description 5
• MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 5
• 210000000172 cytosol Anatomy 0.000 description 5
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 229930182833 estradiol Natural products 0.000 description 5
• 239000012091 fetal bovine serum Substances 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 238000004809 thin layer chromatography Methods 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 5
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 description 4
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 4
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 4
• MNSDXQDMZMYLNL-UHFFFAOYSA-N 1-(2-chloroethoxy)-4-(chloromethyl)benzene Chemical compound ClCCOC1=CC=C(CCl)C=C1 MNSDXQDMZMYLNL-UHFFFAOYSA-N 0.000 description 4
• CHIFTAQVXHNVRW-UHFFFAOYSA-N 1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=C1 CHIFTAQVXHNVRW-UHFFFAOYSA-N 0.000 description 4
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
• 102100021943 C-C motif chemokine 2 Human genes 0.000 description 4
• 108020004414 DNA Proteins 0.000 description 4
• 229920002307 Dextran Polymers 0.000 description 4
• 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 4
• 239000005089 Luciferase Substances 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 206010028980 Neoplasm Diseases 0.000 description 4
• 229910006121 SOBr2 Inorganic materials 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• DFXWVJDNAQELDD-UHFFFAOYSA-N [4-(2-chloroethoxy)phenyl]methanol Chemical compound OCC1=CC=C(OCCCl)C=C1 DFXWVJDNAQELDD-UHFFFAOYSA-N 0.000 description 4
• 125000004423 acyloxy group Chemical group 0.000 description 4
• 239000000556 agonist Substances 0.000 description 4
• 150000005215 alkyl ethers Chemical class 0.000 description 4
• 125000000217 alkyl group Chemical group 0.000 description 4
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 4
• MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 4
• 230000001076 estrogenic effect Effects 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
• 150000007857 hydrazones Chemical class 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 229960004622 raloxifene Drugs 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 229960001603 tamoxifen Drugs 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 238000001890 transfection Methods 0.000 description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
• 239000011592 zinc chloride Substances 0.000 description 4
• 235000005074 zinc chloride Nutrition 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
• 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 3
• KQBDLOVXZHOAJI-UHFFFAOYSA-N (4-phenylmethoxyphenyl)azanium;chloride Chemical compound Cl.C1=CC(N)=CC=C1OCC1=CC=CC=C1 KQBDLOVXZHOAJI-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• MKYMYZJJFMPDOA-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCC1=CC=CC=C1 MKYMYZJJFMPDOA-UHFFFAOYSA-N 0.000 description 3
• BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 3
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 206010014733 Endometrial cancer Diseases 0.000 description 3
• 206010014759 Endometrial neoplasm Diseases 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• MMCPOSDMTGQNKG-UHFFFAOYSA-N anilinium chloride Chemical compound Cl.NC1=CC=CC=C1 MMCPOSDMTGQNKG-UHFFFAOYSA-N 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 229940073608 benzyl chloride Drugs 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000009977 dual effect Effects 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
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• 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 3
• 238000011156 evaluation Methods 0.000 description 3
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• 150000003840 hydrochlorides Chemical class 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000003756 stirring Methods 0.000 description 3
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 238000001665 trituration Methods 0.000 description 3
• 0 ***C1=CCC(C[n]2c(-c3c(*)cc(*)cc3)c(*)c3c2ccc(*)c3)C=C1 Chemical compound ***C1=CCC(C[n]2c(-c3c(*)cc(*)cc3)c(*)c3c2ccc(*)c3)C=C1 0.000 description 2
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