RU2738646C2 - Модуляторы эстрогеновых рецепторов - Google Patents
Модуляторы эстрогеновых рецепторов Download PDFInfo
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- RU2738646C2 RU2738646C2 RU2018132037A RU2018132037A RU2738646C2 RU 2738646 C2 RU2738646 C2 RU 2738646C2 RU 2018132037 A RU2018132037 A RU 2018132037A RU 2018132037 A RU2018132037 A RU 2018132037A RU 2738646 C2 RU2738646 C2 RU 2738646C2
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- Russia
- Prior art keywords
- mmol
- methyl
- indol
- compound
- group
- Prior art date
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- 239000002834 estrogen receptor modulator Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 170
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 62
- 239000001257 hydrogen Substances 0.000 claims abstract description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 58
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 40
- 102100038595 Estrogen receptor Human genes 0.000 claims abstract description 37
- 108010038795 estrogen receptors Proteins 0.000 claims abstract description 29
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 23
- 150000002367 halogens Chemical class 0.000 claims abstract description 23
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 17
- 230000001419 dependent effect Effects 0.000 claims abstract description 17
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 16
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
- 230000001404 mediated effect Effects 0.000 claims abstract description 16
- 108010007005 Estrogen Receptor alpha Proteins 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 14
- 102000015694 estrogen receptors Human genes 0.000 claims abstract description 8
- 239000000262 estrogen Substances 0.000 claims abstract description 7
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 138
- -1 difluorocyclobutyl Chemical group 0.000 claims description 102
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 36
- 150000002431 hydrogen Chemical class 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 17
- 239000003085 diluting agent Substances 0.000 claims description 10
- MAWOHFOSAIXURX-UHFFFAOYSA-N cyclopentylcyclopentane Chemical group C1CCCC1C1CCCC1 MAWOHFOSAIXURX-UHFFFAOYSA-N 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- GDGULTXZDPTNNZ-NSCUHMNNSA-N methyl (E)-3-(3,5-difluoro-4-formylphenyl)prop-2-enoate Chemical compound COC(=O)\C=C\c1cc(F)c(C=O)c(F)c1 GDGULTXZDPTNNZ-NSCUHMNNSA-N 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 230000010261 cell growth Effects 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 206010014733 Endometrial cancer Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 168
- 201000010099 disease Diseases 0.000 abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 21
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 14
- 239000000126 substance Substances 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 6
- 102000005962 receptors Human genes 0.000 abstract description 5
- 108020003175 receptors Proteins 0.000 abstract description 5
- 229940011871 estrogen Drugs 0.000 abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 3
- 230000004663 cell proliferation Effects 0.000 abstract description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 390
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 258
- 239000000243 solution Substances 0.000 description 198
- 235000019439 ethyl acetate Nutrition 0.000 description 159
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 136
- 239000011541 reaction mixture Substances 0.000 description 131
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 115
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 110
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 100
- 239000012044 organic layer Substances 0.000 description 99
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
- 239000007787 solid Substances 0.000 description 78
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 71
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 70
- 229910004298 SiO 2 Inorganic materials 0.000 description 70
- 229910052938 sodium sulfate Inorganic materials 0.000 description 70
- 235000011152 sodium sulphate Nutrition 0.000 description 70
- 125000001072 heteroaryl group Chemical group 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- 125000003118 aryl group Chemical group 0.000 description 43
- 238000003818 flash chromatography Methods 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 239000011734 sodium Substances 0.000 description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 31
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
- 229960000583 acetic acid Drugs 0.000 description 29
- 125000004429 atom Chemical group 0.000 description 29
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 28
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
- 125000000392 cycloalkenyl group Chemical group 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 25
- 238000002347 injection Methods 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 25
- 229920006395 saturated elastomer Polymers 0.000 description 24
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 23
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 22
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 20
- 238000004808 supercritical fluid chromatography Methods 0.000 description 19
- 239000010410 layer Substances 0.000 description 18
- 125000003342 alkenyl group Chemical group 0.000 description 17
- 125000000304 alkynyl group Chemical group 0.000 description 17
- 239000007788 liquid Substances 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- QSQQQURBVYWZKJ-MRVPVSSYSA-N (2r)-1-(1h-indol-3-yl)propan-2-amine Chemical compound C1=CC=C2C(C[C@H](N)C)=CNC2=C1 QSQQQURBVYWZKJ-MRVPVSSYSA-N 0.000 description 16
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 235000019253 formic acid Nutrition 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- 229910002091 carbon monoxide Inorganic materials 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 238000000746 purification Methods 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 125000003545 alkoxy group Chemical group 0.000 description 11
- 239000006184 cosolvent Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 125000002947 alkylene group Chemical group 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 125000001188 haloalkyl group Chemical group 0.000 description 10
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 10
- 238000004007 reversed phase HPLC Methods 0.000 description 10
- 239000012279 sodium borohydride Substances 0.000 description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 229960002258 fulvestrant Drugs 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- OJFXAMILNHYNSV-UHFFFAOYSA-N (2-fluoro-2-methylpropyl) trifluoromethanesulfonate Chemical compound CC(C)(F)COS(=O)(=O)C(F)(F)F OJFXAMILNHYNSV-UHFFFAOYSA-N 0.000 description 7
- VKLJLIUSOUUEQR-LYIQJEATSA-N (E)-3-[3-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-1-bicyclo[1.1.1]pentanyl]prop-2-enoic acid Chemical compound FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C12CC(C1)(C2)/C=C/C(=O)O)(C)C VKLJLIUSOUUEQR-LYIQJEATSA-N 0.000 description 7
- 229940125944 selective estrogen receptor degrader Drugs 0.000 description 7
- 125000003107 substituted aryl group Chemical group 0.000 description 7
- HGFYTUMJTQXEII-JMAUQWQESA-N (E)-3-[4-[(1R,3R)-2-(1-bicyclo[1.1.1]pentanyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]prop-2-enoic acid Chemical compound C[C@@H]1Cc2c([nH]c3ccccc23)[C@H](N1C12CC(C1)C2)c1c(F)cc(\C=C\C(O)=O)cc1F HGFYTUMJTQXEII-JMAUQWQESA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- DFBDRVGWBHBJNR-BBNFHIFMSA-N (e)-3-[3,5-difluoro-4-[(1r,3r)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]prop-2-enoic acid Chemical compound C1([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H](N2CC(C)(C)F)C)=C(F)C=C(\C=C\C(O)=O)C=C1F DFBDRVGWBHBJNR-BBNFHIFMSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 5
- BVOINHANKYWPHF-OPGSHWCFSA-N N-[(2R)-1-(1H-indol-3-yl)propan-2-yl]bicyclo[1.1.1]pentan-1-amine Chemical compound C[C@H](Cc1c[nH]c2ccccc12)NC12CC(C1)C2 BVOINHANKYWPHF-OPGSHWCFSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- ORCXPYPDHLVQFP-UHFFFAOYSA-N bicyclo[1.1.1]pentane-3-carboxylic acid Chemical compound C1C2CC1(C(=O)O)C2 ORCXPYPDHLVQFP-UHFFFAOYSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 125000005647 linker group Chemical group 0.000 description 5
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 5
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- VKLJLIUSOUUEQR-RRDDARCESA-N (E)-3-[3-[(1S,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-1-bicyclo[1.1.1]pentanyl]prop-2-enoic acid Chemical compound FC(CN1[C@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C12CC(C1)(C2)/C=C/C(=O)O)(C)C VKLJLIUSOUUEQR-RRDDARCESA-N 0.000 description 4
- HGFYTUMJTQXEII-BNZUIEHPSA-N (E)-3-[4-[(1R,3R)-2-(1-bicyclo[1.1.1]pentanyl)-1-deuterio-3-methyl-4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]prop-2-enoic acid Chemical compound C12(CC(C1)C2)N1[C@](C=2NC3=CC=CC=C3C=2C[C@H]1C)([2H])C1=C(C=C(C=C1F)/C=C/C(=O)O)F HGFYTUMJTQXEII-BNZUIEHPSA-N 0.000 description 4
- LUQRDINNYDJOKA-UEVJZNBISA-N (E)-3-[4-[(1R,3R)-2-(1-bicyclo[1.1.1]pentanyl)-3-ethyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]prop-2-enoic acid Chemical compound C12(CC(C1)C2)N1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1CC)C1=C(C=C(C=C1F)/C=C/C(=O)O)F LUQRDINNYDJOKA-UEVJZNBISA-N 0.000 description 4
- QGMBBUQAILNYNG-HDYINOBESA-N (E)-3-[4-[(1R,3R)-2-(1-bicyclo[1.1.1]pentanylmethyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]prop-2-enoic acid Chemical compound C[C@@H]1Cc2c([nH]c3ccccc23)[C@H](N1CC12CC(C1)C2)c1c(F)cc(\C=C\C(O)=O)cc1F QGMBBUQAILNYNG-HDYINOBESA-N 0.000 description 4
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| CA3192617A1 (en) * | 2020-09-20 | 2022-03-24 | Matthew BAGGOTT | Advantageous tryptamine compositions for mental disorders or enhancement |
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2017
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