ES2443845T3 - Sulfonamidas como inhibidores de proteínas de la familia BCL-2 para el tratamiento del cáncer - Google Patents

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Publication number

ES2443845T3

ES2443845T3 ES10750124.9T ES10750124T ES2443845T3 ES 2443845 T3 ES2443845 T3 ES 2443845T3 ES 10750124 T ES10750124 T ES 10750124T ES 2443845 T3 ES2443845 T3 ES 2443845T3

Authority

ES

Spain

Prior art keywords

alkylene

alkyl

pyrimidin

substituted

methyl

Prior art date

2009-09-10

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.)

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• 206010028980 Neoplasm Diseases 0.000 title description 18
• 238000011282 treatment Methods 0.000 title description 15
• 201000011510 cancer Diseases 0.000 title description 12
• 229940124530 sulfonamide Drugs 0.000 title description 9
• 150000003456 sulfonamides Chemical class 0.000 title description 6
• 102000051485 Bcl-2 family Human genes 0.000 title description 5
• 108700038897 Bcl-2 family Proteins 0.000 title description 5
• 239000012268 protein inhibitor Substances 0.000 title description 4
• 229940121649 protein inhibitor Drugs 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 148
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 83
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 54
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 47
• 150000002367 halogens Chemical class 0.000 claims abstract description 45
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 29
• 125000001424 substituent group Chemical group 0.000 claims abstract description 27
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims abstract description 25
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 23
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 21
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 10
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 8
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 7
• 125000004450 alkenylene group Chemical group 0.000 claims abstract description 7
• 229910052805 deuterium Inorganic materials 0.000 claims abstract description 7
• -1 bicyclic radical Chemical class 0.000 claims description 482
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 54
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 49
• 150000003839 salts Chemical class 0.000 claims description 42
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 26
• 229910052801 chlorine Inorganic materials 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 18
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
• 125000003386 piperidinyl group Chemical group 0.000 claims description 13
• 125000004193 piperazinyl group Chemical group 0.000 claims description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
• 230000001028 anti-proliverative effect Effects 0.000 claims description 8
• 125000001624 naphthyl group Chemical group 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
• 125000001188 haloalkyl group Chemical group 0.000 claims description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• 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 claims description 3
• WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 7
• 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 abstract description 26
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 161
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 131
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
• 238000004128 high performance liquid chromatography Methods 0.000 description 95
• 230000014759 maintenance of location Effects 0.000 description 84
• 238000002531 positive electrospray ionisation time-of-flight mass spectrometry Methods 0.000 description 78
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• 239000000543 intermediate Substances 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
• 238000006243 chemical reaction Methods 0.000 description 50
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 46
• 238000000034 method Methods 0.000 description 39
• 239000000243 solution Substances 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 38
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
• 239000000203 mixture Substances 0.000 description 38
• 238000005160 1H NMR spectroscopy Methods 0.000 description 35
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• 239000011541 reaction mixture Substances 0.000 description 34
• 238000003818 flash chromatography Methods 0.000 description 32
• 235000019439 ethyl acetate Nutrition 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 30
• 229910002027 silica gel Inorganic materials 0.000 description 30
• 229910052757 nitrogen Inorganic materials 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
• 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 22
• 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 22
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
• 239000007787 solid Substances 0.000 description 22
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
• 238000005481 NMR spectroscopy Methods 0.000 description 21
• 239000012267 brine Substances 0.000 description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 20
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• 238000006268 reductive amination reaction Methods 0.000 description 18
• 150000001412 amines Chemical class 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 16
• 201000010099 disease Diseases 0.000 description 16
• 238000004896 high resolution mass spectrometry Methods 0.000 description 16
• XVHVBUNXLXLXKG-CYBMUJFWSA-N (2r)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-amine Chemical compound C([C@@H](N)CSC=1C=CC=CC=1)CN1CCOCC1 XVHVBUNXLXLXKG-CYBMUJFWSA-N 0.000 description 15
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
• 239000007832 Na2SO4 Substances 0.000 description 14
• 150000002576 ketones Chemical class 0.000 description 14
• 230000002829 reductive effect Effects 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• 125000000217 alkyl group Chemical group 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 12
• 239000002253 acid Chemical class 0.000 description 11
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 11
• 241001465754 Metazoa Species 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 150000002430 hydrocarbons Chemical group 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 10
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 9
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 9
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 8
• 125000003118 aryl group Chemical group 0.000 description 8
• 239000013078 crystal Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• AMNYAHNHKFYZOU-LLVKDONJSA-N (3r)-1-n,1-n-dimethyl-4-phenylsulfanylbutane-1,3-diamine Chemical compound CN(C)CC[C@@H](N)CSC1=CC=CC=C1 AMNYAHNHKFYZOU-LLVKDONJSA-N 0.000 description 7
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
• HSDKYMBTTJDKGD-UHFFFAOYSA-N 3-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC(S(=O)(=O)C(F)(F)F)=C1 HSDKYMBTTJDKGD-UHFFFAOYSA-N 0.000 description 7
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• 125000003282 alkyl amino group Chemical group 0.000 description 7
• 125000002619 bicyclic group Chemical group 0.000 description 7
• 239000013058 crude material Substances 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 6
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 6
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 6
• 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 6
• 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 6
• WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000005259 measurement Methods 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 239000011734 sodium Substances 0.000 description 6
• IRBHAVWDSJLCAS-UHFFFAOYSA-N 2-(4-chlorophenyl)benzaldehyde Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC=C1C=O IRBHAVWDSJLCAS-UHFFFAOYSA-N 0.000 description 5
• 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 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
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 238000006880 cross-coupling reaction Methods 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 229910052739 hydrogen Inorganic materials 0.000 description 5
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
• IVHGRBGVNATXFD-UHFFFAOYSA-N 1-chloro-4-[2-(iodomethyl)phenyl]benzene Chemical group C1=CC(Cl)=CC=C1C1=CC=CC=C1CI IVHGRBGVNATXFD-UHFFFAOYSA-N 0.000 description 4
• 239000004215 Carbon black (E152) Substances 0.000 description 4
• 206010008342 Cervix carcinoma Diseases 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 4
• 125000003302 alkenyloxy group Chemical group 0.000 description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 4
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 4
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
• 125000004414 alkyl thio group Chemical group 0.000 description 4
• 125000005133 alkynyloxy group Chemical group 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 201000010881 cervical cancer Diseases 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 125000000623 heterocyclic group Chemical group 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 239000008177 pharmaceutical agent Substances 0.000 description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 4
• 230000002062 proliferating effect Effects 0.000 description 4
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical class [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• KPUWTTSCBIFJQH-UHFFFAOYSA-N 1-[[2-(4-chlorophenyl)phenyl]methyl]piperidin-4-one Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC=C1CN1CCC(=O)CC1 KPUWTTSCBIFJQH-UHFFFAOYSA-N 0.000 description 3
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