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

Sulfonamidas como inhibidores de proteínas de la familia BCL-2 para el tratamiento del cáncer Download PDF

Info

Publication number: ES2443845T3
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.): Active

Application number

ES10750124.9T

Other languages

English (en)

Spanish (es)

Inventor

Karen Miller-Moslin

Bakary-Barry Toure

Michael Scott Visser

Naeem Yusuff

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Novartis AG

Priority date (The priority date 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 date listed.)

2009-09-10

Filing date

2010-09-08

Publication date

2014-02-20

2010-09-08 Application filed by Novartis AG filed Critical Novartis AG

2014-02-20 Application granted granted Critical

2014-02-20 Publication of ES2443845T3 publication Critical patent/ES2443845T3/es

Status Active legal-status Critical Current

2030-09-08 Anticipated expiration legal-status Critical

Links

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
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 3
ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 3
YWOIBRYMVLSMGT-UHFFFAOYSA-N 2-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1S(=O)(=O)C(F)(F)F YWOIBRYMVLSMGT-UHFFFAOYSA-N 0.000 description 3
WDHCLDUKGHLEOU-MRXNPFEDSA-N 4-[[(2r)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound FC(F)(F)S(=O)(=O)C1=CC(S(=O)(=O)N)=CC=C1N[C@@H](CSC=1C=CC=CC=1)CCN1CCOCC1 WDHCLDUKGHLEOU-MRXNPFEDSA-N 0.000 description 3
JOESWBMGEGYULU-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(F)C(S(=O)(=O)C(F)(F)F)=C1 JOESWBMGEGYULU-UHFFFAOYSA-N 0.000 description 3
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
206010033128 Ovarian cancer Diseases 0.000 description 3
206010061535 Ovarian neoplasm Diseases 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000004656 alkyl sulfonylamino group Chemical group 0.000 description 3
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 3
125000000732 arylene group Chemical group 0.000 description 3
210000003719 b-lymphocyte Anatomy 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
125000002837 carbocyclic group Chemical group 0.000 description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
230000001684 chronic effect Effects 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
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000002808 molecular sieve Substances 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
230000008569 process Effects 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 3
239000003039 volatile agent Substances 0.000 description 3
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
JRHPOFJADXHYBR-YUMQZZPRSA-N (1s,2s)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@H]1CCCC[C@@H]1NC JRHPOFJADXHYBR-YUMQZZPRSA-N 0.000 description 2
SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 2
CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 2
REJYKLLPTNVXPI-UHFFFAOYSA-N 1-[(2-bromophenyl)methyl]piperidin-4-one Chemical compound BrC1=CC=CC=C1CN1CCC(=O)CC1 REJYKLLPTNVXPI-UHFFFAOYSA-N 0.000 description 2
WYHIKGPVPWPBDL-UHFFFAOYSA-N 1-[1-[2-(4-chlorophenyl)phenyl]ethyl]piperidin-4-one Chemical compound C=1C=CC=C(C=2C=CC(Cl)=CC=2)C=1C(C)N1CCC(=O)CC1 WYHIKGPVPWPBDL-UHFFFAOYSA-N 0.000 description 2
JMXLTGKPGGITEG-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1C1=CC=C(Cl)C=C1 JMXLTGKPGGITEG-UHFFFAOYSA-N 0.000 description 2
GWXRJFWNNULEBO-UHFFFAOYSA-N 1-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperidin-4-one Chemical compound C1C(C)(C)CCC(C=2C=CC(Cl)=CC=2)=C1CN1CCC(=O)CC1 GWXRJFWNNULEBO-UHFFFAOYSA-N 0.000 description 2
UDTIFDKXJSPYRR-UHFFFAOYSA-N 1-[[2-(4-chlorophenyl)phenyl]methyl]-3-fluoropiperidin-4-one Chemical compound C1CC(=O)C(F)CN1CC1=CC=CC=C1C1=CC=C(Cl)C=C1 UDTIFDKXJSPYRR-UHFFFAOYSA-N 0.000 description 2
AMNYAHNHKFYZOU-UHFFFAOYSA-N 1-n,1-n-dimethyl-4-phenylsulfanylbutane-1,3-diamine Chemical compound CN(C)CCC(N)CSC1=CC=CC=C1 AMNYAHNHKFYZOU-UHFFFAOYSA-N 0.000 description 2
YEELLYVNKHEHJV-UHFFFAOYSA-N 1-phenylsulfanylbutan-2-amine Chemical compound CCC(N)CSC1=CC=CC=C1 YEELLYVNKHEHJV-UHFFFAOYSA-N 0.000 description 2
YAUHFKDKQAMMJE-UHFFFAOYSA-N 1-phenylsulfanylpropan-2-amine Chemical compound CC(N)CSC1=CC=CC=C1 YAUHFKDKQAMMJE-UHFFFAOYSA-N 0.000 description 2
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
GYCGAPQMEYPDIJ-UHFFFAOYSA-N 3-fluoropiperidin-4-one Chemical compound FC1CNCCC1=O GYCGAPQMEYPDIJ-UHFFFAOYSA-N 0.000 description 2
UBYLUXSQTGVKCN-UHFFFAOYSA-N 4-[[2-(4-chlorophenyl)phenyl]methylidene]cyclohexan-1-one Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC=C1C=C1CCC(=O)CC1 UBYLUXSQTGVKCN-UHFFFAOYSA-N 0.000 description 2
NNPPZBMARQNZGH-UHFFFAOYSA-N 4-benzylidenecyclohexan-1-one Chemical compound C1CC(=O)CCC1=CC1=CC=CC=C1 NNPPZBMARQNZGH-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
SPFJLSWAUXUXMW-UHFFFAOYSA-N 8-[1-[2-(4-chlorophenyl)phenyl]ethyl]-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound C=1C=CC=C(C=2C=CC(Cl)=CC=2)C=1C(C)N(CC1)CCC21OCCO2 SPFJLSWAUXUXMW-UHFFFAOYSA-N 0.000 description 2
JJDMEZRNFGRYKQ-UHFFFAOYSA-N 8-[[2-(4-chlorophenyl)phenyl]methyl]-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC=C1CN1CCC2(OCCO2)CC1 JJDMEZRNFGRYKQ-UHFFFAOYSA-N 0.000 description 2
206010000830 Acute leukaemia Diseases 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
102100026596 Bcl-2-like protein 1 Human genes 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
206010005003 Bladder cancer Diseases 0.000 description 2
208000003174 Brain Neoplasms Diseases 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
YSCYJXBWRZKTNM-GOSISDBHSA-N CCN1CCN(CC[C@H](CSC2=CC=CC=C2)NC(C(S(C(F)(F)F)(=O)=O)=CC=C2)=C2S(N)(=O)=O)CC1 Chemical compound CCN1CCN(CC[C@H](CSC2=CC=CC=C2)NC(C(S(C(F)(F)F)(=O)=O)=CC=C2)=C2S(N)(=O)=O)CC1 YSCYJXBWRZKTNM-GOSISDBHSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
206010009944 Colon cancer Diseases 0.000 description 2
229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
201000008808 Fibrosarcoma Diseases 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
208000034578 Multiple myelomas Diseases 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
206010061902 Pancreatic neoplasm Diseases 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
206010035226 Plasma cell myeloma Diseases 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
206010060862 Prostate cancer Diseases 0.000 description 2
208000000236 Prostatic Neoplasms Diseases 0.000 description 2
208000000453 Skin Neoplasms Diseases 0.000 description 2
206010041067 Small cell lung cancer Diseases 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
208000021712 Soft tissue sarcoma Diseases 0.000 description 2
238000006069 Suzuki reaction reaction Methods 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
208000002495 Uterine Neoplasms Diseases 0.000 description 2
AMPOWGGQSPQVIE-UHFFFAOYSA-N [2-(4-chlorophenyl)phenyl]methanol Chemical compound OCC1=CC=CC=C1C1=CC=C(Cl)C=C1 AMPOWGGQSPQVIE-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
239000002585 base Substances 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
229960002685 biotin Drugs 0.000 description 2
239000011616 biotin Substances 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
150000001728 carbonyl compounds Chemical class 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
208000024207 chronic leukemia Diseases 0.000 description 2
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 2
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
238000001514 detection method Methods 0.000 description 2
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 2
YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
230000002183 duodenal effect Effects 0.000 description 2
238000010828 elution Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
201000003444 follicular lymphoma Diseases 0.000 description 2
239000012458 free base Substances 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
201000010536 head and neck cancer Diseases 0.000 description 2
208000014829 head and neck neoplasm Diseases 0.000 description 2
206010073071 hepatocellular carcinoma Diseases 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
208000013403 hyperactivity Diseases 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
239000011630 iodine Substances 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
208000014018 liver neoplasm Diseases 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
230000003211 malignant effect Effects 0.000 description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
201000001441 melanoma Diseases 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
125000004430 oxygen atom Chemical group O* 0.000 description 2
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 2
201000002528 pancreatic cancer Diseases 0.000 description 2
208000008443 pancreatic carcinoma Diseases 0.000 description 2
YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
229940068977 polysorbate 20 Drugs 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
239000000047 product Substances 0.000 description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
208000000587 small cell lung carcinoma Diseases 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
235000017550 sodium carbonate Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
239000012453 solvate Substances 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
HGFYKMIOCPRKGC-UHFFFAOYSA-N tert-butyl 3-bromo-5,6,8,9-tetrahydro-[1,2,4]triazolo[4,3-d][1,4]diazepine-7-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC2=NN=C(Br)N21 HGFYKMIOCPRKGC-UHFFFAOYSA-N 0.000 description 2
FHMYTVUBQZSSNY-UHFFFAOYSA-N tert-butyl 4-trimethylsilyloxy-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O[Si](C)(C)C)=CC1 FHMYTVUBQZSSNY-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
201000005112 urinary bladder cancer Diseases 0.000 description 2
206010046766 uterine cancer Diseases 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
INVLEINDDDKUHB-AWEZNQCLSA-N (2s)-1-[[2-(4-chlorophenyl)phenyl]methyl]-2-methylpiperidin-4-one Chemical compound C[C@H]1CC(=O)CCN1CC1=CC=CC=C1C1=CC=C(Cl)C=C1 INVLEINDDDKUHB-AWEZNQCLSA-N 0.000 description 1
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 1
125000004958 1,4-naphthylene group Chemical group 0.000 description 1
WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
PIMNFNXBTGPCIL-UHFFFAOYSA-N 1-(2-bromophenyl)ethanone Chemical group CC(=O)C1=CC=CC=C1Br PIMNFNXBTGPCIL-UHFFFAOYSA-N 0.000 description 1
LOIWOOLGAMNHAM-UHFFFAOYSA-N 1-[[2-(4-fluorophenyl)phenyl]methyl]piperidin-4-one Chemical compound C1=CC(F)=CC=C1C1=CC=CC=C1CN1CCC(=O)CC1 LOIWOOLGAMNHAM-UHFFFAOYSA-N 0.000 description 1
LZSYGJNFCREHMD-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)benzene Chemical compound BrCC1=CC=CC=C1Br LZSYGJNFCREHMD-UHFFFAOYSA-N 0.000 description 1
LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
BQXMUFXVGNBTRD-UHFFFAOYSA-N 1-phenylsulfanylbutane-1,3-diamine Chemical compound C1(=CC=CC=C1)SC(CC(C)N)N BQXMUFXVGNBTRD-UHFFFAOYSA-N 0.000 description 1
NITMACBPVVUGOJ-UHFFFAOYSA-N 2,2,2-trifluoroethanimidamide Chemical compound NC(=N)C(F)(F)F NITMACBPVVUGOJ-UHFFFAOYSA-N 0.000 description 1
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
125000004959 2,6-naphthylene group Chemical group [H]C1=C([H])C2=C([H])C([*:1])=C([H])C([H])=C2C([H])=C1[*:2] 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
OKNMCTUMUNVERL-UHFFFAOYSA-N 2-[[4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrobenzenesulfonamide Chemical compound [O-][N+](=O)C=1C=CC=C(S(N)(=O)=O)C=1NC(CCN(C)C)CSC1=CC=CC=C1 OKNMCTUMUNVERL-UHFFFAOYSA-N 0.000 description 1
WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
LSYXNECZRAJSMM-UHFFFAOYSA-N 2-methyl-4-oxopiperidine-1-carboxylic acid Chemical compound CC1CC(=O)CCN1C(O)=O LSYXNECZRAJSMM-UHFFFAOYSA-N 0.000 description 1
MUMNFEPQABVDQS-UHFFFAOYSA-N 2-methylsulfonylbenzenesulfonamide Chemical compound CS(=O)(=O)C1=CC=CC=C1S(N)(=O)=O MUMNFEPQABVDQS-UHFFFAOYSA-N 0.000 description 1
FRDZGSBXKJXGNR-UHFFFAOYSA-N 2-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN(C)C1CCCCC1N FRDZGSBXKJXGNR-UHFFFAOYSA-N 0.000 description 1
RZCJYMOBWVJQGV-UHFFFAOYSA-N 2-naphthyloxyacetic acid Chemical compound C1=CC=CC2=CC(OCC(=O)O)=CC=C21 RZCJYMOBWVJQGV-UHFFFAOYSA-N 0.000 description 1
UBKQRASXZMLQRJ-UHFFFAOYSA-N 2-phenylsulfanylethanamine Chemical compound NCCSC1=CC=CC=C1 UBKQRASXZMLQRJ-UHFFFAOYSA-N 0.000 description 1
BIAGBHUIRSMWRI-UHFFFAOYSA-N 3,4,5-trifluorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC(F)=C(F)C(F)=C1 BIAGBHUIRSMWRI-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
SRZNQVHSYCRAEI-MRXNPFEDSA-N 3-cyano-4-[[(2r)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]benzenesulfonamide Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(N)(=O)=O)C#N)SC1=CC=CC=C1 SRZNQVHSYCRAEI-MRXNPFEDSA-N 0.000 description 1
HVKUPIBRYPDOBG-UHFFFAOYSA-N 3-cyano-4-fluorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(F)C(C#N)=C1 HVKUPIBRYPDOBG-UHFFFAOYSA-N 0.000 description 1
BUYCLJIISQGRBR-UHFFFAOYSA-N 3-fluoro-4-oxopiperidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(=O)C(F)C1 BUYCLJIISQGRBR-UHFFFAOYSA-N 0.000 description 1
TXTQURPQLVHJRE-UHFFFAOYSA-N 3-nitrobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 TXTQURPQLVHJRE-UHFFFAOYSA-N 0.000 description 1
ATCSMYCOMZVYSQ-UHFFFAOYSA-N 3-oxopiperidine-1,4-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)CC1=O ATCSMYCOMZVYSQ-UHFFFAOYSA-N 0.000 description 1
FCYGNKOIPXKBDL-CYBMUJFWSA-N 4-[[(2r)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3,5-difluorobenzenesulfonamide Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1F)S(N)(=O)=O)F)SC1=CC=CC=C1 FCYGNKOIPXKBDL-CYBMUJFWSA-N 0.000 description 1
ICESDMPJTDFSIN-CQSZACIVSA-N 4-[[(2r)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethyl)benzenesulfonamide Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(N)(=O)=O)C(F)(F)F)SC1=CC=CC=C1 ICESDMPJTDFSIN-CQSZACIVSA-N 0.000 description 1
OOEXGWMRYHXJRH-CQSZACIVSA-N 4-[[(2r)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(N)(=O)=O)S(=O)(=O)C(F)(F)F)SC1=CC=CC=C1 OOEXGWMRYHXJRH-CQSZACIVSA-N 0.000 description 1
GVJKLSTZIFMTKH-CQSZACIVSA-N 4-[[(2r)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrobenzenesulfonamide Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(N)(=O)=O)[N+]([O-])=O)SC1=CC=CC=C1 GVJKLSTZIFMTKH-CQSZACIVSA-N 0.000 description 1
WCPSYNKTIQZHIB-HXUWFJFHSA-N 4-[[(2r)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-n-(6,7,8,9-tetrahydro-5h-[1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)-3-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound C([C@@H](NC1=CC=C(C=C1S(=O)(=O)C(F)(F)F)S(=O)(=O)NC=1N2CCNCCC2=NN=1)CSC=1C=CC=CC=1)CN1CCOCC1 WCPSYNKTIQZHIB-HXUWFJFHSA-N 0.000 description 1
QJANYMHEGRILIE-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(F)C(C(F)(F)F)=C1 QJANYMHEGRILIE-UHFFFAOYSA-N 0.000 description 1
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
XVHVBUNXLXLXKG-UHFFFAOYSA-N 4-morpholin-4-yl-1-phenylsulfanylbutan-2-amine Chemical compound C=1C=CC=CC=1SCC(N)CCN1CCOCC1 XVHVBUNXLXLXKG-UHFFFAOYSA-N 0.000 description 1
DEZDAWMKBCUPKF-UHFFFAOYSA-N 4-oxo-1,5,6,8-tetrahydropyrido[3,4-d]pyrimidine-7-carboxylic acid Chemical compound N1C=NC(=O)C2=C1CN(C(=O)O)CC2 DEZDAWMKBCUPKF-UHFFFAOYSA-N 0.000 description 1
WQVABAVMEUTQTA-UHFFFAOYSA-N 4-oxoazepane-1-carboxylic acid Chemical compound OC(=O)N1CCCC(=O)CC1 WQVABAVMEUTQTA-UHFFFAOYSA-N 0.000 description 1
FOWOXWLATUAFNQ-UHFFFAOYSA-N 4-oxopiperidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(=O)CC1 FOWOXWLATUAFNQ-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
102000004400 Aminopeptidases Human genes 0.000 description 1
108090000915 Aminopeptidases Proteins 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 1
102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 1
208000003950 B-cell lymphoma Diseases 0.000 description 1
239000012664 BCL-2-inhibitor Substances 0.000 description 1
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
229940123711 Bcl2 inhibitor Drugs 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
229940122361 Bisphosphonate Drugs 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
SSTFESZLQRSZBE-UHFFFAOYSA-N C(C)(CC)NSC1=CC=CC=C1 Chemical compound C(C)(CC)NSC1=CC=CC=C1 SSTFESZLQRSZBE-UHFFFAOYSA-N 0.000 description 1
125000006519 CCH3 Chemical group 0.000 description 1
125000006414 CCl Chemical group ClC* 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
229940122444 Chemokine receptor antagonist Drugs 0.000 description 1
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
208000034951 Genetic Translocation Diseases 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
208000002250 Hematologic Neoplasms Diseases 0.000 description 1
102100024025 Heparanase Human genes 0.000 description 1
101000765923 Homo sapiens Bcl-2-like protein 1 Proteins 0.000 description 1
101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
208000008839 Kidney Neoplasms Diseases 0.000 description 1
102000010638 Kinesin Human genes 0.000 description 1
108010063296 Kinesin Proteins 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
229940124761 MMP inhibitor Drugs 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
102000029749 Microtubule Human genes 0.000 description 1
108091022875 Microtubule Proteins 0.000 description 1
101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-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
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-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
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229940079156 Proteasome inhibitor Drugs 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
108091030071 RNAI Proteins 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
229940127395 Ribonucleotide Reductase Inhibitors Drugs 0.000 description 1
MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
239000004809 Teflon Substances 0.000 description 1
229920006362 Teflon® Polymers 0.000 description 1
LCKIEQZJEYYRIY-UHFFFAOYSA-N Titanium ion Chemical compound [Ti+4] LCKIEQZJEYYRIY-UHFFFAOYSA-N 0.000 description 1
101710183280 Topoisomerase Proteins 0.000 description 1
239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
YKAYTEWKZUOACN-UHFFFAOYSA-N [N].OC(=O)C(F)(F)F Chemical compound [N].OC(=O)C(F)(F)F YKAYTEWKZUOACN-UHFFFAOYSA-N 0.000 description 1
239000000370 acceptor Substances 0.000 description 1
CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 1
150000008043 acidic salts Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
229960001570 ademetionine Drugs 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
NMVVJCLUYUWBSZ-UHFFFAOYSA-N aminomethylideneazanium;chloride Chemical compound Cl.NC=N NMVVJCLUYUWBSZ-UHFFFAOYSA-N 0.000 description 1
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000012491 analyte Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000001772 anti-angiogenic effect Effects 0.000 description 1
229940046836 anti-estrogen Drugs 0.000 description 1
230000001833 anti-estrogenic effect Effects 0.000 description 1
229940124599 anti-inflammatory drug Drugs 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000719 anti-leukaemic effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
229940124623 antihistamine drug Drugs 0.000 description 1
239000002814 antineoplastic antimetabolite Substances 0.000 description 1
229940045985 antineoplastic platinum compound Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000003886 aromatase inhibitor Substances 0.000 description 1
229940046844 aromatase inhibitors Drugs 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
125000004069 aziridinyl group Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 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
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
150000004663 bisphosphonates Chemical class 0.000 description 1
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
229960004562 carboplatin Drugs 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000002559 chemokine receptor antagonist Substances 0.000 description 1
230000000973 chemotherapeutic effect Effects 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
239000012829 chemotherapy agent Substances 0.000 description 1
239000012069 chiral reagent Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000010949 copper Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000002993 cycloalkylene group Chemical group 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
230000001934 delay Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
230000002074 deregulated effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000009826 distribution Methods 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
229960003668 docetaxel Drugs 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
229960001433 erlotinib Drugs 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
JYFGIESQUYQLGM-UHFFFAOYSA-N ethyl 1-benzyl-3-oxopiperidine-4-carboxylate Chemical compound C1C(=O)C(C(=O)OCC)CCN1CC1=CC=CC=C1 JYFGIESQUYQLGM-UHFFFAOYSA-N 0.000 description 1
UQOMEAWPKSISII-UHFFFAOYSA-N ethyl 1-benzyl-3-oxopiperidine-4-carboxylate;hydron;chloride Chemical compound Cl.C1C(=O)C(C(=O)OCC)CCN1CC1=CC=CC=C1 UQOMEAWPKSISII-UHFFFAOYSA-N 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
239000011888 foil Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
229960005277 gemcitabine Drugs 0.000 description 1
230000009368 gene silencing by RNA Effects 0.000 description 1
229960001731 gluceptate Drugs 0.000 description 1
KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
229940097042 glucuronate Drugs 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
108010037536 heparanase Proteins 0.000 description 1
125000005549 heteroarylene group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000000592 heterocycloalkyl group Chemical group 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
239000003276 histone deacetylase inhibitor Substances 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000003463 hyperproliferative effect Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
238000012482 interaction analysis Methods 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
238000011835 investigation Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000005865 ionizing radiation Effects 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 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
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
201000010982 kidney cancer Diseases 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
239000003446 ligand Substances 0.000 description 1
238000007477 logistic regression Methods 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
229940124302 mTOR inhibitor Drugs 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229940049920 malate Drugs 0.000 description 1
239000011976 maleic acid Substances 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
239000003628 mammalian target of rapamycin inhibitor Substances 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
229960002510 mandelic acid Drugs 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
210000004688 microtubule Anatomy 0.000 description 1
238000003801 milling Methods 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
239000003607 modifier Substances 0.000 description 1
208000025113 myeloid leukemia Diseases 0.000 description 1
RSOVUTMFSIKQHH-UHFFFAOYSA-N n-(2-phenylsulfanylethyl)acetamide Chemical compound CC(=O)NCCSC1=CC=CC=C1 RSOVUTMFSIKQHH-UHFFFAOYSA-N 0.000 description 1
RGSAYFUMTQODNO-LJQANCHMSA-N n-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl)-4-[[(2r)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide Chemical compound C([C@@H](NC1=CC=C(C=C1S(=O)(=O)C(F)(F)F)S(=O)(=O)NC=1C=2CNCC=2N=CN=1)CSC=1C=CC=CC=1)CN1CCOCC1 RGSAYFUMTQODNO-LJQANCHMSA-N 0.000 description 1
VZBFNUHVIOAUFH-PSXMRANNSA-N n-[7-[1-[[2-(4-chlorophenyl)phenyl]methyl]piperidin-4-yl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]-4-[[(2r)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-nitrobenzenesulfonamide Chemical compound C([C@@H](NC1=CC=C(C=C1[N+](=O)[O-])S(=O)(=O)NC=1C=2CCN(CC=2N=CN=1)C1CCN(CC=2C(=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1)CSC=1C=CC=CC=1)CN1CCOCC1 VZBFNUHVIOAUFH-PSXMRANNSA-N 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
WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
231100001143 noxa Toxicity 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
238000002428 photodynamic therapy Methods 0.000 description 1
229960005141 piperazine Drugs 0.000 description 1
VRJHQPZVIGNGMX-UHFFFAOYSA-N piperidine-4-one Natural products O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
150000003058 platinum compounds Chemical class 0.000 description 1
238000002600 positron emission tomography Methods 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
244000144977 poultry Species 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
239000003207 proteasome inhibitor Substances 0.000 description 1
230000001012 protector Effects 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000002994 raw material Substances 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000012363 selectfluor Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
229940114926 stearate Drugs 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
125000000547 substituted alkyl 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
229940071103 sulfosalicylate Drugs 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000013589 supplement Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
239000003277 telomerase inhibitor Substances 0.000 description 1
SSOWVJRCWPTTLK-UHFFFAOYSA-N tert-butyl 3-bromo-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazine-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCN2C(Br)=NN=C21 SSOWVJRCWPTTLK-UHFFFAOYSA-N 0.000 description 1
JZNWQLLPLOQGOI-UHFFFAOYSA-N tert-butyl 3-fluoro-4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C(F)C1 JZNWQLLPLOQGOI-UHFFFAOYSA-N 0.000 description 1
ANTSTNVAAVRTOL-UHFFFAOYSA-N tert-butyl 4-(benzotriazol-1-yloxy)-5,7-dihydropyrrolo[3,4-d]pyrimidine-6-carboxylate Chemical compound N1=NC2=CC=CC=C2N1OC1=C(CN(C(=O)OC(C)(C)C)C2)C2=NC=N1 ANTSTNVAAVRTOL-UHFFFAOYSA-N 0.000 description 1
VGRWFJOIIYAUPW-JOCHJYFZSA-N tert-butyl 4-[[4-[[(2r)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylamino]-5,7-dihydropyrrolo[3,4-d]pyrimidine-6-carboxylate Chemical compound C([C@@H](NC1=CC=C(C=C1S(=O)(=O)C(F)(F)F)S(=O)(=O)NC=1N=CN=C2CN(CC2=1)C(=O)OC(C)(C)C)CSC=1C=CC=CC=1)CN1CCOCC1 VGRWFJOIIYAUPW-JOCHJYFZSA-N 0.000 description 1
WNPCPHNVHJEGRJ-UHFFFAOYSA-N tert-butyl 4-chloro-2-(trifluoromethyl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound N1=C(C(F)(F)F)N=C2CN(C(=O)OC(C)(C)C)CCC2=C1Cl WNPCPHNVHJEGRJ-UHFFFAOYSA-N 0.000 description 1
XYHXUYOSXZHUSZ-UHFFFAOYSA-N tert-butyl 4-chloro-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound N1=CN=C2CN(C(=O)OC(C)(C)C)CCC2=C1Cl XYHXUYOSXZHUSZ-UHFFFAOYSA-N 0.000 description 1
BXXXVYDHJCLIKQ-UHFFFAOYSA-N tert-butyl 4-oxo-5,7-dihydro-1h-pyrrolo[3,4-d]pyrimidine-6-carboxylate Chemical compound N1=CNC(=O)C2=C1CN(C(=O)OC(C)(C)C)C2 BXXXVYDHJCLIKQ-UHFFFAOYSA-N 0.000 description 1
ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
GLJYPTWEXBUATJ-UHFFFAOYSA-N tert-butyl 5-oxo-1,4-diazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(=O)CC1 GLJYPTWEXBUATJ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 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
230000009466 transformation Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000004950 trifluoroalkyl group Chemical group 0.000 description 1
CVYXKEPHZZIZMK-UHFFFAOYSA-N trifluoromethyl 6,8-dihydro-5H-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound N1=CN=CC2=C1CN(CC2)C(=O)OC(F)(F)F CVYXKEPHZZIZMK-UHFFFAOYSA-N 0.000 description 1
POXSDSRWVJZWCN-UHFFFAOYSA-N triphenylphosphanium;iodide Chemical compound I.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 POXSDSRWVJZWCN-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000005406 washing Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyridine Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

ES10750124.9T 2009-09-10 2010-09-08 Sulfonamidas como inhibidores de proteínas de la familia BCL-2 para el tratamiento del cáncer Active ES2443845T3 (es)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US24125109P	2009-09-10	2009-09-10
US241251P		2009-09-10
PCT/EP2010/063169 WO2011029842A1 (en)	2009-09-10	2010-09-08	Sulfonamides as inhibitors of bcl-2 family proteins for the treatment of cancer

Publications (1)

Publication Number	Publication Date
ES2443845T3 true ES2443845T3 (es)	2014-02-20

Family

ID=43016684

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES10750124.9T Active ES2443845T3 (es)	2009-09-10	2010-09-08	Sulfonamidas como inhibidores de proteínas de la familia BCL-2 para el tratamiento del cáncer

Country Status (12)

Country	Link
US (1)	US8809352B2 (2)
EP (1)	EP2475661B1 (2)
JP (1)	JP2013504536A (2)
KR (1)	KR20120078715A (2)
CN (1)	CN102498111A (2)
AU (1)	AU2010294292B2 (2)
BR (1)	BR112012005343A2 (2)
CA (1)	CA2772989A1 (2)
EA (1)	EA020586B1 (2)
ES (1)	ES2443845T3 (2)
MX (1)	MX2012003007A (2)
WO (1)	WO2011029842A1 (2)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2668180B1 (en) *	2011-01-25	2018-08-01	The Regents of The University of Michigan	Bcl-2/bcl-xl inhibitors for use in the treatment of cancer
EP2794591A1 (en)	2011-12-23	2014-10-29	Novartis AG	Compounds for inhibiting the interaction of bcl2 with binding partners
US9126980B2 (en)	2011-12-23	2015-09-08	Novartis Ag	Compounds for inhibiting the interaction of BCL2 with binding partners
LT6064B (lt)	2012-10-15	2014-08-25	Vilniaus Universitetas	Fluorinti benzensulfonamidai kaip karboanhidrazės inhibitoriai
ES2670550T3 (es)	2013-10-14	2018-05-30	Eisai R&D Management Co., Ltd.	Derivados de quinolina selectivamente sustituidos
SG10202103278TA (en)	2013-10-14	2021-04-29	Eisai R&D Man Co Ltd	Selectively substituted quinoline compounds
US10195213B2 (en)	2015-03-13	2019-02-05	Unity Biotechnology, Inc.	Chemical entities that kill senescent cells for use in treating age-related disease
US11098021B2 (en)	2015-08-12	2021-08-24	Memorial Sloan-Kettering Cancer Center	Phenylsulfonamido-benzofuran derivatives and uses thereof in the treatment of proliferative diseases
MX2018008507A (es)	2016-01-11	2019-07-04	Merrimack Pharmaceuticals Inc	Inhibición de proteína relacionada con ataxia telangiectasia y rad3 (atr).
JP2019501225A (ja) *	2016-01-11	2019-01-17	メリマックファーマシューティカルズインコーポレーティッド	Ｂ細胞リンパ腫２（ｂｃｌ−２）及び関連タンパク質の阻害
SG11202009933WA (en)	2018-04-29	2020-11-27	Beigene Ltd	Bcl-2 INHIBITORS
MA55556A (fr)	2019-04-02	2022-02-09	Aligos Therapeutics Inc	Composés ciblant prmt5
WO2021083135A1 (en)	2019-10-28	2021-05-06	Beigene, Ltd.	Bcl-2 INHIBITORS
IL296582A (en)	2020-04-15	2022-11-01	Beigene Ltd	bcl-2 inhibitor
US20250333409A1 (en) *	2022-06-10	2025-10-30	Hitgen Inc.	Compound and use thereof in preparation of BCL-XL inhibitor

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2003080586A1 (en) *	2002-03-21	2003-10-02	Abbott Laboratories	N-sulfonylurea apoptosis promoters
US20040157836A1 (en) *	2002-10-08	2004-08-12	Comess Kenneth M.	Sulfonamides having antiangiogenic and anticancer activity
JP2007524596A (ja)	2003-02-28	2007-08-30	トランスフォーム・ファーマシューティカルズ・インコーポレイテッド	共結晶医薬組成物
EP1778206A4 (en) *	2004-08-20	2009-08-05	Univ Michigan	SMALL MOLECULE INHIBITORS FROM MEMBERS OF THE ANTIOPTOTIC BCL-2 FAMILY AND USES THEREOF
EP2094672B1 (en) *	2006-11-15	2013-05-29	Genentech, Inc.	Arylsulfonamide compounds
FR2912145B1 (fr) *	2007-02-02	2009-03-06	Servier Lab	Nouveaux derives tricycliques,leur procede de preparation et les compositions pharmaceutiques qui les contiennent

2010
- 2010-09-08 CA CA2772989A patent/CA2772989A1/en not_active Abandoned
- 2010-09-08 BR BR112012005343A patent/BR112012005343A2/pt not_active IP Right Cessation
- 2010-09-08 EP EP10750124.9A patent/EP2475661B1/en not_active Not-in-force
- 2010-09-08 CN CN2010800396704A patent/CN102498111A/zh active Pending
- 2010-09-08 ES ES10750124.9T patent/ES2443845T3/es active Active
- 2010-09-08 JP JP2012528347A patent/JP2013504536A/ja active Pending
- 2010-09-08 MX MX2012003007A patent/MX2012003007A/es active IP Right Grant
- 2010-09-08 EA EA201200472A patent/EA020586B1/ru not_active IP Right Cessation
- 2010-09-08 AU AU2010294292A patent/AU2010294292B2/en not_active Ceased
- 2010-09-08 KR KR1020127009091A patent/KR20120078715A/ko not_active Withdrawn
- 2010-09-08 WO PCT/EP2010/063169 patent/WO2011029842A1/en not_active Ceased
- 2010-09-08 US US13/394,525 patent/US8809352B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
KR20120078715A (ko)	2012-07-10
AU2010294292A1 (en)	2012-03-01
JP2013504536A (ja)	2013-02-07
CA2772989A1 (en)	2011-03-17
MX2012003007A (es)	2012-04-11
EA020586B1 (ru)	2014-12-30
EP2475661A1 (en)	2012-07-18
US20120165298A1 (en)	2012-06-28
EP2475661B1 (en)	2013-10-23
AU2010294292B2 (en)	2013-07-18
EA201200472A1 (ru)	2012-10-30
BR112012005343A2 (pt)	2016-03-22
WO2011029842A1 (en)	2011-03-17
US8809352B2 (en)	2014-08-19
CN102498111A (zh)	2012-06-13

Publication	Publication Date	Title
ES2443845T3 (es)	2014-02-20	Sulfonamidas como inhibidores de proteínas de la familia BCL-2 para el tratamiento del cáncer
ES2941512T3 (es)	2023-05-23	Compuestos de imidazo-piridina como inhibidores de PAD
ES2955132T3 (es)	2023-11-28	Compuestos heterocíclicos sustituidos con amina como inhibidores de EHMT2 y métodos de uso de los mismos
ES2271618T3 (es)	2007-04-16	Compuestos de quinazolina utiles en terapia.
ES2944937T3 (es)	2023-06-27	Tienopirroles en calidad de inhibidores de la histona desmetilasa
AU2014400628B2 (en)	2019-05-02	Aminopyridazinone compounds as protein kinase inhibitors
ES2935746T3 (es)	2023-03-09	Inhibidores de desmetilasa-1 específica de lisina
ES2734268T3 (es)	2019-12-05	Derivados de urea y amida de aminoalquilpiperazinas y uso de los mismos
ES2829400T3 (es)	2021-05-31	Inhibidores tricíclicos de Rho cinasa
AU2022259328A1 (en)	2023-11-09	Bicyclic substituted aromatic carboxylic acid compounds
CN103930422A (zh)	2014-07-16	杂环化合物及其用途
KR20230175222A (ko)	2023-12-29	Nek7 억제제
CN115867346B (zh)	2025-03-14	激酶抑制剂
TW201410669A (zh)	2014-03-16	作為呼吸道融合病毒之抗病毒劑的新穎經雜環取代之１，３－二氫－２ｈ－苯并咪唑－２－酮衍生物
AU2021285974A1 (en)	2023-01-19	Inhibitors of fibroblast growth factor receptor kinases
PT1465921E (pt)	2006-12-29	Espirocíclico-6, 7-di-idro-5h-pirazolo[1,2-a] pirazol-1-onas que controlam citocinas inflamatórias
PT1427732E (pt)	2006-12-29	Espirocíclico-6, 7-di-idro-5h-pirazolo[1,2-a]pirazol-1-onas que controlam citocinas inflamatórias
WO2019106368A1 (en)	2019-06-06	Pyrrolo[3,2-c]pyridin-4-one derivatives as pfk inhibitors useful for the treatment of protozoal infections
ES2771151T3 (es)	2020-07-06	Derivados de piperidina como inhibidor de señalización wnt
TW202602878A (zh)	2026-01-16	Ａｋｔ１調節劑
WO2024158878A1 (en)	2024-08-02	Fused tetracyclic selective parp1 inhibitors
WO2026015385A1 (en)	2026-01-15	Substituted pyrido[4,3-d]pyrimidines as kras modulators
CA3008653C (en)	2026-01-27	Bruton's tyrosine kinase inhibitors
RU2626883C2 (ru)	2017-08-02	Способы получения изохинолинонов и твердые формы изохинолинонов