CA2578955A1 - Isoindolin-1-one derivatives - Google Patents
Isoindolin-1-one derivatives Download PDFInfo
- Publication number
- CA2578955A1 CA2578955A1 CA002578955A CA2578955A CA2578955A1 CA 2578955 A1 CA2578955 A1 CA 2578955A1 CA 002578955 A CA002578955 A CA 002578955A CA 2578955 A CA2578955 A CA 2578955A CA 2578955 A1 CA2578955 A1 CA 2578955A1
- Authority
- CA
- Canada
- Prior art keywords
- mmol
- substituted
- nmr
- unsubstituted
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical class C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 title description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 151
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 125000003118 aryl group Chemical group 0.000 claims abstract description 24
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 11
- 125000004475 heteroaralkyl group Chemical group 0.000 claims abstract description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 150000003973 alkyl amines Chemical class 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 6
- 239000000651 prodrug Substances 0.000 claims abstract description 6
- 229940002612 prodrug Drugs 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 239000000956 alloy Substances 0.000 claims abstract description 3
- 229910045601 alloy Inorganic materials 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 105
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 claims description 23
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 claims description 23
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- -1 silylethoxymethoxyphenyl Chemical group 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000000524 functional group Chemical group 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 230000003993 interaction Effects 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 235000019441 ethanol Nutrition 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 201
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 182
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 174
- 101150041968 CDC13 gene Proteins 0.000 description 162
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 102
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 91
- 238000005481 NMR spectroscopy Methods 0.000 description 79
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 72
- 239000003921 oil Substances 0.000 description 70
- 235000019198 oils Nutrition 0.000 description 70
- 229940093499 ethyl acetate Drugs 0.000 description 67
- 235000019439 ethyl acetate Nutrition 0.000 description 67
- 239000002904 solvent Substances 0.000 description 64
- 239000007787 solid Substances 0.000 description 62
- 239000000243 solution Substances 0.000 description 49
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 47
- 239000012043 crude product Substances 0.000 description 46
- 239000000203 mixture Substances 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- 238000004587 chromatography analysis Methods 0.000 description 35
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 239000012267 brine Substances 0.000 description 26
- 238000003818 flash chromatography Methods 0.000 description 25
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 25
- 239000000460 chlorine Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 19
- 230000003197 catalytic effect Effects 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 238000009835 boiling Methods 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- LUOAEJWSKPQLJD-UHFFFAOYSA-N syringyl alcohol Chemical compound COC1=CC(CO)=CC(OC)=C1O LUOAEJWSKPQLJD-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000000377 silicon dioxide Substances 0.000 description 15
- FGTYTUFKXYPTML-UHFFFAOYSA-N 2-benzoylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 FGTYTUFKXYPTML-UHFFFAOYSA-N 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 229910008338 Si—(CH3) Inorganic materials 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 238000009472 formulation Methods 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 10
- TULLOGDEENSVLE-UHFFFAOYSA-N 3-chloro-3-(4-chlorophenyl)-2-benzofuran-1-one Chemical compound C1=CC(Cl)=CC=C1C1(Cl)C2=CC=CC=C2C(=O)O1 TULLOGDEENSVLE-UHFFFAOYSA-N 0.000 description 9
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 8
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
- YPSNXWJPAIHCLE-UHFFFAOYSA-N 2,3,7,7a-tetrahydroisoindol-1-one Chemical compound C1=CCC2C(=O)NCC2=C1 YPSNXWJPAIHCLE-UHFFFAOYSA-N 0.000 description 7
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- NUUPJBRGQCEZSI-UHFFFAOYSA-N cyclopentane-1,3-diol Chemical compound OC1CCC(O)C1 NUUPJBRGQCEZSI-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- FVEINXLJOJPHLH-UHFFFAOYSA-N p-tert-Butylbenzyl alcohol Chemical compound CC(C)(C)C1=CC=C(CO)C=C1 FVEINXLJOJPHLH-UHFFFAOYSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- BXGYBSJAZFGIPX-UHFFFAOYSA-N 2-pyridin-2-ylethanol Chemical compound OCCC1=CC=CC=N1 BXGYBSJAZFGIPX-UHFFFAOYSA-N 0.000 description 5
- CAYYZOKWYGGFAV-UHFFFAOYSA-N 3-chloro-3-phenyl-2-benzofuran-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(Cl)C1=CC=CC=C1 CAYYZOKWYGGFAV-UHFFFAOYSA-N 0.000 description 5
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- IKMDAJBBMNDKJY-UHFFFAOYSA-N methyl 2-(4-hydroxybenzoyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 IKMDAJBBMNDKJY-UHFFFAOYSA-N 0.000 description 5
- 239000010502 orange oil Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 4
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 4
- LQHBJMRBTKFLJU-UHFFFAOYSA-N 2-[4-(2-trimethylsilylethoxymethoxy)benzoyl]benzoic acid Chemical compound C1=CC(OCOCC[Si](C)(C)C)=CC=C1C(=O)C1=CC=CC=C1C(O)=O LQHBJMRBTKFLJU-UHFFFAOYSA-N 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 150000001412 amines Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000010432 diamond Substances 0.000 description 4
- 229910003460 diamond Inorganic materials 0.000 description 4
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- MBWRQSUNXYXJTC-UHFFFAOYSA-N methyl 2-[4-(2-trimethylsilylethoxymethoxy)benzoyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C(=O)C1=CC=C(OCOCC[Si](C)(C)C)C=C1 MBWRQSUNXYXJTC-UHFFFAOYSA-N 0.000 description 4
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 4
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- DGWNHIXOANURKW-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-[(4-chlorophenyl)methyl]-3-hydroxyisoindol-1-one Chemical compound O=C1C2=CC=CC=C2C(O)(C=2C=CC(Cl)=CC=2)N1CC1=CC=C(Cl)C=C1 DGWNHIXOANURKW-UHFFFAOYSA-N 0.000 description 3
- SMZYUBOJPKEPHA-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-(3-hydroxycyclopentyl)oxy-2-(2-phenylethyl)isoindol-1-one Chemical compound C1C(O)CCC1OC1(C=2C=CC(Cl)=CC=2)C2=CC=CC=C2C(=O)N1CCC1=CC=CC=C1 SMZYUBOJPKEPHA-UHFFFAOYSA-N 0.000 description 3
- LCURVIQHVBRAPQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-hydroxy-2-[(4-nitrophenyl)methyl]isoindol-1-one Chemical compound O=C1C2=CC=CC=C2C(O)(C=2C=CC(Cl)=CC=2)N1CC1=CC=C([N+]([O-])=O)C=C1 LCURVIQHVBRAPQ-UHFFFAOYSA-N 0.000 description 3
- XTVJFMACICVAGW-UHFFFAOYSA-N 3-amino-2,3-dihydroisoindol-1-one Chemical compound C1=CC=C2C(N)NC(=O)C2=C1 XTVJFMACICVAGW-UHFFFAOYSA-N 0.000 description 3
- RAJIPGGCGZKVSW-UHFFFAOYSA-N 3-chloro-3-[4-(2-trimethylsilylethoxymethoxy)phenyl]-2-benzofuran-1-one Chemical compound C1=CC(OCOCC[Si](C)(C)C)=CC=C1C1(Cl)C2=CC=CC=C2C(=O)O1 RAJIPGGCGZKVSW-UHFFFAOYSA-N 0.000 description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
- 238000012286 ELISA Assay Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DYZWXBMTHNHXML-UHFFFAOYSA-N N-propylbenzamide Chemical compound CCCNC(=O)C1=CC=CC=C1 DYZWXBMTHNHXML-UHFFFAOYSA-N 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 3
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- UYDJAHJCGZTTHB-UHFFFAOYSA-N cyclopentane-1,1-diol Chemical compound OC1(O)CCCC1 UYDJAHJCGZTTHB-UHFFFAOYSA-N 0.000 description 3
- GZMCHCXMIPGZKK-UHFFFAOYSA-N ethyl 4-(2-trimethylsilylethoxymethoxy)benzoate Chemical compound CCOC(=O)C1=CC=C(OCOCC[Si](C)(C)C)C=C1 GZMCHCXMIPGZKK-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- PABKALCIBHIYPY-DEOSSOPVSA-N (2r)-2-[tert-butyl(diphenyl)silyl]oxy-2-(4-methoxyphenyl)ethanamine Chemical compound C1=CC(OC)=CC=C1[C@H](CN)O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 PABKALCIBHIYPY-DEOSSOPVSA-N 0.000 description 2
- GCFBLKUPILHINH-UHFFFAOYSA-N (4-methoxy-3-prop-2-enoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C=C1OCC=C GCFBLKUPILHINH-UHFFFAOYSA-N 0.000 description 2
- SMIXZZMSWYOQPW-UHFFFAOYSA-N (4-nitrophenyl)methylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=C([N+]([O-])=O)C=C1 SMIXZZMSWYOQPW-UHFFFAOYSA-N 0.000 description 2
- SZVHDGIHRNRTMW-UHFFFAOYSA-N (4-prop-2-enoxyphenyl)methanol Chemical compound OCC1=CC=C(OCC=C)C=C1 SZVHDGIHRNRTMW-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 2
- BCFIYRQSIPGUHM-UHFFFAOYSA-N 2-benzyl-3-phenyl-3-propoxyisoindol-1-one Chemical compound O=C1C2=CC=CC=C2C(OCCC)(C=2C=CC=CC=2)N1CC1=CC=CC=C1 BCFIYRQSIPGUHM-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- QUTFSCDBMKXCOO-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-[(4-chlorophenyl)methyl]-3-(3-hydroxycyclopentyl)oxyisoindol-1-one Chemical compound C1C(O)CCC1OC1(C=2C=CC(Cl)=CC=2)C2=CC=CC=C2C(=O)N1CC1=CC=C(Cl)C=C1 QUTFSCDBMKXCOO-UHFFFAOYSA-N 0.000 description 2
- CQOCAHLHVRRANN-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-(3-hydroxycyclopentyl)oxy-2-propylisoindol-1-one Chemical compound CCCN1C(=O)C2=CC=CC=C2C1(C=1C=CC(Cl)=CC=1)OC1CCC(O)C1 CQOCAHLHVRRANN-UHFFFAOYSA-N 0.000 description 2
- QHCMEGFPUGYGGL-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-hydroxy-2-(2-phenylethyl)isoindol-1-one Chemical compound O=C1C2=CC=CC=C2C(O)(C=2C=CC(Cl)=CC=2)N1CCC1=CC=CC=C1 QHCMEGFPUGYGGL-UHFFFAOYSA-N 0.000 description 2
- LVOYNRFNMOZAEK-QSAPEBAKSA-N 3-[[(2r)-2-hydroxy-2-(4-methoxyphenyl)ethyl]amino]-2-(3-hydroxypropyl)-3-phenylisoindol-1-one Chemical compound C1=CC(OC)=CC=C1[C@@H](O)CNC1(C=2C=CC=CC=2)C2=CC=CC=C2C(=O)N1CCCO LVOYNRFNMOZAEK-QSAPEBAKSA-N 0.000 description 2
- NZGTVPDEICZMNU-UHFFFAOYSA-N 3-chloro-3-(4-chlorophenyl)-2-(2-phenylethyl)isoindol-1-one Chemical compound C1=CC(Cl)=CC=C1C1(Cl)C2=CC=CC=C2C(=O)N1CCC1=CC=CC=C1 NZGTVPDEICZMNU-UHFFFAOYSA-N 0.000 description 2
- WXZLAJFGVZTLKZ-UHFFFAOYSA-N 3-chloro-3-(4-chlorophenyl)-2-[(4-chlorophenyl)methyl]isoindol-1-one Chemical compound C1=CC(Cl)=CC=C1CN1C(C=2C=CC(Cl)=CC=2)(Cl)C2=CC=CC=C2C1=O WXZLAJFGVZTLKZ-UHFFFAOYSA-N 0.000 description 2
- BVRJSRRPHSOZHJ-UHFFFAOYSA-N 4-(2-trimethylsilylethoxymethoxy)benzonitrile Chemical compound C[Si](C)(C)CCOCOC1=CC=C(C#N)C=C1 BVRJSRRPHSOZHJ-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- WHKRHBLAJFYZKF-UHFFFAOYSA-N 5-(hydroxymethyl)-2-methoxyphenol Chemical compound COC1=CC=C(CO)C=C1O WHKRHBLAJFYZKF-UHFFFAOYSA-N 0.000 description 2
- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 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
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000010437 gem Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 2
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- VYSGBGYFLODEEZ-UHFFFAOYSA-M sodium;2-(2-benzyl-3-oxo-1-phenylisoindol-1-yl)oxyethanesulfonate Chemical compound [Na+].O=C1C2=CC=CC=C2C(OCCS(=O)(=O)[O-])(C=2C=CC=CC=2)N1CC1=CC=CC=C1 VYSGBGYFLODEEZ-UHFFFAOYSA-M 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 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 2
- 238000001665 trituration Methods 0.000 description 2
- WZFMBOJMKSQRJZ-UHFFFAOYSA-N (3-prop-2-enoxyphenyl)methanol Chemical compound OCC1=CC=CC(OCC=C)=C1 WZFMBOJMKSQRJZ-UHFFFAOYSA-N 0.000 description 1
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- FBKFDSUZBVDZIX-FFGDOFBPSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1h-indol-3-yl)propanoyl]amino]-5-[[1-[[(2s)-1-amino-4-meth Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NC(C)(C)C(=O)N[C@@H](CC=1C=CC(CP(O)(O)=O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=C(Cl)C=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)NC1(CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(C)=O)C1=CC=CC=C1 FBKFDSUZBVDZIX-FFGDOFBPSA-N 0.000 description 1
- PMMUQDOXNLVILC-UHFFFAOYSA-N 1,3-bis[[tert-butyl(dimethyl)silyl]oxy]-1-phenylpropan-2-amine Chemical compound CC(C)(C)[Si](C)(C)OCC(N)C(O[Si](C)(C)C(C)(C)C)C1=CC=CC=C1 PMMUQDOXNLVILC-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- FGFBEHFJSQBISW-UHFFFAOYSA-N 1h-cyclopenta[b]pyridine Chemical compound C1=CNC2=CC=CC2=C1 FGFBEHFJSQBISW-UHFFFAOYSA-N 0.000 description 1
- FAVIALDFVWSZFV-UHFFFAOYSA-N 2,3-dihydroisoindol-1-one;lead Chemical compound [Pb].C1=CC=C2C(=O)NCC2=C1 FAVIALDFVWSZFV-UHFFFAOYSA-N 0.000 description 1
- HHSJOVPBCHTADG-UHFFFAOYSA-N 2,4-dihydroxy-n-(2-hydroxyethyl)benzamide Chemical compound OCCNC(=O)C1=CC=C(O)C=C1O HHSJOVPBCHTADG-UHFFFAOYSA-N 0.000 description 1
- YWECCEXWKFHHQJ-UHFFFAOYSA-N 2-(4-chlorobenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1 YWECCEXWKFHHQJ-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-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
- TZZZMSQQCFPPIY-UHFFFAOYSA-N 2-[tert-butyl(diphenyl)silyl]oxypropan-1-amine Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC(CN)C)C1=CC=CC=C1 TZZZMSQQCFPPIY-UHFFFAOYSA-N 0.000 description 1
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- XSHISXQEKIKSGC-UHFFFAOYSA-N 2-aminoethyl 2-methylprop-2-enoate;hydron;chloride Chemical compound Cl.CC(=C)C(=O)OCCN XSHISXQEKIKSGC-UHFFFAOYSA-N 0.000 description 1
- MWGATWIBSKHFMR-UHFFFAOYSA-N 2-anilinoethanol Chemical compound OCCNC1=CC=CC=C1 MWGATWIBSKHFMR-UHFFFAOYSA-N 0.000 description 1
- SJBXMBRSTWBJRN-UHFFFAOYSA-N 2-benzoyl-4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 SJBXMBRSTWBJRN-UHFFFAOYSA-N 0.000 description 1
- XSGVBEFFCFKLLP-UHFFFAOYSA-N 2-benzyl-3-[(4-methoxyphenyl)methoxy]-3-phenylisoindol-1-one Chemical compound C1=CC(OC)=CC=C1COC1(C=2C=CC=CC=2)C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 XSGVBEFFCFKLLP-UHFFFAOYSA-N 0.000 description 1
- WBLRKHGOFNUMCD-UHFFFAOYSA-N 2-benzyl-3-hydroxy-3-[4-(2-trimethylsilylethoxymethoxy)phenyl]isoindol-1-one Chemical compound C1=CC(OCOCC[Si](C)(C)C)=CC=C1C1(O)C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 WBLRKHGOFNUMCD-UHFFFAOYSA-N 0.000 description 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
- QOTAQTRFJWLFCR-UHFFFAOYSA-N 3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl-(4-methoxycyclohexyl)methanone Chemical compound C1CC(OC)CCC1C(=O)C1=CC=C(N=C2C(CCCO2)=C2)C2=C1 QOTAQTRFJWLFCR-UHFFFAOYSA-N 0.000 description 1
- LHNFPTIDVVYNEL-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-[(4-nitrophenyl)methyl]-3-(2,4,6-trihydroxyphenyl)isoindol-1-one Chemical compound OC1=CC(O)=CC(O)=C1C1(C=2C=CC(Cl)=CC=2)C2=CC=CC=C2C(=O)N1CC1=CC=C([N+]([O-])=O)C=C1 LHNFPTIDVVYNEL-UHFFFAOYSA-N 0.000 description 1
- CRVJNZFTCFETBJ-UHFFFAOYSA-N 3-amino-2-(cyclohexylmethyl)-3-(4-ethoxyphenyl)isoindol-1-one Chemical compound C1=CC(OCC)=CC=C1C1(N)C2=CC=CC=C2C(=O)N1CC1CCCCC1 CRVJNZFTCFETBJ-UHFFFAOYSA-N 0.000 description 1
- ZDFNVYGZZXLBSF-UHFFFAOYSA-N 3-amino-2-(cyclohexylmethyl)-3-[4-(2-methylpropoxy)phenyl]isoindol-1-one Chemical compound C1=CC(OCC(C)C)=CC=C1C1(N)C2=CC=CC=C2C(=O)N1CC1CCCCC1 ZDFNVYGZZXLBSF-UHFFFAOYSA-N 0.000 description 1
- DIGYJEFQLOGPSQ-UHFFFAOYSA-N 3-amino-2-propyl-3-[4-(2-trimethylsilylethoxymethoxy)phenyl]isoindol-1-one Chemical compound CCCN1C(=O)C2=CC=CC=C2C1(N)C1=CC=C(OCOCC[Si](C)(C)C)C=C1 DIGYJEFQLOGPSQ-UHFFFAOYSA-N 0.000 description 1
- IWJJETOBHSCNSQ-UHFFFAOYSA-N 3-benzylsulfanyl-3-(4-chlorophenyl)-2-propylisoindol-1-one Chemical compound CCCN1C(=O)C2=CC=CC=C2C1(C=1C=CC(Cl)=CC=1)SCC1=CC=CC=C1 IWJJETOBHSCNSQ-UHFFFAOYSA-N 0.000 description 1
- AHEPBHDSXYIKED-UHFFFAOYSA-N 3-chloro-3-(4-chlorophenyl)-2-propylisoindol-1-one Chemical compound CCCN1C(=O)C2=CC=CC=C2C1(Cl)C1=CC=C(Cl)C=C1 AHEPBHDSXYIKED-UHFFFAOYSA-N 0.000 description 1
- BPDBQQYWKOIIMN-UHFFFAOYSA-N 3-chloro-3-(4-fluorophenyl)-2-benzofuran-1-one Chemical compound C1=CC(F)=CC=C1C1(Cl)C2=CC=CC=C2C(=O)O1 BPDBQQYWKOIIMN-UHFFFAOYSA-N 0.000 description 1
- KAUMDYDNLPQESC-UHFFFAOYSA-N 3-hydroxy-2,3-dihydroisoindol-1-one Chemical class C1=CC=C2C(O)NC(=O)C2=C1 KAUMDYDNLPQESC-UHFFFAOYSA-N 0.000 description 1
- QWMUMFXFUCDJJI-UHFFFAOYSA-N 4-(2-methylpropoxy)benzonitrile Chemical compound CC(C)COC1=CC=C(C#N)C=C1 QWMUMFXFUCDJJI-UHFFFAOYSA-N 0.000 description 1
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- PJRLUGQMEZZDIY-UHFFFAOYSA-N 4-ethoxybenzonitrile Chemical compound CCOC1=CC=C(C#N)C=C1 PJRLUGQMEZZDIY-UHFFFAOYSA-N 0.000 description 1
- PBCQHHVYHDIRHL-UHFFFAOYSA-N 7,7-dimethyl-10-(4-phenylmethoxyphenyl)-5,6,8,10-tetrahydroindeno[1,2-b]quinoline-9,11-dione Chemical compound C1C(C)(C)CC(=O)C2=C1NC(C1=CC=CC=C1C1=O)=C1C2C(C=C1)=CC=C1OCC1=CC=CC=C1 PBCQHHVYHDIRHL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- DUUXVTZYIRQZQA-UHFFFAOYSA-N C1(CCCCC1)CN.C1(CCCCC1)CNC(C1=CC=CC=C1)=O Chemical compound C1(CCCCC1)CN.C1(CCCCC1)CNC(C1=CC=CC=C1)=O DUUXVTZYIRQZQA-UHFFFAOYSA-N 0.000 description 1
- 101100257262 Caenorhabditis elegans soc-1 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 102100039851 DNA-directed RNA polymerases I and III subunit RPAC1 Human genes 0.000 description 1
- 101710112289 DNA-directed RNA polymerases I and III subunit RPAC1 Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 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 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 1
- 241000255969 Pieris brassicae Species 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000219492 Quercus Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000008430 aromatic amides Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001042 autoregulative effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- YDVJBLJCSLVMSY-UHFFFAOYSA-N carbamoyl cyanide Chemical compound NC(=O)C#N YDVJBLJCSLVMSY-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- HXSNGAHNYZBZTH-UHFFFAOYSA-N cyclopropylmethanamine;hydrochloride Chemical compound Cl.NCC1CC1 HXSNGAHNYZBZTH-UHFFFAOYSA-N 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000012909 foetal bovine serum Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 150000002462 imidazolines Chemical class 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- DAKZISABEDGGSV-UHFFFAOYSA-N n-(2-aminoethyl)acetamide Chemical compound CC(=O)NCCN DAKZISABEDGGSV-UHFFFAOYSA-N 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- LGTPQVBRVVRWDX-UHFFFAOYSA-N n-(cyclohexylmethyl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NCC1CCCCC1 LGTPQVBRVVRWDX-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 description 1
- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 1
- 229960001553 phloroglucinol Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000005522 programmed cell death Effects 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
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003571 reporter gene assay Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N tert-butyl alcohol Substances CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/50—Iso-indoles; Hydrogenated iso-indoles with oxygen and nitrogen atoms in positions 1 and 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0419481.7 | 2004-09-02 | ||
| GBGB0419481.7A GB0419481D0 (en) | 2004-09-02 | 2004-09-02 | Isoindolin-1-one derivatives |
| PCT/GB2005/003345 WO2006024837A1 (en) | 2004-09-02 | 2005-08-26 | Isoindolin-1-one derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2578955A1 true CA2578955A1 (en) | 2006-03-09 |
Family
ID=33155907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002578955A Abandoned CA2578955A1 (en) | 2004-09-02 | 2005-08-26 | Isoindolin-1-one derivatives |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8258175B2 (enExample) |
| EP (1) | EP1786773B1 (enExample) |
| JP (1) | JP5057273B2 (enExample) |
| AU (1) | AU2005278962C1 (enExample) |
| CA (1) | CA2578955A1 (enExample) |
| GB (1) | GB0419481D0 (enExample) |
| WO (1) | WO2006024837A1 (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2346157T3 (es) * | 2006-03-22 | 2010-10-11 | Janssen Pharmaceutica N.V. | Derivados de alquilaminas ciclicas como inhibidores de la interaccion entre mdm2 y p53. |
| ATE470665T1 (de) * | 2006-03-22 | 2010-06-15 | Janssen Pharmaceutica Nv | Cycloalkylaminderivate als inhibitoren der wechselwirkung zwischen mdm2 und p53 |
| WO2007139499A1 (en) * | 2006-05-31 | 2007-12-06 | Aprea Ab | Compounds for use as a medicament |
| EP2103619A4 (en) | 2006-12-14 | 2011-11-23 | Daiichi Sankyo Co Ltd | IMIDAZOTHIAZOLDERIVATE |
| WO2009151069A1 (ja) | 2008-06-12 | 2009-12-17 | 第一三共株式会社 | ４，７－ジアザスピロ［２．５］オクタン環構造を有するイミダゾチアゾール誘導体 |
| GB0811643D0 (en) * | 2008-06-25 | 2008-07-30 | Cancer Rec Tech Ltd | New therapeutic agents |
| JP2013510860A (ja) | 2009-11-12 | 2013-03-28 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン | スピロ−オキシインドールｍｄｍ２アンタゴニスト |
| CU24130B1 (es) | 2009-12-22 | 2015-09-29 | Novartis Ag | Isoquinolinonas y quinazolinonas sustituidas |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CA2817585A1 (en) | 2010-11-12 | 2012-05-18 | The Regents Of The University Of Michigan | Spiro-oxindole mdm2 antagonists |
| DK2684880T3 (en) | 2011-03-10 | 2018-05-22 | Daiichi Sankyo Co Ltd | DISPIROPYRROLIDINE DERIVATIVES |
| ES2624808T3 (es) | 2011-05-11 | 2017-07-17 | The Regents Of The University Of Michigan | Antagonistas de MDM2 espirooxindólicos |
| AR088320A1 (es) | 2011-10-14 | 2014-05-28 | Incyte Corp | Derivados de isoindolinona y pirrolopiridinona como inhibidores de akt |
| JP6171003B2 (ja) | 2012-05-24 | 2017-07-26 | ノバルティス アーゲー | ピロロピロリジノン化合物 |
| TWI586668B (zh) | 2012-09-06 | 2017-06-11 | 第一三共股份有限公司 | 二螺吡咯啶衍生物之結晶 |
| EP2935263B1 (en) | 2012-12-20 | 2018-12-05 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
| US9556180B2 (en) | 2013-01-22 | 2017-01-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction |
| US9403827B2 (en) | 2013-01-22 | 2016-08-02 | Novartis Ag | Substituted purinone compounds |
| CA2913697A1 (en) | 2013-05-27 | 2014-12-04 | Novartis Ag | Imidazopyrrolidinone derivatives and their use in the treatment of disease |
| CA2912986A1 (en) | 2013-05-28 | 2014-12-04 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease |
| CA2912991A1 (en) | 2013-05-28 | 2014-12-04 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives and their use in the treatment of disease |
| MX2016006667A (es) | 2013-11-21 | 2016-07-26 | Novartis Ag | Derivados de pirrolo-pirrolona y su uso como inhibidores. |
| EP3260119B1 (en) | 2015-02-20 | 2023-11-15 | Daiichi Sankyo Company, Limited | Combination method for treating cancer |
| US10485794B2 (en) | 2015-04-13 | 2019-11-26 | Daiichi Sankyo Company, Limited | Treatment method by combined use of MDM2 inhibitor and BTK inhibitor |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| TWI724056B (zh) | 2015-11-19 | 2021-04-11 | 美商卡默森屈有限公司 | Ｃｘｃｒ２抑制劑 |
| TWI734715B (zh) * | 2015-11-19 | 2021-08-01 | 美商卡默森屈有限公司 | 趨化因子受體調節劑 |
| AU2017246453A1 (en) | 2016-04-06 | 2018-11-08 | The Regents Of The University Of Michigan | Monofunctional intermediates for ligand-dependent target protein degradation |
| JP7037500B2 (ja) | 2016-04-06 | 2022-03-16 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Ｍｄｍ２タンパク質分解剤 |
| EP3527226A4 (en) | 2016-10-17 | 2020-06-17 | Daiichi Sankyo Company, Limited | COMBINATION THERAPY PROCEDURE WITH MDM2 INHIBITOR AND DNA METHYL TRANSFERASE INHIBITOR |
| GB201704966D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201704965D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| CN107286074B (zh) * | 2017-08-16 | 2019-08-20 | 厦门华厦学院 | 3-羟基异吲哚-1-酮衍生物及其制备方法 |
| US11207294B2 (en) | 2018-01-08 | 2021-12-28 | Chemocentryx, Inc. | Methods of treating generalized pustular psoriasis with an antagonist of CCR6 or CXCR2 |
| CN109053546B (zh) * | 2018-07-05 | 2021-04-27 | 中国科学院兰州化学物理研究所 | 一种苯酞类衍生物及其制备方法和应用 |
| MX2021003999A (es) | 2018-10-08 | 2021-06-23 | Univ Michigan Regents | Moleculas de bajo peso molecular degradadoras de la proteina mdm2. |
| EP3659964A1 (en) | 2018-11-28 | 2020-06-03 | Hysilabs, SAS | Catalysed process of production of hydrogen from silylated derivatives as hydrogen carrier compounds |
| PE20231066A1 (es) | 2020-02-07 | 2023-07-17 | Gasherbrum Bio Inc | Agonistas heterociclicos de glp-1 |
| IL296451B2 (en) | 2020-03-19 | 2026-05-01 | Kymera Therapeutics Inc | MDM2 joints and their uses |
| JP7858636B2 (ja) | 2020-09-10 | 2026-05-14 | ガシャーブラム・バイオ・インコーポレイテッド | ヘテロ環ｇｌｐ－１アゴニスト |
| IL322686A (en) | 2023-02-16 | 2025-10-01 | Gasherbrum Bio Inc | Heterocyclic glp-1 agonists |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3466298A (en) * | 1967-03-14 | 1969-09-09 | American Home Prod | Process for the preparation of 2-(2-aminoethyl)isoindolines |
| US3763178A (en) * | 1968-09-05 | 1973-10-02 | American Home Prod | Imidazolinyl phenyl carbonyl acid addition salts and related compounds |
| CY787A (en) * | 1970-02-12 | 1976-06-01 | American Home Prod | Novel phtalimidine compounds |
| AR203991A1 (es) * | 1972-03-16 | 1975-11-12 | Rhone Poulenc Sa | Procedimiento para preparar derivados de(hidroxi-2-amino-3-propoxi)-3-isoindolinona-1 |
| FR2217000B1 (enExample) * | 1973-02-08 | 1976-04-09 | Rhone Poulenc Ind | |
| GB1601701A (en) * | 1977-07-22 | 1981-11-04 | Delmar Chem | Production of heterocyclic benzamide compounds |
| US4200759A (en) * | 1978-07-20 | 1980-04-29 | Delmar Chemicals, Limited | Preparation of imidazo[2,1-a]isoindole compounds |
| DE2840800C2 (de) * | 1978-09-20 | 1980-02-14 | Mannesmann Demag Ag, 4100 Duisburg | Kanalbaumaschine |
| US4244966A (en) * | 1979-09-24 | 1981-01-13 | American Home Products Corporation | 1,3-Dihydro-3-(2-hydroxy-, 2-bromo- or 2-chloroethyl)-2H-isoindol-1-one derivatives |
| US4331600A (en) * | 1980-10-31 | 1982-05-25 | Usv Pharmaceutical Corporation | Intermediates for the synthesis of phthalimidines |
| FR2533563A1 (fr) * | 1982-09-23 | 1984-03-30 | Adir | Nouveaux derives de la sulfonyluree, leurs procedes de preparation et les compositions pharmaceutiques les renfermant |
| DE19807423A1 (de) * | 1998-02-21 | 1999-08-26 | Hoechst Marion Roussel De Gmbh | Subustituierte Isoindolone, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| JP2001106673A (ja) * | 1999-07-26 | 2001-04-17 | Banyu Pharmaceut Co Ltd | ビアリールウレア誘導体 |
| AU1466001A (en) * | 1999-11-05 | 2001-05-14 | Phase-1 Molecular Toxicology | Methods of determining individual hypersensitivity to an agent |
| CN100486969C (zh) * | 2001-12-18 | 2009-05-13 | 霍夫曼-拉罗奇有限公司 | 顺式-2,4,5-三苯基-咪唑啉及其在肿瘤治疗中的应用 |
| JP2004217591A (ja) * | 2003-01-16 | 2004-08-05 | Dai Ichi Seiyaku Co Ltd | シス選択的フルオロシクロプロパン誘導体の製造方法 |
| JP2005255660A (ja) * | 2004-03-10 | 2005-09-22 | Katsuhiko Tomooka | 多官能基を有するラクタム類とその製法 |
| EP1751124A4 (en) * | 2004-05-07 | 2010-04-14 | Exelixis Inc | RAF MODULATORS AND METHODS OF USE |
-
2004
- 2004-09-02 GB GBGB0419481.7A patent/GB0419481D0/en not_active Ceased
-
2005
- 2005-08-26 CA CA002578955A patent/CA2578955A1/en not_active Abandoned
- 2005-08-26 US US11/574,531 patent/US8258175B2/en active Active
- 2005-08-26 AU AU2005278962A patent/AU2005278962C1/en not_active Expired
- 2005-08-26 WO PCT/GB2005/003345 patent/WO2006024837A1/en not_active Ceased
- 2005-08-26 EP EP05782577.0A patent/EP1786773B1/en not_active Expired - Lifetime
- 2005-08-26 JP JP2007528986A patent/JP5057273B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1786773B1 (en) | 2017-03-01 |
| AU2005278962A1 (en) | 2006-03-09 |
| EP1786773A1 (en) | 2007-05-23 |
| JP2008511601A (ja) | 2008-04-17 |
| WO2006024837A1 (en) | 2006-03-09 |
| US20080261917A1 (en) | 2008-10-23 |
| JP5057273B2 (ja) | 2012-10-24 |
| GB0419481D0 (en) | 2004-10-06 |
| AU2005278962C1 (en) | 2012-10-25 |
| US8258175B2 (en) | 2012-09-04 |
| AU2005278962B2 (en) | 2012-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2005278962C1 (en) | Isoindolin-1-one derivatives | |
| EP0672031B1 (en) | Catechol diethers as selective pde iv inhibitors | |
| RU2131876C1 (ru) | Бициклические тетрагидропиразолпиридины или их фармацевтически приемлемые соли, фармацевтическая композиция, способ ингибирования фосфодиэстеразы, способ лечения | |
| CA2766328C (en) | Isoindolin-1-one derivatives | |
| HUT71553A (en) | 2-thioindoles (selenoindoles) and related disulfides (selenides) which inhibit protein tyrosine kinases and which have antitumor properties | |
| EA002778B1 (ru) | СЕЛЕКТИВНЫЕ β-АДРЕНЕРГИЧЕСКИЕ АГОНИСТЫ | |
| WO1995007276A1 (en) | Bicyclic heterocyclic sulfonamide and sulfonic ester derivatives | |
| JP5778297B2 (ja) | 癌治療用のｈｄａｃ阻害剤としての新規４−アミノ−ｎ−ヒドロキシ−ベンズアミド | |
| EA015516B1 (ru) | Ингибиторы 11-бета-гидроксистероид дегидрогеназы 1 | |
| GB2216517A (en) | 1-(3-aryl-prop-2-enyl)-4-tricyclyl-piperazines | |
| AU2006263961A1 (en) | Bicyclic derivatives as p38 kinase inhibitors | |
| RU2497812C2 (ru) | Производные имидазолидин-2,4-диона и их применение в качестве лекарственного средства против рака | |
| HK1203943A1 (en) | Quinazolinedione derivative | |
| JP3218243B2 (ja) | ベンズイミダゾール、その製造および使用法 | |
| CN115703761A (zh) | 作为wwp1抑制剂的化合物及其应用 | |
| EP0290145B1 (en) | Aliphatic carboxamides | |
| JPH0471914B2 (enExample) | ||
| JP3079570B2 (ja) | チアゾリン誘導体 | |
| JPH06211788A (ja) | インドール−７−カルボキサミド誘導体 | |
| AU2006263962A1 (en) | Bicyclic derivatives as p38 kinase inhibitors | |
| WO2004106317A1 (ja) | ベンゾフラン化合物、およびそれを含有してなる医薬組成物 | |
| US7250434B2 (en) | CCK-1 receptor modulators | |
| US20250026741A1 (en) | Inhibitors of the oncogenic shp2 phosphatase and uses thereof | |
| JP2009513692A (ja) | 炎症の治療に有用なピラゾール化合物 | |
| JP2021529785A (ja) | ヘッジホッグ経路に関連する状態の治療のための化合物および方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |