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
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Veterinary Medicine (AREA)
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- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| 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)
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|---|---|
| CA2578955A1 true CA2578955A1 (en) | 2006-03-09 |
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| CA002578955A Abandoned CA2578955A1 (en) | 2004-09-02 | 2005-08-26 | Isoindolin-1-one derivatives |
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| 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) |
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| US8088795B2 (en) * | 2006-03-22 | 2012-01-03 | Janssen Pharmaceutica N.V. | Cyclic-alkylamine derivatives as inhibitors of the interaction between MDM2 and p53 |
| BRPI0709077A2 (pt) * | 2006-03-22 | 2012-04-10 | Janssen Pharmaceutica Nv | derivados de alquilaminas cìclicas como inibidores da interação entre mdm2 e p53 |
| WO2007139499A1 (en) * | 2006-05-31 | 2007-12-06 | Aprea Ab | Compounds for use as a medicament |
| CA2672565A1 (en) | 2006-12-14 | 2008-06-19 | Daiichi Sankyo Company, Limited | Imidazothiazole derivatives |
| 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 |
| RU2553269C2 (ru) | 2009-11-12 | 2015-06-10 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Спирооксиндольные антагонисты mdm2 |
| 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 |
| UY33725A (es) | 2010-11-12 | 2012-06-29 | Sanofi Sa | Antagonistas de mdm2 de espiro-oxindol |
| KR101779644B1 (ko) | 2011-03-10 | 2017-09-18 | 다이이찌 산쿄 가부시키가이샤 | 디스피로피롤리딘 유도체 |
| CN103717605B (zh) | 2011-05-11 | 2016-05-18 | 密执安州立大学董事会 | 螺-羟吲哚mdm2拮抗剂 |
| TW201321371A (zh) | 2011-10-14 | 2013-06-01 | Incyte Corp | 做為ａｋｔ抑制劑之異吲哚啉酮及吡咯并吡啶酮衍生物 |
| US9365576B2 (en) | 2012-05-24 | 2016-06-14 | Novartis Ag | Pyrrolopyrrolidinone compounds |
| 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 |
| AR094116A1 (es) | 2012-12-20 | 2015-07-08 | Merck Sharp & Dohme | Imidazopiridinas sustituidas como inhibidores de hdm2 |
| WO2014115077A1 (en) | 2013-01-22 | 2014-07-31 | Novartis Ag | Substituted purinone compounds |
| WO2014115080A1 (en) | 2013-01-22 | 2014-07-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the p53/mdm2 interaction |
| CA2913697A1 (en) | 2013-05-27 | 2014-12-04 | Novartis Ag | Imidazopyrrolidinone derivatives and their use in the treatment of disease |
| ES2656471T3 (es) | 2013-05-28 | 2018-02-27 | Novartis Ag | Derivados de pirazolo-pirrolidin-4-ona como inhibidores de BET y su uso en el tratamiento de enfermedades |
| EP3004112B1 (en) | 2013-05-28 | 2017-08-30 | Novartis AG | Pyrazolo-pyrrolidin-4-one derivatives and their use in the treatment of disease |
| EP3071571A1 (en) | 2013-11-21 | 2016-09-28 | Novartis AG | Pyrrolopyrrolone derivatives and their use as bet inhibitors |
| CN107427501B (zh) | 2015-02-20 | 2023-12-01 | 第一三共株式会社 | 通过联合使用治疗癌症的方法 |
| JP6823587B2 (ja) | 2015-04-13 | 2021-02-03 | 第一三共株式会社 | Ｍｄｍ２阻害剤とｂｔｋ阻害剤との併用治療法 |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| 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 |
| TWI724056B (zh) | 2015-11-19 | 2021-04-11 | 美商卡默森屈有限公司 | Ｃｘｃｒ２抑制劑 |
| AU2017246452C1 (en) | 2016-04-06 | 2021-06-03 | The Regents Of The University Of Michigan | MDM2 protein degraders |
| AU2017246453A1 (en) | 2016-04-06 | 2018-11-08 | The Regents Of The University Of Michigan | Monofunctional intermediates for ligand-dependent target protein degradation |
| KR20190068544A (ko) | 2016-10-17 | 2019-06-18 | 다이이찌 산쿄 가부시키가이샤 | Mdm2 저해제와 dna 메틸트랜스페라아제 저해제의 병용 치료법 |
| GB201704965D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201704966D0 (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 |
| CN111867579B (zh) | 2018-01-08 | 2023-11-24 | 凯莫森特里克斯股份有限公司 | Ccr6或cxcr2拮抗剂治疗泛发性脓疱型银屑病的方法 |
| 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 |
| US11046703B2 (en) | 2018-10-08 | 2021-06-29 | The Regents Of The University Of Michigan | Small molecule MDM2 protein degraders |
| EP3659964A1 (en) | 2018-11-28 | 2020-06-03 | Hysilabs, SAS | Catalysed process of production of hydrogen from silylated derivatives as hydrogen carrier compounds |
| SMT202400344T1 (it) | 2020-02-07 | 2024-11-15 | Gasherbrum Bio Inc | Agonisti di glp-1 eterociclici |
| PH12022552458A1 (en) | 2020-03-19 | 2024-01-22 | Kymera Therapeutics Inc | Mdm2 degraders and uses thereof |
| WO2024169952A1 (en) | 2023-02-16 | 2024-08-22 | 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 |
| GB1325065A (en) * | 1970-02-12 | 1973-08-01 | American Home Prod | Imidazoline derivatives |
| AR203996A1 (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 |
| WO2001032928A2 (en) * | 1999-11-05 | 2001-05-10 | Phase-1 Molecular Toxicology | Methods of determining individual hypersensitivity to an agent |
| MXPA04005906A (es) * | 2001-12-18 | 2004-09-13 | Hoffmann La Roche | Cis-2,4,5-trifenil-.imidazolinas y uso de la misma para tratamiento de tumores. |
| 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 |
| AU2005244736B2 (en) * | 2004-05-07 | 2012-06-28 | Exelixis Patent Company Llc | Raf modulators and methods of use |
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2005
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- 2005-08-26 US US11/574,531 patent/US8258175B2/en active Active
- 2005-08-26 CA CA002578955A patent/CA2578955A1/en not_active Abandoned
- 2005-08-26 JP JP2007528986A patent/JP5057273B2/ja not_active Expired - Lifetime
- 2005-08-26 EP EP05782577.0A patent/EP1786773B1/en not_active Expired - Lifetime
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| WO2006024837A1 (en) | 2006-03-09 |
| EP1786773B1 (en) | 2017-03-01 |
| AU2005278962C1 (en) | 2012-10-25 |
| JP5057273B2 (ja) | 2012-10-24 |
| AU2005278962B2 (en) | 2012-03-01 |
| JP2008511601A (ja) | 2008-04-17 |
| US20080261917A1 (en) | 2008-10-23 |
| US8258175B2 (en) | 2012-09-04 |
| EP1786773A1 (en) | 2007-05-23 |
| AU2005278962A1 (en) | 2006-03-09 |
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