ES2320564T3 - Nuevas 5-acilindolinonas con contenido en cicloalquilo, su preparacion y su uso como medicamentos. - Google Patents

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Publication number

ES2320564T3

ES2320564T3 ES05715812T ES05715812T ES2320564T3 ES 2320564 T3 ES2320564 T3 ES 2320564T3 ES 05715812 T ES05715812 T ES 05715812T ES 05715812 T ES05715812 T ES 05715812T ES 2320564 T3 ES2320564 T3 ES 2320564T3

Authority

ES

Spain

Prior art keywords

alkyl

group

amino

indolinone

baselineskip

Prior art date

2004-03-12

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.)

Expired - Lifetime

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• 238000002360 preparation method Methods 0.000 title claims description 27
• 239000003814 drug Substances 0.000 title claims description 9
• 229940079593 drug Drugs 0.000 title claims description 6
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 143
• 150000001875 compounds Chemical class 0.000 claims abstract description 86
• -1 nitro, cyano, amino Chemical group 0.000 claims abstract description 79
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 43
• 239000000203 mixture Substances 0.000 claims abstract description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 29
• 150000003839 salts Chemical class 0.000 claims abstract description 26
• 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 claims abstract description 18
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 17
• 239000000460 chlorine Substances 0.000 claims abstract description 16
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 16
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 15
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 15
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 14
• 239000011737 fluorine Substances 0.000 claims abstract description 14
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 14
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 13
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 12
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
• 125000001424 substituent group Chemical group 0.000 claims abstract description 11
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 10
• 229910052794 bromium Inorganic materials 0.000 claims abstract description 10
• 125000004434 sulfur atom Chemical group 0.000 claims abstract description 10
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 9
• 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 8
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims abstract description 7
• 125000003118 aryl group Chemical group 0.000 claims abstract description 7
• 125000002431 aminoalkoxy group Chemical group 0.000 claims abstract description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 6
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 4
• 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims abstract description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 4
• 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 claims abstract description 3
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 3
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 3
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 3
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 3
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims abstract description 3
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 3
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims abstract description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 3
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims abstract description 3
• 125000005544 phthalimido group Chemical group 0.000 claims abstract description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 3
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
• 239000002253 acid Substances 0.000 claims description 54
• 239000000126 substance Substances 0.000 claims description 24
• 238000006243 chemical reaction Methods 0.000 claims description 19
• 125000004429 atom Chemical group 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• 238000000034 method Methods 0.000 claims description 10
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000006239 protecting group Chemical group 0.000 claims description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 208000024827 Alzheimer disease Diseases 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 229910052740 iodine Inorganic materials 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 5
• 125000002541 furyl group Chemical group 0.000 claims description 5
• 208000012902 Nervous system disease Diseases 0.000 claims description 4
• 208000025966 Neurological disease Diseases 0.000 claims description 4
• 150000007513 acids Chemical class 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 4
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
• 150000007529 inorganic bases Chemical class 0.000 claims description 4
• 150000007530 organic bases Chemical class 0.000 claims description 4
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
• VLYNCWZASZUTNV-UHFFFAOYSA-N 5-acetyl-3-[1,3-benzodioxol-5-yl-[(1-methylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound C1CN(C)CCC1NC(C=1C=C2OCOC2=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O VLYNCWZASZUTNV-UHFFFAOYSA-N 0.000 claims description 3
• LPJLHHOQHBDNDH-UHFFFAOYSA-N 5-acetyl-3-[furan-3-yl-[(1-methylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound C1CN(C)CCC1NC(C1=COC=C1)=C1C2=CC(C(C)=O)=CC=C2NC1=O LPJLHHOQHBDNDH-UHFFFAOYSA-N 0.000 claims description 3
• 208000020925 Bipolar disease Diseases 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 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
• 230000003412 degenerative effect Effects 0.000 claims description 3
• 150000007522 mineralic acids Chemical class 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000006603 (C1-C3) alkylaminosulfonyl group Chemical group 0.000 claims description 2
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 2
• BBKKUSRWYXUKFH-UHFFFAOYSA-N 5-acetyl-3-[(3,5-dimethoxyphenyl)-[(1-methylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound COC1=CC(OC)=CC(C(NC2CCN(C)CC2)=C2C3=CC(=CC=C3NC2=O)C(C)=O)=C1 BBKKUSRWYXUKFH-UHFFFAOYSA-N 0.000 claims description 2
• WTUCLYCGYZCTRQ-UHFFFAOYSA-N 5-acetyl-3-[(3-methoxyphenyl)-[(1-methylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound COC1=CC=CC(C(NC2CCN(C)CC2)=C2C3=CC(=CC=C3NC2=O)C(C)=O)=C1 WTUCLYCGYZCTRQ-UHFFFAOYSA-N 0.000 claims description 2
• RZGKSKXJUVMZPN-UHFFFAOYSA-N 5-acetyl-3-[(4-methoxyphenyl)-[(1-methylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound C1=CC(OC)=CC=C1C(NC1CCN(C)CC1)=C1C2=CC(C(C)=O)=CC=C2NC1=O RZGKSKXJUVMZPN-UHFFFAOYSA-N 0.000 claims description 2
• SAXWPTUODJSWQT-UHFFFAOYSA-N 5-acetyl-3-[1,3-benzodioxol-5-yl-[(1-ethylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound C1CN(CC)CCC1NC(C=1C=C2OCOC2=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O SAXWPTUODJSWQT-UHFFFAOYSA-N 0.000 claims description 2
• UDNYGVDINCYCAN-UHFFFAOYSA-N 5-acetyl-3-[[(1-ethylpiperidin-4-yl)amino]-phenylmethylidene]-1h-indol-2-one Chemical compound C1CN(CC)CCC1NC(C=1C=CC=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O UDNYGVDINCYCAN-UHFFFAOYSA-N 0.000 claims description 2
• WPYXXIHXRUGCDD-UHFFFAOYSA-N 5-acetyl-3-[[(1-methylpiperidin-4-yl)amino]-phenylmethylidene]-1h-indol-2-one Chemical compound C1CN(C)CCC1NC(C=1C=CC=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O WPYXXIHXRUGCDD-UHFFFAOYSA-N 0.000 claims description 2
• OCLZJKOZHRGWEK-UHFFFAOYSA-N 5-acetyl-3-[phenyl-(thian-4-ylamino)methylidene]-1h-indol-2-one Chemical compound C12=CC(C(=O)C)=CC=C2NC(=O)C1=C(C=1C=CC=CC=1)NC1CCSCC1 OCLZJKOZHRGWEK-UHFFFAOYSA-N 0.000 claims description 2
• CEWZZVGVKPVUOS-UHFFFAOYSA-N 5-acetyl-3-[phenyl-[(1-propylpiperidin-4-yl)amino]methylidene]-1h-indol-2-one Chemical compound C1CN(CCC)CCC1NC(C=1C=CC=CC=1)=C1C2=CC(C(C)=O)=CC=C2NC1=O CEWZZVGVKPVUOS-UHFFFAOYSA-N 0.000 claims description 2
• HJGMRAKQWLKWMH-UHFFFAOYSA-N 8-methyl-8-azabicyclo[3.2.1]octan-3-amine Chemical compound C1C(N)CC2CCC1N2C HJGMRAKQWLKWMH-UHFFFAOYSA-N 0.000 claims description 2
• JEOUETUTMDLIHY-QAQDUYKDSA-N C1C[C@@H](N(C)C)CC[C@@H]1NCCC=C1C2=CC(C(C)=O)=CC=C2NC1=O Chemical compound C1C[C@@H](N(C)C)CC[C@@H]1NCCC=C1C2=CC(C(C)=O)=CC=C2NC1=O JEOUETUTMDLIHY-QAQDUYKDSA-N 0.000 claims description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
• 125000005121 aminocarbonylalkoxy group Chemical group 0.000 claims description 2
• 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 2
• 125000001246 bromo group Chemical group Br* 0.000 claims description 2
• 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 2
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• 229910052739 hydrogen Inorganic materials 0.000 claims description 2
• 239000001257 hydrogen Substances 0.000 claims description 2
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
• 239000011630 iodine Substances 0.000 claims description 2
• 230000003902 lesion Effects 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 150000007524 organic acids Chemical class 0.000 claims description 2
• 235000005985 organic acids Nutrition 0.000 claims description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
• XDXSSNXRFGRBBF-UHFFFAOYSA-N 3-[1,3-benzodioxol-5-yl-[cyclohexyl(dimethylamino)amino]methylidene]-5-propanoyl-1h-indol-2-one Chemical compound C12=CC(C(=O)CC)=CC=C2NC(=O)C1=C(C=1C=C2OCOC2=CC=1)N(N(C)C)C1CCCCC1 XDXSSNXRFGRBBF-UHFFFAOYSA-N 0.000 claims 1
• 239000003701 inert diluent Substances 0.000 claims 1
• 201000001119 neuropathy Diseases 0.000 claims 1
• 230000007823 neuropathy Effects 0.000 claims 1
• 208000033808 peripheral neuropathy Diseases 0.000 claims 1
• 229910052799 carbon Inorganic materials 0.000 abstract description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 2
• 125000004448 alkyl carbonyl group Chemical group 0.000 abstract 9
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
• 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 abstract 1
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 abstract 1
• 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 abstract 1
• 125000005102 carbonylalkoxy group Chemical group 0.000 abstract 1
• 125000006842 cycloalkyleneimino group Chemical group 0.000 abstract 1
• 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 abstract 1
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 abstract 1
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 291
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
• 238000001819 mass spectrum Methods 0.000 description 104
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
• 239000000741 silica gel Substances 0.000 description 80
• 229910002027 silica gel Inorganic materials 0.000 description 80
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• OGDZTLONCPVKCE-UHFFFAOYSA-N 1,5-diacetyl-3h-indol-2-one Chemical compound CC(=O)C1=CC=C2N(C(=O)C)C(=O)CC2=C1 OGDZTLONCPVKCE-UHFFFAOYSA-N 0.000 description 40
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 35
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
• 239000000243 solution Substances 0.000 description 30
• 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 26
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 26
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 238000003756 stirring Methods 0.000 description 24
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
• 150000002148 esters Chemical class 0.000 description 23
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 22
• 235000002639 sodium chloride Nutrition 0.000 description 21
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
• 239000013543 active substance Substances 0.000 description 17
• 229910021529 ammonia Inorganic materials 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• 239000012074 organic phase Substances 0.000 description 15
• 239000012141 concentrate Substances 0.000 description 14
• 239000003112 inhibitor Substances 0.000 description 13
• 238000002390 rotary evaporation Methods 0.000 description 13
• 239000002585 base Substances 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical group C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• 239000003826 tablet Substances 0.000 description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• 239000003480 eluent Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 235000011121 sodium hydroxide Nutrition 0.000 description 9
• 229920002527 Glycogen Polymers 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• 239000008103 glucose Substances 0.000 description 8
• 229940096919 glycogen Drugs 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 229940098779 methanesulfonic acid Drugs 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
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