CN108101886A - 哌啶-2,6-二酮衍生物及其在治疗溃疡性结肠炎中的用途 - Google Patents

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Publication number

CN108101886A

CN108101886A CN201711184758.5A CN201711184758A CN108101886A CN 108101886 A CN108101886 A CN 108101886A CN 201711184758 A CN201711184758 A CN 201711184758A CN 108101886 A CN108101886 A CN 108101886A

Authority

CN

China

Prior art keywords

dione

pharmaceutically acceptable

isoindoline

acceptable salts

dioxopiperidin

Prior art date

2016-11-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 206010009900 Colitis ulcerative Diseases 0.000 title claims abstract description 71
• 201000006704 Ulcerative Colitis Diseases 0.000 title claims abstract description 71
• 150000005459 piperidine-2,6-diones Chemical class 0.000 title claims description 76
• 150000003839 salts Chemical class 0.000 claims description 199
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• 238000011282 treatment Methods 0.000 claims description 35
• 239000008194 pharmaceutical composition Substances 0.000 claims description 33
• 239000003814 drug Substances 0.000 claims description 32
• 125000000217 alkyl group Chemical group 0.000 claims description 31
• -1 1- (2-methoxyethyl) -2, 6-dioxopiperidin-3-yl Chemical group 0.000 claims description 30
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 239000003826 tablet Substances 0.000 claims description 16
• YJIGIPFJUWIKGT-UHFFFAOYSA-N 4-amino-2-[1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CCOC)C(=O)CCC1N1C(=O)C2=C(N)C=CC=C2C1=O YJIGIPFJUWIKGT-UHFFFAOYSA-N 0.000 claims description 14
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• GRUCKRQQDPQFSZ-UHFFFAOYSA-N 4-amino-2-[1-(2-methylsulfanylethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound NC1=C2C(N(C(C2=CC=C1)=O)C1C(N(C(CC1)=O)CCSC)=O)=O GRUCKRQQDPQFSZ-UHFFFAOYSA-N 0.000 claims description 8
• ZADSTGFMEUUWGX-UHFFFAOYSA-N 4-amino-2-[1-(2-ethoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CCOCC)C(=O)CCC1N1C(=O)C2=C(N)C=CC=C2C1=O ZADSTGFMEUUWGX-UHFFFAOYSA-N 0.000 claims description 7
• CCMRGGGYISCMSR-UHFFFAOYSA-N 4-amino-2-[1-(2-methoxyethyl)-3-methyl-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound NC1=C2C(N(C(C2=CC=C1)=O)C1(C(N(C(CC1)=O)CCOC)=O)C)=O CCMRGGGYISCMSR-UHFFFAOYSA-N 0.000 claims description 7
• ZKXKEKBZWWFIAI-UHFFFAOYSA-N 4-amino-2-[1-(2-methoxypropyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound NC1=C2C(N(C(C2=CC=C1)=O)C1C(N(C(CC1)=O)CC(C)OC)=O)=O ZKXKEKBZWWFIAI-UHFFFAOYSA-N 0.000 claims description 7
• WEZXXQKONKSBAB-UHFFFAOYSA-N 4-amino-2-[3-fluoro-1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound NC1=C2C(N(C(C2=CC=C1)=O)C1(C(N(C(CC1)=O)CCOC)=O)F)=O WEZXXQKONKSBAB-UHFFFAOYSA-N 0.000 claims description 7
• YTKVJFRXSXYDDP-UHFFFAOYSA-N N-[2-[2-(2-methoxypropyl)-1,3,2-dioxazinan-4-yl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound N(C(=O)C)C1=C2C(N(C(C2=CC=C1)=O)C1ON(OCC1)CC(C)OC)=O YTKVJFRXSXYDDP-UHFFFAOYSA-N 0.000 claims description 7
• MOBCMXHKIZSDOH-UHFFFAOYSA-N 4,5,6,7-tetrafluoro-2-[1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CCOC)C(=O)CCC1N1C(=O)C(C(F)=C(F)C(F)=C2F)=C2C1=O MOBCMXHKIZSDOH-UHFFFAOYSA-N 0.000 claims description 6
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• PZSGXZMCORYEMH-UHFFFAOYSA-N 4-fluoro-2-[1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CCOC)C(=O)CCC1N1C(=O)C2=C(F)C=CC=C2C1=O PZSGXZMCORYEMH-UHFFFAOYSA-N 0.000 claims description 6
• QUMLVJUSXZISEY-UHFFFAOYSA-N 4-hydroxy-2-[1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound OC1=C2C(N(C(C2=CC=C1)=O)C1C(N(C(CC1)=O)CCOC)=O)=O QUMLVJUSXZISEY-UHFFFAOYSA-N 0.000 claims description 6
• GWDLJKSZNLIRDU-UHFFFAOYSA-N 5-amino-2-[1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound O=C1N(CCOC)C(=O)CCC1N1C(=O)C2=CC(N)=CC=C2C1=O GWDLJKSZNLIRDU-UHFFFAOYSA-N 0.000 claims description 6
• CLIUNIOAUAFMBB-UHFFFAOYSA-N 5-amino-2-[1-(2-methoxypropyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound NC=1C=C2C(N(C(C2=CC=1)=O)C1C(N(C(CC1)=O)CC(C)OC)=O)=O CLIUNIOAUAFMBB-UHFFFAOYSA-N 0.000 claims description 6
• SPKUGKYJZSZFIB-UHFFFAOYSA-N 5-fluoro-2-[1-(2-methoxyethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione Chemical compound FC=1C=C2C(N(C(C2=CC=1)=O)C1C(N(C(CC1)=O)CCOC)=O)=O SPKUGKYJZSZFIB-UHFFFAOYSA-N 0.000 claims description 6
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• ZHYBYDOGOPRYIB-UHFFFAOYSA-N 2-[1-(2-ethoxyethyl)-2,6-dioxopiperidin-3-yl]-4-fluoroisoindole-1,3-dione Chemical compound FC1=C2C(N(C(C2=CC=C1)=O)C1C(N(C(CC1)=O)CCOCC)=O)=O ZHYBYDOGOPRYIB-UHFFFAOYSA-N 0.000 claims description 5
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