PT1228071E - Derivados de isoindolina farmacêuticamente activos - Google Patents

Info

Publication number

PT1228071E

PT1228071E PT00977095T PT00977095T PT1228071E PT 1228071 E PT1228071 E PT 1228071E PT 00977095 T PT00977095 T PT 00977095T PT 00977095 T PT00977095 T PT 00977095T PT 1228071 E PT1228071 E PT 1228071E

Authority

PT

Portugal

Prior art keywords

ethoxy

methoxyphenyl

carbon atoms

mixture

mmol

Prior art date

1999-11-12

Links

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• Global Dossier
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• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical class C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 title claims description 6
• 239000002253 acid Substances 0.000 claims abstract description 7
• 150000003839 salts Chemical class 0.000 claims abstract description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
• 239000000203 mixture Substances 0.000 claims description 148
• -1 methoxy, ethoxy, n-propoxy, isopropoxy, cyclopentoxy, cyclohexoxy, cycloheptoxy , cyclopentyl Chemical group 0.000 claims description 94
• 150000001875 compounds Chemical class 0.000 claims description 72
• 125000004432 carbon atom Chemical group C* 0.000 claims description 54
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 238000011282 treatment Methods 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 206010028980 Neoplasm Diseases 0.000 claims description 23
• 201000010099 disease Diseases 0.000 claims description 23
• 230000033115 angiogenesis Effects 0.000 claims description 19
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 19
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 18
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 239000003826 tablet Substances 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 14
• 230000000694 effects Effects 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 208000030507 AIDS Diseases 0.000 claims description 9
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• 150000002367 halogens Chemical group 0.000 claims description 9
• 206010061218 Inflammation Diseases 0.000 claims description 8
• 230000004054 inflammatory process Effects 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 7
• 206010040070 Septic Shock Diseases 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 239000002552 dosage form Substances 0.000 claims description 7
• 150000002431 hydrogen Chemical class 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 206010006895 Cachexia Diseases 0.000 claims description 6
• 208000011231 Crohn disease Diseases 0.000 claims description 6
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• 230000002757 inflammatory effect Effects 0.000 claims description 6
• 230000001613 neoplastic effect Effects 0.000 claims description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
• 208000011580 syndromic disease Diseases 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• 125000001118 alkylidene group Chemical group 0.000 claims description 5
• 206010003246 arthritis Diseases 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
• 238000002360 preparation method Methods 0.000 claims description 5
• 208000001388 Opportunistic Infections Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 239000002775 capsule Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 201000004792 malaria Diseases 0.000 claims description 4
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 230000035939 shock Effects 0.000 claims description 4
• ZOMMYBFPBGWUAT-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(1h-imidazol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(CC=4NC=CN=4)C=CC=C3C2=O)=O)=C1 ZOMMYBFPBGWUAT-UHFFFAOYSA-N 0.000 claims description 3
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
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• 230000000711 cancerogenic effect Effects 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 231100000315 carcinogenic Toxicity 0.000 claims 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 description 3
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 230000006378 damage Effects 0.000 claims description 3
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• QDZOBXFRIVOQBR-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 QDZOBXFRIVOQBR-UHFFFAOYSA-N 0.000 claims description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 3
• 230000009467 reduction Effects 0.000 claims description 3
• 230000036303 septic shock Effects 0.000 claims description 3
• 208000013223 septicemia Diseases 0.000 claims description 3
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
• 229940124597 therapeutic agent Drugs 0.000 claims description 3
• 125000001425 triazolyl group Chemical group 0.000 claims description 3
• 229920002554 vinyl polymer Polymers 0.000 claims description 3
• HPNGOUOSHMENJP-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(1h-pyrrol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(CC=4NC=CC=4)C=CC=C3C2=O)=O)=C1 HPNGOUOSHMENJP-UHFFFAOYSA-N 0.000 claims description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
• 206010019280 Heart failures Diseases 0.000 claims description 2
• 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 2
• 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 2
• 201000009906 Meningitis Diseases 0.000 claims description 2
• 206010062207 Mycobacterial infection Diseases 0.000 claims description 2
• PAOZAMACNXMCIB-UHFFFAOYSA-N N-[2-[1-(3,4-dimethoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CS(C)(=O)=O)N1C(=O)C2=C(NC(=O)C3CC3)C=CC=C2C1=O PAOZAMACNXMCIB-UHFFFAOYSA-N 0.000 claims description 2
• 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 2
• 208000027418 Wounds and injury Diseases 0.000 claims description 2
• 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims description 2
• 150000001721 carbon Chemical group 0.000 claims description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
• 230000003176 fibrotic effect Effects 0.000 claims description 2
• 230000000004 hemodynamic effect Effects 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
• 208000014674 injury Diseases 0.000 claims description 2
• 201000001441 melanoma Diseases 0.000 claims description 2
• 208000027531 mycobacterial infectious disease Diseases 0.000 claims description 2
• 239000000843 powder Substances 0.000 claims description 2
• 230000005588 protonation Effects 0.000 claims description 2
• 201000004193 respiratory failure Diseases 0.000 claims description 2
• 231100000590 oncogenic Toxicity 0.000 claims 2
• 230000002246 oncogenic effect Effects 0.000 claims 2
• ISPUPFYJUWLMEH-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-4-(1h-pyrrol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)O)N2C(C3=C(CC=4NC=CC=4)C=CC=C3C2=O)=O)=C1 ISPUPFYJUWLMEH-UHFFFAOYSA-N 0.000 claims 1
• NAKSEFFBNWKUJH-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-4-(1h-pyrrol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)=O)N2C(C3=C(CC=4NC=CC=4)C=CC=C3C2=O)=O)=C1 NAKSEFFBNWKUJH-UHFFFAOYSA-N 0.000 claims 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
• 206010003571 Astrocytoma Diseases 0.000 claims 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
• 208000003950 B-cell lymphoma Diseases 0.000 claims 1
• 206010005003 Bladder cancer Diseases 0.000 claims 1
• 206010006187 Breast cancer Diseases 0.000 claims 1
• 208000026310 Breast neoplasm Diseases 0.000 claims 1
• 206010009944 Colon cancer Diseases 0.000 claims 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
• 208000003790 Foot Ulcer Diseases 0.000 claims 1
• 206010018338 Glioma Diseases 0.000 claims 1
• 206010058490 Hyperoxia Diseases 0.000 claims 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
• 206010027406 Mesothelioma Diseases 0.000 claims 1
• 206010028034 Mouth ulceration Diseases 0.000 claims 1
• 208000034578 Multiple myelomas Diseases 0.000 claims 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
• 208000014767 Myeloproliferative disease Diseases 0.000 claims 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
• 201000010133 Oligodendroglioma Diseases 0.000 claims 1
• 208000007117 Oral Ulcer Diseases 0.000 claims 1
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• 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
• 206010060862 Prostate cancer Diseases 0.000 claims 1
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• 206010039491 Sarcoma Diseases 0.000 claims 1
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• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
• 208000010964 acquired adult-onset immunodeficiency Diseases 0.000 claims 1
• 230000003115 biocidal effect Effects 0.000 claims 1
• 150000003857 carboxamides Chemical class 0.000 claims 1
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• XCCGODHJXOPFSU-UHFFFAOYSA-N n-[2-[3-(dimethylamino)-1-(3-ethoxy-4-methoxyphenyl)-3-oxopropyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)N(C)C)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 XCCGODHJXOPFSU-UHFFFAOYSA-N 0.000 claims 1
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• QDZOBXFRIVOQBR-LJQANCHMSA-N n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 QDZOBXFRIVOQBR-LJQANCHMSA-N 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 238
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 204
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• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
• 239000002904 solvent Substances 0.000 description 54
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