ZA200300216B - 3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta. - Google Patents

Info

Publication number

ZA200300216B

ZA200300216B ZA200300216A ZA200300216A ZA200300216B ZA 200300216 B ZA200300216 B ZA 200300216B ZA 200300216 A ZA200300216 A ZA 200300216A ZA 200300216 A ZA200300216 A ZA 200300216A ZA 200300216 B ZA200300216 B ZA 200300216B

Authority

ZA

South Africa

Prior art keywords

gsk

compound

disease

heteroalkyl

hydrogen

Prior art date

2000-07-27

Links

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• 239000003112 inhibitor Substances 0.000 title claims description 33
• LKDTVSJUXXGXKE-UHFFFAOYSA-N 3-(1h-indol-2-yl)-4-phenylpyrrole-2,5-dione Chemical class C=1C2=CC=CC=C2NC=1C=1C(=O)NC(=O)C=1C1=CC=CC=C1 LKDTVSJUXXGXKE-UHFFFAOYSA-N 0.000 title description 4
• 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 title description 2
• 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 238
• -1 cyano, nitro, amino Chemical group 0.000 claims description 227
• 239000000203 mixture Substances 0.000 claims description 89
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
• 229910052739 hydrogen Inorganic materials 0.000 claims description 82
• 239000001257 hydrogen Substances 0.000 claims description 78
• 238000000034 method Methods 0.000 claims description 69
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 67
• 125000000217 alkyl group Chemical group 0.000 claims description 63
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 60
• 201000010099 disease Diseases 0.000 claims description 58
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 54
• 125000000623 heterocyclic group Chemical group 0.000 claims description 51
• 208000006673 asthma Diseases 0.000 claims description 39
• 150000002431 hydrogen Chemical class 0.000 claims description 38
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 239000003814 drug Substances 0.000 claims description 22
• 206010020751 Hypersensitivity Diseases 0.000 claims description 21
• 230000007815 allergy Effects 0.000 claims description 21
• 229910052736 halogen Inorganic materials 0.000 claims description 21
• 239000000126 substance Substances 0.000 claims description 21
• 102000004127 Cytokines Human genes 0.000 claims description 19
• 108090000695 Cytokines Proteins 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 19
• 208000026935 allergic disease Diseases 0.000 claims description 17
• 125000001153 fluoro group Chemical group F* 0.000 claims description 17
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 17
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 13
• 230000001404 mediated effect Effects 0.000 claims description 13
• 125000004442 acylamino group Chemical group 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 11
• 125000001188 haloalkyl group Chemical group 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 208000024827 Alzheimer disease Diseases 0.000 claims description 9
• 125000004414 alkyl thio group Chemical group 0.000 claims description 9
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• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 8
• 125000002947 alkylene group Chemical group 0.000 claims description 8
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• 150000003839 salts Chemical class 0.000 claims description 8
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• 206010028980 Neoplasm Diseases 0.000 claims description 7
• 208000008589 Obesity Diseases 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 125000001041 indolyl group Chemical group 0.000 claims description 7
• 235000020824 obesity Nutrition 0.000 claims description 7
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 7
• 208000011580 syndromic disease Diseases 0.000 claims description 7
• 239000002253 acid Substances 0.000 claims description 5
• 239000002585 base Substances 0.000 claims description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 3
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• 239000000543 intermediate Substances 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims 9
• MZUZXNZGBBUAIM-UHFFFAOYSA-N 3-(1h-indol-3-yl)-4-phenylfuran-2,5-dione Chemical compound C=1NC2=CC=CC=C2C=1C=1C(=O)OC(=O)C=1C1=CC=CC=C1 MZUZXNZGBBUAIM-UHFFFAOYSA-N 0.000 claims 1
• 229910021529 ammonia Inorganic materials 0.000 claims 1
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• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
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• 230000000694 effects Effects 0.000 description 15
• FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 15
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• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• 238000003556 assay Methods 0.000 description 13
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 13
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• 229910052938 sodium sulfate Inorganic materials 0.000 description 13
• 235000011152 sodium sulphate Nutrition 0.000 description 13
• BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 11
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