CA2509565A1 - Mitogen activated protein kinase-activated protein kinase-2 inhibiting compounds - Google Patents
Mitogen activated protein kinase-activated protein kinase-2 inhibiting compounds Download PDFInfo
- Publication number
- CA2509565A1 CA2509565A1 CA002509565A CA2509565A CA2509565A1 CA 2509565 A1 CA2509565 A1 CA 2509565A1 CA 002509565 A CA002509565 A CA 002509565A CA 2509565 A CA2509565 A CA 2509565A CA 2509565 A1 CA2509565 A1 CA 2509565A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- pyridin
- pyrrolo
- tetrahydro
- trifluoroacetate
- 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
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 164
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 82
- 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 title abstract description 127
- 101710141394 MAP kinase-activated protein kinase 2 Proteins 0.000 title abstract description 123
- 238000000034 method Methods 0.000 claims abstract description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
- 208000035475 disorder Diseases 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 230000001404 mediated effect Effects 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 11
- 230000002265 prevention Effects 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- -1 NR b Chemical compound 0.000 claims description 444
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 384
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 365
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 277
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 267
- 125000003118 aryl group Chemical group 0.000 claims description 238
- 125000001072 heteroaryl group Chemical group 0.000 claims description 216
- 125000000623 heterocyclic group Chemical group 0.000 claims description 210
- 125000002950 monocyclic group Chemical group 0.000 claims description 189
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 177
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 177
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 176
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 173
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 171
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 138
- 229920002554 vinyl polymer Polymers 0.000 claims description 130
- 229910052799 carbon Inorganic materials 0.000 claims description 116
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 88
- 229910052757 nitrogen Inorganic materials 0.000 claims description 86
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 84
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 77
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 69
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 66
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 65
- 229910052717 sulfur Inorganic materials 0.000 claims description 63
- 229910052760 oxygen Inorganic materials 0.000 claims description 44
- 125000000304 alkynyl group Chemical group 0.000 claims description 38
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
- 239000001301 oxygen Substances 0.000 claims description 25
- 101100160255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YLR154C-H gene Proteins 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- 239000011593 sulfur Substances 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 101100365011 Arabidopsis thaliana SCL33 gene Proteins 0.000 claims description 19
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 18
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000001475 halogen functional group Chemical group 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 16
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 15
- 101100240521 Caenorhabditis elegans nhr-16 gene Proteins 0.000 claims description 14
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 13
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 12
- 101100240529 Caenorhabditis elegans nhr-25 gene Proteins 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 101100240527 Caenorhabditis elegans nhr-22 gene Proteins 0.000 claims description 9
- 101100294104 Caenorhabditis elegans nhr-34 gene Proteins 0.000 claims description 9
- 101150024084 nhr-28 gene Proteins 0.000 claims description 9
- 101100294103 Caenorhabditis elegans nhr-31 gene Proteins 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 150000003852 triazoles Chemical class 0.000 claims description 8
- 101100240519 Caenorhabditis elegans nhr-13 gene Proteins 0.000 claims description 7
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000013038 irreversible inhibitor Substances 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 101100240523 Caenorhabditis elegans nhr-19 gene Proteins 0.000 claims description 4
- 101150020251 NR13 gene Proteins 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 4
- 125000003106 haloaryl group Chemical group 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 3
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- RJZDECGDCKOHBV-VOTSOKGWSA-N 2-[2-[(e)-2-phenylethenyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C=1C=2C(=O)NCCC=2NC=1C(C=1)=CC=NC=1\C=C\C1=CC=CC=C1 RJZDECGDCKOHBV-VOTSOKGWSA-N 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000008961 swelling Effects 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 4
- 208000014674 injury Diseases 0.000 claims 4
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 3
- 208000027418 Wounds and injury Diseases 0.000 claims 3
- 230000006378 damage Effects 0.000 claims 3
- 201000004624 Dermatitis Diseases 0.000 claims 2
- 208000010668 atopic eczema Diseases 0.000 claims 2
- 210000002808 connective tissue Anatomy 0.000 claims 2
- UDBOTZGGDOYXQB-TYYBGVCCSA-N (e)-4-bromo-n-[4-[4-(4-oxo-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]phenyl]but-2-enamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(NC(=O)/C=C/CBr)=CC=C1C1=CC(C=2NC3=C(C(NCC3)=O)C=2)=CC=N1 UDBOTZGGDOYXQB-TYYBGVCCSA-N 0.000 claims 1
- MGHBHHJUMURWHB-UHFFFAOYSA-N 2-(2-quinolin-3-ylpyridin-4-yl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=CC2=CC(C=3N=CC=C(C=3)C=3NC=4CCNC(C=4C=3)=O)=CN=C21 MGHBHHJUMURWHB-UHFFFAOYSA-N 0.000 claims 1
- XEYBRMOKYVKWJX-UHFFFAOYSA-N 2-(2-quinolin-3-ylpyrimidin-4-yl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C1=CC=CC2=CC(C=3N=CC=C(N=3)C=3NC=4CCNC(C=4C=3)=O)=CN=C21 XEYBRMOKYVKWJX-UHFFFAOYSA-N 0.000 claims 1
- JILNPNRYSYYHTL-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[3-[4-(4-oxo-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]phenyl]acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(F)=CC=C1CC(=O)NC1=CC=CC(C=2N=CC=C(C=2)C=2NC3=C(C(NCC3)=O)C=2)=C1 JILNPNRYSYYHTL-UHFFFAOYSA-N 0.000 claims 1
- SZXTYFWRSOUIKG-UHFFFAOYSA-N 2-(5-fluoro-2-quinolin-3-ylpyridin-4-yl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=CC2=CC(C3=NC=C(C(=C3)C=3NC4=C(C(NCC4)=O)C=3)F)=CN=C21 SZXTYFWRSOUIKG-UHFFFAOYSA-N 0.000 claims 1
- LNNWFYDCPVGVHT-SNAWJCMRSA-N 2-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound FC1=CC=CC(C(=O)\C=C\C=2NC3=C(C(NCC3)=O)C=2)=C1 LNNWFYDCPVGVHT-SNAWJCMRSA-N 0.000 claims 1
- FFZOHQVVYNOFQE-UHFFFAOYSA-N 2-[2-(2-benzylidenehydrazinyl)pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C=1C=2C(=O)NCCC=2NC=1C(C=1)=CC=NC=1NN=CC1=CC=CC=C1 FFZOHQVVYNOFQE-UHFFFAOYSA-N 0.000 claims 1
- VQXHMIMOSVQWDK-UHFFFAOYSA-N 2-[2-(6-hydroxynaphthalen-2-yl)pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.Oc1ccc2cc(ccc2c1)-c1cc(ccn1)-c1cc2c(CCNC2=O)[nH]1 VQXHMIMOSVQWDK-UHFFFAOYSA-N 0.000 claims 1
- AMQFNCGUHNPDBF-IPZCTEOASA-N 2-[2-[(e)-2-(2-chlorophenyl)ethenyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.ClC1=CC=CC=C1\C=C\C1=CC(C=2NC3=C(C(NCC3)=O)C=2)=CC=N1 AMQFNCGUHNPDBF-IPZCTEOASA-N 0.000 claims 1
- NWZSJYCGFJVECK-ZZXKWVIFSA-N 2-[2-[(e)-2-(4-fluorophenyl)ethenyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1\C=C\C1=CC(C=2NC3=C(C(NCC3)=O)C=2)=CC=N1 NWZSJYCGFJVECK-ZZXKWVIFSA-N 0.000 claims 1
- UQTOKBIQNSIBSP-DYVSEJHDSA-N 2-[2-[(e)-2-(4-morpholin-4-ylphenyl)ethenyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=2C(=O)NCCC=2NC=1C(C=1)=CC=NC=1\C=C\C(C=C1)=CC=C1N1CCOCC1 UQTOKBIQNSIBSP-DYVSEJHDSA-N 0.000 claims 1
- REEXJMQJOIRHRR-IPZCTEOASA-N 2-[2-[(e)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=2C(=O)NCCC=2NC=1C(C=1)=CC=NC=1\C=C\C(C=C1)=CC=C1CN1CCOCC1 REEXJMQJOIRHRR-IPZCTEOASA-N 0.000 claims 1
- ZGNZCNYPSKYIHS-UHFFFAOYSA-N 2-[2-[2-[[4-[2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]phenyl]methylidene]hydrazinyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C=1C=C(C=NNC=2N=CC=C(C=2)C=2NC3=C(C(NCC3)=O)C=2)C=CC=1C(=O)N1CCCC1CN1CCCC1 ZGNZCNYPSKYIHS-UHFFFAOYSA-N 0.000 claims 1
- AIJJVRCONBPNBM-UHFFFAOYSA-N 2-[2-[[(4-methylsulfonylphenyl)hydrazinylidene]methyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NN=CC1=CC(C=2NC3=C(C(NCC3)=O)C=2)=CC=N1 AIJJVRCONBPNBM-UHFFFAOYSA-N 0.000 claims 1
- CLUBZMIJLZBMEI-UHFFFAOYSA-N 2-[2-[[[4-(morpholine-4-carbonyl)phenyl]hydrazinylidene]methyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C=1C=C(NN=CC=2N=CC=C(C=2)C=2NC3=C(C(NCC3)=O)C=2)C=CC=1C(=O)N1CCOCC1 CLUBZMIJLZBMEI-UHFFFAOYSA-N 0.000 claims 1
- YABWZEJIFVZQNM-UHFFFAOYSA-N 2-[2-[[[4-(pyrrolidine-1-carbonyl)phenyl]hydrazinylidene]methyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C=1C=C(NN=CC=2N=CC=C(C=2)C=2NC3=C(C(NCC3)=O)C=2)C=CC=1C(=O)N1CCCC1 YABWZEJIFVZQNM-UHFFFAOYSA-N 0.000 claims 1
- KVYUKAZVKCBZLT-UHFFFAOYSA-N 2-[2-[[methyl-[4-(morpholine-4-carbonyl)phenyl]hydrazinylidene]methyl]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C(C=2NC3=C(C(NCC3)=O)C=2)=CC=NC=1C=NN(C)C(C=C1)=CC=C1C(=O)N1CCOCC1 KVYUKAZVKCBZLT-UHFFFAOYSA-N 0.000 claims 1
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| PCT/US2003/040811 WO2004058762A1 (en) | 2002-12-20 | 2003-12-19 | Mitogen activated protein kinase-activated protein kinase-2 inhibiting compounds |
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Cited By (1)
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| WO2006059245A3 (en) * | 2004-11-16 | 2006-10-05 | Neurochem Int Ltd | Compounds for the treatment of cns and amyloid associated diseases |
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| EP1663204B1 (en) * | 2003-08-29 | 2014-05-07 | Exelixis, Inc. | C-kit modulators and methods of use |
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| ES2377430T3 (es) * | 2004-09-02 | 2012-03-27 | Genentech, Inc. | Inhibidores piridílicos de la señalización de hedgehog |
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| DE102004054665A1 (de) * | 2004-11-12 | 2006-05-18 | Bayer Cropscience Gmbh | Substituierte bi- und tricyclische Pyrazol-Derivate Verfahren zur Herstellung und Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| US20060115453A1 (en) * | 2004-11-12 | 2006-06-01 | Yaffe Michael B | Methods and compositions for treating cellular proliferative diseases |
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| BRPI0612287A8 (pt) * | 2005-06-27 | 2019-01-22 | Exelixis Inc | composição para uso farmacêutico no tratamento de doenças através da medicina nuclear e métodos de uso e para modulação de atividade de receptor nuclear |
| GB0520958D0 (en) * | 2005-10-14 | 2005-11-23 | Cyclacel Ltd | Compound |
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| WO2007063946A1 (ja) * | 2005-11-30 | 2007-06-07 | Fujifilm Ri Pharma Co., Ltd. | アミロイドの凝集及び/又は沈着に起因する疾患の診断薬及び治療薬 |
| US20070142414A1 (en) * | 2005-12-16 | 2007-06-21 | Pharmacia Italia S.P.A. | N-substituted pyrrolopyridinones active as kinase inhibitors |
| US7618982B2 (en) * | 2005-12-19 | 2009-11-17 | Nerviano Medical Sciences S.R.L. | Heteroarylpyrrolopyridinones active as kinase inhibitors |
| CA2635531C (en) * | 2005-12-29 | 2014-06-17 | Lexicon Pharmaceutical Inc. | Multicyclic amino acid derivatives and methods of their use |
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| US6514977B1 (en) * | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| US6489325B1 (en) * | 1998-07-01 | 2002-12-03 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| US6251914B1 (en) * | 1997-07-02 | 2001-06-26 | Smithkline Beecham Corporation | Cycloalkyl substituted imidazoles |
| ES2339196T3 (es) * | 1997-07-18 | 2010-05-17 | Novo Nordisk Health Care Ag | Uso de fviia o fviiai para el tratamiento de disfuncion endotelial y para la inhibicion de angiogenesis, respectivamente. |
| US6022884A (en) * | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
| AU1924699A (en) * | 1997-12-19 | 1999-07-12 | Smithkline Beecham Corporation | Compounds of heteroaryl substituted imidazole, their pharmaceutical compositionsand uses |
| US6197954B1 (en) * | 1998-01-30 | 2001-03-06 | The Trustees Of Columbia University In The City Of New York | Intermediates for the synthesis of debromohymenialdisine and processes thereof |
| MXPA01002173A (es) * | 1998-08-28 | 2003-07-14 | Scios Inc | Inhibidores de p38-alfa cinasa. |
| US6143892A (en) * | 1998-11-20 | 2000-11-07 | G. D. Searle & Co. | Process for making 5-substituted pyrazoles |
| CN1136217C (zh) * | 1998-12-17 | 2004-01-28 | 霍夫曼-拉罗奇有限公司 | 作为jnk蛋白质激酶抑制剂的4-芳基羟吲哚 |
| WO2000040243A1 (en) * | 1999-01-08 | 2000-07-13 | Smithkline Beecham Corporation | Novel compounds |
| US6211361B1 (en) * | 1999-07-20 | 2001-04-03 | State Of Oregon Acting By And Through The Oregon State Board Of Higher Education On Behalf Of Oregon, State Univeristy | Method for making debromohymenialdisine and analogs thereof |
| KR20010111298A (ko) * | 2000-02-05 | 2001-12-17 | 버텍스 파마슈티칼스 인코포레이티드 | Erk의 억제제로서 유용한 피라졸 조성물 |
| HUP0301932A3 (en) * | 2000-05-22 | 2007-09-28 | Leo Pharma As | Benzophenones as inhibitors of il-1 beta and tnf-alpha, pharmaceutical compositions containing them and use of them for producing pharmaceutical compositions |
-
2003
- 2003-12-19 ZA ZA200504898A patent/ZA200504898B/en unknown
- 2003-12-19 AU AU2003301226A patent/AU2003301226A1/en not_active Withdrawn
- 2003-12-19 BR BR0317430-1A patent/BR0317430A/pt not_active Application Discontinuation
- 2003-12-19 JP JP2004563888A patent/JP2006514043A/ja not_active Withdrawn
- 2003-12-19 KR KR1020057011474A patent/KR20050104339A/ko not_active Withdrawn
- 2003-12-19 WO PCT/US2003/040811 patent/WO2004058762A1/en not_active Ceased
- 2003-12-19 US US10/742,494 patent/US20040152739A1/en not_active Abandoned
- 2003-12-19 MX MXPA05006568A patent/MXPA05006568A/es not_active Application Discontinuation
- 2003-12-19 WO PCT/US2003/040932 patent/WO2004058176A2/en not_active Ceased
- 2003-12-19 BR BR0317525-1A patent/BR0317525A/pt not_active IP Right Cessation
- 2003-12-19 US US10/742,072 patent/US20040209897A1/en not_active Abandoned
- 2003-12-19 CN CNA2003801096266A patent/CN1747949A/zh active Pending
- 2003-12-19 RU RU2005119173/04A patent/RU2005119173A/ru not_active Application Discontinuation
- 2003-12-19 JP JP2004563946A patent/JP2006511583A/ja not_active Withdrawn
- 2003-12-19 AU AU2003297431A patent/AU2003297431A1/en not_active Abandoned
- 2003-12-19 PL PL377461A patent/PL377461A1/pl unknown
- 2003-12-19 EP EP03814309A patent/EP1572682A4/en not_active Withdrawn
- 2003-12-19 CA CA002509565A patent/CA2509565A1/en not_active Abandoned
- 2003-12-19 CA CA002510298A patent/CA2510298A1/en not_active Abandoned
- 2003-12-19 MX MXPA05006569A patent/MXPA05006569A/es unknown
- 2003-12-19 EP EP03814268A patent/EP1572693A1/en not_active Withdrawn
-
2005
- 2005-06-15 IL IL169177A patent/IL169177A0/en unknown
- 2005-07-13 NO NO20053396A patent/NO20053396L/no not_active Application Discontinuation
-
2007
- 2007-12-17 US US11/958,229 patent/US20080113971A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006059245A3 (en) * | 2004-11-16 | 2006-10-05 | Neurochem Int Ltd | Compounds for the treatment of cns and amyloid associated diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| PL377461A1 (pl) | 2006-02-06 |
| CN1747949A (zh) | 2006-03-15 |
| NO20053396L (no) | 2005-09-12 |
| WO2004058762A1 (en) | 2004-07-15 |
| AU2003297431A1 (en) | 2004-07-22 |
| NO20053396D0 (no) | 2005-07-13 |
| CA2510298A1 (en) | 2004-07-15 |
| JP2006514043A (ja) | 2006-04-27 |
| IL169177A0 (en) | 2007-07-04 |
| JP2006511583A (ja) | 2006-04-06 |
| ZA200504898B (en) | 2006-11-29 |
| AU2003301226A1 (en) | 2004-07-22 |
| KR20050104339A (ko) | 2005-11-02 |
| EP1572682A4 (en) | 2008-01-23 |
| MXPA05006569A (es) | 2005-09-22 |
| AU2003301226A2 (en) | 2004-07-22 |
| RU2005119173A (ru) | 2006-02-27 |
| WO2004058176A3 (en) | 2004-09-16 |
| EP1572693A1 (en) | 2005-09-14 |
| EP1572682A2 (en) | 2005-09-14 |
| US20040152739A1 (en) | 2004-08-05 |
| US20040209897A1 (en) | 2004-10-21 |
| BR0317430A (pt) | 2005-10-25 |
| BR0317525A (pt) | 2005-11-16 |
| US20080113971A1 (en) | 2008-05-15 |
| WO2004058176A2 (en) | 2004-07-15 |
| MXPA05006568A (es) | 2005-09-22 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20070917 |