JP2010505932A5 - - Google Patents
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- Publication number
- JP2010505932A5 JP2010505932A5 JP2009531918A JP2009531918A JP2010505932A5 JP 2010505932 A5 JP2010505932 A5 JP 2010505932A5 JP 2009531918 A JP2009531918 A JP 2009531918A JP 2009531918 A JP2009531918 A JP 2009531918A JP 2010505932 A5 JP2010505932 A5 JP 2010505932A5
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- dihydro
- isoindol
- methanone
- dihydroxy
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 169
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- 239000001257 hydrogen Substances 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 83
- -1 NR c Inorganic materials 0.000 claims description 81
- 229910052760 oxygen Inorganic materials 0.000 claims description 69
- 125000001424 substituent group Chemical group 0.000 claims description 68
- 125000000623 heterocyclic group Chemical group 0.000 claims description 64
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 57
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 55
- 229910052736 halogen Inorganic materials 0.000 claims description 49
- 150000002367 halogens Chemical class 0.000 claims description 49
- 229910052717 sulfur Inorganic materials 0.000 claims description 47
- 229910005965 SO 2 Inorganic materials 0.000 claims description 41
- 125000005842 heteroatom Chemical group 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 34
- 125000002837 carbocyclic group Chemical group 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 30
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 30
- 241000124008 Mammalia Species 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 201000010099 disease Diseases 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 20
- 229940116871 l-lactate Drugs 0.000 claims description 19
- 208000024891 symptom Diseases 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000002950 monocyclic group Chemical group 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 230000002159 abnormal effect Effects 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 230000001404 mediated effect Effects 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 11
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
- 230000004663 cell proliferation Effects 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 150000001204 N-oxides Chemical class 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 239000001301 oxygen Chemical group 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- YYVAXCVMFDJHBF-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(4-methylpiperazin-1-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)N2CCN(C)CC2)=C1O YYVAXCVMFDJHBF-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- LOLPPWBBNUVNQZ-UHFFFAOYSA-N chembl495727 Chemical compound C=1NN=C(C=2NC3=CC=C(CN4CCOCC4)C=C3N=2)C=1NC(=O)NC1CC1 LOLPPWBBNUVNQZ-UHFFFAOYSA-N 0.000 claims description 5
- RKWHYDXSPNNDBR-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[4-(3-morpholin-4-ylpropoxy)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(OCCCN4CCOCC4)C=CC=C3C2)=C1O RKWHYDXSPNNDBR-UHFFFAOYSA-N 0.000 claims description 4
- JVQQVJXMYAIHFT-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(4-hydroxy-1-methylpiperidin-4-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)C2(O)CCN(C)CC2)=C1O JVQQVJXMYAIHFT-UHFFFAOYSA-N 0.000 claims description 4
- HIIKFACAQJEYEI-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(1-methylpiperidin-4-yl)amino]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(NC4CCN(C)CC4)=CC=C3C2)=C1O HIIKFACAQJEYEI-UHFFFAOYSA-N 0.000 claims description 4
- IMCANAAIYOYWDU-UHFFFAOYSA-N (5-chloro-2,4-dihydroxyphenyl)-[5-(4-methylpiperazin-1-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1CN(C)CCN1C1=CC=C(CN(C2)C(=O)C=3C(=CC(O)=C(Cl)C=3)O)C2=C1 IMCANAAIYOYWDU-UHFFFAOYSA-N 0.000 claims description 4
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 230000000903 blocking effect Effects 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- IFRGXKKQHBVPCQ-UHFFFAOYSA-N onalespib Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCN(C)CC4)=CC=C3C2)=C1O IFRGXKKQHBVPCQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000029812 viral genome replication Effects 0.000 claims description 4
- 230000009385 viral infection Effects 0.000 claims description 4
- 230000003612 virological effect Effects 0.000 claims description 4
- YCAYPVJEOCBCCR-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(5-piperazin-1-yl-1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)N2CCNCC2)=C1O YCAYPVJEOCBCCR-UHFFFAOYSA-N 0.000 claims description 3
- JGSGWWWQXTYLGD-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(dimethylamino)methyl]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(CN(C)C)=CC=C3C2)=C1O JGSGWWWQXTYLGD-UHFFFAOYSA-N 0.000 claims description 3
- QVVRLPMMRCAKBP-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[2-(dimethylamino)ethoxy]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(OCCN(C)C)=CC=C3C2)=C1O QVVRLPMMRCAKBP-UHFFFAOYSA-N 0.000 claims description 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 3
- 230000032823 cell division Effects 0.000 claims description 3
- 230000033077 cellular process Effects 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- SSZRLOSKSNZFFK-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(4-fluoro-1,3-dihydroisoindol-2-yl)methanone;hydrochloride Chemical compound Cl.C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(F)C=CC=C3C2)=C1O SSZRLOSKSNZFFK-UHFFFAOYSA-N 0.000 claims description 2
- KPWQHNKPRDITRE-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(5-fluoro-1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(F)=CC=C3C2)=C1O KPWQHNKPRDITRE-UHFFFAOYSA-N 0.000 claims description 2
- CGDIZMUZKWJVOO-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(5-hydroxy-1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(O)=CC=C3C2)=C1O CGDIZMUZKWJVOO-UHFFFAOYSA-N 0.000 claims description 2
- XGWIZXRDVRVZEK-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(5-methoxy-1,3-dihydroisoindol-2-yl)methanone Chemical compound C1C2=CC(OC)=CC=C2CN1C(=O)C1=CC(C(C)C)=C(O)C=C1O XGWIZXRDVRVZEK-UHFFFAOYSA-N 0.000 claims description 2
- JUTGATVTVPQMEL-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(5-methyl-1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(C)=CC=C3C2)=C1O JUTGATVTVPQMEL-UHFFFAOYSA-N 0.000 claims description 2
- LUCGOGCKXFESLJ-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-(5-morpholin-4-yl-1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)N2CCOCC2)=C1O LUCGOGCKXFESLJ-UHFFFAOYSA-N 0.000 claims description 2
- BHIGZZZLNMKWKD-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[4-(4-methylpiperazin-1-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(N4CCN(C)CC4)C=CC=C3C2)=C1O BHIGZZZLNMKWKD-UHFFFAOYSA-N 0.000 claims description 2
- HHHYTVUIDNOPQP-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[4-(piperidin-4-ylamino)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(NC4CCNCC4)C=CC=C3C2)=C1O HHHYTVUIDNOPQP-UHFFFAOYSA-N 0.000 claims description 2
- HXJZVSQZQZCYGZ-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[4-[2-(2-methoxyethoxy)ethoxy]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1C=2C(OCCOCCOC)=CC=CC=2CN1C(=O)C1=CC(C(C)C)=C(O)C=C1O HXJZVSQZQZCYGZ-UHFFFAOYSA-N 0.000 claims description 2
- IVIKKSNFTPZPFF-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[4-[2-(dimethylamino)ethoxy]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(OCCN(C)C)C=CC=C3C2)=C1O IVIKKSNFTPZPFF-UHFFFAOYSA-N 0.000 claims description 2
- LYUXFHBOSWVIRE-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(2-methoxyethoxy)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1C2=CC(OCCOC)=CC=C2CN1C(=O)C1=CC(C(C)C)=C(O)C=C1O LYUXFHBOSWVIRE-UHFFFAOYSA-N 0.000 claims description 2
- AMUHXLKGSWMZEA-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(3-morpholin-4-ylpropoxy)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(OCCCN4CCOCC4)=CC=C3C2)=C1O AMUHXLKGSWMZEA-UHFFFAOYSA-N 0.000 claims description 2
- SVHNLCFHSPNERJ-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(4-hydroxypiperidin-4-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)C2(O)CCNCC2)=C1O SVHNLCFHSPNERJ-UHFFFAOYSA-N 0.000 claims description 2
- UONLQFDHEGREOV-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(4-morpholin-4-ylpiperidin-1-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)N2CCC(CC2)N2CCOCC2)=C1O UONLQFDHEGREOV-UHFFFAOYSA-N 0.000 claims description 2
- PEDLIUGWZBQXFP-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(4-piperazin-1-ylphenyl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)C=2C=CC(=CC=2)N2CCNCC2)=C1O PEDLIUGWZBQXFP-UHFFFAOYSA-N 0.000 claims description 2
- MTRYSRYJRINGBV-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(4-propan-2-ylpiperazin-1-yl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1CN(C(C)C)CCN1C1=CC=C(CN(C2)C(=O)C=3C(=CC(O)=C(C(C)C)C=3)O)C2=C1 MTRYSRYJRINGBV-UHFFFAOYSA-N 0.000 claims description 2
- IBDJXXHTJPHOJQ-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(morpholin-4-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCOCC4)=CC=C3C2)=C1O IBDJXXHTJPHOJQ-UHFFFAOYSA-N 0.000 claims description 2
- AFCDQRNSLCTCHH-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(piperidin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCCCC4)=CC=C3C2)=C1O AFCDQRNSLCTCHH-UHFFFAOYSA-N 0.000 claims description 2
- ZSOPJQACGPRLBY-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-(piperidin-4-ylamino)-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(NC4CCNCC4)=CC=C3C2)=C1O ZSOPJQACGPRLBY-UHFFFAOYSA-N 0.000 claims description 2
- RKICJLSKDUSLPK-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[2-(2,2-dimethylpropylamino)ethoxy]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(OCCNCC(C)(C)C)=CC=C3C2)=C1O RKICJLSKDUSLPK-UHFFFAOYSA-N 0.000 claims description 2
- RHYWLHRFSBDYOC-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[2-(propan-2-ylamino)ethoxy]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1C2=CC(OCCNC(C)C)=CC=C2CN1C(=O)C1=CC(C(C)C)=C(O)C=C1O RHYWLHRFSBDYOC-UHFFFAOYSA-N 0.000 claims description 2
- QHIUCJMWZIQBCV-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[4-(2-hydroxyethyl)piperazin-1-yl]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(=CC=C3C2)N2CCN(CCO)CC2)=C1O QHIUCJMWZIQBCV-UHFFFAOYSA-N 0.000 claims description 2
- IOBATCZTSZQFKE-UHFFFAOYSA-N (2,4-dihydroxy-5-propan-2-ylphenyl)-[6-[2-(dimethylamino)ethoxy]-4-methyl-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(C)C=C(OCCN(C)C)C=C3C2)=C1O IOBATCZTSZQFKE-UHFFFAOYSA-N 0.000 claims description 2
- RDXRYKAWPOKHKF-UHFFFAOYSA-N (3-butan-2-yl-4-hydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)CC)=CC(C(=O)N2CC3=CC=CC=C3C2)=C1 RDXRYKAWPOKHKF-UHFFFAOYSA-N 0.000 claims description 2
- AGHRSYDXIACWAH-UHFFFAOYSA-N (3-tert-butyl-4-hydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)(C)C)=CC(C(=O)N2CC3=CC=CC=C3C2)=C1 AGHRSYDXIACWAH-UHFFFAOYSA-N 0.000 claims description 2
- NRRDDJRMRDLCEE-UHFFFAOYSA-N (3-tert-butyl-4-hydroxyphenyl)-(2,3-dihydroindol-1-yl)methanone Chemical compound C1=C(O)C(C(C)(C)C)=CC(C(=O)N2C3=CC=CC=C3CC2)=C1 NRRDDJRMRDLCEE-UHFFFAOYSA-N 0.000 claims description 2
- DOBRSHLMCIYEEI-UHFFFAOYSA-N (4,7-difluoro-1,3-dihydroisoindol-2-yl)-(2,4-dihydroxy-5-propan-2-ylphenyl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=C(C(=CC=C3F)F)C2)=C1O DOBRSHLMCIYEEI-UHFFFAOYSA-N 0.000 claims description 2
- JGKVBQVQYZFVMN-UHFFFAOYSA-N (5-amino-1,3-dihydroisoindol-2-yl)-(2,4-dihydroxy-5-propan-2-ylphenyl)methanone Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(N)=CC=C3C2)=C1O JGKVBQVQYZFVMN-UHFFFAOYSA-N 0.000 claims description 2
- OTKZPCDLOLLPPV-UHFFFAOYSA-N (5-bromo-2,4-dihydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(Br)C(O)=CC(O)=C1C(=O)N1CC2=CC=CC=C2C1 OTKZPCDLOLLPPV-UHFFFAOYSA-N 0.000 claims description 2
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| US82922106P | 2006-10-12 | 2006-10-12 | |
| US60/829,221 | 2006-10-12 | ||
| PCT/GB2007/003891 WO2008044045A1 (en) | 2006-10-12 | 2007-10-12 | Pharmaceutical combinations |
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Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI372050B (en) * | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| US8110573B2 (en) | 2004-12-30 | 2012-02-07 | Astex Therapeutics Limited | Pyrazole compounds that modulate the activity of CDK, GSK and aurora kinases |
| PT2332909E (pt) | 2005-04-13 | 2014-12-17 | Astex Therapeutics Ltd | Derivados de hidroxibenzamida e sua utilização como inibidores de hsp90 |
| EP1968579A1 (en) * | 2005-12-30 | 2008-09-17 | Astex Therapeutics Limited | Pharmaceutical compounds |
| US7754725B2 (en) | 2006-03-01 | 2010-07-13 | Astex Therapeutics Ltd. | Dihydroxyphenyl isoindolymethanones |
| JP2009542608A (ja) * | 2006-06-29 | 2009-12-03 | アステックス・セラピューティクス・リミテッド | 医薬組合せ剤 |
| JP5523829B2 (ja) * | 2006-06-29 | 2014-06-18 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| JP5410285B2 (ja) * | 2006-10-12 | 2014-02-05 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| EP2073807A1 (en) | 2006-10-12 | 2009-07-01 | Astex Therapeutics Limited | Pharmaceutical combinations |
| GB0620259D0 (en) * | 2006-10-12 | 2006-11-22 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| JP5518478B2 (ja) * | 2006-10-12 | 2014-06-11 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| JP5528806B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| GB0806527D0 (en) | 2008-04-11 | 2008-05-14 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| EP2424843B1 (en) | 2009-04-30 | 2014-03-26 | Novartis AG | Imidazole derivatives and their use as modulators of cyclin dependent kinases |
| US10774278B2 (en) * | 2013-02-27 | 2020-09-15 | Mitsubishi Heavy Industries Engineering, Ltd. | CO shift catalyst, CO shift reaction apparatus, and method for purifying gasified gas |
| KR102408261B1 (ko) | 2014-02-03 | 2022-06-10 | 비타이 파마슈티컬즈, 엘엘씨 | Ror-감마의 디하이드로피롤로피리딘 저해제 |
| DK3207043T6 (da) | 2014-10-14 | 2020-01-20 | Vitae Pharmaceuticals Llc | Dihydropyrrolopyridin-inhibitorer af ror-gamma |
| US9663515B2 (en) | 2014-11-05 | 2017-05-30 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| US9845308B2 (en) | 2014-11-05 | 2017-12-19 | Vitae Pharmaceuticals, Inc. | Isoindoline inhibitors of ROR-gamma |
| US10301261B2 (en) | 2015-08-05 | 2019-05-28 | Vitae Pharmaceuticals, Llc | Substituted indoles as modulators of ROR-gamma |
| EP3868750A1 (en) | 2015-11-20 | 2021-08-25 | Vitae Pharmaceuticals, LLC | Modulators of ror-gamma |
| TWI757266B (zh) | 2016-01-29 | 2022-03-11 | 美商維它藥物有限責任公司 | ＲＯＲ－γ調節劑 |
| US9481674B1 (en) | 2016-06-10 | 2016-11-01 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| US10927076B2 (en) | 2017-01-12 | 2021-02-23 | University Of Kansas | HSP90B N-terminal isoform-selective inhibitors |
| CN111225914B (zh) | 2017-07-24 | 2022-10-11 | 生命医药有限责任公司 | RORγ的抑制剂 |
| WO2019018975A1 (en) | 2017-07-24 | 2019-01-31 | Vitae Pharmaceuticals, Inc. | INHIBITORS OF ROR GAMMA |
Family Cites Families (240)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2512572A (en) | 1950-06-20 | Substituted pteridines and method | ||
| US1973A (en) | 1841-02-10 | Method oe cowstettctiitg clocks | ||
| US2802005A (en) | 1957-08-06 | S-eluorourace | ||
| US2917432A (en) | 1954-10-05 | 1959-12-15 | Burroughs Wellcome Co | Leukemia treatment |
| US2848455A (en) | 1955-07-18 | 1958-08-19 | Ciba Pharm Prod Inc | Alpha-(p-amino-phenyl)-alpha-lower alkyl glutarimides |
| US2891079A (en) | 1959-01-23 | 1959-06-16 | Searle & Co | 6-methyl-4, 6-pregnadiene-3, 20-dione and 17alpha-acyloxy derivatives thereof |
| US3046301A (en) | 1959-10-29 | 1962-07-24 | Burroughs Wellcome Co | Method of making chlorambucil |
| US3116282A (en) | 1960-04-27 | 1963-12-31 | Upjohn Co | Pyrimidine nucleosides and process |
| BE637389A (enExample) | 1962-09-13 | |||
| US3432549A (en) | 1965-04-22 | 1969-03-11 | Egyt Gyogyszervegyeszeti Gyar | Pharmacologically active new substituted benzamides |
| US3732340A (en) | 1966-07-11 | 1973-05-08 | Asta Werke Ag Chem Fab | N',o-propylene phosphoric acid ester diamides |
| US3803124A (en) | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| CH527207A (de) | 1968-05-08 | 1972-08-31 | Ceskoslovenska Akademie Ved | Verfahren zur Herstellung von 1-Glycosyl-5-azacytosinen |
| GB1235022A (en) | 1969-06-04 | 1971-06-09 | Laeaeke Ag | A new method for the production of cyclophosphamide |
| CH526500A (de) | 1969-12-31 | 1972-08-15 | Hoffmann La Roche | Verfahren zur Herstellung von Polyenverbindungen |
| DE2124023C3 (de) | 1970-05-27 | 1980-07-10 | Richter Gedeon Vegyeszeti Gyar R.T., Budapest | Verfahren zur selektiven Gewinnung von Vinblastin, Vinleurosin und Vincristin oder von deren Sulfaten |
| GB1354939A (en) | 1971-10-28 | 1974-06-05 | Ici Ltd | Process for the manufacture of 1,1,2-triphenylalk-1-enes |
| JPS4910506A (enExample) | 1972-05-31 | 1974-01-30 | ||
| CH588505A5 (enExample) | 1972-06-08 | 1977-06-15 | Research Corp | |
| AR204004A1 (es) | 1973-04-02 | 1975-11-12 | Lilly Co Eli | Procedimientos para preparar derivados de vinblastina leurosidina y leurocristina |
| US3914412A (en) | 1973-10-11 | 1975-10-21 | Abbott Lab | {8 Des{13 Gly{9 {0 10 -Gn{13 RH nonapeptide amide analogs in position 6 having ovulation-inducing activity |
| US4005063A (en) | 1973-10-11 | 1977-01-25 | Abbott Laboratories | [Des-gly]10 -GnRH nonapeptide anide analogs in position 6 having ovulation-inducing activity |
| GB1457632A (en) | 1974-03-22 | 1976-12-08 | Farmaceutici Italia | Adriamycins |
| US4020270A (en) | 1974-05-02 | 1977-04-26 | Societa' Farmaceutici Italia S.P.A. | L-lyxohex-1-enopyranose derivative |
| GB1467383A (en) | 1974-06-12 | 1977-03-16 | Farmaceutici Italia | Daunomycin analogues |
| DE2438350C3 (de) | 1974-08-09 | 1979-06-13 | Hoechst Ag, 6000 Frankfurt | Peptide mit starker LH-RH/FSH-RH-Wirkung, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen |
| GB1524747A (en) | 1976-05-11 | 1978-09-13 | Ici Ltd | Polypeptide |
| JPS6041077B2 (ja) | 1976-09-06 | 1985-09-13 | 喜徳 喜谷 | １，２‐ジアミノシクロヘキサン異性体のシス白金（２）錯体 |
| US4197249A (en) | 1977-08-15 | 1980-04-08 | American Cyanamid Company | 1,4-Bis(substituted-amino)-5,8-dihydroxyanthraquinones and leuco bases thereof |
| US4307100A (en) | 1978-08-24 | 1981-12-22 | Agence Nationale De Valorisation De La Recherche (Anvar) | Nor bis-indole compounds usable as medicaments |
| DE2845574A1 (de) | 1978-10-19 | 1980-04-24 | Deutsches Krebsforsch | Durch heterocyclische ringe oder alkylreste substituierte analoga von ccnu und verfahren zu deren herstellung |
| DE3046719C2 (de) | 1980-12-11 | 1983-02-17 | Klinge Pharma GmbH, 8000 München | 1,1,2-Triphenyl-but-1-en-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel |
| US4357324A (en) | 1981-02-24 | 1982-11-02 | The United States Of America As Represented By The Department Of Health And Human Services | Prodrug derivatives of 9β-D-arabinofuranosyl-2-fluoroadenine |
| US4418068A (en) | 1981-04-03 | 1983-11-29 | Eli Lilly And Company | Antiestrogenic and antiandrugenic benzothiophenes |
| OA07174A (fr) | 1981-08-24 | 1984-04-30 | May & Baker Ltd | Nouvelles imidazotétrazionones, leur préparation et les médicaments qui les contiennent. |
| GB2126576B (en) | 1982-06-25 | 1985-06-19 | Farmos Group Limited | Alkane and alkene derivatives |
| LU88769I2 (fr) | 1982-07-23 | 1996-11-05 | Zeneca Ltd | Bicalutamide et ses sels et esters pharmaceutiquement acceptables (Casodex (R)) |
| EP0111058B1 (en) | 1982-11-26 | 1987-11-04 | Nippon Kayaku Kabushiki Kaisha | Process for producing 4'-demethyl-epipodophyllotoxin-beta-d-ethylidene-glucoside and acyl-derivative thereof |
| US4526988A (en) | 1983-03-10 | 1985-07-02 | Eli Lilly And Company | Difluoro antivirals and intermediate therefor |
| JPS6019790A (ja) | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | 新規なカンプトテシン誘導体 |
| GB8327256D0 (en) | 1983-10-12 | 1983-11-16 | Ici Plc | Steroid derivatives |
| US4582909A (en) * | 1984-02-02 | 1986-04-15 | Warner-Lambert Company | Benzobicyclic lactam acids and derivatives as cognition activators |
| US4666828A (en) | 1984-08-15 | 1987-05-19 | The General Hospital Corporation | Test for Huntington's disease |
| US4760064A (en) * | 1984-12-18 | 1988-07-26 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril compounds, compositions containing same and processes for preparing same |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US5003011A (en) | 1985-04-09 | 1991-03-26 | The Administrators Of The Tulane Educational Fund | Therapeutic decapeptides |
| US4801531A (en) | 1985-04-17 | 1989-01-31 | Biotechnology Research Partners, Ltd. | Apo AI/CIII genomic polymorphisms predictive of atherosclerosis |
| US4691918A (en) | 1985-10-08 | 1987-09-08 | Diversified Products Corporation | Multiple exercise device |
| US4978672A (en) | 1986-03-07 | 1990-12-18 | Ciba-Geigy Corporation | Alpha-heterocyclc substituted tolunitriles |
| JPS62220196A (ja) | 1986-03-20 | 1987-09-28 | Kyowa Hakko Kogyo Co Ltd | 新規物質ｕｃｎ―０１ |
| IN164232B (enExample) | 1986-04-11 | 1989-02-04 | Hoechst India | |
| FR2601675B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2601676B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Procede de preparation du taxol et du desacetyl-10 taxol |
| NZ224714A (en) | 1987-06-01 | 1990-03-27 | Janssen Pharmaceutica Nv | Substituted benzotriazole derivatives and pharmaceutical compositions |
| GB8714013D0 (en) | 1987-06-16 | 1987-07-22 | Ici Plc | (substituted-aralkyl)heterocyclic compounds |
| US5004758A (en) | 1987-12-01 | 1991-04-02 | Smithkline Beecham Corporation | Water soluble camptothecin analogs useful for inhibiting the growth of animal tumor cells |
| CA1340191C (en) | 1988-06-13 | 1998-12-15 | Katsuhiro Imaki | Derivatives of p-substituted phenyl ester of pivalic acid |
| US4990511A (en) | 1988-08-03 | 1991-02-05 | Takeda Chemical Industries, Ltd. | Amide compounds, their production and use |
| US5272057A (en) | 1988-10-14 | 1993-12-21 | Georgetown University | Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase |
| US5192659A (en) | 1989-08-25 | 1993-03-09 | Genetype Ag | Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes |
| GB8926560D0 (en) | 1989-11-24 | 1990-01-17 | Zambeletti Spa L | Pharmaceuticals |
| IL96531A (en) | 1989-12-11 | 1995-08-31 | Univ Princeton | History of Acid N- (Diomeric-H1-Pyrolo] D-2,3 [Pyrimidine-3-Ilacyl (-glutamic, preparation and pharmaceutical preparations containing them) |
| US5124350A (en) * | 1990-06-28 | 1992-06-23 | G. D. Searle & Co. | Leukotriene b4 antagonists |
| US5177064A (en) | 1990-07-13 | 1993-01-05 | University Of Florida | Targeted drug delivery via phosphonate derivatives |
| ZA916555B (en) | 1990-08-27 | 1993-04-28 | Lilly Co Eli | Method of treating inflammatory bowel disease |
| TW295589B (enExample) | 1990-08-30 | 1997-01-11 | Hoechst Ag | |
| FR2669029B1 (fr) | 1990-11-14 | 1994-09-02 | Adir | Nouveaux derives de la n-benzoyl proline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| MX9102128A (es) | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene |
| US5280046A (en) | 1991-02-22 | 1994-01-18 | The University Of Colorado Foundation, Inc. | Method of treating type I diabetes |
| WO1992017467A1 (en) | 1991-04-06 | 1992-10-15 | Dr Lo. Zambeletti S.P.A. | Substituted azacyclic compounds, process for their preparation and their use as analgesics |
| EP0590058B1 (en) | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| GB9112859D0 (en) | 1991-06-14 | 1991-07-31 | Ici Plc | Peptide process |
| IT1250692B (it) | 1991-07-23 | 1995-04-21 | Procedimento per la preparazione di demetilepipodofillotossina- beta-d-glucosidi. | |
| TW225528B (enExample) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| EP0983992B1 (en) | 1992-04-22 | 2005-10-26 | Ligand Pharmaceuticals Incorporated | Compounds having selectivity for retinoid x receptors |
| DE4222910A1 (de) | 1992-07-11 | 1994-01-13 | Asta Medica Ag | Neue Phospholipidderivate |
| EP1238986B1 (en) | 1992-10-28 | 2008-06-25 | Genentech, Inc. | Use of Vascular endothelial cell growth factor antagonists |
| ES2091684T3 (es) | 1992-11-13 | 1996-11-01 | Idec Pharma Corp | Aplicacion terapeutica de anticuerpos quimericos y radiomarcados contra el antigeno de diferenciacion restringida de los linfocitos b humanos para el tratamiento del linfoma de las celulas b. |
| US5466861A (en) | 1992-11-25 | 1995-11-14 | Sri International | Bridged bicyclic aromatic compounds and their use in modulating gene expression of retinoid receptors |
| US5595721A (en) | 1993-09-16 | 1997-01-21 | Coulter Pharmaceutical, Inc. | Radioimmunotherapy of lymphoma using anti-CD20 |
| ATE233245T1 (de) | 1993-11-30 | 2003-03-15 | Searle & Co | Substituierte pyrazolyl-benzolsulfonamide und ihre verwendung als cyclooxygenaseii inhibitoren |
| US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
| US5476932A (en) | 1994-08-26 | 1995-12-19 | Hoffmann-La Roche Inc. | Process for producing N4-acyl-5'-deoxy-5-fluorocytidine derivatives |
| US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
| US5633283A (en) | 1995-01-23 | 1997-05-27 | Eli Lilly And Company | Method for treating multiple sclerosis |
| DE69536015D1 (de) | 1995-03-30 | 2009-12-10 | Pfizer Prod Inc | Chinazolinone Derivate |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| US5843901A (en) | 1995-06-07 | 1998-12-01 | Advanced Research & Technology Institute | LHRH antagonist peptides |
| AU6267896A (en) | 1995-06-07 | 1996-12-30 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth oftumors |
| WO1998004689A1 (en) | 1995-07-31 | 1998-02-05 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate disease |
| US6218529B1 (en) | 1995-07-31 | 2001-04-17 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer |
| US5675024A (en) | 1995-11-22 | 1997-10-07 | Allergan | Aryl or heteroaryl amides of tetrahydronaphthalene, chroman, thiochroman and 1,2,3,4,-tetrahydroquinoline carboxylic acids, having an electron withdrawing substituent in the aromatic or heteroaromatic moiety, having retinoid-like biological activity |
| US5663357A (en) | 1995-11-22 | 1997-09-02 | Allergan | Substituted heteroarylamides having retinoid-like biological activity |
| FR2741881B1 (fr) | 1995-12-01 | 1999-07-30 | Centre Nat Rech Scient | Nouveaux derives de purine possedant notamment des prorietes anti-proliferatives et leurs applications biologiques |
| JP3855026B2 (ja) | 1996-01-16 | 2006-12-06 | 富士レビオ株式会社 | アミド誘導体の製造方法 |
| DE69739970D1 (de) | 1996-01-29 | 2010-10-07 | Univ California | Methode zur behandlung sexueller fehlfunktionen |
| GB9606187D0 (en) | 1996-03-23 | 1996-05-29 | Inst Of Food Research | Production of vanillin |
| WO1997036876A1 (en) | 1996-04-03 | 1997-10-09 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| AU714477B2 (en) | 1996-04-19 | 2000-01-06 | Regents Of The University Of California, The | Treatment of mood/affective disorders by glutamatergic upmodulators |
| IL118657A0 (en) | 1996-06-14 | 1996-10-16 | Arad Dorit | Inhibitors for picornavirus proteases |
| ATE265997T1 (de) | 1996-06-21 | 2004-05-15 | Allergan Inc | Substituierte tetrahydronaphthalin- und dihydronaphthalin-derivate mit einer retinoiden und/oder retinoid antagonist-ähnlichen biologischen aktivität |
| US5723632A (en) | 1996-08-08 | 1998-03-03 | Mgi Pharma, Inc. | Total synthesis of antitumor acylfulvenes |
| EP0827742A1 (en) | 1996-09-04 | 1998-03-11 | Vrije Universiteit Brussel | Use of histone deacetylase inhibitors for treating fribosis or cirrhosis |
| ES2301194T3 (es) | 1997-02-05 | 2008-06-16 | Warner-Lambert Company Llc | Pirido 2,3-d pirimidinas y 4-aminopirimidinas como inhibidores de la proliferacion celular. |
| CO4950519A1 (es) | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| JP2001514631A (ja) | 1997-03-07 | 2001-09-11 | ノボ ノルディスク アクティーゼルスカブ | ４，５，６，７−テトラヒドロ−チエノ［３，２−ｃ］ピリジン誘導体類、それらの製造方法及び使用 |
| UY24949A1 (es) | 1997-04-08 | 2001-04-30 | Smithkline Beecham Corp | Compuestos calcilíticos |
| JP2001526643A (ja) | 1997-04-18 | 2001-12-18 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５ｈｔ１ａ、５ｈｔ１ｂおよび５ｈｔ１ｄ受容体アンタゴニスト活性を合わせ持つ化合物を含む二環式アリールまたは二環式複素環 |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| US6329368B1 (en) | 1997-05-09 | 2001-12-11 | The Regents Of The University Of California | Endocrine modulation with positive modulators of AMPA type glutamate receptors |
| GB9719426D0 (en) | 1997-09-13 | 1997-11-12 | Johnson Matthey Plc | Novel process |
| ES2258825T3 (es) | 1997-10-27 | 2006-09-01 | Cortex Pharmaceuticals, Inc. | Tratamiento de la esquizofrenia con ampakinas y neurolepticos. |
| AU1804299A (en) | 1997-12-08 | 1999-06-28 | Glycomed Incorporated | Sialyl lewis x and sialyl lewis a glycomimetics |
| GB9800569D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| WO2000042012A1 (en) | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| WO2000059867A1 (en) | 1999-03-30 | 2000-10-12 | Pharmacor Inc. | Hydroxyphenyl derivatives with hiv integrase inhibitory properties |
| EP2308833A3 (en) | 1999-04-15 | 2011-09-28 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| US6166244A (en) | 1999-05-07 | 2000-12-26 | Allergan Sales, Inc. | Oxygen, sulfur and nitrogen substituted cyclohexene and cyclohexane derivatives having retinoid-like biological activity |
| US6127382A (en) | 1999-08-16 | 2000-10-03 | Allergan Sales, Inc. | Amines substituted with a tetrahydroquinolinyl group an aryl or heteroaryl group and an alkyl group, having retinoid-like biological activity |
| EP1686120A3 (en) | 1999-10-27 | 2007-05-30 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| US6545004B1 (en) | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| EE05330B1 (et) | 1999-11-05 | 2010-08-16 | Astrazeneca Ab | Kinasoliini derivaadid kui VEGF-i inhibiitorid |
| DE19955283A1 (de) | 1999-11-17 | 2001-05-23 | Aventis Res & Tech Gmbh & Co | Verfahren zur enantioselektiven Gewinnung von Aminosäuren und Aminosäurederivaten unter Verwendung von Racemisierungskatalysatoren |
| WO2001036351A2 (en) | 1999-11-19 | 2001-05-25 | Corvas International, Inc. | Plasminogen activator inhibitor antagonists related applications |
| MY125768A (en) | 1999-12-15 | 2006-08-30 | Bristol Myers Squibb Co | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
| YU54202A (sh) | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
| HN2001000008A (es) | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
| AU2001243158A1 (en) | 2000-02-18 | 2001-08-27 | Merck And Co., Inc. | Inhibitors of prenyl-protein transferase |
| EP1261341A2 (en) | 2000-02-29 | 2002-12-04 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitor combinations with camptothecin compounds |
| US6613917B1 (en) | 2000-03-23 | 2003-09-02 | Allergan, Inc. | Amines substituted with a dihydronaphthalenyl, chromenyl, or thiochromenyl group, an aryl or heteroaryl group and an alkyl group, having retinoid-like biological activity |
| JP2004507456A (ja) * | 2000-05-11 | 2004-03-11 | ブリストル−マイヤーズ スクイブ カンパニー | 成長ホルモン分泌促進薬として有用なテトラヒドロイソキノリン類縁体 |
| AU2001256733A1 (en) | 2000-05-16 | 2001-11-26 | Takeda Chemical Industries Ltd. | Melanin-concentrating hormone antagonist |
| CA2308994A1 (en) * | 2000-05-19 | 2001-11-19 | Aegera Therapeutics Inc. | Neuroprotective compounds |
| DE10024939A1 (de) * | 2000-05-19 | 2001-11-29 | Bayer Ag | Neue Diphenylmethanderivate für Arzneimittel |
| IL136458A0 (en) | 2000-05-30 | 2001-06-14 | Peptor Ltd | Protein kinase inhibitors |
| IL153246A0 (en) | 2000-06-28 | 2003-07-06 | Astrazeneca Ab | Substituted quinazoline derivatives and their use as inhibitors |
| AU7307101A (en) | 2000-06-30 | 2002-01-14 | Glaxo Group Ltd | Quinazoline ditosylate salt compounds |
| FR2812876B1 (fr) | 2000-08-08 | 2002-09-27 | Galderma Res & Dev | Nouveaux composes bi-aromatiques activateurs des recepteurs de type ppar-gamma et leur utilisation dans des compositions cosmetiques ou pharmaceutiques |
| CA2416527C (en) | 2000-08-10 | 2009-12-22 | Pharmacia Italia S.P.A. | Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| MXPA03001654A (es) | 2000-08-25 | 2004-09-10 | Warner Lambert Co | Proceso para la elaboracion del acido n-aril-antranilico y sus derivados. |
| ES2302106T3 (es) | 2000-09-11 | 2008-07-01 | Novartis Vaccines And Diagnostics, Inc. | Procedimiento de preparacion de derivados de bencimidazol-2-il quinolina. |
| AU2002217866A1 (en) | 2000-11-06 | 2002-05-15 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Geldanamycin derivatives useful for the treatment of cancer |
| US6455559B1 (en) | 2001-07-19 | 2002-09-24 | Pharmacia Italia S.P.A. | Phenylacetamido-pyrazole derivatives, process for their preparation and their use as antitumor agents |
| UA82827C2 (en) * | 2000-12-18 | 2008-05-26 | Inhibitors against the production and release of inflammatory cytokines | |
| HUP0400639A3 (en) | 2000-12-21 | 2010-03-29 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors and pharmaceutical compositions containing them |
| BR0116792A (pt) | 2000-12-22 | 2004-02-17 | Ortho Mcneil Pharm Inc | Derivados de diamina de triazol substituìdos como inibidores de quinase |
| AU2002252179A1 (en) | 2001-03-01 | 2002-09-19 | Conforma Therapeutics Corp. | Methods for treating genetically-defined proliferative disorders with hsp90 inhibitors |
| IL159120A0 (en) | 2001-05-29 | 2004-05-12 | Schering Ag | Cdk inhibiting pyrimidines, production thereof and their use as medicaments |
| AU2002330998A1 (en) | 2001-08-06 | 2003-02-24 | Kosan Biosciences, Inc. | Benzoquinone ansamycins |
| CN100378079C (zh) | 2001-09-24 | 2008-04-02 | 康福玛医药公司 | 用于制备17-烯丙基氨基格尔德霉素(17-aag)以及其它袢霉素的方法 |
| WO2003051877A1 (en) | 2001-12-18 | 2003-06-26 | Bayer Corporation | 2-substituted pyrrolo[2.1-a]isoquinolines against cancer |
| AU2002366811B2 (en) | 2001-12-20 | 2009-01-15 | Osi Pharmaceuticals, Inc. | Pyrimidine A2B selective antagonist compounds, their synthesis and use |
| JP4399265B2 (ja) | 2001-12-21 | 2010-01-13 | ヴァーナリス（ケンブリッジ）リミテッド | ３，４−ジアリールピラゾール、および癌の治療におけるそれらの使用 |
| SE0104462D0 (sv) | 2001-12-29 | 2001-12-29 | Carlbiotech Ltd As | Peptide purifcation (Peptidrening) |
| WO2003061385A1 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | Tricyclic nucleoside library compounds, synthesis, and use as antiviral agents |
| AU2002316231A1 (en) | 2002-02-19 | 2003-09-29 | Xenoport, Inc. | Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof |
| US20030203915A1 (en) | 2002-04-05 | 2003-10-30 | Xinqin Fang | Nitric oxide donors, compositions and methods of use related applications |
| AU2003224341A1 (en) | 2002-04-26 | 2003-11-10 | Warner-Lambert Company Llc | Inhibitors of checkpoint kinases (wee1 and chk1) |
| TW200410671A (en) * | 2002-06-05 | 2004-07-01 | Inst Med Molecular Design Inc | Medicines for inhibiting the activation of AP-1 |
| CN101103977A (zh) * | 2002-06-05 | 2008-01-16 | 株式会社医药分子设计研究所 | 糖尿病治疗药 |
| AU2003242131A1 (en) | 2002-06-05 | 2003-12-22 | Institute Of Medicinal Molecular Design, Inc. | Immunity-related protein kinase inhibitors |
| CN1658872B (zh) * | 2002-06-06 | 2010-09-22 | 株式会社医药分子设计研究所 | 抗过敏药 |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| SE0202133D0 (sv) | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| CA2393720C (en) | 2002-07-12 | 2010-09-14 | Eli Lilly And Company | Crystalline 2,5-dione-3-(1-methyl-1h-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1h-indol-3-yl]-1h-pyrrole mono-hydrochloride |
| NZ537853A (en) * | 2002-07-16 | 2007-02-23 | Amura Therapeutics Ltd | Inhibitors of cathepsin K and related cysteine protesases of the CA clan |
| US6800655B2 (en) | 2002-08-20 | 2004-10-05 | Sri International | Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents |
| EP1554271A1 (en) * | 2002-10-15 | 2005-07-20 | Rigel Pharmaceuticals, Inc. | Substituted indoles and their use as hcv inhibitors |
| AU2003302589A1 (en) | 2002-12-02 | 2004-06-23 | Kyukyu Pharmaceutical Co., Ltd. | Method for producing orally administrable edible agent of laminate film form and pressure bonding apparatus of the agent. |
| TWI228885B (en) * | 2003-01-23 | 2005-03-01 | Mediatek Inc | Method for controlling a mobile communication device to enter a power-saving mode and to recover timing after the mobile communication device leaves the power-saving mode |
| EA009919B1 (ru) | 2003-02-11 | 2008-04-28 | Вернэлис (Кембридж) Лимитед | Соединения изоксазола |
| CN1764375A (zh) * | 2003-02-20 | 2006-04-26 | 康涅狄格大学健康中心 | 使用包括热休克蛋白或α－2－巨球蛋白的组合物治疗癌症和传染病的方法 |
| EP1597256A1 (en) | 2003-02-21 | 2005-11-23 | Pfizer Inc. | N-heterocyclyl-substituted amino-thiazole derivatives as protein kinase inhibitors |
| KR100983462B1 (ko) | 2003-02-26 | 2010-09-27 | 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 | 디하이드로프테리디논, 이의 제조방법 및 약제로서의 이의 용도 |
| US6943249B2 (en) | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| US6887855B2 (en) | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| US7038038B2 (en) | 2003-03-17 | 2006-05-02 | Pharmion Corporation | Synthesis of 5-azacytidine |
| MXPA05009303A (es) | 2003-04-03 | 2005-10-05 | Pfizer | Formas de dosificacion y procedimientos de tratamiento que usan inhibidores del vegfr. |
| EP1622866B1 (en) | 2003-04-30 | 2012-07-25 | Novartis AG | Aminopropanol derivatives as sphingosine-1-phosphate receptor modulators |
| GB0315111D0 (en) | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| KR101129215B1 (ko) | 2003-06-27 | 2012-04-13 | 교와 핫꼬 기린 가부시키가이샤 | Ｈｓｐ90 패밀리 단백질 저해제 |
| TWI312345B (en) | 2003-06-30 | 2009-07-21 | Mitsubishi Tanabe Pharma Corp | Process of preparating 3-acylaminobenzofuran-2-carboxylic acid derivatives |
| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| JPWO2005007151A1 (ja) * | 2003-07-16 | 2006-08-31 | 株式会社医薬分子設計研究所 | 皮膚色素沈着の治療剤 |
| CA2532965C (en) | 2003-07-22 | 2013-05-14 | Astex Therapeutics Limited | 3, 4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
| ZA200510137B (en) | 2003-07-24 | 2007-04-25 | Leo Pharma As | Novel aminobenzophenone compounds |
| AU2004261610B2 (en) | 2003-07-28 | 2010-05-20 | Janssen Pharmaceutica N.V. | Benzimidazole, benzthiazole and benzoxazole derivatives and their use as LTA4H modulators |
| DE10335584B4 (de) | 2003-07-31 | 2006-06-29 | Philipps-Universität Marburg | Verfahren zur Herstellung zyklischer Moleküle |
| DE10335726A1 (de) * | 2003-08-05 | 2005-03-03 | Bayer Cropscience Gmbh | Verwendung von Hydroxyaromaten als Safener |
| WO2005016889A1 (en) | 2003-08-08 | 2005-02-24 | Virginia Commonwealth University | Compounds having antiestrogenic and tissue selective estrogenic properties |
| CA2572750A1 (en) | 2003-09-10 | 2005-03-17 | Anil Koul | Heterobicyclic compounds as pharmaceutically active agents |
| CN103145715B (zh) | 2003-10-14 | 2016-08-03 | F·霍夫曼-罗须公司 | 作为hcv复制抑制剂的巨环羧酸和酰基磺酰胺 |
| ES2344007T3 (es) | 2003-10-14 | 2010-08-16 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Inhibidores proteina quinasa. |
| KR101167573B1 (ko) | 2003-11-07 | 2012-07-30 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 개선된 약학적 성질을 갖는 퀴놀리논 화합물의 약학적으로허용가능한 염 |
| BRPI0415874A (pt) | 2003-11-10 | 2007-01-09 | Schering Ag | compostos de amina de éter benzìlico como antagonistas de ccr-5 |
| DE602004020654D1 (de) | 2003-11-18 | 2009-05-28 | Novartis Ag | Hemmer der mutanten form von kit |
| US7282493B2 (en) | 2003-12-23 | 2007-10-16 | Infinity Pharmaceuticals, Inc. | Analogs of benzoquinone-containing ansamycins and methods of use thereof |
| EP1704856A4 (en) | 2003-12-26 | 2009-08-19 | Kyowa Hakko Kirin Co Ltd | PROTEIN INHIBITOR OF THE HSP90 FAMILY |
| TWI338004B (en) | 2004-02-06 | 2011-03-01 | Bristol Myers Squibb Co | Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors |
| US7652146B2 (en) | 2004-02-06 | 2010-01-26 | Bristol-Myers Squibb Company | Process for preparing 2-aminothiazole-5-carboxamides useful as kinase inhibitors |
| US20050256097A1 (en) | 2004-05-11 | 2005-11-17 | Kosan Biosciences, Inc. | Pharmaceutical solution formulations containing 17-AAG |
| ES2299080T3 (es) | 2004-05-14 | 2008-05-16 | Millennium Pharmaceuticals, Inc. | Compuestos y metodos para inhibir la progresion mitotica mediante la inhibicion de quinasas aurora. |
| US7351709B2 (en) * | 2004-06-09 | 2008-04-01 | Wyeth | Estrogen receptor ligands |
| US20060014949A1 (en) | 2004-07-13 | 2006-01-19 | Supergen Inc. | Compositions and formulations of decitabine polymorphs and methods of use thereof |
| JP2008508303A (ja) * | 2004-07-27 | 2008-03-21 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | ピロロ−ピリジンキナーゼモジュレーター |
| US7728134B2 (en) | 2004-08-14 | 2010-06-01 | Boehringer Ingelheim International Gmbh | Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament |
| US20060035903A1 (en) | 2004-08-14 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Storage stable perfusion solution for dihydropteridinones |
| US7759485B2 (en) | 2004-08-14 | 2010-07-20 | Boehringer Ingelheim International Gmbh | Process for the manufacture of dihydropteridinones |
| KR20070046180A (ko) | 2004-08-20 | 2007-05-02 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | 항세포사멸 ｂｃｌ-2군 구성원의 소분자 억제제 및 이의용도 |
| US20060069060A1 (en) | 2004-09-27 | 2006-03-30 | Sanjeev Redkar | Salts of decitabine |
| US20060067953A1 (en) | 2004-09-29 | 2006-03-30 | Conforma Therapeutics Corporation | Oral pharmaceutical formulations and methods for producing and using same |
| DE102004049078A1 (de) | 2004-10-08 | 2006-04-13 | Merck Patent Gmbh | Phenylpyrazole |
| US7208630B2 (en) | 2004-10-27 | 2007-04-24 | University Of Kansas | Heat shock protein 90 inhibitors |
| WO2006048746A2 (en) | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Methods for the removal of heavy metals |
| CA2586176A1 (en) | 2004-11-02 | 2006-05-11 | Srinivasan Babu | Methods for preparing indazole compounds |
| WO2006050373A2 (en) | 2004-11-02 | 2006-05-11 | The Regents Of The University Of California | Methods and compositions for modulating apoptosis |
| EP1813270A4 (en) | 2004-11-09 | 2009-07-01 | Kyowa Hakko Kirin Co Ltd | PROTEIN INHIBITORS OF THE HSP90 FAMILY |
| EP1817295B1 (en) | 2004-11-18 | 2012-11-07 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| US8110573B2 (en) | 2004-12-30 | 2012-02-07 | Astex Therapeutics Limited | Pyrazole compounds that modulate the activity of CDK, GSK and aurora kinases |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| HRP20100076T1 (hr) | 2005-02-07 | 2010-03-31 | F. Hoffmann - La Roche Ag | Heterociklički supstituirani fenil metanoni kao inhibitori glicin transportera 1 |
| WO2006088954A1 (en) * | 2005-02-15 | 2006-08-24 | Janssen Pharmaceutica, N.V. | Dihydroindolyl methanones as alpha 1a/1d adrenoreceptor modulators for the treatment of benign prostatic hypertrophy and lower urinary tract symptoms |
| CA2599046A1 (en) | 2005-02-21 | 2006-08-24 | Kyowa Hakko Kogyo Co., Ltd. | Antitumor agent |
| PT2332909E (pt) * | 2005-04-13 | 2014-12-17 | Astex Therapeutics Ltd | Derivados de hidroxibenzamida e sua utilização como inibidores de hsp90 |
| WO2006117669A1 (en) | 2005-05-03 | 2006-11-09 | Pfizer Inc. | Amide resorcinol compounds |
| AU2006247136C1 (en) | 2005-05-17 | 2020-01-16 | Bausch + Lomb Ireland Limited | Compositions and methods for treatment of eye disorders |
| WO2007050124A1 (en) | 2005-05-19 | 2007-05-03 | Xenon Pharmaceuticals Inc. | Fused piperidine derivatives and their uses as therapeutic agents |
| US7425633B2 (en) * | 2005-08-26 | 2008-09-16 | National Health Research Institutes | Pyrrolidine compounds |
| EP1968579A1 (en) | 2005-12-30 | 2008-09-17 | Astex Therapeutics Limited | Pharmaceutical compounds |
| US7785275B2 (en) * | 2006-01-31 | 2010-08-31 | Cook Incorporated | Wire guide having distal coupling tip |
| US7754725B2 (en) * | 2006-03-01 | 2010-07-13 | Astex Therapeutics Ltd. | Dihydroxyphenyl isoindolymethanones |
| GB0620259D0 (en) * | 2006-10-12 | 2006-11-22 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| JP5528806B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| JP5518478B2 (ja) * | 2006-10-12 | 2014-06-11 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| JP5410285B2 (ja) | 2006-10-12 | 2014-02-05 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| EP2073807A1 (en) | 2006-10-12 | 2009-07-01 | Astex Therapeutics Limited | Pharmaceutical combinations |
| JP5721949B2 (ja) * | 2006-10-12 | 2015-05-20 | アステックス、セラピューティックス、リミテッドＡｓｔｅｘ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ | 複合薬剤 |
| WO2008053319A1 (en) | 2006-10-30 | 2008-05-08 | Pfizer Products Inc. | Amide resorcinol compounds |
| CN102014644B (zh) * | 2008-06-11 | 2013-03-13 | 森永乳业株式会社 | 发酵乳的制造方法 |
-
2007
- 2007-10-12 EP EP07824143A patent/EP2073807A1/en not_active Withdrawn
- 2007-10-12 JP JP2009531918A patent/JP5528807B2/ja not_active Expired - Fee Related
- 2007-10-12 US US12/445,136 patent/US8883790B2/en not_active Expired - Fee Related
- 2007-10-12 WO PCT/GB2007/003891 patent/WO2008044045A1/en not_active Ceased
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