JP2010505931A5 - - Google Patents
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- Publication number
- JP2010505931A5 JP2010505931A5 JP2009531917A JP2009531917A JP2010505931A5 JP 2010505931 A5 JP2010505931 A5 JP 2010505931A5 JP 2009531917 A JP2009531917 A JP 2009531917A JP 2009531917 A JP2009531917 A JP 2009531917A JP 2010505931 A5 JP2010505931 A5 JP 2010505931A5
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- phenyl
- methanone
- isoindol
- 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 185
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 239000001257 hydrogen Substances 0.000 claims description 77
- 238000000034 method Methods 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 52
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
- -1 NR c Inorganic materials 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 31
- 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
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 241000124008 Mammalia Species 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 25
- 125000002837 carbocyclic group Chemical group 0.000 claims description 24
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 239000011737 fluorine Substances 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 208000024891 symptom Diseases 0.000 claims description 19
- 230000002159 abnormal effect Effects 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 230000001404 mediated effect Effects 0.000 claims description 13
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 230000004663 cell proliferation Effects 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 11
- 150000001204 N-oxides Chemical class 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 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
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- CCUXEBOOTMDSAM-UHFFFAOYSA-N 4-[(2,6-dichlorobenzoyl)amino]-n-(1-methylsulfonylpiperidin-4-yl)-1h-pyrazole-5-carboxamide Chemical compound C1CN(S(=O)(=O)C)CCC1NC(=O)C1=C(NC(=O)C=2C(=CC=CC=2Cl)Cl)C=NN1 CCUXEBOOTMDSAM-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- CXBHMSHVCKEEGW-UHFFFAOYSA-N 4-(2,6-difluorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide Chemical compound FC1=CC=CC(F)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 CXBHMSHVCKEEGW-UHFFFAOYSA-N 0.000 claims description 4
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 230000000903 blocking effect Effects 0.000 claims description 4
- 230000033077 cellular process Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- OVPNQJVDAFNBDN-UHFFFAOYSA-N 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide Chemical compound ClC1=CC=CC(Cl)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 OVPNQJVDAFNBDN-UHFFFAOYSA-N 0.000 claims description 3
- 230000032823 cell division Effects 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 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
- JUVRJNYFHAUUEF-UHFFFAOYSA-N (5-butan-2-yl-2,4-dihydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)CC)=CC(C(=O)N2CC3=CC=CC=C3C2)=C1O JUVRJNYFHAUUEF-UHFFFAOYSA-N 0.000 claims description 2
- FBMKRVXJVXRCOJ-UHFFFAOYSA-N (5-chloro-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(Cl)=CC=C3C2)=C1O FBMKRVXJVXRCOJ-UHFFFAOYSA-N 0.000 claims description 2
- ZGNOUNLCAKAXLK-UHFFFAOYSA-N (5-chloro-2,4-dihydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(Cl)C(O)=CC(O)=C1C(=O)N1CC2=CC=CC=C2C1 ZGNOUNLCAKAXLK-UHFFFAOYSA-N 0.000 claims description 2
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| US9845308B2 (en) | 2014-11-05 | 2017-12-19 | Vitae Pharmaceuticals, Inc. | Isoindoline inhibitors of ROR-gamma |
| WO2016135633A1 (en) * | 2015-02-24 | 2016-09-01 | King Abdullah University Of Science & Technology | Cholesteryl ester transfer protein (cetp) inhibition in the treatment of cancer |
| DK3331876T3 (da) | 2015-08-05 | 2021-01-11 | Vitae Pharmaceuticals Llc | Modulators of ror-gamma |
| MA53943A (fr) | 2015-11-20 | 2021-08-25 | Vitae Pharmaceuticals Llc | Modulateurs de ror-gamma |
| EP3380086B1 (en) * | 2015-11-25 | 2021-10-13 | IO Therapeutics, Inc. | Cyp26-resistant rar-alpha selective agonists in the treatment of cancer |
| 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 |
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| WO2019027203A1 (ko) * | 2017-08-02 | 2019-02-07 | 계명대학교 산학협력단 | Ｈｓｐ９０ 억제 활성을 갖는 디히드록시페닐계 입체이성질체 및 이의 의학적 용도 |
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Family Cites Families (242)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2802005A (en) | 1957-08-06 | S-eluorourace | ||
| US2512572A (en) | 1950-06-20 | Substituted pteridines and method | ||
| GB620259A (en) | 1946-03-12 | 1949-03-22 | Robert Rufus Carver | Churns |
| 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 (https=) | 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 |
| JPS4910506Y1 (https=) | 1970-10-20 | 1974-03-13 | ||
| GB1354939A (en) | 1971-10-28 | 1974-06-05 | Ici Ltd | Process for the manufacture of 1,1,2-triphenylalk-1-enes |
| CH605550A5 (https=) | 1972-06-08 | 1978-09-29 | Research Corp | |
| AR204004A1 (es) | 1973-04-02 | 1975-11-12 | Lilly Co Eli | Procedimientos para preparar derivados de vinblastina leurosidina y leurocristina |
| US4005063A (en) | 1973-10-11 | 1977-01-25 | Abbott Laboratories | [Des-gly]10 -GnRH nonapeptide anide analogs in position 6 having ovulation-inducing activity |
| 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 |
| 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 |
| ATE28864T1 (de) | 1982-07-23 | 1987-08-15 | Ici Plc | Amide-derivate. |
| 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 (https=) | 1986-04-11 | 1989-02-04 | Hoechst India | |
| FR2601676B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Procede de preparation du taxol et du desacetyl-10 taxol |
| FR2601675B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
| 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 |
| KR0143565B1 (ko) | 1988-06-13 | 1998-07-15 | 사노 가즈오 | 피발산의 p-치환된 페닐 에스테르 유도체, 그의 제조 방법 및 이를 포함하는 조성물. |
| 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 (https=) | 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 |
| GB9112859D0 (en) | 1991-06-14 | 1991-07-31 | Ici Plc | Peptide process |
| EP1400536A1 (en) | 1991-06-14 | 2004-03-24 | Genentech Inc. | Method for making humanized antibodies |
| IT1250692B (it) | 1991-07-23 | 1995-04-21 | Procedimento per la preparazione di demetilepipodofillotossina- beta-d-glucosidi. | |
| TW225528B (https=) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| ATE195716T1 (de) | 1992-04-22 | 2000-09-15 | Ligand Pharm Inc | Retinoid-x rezeptor selektive verbindungen |
| DE4222910A1 (de) | 1992-07-11 | 1994-01-13 | Asta Medica Ag | Neue Phospholipidderivate |
| AU687727B2 (en) | 1992-10-28 | 1998-03-05 | Genentech Inc. | Vascular endothelial cell growth factor antagonists |
| DK0752248T3 (da) | 1992-11-13 | 2000-11-13 | Idec Pharma Corp | Terapeutisk anvendelse af kimæriske og radioaktivt mærkede antistoffer mod humant B-lymfocytbegrænset differentieringsantig |
| 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 |
| DE69422306T4 (de) | 1993-11-30 | 2000-09-07 | G.D. Searle & Co., Chicago | Substituierte pyrazolyl-benzolsulfonamide zur behandlung von entzündungen |
| 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 |
| JPH11507535A (ja) | 1995-06-07 | 1999-07-06 | イムクローン システムズ インコーポレイテッド | 腫瘍の成長を抑制する抗体および抗体フラグメント類 |
| US5843901A (en) | 1995-06-07 | 1998-12-01 | Advanced Research & Technology Institute | LHRH antagonist peptides |
| JPH0910506A (ja) | 1995-06-30 | 1997-01-14 | Toshiba Corp | 脱気器 |
| US6218529B1 (en) | 1995-07-31 | 2001-04-17 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer |
| EP0951541B1 (en) | 1995-07-31 | 2005-11-30 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate disease |
| 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 |
| AU709113B2 (en) | 1996-01-29 | 1999-08-19 | Regents Of The University Of California, The | Method for treating sexual dysfunctions |
| 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 |
| JP2000511558A (ja) | 1996-06-21 | 2000-09-05 | アラーガン・セイルズ・インコーポレイテッド | レチノイドおよび／またはレチノイド拮抗剤様生物学的活性を有する置換テトラヒドロナフタレンおよびジヒドロナフタレン誘導体 |
| 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 |
| WO1998033798A2 (en) | 1997-02-05 | 1998-08-06 | Warner Lambert Company | Pyrido[2,3-d]pyrimidines and 4-amino-pyrimidines as inhibitors of cell proliferation |
| CO4950519A1 (es) | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| EP0973778A1 (en) | 1997-03-07 | 2000-01-26 | Novo Nordisk A/S | 4,5,6,7-TETRAHYDRO-THIENO 3,2-c]PYRIDINE DERIVATIVES, THEIR PREPARATION AND USE |
| UY24949A1 (es) | 1997-04-08 | 2001-04-30 | Smithkline Beecham Corp | Compuestos calcilíticos |
| EP0975614A1 (en) | 1997-04-18 | 2000-02-02 | Smithkline Beecham Plc | A bicyclic aryl or a bicyclic heterocyclic ring containing compounds having a combined 5ht1a, 5ht1b and 5ht1d receptor antagonistic activity |
| 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 |
| DK1026950T3 (da) | 1997-10-27 | 2006-06-26 | Univ California | Behandling af skizofreni med ampakiner og neuroleptika |
| AU1804299A (en) | 1997-12-08 | 1999-06-28 | Glycomed Incorporated | Sialyl lewis x and sialyl lewis a glycomimetics |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| EP1140840B1 (en) | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| EP1165492A1 (en) | 1999-03-30 | 2002-01-02 | Pharmacor Inc. | Hydroxyphenyl derivatives with hiv integrase inhibitory properties |
| EP1169038B9 (en) | 1999-04-15 | 2013-07-10 | 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 |
| CZ20021428A3 (cs) | 1999-10-27 | 2002-11-13 | Cytokinetics, Inc. | Způsoby a kompozice vyuľívající chinazoliny |
| US6545004B1 (en) | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| KR100881105B1 (ko) | 1999-11-05 | 2009-02-02 | 아스트라제네카 아베 | Ｖｅｇｆ 억제제로서의 퀴나졸린 유도체 |
| 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 |
| US6677473B1 (en) | 1999-11-19 | 2004-01-13 | Corvas International Inc | Plasminogen activator inhibitor antagonists |
| 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 |
| WO2001064194A2 (en) | 2000-02-29 | 2001-09-07 | 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 |
| ATE310728T1 (de) * | 2000-05-11 | 2005-12-15 | Bristol Myers Squibb Co | Tetrahydroisochinolin-analoga als wachstumshormon-sekretagoga |
| US7229986B2 (en) * | 2000-05-16 | 2007-06-12 | Takeda Pharmaceutical Company Ltd. | Melanin-concentrating hormone antagonist |
| DE10024939A1 (de) | 2000-05-19 | 2001-11-29 | Bayer Ag | Neue Diphenylmethanderivate für Arzneimittel |
| CA2308994A1 (en) | 2000-05-19 | 2001-11-19 | Aegera Therapeutics Inc. | Neuroprotective compounds |
| 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 |
| AU2001273071B2 (en) | 2000-06-30 | 2005-09-08 | Glaxo Group Limited | 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 |
| DK1320531T3 (da) | 2000-08-10 | 2011-01-03 | Pfizer Italia Srl | Bicyclo-pyrazoler, der er aktive som kinase inhibitorer, fremgangsmåde til fremstilling deraf og farmaceutiske sammensætninger, der indeholder disse |
| SK2072003A3 (en) | 2000-08-25 | 2004-01-08 | Warner Lambert Co | Process for making N-aryl-anthranilic acids and their derivatives |
| DE60115069T2 (de) | 2000-09-11 | 2006-08-03 | Chiron Corp., Emeryville | Chinolinonderivate als tyrosin-kinase inhibitoren |
| 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 |
| JP4224566B2 (ja) | 2000-12-18 | 2009-02-18 | 株式会社医薬分子設計研究所 | 炎症性サイトカイン産生遊離抑制剤 |
| US6989385B2 (en) | 2000-12-21 | 2006-01-24 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| MXPA03005777A (es) | 2000-12-22 | 2005-02-14 | Johnson & Johnson | Derivados de triazol diaminas sustituidos como inhibidores de cinasa. |
| CA2440809A1 (en) | 2001-03-01 | 2002-09-12 | Conforma Therapeutics Corp. | Methods for treating genetically-defined proliferative disorders with hsp90 inhibitors |
| BR0209774A (pt) | 2001-05-29 | 2004-06-01 | Schering Ag | Pirimidinas inibidoras de cdk, sua preparação e aplicação como medicamento |
| AU2002330998A1 (en) | 2001-08-06 | 2003-02-24 | Kosan Biosciences, Inc. | Benzoquinone ansamycins |
| CA2460498A1 (en) | 2001-09-24 | 2003-04-03 | Conforma Therapeutics Corporation | Process for preparing 17-allyl amino geldanamycin (17-aag) and other ansamycins |
| WO2003051877A1 (en) | 2001-12-18 | 2003-06-26 | Bayer Corporation | 2-substituted pyrrolo[2.1-a]isoquinolines against cancer |
| CN1620294A (zh) | 2001-12-20 | 2005-05-25 | Osi药物公司 | 嘧啶a2b选择性拮抗剂化合物,它们的合成及用途 |
| ATE374753T1 (de) | 2001-12-21 | 2007-10-15 | Vernalis Cambridge Ltd | 3-(2,4)dihydroxyphenyl-4-phenylpyrazole und deren medizinische verwendung |
| 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 |
| AU2003223491A1 (en) | 2002-04-05 | 2003-10-27 | Nitromed, Inc. | Nitric oxide donors, compositions and methods of use |
| WO2003091255A1 (en) | 2002-04-26 | 2003-11-06 | Warner-Lambert Company Llc | Inhibitors of checkpoint kinases (wee1 and chk1) |
| 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 |
| CN1658854A (zh) | 2002-06-05 | 2005-08-24 | 株式会社医药分子设计研究所 | 免疫关联蛋白激酶抑制剂 |
| EP1512396A4 (en) | 2002-06-05 | 2008-12-31 | Inst Med Molecular Design Inc | HEMMER AGAINST ACTIVATION OF AP-1 AND NFAT |
| EA009701B1 (ru) | 2002-06-06 | 2008-02-28 | Инститьют Оф Медисинал Молекьюлар Дизайн. Инк. | Противоаллергические средства |
| 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 |
| WO2004007501A1 (en) | 2002-07-16 | 2004-01-22 | Amura Therapeutics Limited | Biologically active compounds |
| US6800655B2 (en) | 2002-08-20 | 2004-10-05 | Sri International | Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents |
| WO2004035571A1 (en) | 2002-10-15 | 2004-04-29 | 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 |
| SI1611112T1 (sl) | 2003-02-11 | 2012-12-31 | Vernalis (R&D) Limited | Izoksazolne spojine kot inhibitorji vroäśinskih ĺ ok proteinov |
| CA2514500A1 (en) * | 2003-02-20 | 2004-09-10 | University Of Connecticut Health Center | Methods for using compositions comprising heat shock proteins or alpha-2-macroglobulin in the treatment of cancer and infectious disease |
| MXPA05008878A (es) | 2003-02-21 | 2005-10-05 | Pfizer | Derivados de aminotiazol sustituidos con cicloalquilo que contiene n y composiciones farmaceuticas para inhibir la proliferacion celular, y metodos para su uso. |
| JP3876265B2 (ja) | 2003-02-26 | 2007-01-31 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | ジヒドロプテリジノン、その製造方法及び薬物形態での使用 |
| US7038038B2 (en) | 2003-03-17 | 2006-05-02 | Pharmion Corporation | Synthesis of 5-azacytidine |
| US6887855B2 (en) | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| US6943249B2 (en) | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| AU2004226586B2 (en) | 2003-04-03 | 2008-12-11 | Pfizer Inc. | Dosage forms comprising AG013736 |
| MXPA05011597A (es) | 2003-04-30 | 2005-12-15 | Novartis Ag | Derivados de aminopropanol como moduladores del receptor 1-fosfato de esfingosina. |
| AU2004251949B2 (en) | 2003-06-27 | 2009-05-07 | Kyowa Hakko Kirin Co., Ltd. | Hsp90 family protein inhibitors |
| GB0315111D0 (en) | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| 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 |
| US6989649B2 (en) * | 2003-07-09 | 2006-01-24 | A. O. Smith Corporation | Switch assembly, electric machine having the switch assembly, and method of controlling the same |
| 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 |
| DE602004027504D1 (de) | 2003-07-24 | 2010-07-15 | Leo Pharma As | Aminobenzophenonverbindungen |
| ATE403654T1 (de) | 2003-07-28 | 2008-08-15 | Janssen Pharmaceutica Nv | Benzimidazol-, benzothiazol- und benzoxazolderivate und deren verwendung als lta4h-modulatoren |
| 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 |
| WO2005023818A2 (en) | 2003-09-10 | 2005-03-17 | Gpc Biotech Ag | Heterobicyclic compounds as pharmaceutically active agents |
| JP4845736B2 (ja) | 2003-10-14 | 2011-12-28 | アリゾナ ボード オブ リージェンツ オン ビハーフ ザ ユニバーシティー オブ アリゾナ | プロテインキナーゼ阻害剤 |
| WO2005037214A2 (en) | 2003-10-14 | 2005-04-28 | Intermune, Inc. | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication |
| US20050209247A1 (en) | 2003-11-07 | 2005-09-22 | Chiron Corporation | Pharmaceutically acceptable salts of quinolinone compounds having improved pharmaceutical properties |
| KR20060123292A (ko) | 2003-11-10 | 2006-12-01 | 쉐링 악티엔게젤샤프트 | Ｃｃｒ-5 길항제로서 유용한 벤질에테르 아민 화합물 |
| CN101693031A (zh) | 2003-11-18 | 2010-04-14 | 诺瓦提斯公司 | Kit突变形式的抑制剂 |
| AU2004309395C1 (en) | 2003-12-23 | 2012-10-04 | Infinity Discovery, Inc. | Analogs of benzoquinone-containing ansamycins for the treatment of cancer |
| JPWO2005063222A1 (ja) | 2003-12-26 | 2007-07-19 | 協和醗酵工業株式会社 | Ｈｓｐ９０ファミリー蛋白質阻害剤 |
| US7652146B2 (en) | 2004-02-06 | 2010-01-26 | Bristol-Myers Squibb Company | Process for preparing 2-aminothiazole-5-carboxamides useful as kinase inhibitors |
| TWI338004B (en) | 2004-02-06 | 2011-03-01 | Bristol Myers Squibb Co | Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors |
| US20050256097A1 (en) | 2004-05-11 | 2005-11-17 | Kosan Biosciences, Inc. | Pharmaceutical solution formulations containing 17-AAG |
| AU2005243175B2 (en) | 2004-05-14 | 2011-12-01 | Millennium Pharmaceuticals, Inc. | Compounds and methods for inhibiting mitotic progression by inhibition of Aurora kinase |
| 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 |
| WO2006015123A1 (en) | 2004-07-27 | 2006-02-09 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| 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 |
| AU2005277223C1 (en) | 2004-08-20 | 2009-05-21 | The Regents Of The University Of Michigan | Small molecule inhibitors of anti-apoptotic Bcl-2 family members and the uses thereof |
| 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 |
| WO2006050333A2 (en) | 2004-11-02 | 2006-05-11 | The Regents Of The University Of California | Methods and compositions for modulating apoptosis |
| KR20070058689A (ko) | 2004-11-02 | 2007-06-08 | 화이자 인코포레이티드 | 인다졸 화합물의 제조 방법 |
| WO2006048746A2 (en) | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Methods for the removal of heavy metals |
| WO2006051808A1 (ja) | 2004-11-09 | 2006-05-18 | Kyowa Hakko Kogyo Co., Ltd. | Hsp90ファミリー蛋白質阻害剤 |
| EP1817295B1 (en) | 2004-11-18 | 2012-11-07 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| MX2007008008A (es) | 2004-12-30 | 2007-11-12 | Astex Therapeutics Ltd | Compuestos de pirazol que modulan la actividad de las cinasas cdk, gsk y aurora. |
| WO2006074416A1 (en) | 2005-01-07 | 2006-07-13 | Health Research Inc. | 5-amino-4-imidazolecarboxamide riboside and its nucleobase as potentiators of antifolate transport and metabolism |
| 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. |
| AR053662A1 (es) | 2005-01-21 | 2007-05-16 | Astex Therapeutics Ltd | Compuestos de pirazol inhibidores de la actividad quinasa cdk y gsk |
| DE602006010665D1 (en) * | 2005-02-07 | 2010-01-07 | Hoffmann La Roche | Heterocyclsche substituierte phenylmethanone als inhibitoren des glycintransporters 1 |
| US20060183902A1 (en) * | 2005-02-15 | 2006-08-17 | Baxter Ellen W | Dihydroindolyl methanones as alpha 1a/1d adrenoreceptor modulators for the treatment of benign prostatic hypertrophy and lower urinary tract symptoms |
| US20090042883A1 (en) | 2005-02-21 | 2009-02-12 | Kyowa Hakkokogyo Co. | Antitumor agent |
| JP5154406B2 (ja) * | 2005-04-13 | 2013-02-27 | 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 |
| JP2008540395A (ja) * | 2005-05-03 | 2008-11-20 | ファイザー・インク | アミドレソルシノール化合物 |
| DK2444079T3 (en) | 2005-05-17 | 2017-01-30 | Sarcode Bioscience Inc | Compositions and Methods for the Treatment of Eye Diseases |
| 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 |
| US7754725B2 (en) * | 2006-03-01 | 2010-07-13 | Astex Therapeutics Ltd. | Dihydroxyphenyl isoindolymethanones |
| WO2008044041A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| GB0620259D0 (en) | 2006-10-12 | 2006-11-22 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| EP2073807A1 (en) | 2006-10-12 | 2009-07-01 | Astex Therapeutics Limited | Pharmaceutical combinations |
| EP2073802A1 (en) | 2006-10-12 | 2009-07-01 | Astex Therapeutics Limited | Pharmaceutical combinations |
| 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 |
| WO2008053319A1 (en) | 2006-10-30 | 2008-05-08 | Pfizer Products Inc. | Amide resorcinol compounds |
| US20090019958A1 (en) * | 2007-07-20 | 2009-01-22 | Craig Howard Zeyher | Planetary gyroscopic drive system with transmission |
-
2007
- 2007-10-12 WO PCT/GB2007/003879 patent/WO2008044041A1/en not_active Ceased
- 2007-10-12 EP EP07824133.8A patent/EP2073803B1/en not_active Not-in-force
- 2007-10-12 US US12/445,180 patent/US8916552B2/en not_active Expired - Fee Related
- 2007-10-12 JP JP2009531917A patent/JP5528806B2/ja not_active Expired - Fee Related
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