JP2010505928A5 - - Google Patents
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- Publication number
- JP2010505928A5 JP2010505928A5 JP2009531913A JP2009531913A JP2010505928A5 JP 2010505928 A5 JP2010505928 A5 JP 2010505928A5 JP 2009531913 A JP2009531913 A JP 2009531913A JP 2009531913 A JP2009531913 A JP 2009531913A JP 2010505928 A5 JP2010505928 A5 JP 2010505928A5
- 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 148
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 31
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 31
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 31
- 241000124008 Mammalia Species 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- -1 NR c Inorganic materials 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 230000002159 abnormal effect Effects 0.000 claims description 18
- 125000002837 carbocyclic group Chemical group 0.000 claims description 18
- 208000024891 symptom Diseases 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 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
- 230000004663 cell proliferation Effects 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 150000001204 N-oxides Chemical class 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 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
- 239000003937 drug carrier Substances 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
- 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
- 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
- 230000027455 binding Effects 0.000 claims description 3
- 230000032823 cell division Effects 0.000 claims description 3
- 230000033077 cellular process Effects 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
- 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
- KJBMWHODWAFZCN-UHFFFAOYSA-N (5-chloro-2-hydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound OC1=CC=C(Cl)C=C1C(=O)N1CC2=CC=CC=C2C1 KJBMWHODWAFZCN-UHFFFAOYSA-N 0.000 claims description 2
- JQSCFWZZAQFLTE-UHFFFAOYSA-N (5-chloro-6-hydroxy-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)=C(O)C=C3C2)=C1O JQSCFWZZAQFLTE-UHFFFAOYSA-N 0.000 claims description 2
- OUHQXCXLZQKCKS-UHFFFAOYSA-N (5-chloro-6-methoxy-1,3-dihydroisoindol-2-yl)-(2,4-dihydroxy-5-propan-2-ylphenyl)methanone Chemical compound C1C=2C=C(Cl)C(OC)=CC=2CN1C(=O)C1=CC(C(C)C)=C(O)C=C1O OUHQXCXLZQKCKS-UHFFFAOYSA-N 0.000 claims description 2
- OHYDZLGYBUJAFY-UHFFFAOYSA-N (5-cyclopropyl-2,4-dihydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound OC1=CC(O)=C(C(=O)N2CC3=CC=CC=C3C2)C=C1C1CC1 OHYDZLGYBUJAFY-UHFFFAOYSA-N 0.000 claims description 2
- FUNJEJVGXFUOOI-UHFFFAOYSA-N (5-tert-butyl-2,4-dihydroxyphenyl)-(1,3-dihydroisoindol-2-yl)methanone Chemical compound C1=C(O)C(C(C)(C)C)=CC(C(=O)N2CC3=CC=CC=C3C2)=C1O FUNJEJVGXFUOOI-UHFFFAOYSA-N 0.000 claims description 2
- DPKGPEGXWFTAIR-UHFFFAOYSA-N 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=CC=C3C2)=C1O DPKGPEGXWFTAIR-UHFFFAOYSA-N 0.000 claims description 2
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| WO2010018481A1 (en) | 2008-08-13 | 2010-02-18 | Pfizer Inc. | 2-amino pyrimidine compounds as potent hsp-90 inhibitors |
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| HRP20240056T1 (hr) | 2012-03-20 | 2024-03-29 | Eagle Pharmaceuticals, Inc. | Formulacije bendamustina |
| US20140079636A1 (en) | 2012-04-16 | 2014-03-20 | Dinesh U. Chimmanamada | Targeted therapeutics |
| CN104812898B (zh) | 2012-05-25 | 2018-01-30 | 博格有限责任公司 | 通过调节热休克蛋白质(HSP)90‑β治疗代谢综合征的方法 |
| AU2014251038A1 (en) | 2013-04-08 | 2015-11-26 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| AU2014293013A1 (en) | 2013-07-26 | 2016-03-17 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
| AU2014318826B2 (en) | 2013-09-10 | 2019-10-10 | Madrigal Pharmaceuticals, Inc. | Targeted therapeutics |
| WO2015066053A2 (en) | 2013-10-28 | 2015-05-07 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| WO2015116774A1 (en) | 2014-01-29 | 2015-08-06 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| KR102408261B1 (ko) | 2014-02-03 | 2022-06-10 | 비타이 파마슈티컬즈, 엘엘씨 | Ror-감마의 디하이드로피롤로피리딘 저해제 |
| US11039620B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| US9622483B2 (en) | 2014-02-19 | 2017-04-18 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| US11039621B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| AU2015224576A1 (en) | 2014-03-03 | 2016-09-22 | Madrigal Pharmaceuticals, Inc. | Targeted therapeutics |
| MA39483A (fr) | 2014-03-18 | 2015-09-24 | Synta Pharmaceuticals Corp | Agents thérapeutiques cibles |
| EP3119398A1 (en) * | 2014-03-20 | 2017-01-25 | Otsuka Pharmaceutical Co., Ltd. | Pharmaceutical formulation comprising a substitued phenyl- (1, 3-dihydro-isoindol-2-yl) -methanone |
| SG11201608303QA (en) | 2014-04-04 | 2016-11-29 | Del Mar Pharmaceuticals | Use of dianhydrogalactitol and analogs or derivatives thereof to treat non-small-cell carcinoma of the lung and ovarian cancer |
| WO2015188198A2 (en) | 2014-06-06 | 2015-12-10 | Berg Llc | Methods of treating a metabolic syndrome by modulating heat shock protein (hsp) 90-beta |
| UA118989C2 (uk) | 2014-10-14 | 2019-04-10 | Вітае Фармасьютікалс, Інк. | Дигідропіролопіридинові інгібітори ror-гамма |
| US9845308B2 (en) | 2014-11-05 | 2017-12-19 | Vitae Pharmaceuticals, Inc. | Isoindoline inhibitors of ROR-gamma |
| US9663515B2 (en) | 2014-11-05 | 2017-05-30 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| EP3331876B1 (en) | 2015-08-05 | 2020-10-07 | Vitae Pharmaceuticals, LLC | Modulators of ror-gamma |
| EP3364976A4 (en) | 2015-10-19 | 2019-06-05 | Board of Regents, The University of Texas System | PIPERAZINYL-NORBENZOMORPHAN COMPOUNDS AND METHOD FOR USE THEREOF |
| KR20180086221A (ko) | 2015-11-20 | 2018-07-30 | 비타이 파마슈티컬즈, 인코포레이티드 | Ror-감마의 조절물질 |
| 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 |
| CA3022512A1 (en) * | 2016-04-29 | 2017-11-02 | Board Of Regents, The University Of Texas System | Sigma receptor binders |
| US9481674B1 (en) | 2016-06-10 | 2016-11-01 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| KR20200016875A (ko) | 2017-06-20 | 2020-02-17 | 마드리갈 파마슈티칼스 인코포레이티드 | 표적화 치료제 |
| AU2018289349A1 (en) | 2017-06-20 | 2020-01-02 | Madrigal Pharmaceuticals, Inc. | Combination therapies comprising targeted therapeutics |
| IL298639A (en) | 2017-07-24 | 2023-01-01 | Vitae Pharmaceuticals Llc | Inhibitors of gamma ror |
| WO2019018975A1 (en) | 2017-07-24 | 2019-01-31 | Vitae Pharmaceuticals, Inc. | INHIBITORS OF ROR GAMMA |
| CA3232086A1 (en) * | 2021-10-15 | 2023-04-20 | Peter Jarrett | Prodrugs of axitinib |
Family Cites Families (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4910506A (enExample) | 1972-05-31 | 1974-01-30 | ||
| US4582909A (en) | 1984-02-02 | 1986-04-15 | Warner-Lambert Company | Benzobicyclic lactam acids and derivatives as cognition activators |
| US4760064A (en) | 1984-12-18 | 1988-07-26 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril compounds, compositions containing same and processes for preparing same |
| 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 |
| GB8926560D0 (en) | 1989-11-24 | 1990-01-17 | Zambeletti Spa L | Pharmaceuticals |
| US5124350A (en) | 1990-06-28 | 1992-06-23 | G. D. Searle & Co. | Leukotriene b4 antagonists |
| CA2049481A1 (en) | 1990-08-27 | 1992-02-28 | Jill Ann Panetta | Method of treating inflammatory bowel disease |
| 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. |
| 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 |
| US5633283A (en) | 1995-01-23 | 1997-05-27 | Eli Lilly And Company | Method for treating multiple sclerosis |
| 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 |
| EP0883403B1 (en) | 1996-01-29 | 2010-08-25 | The Regents of The University of California | Method for treating sexual dysfunctions |
| GB9606187D0 (en) | 1996-03-23 | 1996-05-29 | Inst Of Food Research | Production of vanillin |
| AU715658B2 (en) | 1996-04-03 | 2000-02-10 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| CA2250856A1 (en) | 1996-04-19 | 1997-10-30 | The Regents Of The University Of California | Treatment of mood/affective disorders by glutamatergic upmodulators |
| IL118657A0 (en) | 1996-06-14 | 1996-10-16 | Arad Dorit | Inhibitors for picornavirus proteases |
| WO1998040385A1 (en) | 1997-03-07 | 1998-09-17 | 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 |
| 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 |
| BR9814106A (pt) | 1997-10-27 | 2000-10-03 | Cortex Pharma Inc | Processo para tratar da esquizofrenia em um indivìduo, e, conjunto |
| AU1804299A (en) | 1997-12-08 | 1999-06-28 | Glycomed Incorporated | Sialyl lewis x and sialyl lewis a glycomimetics |
| EP1165492A1 (en) | 1999-03-30 | 2002-01-02 | Pharmacor Inc. | Hydroxyphenyl derivatives with hiv integrase inhibitory properties |
| 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 |
| WO2001060369A1 (en) | 2000-02-18 | 2001-08-23 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| ATE310728T1 (de) | 2000-05-11 | 2005-12-15 | Bristol Myers Squibb Co | Tetrahydroisochinolin-analoga als wachstumshormon-sekretagoga |
| EP1283199A4 (en) | 2000-05-16 | 2003-12-17 | Takeda Chemical Industries Ltd | MELANINE CONCENTRATING HORMONE ANTAGONISTS |
| 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 |
| 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 |
| BR0113520A (pt) | 2000-08-25 | 2003-06-24 | Warner Lambert Co | Processo de preparação de ácidos n-aril-antranìlicos e seus derivados |
| UA82827C2 (en) | 2000-12-18 | 2008-05-26 | Inhibitors against the production and release of inflammatory cytokines | |
| AU2002366362A1 (en) | 2001-12-18 | 2003-06-30 | Bayer Aktiengesellschaft | 2-substituted pyrrolo(2.1-a)isoquinolines against cancer |
| BR0215202A (pt) | 2001-12-20 | 2004-10-13 | Osi Pharm Inc | Compostos antagonistas seletivos a2b de pirimidina, sua sìntese e uso |
| 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 |
| US20030203915A1 (en) | 2002-04-05 | 2003-10-30 | Xinqin Fang | Nitric oxide donors, compositions and methods of use related applications |
| TWI280876B (en) | 2002-06-05 | 2007-05-11 | Inst Med Molecular Design Inc | Therapeutic drug for diabetes |
| AU2003242131A1 (en) | 2002-06-05 | 2003-12-22 | Institute Of Medicinal Molecular Design, Inc. | Immunity-related protein kinase inhibitors |
| CA2487891A1 (en) | 2002-06-05 | 2003-12-18 | Institute Of Medicinal Molecular Design, Inc. | Inhibitors against the activation of ap-1 and nfat |
| 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 |
| SE0202133D0 (sv) | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| AU2003255711B2 (en) | 2002-07-16 | 2008-11-13 | Amura Therapeutics Limited | Biologically active compounds |
| WO2004035571A1 (en) | 2002-10-15 | 2004-04-29 | Rigel Pharmaceuticals, Inc. | Substituted indoles and their use as hcv inhibitors |
| 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 |
| JP2006514088A (ja) | 2003-02-20 | 2006-04-27 | ユニバーシティー オブ コネティカット ヘルス センター | 癌および感染症の治療における熱ショックタンパク質またはα−２−マクログロブリンを含む組成物の使用方法 |
| WO2004074283A1 (en) | 2003-02-21 | 2004-09-02 | Pfizer Inc. | N-heterocyclyl-substituted amino-thiazole derivatives as protein kinase inhibitors |
| BRPI0409977A (pt) | 2003-04-30 | 2006-05-09 | Novartis Ag | derivados de aminopropanol como moduladores de receptores esfingosina-1-fosfato |
| GB0315111D0 (en) | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| CA2530374C (en) | 2003-06-27 | 2012-05-15 | Kyowa Hakko Kogyo Co., Ltd. | Hsp90 family protein inhibitors |
| TWI312345B (en) | 2003-06-30 | 2009-07-21 | Mitsubishi Tanabe Pharma Corp | Process of preparating 3-acylaminobenzofuran-2-carboxylic acid derivatives |
| CN100406006C (zh) | 2003-07-16 | 2008-07-30 | 株式会社医药分子设计研究所 | 皮肤色素沉着的治疗剂 |
| WO2005009940A1 (en) | 2003-07-24 | 2005-02-03 | Leo Pharma A/S | Novel aminobenzophenone compounds |
| CN100591679C (zh) | 2003-07-28 | 2010-02-24 | 詹森药业有限公司 | 苯并咪唑、苯并噻唑和苯并唑衍生物及其作为lta4h调节剂的应用 |
| 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 |
| EP1670804A2 (en) | 2003-09-10 | 2006-06-21 | GPC Biotech AG | Heterobicyclic compounds as pharmaceutically active agents |
| JP2007513082A (ja) | 2003-11-10 | 2007-05-24 | シエーリング アクチエンゲゼルシャフト | Ｃｃｒ−５アンタゴニストとして有用なベンジルエーテルアミン化合物 |
| WO2005063222A1 (ja) | 2003-12-26 | 2005-07-14 | Kyowa Hakko Kogyo Co., Ltd. | Hsp90ファミリー蛋白質阻害剤 |
| US7351709B2 (en) | 2004-06-09 | 2008-04-01 | Wyeth | Estrogen receptor ligands |
| EP1781654A1 (en) | 2004-07-27 | 2007-05-09 | SGX Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| 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 |
| 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 |
| EP1813270A4 (en) | 2004-11-09 | 2009-07-01 | Kyowa Hakko Kirin Co Ltd | PROTEIN INHIBITORS OF THE HSP90 FAMILY |
| DK1848694T3 (da) | 2005-02-07 | 2010-01-25 | Hoffmann La Roche | Heterocykliske substituerede phenylmethanoner som inhibitorer af glycintransporter |
| 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 |
| ES2523565T3 (es) | 2005-04-13 | 2014-11-27 | Astex Therapeutics Limited | Derivados de hidroxibenzamida y sus usos como inhibidores de la hsp90 |
| US20090215742A1 (en) | 2005-05-03 | 2009-08-27 | Pfizer, Inc. | Amide resorcinol compounds |
| 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 |
-
2007
- 2007-10-12 WO PCT/GB2007/003864 patent/WO2008044029A1/en not_active Ceased
- 2007-10-12 EP EP07824118A patent/EP2073802A1/en not_active Withdrawn
- 2007-10-12 JP JP2009531913A patent/JP5721949B2/ja active Active
- 2007-10-12 US US12/445,141 patent/US8277807B2/en not_active Expired - Fee Related
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