JP4243628B2 - 治療剤としてのヒドロキサメート - Google Patents
治療剤としてのヒドロキサメート Download PDFInfo
- Publication number
- JP4243628B2 JP4243628B2 JP2006509735A JP2006509735A JP4243628B2 JP 4243628 B2 JP4243628 B2 JP 4243628B2 JP 2006509735 A JP2006509735 A JP 2006509735A JP 2006509735 A JP2006509735 A JP 2006509735A JP 4243628 B2 JP4243628 B2 JP 4243628B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- benzamide
- ethoxy
- ylcarbonylamino
- benzofuran
- 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.)
- Expired - Lifetime
Links
- 239000003814 drug Substances 0.000 title description 17
- 229940124597 therapeutic agent Drugs 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 497
- -1 aralkenyl Chemical group 0.000 claims description 634
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 224
- 125000000217 alkyl group Chemical group 0.000 claims description 104
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
- 125000001072 heteroaryl group Chemical group 0.000 claims description 73
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 48
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 41
- 125000001188 haloalkyl group Chemical group 0.000 claims description 39
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 31
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 30
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 30
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 26
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 23
- 125000002947 alkylene group Chemical group 0.000 claims description 21
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 18
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 12
- DSIBSRXKQRYPJP-UHFFFAOYSA-N 1,2-oxazole-5-carboxamide Chemical compound NC(=O)C1=CC=NO1 DSIBSRXKQRYPJP-UHFFFAOYSA-N 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000004660 phenylalkylthio group Chemical group 0.000 claims description 8
- 125000006345 2,2,2-trifluoroethoxymethyl group Chemical group [H]C([H])(*)OC([H])([H])C(F)(F)F 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- GXOFMHYSDHBUFQ-UHFFFAOYSA-N 4-(2-benzamidoethoxy)-n-hydroxybenzamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC=CC=C1 GXOFMHYSDHBUFQ-UHFFFAOYSA-N 0.000 claims description 3
- GUYCSHUDCXKIOO-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC=CC=C2O1 GUYCSHUDCXKIOO-UHFFFAOYSA-N 0.000 claims description 3
- CNSOVOBKISGHJM-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzothiophene-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC=CC=C2S1 CNSOVOBKISGHJM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- WQNMNXAAZGGIHS-UHFFFAOYSA-N 3-(diethylaminomethyl)-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(CN(CC)CC)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 WQNMNXAAZGGIHS-UHFFFAOYSA-N 0.000 claims description 2
- SPCMUBFTADOPCN-UHFFFAOYSA-N 3-[(2-fluorophenoxy)methyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(COC=2C(=CC=CC=2)F)C2=CC=CC=C2O1 SPCMUBFTADOPCN-UHFFFAOYSA-N 0.000 claims description 2
- ZOGHSHODVZFVMT-UHFFFAOYSA-N 3-[(3-fluorophenoxy)methyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(COC=2C=C(F)C=CC=2)C2=CC=CC=C2O1 ZOGHSHODVZFVMT-UHFFFAOYSA-N 0.000 claims description 2
- CBBDSQMDJTUDIZ-UHFFFAOYSA-N 3-[(4-fluorophenoxy)methyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(COC=2C=CC(F)=CC=2)C2=CC=CC=C2O1 CBBDSQMDJTUDIZ-UHFFFAOYSA-N 0.000 claims description 2
- TWPNXPWOFUGHMH-UHFFFAOYSA-N 3-[(4-fluorophenyl)sulfanylmethyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(CSC=2C=CC(F)=CC=2)C2=CC=CC=C2O1 TWPNXPWOFUGHMH-UHFFFAOYSA-N 0.000 claims description 2
- CPSKDJNEHCHIIK-UHFFFAOYSA-N 3-[(4-fluorophenyl)sulfinylmethyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(CS(=O)C=2C=CC(F)=CC=2)C2=CC=CC=C2O1 CPSKDJNEHCHIIK-UHFFFAOYSA-N 0.000 claims description 2
- CWUMLIHCNDIGAW-UHFFFAOYSA-N 3-[(4-fluorophenyl)sulfonylmethyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(CS(=O)(=O)C=2C=CC(F)=CC=2)C2=CC=CC=C2O1 CWUMLIHCNDIGAW-UHFFFAOYSA-N 0.000 claims description 2
- MAUCONCHVWBMHK-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide Chemical compound O1C2=CC=CC=C2C(CN(C)C)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 MAUCONCHVWBMHK-UHFFFAOYSA-N 0.000 claims description 2
- LHTGSOKWKKDJTK-UHFFFAOYSA-N 3-chloro-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzothiophene-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(Cl)C2=CC=CC=C2S1 LHTGSOKWKKDJTK-UHFFFAOYSA-N 0.000 claims description 2
- QKJUPULAJQGBPV-UHFFFAOYSA-N 3-ethyl-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(CC)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 QKJUPULAJQGBPV-UHFFFAOYSA-N 0.000 claims description 2
- DISACWVFSPDPOV-UHFFFAOYSA-N 5-[4-(dimethylamino)phenyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]pyridine-3-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1C1=CN=CC(C(=O)NCCOC=2C=CC(=CC=2)C(=O)NO)=C1 DISACWVFSPDPOV-UHFFFAOYSA-N 0.000 claims description 2
- UZVIOYRAHHQIIX-UHFFFAOYSA-N 5-chloro-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(Cl)=CC=C2O1 UZVIOYRAHHQIIX-UHFFFAOYSA-N 0.000 claims description 2
- SGIBRTOPUZCDIT-UHFFFAOYSA-N 5-fluoro-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzothiophene-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(F)=CC=C2S1 SGIBRTOPUZCDIT-UHFFFAOYSA-N 0.000 claims description 2
- IGDCPMOWUIGWMK-UHFFFAOYSA-N 5-fluoro-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1h-indole-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(F)=CC=C2N1 IGDCPMOWUIGWMK-UHFFFAOYSA-N 0.000 claims description 2
- KJVCSKFLSHMYRN-UHFFFAOYSA-N 6-(4-acetamidophenoxy)-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]pyridine-2-carboxamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1=CC=CC(C(=O)NCCOC=2C=CC(=CC=2)C(=O)NO)=N1 KJVCSKFLSHMYRN-UHFFFAOYSA-N 0.000 claims description 2
- ARGQVIRZWCBQDN-UHFFFAOYSA-N 6-fluoro-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-2-methyl-3,4-dihydro-2h-quinoline-1-carboxamide Chemical compound CC1CCC2=CC(F)=CC=C2N1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 ARGQVIRZWCBQDN-UHFFFAOYSA-N 0.000 claims description 2
- RFGQHRWJEYIGQL-UHFFFAOYSA-N 7-[(dimethylamino)methyl]-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide Chemical compound O1C=2C(CN(C)C)=CC=CC=2C=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 RFGQHRWJEYIGQL-UHFFFAOYSA-N 0.000 claims description 2
- MGASVJKARQUVMG-UHFFFAOYSA-N 7-fluoro-n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-4-(phenoxymethyl)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C(OC1=C(F)C=C2)=CC1=C2COC1=CC=CC=C1 MGASVJKARQUVMG-UHFFFAOYSA-N 0.000 claims description 2
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
- IKNRXNNRYAUAPH-GFCCVEGCSA-N n-[(2r)-1-[4-(hydroxycarbamoyl)phenoxy]propan-2-yl]-1-benzothiophene-2-carboxamide Chemical compound C([C@@H](C)NC(=O)C=1SC2=CC=CC=C2C=1)OC1=CC=C(C(=O)NO)C=C1 IKNRXNNRYAUAPH-GFCCVEGCSA-N 0.000 claims description 2
- DGMQBDGIHQCENK-GFCCVEGCSA-N n-[(2r)-2-[4-(hydroxycarbamoyl)phenoxy]propyl]-1-benzofuran-2-carboxamide Chemical compound O([C@@H](CNC(=O)C=1OC2=CC=CC=C2C=1)C)C1=CC=C(C(=O)NO)C=C1 DGMQBDGIHQCENK-GFCCVEGCSA-N 0.000 claims description 2
- GNYSGYIKVGOQKB-GFCCVEGCSA-N n-[(2r)-2-[4-(hydroxycarbamoyl)phenoxy]propyl]-1-benzothiophene-2-carboxamide Chemical compound O([C@@H](CNC(=O)C=1SC2=CC=CC=C2C=1)C)C1=CC=C(C(=O)NO)C=C1 GNYSGYIKVGOQKB-GFCCVEGCSA-N 0.000 claims description 2
- YKTPNMTYLBLHDF-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-methylindole-2-carboxamide Chemical compound C=1C2=CC=CC=C2N(C)C=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 YKTPNMTYLBLHDF-UHFFFAOYSA-N 0.000 claims description 2
- QIAJBUWBUHPYNI-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1h-indole-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC=CC=C2N1 QIAJBUWBUHPYNI-UHFFFAOYSA-N 0.000 claims description 2
- BIQDGQTWPYIISV-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-(2-methoxyethoxymethyl)-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(COCCOC)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 BIQDGQTWPYIISV-UHFFFAOYSA-N 0.000 claims description 2
- URORAPDNVOXUNV-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-(3-hydroxypropoxymethyl)-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(COCCCO)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 URORAPDNVOXUNV-UHFFFAOYSA-N 0.000 claims description 2
- YXTWTFJVNNXBFR-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-(morpholin-4-ylmethyl)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(CN2CCOCC2)C2=CC=CC=C2O1 YXTWTFJVNNXBFR-UHFFFAOYSA-N 0.000 claims description 2
- YNYRFHRGWUGTIU-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-(pyridin-4-yloxymethyl)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(COC=2C=CN=CC=2)C2=CC=CC=C2O1 YNYRFHRGWUGTIU-UHFFFAOYSA-N 0.000 claims description 2
- BEXWSUXJRSGRJN-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-[(2-oxopyridin-1-yl)methyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=C(CN2C(C=CC=C2)=O)C2=CC=CC=C2O1 BEXWSUXJRSGRJN-UHFFFAOYSA-N 0.000 claims description 2
- QGWRXFKSRBXFDE-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-methyl-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(C)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 QGWRXFKSRBXFDE-UHFFFAOYSA-N 0.000 claims description 2
- AFYNUTNBQQXGOK-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-3-methyl-1-benzothiophene-2-carboxamide Chemical compound S1C2=CC=CC=C2C(C)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 AFYNUTNBQQXGOK-UHFFFAOYSA-N 0.000 claims description 2
- TXFURINEOMPIIK-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-4-(3,3,3-trifluoropropoxy)quinoline-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC(OCCC(F)(F)F)=C(C=CC=C2)C2=N1 TXFURINEOMPIIK-UHFFFAOYSA-N 0.000 claims description 2
- OVNPHDQHHWAYEZ-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-4-(trifluoromethyl)-1-benzothiophene-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=C(C(F)(F)F)C=CC=C2S1 OVNPHDQHHWAYEZ-UHFFFAOYSA-N 0.000 claims description 2
- NBIDEDQYPJCKHE-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-5-yl]benzamide Chemical compound C1CN(C)CCN1C1=NC=C(C=2C=CC(=CC=2)C(=O)NCCOC=2C=CC(=CC=2)C(=O)NO)S1 NBIDEDQYPJCKHE-UHFFFAOYSA-N 0.000 claims description 2
- XENSCEKVLVTGFX-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-4-[2-(pyridin-4-ylamino)-1,3-thiazol-5-yl]benzamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC=C(C=2SC(NC=3C=CN=CC=3)=NC=2)C=C1 XENSCEKVLVTGFX-UHFFFAOYSA-N 0.000 claims description 2
- XABGSWLFDQCEED-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-4-[4-(morpholin-4-ylmethyl)-1,3-thiazol-5-yl]benzamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC=C(C2=C(N=CS2)CN2CCOCC2)C=C1 XABGSWLFDQCEED-UHFFFAOYSA-N 0.000 claims description 2
- ZBNQLIAVQGXXKM-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5,6-dimethoxy-1h-indole-2-carboxamide Chemical compound N1C=2C=C(OC)C(OC)=CC=2C=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 ZBNQLIAVQGXXKM-UHFFFAOYSA-N 0.000 claims description 2
- AJQXZWBVDWICFR-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-(2,2,2-trifluoroethoxy)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(OCC(F)(F)F)=CC=C2O1 AJQXZWBVDWICFR-UHFFFAOYSA-N 0.000 claims description 2
- HPROQNZHCAGZBE-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-(2-methoxyethoxy)-1-benzofuran-2-carboxamide Chemical compound C=1C2=CC(OCCOC)=CC=C2OC=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 HPROQNZHCAGZBE-UHFFFAOYSA-N 0.000 claims description 2
- QVLAIXIUJXAFAP-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(OCCN3CCOCC3)=CC=C2O1 QVLAIXIUJXAFAP-UHFFFAOYSA-N 0.000 claims description 2
- VMHAHWMKQDRASA-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-(oxan-4-yloxy)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(OC3CCOCC3)=CC=C2O1 VMHAHWMKQDRASA-UHFFFAOYSA-N 0.000 claims description 2
- HSDJRSDTOVISHL-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-(pyridin-3-ylmethoxy)-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(OCC=3C=NC=CC=3)=CC=C2O1 HSDJRSDTOVISHL-UHFFFAOYSA-N 0.000 claims description 2
- LUQULKOGXFUUKL-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-methoxy-1-benzofuran-2-carboxamide Chemical compound C=1C2=CC(OC)=CC=C2OC=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 LUQULKOGXFUUKL-UHFFFAOYSA-N 0.000 claims description 2
- WRIKQNZZNFHGNM-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-methoxy-1-benzothiophene-2-carboxamide Chemical compound C=1C2=CC(OC)=CC=C2SC=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 WRIKQNZZNFHGNM-UHFFFAOYSA-N 0.000 claims description 2
- AJKLQZFBULFAIG-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-methoxy-1h-indole-2-carboxamide Chemical compound C=1C2=CC(OC)=CC=C2NC=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 AJKLQZFBULFAIG-UHFFFAOYSA-N 0.000 claims description 2
- OIRUXNYCKRTXQK-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-methyl-1-benzofuran-2-carboxamide Chemical compound C=1C2=CC(C)=CC=C2OC=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 OIRUXNYCKRTXQK-UHFFFAOYSA-N 0.000 claims description 2
- HBNDSYLZWKDTCY-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-methyl-1-benzothiophene-2-carboxamide Chemical compound C=1C2=CC(C)=CC=C2SC=1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 HBNDSYLZWKDTCY-UHFFFAOYSA-N 0.000 claims description 2
- MQTDQDAELMSCOS-UHFFFAOYSA-N n-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-5-piperidin-4-yloxy-1-benzofuran-2-carboxamide Chemical compound C1=CC(C(=O)NO)=CC=C1OCCNC(=O)C1=CC2=CC(OC3CCNCC3)=CC=C2O1 MQTDQDAELMSCOS-UHFFFAOYSA-N 0.000 claims description 2
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07—ORGANIC CHEMISTRY
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Description
本発明は、C型肝炎の治療において有用である所定のヒドロキサメート誘導体に関する。これらの化合物は、ヒストンデアセチラーゼの阻害物質でもあり、従ってヒストンデアセチラーゼ活性に関連した疾患の治療において有用である。これらの化合物を調製するための医薬組成物及び方法が開示されている。
C型肝炎:
慢性C型肝炎は、疾病率及び死亡率に対して有意な影響を有する序々に進行する疾患である。C型肝炎にかかる患者の多くは、サブクリニカル(sub clinical)又は穏和な疾患を有する一方で、HCVにかかる個体の80%以上が慢性感染症を発症する。これらの20〜50%は最終的に肝硬変へと進みそして1〜2%が肝がんを発症する (Hoofnagle, J. H.; 1997 ; Hepatology 26: 15S-20S)。世界中で1億7000万人のHCVキャリアがおり、そしてHCVに関連した最終段階の肝臓疾病は今や肝臓移植につながる原因の1つである。米国単独で、C型肝炎は年間8,000〜10,000の死亡原因である。
医薬開発のためのターゲットとしてのヒストンデアセチラーゼ酵素(HDAC)における注目が、細胞周期進行及び進展及びガンの進行に関連した遺伝子を調節することにおいて、HDACの役割の中心をなしている(Kramerらのレビュー. 2001.Trends Endocrinol. Metab. vol.12:pp.294〜300)。複数の研究により、様々な細胞系統をHDAC阻害物質で処理することによりヒストンタンパク質の超アセチル化がもたらされそして細胞周期をG1晩期において又はG2M転移期でとめることが示されている。この細胞周期に関わりHDAC阻害物質によってアップレギュレーションされることが示されている遺伝子としては、p21、p27、p53 及びサイクリンEが挙げられる。サイクリンA及びサイクリンDは、HDAC阻害物質によってダウンレギュレーションされることが報じられている。いくつかの研究により、腫瘍細胞系統において、HDAC阻害物質により処理することで増殖阻害、増殖停止、最終分化及び/又はアポトーシスにつながりうることが示されてきた。In vivo研究により、HDAC阻害物質による処理の結果として、腫瘍の増殖阻害及び腫瘍転移の減少が証明されている。
最初の観点において、本発明は式(I) :
R1は水素又はアルキルであり;
Xは-O-、-NR2-、又は-S(O)n-であり、ここでnは0〜2でありそしてR2は水素又はアルキルであり;
Yは、シクロアルキル、任意に置換されたフェニル、アルキルチオ、アルキルスルフィニル、アルキルスルホニル、任意に置換されたフェニルアルキルチオ、任意に置換されたフェニルアルキルスルホニル、ヒドロキシ、又は任意に置換されたフェノキシにより任意に置換されたアルキレンであり;
Ar1はフェニレン又はヘテロアリーレンであり、ここで前記Ar1はアルキル、ハロ、ヒドロキシ、アルコキシ、ハロアルコキシ、又はハロアルキルから独立して選択された1又は2個の基で任意に置換されており;
R3は、水素、アルキル、ヒドロキシアルキル、又は任意に置換されたフェニルであり;そして
Ar2はアリール、アラルキル、アラルケニル、ヘテロアリール、ヘテロアラルキル、ヘテロアラルケニル、シクロアルキル、シクロアルキルアルキル、ヘテロシクロアルキル、又はヘテロシクロアルキルアルキルである)
の化合物;又は
医薬的に許容できるその塩を含んで成る。
(i)式(III):
と式NH2OR"(式中、R"は水素、アルキル、又は酸素保護基である)を有するヒドロキシルアミンを反応させる;又は
(ii)式(IV):
の化合物を酸と反応させ;しかる後にNH2OR"(式中、R"は水素、アルキル、又は酸素保護基である)により処理し;式(V):
(iii)任意に化合物(V)中のR"基を除去し式(I)(式中、R1は水素である)を与え;
(iv)任意に上記段階(i)、(ii)、又は(iii)において形成された産物の酸付加塩を形成させ;
(v)任意に上記段階(i)、(ii)、(iii)、又は(iv)において形成された産物の遊離塩基を形成させる;又は
(vi)任意に上記段階(i)、(ii)、(iii)、(iv)又は(v)において形成された産物中のX、Y、R1、R2、R3、Ar1及びAr2基のいずれかを修飾すること、
を含んで成る。
定義:
他に規定されない限り、本明細書中及び特許請求の範囲において使用されている下の用語は、本願の目的を規定しており、次のような意味を有する。
(1)疾患を予防すること、即ち、当該疾患の臨床症状を、当該疾患に曝された又はかかりやすい哺乳動物において生じさせないことだけならず当該疾患の症状を受けない又は示さないようにすること;
(2)疾患を阻害すること、即ち、疾患又はその臨床症状の進行を止める又は抑制することを;又は
(3)疾患を軽減すること、即ち、疾患又はその臨床症状を衰退させることを意味する。
N-ヒドロキシ-4-(2-ベンゼンカルボニルアミノ-エトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-トランス-シンナモイルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-トランス-2-フェニルシクロプロピルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-トランス-4-メトキシシンナモイルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(2-フェニルエチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-3-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-(2-チオフェン-2-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-ピリジン-3-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-ビフェン-4-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-ビフェン-3-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(5-フェニルチオフェン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(チオフェン-2-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ナフタ-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-6-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-tert-ブチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-ピリジン-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピロール-1-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-シクロヘキセン-3-オキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチアゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾオキサゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(オクタヒドロイソキノリン-2-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-4-イルピペラジン-1-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(フラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-3-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-2-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾイミダゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ベンゾイルアミノフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-4-イルチアゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(アドマンチル-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,4-ジフルオロフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-トランス-3,4-メレンジオキシフェニルアクリロイルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(3,4-メチレンジオキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3,4-ジメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3,5-ジメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3,4-ジフルオロフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,5-ジメチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,3-ジクロロフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,3-ジメチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-クロロ-2-メトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-エトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシ-2-メチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-フルオロ-4-メトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-チオフェン-2-イルメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-チオフェン-2-イルメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ビフェン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-5-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-8-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インダゾール-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-ベンゾトリアゾール-5-イオカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(イソキノリン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(イソキノリン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノキサリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ナフタ-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-ピロール-1-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-フルオロナフチル-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(H-ベンゾイミダゾール-5-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1-メチルインドール-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-メトキシナフタ-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-メトキシナフタ-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-4-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-メチルシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-N,N-ジメチルアミノメチルベンゾフラン-5-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-(2-インドリン-1-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(1,2,3,4-テトラヒドロキノリン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2S-[トランス-3-(5-ヒドロキシベンゾフラン-2-イル)ブト-2-エノイルアミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[トランス-3-(5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イル)ブタ-2-エノイル-アミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)-4-フェニルブトキシ)ベンズアミド;
N-ヒドロキシ-4-{2-[5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(1-(2,2,2-トリフルオロエチル)ピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニル-アミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2R-(ベンゾフラン-2-イルカルボニルアミノ)-3-ベンジルスルホニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(ベンゾフラン-2-イルカルボニルアミノ)-3-ベンジルチオプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-(5-メトキシベンゾフラン-2-イル)ブト-2-エノイルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1,2,3,4-テトラヒドロイソキノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(イソインドリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(モルホリン-4-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ベンジルピペラジン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3(R)-ヒドロキシピロリドン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ピペリジン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-メチル-1,2,3,4-テトラヒドロキノリン-1-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(2-メチルインドリン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(イソインドリン-1-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[3-(トランス-シンナモイルアミノ)プロポキシ]ベンズアミド;
N-ヒドロキシ-4-[3-(トランス-4-メトキシシンナモイルアミノ)プロポキシ]ベンズアミド;
N-ヒドロキシ-4-[3-(4-フェニルチアゾール-2-イルカルボニルアミノ)プロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)プロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)プロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-4-メチルペントキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-シクロヘキシルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-メチルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-フェニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-フェニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-4-メチルペントキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-メチルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2RS-(トランス-シンナモイルアミノ)ヘキシルオキシ]ベンズアミド;
N-ヒドロキシ-4-[2RS-(トランス-シンナモイルアミノ)-3-(4-クロロフェニル)プロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-4-メチルチオブトキシ)ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-4-メチルチオブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-2-フェニルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-2-フェニルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-4-メチルスルホニルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-4-メチルスルホニルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-ベンジルスルホニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(チオフェン-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ビフェン-4-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ナフタ-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-ベンジルチオプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゼンカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンジルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(2-フェニルエチルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-ヒドロキシプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-4-メトキシシンナモイルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(2-N,N-ジメチルアミノメチルベンゾフラン-5-イルカルボニルアミノ)ブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-シンナモイルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-シンナモイルアミノ)-1S-メチルエトキシル)ベンズアミド;
N-ヒドロキシ-4-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ビフェン-4-イルカルボニルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-4-メキシシンナモイルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-ピリジン-2-イルチアゾール-5-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(7-クロロ-4-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-(4-メチルピペラジン-1-イル)チアゾール-5-イル)フェニルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-ピリジン-4-イルアミノチアゾール-5-イル)フェニルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(4-メチルピペラジン-1-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(4-ヒドロキシピペリジン-1-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(4-モルホリン-4-イルメチルチアゾール-5-イル)フェニルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(7-フルオロ-4-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-2-[7-フルオロ-4-(2-メトキシエトキシメチル)ベンゾフラン-2-イルカルボニルアミノ)-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(4-ヒドロキシキノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(7-フルオロ-4-フェノキシメチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-2-[4-(2-(4-メチルピペラジン-1-イルメチル)チアゾール-5-イル)フェニルカルボニル-アミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(ピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-ヒドロキシピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-ヒドロキシピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[6-(4-ニトロフェノキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-メトキシエトキシ)キノリン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(6-ブロモピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(5-ブロモピリジン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(4-メトキシキノリン-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1-メトキシナフタ-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシキノリン-2-イルカルボニルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(5-フェニルピリジン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-ベンジルオキシピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-メチルプロピルオキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-フェニルエチルオキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(3,3,3-トリフルオロプロピルオキシ)キノリン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[4-(3,3,3-トリフルオロプロピルオキシ)キノリン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(3,3,3-トリフルオロプロピルオキシ)キノリン-2-イルカルボニルアミノ]-1R-メチル-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-ヒドロキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-4-ヒドロキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[3'-(2-ヒドロキシエチル)ビフェン-4-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3'-(2-ヒドロキシエチル)ビフェン-3-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[2'-(2-ヒドロキシエチル)ビフェン-4-イルカルボニルアミン]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-ベンゾフラン-2-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[2'-(2-ヒドロキシエチル)ビフェン-3-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(チオフェン-3-イル)ピリジン-3-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[6-(4-アセチルアミノフェノキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(4-アミノフェノキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-メトキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-メトキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[5-(4-ジメチルアミノフェニル)ピリジン-3-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-(5-ブロモチオフェン-2-イル)アクリロイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-フラン-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-チオフェン-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-チオフェン-2-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-メチルシンナモイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-(ベンゾフラン-2-イル)ブタ-2-エノイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[シス-3-(ベンゾフラン-2-イル)ブタ-2-エノイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-4-ジメチルアミノシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-([2-(トランス-3-インドール-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-2-メチルシンナモイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-ヒドロキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-(7-メトキシベンゾフラン-2-イル)アクリロイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2R-[トランス-3-(7-メトキシベンゾフラン-2-イル)アクリロイルアミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[トランス-3-(5-メトキシベンゾフラン-2-イル)ブタ-2-エノイルアミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-フラン-2-イルアクリロイルアミノ)エトキシ]ベンズアミド;及び
N-ヒドロキシ-4-{2-[4-(4-(2-モルホリン-4-イルエチル)チアゾール-2-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド。
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-ヒドロキシエチルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-フェニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-メチルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-ベンゾチオフェン-2-イル-N-イソプロピルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-イソプロピルアミノエトキシ)ベンズアミド;及び
N-ヒドロキシ-4-(3-N-トランス-シンナモイル-N-メチルアミノプロポキシ)ベンズアミド。
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(1-メチルインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[3-(ベンゾチオフェン-2-イルカルボニルアミノ)プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[3-(ベンゾフラン-2-イルカルボニルアミノ)プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾチオフェン-2-イルカルボニルアミノ)-3-メチルブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾチオフェン-2-イルカルボニルアミノ)ブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾチオフェン-2-イルカルボニルアミノ)-プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[2R-(ベンゾチオフェン-2-イルカルボニルアミノ)-プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)ブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イルカルボニルアミノ)-1R-メチルエトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イルカルボニルアミノ)-1S-メチルエトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)-1R-メチルエトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(6-メトキシベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メチルベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(3-クロロベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(6-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(4-トリフルオロメチルベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-フルオロベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メトキシベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-クロロベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(7-メトキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メトキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-メトキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-モルホリン-4-イルエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ)-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(ピリジン-3-イルメトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(3-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(3-メチルベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-N,N-ジメチルアミノエトキシ)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-メトキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-モルホリン-4-イルエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(ピリジン-3-イルメトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(3-エチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-フルオロインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メトキシインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(メトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(フェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(5,6-ジメトキシインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(モルホリン-4-イルメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N,N-ジメチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(i-プロポキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(フェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(メトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(モルホリン-4-イルメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(N,N-ジメチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{3-[5-(メチル)ベンゾチオフェン-2-イルカルボニルアミノ]プロポキシ}-ベンズアミド;
N-ヒドロキシ-4-{3-[6-(メトキシ)ベンゾチオフェン-2-イルカルボニルアミノ]プロポキシ}-ベンズアミド;
N-ヒドロキシ-4-{3-[7-(メトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]プロポキシ)-ベンズアミド;
N-ヒドロキシ-4-{3-[7-(フェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]プロポキシ}-ベンズアミド;及び
N-ヒドロキシ-4-{2-[5-(2-メトキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ}ベンズアミド;
N-ヒドロキシ-4-(2R-ベンゾフラン-2-イルカルボニルアミノ-3-メチルチオプロポキシ)ベンズアミド;
N-ヒドロキシ-4-(2R-ベンゾフラン-2-イルカルボニルアミノ-3-メチルスルホニルプロポキシ)ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-フェニルエチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-メチル-N-2-フェニルエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロピルチオメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロピルスルフィニルメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロピルスルホニルメチル)ベンゾフラン-2-イルカルボニルアミノl-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-メチル-N-2-インドール-3-イルエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-(3-トリフルオロメチルフェニル)エチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-(3-トリフルオロメトキシフェニル)エチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-ヒドロキシアミノカルボニルメチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-カルボキシエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)-1RS-フェノキシメチルエトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロポキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-フルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-フルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-メトキシエチルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ)-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(ピリジン-4-イルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-オキソピリジン-1-イルメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-イミダゾール-1-イルフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-[1.2.4]-トリアジン-1-イルフェノキシメチル)ベンゾフラン-2-イルカルボニル-アミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(ピロリジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(ピペリジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-トリフルオロメチルピペリジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-メチルピペラジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3,3,3-トリフルオロプロピルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(4-メチルベンゾフラン-2-イルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェニルチオメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェニルスルフィニルメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェニルスルホニルメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(4-ヒドロキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(5-クロロベンゾフラン-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(5-クロロベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-3-イルメチルオキシメチルベンゾフラン-2-イルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-メトキシエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ)エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシインドール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2S-[3-(2-メトキシエチルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-メトキシエチルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチル-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N,N-ジエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(2-メトキシエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(テトラヒドロピラン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(テトラヒドロピラン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(テトラヒドロピラン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチル-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2,2,2-トリフルオロエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-{5-(2-ピロリドン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(2-ピロリジン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-ピロリジン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチル-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(ピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)-4-メチルチオブトキシ]ベンズアミド;及び
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)-4-メチルスルホニルブトキシ]ベンズアミド
N-ヒドロキシ-3-[2S-(ビフェン-4-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ベンゾフラン-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(トランス-シンナモイルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(4-(2-エトキシフェニル)フェニルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ビフェン-3-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ビフェン-4-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-いるカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(3-メチルビフェン-4-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-[2'-エトキシルビフェン-4-イルカルボニルアミノ)エトキシ]イソオキゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(3-メチルビフェン-4-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(4-フェニルチアゾール-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ナフタ-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ナフタ-1-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-{3-[2-(2-フェニルエチル)フェニルカルボニルアミノ]プロポキシ}イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-1-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ベンゾフラン-2-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ビフェン-3-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ベンゾフラン-2-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-3-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-3-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-4-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-{2-[2-(2-フェニルエチル)フェニルカルボニルアミノ]エトキシ}イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ビフェン-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ナフタ-2-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ナフタ-1-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-2-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-1-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ベンゾフラン-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(トランス-シンナモイルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;及び
N-ヒドロキシ-3-[2-(3-フェノキシメチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イル-カルボキサミド。
本発明の最も広い定義は発明の概要の中に開示されているが、式(I)の所定の化合物が好適である。例えば:
I.式(I)の化合物の好適な基はここで:
R1は水素又はアルキルであり;
Xは-O-、-NR2-、又は-S(O)n(式中、nは0〜2であり且つR2は水素又はアルキルである)であり;
Yは、シクロアルキル、任意に置換されたフェニル、アルキルチオ、アルキルスルホニル、任意に置換されたフェニルアルキルチオ、任意に置換されたフェニルアルキルスルホニル、又はヒドロキシで任意に置換されたアルキレンであり;
Ar1は、フェニルレン又はヘテロアリーレンであり、ここで当該Ar1は、アルキル、ハロ、ヒドロキシ、アルコキシ、ハロアルコキシ又はハロアルキルから成る群から独立して選択された1又は2個の基により任意に置換されており;
R3は、水素、アルキル、ヒドロキシアルキル又は任意に置換されたフェニルであり;そして
Ar2は、アリール、アラルキル、アラルケニル、ヘテロアリール、ヘテロアラルキル、ヘテロアラルケニル、シクロアルキル、シクロアルキルアルキル、ヘテロシクロアルキル、又はヘテロシクロアルキルアルキルであり;
ここで用語、上の好適な集団Iの範囲内に含まれた用語アリール、ヘテロアリール、ヘテロシクロアルキル、任意に置換されたフェニル、任意に置換されたヘテロアリール、任意に置換されたヘテロシクロアルキル、及び単独で又は他の用語の一部としてアミノアルキル(例えば、アラルキル、任意に置換されたフェニルアルキルチオ、アミノアルコキシ、任意に置換されたフェニルカルボニルアミノ、任意に置換されたヘテロアリールなど)は、下の意味を有する。
で示されている。
本発明の化合物は、下に示す反応スキームに描かれた方法によって行われて良い。
本発明の化合物の実用性は、ヒストンデアセチラーゼ酵素の阻害物質であり従って、増殖性疾患の例えば、がんの例えば、肺がん、結腸癌、AML、MML、皮膚がん、乳がん、卵巣がん、前立腺がん、肝がん、脳の及び皮膚のがん、乾癬、繊維性増殖疾患の例えば、肝繊症、平滑筋増殖性疾患の例えば、アテローム性動脈硬化症及び再狭窄、炎症性疾患の例えば、関節炎、脈管形成を伴う疾患の例えば、がん、糖尿病性レチノパチー、造血疾患の例えば、貧血、真菌、寄生生物及び細菌感染症、ウィルス感染症、自己免疫疾患の例えば、関節炎、多発性硬化症、ループス、アレルギー、喘息、アレルギー性鼻炎、及び器官移植、並びに双極性障害の治療において有効である。更に、本発明の化合物は、C型肝炎感染症の治療において有用である。
ヒストンデアセチラーゼを阻害する本発明の化合物の性能は、下の例1及び2に記載のin vivo及びin vitro生物学的アッセイにおいて試験されて良い。本発明の化合物のhcv活性をGeorgetown Universityにおいてhcvレプリコンアッセイにおいて試験した。化合物は、Korner, V. L.ら, Science 1999 Jul.2: vol.285 (No.5424): pp.110〜3に記載のレプリコンアッセイを使用することでhcv活性に関しても試験されて良い。
一般に本発明の化合物は、類似する有効性を担う薬剤のための許容されている任意の投与方法によって治療上有効な量において投与されて良い。本発明の化合物、即ち、活性成分の実際の量は、治療される疾患の症度、対象者の年齢及び相対的な健康状態、使用される化合物の能力、投与の経路及び形態、並びに他の因子に依存する。
以下の調製及び例は、当業者が一層容易に本発明を理解し且つ行うことができるように与えてある。それらは本発明の範囲を限定するものと解されるべきではないが、例示及び代表例にすぎない。
実施例1
N-ヒドロキシ-4-(2-ベンゼンカルボニルアミノ-エトキシ)ベンズアミドの合成
THF(10ml)中の2-アミノエタノール(3.1g、50mmol)の溶液に対してtert-THF(150ml)中無水ブトキシカルボニル(10.9g、50mmol)を加えた。この反応混合物を3時間に渡り撹拌して、次いで酢酸エチルで希釈し、0.5Mの水性HCl、及び塩水で希釈した。有機層を乾燥させ(MgSO4)、ろ過しin vacuoで濃縮し2-N-Boc-アミノエタノールを得て、それを次の段階で直接使用した。
無水THF(135ml)中のトリフェニルフォスフィン(17.7g、67.5mmol)の溶液に対してDIAD(13.6g、67.5mmol)を加えた。この溶液を白色沈殿が形成されるまで撹拌した(2〜10分)。更に60分後、THF(25ml)中の2-N-Bocアミノ-エタノール(7.2g、45mmol)の溶液及びメチル4-ヒドロキシベンゾエート(6.8g、45mmol)を加えて5時間に渡り連続して撹拌した。この反応混合物をin vacuoで濃縮してフラッシュクロマトグラフィーによって精製し、メチル4-(2-N-Bocアミノエトキシ)ベンゾエートを獲得した。代替的に、粗製の物質が次の段階で直接使用されて良い。
メタノール(20ml)中、粗製のメチル4-(2-N-Bocアミノエトキシ)ベンゾエートの溶液に対して4MのHCI/ジオキサン(180ml)を加えた。3時間に渡り撹拌した後、ジエチルエーテル(300ml)を加え、白色の沈殿を提供した。この固体を回収し、酢酸エチル中に懸濁させ、そして15〜20分に渡り撹拌した。この固体を再度回収し、そして高vacuo下で乾燥させてメチル4-(2-アミノエトキシ)ベンゾエートヒドロクロリド6.3g(段階2の60%超)を獲得した。
THF(6ml)中のメチル4-(2-アミノ-エトキシ)ベンゾエートヒドロクロリド(0.232g,1mmol)の懸濁に対して塩化ベンゾイル(0.140g、1mmol)を加え、しかる後にトリエチルアミン(0.121g、1.2mmol)を加えた。反応混合物を1時間に渡り撹拌し、そして酢酸エチルで希釈した。有機層を0.5M水性HCl、飽和重炭酸ナトリウム溶液及び塩水で洗浄した。この有機層をin vacuoで濃縮してメチル4-(2-ベンゼンカルボニルアミノ-エトキシ)ベンゾエートを加え、それを次の段階で直接使用した。
THF/メタノールの1:1混合物(20ml)中の粗製のメチル4-(2-ベンゼンカルボニルアミノ-エトキシ)ベンゾエート(0.5mmol)の溶液に対して50重量%の水性ヒドロキシルアミン(3ml)を、しかる後に1Mの水性NaOH(1ml)を加え、pHを10〜11に調節した。この反応混合を14時間に渡り撹拌し、pH=7〜8へと6Mの水性HCIで中和し、そしてin vacuoで濃縮した。沈殿物を回収しそしてHPLCによって精製し、表題の化合物を白色固体として獲得した。
1H NMR(DMSO-d6):δ8.69(t,J=5.8Hz,1H),7.83(d,J=7.5Hz,2H),7.69(d,J=9.1Hz,2H),7.46(m,3H),6.99(d,J=9.1Hz,2H),4.16(t,J=5.8Hz,2H),3.63(q,J=5.8Hz,2H). EM(計算値):300.1;MS(ESI) m/e:301.1(M-1)+,299.0(M+1)-.
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イル-カルボニルアミノ)-エトキシ]-ベンズアミドの合成
ベンゾフラン-2-カルボン酸(0.162g、1mmol)、EDC・HCI(0.268g、1.4mmol)及びHOBT(0.203g、1.5mmol)のDMF(6ml)中での混合物を2時間に渡り撹拌した。メチル4-(2-アミノエトキシ)ベンゾエートヒドロクロリド(0.232g、1mmol)を加え、しかる後にトリエチルアミン(0.121g、1.2mmol)を加えた。この反応混合物を2時間に渡り撹拌し、そして酢酸エチルで希釈し、飽和重炭酸ナトリウムで、そして塩水で洗浄した。有機層をin vacuoで濃縮して粗製の4-[2-(ベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンゾエートを、上の例1、段階に記載のように、表題の化合物に転換した。
1H NMR(DMSO-d6)δ11.05(s,1H),8.92(t,J=5.6Hz,1H),8.88(s,1H),7.76(d,J=8.0Hz,1H),7.70(d,J=9.2Hz,2H),7.64(d,J=8.0Hz,1H),7.55(s,1H),7.46(t,J=6.8Hz,1H),7.32(t,J=8.0Hz,1H),7.01(d,J=8.2Hz,2H),4.18(t,J=5.6Hz,2H),3.67(m,2H).EM(計算値):340.1;MS(ESI)m/e:(M+1H)+:341.0,(M-1H)-:339.1。
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イル-カルボニルアミノ)-エトキシ]-ベンズアミドの合成
N-ヒドロキシ-4-[2-(3-ジメチルアミノベンゾフラン-2-イルカルボニルアミノ)-エトキシ]-ベンズアミドの合成
THF(25ml)中3-メチル-ベンゾフラン-2-カルボン酸(0.98g、5.6mmol)及び5滴のDMFの溶液に対して塩化オキサリル(0.53ml、6.1mmol)を加えた。この溶液を1時間に渡り室温で撹拌した後、メタノール(20ml)及びTEA(7ml)を加えた。スラリーを室温で一晩乾燥させ、次いで濃縮して酢酸エチル(100ml)に溶かし、そして中性NaHC03(100ml)により洗浄した。有機層を乾燥(MgS04)させ、ろ過して濃縮し3-メチルベンゾフラン-2-カルボン酸メチルエステル(1g)を褐色の固体として獲得した。粗製のメチルエステルを更なる精製を伴わずに使用した。
3-メチルベンゾフラン-2-カルボン酸メチルエステル(1.0g、5.3mmol)、NBS(0.95g、5.3mmol)及びAIBN(87mg、0.53mmol)の溶液を加熱してCCl4(40ml)中で3時間に渡り還流し、次いで室温へと冷却して濃縮した。残留物を酢酸エチル(100ml)中に溶かして水(100ml)で洗浄した。有機層を乾燥(MgS04)させ、ろ過して濃縮して3-ブロモメチルベンゾフラン-2-カルボン酸メチルエステル(1.55g)の褐色/黄色固体を回収し、それを次の段階で更なる精製を伴わずに使用した。
3-ブロモメチルベンゾフラン-2-カルボン酸メチルエステル(269mg、1mmol)を無水DMF中に溶かして2Mのジメチルアミン/THF溶液(1.5ml、3mmol)を加えた。1〜2時間後、この反応混合物をEtOAcで希釈し、そして飽和NaHC03(水性)及び塩水で2回洗浄した。有機抽出物をNa2SO4上で乾燥させ、次いでin vacuoで濃縮した。この粗製物をシリカゲルカラム(ジクロロメタン中5%MeOH)上で精製し、3-ジメチルアミノメチルベンゾフラン-2-カルボン酸メチルエステル(131mg)を獲得した。
MeOH中の3-ジメチルアミノメチルベンゾフラン-2-カルボン酸メチルエステル(131mg、0.56mmol)の溶液に対して1NのNaOH(水性)を、溶液のpHが13になるまで加えた。この反応混合物を60〜90分に渡り撹拌した。終了後、反応混合物をHCl(水性)により酸性化してpH3にして濃縮し、乾燥させ3-ジメチルアミノメチルベンゾフラン-2-カルボン酸をHCl塩として獲得し、それを更なる生成をせずに次の段階で使用した。
3-ジメチルアミノメチルベンゾフラン-2-カルボン酸(140mg、0.56mmol)に対して無水DMF中EDC.HCI(150mg、0.784mmol)及びHOBt.H2O(114mg、0.84mmol)を加えた。この反応混合物を30〜60分に渡り撹拌し、その後メチル-(4-(2-エトキシアミン))ベンゾエート塩化水素塩(130mg、0.56mmol)及びトリエチルアミン(94μL、0.672mmol)を加え、そしてこの反応混合を一晩撹拌した。この反応混合物をEtOAcで希釈しそして飽和NaHCO3(水性)及び塩水で2回洗浄した。有機抽出物をin vacuoで濃縮し、メチル4-[2-(3-ジメチルアミノベンゾフラン-2-イル-カルボニルアミノ)エトキシ]ベンゾエートを獲得し、それを次いで更なる精製をせずに使用した。
MeOH及びTHF中の粗製のメチル4-[2-(3-ジメチルアミノベンゾフラン-2-イル-カルボニルアミノ)-エトキシ]-ベンゾエートの溶液に対して過剰の水性ヒドロキシルアミン溶液及びNaOH(水性)を加え、pH10〜11にした。この反応混合物を一晩撹拌し、次いで水性塩化水素酸によりpH7〜8にし、そしてin vacuoで濃縮した。残留物をアセトニトリル及び水中に溶かし、そしてプレHPLCにより精製し表題の化合物(107mg)を獲得した。
1H NMR(400MHz,DMSO-d6)δ9.88(m,1H),9.31(t,J=6.0Hz,1H),8.04(d,J=7.6Hz,1H),7.70(m,3H),7.57(t,J=7.6Hz,1H),7.45(t,J=7.6Hz,1H),6.99(d,J=9.2Hz,2H),4.76(d,J=4.8Hz,2H),4.23(t,J=6.0Hz,2H),3.71(m,2H),2.84(s,3H),2.83(s,3H).EM(計算値):397.2;MS(ESI)m/e(M+1H)+:398.1,(M-1H)-:396.2.
水素化ナトリウム(15mg、0.56mmol)を無水DMF中に溶かしてN2(ガス)の下で撹拌した。2,2,2-トリフルオロエタノール(270μL、3.7mmol)を加え、そしてこの反応混合物を15〜20分に渡り撹拌した後、3-ブロモメチルベンゾフラン-2-カルボン酸メチルエステルを加えた。8時間後、1NのNaOH(水性)を加え、そしてこの反応混合物を10〜15分に渡り撹拌した。この反応混合物を水性塩化水素酸により酸性化してpH3にし、そして産物をEtOAcで抽出した。有機層をNa2SO4上で乾燥させin vacuoで濃縮し3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-カルボン酸(38mg)を加え、次いでそれを更なる精製を伴わずに使用した。
無水DMF中の3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-カルボン酸(38mg、0.139mmol)の溶液に対してEDC.HCl(37mg、0.195mmol)及びHOBt.H20(26mg、0.195mmol)を加えた。60〜90分後、メチル-(4-(2-エトキシアミン))ベンゾエート塩化水素酸塩(32mg、0.139mmol)及びトリエチルアミン(23μL、0.167mmol)を加え、そして反応混合物を1〜2時間に渡り撹拌した。この反応混合物をEtOAc希釈し、そして飽和NaHCO3(水性)で2回洗浄し、そして有機抽出物を濃縮しメチル4-{2-[3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-イル-カルボニルアミノ]エトキシ}ベンゾエートを獲得し、それを次いで更なる精製を伴わずに使用した。
4-{2-[3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-イル-カルボニルアミノ]-エトキシ}-ベンゾエートをMeOH中に溶かし、そして過剰のヒドロキシルアミン溶液及びNaOH(水性)を加えてpHを10〜11にした。この反応混合物を、一晩撹拌した後、水性塩化水素酸で中和しpH7〜8にした。この反応混合物をin vacuoで濃縮して固体を獲得し、それを回収し、そして水で洗浄し、次いでアセトニトリルと水の中に溶かし、そしてプレHPLCにより精製し表題の化合物(35mg)を獲得した。
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.95(t,J=5.6Hz,1H),8.89(s,1H),7.81(d,J=7.6Hz,1H),7.70(d,J=8.8Hz,2H),7.63(d,J=8.8Hz,1H),7.50(t,J=8.8Hz,1H),7.36(t,J=8.0Hz,1H),7.00(d,J=9.2Hz,2H),5.25(s,2H),4.18(m,4H),3.67(m,2H)EM(計算):452.1;MS(ESI)m/e(M+1H)+:453.0,(M-1H)-:451.0。
N-ヒドロキシ-4-{2-[5-(2-ピロリジン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミドの合成
5-メトキシベンゾフラン-2-カルボン酸(5.04g、26mmol)を、撹拌棒、セプタム及び窒素ガス導入部を備えた200mlの丸底フラスコに秤量した。無水MeOH(50ml)を窒素雰囲気下で加えた。この溶液を氷浴で冷却し、そして塩化チオニル(2.3ml、32mmol)を激しく撹拌しながら滴下して加えた。室温で72時間に渡り撹拌した後、この反応混合物を水中(150ml)に注ぎ、そして白色固体を回収した。この固体をトルエン中に溶かし(100ml)、そしてこの溶液を1MのNaHCO3及び塩水で洗浄し、そしてMgSO4上で乾燥させた。有機層を除去し5-メトキシべノフラン-2-カルボン酸メチルエステルを白色固体(5.15g)として獲得した。
無水塩化メチレン(15ml)中5-メトキシベンゾフラン-2-カルボン酸メチルエステル(5.15g、25mmol)を窒素雰囲気下で−40℃に冷却した。CH2Cl2(27ml、1.0M)中の三臭化ホウ素を1時間に渡りシリンジポンプを使用することで加えた。この反応混合物を室温に暖めた。16時間後、この反応混合物を氷浴中で冷却し、MeOH(15ml)で冷却した。この反応混合物を塩水中に溶かし(100ml)そしてEtOAcで抽出した。この有機抽出物を無水MgSO4上で乾燥させ、そして溶媒をロータリーエバポレーターにより除去した。残留物をヘキサンで粉砕し、そして黄色の固体をろ過して無水MeOH(30ml)中に溶かした。この溶液を氷浴中で冷却し、そして塩化チオニル(1.9ml、26mmol)を滴下して加えた。72時間後、水(100ml)を加えて固体を回収した。5×15cmで詰め込んだ300cm3シリカゲル上でのEtOAcを使用する粗製の産物の精製により5-ヒドロキシ-ベンゾフラン-2-カルボン酸メチルエステル(4.53g)を獲得した。
無水テトラヒドロフラン(15ml)を5-ヒドロキシベンゾフラン-2-カルボン酸メチルエステル(1.10g.5.7mmol)、トリフェニルフォスフィン(1.50g、5.7mmol)、及び1-(2-ヒドロキシエチル)-ピロリジンの混合物(0.66g、5.7mmol)に対して窒素雰囲気の下で加えた。ジイソプロピルアゾジカルボキシレート(1.15ml、5.8mmol)をこの溶液に対して室温で序々に加えた。2日後、溶媒を除去しそして残留物をEt2O:EtOAcの2:1混合物(150ml)に溶かした。この溶液を1.0Mの水性NaOHで洗浄した。産物を1.0Mの塩化水素酸中へと抽出し、そして組み合わさった酸抽出物をEt2Oで洗浄した。この抽出物を冷却し、そして抽出物のpHを50%の水性NaOHにより12に調整した。この塩基性溶液をCH2Cl2で抽出し、そして有機層を無水MgSO4上で乾燥させて5-(2-ピロリドン-1-イル-エトキシ)ベンゾフラン-2-カルボン酸メチルエステル(0.96g)を琥珀色の固体として獲得した。
5-(2-ピロリジン-1-イルエトキシ)ベンゾフラン-2-カルボン酸メチルエステル(960mg、3.3mmol)無水エチレングリコールジメチルエーテル(10ml)の氷冷溶液に対して脱気した水性水酸化リチウム溶液(2.0ml、2.0M)を滴下して加えた。室温で4時間に渡る撹拌後、この溶液を冷却してpHをジオキサン中4.0MのHClにより2に調整した。粘着性の褐色の沈殿が形成された。この溶媒を除去し、そして粘着性の残留物を凍らせて凍結乾燥させた。この褐色の固体を沸騰2-プロパノール(90ml)に溶かし、この溶液を熱いままろ過し、次いで5-(2-ピロリジン-1-イル-エトキシ)-ベンゾフラン-2-カルボン酸をベージュ色の針状晶(528mg)として獲得した。更に153mgを母液から獲得した。
20mlバイアルにおいて、DMF(4.5ml)中の5-(2-ピロリジン-1-イルエトキシ)ベンゾフラン-2-カルボン酸(156mg、0.50mmol)及び4-(2-アミノエトキシ)安息香酸メチルエステルヒドロクロリド(129mg、0.56mmol)の溶液に対してジイソロピルエチルアミン(0.88ml、5.1mmol)を加えた。DMF中、O-(7-アザベンゾトリアゾール-1-イル)-1,1,3,3-テトラメチルウロニウムヘキサフルオロフォスフェート(740μL,0.82M、0.61mmol)を加えて、明黄色の溶液を獲得した。このバイアルを窒素でパージしそして室温で18時間に渡り撹拌した。この溶液を除去し、そして残留物をEtOAc(25ml)中に溶かし、そしてH2O、1.0Mの水性K2CO3及び塩水で洗浄した。この有機層を無水MgSO4上で乾燥させ、そしてロータリーエバポレーターにより溶媒を除去した。93:5:2のCH2Cl2:MeOH:TEA溶離液を使用するシリカゲルによるカラムクロマトグラフィーによりこの残留物を精製し、4-{2-[5-(2-ピロリジン-1-イルエトキシ)ベンゾフラン-2-カルボニルアミノ]-エトキシ}-安息香酸メチルエステルをベージュ色の固体(174mg)として獲得した。
メタノール(8ml)及びテトラヒドロフラン(4ml)中の4-{2-[5-(2-ピロリドン-1-イルエトキシ)ベンゾフラン-2-カルボニルアミノ]-エトキシ}-安息香酸メチルエステル(169mg、0.37mmol)の溶液に対して水中ヒドロキルアミン(2.9mlの50wt.%溶液)及び水酸化ナトリウムの4.0M水性溶液(0.65ml)を加えた。18時間に渡り撹拌した後、この有機物を除去し、そして水性溶液を氷/水浴中で冷却し、そしてpHを4.4mlの1.0M塩化水素酸により約8に調整して沈殿を生じさせた。この均一な溶液を室温に温めそしてアセトニトリルを沈殿が溶解するまで加えた。この溶液をC-18逆相HPLCによるクロマトグラフィーに委ねた。214nmにおける吸光度を伴う画分を回収し、凍結させ、そして凍結乾燥させ表題の化合物(31mg)を獲得した。
1H NMR(400MHz,DMSO-d6)δ:11.05(s,1H),10.4(s,1H),8.91(s,2H),7.70(d,2H,J=7.4),7.59(dd,1H,J=3.7,9.1Hz),7.51(d,1H,J=3.7Hz),7.35(s,1H),7.13(d,1H),J=9.0Hz),7.00(d,2H,J=7.4Hz),4.37(m,2H),4.18(m,2H),3.62(m,6H),3.12(m,2H),2.02(m,2H),1.89(m,2H).EM(計算値):453.2;MS(ESI)m/e(M+1H)+:454.1,(M-1H)-:452.2.
N-ヒドロキシ-4-[2-(3-ジメチルアミノベンゾフラン-2-イルカルボニルアミノ)-エトキシ]-ベンズアミドヒドロクロリドの合成
(2-ヒドロキシエチル)カルバミン酸tert-ブチルエステル(152.0g、0.942mol)及び4-ヒドロキシ-安息香酸メチルエステル(174.0g、1.12mol)をテトラヒドロフラン(2000ml)中に溶かし、そして0〜5℃に冷却した。トリフェニルフォスフィン(292.8g、1.116mol)をこの冷却した混合物に対して加えた。テトラヒドロフラン(400ml)中、ジイソプロピルアゾジカルボキシレート(246.0g、1.218mol)の溶液を、10℃未満の反応温度を維持しながら1〜2時間に渡り滴下して加えた。添加後、この反応を序々に周囲温度にして一晩撹拌した。反応終了後、溶媒を減圧下で蒸留して生じる油をエタノール(500ml)及び酢酸エチル(2000ml)中に溶かした。塩化アセチル(222.0g、2.826mol)を15分に渡り温度を40℃へと高めながら滴下して加えた。生じる懸濁を反応が完了するまで40℃で撹拌した。反応が完了した後、生じる結晶を粗いフリット(coarse frit)によりろ過し、そして酢酸エチル(300mL)で洗浄した。物質をin vacuoで乾燥させ、4-(2-アミノエトキシ)安息香酸メチルエステルヒドロクロリド(204.1g)を白色結晶質固体として獲得した。
4-(2-アミノエトキシ)安息香酸メチルエステルヒドロクロリド(78.90g、0.340mol)及び3-メチルベンゾフラン-2-カルボン酸(60.0g、0.340mol)をアセトニトリル(360ml)中で懸濁させて0〜5℃に冷却させた。ピリジン(137.6mL、1.702mol)を迅速に加えた。アセトニトリル(60ml)中のオキシ塩化リン(52.2g、0.340mol)を30〜45分に渡り温度を20℃未満に維持しながら滴下して加えた。この反応混合物を1時間に渡り撹拌し、そして序々に周囲温度へと加温した。反応が終了した後、この溶液を、迅速に撹拌したクロロベンゼン(1000ml)と1N塩化水素酸(1000ml)の0.5℃混合物に加えた。この反応混合物を迅速に撹拌し、そして室温へと加温した。この有機層を水、3%水酸化カルシウムで洗浄し、そして再度水で洗浄した。クロロベンゼン(100ml)をこの洗浄した有機層加えた。次いで、溶媒(100ml)を大気圧下で、容器温度が132℃に到達するまで蒸留した。周囲温度に冷却した後、4-{2-[(3-メチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸メチルエステルを次の段階において使用するために溶液中で保存した。
クロロベンゼン(1000ml)中の4-{2-[(3-メチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸メチルエステル(0.340mol)の溶液を2,2'-アゾビスイソブチロニトリル(5.60g、0.017mol)及びN-ブロモスクシンイミド(75.76g、0.426mol)で処理した。生じる混合物を80℃に加熱し、そして1時間に渡り撹拌した。反応終了後、この反応混合物を周囲温度に冷却し、そして水、3%亜硫酸水素ナトリウムで洗浄し、そして再度水で洗浄した。溶媒を減圧下で蒸留し、そして周囲温度に冷却した後、ジクロロメタンを加え、そして4-{2-[(3-ブロモ-メチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸メチルエステルを獲得し、それを次の段階で使用した。
クロロベンゼン(200ml)及びジクロロメタン(800ml)中の4-{2-[(3-ブロモメチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸メチルエステル(0.340mol)の溶液を、テトラヒドロフラン中0〜5℃の2Mジメチルアミン(510ml、1.022mol)の溶液に、温度を20℃未満に維持しながら30分に渡り加えた。生じる混合物を1時間に渡り撹拌し、そして周囲温度に加温した。反応が終了した後、この反応混合物を5%炭酸カリウム及び水で洗浄した。溶媒を容器温度が100℃に到達するまで周囲温度で蒸留した。約50℃に冷却した後、アセトニトリル(400ml)及び酢酸エチル(400ml)をこの容器に加えた。この反応混合物を、全固体が溶解する迄還流させた。この反応混合物を冷却し4-{2-[(3-ジメチルアミノメチル-ベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸メチルエステル(76.6g)をオフホワイトの粉末として獲得した。
4-{2-[(3-ジメチルアミノメチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸メチルエステル(70.0g、0.177mol)をメタノール中で懸濁させた(350ml)。50%水酸化カリウム(139.8g、1.062mol)を加え、そしてこの反応混合物を反応が完了するまで60℃に加熱した。室温に冷却した後、生じる結晶を粗いフリットでろ過し、そしてメタノールで洗浄した。結晶をin vacuoで乾燥し4-{2-[(3-ジメチルアミノメチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸カリウム塩(72.0g)を白色固体として獲得した。
4-{2-[(3-ジメチルアミノメチルベンゾフラン-2-カルボニル)アミノ]エトキシ}安息香酸カリウム塩(20.0g、0.0476mol)をN,N-ジメチルホルムアミド(100ml)中で懸濁させた。ジオキサン中4Mの塩化水素酸(11.9ml、0.0476mol)をこの懸濁に対して加えた。周囲温度で30分に渡り撹拌した後、この反応混合物を中程度のフリットを通じてろ過した。1-[3-(ジメチルアミノ)プロピル]-3-エチルカルボジイミドヒドロクロリド(10.94g、0.0571mol)及び1-ヒドロキシベンゾトリアゾール(7.71g、0.0571mol)をこの溶液に対して加え、そしてこの反応混合物を1時間に渡り周囲温度で撹拌した。別な容器において、塩酸ヒドロキシルアミン(13.2g、1.904mol)をN,N-ジメチルホルムアミド(100ml)中に懸濁させ、そしてトリエチルアミン(33.1ml、2.380mol)で処理した。この反応混合物を1時間に渡り撹拌した後、塩をろ過して除去し、そして生じる溶液を上記活性化された酸溶液に加え、そして周囲温度で反応が完了するまで撹拌した。産物が結晶化し始めた後、メタノール(150ml)を30分に渡り序々に加えた。この反応混合物を1時間に渡り室温で撹拌し、次いで0〜5℃に冷却し、そして更なる時間に渡り撹拌した。結晶をろ過して、in vacuoで乾燥させる前にメタノール(40ml)で洗浄し、3-ジメチルアミノメチルベンゾフラン-2-カルボン酸[2-(4-ヒドロキシ-カルバモイルフェノキシ)エチル]アミド(11.88g)を白色固体として獲得した。粗製の物質(13.25g、0.033mol)をN,N-ジメチルホルムアミド(80ml)中に溶かし、そして100℃に加熱して溶液を獲得した。冷却後、エタノール(80ml)を30分に渡り滴下して加え、そして生じる懸濁を1時間に渡り冷却した。結晶をろ過してエタノール(40ml)で洗浄して乾燥させ、そして純粋な産物(9.82g)を白色固体として獲得した。
3-ジメチルアミノメチルベンゾフラン-2-カルボン酸[2-(4-ヒドロキシ-カルバモイルフェノキシ)エチル]アミド(22.7g、0.057mol)を2-プロパノール(220ml)中で懸濁させた。12MのHCl(5.2ml、0.063mol)を小分けにして加えて生じる混合物を還流温度に加熱した。水(44ml)を均一な溶液を獲得する迄加えた。反応混合物を冷却して一晩結晶化させた。1時間に渡り5℃未満に冷却した後、この結晶をろ過して、in vacuoで乾燥させる前に2-プロパノールにより処理し、表題の化合物(22.0g)を白色固体として獲得した。
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)-エチルスルファニル]ベンズアミドの合成
THF(100ml)中、ジイソプロピルアゾジカルボキシレート(DIAD、4.04g、20mmol)の溶液に対して0℃でトリフェニルフォスフィン(5.25g、20mmol)を加えた。1時間後、THF(10ml)中のBoc-エタノールアミン(3.22g、20mmol)の溶液を加えた。20分後、THF(10ml)中のメチル4-ベルカプトベンゾエート(3.86g、20mmol)の溶液を加え、そしてこの反応混合物を室温で一晩撹拌した。この反応混合物を濃縮しそして酢酸エチル(150ml)を加えた。この溶液を1MのHCl、飽和水性NaHCO3、塩水で洗浄し、MgSO4上で乾燥させ、ろ過し、そして蒸発させて乾燥させた。油状の黄色残留物を、シリカゲル(ヘキサン中0〜20%酢酸エチルを移動層とする)の詰物を通じて溶出させ、そしてこの産物をエーテル及びヘキサンから再結晶化してメチル4-(2-tert-ブトキシカルボニルアミノエチルスルファニル)ベンゾエート(4.00g)を獲得した。
ジクロロメタン(8ml)中のメチル4-(2-tert-ブトキシカルボニルアミノエチルスルファニル)ベンゾエート(1.00g、3.21mmol)をジオキサン中のHCl(4M、8ml、10当量)の溶液で3時間に渡り室温で処理した。エーテル(100ml)を加え、そしてこの混合物をろ過し、エーテルで洗浄し、そしてポンプ乾燥してメチル4-(2-アミノエチルスルファニル)ベンゾエートヒドロクロリドを獲得した。
メチル4-(2-アミノエチルスルファニル)ベンゾエートヒドロクロリド(0.248g、1.00mmol)をDMF(5ml)中ベンゾフラン-2-カルボン酸(0.162g、1.00mmol)及びHBTU(0.379g、1.00mmol)と室温で組み合わせた。トリエチルアミン(0.307ml、2.2mmol)を加え、そしてこの反応混合物を室温で一晩撹拌した。飽和水性NaHCO3(15ml)を加えて沈殿させ、それを、水(20ml)を加えることによって破壊した。固体をろ過してケーキを酢酸エチル中で溶解させた。残った水をピペットによって除去し、そしてヘキサンを加えてメチル4-{2-[(ベンゾフラン-2-イルカルボニル)-アミノ]エチルスルファニル}ベンゾエート(0.138g)をガムとして獲得し、それを更なる精製を伴わずに次の段階で使用した。
THF(2ml)中のメチル4-{2-[(ベンゾフラン-2-イル-カルボニル)アミノ]エチルスルファニル}-ベンゾエートの溶液に対して水中(4ml)の50%ヒドロキシルアミンの溶液を加えた。メタノール(2ml)及び0.1MのNaOH(0.1ml)を加えた。この反応混合物を3日に渡り室温で撹拌した。この溶媒を蒸発させ、そして残留物をジクロロメタン/酢酸エチルから結晶化し、表題の化合物(46mg)を獲得した。
1HNMR(DMSO-d6):3.12(2H,m);3.5(2H,m);7.33(1H,t);7.42(2H,d);7.45(1H,m*);7.53(1H,s);7.62(1H,d);7.7(2H,d);7.78(1H,d);8.96(1H,t);8.99(1H,br.s).MS(M+1):357.
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)エチルスルホル]ベンズアミドの合成
メタノール/水(1:1、100ml)中のメチル4-(2-tert-ブトキシカルボニルアミノエチルスルファニル)-ベンゾエート(3.00g、9.63mmol)の溶液に対してオキソン(登録商標) (13.03g、21.19mmol)を加えた。48時間後、メタノールを減圧下で除去し、そして残留物を酢酸エチル(150ml)と飽和水性NaHCO3(150ml)の間で分離させた。この有機層を塩水(100ml)で洗浄し、MgSO4上で乾燥させ、ろ過し、in vacuoで濃縮し、そして残留物を酢酸エチル/ヘキサンから再結晶化し、メチル4-(2-tert-ブトキシカルボニルアミノ-エチルスルホニル)ベンゾエート(2.86g)の産物を獲得した。
ジクロロメタン(20ml)中のメチル4-(2-tert-ブトキシカルボニルアミノエチルスルホニル)ベンゾエート(2.86g、8.33mmol)の溶液をジオキサン(20ml)中4MのHClで2時間に渡り処理した。エーテル(200ml)を加え、そして懸濁をろ過し、エーテル(2×50ml)、ヘキサン(50ml)で洗浄し、そしてポンプ乾燥しメチル4-(2-アミノエチルスルホニル)ベンゾエートヒドロクロリド(2.23g)を獲得し、それを上記のようにベンゾフラン2-カルボン酸と組み合わせ、表題の化合物を獲得した。MS(M+1):388.
化合物.1
1H NMR(400MHz,DMSO-d6)δ8.69(t,J=5.8Hz,1H),7.83(d,J=7.5Hz,2H),7.69(d,J=9.1Hz,2H),7.46(m,3H),6.99(d,J=9.1Hz,2H),4.16(t,J=5.8Hz,2H),3.63(q,J=5.8Hz,2H).EM(計算値):300.1;MS(ESI)m/e:301.1(M-1)+,299.0(M+1)-.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.92(s,1H),8.41(t,J=6Hz,1H),7.74(d,J=8.8Hz,2H),7.58(d,J=6.8Hz,2H),7.46(d,J=15.6Hz,1H),7.45-7.37(m,3H),7.03(d,J=8.8Hz,2H0,6.72(d,J=15.6Hz,1H),4.13(t,J=5.2Hz,2H),3.60(q,J=5.6Hz,2H).EM(計算値):326.1;MS(ESI)m/e(M+1H)+:327.1,(M-1H)-:325.2.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.91(s,1H),8.42(t,J=4.8Hz,1H),7.72(d,J=8.4Hz,2H),7.27(t,J=7.2Hz,2.0Hz),7.18(t,J=7.2Hz,1H),7.13(d,J=7.2Hz,2H),7.01(d,J=8.8Hz,2H),4.07(t,J=5.6Hz,2H),3.49(dq,J1=5.6Hz,J2=1.6Hz,2H),2.28(ddd,J1=4.0Hz,J2=5.6Hz,J3=9.6Hz,1H),1.95(ddd,J1=4.1Hz,J2=5.2Hz,J3=8.4Hz,1H),1.39(ddd,J1=4.0Hz,J2=5.2Hz,J3=9.2Hz,1H),1.24(ddd,J1=4.0Hz,J2=6.4Hz,J3=10.4Hz,1H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.2,(M-1H)-:339.2.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.92(s,1H),8.31(t,J=5.6Hz,1H),7.73(d,J=9.2Hz,2H),7.52(d,J=9.2Hz,2H),7.41(d,J=15.6Hz,1H),7.03(d,J=8.8Hz,2H),6.99(d,J=8.8Hz,2H),6.55(d,J=15.6Hz,1H),4.12(t,J=5.6Hz,2H),3.81(s,3H),3.58(q,J=5.6Hz,2H).EM(計算値):356.1;MS(ESI)m/e(M+1H)+:357.2,(M-1H)-:355.2.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.80(s,1H),8.01(t,J=4.8Hz,1H),7.61(d,J=8.8Hz,2H),7.14-7.02(m,5H),6.86(d,J=8.8Hz,2H),3.32(q,J=5.6Hz,2H),2.71(t,J=7.2,2H),2.30(t,J=7.6Hz,2H).EM(計算値):328.1;MS(ESI)m/e(M+1H)+:329.2,(M-1H)-:327.0.
1H NMR(400MHz,DMSO-d6)δ11.11(s,1H),10.89(s,1H),8.95(brs,1H),8.22(t,J=5.6Hz,1H),7.76(d,J=8.8Hz,2H),7.56(d,J=8.0Hz,1H),7.37(d,J=8.4Hz,1H),7.22(d,J=2.0Hz,1H),7.08(t,J=7.6Hz,1H),7.02(d,J=8.4Hz,2H),6.93(t,J=8.4Hz,1H),4.09(疑t,J=6.0Hz,2H),3.58(s,2H),3.50(疑q,J=5.6Hz,2H).EM(計算値):353.1;MS(ESI)m/e(M+1H)+:353.9,(M-1H)-:252.0.
1H NMR(400MHz,DMSO-d6)δ11.11(s,1H),8.80(t,J=5.6Hz,1H),7.82(d,J=7.6Hz,1H),7.81(d,J=8.0Hz,1H),7.76(d,J=8.4Hz,2H),7.19(t,J1=5.2Hz,1H),7.06(d,J=8.8Hz,2H),4.21(疑t,J=6.0Hz,2H),3.67(疑q,J=5.6Hz,2H).EM(計算値):306.1;MS(ESI)m/e(M+1H)+:307.0,(M-1H)-:304.9.
1H NMR(400MHz,DMSO-d6)δ8.98(s,1H),8.9(t,J=5.4Hz,1H),8.67(d,J=4.6Hz,1H),8.16(d,J=8.1Hz,1H),7.69(d,J=8.9Hz,2H),7.48(m,1H),6.99(d,J=8.9Hz,2H),4.17(t,J=5.4Hz,2H),3.65(m,2H).EM(計算値):301.11;MS(ESI)m/e(M-1H)-:300.0.
1H NMR(400MHz,DMSO-d6)δ11.03(1H,s),8.87(1H,bs),8.74(1H,t,J=5.6Hz),7.93(2H,d,J=8.0Hz),7.75(2H,d,J=8.0Hz),7.69(3H,m),7.47(1H,t,J=8.0Hz),7.39(2H,m),6.99(2H,d,J=8.9Hz),4.18(2H,t,J=5.6Hz),3.66(2H,m).EM(計算値):376.41;MS(ESI)m/e(M+1H)+:377.1,(M-1H)-:375.0.
EM(計算値):376.1;MS(ESI)m/e(M+1)+:376.9,(M-1)-:375.1.
1H NMR(400MHz,DMSO-d6)δ11.11(s,1HO,8.95(s,1H),8.84(t,J=6.0Hz,1H),7.83(d,J=4.0Hz,1H),7.77(d,J=9.2Hz,2H),7.75(d,J=7.2Hz,2H),7.59(d,J=4.0Hz,1H),7.49(疑t,J=7.2Hz,2H),7.41(疑t,J=7.6Hz,1H),7.07(d,J=8.8Hz,2H),4.22(疑t,J=5.6Hz,2H),3.69(疑q,J=5.2Hz,2H).EM(計算値):382.1;MS(ESI)m/e(M+1H)+:383.1,(M-1H)-:381.0.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),10.15(s,1H),8.36(t,J=5.6Hz,1H),7.70(d,J=8.8Hz,2H),7.32(m,1H),6.97(d,J=8.8Hz,2H),6.92(m,1H),6.88(m,1H),4.04(t,J=5.6Hz,2H),3.66(s,2H),3.45(m,2H).EM(計算値):320.1;MS(ESI)m/e(M+1H)+:320.9,(M-1H)-:319.0.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.87(m,2H),8.45(s,1H),7.97(m,4H),7.71(d,J=8.8Hz,2H),7.59(m,2H),7.02(d,J=8.8Hz,2H),4.21(t,J=5.6Hz,2H),3.71(m,2H).EM(計算値):350.1;MS(EST)m/e(M+1H)+:350.9,(M-1H)-:349.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.98(m,2H),8.52(m,2H),8.19(d,J=8.8Hz,1H),8.08(d,J=8.8Hz,1H),7.71(d,J=8.8Hz,2H),7.62(m,1H),7.02(d,J=8.8Hz,2H),4.22(t,J=5.6Hz,2H),3.72(m,2H).EM(計算値):351.1;MS(ESI)m/e(M+1H)+:351.8,(M-1H)-:349.9.
EM(計算値):383.1;MS(ESI)m/e(M+1)+:383.9,(M-1)-:382.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.88(s,1H),8.61(t,J=4.8Hz,1H),7.78(d,J=8.4Hz,2H),7.70(d,J=8.8Hz,2H),7.46(d,J=8.8Hz,2H),6.99(d,J=8.6Hz,2H),4.15(t,J=5.6Hz,2H),3.62(m,2H),1.29(s,9H).EM(計算値):356.2;MS(ESI)m/e(M+1H)+:357.0,(M-1H)-:355.1.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1H),8.95(s,1H),8.72(d,J=5.2Hz,1H),8.56(t,J=4.8Hz,1H),8.40(d,J=7.6Hz,1H),7.80(m,1H),7.71(d,J=8.8Hz,2H),7.55(d,J=16.0Hz,1H),7.00(d,J=8.8Hz,2H),6.90(d,J=16.0Hz,1H),4.12(t,J=5.6Hz,2H),3.59(m,2H).EM(計算値):327.1;MS(ESI)m/e(M+1H)+:328.1,(M-1H)-:326.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.88(s,1H),8.73(t,J=5.6Hz,1H),7.93(d,J=9.2Hz,2H),7.69(m,4H),7.47(t,J=2.4Hz,2H),7.01(d,J=9.2Hz,2H),6.29(t,J=2.4Hz,2H),4.18(t,J=5.6Hz,2H),3.66(m,2H).EM(計算値):365.1;MS(ESI)m/e(M+1H)+:366.0,(M-1H)-:364.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.53(t,J=5.6Hz,1H),7.80(d,J=9.2Hz,2H),7.70(d,J=9.2Hz,2H),6.99(m,4H),5.95(m,1H),5.80(m,1H),4.96(s,1H),4.14(t,J=5.6Hz,2H),3.60(m,2H),2.00(m,3H),1.72(m,3H).EM(計算値):396.2;MS(ESI)m/e(M+1H)+:397.1,(M-1H)-:395.2.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.35(t,J=5.6Hz,1H),8.25(d,J=7.6Hz,1H),8.15(d,J=8.0Hz,1H),7.73(d,J=8.8Hz,2H),7.68-7.58(m,2H),7.03(d,J=9.2Hz,2H),4.23(疑t,J=6.4Hz,2H),3.74(疑q,J=6.0Hz,2H).EM(計算値):357.1;MS(ESI)m/e(M+1H)+:358.1,(M-1H)-:356.0.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),9.47(t,J=5.6Ha,1H),7.90(疑t,J=9.2Hz,2H),7.73(d,J=8.8Hz,2H),4.59(td,J1=7.6Hz,J2=0.8Hz,1H),7.52(td,J2=8.0Hz,J2=1.2Hz,1H),7.03(d,J=8.8Hz,2H),4.24(t,J=6.0Hz,2H),3.72(疑q,J=6.0Hz,2H).EM(計算値):341.1;MS(ESI)m/e(M+1H)+:342.1,(M-1H)-:340.2.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),9.70(s,1H),8.91,(t,J=5.6Hz,1H),7.72(d,J=8.4Hz,2H),6.97(d,J=8.4Hz,2H),4.10(m,2H),3.93(m,2H),3.54(m,2H),3.27(m,2H),3.08(m,2H),2.21(m,1H),2.01(m,1H),1.51(m,10H).EM(計算値):375.2;MS(ESI)m/e(M+1H)+:376.1,(M-1H)-:374.1.
1H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.35(d,J=6.8Hz,2H),7.72(d,J=9.2Hz,2H),7.25(d,J=6.8Hz,2H),6.98(d,J=9.2Hz,2H),4.10(t,J=5.6Hz,2H),3.97(m,2H),3.54(m,10H).EM(計算値):399.2;MS(ESI)m/e(M+1H)+:400.1,(M-1H)-:398.1.
EM(計算値):290.1;MS(ESI)m/e(M+1)+:291.1,(M-1)-:289.2.
EM(計算値):377.1;MS(ESI)m/e(M+1)+:377.9,(M-1)-:376.0.
EM(計算値):377.1;MS(ESI)m/e(M+1)+:378.0,(M-1)-:375.9.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.11(t,J=5.6Hz,1H),7.70(d,J=9.2Hz,2H),7.62(m,2H),7.29(m,2H),7.01(d,J=9.2Hz,2H),4.21(t,J=5.6Hz,2H),3.71(m,2H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.0,(M-1H)-:339.1.
EM(計算値):289.1;MS(ESI)m/e(M+1H)+:290.0,(M-1H)-:287.8.
1H NMR(400MHz,DMSO-d6)δ11.04(s1H),10.43(s,1H),8.62(t,J=6.0Hz,1H),7.94(d,J=6.4Hz,2H),7.853(m,4H),7.70(d,J=9.2Hz,2H),7.60(m,1H),7.52(m,2H),7.00(d,J=9.2Hz,2H),4.16(t,J=6.0Hz,2H),3.63(dt,J1=5.6Hz,J2=6.0Hz,2H).EM(計算値):419.2;MS(ESI)m/e(M+1H)+:420.2,(M-1H)-:418.3.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.23(t,J=6.0Hz,1H),9.01(s,1H),8.89(d,J=6.8Hz,2H),8.38(d,J=6.4Hz,2H),7.70(d,J=9.2Hz,2H),7.00(d,J=9.2Hz,2H),4.22(t,J=5.6Hz,2H),3.71(m,2H).EM(計算値):384.1;MS(ESI)m/e(M+1H)+:384.9,(M-1H)-:382.9.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),7.69(d,J=8.4Hz,2H),7.56(t,J=5.6Hz,1H),7.01(d,J=8.8Hz,2H),4.01(t,J=5.6Hz,2H),3.40(m,2H),1.95(m,3H),1.69(m,12H).EM(計算値):358.2;MS(ESI)m/e(M+1H)+:358.9,(M-1H)-:357.2.
EM(計算値):336.09;MS(ESI)m/e(M-1H)-:335.3.
EM(計算値):370.12;MS(ESI)m/e(M-1H)-:369.0.
EM(計算値):344.10;MS(ESI)m/e(M+1H)+:345.0,(M-1H)-:343.1.
EM(計算値):360.13;MS(ESI)m/e(M-1H)-:359.1.
EM(計算値):344.10;MS(ESI)m/e(M-1H)-:358.8.
EM(計算値):336.09;MS(ESI)m/e(M+1H)+:337.2,(M-1H)-:335.0.
EM(計算値):328.14;MS(ESI)m/e(M+1H)+:329.2,(M-1H)-:327.2.
EM(計算値):368.03;MS(ESI)m/e(M-1H)+:367.0.
EM(計算値):328.14;MS(ESI)m/e(M+1H)+:328.8,(M-1H)-:327.2.
EM(計算値):364.08;MS(ESI)m/e(M+1H)+:365.1,(M-1H)-:363.2.
EM(計算値):344.14;MS(ESI)m/e(M+1H)+:345.1,(M-1H)-:343.1.
EM(計算値):344.14;MS(ESI)m/e(M+1H)+:345.0,(M-1H)-:343.2.
EM(計算値):348.11;MS(ESI)m/e(M+1H)+:348.8,(M-1H)-:346.9.
EM(計算値):412.11;MS(ESI)m/e(M+1H)+:413.3,(M-1H)-:411.0.
EM(計算値):412.11;MS(ESI)m/e(M+1H)+:413.2,(M-1H)-:411.1.
EM(計算値):376.14;MS(ESI)m/e(M+1H)+:377.0,(M-1H)-:375.2.
EM(計算値):339.12;MS(ESI)m/e(M+1H)+:340.1,(M-1H)-:338.3.
1H NMR(400MHz,DMSO-d6)δ11.53(s,1H),11.04(s,1H),8.12(d,J=7.6Hz,2H),8.01(s,1H),7.70(d,J=9.2Hz,2H),7.40(d,J=8.0,Hz,1H),7.10(m,2H),7.017(d,J=8.8Hz,2H),4.16(t,J=5.6Hz,2H),3.64(m,2H).EM(計算値):339.1;MS(ESI)m/e(M+1H)+:340.0,(M-1H)-:338.1.
1H NMR(400MHz,DMSO-d6)δ9.37(s,1H),9.21(t,J=5.2Hz,1H),9.02(s,1H),8.15(t,J=9.2Hz,2H),7.94(m,1H),7.74(m,3H),7.02(d,J=8.8Hz,2H),4.24(t,J=5.6Hz,2H),3.75(m,2H).EM(計算値):351.1;MS(ESI)m/e(M+1H)+:352.0,(M-1H)-:349.9.
1H NMR(400MHz,DMSO-d6)δ11.11(s,1H)9.09(d,J=4.4Hz,1H),8.70(d,J=7.6Hz,1H),8.65(d,J=7.6Hz,1H),8.29(d,J=8.0Hz,1H),7.79(m,4H),7.10(d,J=8.8Hz,2H),4.30(t,J=5.6Hz,2H),3.89(m,2H).EM(計算値):351.1;MS(ESI)m/e(M+1H)+:352.0,(M-1H)-:349.9.
1H NMR(400MHz,DMSO-d6)δ13.57(s,1H),11.04(s,1H),8.88(s,1H),8.53(t,J=5.6Hz,1H),8.16(d,J=8.0Hz,1H),7.70(d,J=8.8Hz,2H),7.60(d,J=8.4Hz,1H),7.40(t,J=8.0Hz,1H),7.23(t,J=8.0Hz,1H),7.01(d,J=8.8Hz,2H),4.19(t,J=6.0Hz,2H),3.68(m,2H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.1,(M-1H)-:339.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.89(m,2H),8.45(s,1H),7.93(s,2H),7.70(d,J=8.4Hz,2H),7.01(d,J=8.8Hz,2H),4.20(t,J=5.6Hz,2H),3.69(m,2H).EM(計算値):341.1;MS(ESI)m/e(M+1H)+:341.8,(M-1H)-:340.0.
1H NMR(400MHz,DMSO-d6)δ9.07(s,1H),9.24(d,J=8.0Hz,1H),8.53(m1H),8.03(m,2H),7.82(t,J=6.8Hz,1H),7.71(m,3H),7.03(d,J=8.4Hz,2H),4.24(t,J=4.8Hz,2H),3.76(m,2H).EM(計算値):351.1;MS(ESI)m/e(M+1H)+:351.9,(M-1H)-:350.1.
1H NMR(400MHz,DMSO-d6)δ9.39(s,1H),9.11(s,1H),8.59(s,1H),8.25(m,1H),7.87(m,2H),7.70(m,2H),7.02(m,2H),4.23(s,2H),3.76(s,2H).EM(計算値):351.1;MS(ESI)m/e(M+1H)+:3518,(M-1H)-:349.9.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.47(m,1H),9.23(m,1H),8.19(m,2H),7.98(m,2H),7.70(d,J=8.8Hz,2H),7.02(d,J=8.4Hz,2H),4.25(t,J=5.2Hz,2H),3.78(m,2H).EM(計算値):352.1;MS(ESI)m/e(M+1H)+:352.8,(M-1H)-:350.9.
EM(計算値):350.11;MS(ESI)m/e(M+1H)++:351.1,(M-1H)-:349.1.
EM(計算値):351.12;MS(ESI)m/e(M+1H)+:352.2,(M-1H)-:350.0.
EM(計算値):365.14;MS(ESI)m/e(M+1H)+:366.0,(M-1H)-:364.2.
EM(計算値):368.12;MS(ESI)m/e(M+1H)+:369.0,(M-1H)-:367.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.88(s,1H),8.68(t,J=5.6Hz,1H),8.34(s,1H),8.14(s,1H),7.75(d,J=8.0Hz,1H),7.70(d,J=8.4Hz,2H),7.61(d,J=8.0Hz,1H),7.01(d,J=8.8Hz,2H),4.18(t,J=6.0Hz,2H),3.66(m,2H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.0,(M-1H)-:339.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.11(m,2H),7.98(s,1H),7.70(d,J=9.2Hz,2H),7.47(d,J=7.6Hz,1H),7.20(t,J=8.4Hz,1H),7.13(t,J=6.8Hz,1H),7.01(d,J=9.2Hz,2H),4.15(t,J=6.0Hz,2H),3.82(s,3H),3.62(m,2H).EM(計算値):353.1;MS(ESI)m/e(M+1H)+:354.0,(M-1H)-:351.9.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.14(t,J=5.6Hz,1H),8.19(d,J=8.4Hz,1H),8.08(d,J=8.4Hz,1H),7.85(t,J=8.4Hz,1H),7.69(m,4H),7.03(d,J=8.8Hz,2H),4.24(t,J=6.0Hz,2H),4.15(s,3H),3.78(m,2H).EM(計算値):381.1;MS(ESI)m/e(M+1H)+:381.9,(M-1H)-:380.1.
EM(計算値):380.14;MS(ESI)m/e(M+1H)+:381.0,(M-1H)-:379.0.
EM(計算値):380.14;MS(ESI)m/e(M+1H)+:381.2,(M-1H)-:378.9.
EM(計算値):351.12;MS(ESI)m/e(M+1H)+:352.0,(M-1H)-:350.0.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.26(t,J=5.6Hz,1H),7.70(d,J=8.8Hz,2H),7.41-7.35(m,4H),7.29(m,1H),7.21(s,1H),7.00(d,J=9.2,2H),4.12(t,J=6.0Hz,2H),3.54(疑q,J=6.0Hz,2H),2.01(s,3H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:340.9,(M-1H)-:339.2.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.72(brs,1H),8.81(t,J=5.2Hz,1H),7.94(dd,J1=8.4Hz,J2=2.0Hz,1H),7.73(d,J=8.8Hz,2H),7.32(s,1H),7.03(d,J=9.2Hz,2H),4.60(s,2H),4.13(疑t,J=5.6Hz,2H),3.70(疑q,J=5.2Hz,2H),2.83(s,6H).EM(計算値):397.2;MS(ESI)m/e(M+1H)+:398.1,(M-1H)-:396.0.
1H NMR(DMSO-d6):0.92(3H,t,7Hz);1.53(1H,m);1.72(1H,m);2.48(3H,s);3.94(1H,m);4.03(2H,m);6.62(1H,s);6.78(1H,dd);6.92(1H,d);7.01(2H,d);7.08(1H,s);7.31(1H,d);7.7(2H,d);8.27(2H,d,7Hz);9.25(1H,s).MS(M+1):425.
1H NMR(DMSO-d6):0.90(2H,dd);0.91(3H,t,7Hz);1.1(2H,br.S);1.52(1H,m);1.68(1H,m);1.92(1H,m);2.0-2.1(3H,m*);2.25(1H,m);2.48(3H,s);3.24(1H,m);3.37(4H,m);3.54(1H,m);3.95(1H,m);4.03(2H,m);6.66(1H,s);6.97(1H,m);6.99(2H,d,9Hz);7.07(1H,dd,9,2Hz);7.12(1H,d,6Hz):7.28(1H,dd,20,2Hz);7.45(1H,t,9Hz),7.7(2H,d,9Hz);8.29(1H,d,8Hz).MS(M+1):548.
1H NMR(DMSO-d6):2.00(2H,m);2.64(1H,m);2.75(1H,m);4.1(1H,m);4.18(1H,m);4.39(1H,m);6.98(2H,d,9Hz);7.14(1H,m);7.19-7.28(5H,m);7.32(1H,t,8Hz);7.45(1H,m);7.58(1H,s);7.65(1H,d,7Hz);7.68(2H,d,9Hz);7.76(1H,d,J=7Hz)8.74(1H,d,7Hz).MS(M-1):443.
1H NMR(DMSO-d6):3.56(2H,m);4.15(1H,m);4.23(1H,m);4.57(2H,s);4.94(1H,m);6.99(2H,d,9Hz);7.33(1H,t,7Hz);7.38(5H,s);7.47(1H,t,7Hz)7.58(1H,s);7.65(1H,d,8Hz);7.70(2H,d,9Hz);7.77(1H,d,8Hz);8.90(1H,s);9.0(1H,d,8Hz).MS(M+1):509.
1H NMR(DMSO-d6):2.7-2.81(2H,m);3.78(2H,s);4.12(1H,dd,10.5Hz);4.22(1H,dd,10.7Hz);4.51(1H,m);6.97(2H,d,9Hz);7.22(1H,m);7.28(2H,m);7.29(2H,s);7.33(1H,t,7Hz);7.46(1H,td,7.1Hz);7.58(1H,s);7.65(1H,d,8Hz);7.70(2H,d,9Hz);7.77(2H,d,8Hz);8.79(1H,d,8Hz).MS(M+1):475.
1H NMR(DMSO-d6):2.47(3H,d,1Hz);3.57-3.62(3H,m);3.77(3H,s);4.08(1H,t,6Hz);6.64(1H,s);6.92(1H,dd,9,3Hz);6.99(2H,d,9Hz);7.12-7.15(2H,s+d);7.42(1H,d,9Hz);7.7(2H,d,9Hz);8.49(1H,t,6Hz);8.88(1H,s).MS(M+1):411.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.91(s,1H),8.24(t,J=5.6Hz,1H),7.73(d,J=9.2Hz,2H),7.57(d,J=6.8Hz,2H),7.44(d,J=16.0Hz,1H,7.41においてmの下に埋もれた),7.41(m,3H),7.00(d,J=8.8Hz,2H),6.63(d,J=16.0Hz,1H),4.10(疑t,J=6.0Hz,2H),3.37(疑q,J=6.4Hz,2H),1.96(疑p,J=6.4Hz,2H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.2,(M-1H)-:339.3.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.15(s,1H),7.73(d,J=8.4Hz,2H),7.51(d,J=8.4Hz,2H),7.38(d,J=15.6Hz,1H),6.99(m,4H),6.48(d,J=15.6Hz,1H),4.09(疑t,J=6.0Hz,2H),3.80(s,3H),3.35(疑q,J=5.2Hz,2H),1.94(疑q,J=6.0Hz,2H).EM(計算値):370.2;MS(ESI)m/e(M+1H)+:371.0,(M-1H)-:368.9.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.90(t,J=5.6Hz,1H),8.31(s,1H),7.98(dd,J1=7.2Hz,J2=1.6Hz,2H),7.62(d,J=8.4Hz,2H),7.40(疑t,J=7.2Hz,2H),7.31(疑tt,J1=7.2Hz,J2=2.0Hz,1H),6.90(d,J=9.2Hz,2H),4.03(t,J=5.6Hz,2H),3.42(疑q,J=6.0Hz,2H),1.98(疑p,J=6.0Hz,2H).EM(計算値):397.1;MS(ESI)m/e(M+1H)+:397.9,(M-1H)-:396.0.
1H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.26(d,J=7.2Hz,1H),7.74(d,J=8.4Hz,2H),7.58(d,J=7.2Hz,2H),7.44(m,4H),7.05(d,J=8.8Hz,2H),6.68(d,J=16.4Hz,1H),4.27(m,1H),4.07(m,1H),3.96(m,1H),1.25(d,J=6.8Hz,3H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.1,(M-1H)-:339.1.
1H NMR(400MHz,DMSO-d6)δ11.09(s,1H),8.27(d,J=8.0Hz,1H),7.74(d,J=8.8Hz,2H),7.58(d,J=7.2Hz,2H),7.46(d,J=16.0Hz,1H),7.42(m,3H),7.04(d,J=9.2Hz,2H),6.68(d,J=16.4Hz,1H),4.27(疑p,J=6.8Hz,1H),4.07(dd,J1=5.6Hz,J2=10.0Hz,1H),3.96(dd,J1=5.6Hz,J2=9.6Hz,1H),1.25(d,J=7.2Hz,3H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.1,(M-1H)-:339.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.87(s,1H),8.12(d J=8.0Hz,1H),7.67(dt,J1=8.8Hz,J2=2.0Hz,1H),7.54(dd,J1=8.4Hz,J2=1.6Hz,2H),7.43-7.33(m,4H),6.99(dt J1=9.2Hz,J2=2Hz,2H),6.65(d,J=15.6Hz,1H),4.26(m,1H),4.01(dd,J1=9.6Hz,J2=4.8Hz,1H),3.94(dd J1=9.6Hz,J2=5.6Hz,1H),1.66(m,1H),1.49(m,2H),0.91(d J=6.8Hz,3H),0.87(d,J=6.4Hz,3H).EM(計算値):382.2;MS(ESI)m/e(M+1H)+:383.0,(M-1H)-:381.1.
1H NMR(400MHz,DMSO-d6)δ10.95(s,1H),8.81(s,1H),8.05(d,J=8.4Hz,1H),7.62(d,J=8.8Hz,2H),7.47(d,J=6.8Hz,2H),7.37-7.28(m,4H),6.92(dt,J1=8.4Hz,J2=1.6Hz,2H),6.61(d,J=16Hz,1H),4.21(m,1H),3.94(m,1H),3.86(m,1H),1.69(d.J=12.4Hz,1H),1.59-1.52(m,4H),1.42(t,J=7.2Hz,2H),1.28(m,1H),1.15-1.05(m,3H),090(m,1H),0.77(m,1H).EM(計算値):422.2;MS(ESI)m/e(M+1H)+:423.2,(M-1H)-:421.2.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.88(s,1H),8.09(d,J=8.4Hz,1H),7.69(dt,J1=8.8Hz,J2=2.8Hz,2H),7.432-7.32(連続(series)m,4H),6.99(dt,J1=9.2Hz,J2=2.4Hz,2H),6.73(d,J=15.6Hz,1H),4.05(s,3H),1.98(m,1H),0.95(d,J=2.4Hz,3H),0.93(d,J=2.4Hz,3H).EM(計算値):368.2;MS(ESI)m/e(M+1H)+:368.7,(M-1H)-:367.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.32(d,J=8Hz,1H),7.69(d,J=9.2Hz,2H),7.53(m,2H),7.43-7.34(m,4H),7.28-7.22(m,3H),7.18(m,2H),6.99(d,J=9.2Hz,2H),6.63(d,J=16Hz,1H),4.38(m,1H),4.02(d,J=6.4Hz,2H),2.99(m,1H),2.88(m,1H).OH又はNHを失う.EM(計算値):416.2;MS(ESI)m/e(M+1H):417.3,(M-1H):415.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.78(s,1H),8.32(d,J=8Hz,1H),7.69(d,J=8.8Hz,2H),7.52(dd,J1=8.4Hz,J2=1.6Hz,2H),7.41-7.34(m,4H),7.28-7.23(m,4H),7.19-7.15(m,1H),6.99(d,J=9.2Hz,2H),6.63(d,J=15.6Hz,1H),4.38(m,1H),4.01(d,J=4.4Hz,2H),2.99(dd,J1=13.6Hz,J2=6Hz,1H),2.88(dd,J1=14Hz,J2=8Hz,1H).EM(計算値):416.2;MS(ESI)m/e(M+1H)+:417.2,(M-1H)-:415.2.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.87(s,1H),8.12(d,J=8.0Hz,1H),7.69(d,J=8.4Hz,2H),7.53(d,J=7.2Hz,2H),7.43-7.33(m,4H),6.99(d,J=9.2Hz,2H),6.65(d,J=15.6Hz,1H),4.25(m,1H),4.01(dd,J=9.6Hz,4.8Hz,1H),3.94(dd J1=9.6Hz,J2=5.6Hz,1H),1.66(m,1H),11.48(m,2H),0.91(d J=6.8Hz,3H),0.87(d,J=6.4Hz,3H).EM(計算値):382.2;MS(ESI)m/e(M+1H)+:383.2,(M-1H):381.2.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.87(s,1H),8.08(d,J=8Hz,1H),7.69(d,J=8.8Hz,2H),7.55(d,J=1.2Hz,2H),7.43-7.32(m,4H),6.99(d,J=9.2Hz,2H),6.73(d,J=16Hz,1H)4.05(s,3H),1.98(m,1H),0.946(d,J=2Hz,3H),0.93(d,J=2.4Hz,3H).EM(計算値):368.2;MS(ESI)m/e(M+1H)+:369.1,(M-1H)-:367.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.14(d,J=8.4Hz,1H),7.69(dt,J1=8.8Hz,J2=2.8Hz,2H),7:54(dd,J1=6.8,J2=1.2Hz,2H),7.43-7.32(m,4H),6.99(dt,J1=8.8Hz,J2=3.2Hz,2H),6.66(d,J=15.6Hz,1H),4.16(m,1H),4.03(dd,J1=10Hz,J2=5.6Hz,1H),3.96(dd,J1=10Hz,J2=5.2Hz,1H),1.67(m,1H),1.53(m,1H),1.36-1.27(m,4H),0.87(t,J=6.4Hz,3H).1H,NH又はOHを失う.EM(計算値):382.2;MS(ESI)m/e(M+1H)+:383.1,(M-1H)-:381.1.
1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),8.25(d,J=8.4Hz,1H),7.64(dt,J1=8.8Hz,J2=2Hz,2H),7.46(dd,J1=7.6Hz,J2=2Hz,2H),7.34-7.18(連続m,6H),6.93(dt,J1=9.2Hz,J2=2.8Hz,2H),6.54(d,J=15.6Hz,1H),4.31(m,1H),3.95(d,J=4.8Hz,2H),2.93(dd,J1=13.6Hz,J2=5.6Hz,1H),2.79(dd,J1=13.6Hz,J2=8.4Hz,1H).EM(計算値):450.1;MS(ESI)m/e(M+1H)+:451.2;(M-1H):449.2.
1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),8.07(d,J=8Hz,1H),7.62(dt,J1=8.8Hz,J2=2.8Hz,2H),7.47(dd,Je=8.8Hz,J2=1.6Hz,2H),7.34-7.26(連続m,4H),6.93(dt,J1=8.8Hz,J2=2.8Hz,2H),6.61(d,J=15.6Hz,1H),4.04(m,1H),3.98(dd,J1=15.6Hz,J2=5.6Hz,1H),3.90(dd,J1=9.2,J2=5.6Hz,1H),1.64(m,1H),1.46(m,1H),0.85(t,J=6.8Hz,3H).EM(計算値):354.2;MS(ESI)m/e(M+1H)+:354.6,(M-1H)-:353.2.
1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),8.07(d,J=8Hz,1H),7.62(d J=8.8Hz,2H),7.47(dd,J1=6.8Hz,J2=1.6Hz,2H),7.35-7.62(連続m,4H),6.93(dt,J1=9.2,J2=2Hz,2H),6.61(d,J=15.6Hz,1H),3.98(dd,J1=9.6Hz,J2=5.6Hz,1H),3.90(dd,J1=9.6,J2=4.8Hz,1H),1.65(m,1H),1.49(m,1H),0.85(t,J=7.2Hz,3H).EM(計算値):354.2;MS(ESI)m/e(M+1H)+:354.8,(M-1H)+:353.1.
EM(計算値):400.49;MS(ESI)m/e(M+1):401.0,(M-1):399.0.
EM(計算値):400.49;MS(ESI)m/e(M+1):401.1,(M-1):399.2.
1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),8.80(brs,1H),8.73(d,J=8.4Hz,1H),7.62(d,J=9.2Hz,2H),7.48(d,J=6.8Hz,2H),7.38-7.27(連続m,8H),7.21(t,J=7.2Hz,1H),6.93(d,J=8.8,2H),6.69(d,J=15.6Hz,1H),5.30(dd,J1=13.6Hz,J2=7.6Hz,1H),4.19(d,J=6.4Hz,2H).EM(計算値):402.2;MS(ESI)m/e(M+1H)+:403.2,(M-1H)-:400.9.
1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),8.80(brs,1H),8.74(d,J=8Hz,1H),7.62(dt,J1=8.8Hz,J2=2Hz,2H),7.48(dd,J1=6.4Hz,J2=1.6Hz,2H),7.39-7.27(連続m,8H),7.21(tt,J1=7.6Hz,J2=1.2Hz,1H),6.93(dt,J1=9.2Hz,J2=2.4Hz,2H),6.69(d,J=15.6,1H),5.29(dd,J1=8Hz,J2=6.4Hz,1H),4.18(d,J=6.4Hz,2H).EM(計算値):402.2;MS(ESI)m/e(M+1H)+:402.9,(M-1H)+:401.2.
1H NMR(400MHz,DMSO-d6)δ8.25(d,J=8Hz,1H),7.83(d,J=8.8Hz,2H),7.48(d,J=6.4Hz,2H),7.39-7.27(連続m,4H),7.01(d,J=8.8Hz,2H),6.58(d,J=16.4Hz,1H),4.25(m,1H),4.03(m,2H),3.73(s,3H),3.12(m,2H),2.06(m,1H),1.93(m,1H).EM(計算値):432.1;MS(ESI)m/e(M+1H)+:433.2,(M-1H)-:430.0.
1H NMR(400MHz,DMSO-d6)δ8.24(d,J=8Hz,1H),7.82(d,J=8.8Hz,2H),7.48(d,J=8.8Hz,2H),7.84-7.29(連続m,4H),7.01(d,J=8.8Hz,2H),6.58(d,J=16.4Hz,1H),4.35(m,1H),4.03(m,2H),3.70(s,3H),3.13(m,2H),2.06(m,1H),1.93(m1H).EM(計算値):432.1;MS(ESI)m/e(M+1H)+:432.2,(M-1H)-:430.2.
1H NMR(400MHz,DMSO-d6)δ8.50(d,J=8.0Hz,1H),7.83(dt,J1=9.2Hz,J2=2.8Hz,2H),7.48(dd,J1=6Hz,J2=1.6Hz,2H),7.39(d,J=16Hz,1H),7.31(m,9H),6.97(dt,J1=9.2Hz,J2=2.4Hz,2H),6.57(d,J=16Hz,1H),4.72(m,1H),4.50(s,1H),4.16(dd,J1=9.6Hz,J2=5.2Hz),1H,4.08(dd,J1=10Hz,J2=4.8Hz,1H),3.45(dd,J1=14.4Hz,J2=5.6Hz,1H),3.36(dd,J1=14.4Hz,J2=6.8Hz,1H).EM(計算値):492.2;MS(ESI)m/e(M+1H)+:494.3,(M-1H)-:492.2.
1H NMR(400MHz,DMSO)δ11.07(brs,1H),8.38(d,J=7.6Hz,2H),7.84(dd,J1=3.6Hz,J2=1.2Hz,1H),7.77(dd,J1=4.8Hz,J2=1.2Hz,1H),7.72(d,J=8.4Hz,2H),7.16(dd,J1=3.6Hz,J2=5.2Hz,1H),7.02(d,J1=8.4Hz,2H),4.20(m,1H),4.13(dd,J1=6.4Hz,J2=9.6Hz,1H),4.04(dd,J1=5.2Hz,J2=9.2Hz,2H)1.77(m1H),1.63(m,1H),1.21(d,J=6.4Hz,1H),0.96(t,J=7.2Hz,3H).EM(計算値):334.1;MS(ESI)m/e(M+1H)+:335.0,(M-1H)-:333.0.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.37(d,J=8.0Hz,1H),7.94(d,J=8.4Hz,2H),7.72(m,6H),7.48(m,2H),7.39(m,1H),7.00(d,J=8.4Hz,2H),4.24(m,1H),4.06(m,2H),1.74(m,2H),0.95(t,J=7.2Hz,3H).EM(計算値):404.2;MS(ESI)m/e(M+1H)+:405.2,(M-1H)-:403.2.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.87(s,1H),8.50(d,J=8.4Hz,1H),8.44(s,1H),7.97(m,4H),7.70(d,J=8.8Hz,2H),7.59(m,2H),7.02(d,J=8.8Hz,2H),4.29(m,1H),4.14(m,2H),1.68(m,2H),0.98(t,J=7.2Hz,3H).EM(計算値):378.2;MS(ESI)m/e(M+1H)+:378.9,(M-1H)-:377.0.
1H NMR(400MHz,DMSO-d6)δ10.98(s,1H),8.82(s,1H),8.27(d,J=8.4Hz,1H),7.64(d,J=9.2Hz,2H),7.48(dd,J1=6.4Hz,J2=1.6Hz,2H),7.38(d,J=15.6Hz,1H),7.36-7.27(m,3H),7.23-7.19(m,4H),7.14(m,1H),6.92(d,J=8.8Hz,2H),6.61(d,J=15.6Hz,1H),4.29(m,1H),4.08(dd,J1=9.6Hz,J2=5.6Hz,1H),3.98(dd,J1=9.6Hz,J2=4.4Hz,1H),3.70(d,J=2.4Hz,2H),2.67(dd,J1=6.8Hz,J2=13.6Hz,1H),2.58(dd,J1=13.2Hz,J2=7.2Hz,1H).EM(計算値):460.2;MS(ES1)m/e(M-1H)-:460.8.
1H NMR(400MHz,DMSO-d6)δ11.02(s,1H),8.31(d,J=8.4Hz,1H),7.83(d,J=7.2Hz,2H),7.68(d,J=8.8Hz,2H),7.52-7.42(m,3H),6.99(d,J=9.2Hz,2H),4.22(m,1H),4.11(dd,J1=6.4Hz,J2=10.0Hz,1H),4.01(dd,J1=6.0Hz,J2=9.6Hz,1H),1.73(m1HO,1.62(m,1H),0.93(t,J=7.6Hz,3H).EM(計算値):328.1;MS(ESI)m/e(M+1H)+:329.1.(M-1H)-:327.0.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.08(d,J=7.2Hz,1H),7.69(d,J=8.8Hz,2H),7.24(m,5H),6.96(d,J=9.2Hz,2H),3.94(m3H),3.43(s,2H),1.64(m,1H),1.47(m,1H),0.86(t,7.2Hz,3H).EM(計算値):342.2;MS(ESI)m/e(M+1H)+:343.0,(M-1H)-:341.1.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),7.81(d,J=7.6Hz,1H),7.69(d,J=8.4Hz,2H),7.23-7.10(m,5H),6.94(d,J=9.2Hz,2H),3.94(m,2H),3.84(m,1H),2.81(t,J=7.2Hz,2H),2.40(t,J=7.6Hz,2H),1.61(ddd,J1=4.4Hz,J2=7.6Hz,J3=18.4Hz,1H),1.41(m,1H),0.81(t,J=6.8Hz,3H).EM(計算値):356.2;MS(ESI)m/e(M+1H)+:357.1,(M-1H)-:355.1.
EM(計算値):356.38;MS(ESI)m/e(M+1):357.0,(M-1):355.1.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.65(d,J=8.8Hz,1H),8.33(s,1H),8.00(d,J=7.2Hz,2H),7.62(d,J=8.4Hz,2H),7.39(疑t,J=7.2Hz,2H),7.30(疑t,J=7.6Hz,1H),6.93(d,J=9.2Hz,2H),4.20(m,1H),4.23(dd4.20において部分的に埋もれている)J1=9.2Hz,J2=16.8Hz,1H),4.05(dd,J1=10.0Hz,J2=4.8Hz,1H),1.69(m1H),1.62(m,1H),0.88(t,J=7.2Hz,3H).EM(計算値):411.1;MS(ESI)m/e(M-1H)-:410.1.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.03(d,J=7.6Hz,1H),7.69(d,J=8.8Hz,2H),7.48(d,J=9.2Hz,2H),7.36(d,J=15.6Hz,1H),6.99(d,J=9.2Hz,2H),6.95(d,J=8.8Hz,2H),6.52(d,J=15.6Hz,1H),4.09(m,1H),4.04(dd,J1=5.2Hz,J2=9.6Hz,1H),3.95(dd,J1=5.2Hz,J2=9.6Hz,1H),3.77(s,3H),1.71(m,1H),1.52(m,1H),0.91(t,J=6.8Hz,3H).EM(計算値):384.2;MS(ESI)m/e(M+1H)+:385.0,(M-1H)-:383.2.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),10.62(brs,1H),8.43(d,J=8.0Hz,1H),8.28(d,J=1.6Hz,1H),7.94(dd,J1=8.4Hz,J2=2.0Hz,1H),7.23(d,J=8.4Hz,2H),7.32(s,1H),7.03(d,J=8.8Hz,2H),4.60(s,2H),4.28(m,1H),4.17(dd1,J1=10.0Hz,J2=6.8Hz,1H),4.08(dd,J1=10.4Hz,J2=6.0Hz,1H),2.84(s,6H),1.80(m,1H),1.65(m,1H),0.98(t,J=7.6Hz,3H).EM(計算値):425.2;MS(ESI)m/e(M+1H)+:426.2,(M-1H)-:424.1.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.80(s,1H),8.27(t,J=5.2Hz,1H),7.62(J=8.8Hz,2H),7.46(d,J=6.8Hz,2H),7.36(d,J=12.8Hz,1H),7.33-7.28(m,3H),6.95(d,J=8.4Hz,2H0,6.60(d,J=12.8Hz,1H),4.53(ddd,J=5.6Hz,1H),3.40(m,1H),3.29(m,1H,水のピークの下に埋もれた),1.19(d,J=6.4Hz,3H).EM(計算値):340.1.
1H NMR(400MHz,DMSO-d6)δ11.02(s,1H),8.87(s,1H),8.34(t,J=5.6Hz,1H),7.68(d,J=8.4Hz,2H),7.53(d,J=8.8Hz,2H),7.43(d,J=13.2Hz,1H),7.40-7.35(m,3H),7.02(d,J=8.8Hz,2H),6.67(d,J=16Hz,1H),4.60(ddd,J1=6.0Hz,J2=11.6Hz,J3=17.6Hz,1H),3.47(m,1H),3.36(m,1H,水のピークの下に埋もれた),1.26(d,J=6.0Hz,3H).EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.0,(M-1H)-:339.2.
EM(計算値):397.1;MS(ESI)m/e(M-1H)-:396.1.
EM(計算値):397.1;MS(ESI)m/e(M+1H)+:398.2,(M-1H)-:396.2.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.69(t,J=5.6Hz,1H),7.84(d,J=8.4Hz,2H),7.67(d,J=8.4Hz,1H),7.63(m,4H),7.40(t,J=7.6Hz,2H),7.32(m,1H),6.98(d,J=12.0Hz,2H),4.62(ddd,J1=6.0Hz,J2=12.0Hz,J3=18.0Hz,1H),3.52(ddd,J1=6.4Hz,J2=13.6Hz,J3=19.6Hz,1H),3.31(m,1H,水のピークの下で埋もれた),1.23(d,J=6.0Hz,3H).EM(計算値):390.2;MS(ESI)m/e(M+1H)+:391.3,(M-1H)-:389.0.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.24(t,J=5.2Hz,1H),7.68(d,J=8.8Hz,2H),7.48(d,J=8.8Hz,2H),7.37(d,J=15.6Hz,1H),7.02(d,J=8.8Hz,2H),6.95(d,J=8.8Hz,2H),6.51(d,J=15.6Hz,1H0),4.58(疑q,J=5.6Hz,1H),3.77(s,3H),3.46(ddd,J1=4.8Hz,J2=13.2Hz,J3=19.2Hz,1H),3.32(ddd,J1=5.2Hz,J2=10.8Hz,J3=13.2Hz,1H),1.25(d,J=6.0Hz,3H).EM(計算値):370.2;MS(ESI)m/e(M+1H)+:371.0,(M-1H)-:369.1.
1H NMR(DMSO-d6):3.67(q,2H),4.18(t,2H),7.01(d,2H),7.7(d,2H),7.98(d,2H),8.12(d,2H),8.17(d,2H),8.55(s,1H),8.79(m,3H),11.05(s,1H).LC\MS:(M+1)+1461.2,(M-1)-1459.0.
1H NMR(400MHz,DMSO-d6)δ:11.08(s,1H),8.94(m,2H),7.75(m,3H),7.47(d,1H,J=8.1Hz),7.16(d,1H,J=8.1Hz),7.04(d,2H,J=9.6Hz),4.22(t,2H,J=5.5Hz),3.71(t,2H,J=5.5Hz),3.36(s,3H).EM(計算値):388.08;MS(ESI)m/e(M+1H)+:388.9,(M-1H)-:387.1.
1H NMR(DMSO-d6):2.85(s,3H),3.4(s,8H),3.65(q,2H),4.17(t,2H),7.00(d,2H),7.54(s,1H),7.7(d,2H),7.9(dd,4H),8.74(t,1H),8.9(s,1H),10.2(s,1H),11.05(s,1H).LC\MS:(M+1)+1482.0,(M-1)-1480.2.
1H NMR(DMSO-d6):3.66(q,2H),4.18(t,2H),7.01(d,2H),7.69(m,4H),7.91(d,2H),8.02(d,3H),8.33(dd,2H),8.75(t,1H),9.16(s,1H),10.99(s,1H),11.05(s,1H).LC\MS:(M+1)+1476.1,(M-1)-1474.2.
1H NMR(DMSO-d6):2.85(s,3H),3.01(m,4H),3.51(d,2H),3.60(q,2H),4.00(d,2H),4.13(t,2H),6.98(dd,4H),7.74(dd,4H),8.48(t,1H),9.97(s,1H),11.05(s,1H).LC\MS:(M+1)+1399.3,(M-1)-1397.2.
1H NMR(DMSO-d6):1.4(m,2H),1.8(m,2H),2.95(m,2H),3.6(m,5H),4.12(t,2H),4.69(s,1H),6.91(d,2H),6.99(d,2H),7.7(dd,4H),8.36(t,1H),8.87(s,1H),11.03(s,1H).LC\MS:(M+1)+1400.2,(M-1)-1398.3.
1H NMR(400MHz,DMSO-d6)δ:9.02(t,2H,J=5.3Hz),7.77-7.72(m,3H),7.27(m,1H),7.11(m,1H),7.03(d,2H,J=8.8Hz),4.22(t,2H,J=5.3Hz),3.70(t,2H,J=5.3Hz),2.51(s,3H).EM(計算値):372;MS(ESI)m/e(M+1H)+:373.0,(M-1H)-:371.0.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),10.04(s,1H),9.02(t,1H,J=5.7Hz),7.74(d,1H,J=2.7Hz),7.70(d,2H,J=8.5Hz),7.32(m,1H),7.25(m,1H),7.00(d,2H,J=8.5Hz),4.72(s,2H),4.19(t,2H,J=5.7Hz),3.67(m,2H),3.59(m,2H),3.48(m,2H),3.24(s,3H).EM(計算値):446.15;MS(ESI)m/e(M+1H)+:447.4,(M-1H)-:445.3.
1H NMR(400MHz,DMSO-d6)δ:11.04(brs,1H),9.25(t,1H,J=5.9Hz),8.07(d,1H,J=8.6Hz),7.96(d,1H,J=8.6Hz),7.70(m,3H),7.39(t,1H,J=7.6Hz),7.01(d,2H,J=9.1Hz),6.88(brs,1H),4.21(t,2H,J=5.9Hz),3.70(q,2H,J=5.9Hz).EM(計算値):367;MS(ESI)m/e(M+1H)+:368.0,(M-1H)-:366.2.
1H NMR(400MHz,DMSO-d6)δ:11.04(brs,1H),9.04(t,1H,J=5.9Hz),7.80(d,1H,J=2.6Hz),7.70(d,1H,J=8.7Hz),7.40(m,2H),7.28(t,1H,J=8.1Hz),7.05-6.92(m,5H),5.35(s,2H),4.18(t,2H,J=5.9Hz),3.66(q,2H,J=5.9Hz).EM(計算値):464;MS(ESI)m/e(M+1H)+:465.3,(M-1H)-:463.1.
1H NMR(DMSO-d6):2.55(t,3H),2.80(s,3H),3.07(d,3H),3.4(d,2H),3.65(q,2H),4.02(s,2H),4.17(t,2H),6.99(d,2H),7.69(d,2H),7.91(d,2H),8.01(d,2H),8.23(s,1H),8.75(t,1H),9.6(s,1H),11.05(s,1H).LC\MS:(M+1)+1496.3,(M-1)-1494.4
MS(ESI)m/e:(M+1H)+:302.0,(M-1H)-:300.2.
MS(ESI)m/e:(M+1H)+:318.1,(M-1H)-:316.1.
MS(ESI)m/e:(M+1H)+:318.1,(M-1H)-:316.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.28(m,2H),8.15(m,1H),7.94(m,2H),7.66(m,2H),7.41(m,3H),6.89(m,2H),4.10(m,2H),3.63(m,2H).MS(ESI)m/e:(M+1H)+:439.2,(M-1H)-:437.2.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.10(t,J=8.0Hz,1H),8.18(d,J=8.0Hz,1H),8.06(d,J=8.0Hz,1H),7.85(t,J=8.0Hz,1H),7.67(m,4H),7.04(d,J=8.0Hz,2H),4.45(m,2H),4.23(t,J=8.0Hz,2H),3.84(m,2H),3.76(m,2H).MS(ESI)m/e:(M+1H)+:426.3,(M-1H)-:424.2.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1H),10.31(s,1H),9.10(t,J=8.0Hz,1H),8.40(d,J=8.0Hz,1H),8.07(d,J=8.0Hz,1H),7.86(t,J=8.0Hz,1H),7.69(m,4H),7.02(d,J=8.0Hz,2H),4.74(m,2H),4.23(t,J=8.0Hz,2H),3.77(m,2H),3.70(m,2H).MS(ESI)m/e:(M+1H)+:439.3,(M-1H)-:437.3.
MS(ESI)m/e:(M+1H)+:379.9,(M-1H)-:379.9.
MS(ESI)m/e:(M+1H)+:379.9,(M-1H)-:379.9.
1H NMR(400MHz,DMSO-d6)5:11.04(brs,1H),8.85(d,1H,J=9.0Hz),8.20(d,1H,J=1.2Hz),8.18(d,1H,J=1.2Hz),7.85(m,1H),7.70-7.65(m,4H),7.01(t,2H,J=8.7Hz),4.32(m,1H),4.25(m,1H),4.15(s,3H),4.13(m,1H),1.77(m,2H),0.95(t,3H,J=7.0).EM(計算値):409;MS(ESI)m/e(M+1H)+:410.2,(M-1H)-:408.2.
1H NMR(400MHz,DMSO-d6)δ:11.05(s,1H),10.17(s,1H),8.65(m,1H),8.14(m,1H),7.95(m,1H),7.88(d,1H,J=8.2Hz),7.73-7.66(m,3H),7.62-7.59(m,2H),7.05(m,2H),4.24(m,2H),3.89(s,3H),3.73(m,2H).EM(計算値):380;MS(ESI)m/e(M+1H)+:381.0,(M-1H)-:379.1.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),9.14(t,1H,J=6.0Hz),8.18(d,1H,J=7.7Hz),8.07(d,1H,J=8.2Hz),7.85(t,1H,J=7.7Hz),7.72-7.64(m,4H),7.08(d,2H,J=9.1Hz),4.78(m,1H),4.14(s,3H),3.66(m,1H),3.55(m,1H),1.31(d,3H,J=6.1Hz).EM(計算値):395;MS(ESI)m/e(M+1H)+:396.1,(M-1H)-:394.2.
MS(ESI)m/e:(M+1H)+:377.9,(M-1H)-:376.1.
MS(ESI)m/e:(M+1H)+:408.3,(M-1H)-:406.2.
MS(ESI)m/e:(M+1H)+:373.9,(M-1H)-:372.1.
MS(ESI)m/e:(M+1H)+:422.3,(M-1H)-:420.3.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),9.10(t,1H,J=5.9Hz),8.16(d,1H,J=8.4Hz),8.07(d,1H,J=8.4Hz),7.85(t,1H,J=7.9Hz),7.71-7.65(m,4H),7.03(d,2H,J=8.9Hz),4.60(t,2H,J=5.9Hz),4.23(t,2H,J=5.1Hz),3.75(q,2H,J=5.9Hz),3.00(m,2H).EM(計算値):463;MS(ESI)m/e(M+1H)+:464.3,(M-1H)-:462.2.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),8.78(d,1H,J=9.0Hz),8.15(d,1H,J=8.3Hz),8.09(d,1H,J=8.5Hz),7.85(t,1H,J=6.7Hz),7.68(m,4H),7.00(d,2H,J=9.0Hz),4.61(t,2H,J=5.9Hz),4.32(m,1H),4.24(m,1H),4.14(m,1H),3.00(m,2H),1.76(m,2H),0.95(t,3H,J=7.0Hz).EM(計算値):491;MS(ESI)m/e(M+1H)+:492.1,(M-1H)-:490.1.
1H NMR(400MHz,DMSO-d6)δ:9.13(t,1H,J=6.1Hz),8.15(d,1H,J=8.1Hz),8.07(d,1H,J=8.3Hz),7.86(t,1H,J=6.7Hz),7.71-7.67(m,4H),7.08(d,2H,J=8.7Hz),4.78(m,1H),4.61(t,1H,J=5.5Hz),3.65(m,1H),3.55(m,1H),3.00(m,2H),1.31(d,3H,J=6.0Hz).EM(計算値):477;MS(ESI)m/e(M+1H)+:477.9,(M-1H)-:476.1.
1H NMR(DMSO-d6):3.56(s,2H),4.09(t,2H),6.57(d,1H),6.77(d,1H),6.95(m,3H),7.18(t,1H),7.32(d,2H),7.69(d,2H),8.38(t,1H),9.6(s,1H),11.05(s,1H).LC\MS:(M+1)+1343.2,(M-1)-1341.3.
1H NMR(DMSO-d6):3.55(s,2H),4.08(t,2H),6.4(d,1H),6.8(d,2H),7.0(d,2H),7.35(d,1H),7.4(d,2H),7.69(d,2H),8.25(t,1H),9.85(s,1H),11.05(s,1H).LC\MS:(M+1)+1343.1,(M-1)-1341.1.
EM(計算値):420.17;MS(ESI)m/e(M+1H)+:421.2,(M-1H)-:419.5.
EM(計算値):420.17;MS(ESI)m/e(M+1H)+:421.3,(M-1H)-:419.3.
EM(計算値):420.17;MS(ESI)m/e(M+1H)+:421.3,(M-1H)-:419.3.
1H NMR(DMSO-d6)δ8.89(1H,s),8.58(1H,m),7.71(2H,m),7.65(1H,d),7.56(1H,d),7.41(1H,d),7.36(1H,t),7.25(1H,t),7.21(1H,s),7.00(2H,d),6.74(1H,dd),4.11(2H,t),3.58(2H,q).
EM(計算値):420.17;MS(ESI)m/e(M+1H)+:421.2,(M-1H)-:419.3.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),9.14(s,1H),9.11(t,J=8.0Hz,1H),8.93(s,1H),8.63(t,J=4.0Hz,1H),8.17(m,1H),7.72(m,4H),7.00(d,J=8.0Hz,2H),4.20(t,J=8.0Hz,2H),3.71(m,2H).MS(ESI)m/e:(M+1H)+:384.1,(M-1H)-:382.0.
MS(ESI)m/e:(M+1H)+:451.0,(M-1H)-:449.2.
MS(ESI)m/e:(M+1H)+:409.3,(M-1H)-:407.2.
1H NMR(DMSO-d6):3.54(q,2H),3.84(s,3H),4.08(t,2H),6.6(d,1H),6.98(m,4H),7.35(t,1H),7.5(d,1H),7.65(d,1H),7.69(d,2H),8.36(t,1H),8.9(s,1H),11.04(s,1H).LC\MS:(M+1)+1356.9,(M-1)-1355.2.
1H NMR(DMSO-d6):3.56(q,2H),3.77(s,3H),4.09(t,2H),6.66(d,1H),6.93(m,2H),6.99(d,2H),7.1(d,2H),7.29(t,1H),7.39(d,1H),7.70(d,2H),7.87(d,1H),8.36(t,1H),8.9(s,1H),11.05(s,1H).LC\MS:(M+1)+1357.1,(M-1)-1355.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.21(t,J=8.0Hz,1H),9.07(s,1H),8.92(s,1H),8.67(s,1H),7.70(m,4H),7.01(d,J=8.0Hz,2H),6.92(m,1H),4.21(t,J=8.0Hz,2H),3.71(m,2H).MS(ESI)m/e:(M+1H)+:421.2,(M-1H)-:419.4.
1H NMR(DMSO-d6)δ8.91(1H,s),8.44(1H,t),7.73(2H,d),7.72(1H,s),7.57(1H,d),7.44(1H,d),7.02(2H,d),6.50(1H,d),4.11(2H,t),3.58(2H,q).LC\MS,M+1:413.1.
1H NMR(DMSO-d6):3.54(q,2H),4.07(t,2H),6.36(d,1H),6.68(s,1H),6.98(d,2H),7.32(d,1H),7.69(m,3H),7.98(s,1H),8.27(t,1H),8.9(s,1H),11.04(s,1H).LC\MS:(M+1)+1316.9,(M-1)-1315.3.
1H NMR(DMSO-d6):3.55(q,2H),4.08(t,2H),6.47(d,1H),6.98(d,2H),7.31(d,1H),7.42(d,1H),7.58(m,1H),7.69(d,2H),7.78(s,1H),8.30(t,1H),8.9(s,1H),11.04(s,1H).LC\MS:(M+1)+1333.0,(M-1)-1331.0.
1H NMR(DMSO-d6)δ8.91(1H,s),8.40(1H,t),7.73(2H,d),7.61(2H,m),7.38(1H,d),7.11(1H,dd),7.01(2H,d),6.43(1H,d),4.11(2H,t),3.57(2H,q).LC\MS,M+1:333.0.
1H NMR(DMSO-d6):2.31(s,3H),3.55(q,2H),4.09(t,2H),6.6(d,1H),6.99(d,2H),7.2-7.4(m,6H),7.70(d,2H),8.33(t,1H),8.9(s,1H),11.04(s,1H).LC\MS:(M+1)+1341.1,(M-1)-1339.1.
1H NMR(DMSO-d6):2.31(s,3H),3.55(q,2H),4.09(t,2H),6.6(d,1H),6.99(d,2H),7.2(d,2H),7.38(d,1H),7.42(d,2H),7.69(d,2H),8.33(t,1H),8.9(s,1H),11.04(s,1H).LC\MS:(M+1)+1341.2,(M-1)-1339.2.
1H NMR(DMSO-d6)δ8.87(1H,s),8.52(1H,t),7.70(2H,d),7.64(1H,d),7.52(1H,d),7.34(1H,m),7.24(1H,t),7.22(1H,s),6.99(2H,d),6.67(1H,m),4.09(2H,t),3.52(2H,q),2.48(3H,m).LC\MS,M+1:381.0.
1H NMR(DMSO-d6)δ8.88(1H,s),8.33(1H,t),7.68(2H,d),7.54(1H,m),7.41(1H,d),7.28(1H,s),7.24(1H,m),7.19(1H,m),6.95(2H,d),6.07(1H,m),4.11(2H,t),3.52(2H,q),2.15(3H,m).LC\MS,M+1:381.1.
1H NMR(DMSO-d6):2.94(s,6H),3.54(q,2H),4.07(t,2H),6.38(d,1H),6.69(d,2H),6.98(d,2H),7.29(d,1H),7.35(d,2H),7.69(d,2H),8.15(t,1H),8.87(s,1H),11.04(s,1H).LC\MS:(M+1)+1370.1,(M-1)-1368.3.
1H NMR(DMSO-d6):3.57(q,2H),4.10(t,2H),6.65(d,1H),7.0(d,2H),7.14(m,2H),7.42(m,1H),7.6(d,1H),7.72(m,3H),7.87(d,1H),8.149(t,1H),8.87(s,1H),11.04(s,1H),11.52(s,1H).LC\MS:(M+1)+1366.2,(M-1)-1364.4.
1H NMR(DMSO-d6):2.36(s,3H),3.56(q,2H),4.10(t,2H),6.56(d,1H),7.00(d,2H),7.23(m,3H),7.5(d,1H),7.65(d,1H),7.7(d,2H),8.4(t,1H),8.87(s,1H),11.04(s,1H).LC\MS:(M+1)+1341.2,(M-1)-1339.3.
1H NMR(DMSO-d6):3.55(q,2H),3.93(s,3H),4.08(t,2H),6.66(d,1H),6.79(t,1H),6.86(d,1H),6.98(d,2H),7.15(m,1H),7.4(d,1H),7.65(d,1H),7.7(d,2H),8.31(t,1H),10.0(s,1H),11.04(s,1H).LC\MS:(M+1)+1343.1,(M-1)-1340.9.
1H NMR(DMSO-d6):3.57(q,2H),3.93(s,3H),4.09(t,2H),6.75(d,1H),6.98(m,3H),7.18(m,3H),7.38(d,1H),7.7(d,2H),8.5(t,1H),8.87(s,1H),11.04(s,1H).LC\MS:(M+1)+1396.7,(M-1)-1395.0.
1H NMR(DMSO-d6):0.922(t,3H),1.5-1.8(m,2H),3.93(s,3H),3.95-4.07(m,3H),6.8(d,1H),6.98(m,3H),7.19(m,3H),7.36(d,1H),7.69(d,2H),8.3(d,1H),11.03(s,1H).LC\MS:(M+1)+1425.2,(M-1)-1423.2.
1H NMR(DMSO-d6):0.95(3H,t,7Hz);1.53(1H,m);1.72(1H,m);2.52(3H,s);3.79(3H,s);3.94(1H,m);4.06(2H,m);6.66(1H,s);6.93(1H,dd);7.02(2H,d);7.15(2H,m);7.42(1H,d);7.7(2H,d);8.27(2H,d,7Hz);8.87(1H,d,2Hz).MS(M+1):439.
1H NMR(DMSO-d6):3.54(q,2H),4.08(t,2H),6.44(d,1H),6.56(s,1H),6.75(s,1H),6.98(d,2H),7.23(d,1H),7.70(d,2H),7.75(s,1H),8.41(t,1H),8.9(s,1H),11.04(s,1H).LC\MS:(M+1)+1317.0,(M-1)-1315.2.
1H NMR(DMSO-d6):3.5-4.05(m,14H),4.18(t,2H),6.99(d,2H),7.69(d,2H),7.93(d,2H),8.02(d,2H),8.2(s,1H),8.76(t,1H),8.97(s,1H),11.05(s,1H).LC\MS:(M+1)+1497.4,(M-1)-1495.4.
化合物.1
EM(計算値):370.2;MS(ESI)m/e(M+1)+:371.1,(M-1)-:369.2.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.88(s,1H),7.67(d,J=9.2Hz,2H),7.51(m,3H),7.36(m,8H),6.92(d,J=9.2Hz,2H),6.27(d,J=15.2Hz,1H),4.16(m,4H).EM(計算値):402.2;MS(ESI)m/e(M+1H)+:403.1,(M-1H)-:401.1.
EM(計算値):340.1;MS(ESI)m/e(M+1H)+:341.0,(M-1H)-:339.4.
EM(計算値):398.13;MS(ESI)m/e(M+1H)+:399.0,(M-1H)-:397.1.
EM(計算値):368.17;MS(ESI)m/e(M+1H)+:368.8,(M-1H)-:367.2.
EM(計算値):354.1;MS(ESI)m/e(M+1H)+:354.8,(M-1H)-:353.2.
化合物.1
1H NMR(400MHz,DMSO-d6)δ11.11(s,1H),9.07(t,J=5.2Hz,1H),8.94(s,1H),8.16(s,1H),8.07(dd,J1=2.4Hz,J2=8.4Hz,1H),7.99(dd,J1=2.4Hz,J2=6.8Hz,1H),7.77(d,J=9.2Hz,2H),7.50(m.2H),7.08(d,J=8.8Hz,2H),4.25(疑t,J=5.6Hz,2H),3.73(疑q,J=5.2Hz,2H).EM(計算値):358.1;MS(ESI)m/e(M+1H)+:357.0,(M-1H)-:355.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.92(t,J=5.6Hz,1H),8.88(s,1H),7.76(d,J=8.0Hz,1H),7.70(d,J=9.2Hz,2H),7.64(d,J=8.0Hz,1H),7.55(s,1H),7.46(t,J=6.8Hz,1H),7.32(t,J=8.0Hz,1H),7.01(d,J=8.2Hz,2H),4.18(t,J=5.6Hz,2H),3.67(m,2H).EM(計算値):340.1;MS(ESI)m/e:(M+1H)+:341.0,(M-1H)-:339.1.
1H NMR(400MHz,DMSO-d6)δ:11.57(s,1H),11.04(s,1H),8.71(t,J=5.6Hz,1H),7.70(d,J=8.8Hz,2H),7.59(d,J=8.4Hz,1H),7.40(d,J=8.4Hz,1H),7.16(t,J=8.4Hz,1H),7.12(m,1H),7.00(m,3H),4.18(t,J=5.6Hz,2H),3.68(m,2H).EM(計算値):339.1;MS(ESI)m/e(M+1H)+:340.1,(M-1H)-:338.3.
EM(計算値):353.1;MS(ESI)m/e(M+1)+:354.1,(M-1)-:352.2.
1H NMR(400MHz,DMSO-d6)δ8.84(t,J=5.6Hz,1H),8.05(s,1H),7.99(dd,J1=6.0Hz,J2=2.0Hz,1H),7.91(dd,J1=6.4Hz,J2=2.0Hz,1H),7.65(d,J=8.8Hz,2H),7.42(m,2H),6.88(d,J=8.4Hz,2H),4.06(t,J=6.0Hz,2H),3.43(疑q,J=5.6Hz,2H),2.00(疑p,J=6.0Hz,2H).EM(計算値):370.1;MS(ESI)m/e(M+1H)+:371.1,(M-1H)-:369.0.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.74(t,J=6.0Hz,1H),7.67(d,J=7.6Hz,1H),7.62(d,J=8.4Hz,2H),7.44(s,1H),7.55(dd,J1=8.4Hz,J2=0.8Hz,1H),7.43(d,J=0.8Hz,1H),7.37(td,J1=7.2Hz,J2=1.2Hz,1H),7.241(td,J1=8.0HZ,J2=0.8Hz,1H),6.89(d,J=8.8Hz,2H),4.01(t,J=6.4Hz,2H),3.37(疑q,J=6.0Hz,2H),1.94(疑p,J=6.0Hz,2H).EM(計算値):354.1;MS(ESI)m/e(M+1H)+:355.2,(M-1H)-:353.1.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.91(s,1H),8.65(brd,J=7.2Hz,1H),8.20(s,1H),8.03(m,1H),7.95(m,1H),7.72(d,J=8.4Hz,2H),7.46(m,2H),7.03(d,J=8.8Hz,2H),4.20(m,3H),2.08(m,1H),1.02(d,J=6.8Hz,6H).EM(計算値):398.1;MS(ESI)m/e(M+1H)+:399.0,(M-1H)-:397.1.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.91(s,1H),8.68(d,J=8.0Hz,1H),8.17(s,1H),8.03(dd,J1=2.0Hz,J2=6.4Hz,1H),7.96(dd,J1=4.0Hz,J2=6.8Hz,1H),7.73(d,J=8.8Hz,2H),7.46(m,4H),7.04(d,J=9.2Hz,2H),4.24(m,1H),4.18(dd,J1=6.8Hz,J2=10.0Hz,1H),4.09(dd,J1=5.2Hz,J2=9.6Hz,),1.81(m,1H),1.67(m,1H),0.99(t,J=7.6Hz,3H).EM(計算値):384.1;MS(ESI)m/e(M+1H)+:385.0,(M-1H)-:383.1.
1H NMR(400MHz,DMSO-d6)δ11.11(s,1H),8.95(brs,1H),8.80(d,J=8.0Hz,1H),8.19(s,1H),8.06(dd,J1=5.6Hz,J2=1.6Hz,1H),7.98(dd,J1=6.8Hz,J2=1.6Hz,1H),7.76(d,J=8.4Hz,2H),7.49(m,2H),7.08(d,J=8.8Hz,2H),4.42(p,J=6.4Hz,1H),4.20(dd,J1=9.6Hz,J2=6.4Hz,1H),4.07(dd,J1=9.6Hz,J2=5.6Hz,1H),1.36(d,J=6.8Hz,3H).EM(計算値):370.1;MS(ESI)m/e(M+1H)+:371.0,(M-1H)-:368.9.
1H NMR(400MHz,DMSO-d6)δ10.95(s,1H0,8.65(d,J=7.6Hz,1H),8.04(s,1H),7.91(d,J=7.2Hz,1H),7.83(d,J=6.4Hz,1H),7.61(d,J=8.8Hz,2H),7.34(m,2H),6.93(d,J=8.8Hz,2H),4.27(p.J=6.4Hz,1H),4.05(dd,J1=6.8Hz,J2=10.0Hz,1H),3.92(dd,J1=10.0Hz,J2=6.0Hz,1H),1.21(d,J=5.2Hz,3H).EM(計算値):370.1;MS(ESI)m/e(M+1H)+:370.9,(M-1H)-:369.0.
1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),8.54(d,J=8.4Hz,1H),7.68(d,J=7.6Hz,1H),7.61(d,J=8.4Hz,2H),7.58(d,J=8.4Hz,1H),7.48(d,J=0.8Hz,1H),7.38(td,J1=8.0Hz,J2=0.8Hz,1H),7.25(td,J1=7.2Hz,J2=0.8Hz,1H),6.92(d,J=8.8Hz,2H),4.19(m,1H),4.07(dd,J1=10.4Hz,J2=6.4Hz,1H),3.99(dd,J1=10.0Hz,J2=5.6Hz,1H),1.68(m,1H),1.55(m,1H),0.86(t,J=7.2Hz,3H).EM(計算値):368.1;MS(ESI)m/e(M-1H)-:367.1.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1H),9.03(t,J=6.0Hz,1H),8.11(s,1H),8.03(d,J=7.2Hz,1H),7.94(d,J=6.4Hz,1H),7.72(d,J=8.8Hz,2H),7.46(m,2H),7.07(d,J=9.2Hz,2H),4.72(疑q,J=5.6Hz,1H),3.62(m,1H),3.42(m,1H),1.34(d,J=6.4Hz,3H).EM(計算値):370.1;MS(ESI)m/e(M+1H)+:371.0,(M-1H)-:369.1.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1H),9.03,(t,J=5.6Hz,1H),8.11(s,1H),8.03(d,J=6.8Hz,1H),7.94(d,J=7.2Hz,1H),7.72(d,J=8.4Hz,2H),7.46(疑p,J=5.6Hz,2H),7.07(d,J=8.4Hz,2H),4.74(疑q,J=5.6Hz,1H),3.63(m,1H),3.42(m,1H),1.34(d,J6.0Hz,3H).EM(計算値):370.1;MS(ESI)m/e(M+1H)+:371.0,(M-1H)-:369.1.
1H NMR(400MHz,DMSO-d6)δ11.02(s,1H),8.92(t,J=6.0Hz,1H),7.75(d,J=7.6Hz,1H),7.68(d,J=8.8Hz,2H),7.54(d,J=0.8Hz,1H),7.44(td,J1=7.2Hz,J2=0.8Hz,1H),7.31(td,J=7.6Hz,J2=0.8Hz,1H),7.03(d,J=9.2Hz,2H),4.69(疑q,J=6.4Hz,1H),3.59(ddd,J1=6.4Hz,J2=13.6Hz,J3=19.6Hz,1H),3.39(ddd,J1=6.0Hz,J2=12.4Hz,J3=19.6Hz,1H),1.29(d,J=6.4Hz,3H).EM(計算値):354.1;MS(ESI)m/e(M+1H)+:354.7,(M-1H)-:353.1.
EM(計算値):386.09;MS(ESI)m/e(M-1H)-:384.7.
EM(計算値):370.10;MS(ESI)m/e(M-1H)-:369.0.
EM(計算値):390.0;MS(ESI)m/e(M+1H)+:391.2.
EM(計算値):354.12;MS(ESI)m/e(M-1H)-:353.2.
EM(計算値):354.12;MS(ESI)m/e(M-1H)-:353.1.
EM(計算値):424.07;MS(ESI)m/e(M-1H)-:423.9.
EM(計算値):374.0;MS(ESI)m/e(M+1)+:375.0,(M-1)-:373.0.
EM(計算値):386.1;MS(ESI)m/e(M+1)+:387.1,(M-1)-:384.7.
EM(計算値):374.1;MS(ESI)m/e(M+1)+:374.9,(M-1)-:372.9.
EM(計算値):370.1;MS(ESI)m/e(M+1)+:370.8,(M-1)-:369.0.
EM(計算値):370.1;MS(ESI)m/e(M+1)+:371.0,(M-1)-:369.1.
EM(計算値):414.14;MS(ESI)m/e(M+1H)+:415.2,(M-1H)-:413.2.
EM(計算値):469.18;MS(ESI)m/e(M+1H)+:470.1,(M-1H)-:468.4.
EM(計算値):447.14;MS(ESI)m/e(M+1H)+:448.1,(M-1H)-:446.2.
EM(計算値):354.1;MS(ESI)m/e(M+1)+:355.1,(M-1)-:353.1.
EM(計算値):370.1;MS(ESI)m/e(M+1)+:371.0,(M-1)-:368.9.
EM(計算値):400.1;MS(ESI)m/e(M+1H)+:401.0,(M-1H)-:399.2.
EM(計算値):427.1;MS(ESI)m/e(M+1H)+:428.2,(M-1H)-:426.2.
EM(計算値):414.1;MS(ESI)m/e(M+1)+:415.4,(M-1)-:413.2.
EM(計算値):469.2;MS(ESI)m/e(M+1)+:470.1,(M-1)-:468.3.
EM(計算値):447.1;MS(ESI)m/e(M+1)+:448.2,(M-1)-:446.5.
EM(計算値):368.1;MS(ESI)m/e(M+1)+:369.0,(M-1)-:367.2.
1H NMR(400MHz,DMSO-d6)δ11.69(s,1H),11.04(s,1H),8.77(t,J=5.6Hz,1H),7.70(d,J=8.4Hz,2H),7.39(m,2H),7.11(s,1H),7.05(m,1H),7.01(d,J=8.4Hz,2H),4.18(t,J=6.0Hz,2H),3.67(m,2H).EM(計算値):357.1;MS(ESI)m/e(M+1H)+:357.8,(M-1H)-:356.2.
1H NMR(400MHz,DMSO-d6)S11.42(s,1H),11.05(s,1H),8.66,(t,J=5.6Hz,1H),7.70(d,J=9.2Hz,2H),7.29(d,J=8.4Hz,1H),7.03(m,4H),6.81(m,1H),4.17(t,J=5.6Hz,2H),3.75(s,3H),3.66(m,2H).EM(計算値):369.1;MS(ESI)m/e(M+1H)+:369.9,(M-1H)-:368.2.
EM(計算値):384.13;MS(ESI)m/e(M+1H)+:384.9,(M-1H)-:383.2.
EM(計算値):446.15;MS(ESI)m/e(M+1H)+:447.2,(M-1H)-:445.4.
1H NMR(400MHz,DMSO-d6)δ11.28(s,1H),11.04(s,1H),8.53(t,J=5.6Hz,1H),7.70(d,J=9.2Hz,2H),7.02(m,4H),6.86(s,1H),4.16(t,J=5.6Hz,2H),3.76(s,3H),3.75(s,3H),3.63(m,2H).EM(計算値):399.1;MS(ESI)m/e(M+1H)+:400.0,(M-1H)-:398.1.
1H NMR(400MHz,DMSO-d6)δ11.09(bs,1H),10.60(bs,1H),9.29(t,J=6.0Hz,1H),8.08(d,J=8.0Hz;1H),7.70(m,3H),7.57(t,J=7.2Hz,1H),7.45(t,J=7.2Hz,1H),7.00(d,J=9.2Hz,2H),4.83(m,2H),4.23(t,J=6.0Hz,2H),3.94(m,2H),3.73(m,4H),3.44(m,2H),3.27(m,2H).EM(計算値):439.2;MS(ESI)m/e(M+1H)+:439.8,(M-1H)-:438.2.
EM(計算値):412.16;MS(ESI)m/e(M+1H)+:413.1,(M-1H)-:411.3.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.92(t,J=5.2Hz,1H),7.74(d,J=7.6Hz,1H),7.70(d,J=8.8Hz,2H),7.59(s,1H),7.55(d,J=6.8HZ,1H),7.32(m,3H),7.06(d,J=7.6Hz,2H),7.00(d,J=9.2Hz,2H),6.95(t,J=7.2Hz,1H),5.44(s,2H),4.19(t,J=6.0Hz,2H),3.69(m,2H).EM(計算値):446.2;MS(ESI)m/e(M+1H)+:447.2,(M-1H)-:445.3.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),8.91(t,J=5.6Hz,1H),7.71(m,3H),7.58(s,1H),7.44(d,J=7.6Hz,1H),7.32(t,J=7.6Hz,1H),7.03(d,J=8.8Hz,2H),4.78(s,2H),4.20(t,J=6.0Hz,2H),3.69(m,2H),3.36(s,3H).EM(計算値):384.1;MS(ESI)m/e(M+1H)+:385.9,(M-1H)-:383.2.
1H NMR(400MHz,DMSO-d6)δ11.33(s,1H),11.09(s,1H),9.32(t,J=5.6Hz,1H),7.88(d,J=8.4Hz,1H),7.71(m,3H),7.61(s,1H),7.43(t,J=7.6Hz,1H),7.03(d,J=8.8Hz,1H),4.68(s,2H),4.23(t,J=5.6Hz,2H),3.83(m,6H),3.37(m,2H),3.20(m,2H).EM(計算値):439.2;MS(ESI)m/e(M+1H)+:440.2,(M-1H)-:438.4.
1H NMR(400MHz,DMSO-d6)δ11.09(s,1H)10.74(s,1H),9.31(t,J=5.6Hz,1H),7.88(d,J=8.0Hz,1H),7.72(d,J=8.6Hz,2H),7.65(d,J=7.2Hz,1H),7.62(s,1H),7.42(t,J=8.0Hz,1H),7.02(d,J=8.8Hz,2H),4.63(d,J=5.2Hz,2H),4.23(t,J=6.0Hz,2H),3.70(m,2H),2.78(s,3H),2.770(s,3H).EM(計算値):397.2;MS(ESI)m/e(M+1H)+:398.0,(M-1H)-:396.1.
EM(計算値):384.1;MS(ESI)m/e(M-1)-:382.9.
EM(計算値):400.1;MS(ESI)m/e(M-1)-:398.7.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),8.78(t,J=6.0Hz,1H),7.71(m,3H),7.54(s,1H),7.43(d,J=7.2Hz,1H),7.32(d,J=7.6Hz,1H),6.99(d,J=8.4Hz,2H),4.77(s,2H),4.10(t,J=6.0Hz,2H),3.47(m,2H),3.36(s,3H),2.02(m,2H).EM(計算値):398.2;MS(ESI)m/e(M+1H)+:399.1,(M-1H)-:397.1.
1H NMR(400MHz,DMSO-d6)δ8.82(t,J=5.6Hz,1H),7.71(m,3H),7.54(m,2H),7.31(m,3H),7.06(d,J=8.0Hz,2H),6.95(m,3H),5.43(s,2H),4.09(t,J=6.0Hz,2H),3.47(m,2H),2.02(m,2H).EM(計算値):460.2;MS(ESI)m/e(M+1H)+:461.0,(M-1H)-:459.1.
EM(計算値):428.16;MS(ESI)m/e(M+1H)+:428.9,(M-1H)-:427.1.
1H NMR(DMSO-d6):2.11(3H,s);2.78(1H,dd,14,8Hz);2.86(1H,dd,14,5Hz);4.17(1H,dd,10,4Hz);4.23(1H,dd,10,6Hz);4.49(1H,m);7.00(2H,d,9Hz);7.32(1H,t,7Hz);7.46(1H,td,8,1Hz);7.56(1H,s);7.64(1H,d,8Hz);7.70(2H,d,9Hz);7.77(1H,d,8Hz);8.77(1H,d,8Hz);8.88(1H,s).MS(M+1):401.
1H NMR(DMSO-d6):3.31(3H,s);3.53(1H,dd,13,3.5Hz);3.66(1H,dd,13,8Hz);4.16(1H,dd,9,6Hz);4.24(1H,dd,9,8Hz);4.87(1H,m);7.00(2H,d,9Hz);7.33(1H,t,7Hz);7.47(1H,t,8Hz);7.57(1H,s);7.65(1H,d,8Hz);7.70(2H,d,9Hz);7.77(1H,d,8Hz);8.89(1H,s);9.0(1H,d,8Hz).MS(M-1):431.
1H NMR(400MHz,DMSO-d6)δ:7.92(brs,1H),8.76(t,1H,J=5.9Hz),7.75(m,3H),7.60(d,1H,J=7.6Hz),7.48(t,1H,J=8.0Hz),7.32(t,1H,J=8.0Hz),7.27(m,5H),7.17(m,1H),7.04(m,2H),4.21(t,2H,J=5.9Hz),3.69(m,2H)3.39(m,2H),2.96(t,2H,J=8.3Hz).EM(計算値):444;MS(ESI)m/e(M+1H)+:445.3,(M-1H)-:443.3.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),9.38(s,1H),8.90(s,1H),7.94(d,J=8.0Hz,1H),7.57(m,10H),6.97(d,J=8.0Hz,2H),4.80(m,2H),4.20(s,2H),3.70(m,2H),3.31(m,3H),2.66(m,2H).MS(ESI)m/e:(M+1H)+:474.4,(M-1H)-:472.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.73(m,1H),8.89(s,1H),7.75(d,J=8.0Hz,2H),7.70(t,J=8.0Hz,2H),7.61(d,J=8.0HZ,1H),7.43(t,8.0Hz,1H),7.18(m,6H),6.98(d,J=8.0Hz,2H),4.13(t,J=8.0Hz,2H),3.95(m,2H),3.58(m,2H),2.78(m,2H),2.65(m,2H),1.24(s,3H).MS(ES1)m/e:(M+1H)+:487.9,(M-1H)-:486.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.88(s,1H),8.84(t,J=8.0Hz,1H),7.82(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.59(d,J=8.0Hz,1H),7.48(t,J=8.0Hz,1H),7.34(t,J=8.0Hz,1H),7.00(d,J=8.0Hz,2H),4.31(s,2H),4.18(t,J=8.0Hz,2H),3.66(m,2H),3.38(m,2H),2.45(t,J=8.0Hz,2H),1.65(m,2H).MS(ESI)m/e:(M+1H)+:445.2,(M-1H)-:443.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.04(t,J=8.0Hz,1H),7.86(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.63(d,J=8.0Hz,1H),7.50(t,J=8.0Hz,1H),7.36(t,J=8.0Hz,1H),7.00(d,J=8.0Hz,2H),4.57(m,2H),4.18(t,J=8.0Hz,2H),3.65(m,2H),3.46(t,J=8.0Hz,2H),2.77(m,2H),1.80(m,2H).MS(ESI)m/e:(M+1H)+:461.0,(M-1H)-:459.1.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.05(t,J=8.0Hz,1H),7.87(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.64(d,J=8.0Hz,1H),7.51(t,J=8.0Hz,1H),7.38(t,J=8.0Hz,1H),7.00(d,J=8.0Hz,2H),5.11(s,2H),4.19(t,J=8.0Hz,2H),3.68(m,2H),3.44(t,J=8.0Hz,2H),3.13(m,2H),1.83(m,2H).MS(ESI)m/e:(M+1H)+:477.0,(M-1H)-:475.0.
MS(ESI)m/e:(M+1H)+:527.6,(M-1H)-:525.5.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),8.88(brs,1H),8.73(t,1H,J=5.9Hz),7.75-7.69(m,3H),7.57-7.42(m,6H),7.28(t,1H,J=7.7Hz),7.00(d,2H,J=8.7Hz),4.17(t,2H,J=5.9Hz),3.65(q,2H,J=5.9Hz)3.40(t,2H,J=6.9Hz),3.04(t,2H,J=6.9Hz).EM(計算値):512;MS(ESI)m/e(M+1H)+:513.3,(M-1H)-:511.2.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),8.87(brs,1H),8.83(t,1H,J=5.9Hz),7.70(m,3H),7.55(d,1H,J=8.3Hz),7.43(t,1H,J=7.4Hz),7.34(t,1H,J=8.0Hz),7.28-7.20(m,3H),7.11(d,1H,8.0Hz),7.00(d,2H,J=8.6Hz),4.17(t,2H,J=5.9Hz),3.65(q,2H,J=5.9Hz)3.38(t,2H,J=8.3Hz),3.00(t,2H,J=8.3Hz).EM(計算値):528;MS(ESI)m/e(M+1H)+:529.4,(M-1H)-:527.5.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1H),10.93(s,1H),9.32(m,2H),9.23(s,1H),8.89(s,1H),7.96(d,J=8.0Hz,1H),7.70(m,3H),7.56(t,J=8.0Hz,1H),7.44(t,J=8.0Hz,1H),7.00(d,.J=8.0Hz,2H),4.64(s,2H),4.23(t,J=8.0Hz,2H),3.71(m,4H).MS(ESI)m/e:(M+1H)+:443.4,(M-1H)-:441.4.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1),9.33(t,J=8.0Hz,1H),8.89(s,1H),8.00(d,J=8.0Hz,1H),7.71(m,3H),7.56(t,J=8.0Hz,1H),7.43(t,J=8.0Hz,3H),7.00(d,J=8.0Hz,2H),4.60(s,2H),4.23(t,J=8.0Hz,2H),3.71(m,2H),3.20(t,J=8.0Hz,2H),2.72(t,J=8.0Hz,2H).MS(ESI)m/e:(M+1H)+:442.3,(M-1H)-:440.1.
1H NMR(400MHz,DMSO-d6)δ:,9.11(t,1H,J=6.0Hz),7.82(d,,1H,J=7.7Hz),7.76(d,2H,J=8.5Hz),7.69(d,1H,J=8.5Hz),7.62(s,1H),7.51(t,1H,J=8.5Hz),7.40-7.30(m,3H),7.21(d,2H,J=8.5Hz),7.00-6.97(m,3H),4.99(m,1H),4.35(m,1H),4.27(m,1H),3.78(m,1H),3.70(m,1H).EM(計算値):446.15;MS(ESI)m/e(M+1H)+:447.4,(M-1H)-:445.3.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.86(t,J=4.0Hz,1H),7.83(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.61(d,J=8.0HZ,1H),7.47(t,J=8.0Hz,1H),7.33(t,J=4.0Hz,1H),7.00(d,J=8.0Hz,2H),5.02(s,2H),4.18(t,J=8.0Hz,2H),3.65(m,2H),3.52(t,J=8.0Hz,2H),3.44(t,J=8.0Hz,2H),1.68(m,2H).MS(ESI)m/e:(M+1H)+:429.1,(M-1H):426.9.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),9.03(t,1H,J=5.9Hz),7.86(d,1H,J=9.2Hz),7.70(d,2H,J=8.3Hz),7.63(d,1H,J=8.3Hz),7.49(t,1H,J=8.8Hz),7.36(t,1H,J=7.0Hz),7.29(t,1H,J=8.8Hz),7.18(m,1H),7.07(t,1H,J=7.0Hz),7.00(d,1H,J=8.3Hz),6.91(m,1H),5.78(s,2H),4.20(t,2H,J=5.9Hz),3.68(q,2H,J=5.9Hz).EM(計算値):464;MS(ESI)m/e(M+1H)+:465.1,(M-1H)-:463.1.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),9.04(t,1H,J=5.9Hz),9.00(brs,1H),7.84(d,1H,J=7.3Hz),7.70(d,2H,J=9.2Hz),7.63(d,1H,J=8.1Hz),7.49(t,1H,J=8.6Hz),7.35(t,1H,J=7.7Hz),7.27(m,1H),7.18(m,1H),7.00(d,1H,J=9.2Hz),6.95(m,1H),6.87(m,1H),6.74(m,1H),5.71(s,2H),4.21(t,2H,J=5.9Hz),3.69(q,2H,J=5.9Hz).EM(計算値):464;MS(ESI)m/e(M+1H)+:465.0,(M-1H)-:463.1.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),9.00(t,1H,J=5.9Hz),7.84(d,1H,J=8.4Hz),7.70(d,2H,J=9.2Hz),7.62(d,1H,J=8.8Hz),7.48(t,1H,J=8.4Hz),7.34(t,1H,J=7.3Hz),7.10-7.00(m,6H),5.67(s,2H),4.20(t,2H,J=5.9Hz),3.68(q,2H,J=5.9Hz).EM(計算値):464;MS(ESI)m/e(M+1H)+:464.9,(M-1H)-:463.0.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.88(m,2H),7.86(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.61(d,J=8.0HZ,1H),7.47(t,J=8.0Hz,1H),7.33(t,J=4.0Hz,1H),7.00(d,J=8.0Hz,2H),5.05(s,2H),4.19(t,J=8.0Hz,2H),3.65(m,2H),3.59(m,2H),3.47(m,2H),3.23(s,3H).MS(ESI)m/e:(M+1H)+:428.9,(M-1H)-:426.9.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.20(t,J=4.0Hz,1H),8.83(d,J=8.0Hz,2H),7.86(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,2H),7.66(d,J=8.0Hz,1H),7.51(t,J=8.0Hz,1H),7.38(t,J=8.0Hz,1H),7.25(d,J=8.0Hz,2H),6.98(d,J=8.0Hz,2H),6.07(s,2H),4.21(t,J=8.0Hz,2H),3.70(m,2H).MS(ESI)m/e:(M+1H)+:448.0,(M-1H)-:446.4.
1H NMR(400MHz,DMSO-d6)δ:8.86(m,1H),8.81(brs,1H),7.80(d,1H,J=8.2Hz),7.63(d,2H,J=9.4Hz),7.57(d,1H,J=8.2Hz),7.44(t,1H,J=7.8Hz),7.32(t,1H,J=7.0Hz),7.12(t,1H,J=9.0Hz),6.91(t,1H,J=8.6Hz),5.64(s,2H),4.06(t,2H,J=6.0Hz),3.54(t,2H,J=6.0Hz).EM(計算値):500.13;MS(ESI)m/e(M+1H)+:501.5,(M-1H)-:499.3.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.14(t,J=4.0Hz,1H),7.89(m,1H),7.70(m,3H),7.61(d,J=8.0Hz,1H),7.46(m,1H),7.40(m,ITI),7.29(t,J=4.0Hz,1H),7.02(d,J=8.0Hz,2H),6.43(d,J=8.0Hz,1H),6.23(t,J=4.0Hz,1H),5.62(s,2H),4.23(t,J=4.0Hz,2H),3.72(m,2H).MS(ESI)m/e:(M+1H)+:448.2,(M-1H)-:446.4.
1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),8.96(t,J=4.0Hz,1H),8.88(s,1H),7.82(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.63(d,J=8.0Hz,1H),7.50(t,J=8.0Hz,1H),7.36(t,J=8.0Hz,1H),7.00(d,J=8.0Hz,2H),5.24(s,2H),4.18(m,4H),3.66(m,2H).MS(ESI)m/e:(M+1H)+:453.3,(M-1H)-:451.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.04(t,J=4.0Hz,1H),8.89(s,1H),8.09(s,1H),7.87(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.63(d,J=8.0Hz,1H),7.89(m,1H),7.50(m,3H),7.35(t,J=8.0Hz,1H),7.17(d,J=8.0Hz,2H),7.03(m,3H),5.77(s,2H),4.22(t,J=8.0Hz,2H),3.70(m,2H).MS(ESI)m/e:(M+1H)+:513.1,(M-1H)-:511.1.
1H NMR(400MHz,DMSO-d6)δ:9.05(s,1H),8.97(t,1H,J=5.9Hz),8.81(s,1H),8.08(s,1H),7.80(d,1H,J=7.6Hz),7.66-7.62(m,4H),7.56(d,1H,J=8.6Hz),7.42(t,1H,J=8.1Hz),7.28(t,1H,J=7.6Hz),7.15(m,2H),6.94(d,2H,J=8.6Hz),5.70(s,2H),4.15(t,2H,J=5.9Hz),3.64(t,2H,J=5.9Hz).EM(計算値):513.16;MS(ESI)m/e(M+1H)+:514.2,(M-1H)-:512.2.
1H NMR(400MHz,DMSO-d6)δ11.08(s,1H),10.33(s,1H),9.25(t,J=4.0Hz,1H),8.11(d,J=8.0Hz,1H),7.70(m,3H),7.53(t,J=8.0Hz,1H),7.44(t,J=8.OHz,1H),6.99(d,J=8.0Hz,2H),4.84(d,J=4.0Hz,2H),4.23(t,J=8.0Hz,2H),3.70(m,2H),3.48(m,2H),3.23(m,2H),2.04(m,2H),1.90(m,2H).MS(ESI)m/e:(M+1H)+:424.1,(M-1H):422.3.
1H NMR(400MHz,DMSO-d6)δ11.06(s,1H),9.87(s,1H),9.29(t,J=4.0Hz,1H),8.03(d,J=8.0Hz,1H),7.71(m,3H),7.57(t,J=8.0Hz,1H),7.45(t,J=8.0Hz,1H),6.99(d,J=8.0Hz,2H),4.77(s,2H),4.23(t,J=8.0Hz,2H),3.70(m,2H),3.48(m,2H),3.04(m,2H),1.73(m,SH),1.38(m,1H).MS(ESI)m/e:(M+1H)+:438.0,(M-1H)-:436.3.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),9.55(t,J=4.0Hz,1H),8.89(s,1H),7.89(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.61(d,J=8.0Hz,1H),7.45(t,J=8.0Hz,1H),7.33(t,J=8.0Hz,1H),6.99(d,J=8.0Hz,2H),4.19(t,J=8.0Hz,2H),3.96(s,2H),3.68(m,2H),2.95(m,2H),2.28(m,1H),2.09(m,2H),1.78(m,2H),1.44(m,2H).MS(ESI)m/e:(M+1H)+:506.1,(M-1H)-:504.2.
1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),9.18(s,1H),8.04(s,1H),7.70(m,3H),7.53(t,J=8.0Hz,1H),7.39(t,J=8.0Hz,1H),7.00(d,J=8.0Hz,2H),4.21(t,J=8.0Hz,2H),3.70(m,12H),2.76(s,3H).MS(ESI)m/e:(M+1H)+:453.0,(M-1H)-:451.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.90(m,2H),7.83(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,2H),7.61(d,J=8.0Hz,1H),7.48(t,J=8.0Hz,1H),7.34(t,J=8.0Hz,1H),7.00(d,J=8.0Hz,2H),5.08(s,2H),4.19(t,J=8.0Hz,2H),3.68(m,4H),2.58(m,2H).MS(ESI)m/e:(M+1H)+:467.0,(M-1H)-:465.1.
1H NMR(400MHz,DMSO-d6)δ:11.07(s,1H),8.91(m,2H),7.73(d,2H,J=9.0Hz),7.66(s,1H),7.47(d,1H,J=8.7Hz),7.37(t,1H,J=8.4Hz),7.15(d,1H,J=7.4Hz),7.04(d,2H,J=9.0Hz),4.21(t,1H,J=5.7Hz),3.69(t,2H,J=5.7Hz),3.36(s,3H).EM(計算値):354.12;MS(ESI)m/e(M+1H)+:354.7,(M-1H)-:353.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.88(s,1H),8.80(t,J=8.0Hz,1H),7.76(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,2H),7.57(d,J=8.0Hz,1H),7.46(t,J=8.0Hz,1H),7.32(m,3H),7.03(m,4H),4.76(s,2H),4.15(t,J=8.0Hz,2H),3.62(m,2H).MS(ESI)m/e:(M+1H)+:481.1,(M-1H)-:479.0.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.88(m,2H),7.71(d,J=8.0Hz,2H),7.55(m,4H),7.46(t,J=8.0Hz,1H),7.28(m,3H),7.00(d,J=8.0Hz,2H),4.77(s,2H),4.15(t,J=8.0Hz,2H),3.60(m,2H).MS(ESI)m/e:(M+1H)+:497.3,(M-1H)-:495.1.
1H NMR(400MHz,DMSO-d6)δ11.05(s,1H),8.89(s,1H),8.82(t,J=8.0Hz,1H),7.74(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,2H),7.63(m,3H),7.50(t,J=8.0Hz,1H),7.34(m,3H),7.00(d,J=8.0Hz,2H),5.32(s,2H),4.06(t,J=8.0Hz,2H),3.49(m,2H).MS(ESI)m/e:(M+1H)+:513.2,(M-1H)-:511.2.
1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),8.88(s,1H),8.68(d,J=8.0Hz,1H),7.81(d,J=8.0Hz,1H),7.69(d,J=8.0Hz,2H),7.64(d,J=8.0Hz,1H),7.50(t,J=8.0Hz,1H),7.36(t,J=8.0Hz,1H),6.98(d,J=8.0Hz,2H),5.25(s,2H),4.18(m,SH),1.72(m,2H),0.94(t,J=8.0Hz,3H).MS(ESI)m/e:(M+1H)+:481.2,(M-1H)-:479.2.
1H NMR(400MHz,DMSO-d6)δ:11.94(s,1H),11.04(m,1H),9.36(m,1H),8.88(brs,1H),8.63(s,1H),7.71(d,2H,J=8.5Hz),7.22(t,1H,J=8.1Hz),7.07(dd,1H,J=8.1,1.7Hz),7.02(d,2H,J=8.5Hz),6.65(dd,1H,J=7.6,1.6Hz),4.21(t,2H,J=5.6Hz),3.73(2H,q,J=5.2Hz).EM(計算値):356;MS(ESI)m/e(M+1H)+:357.2,(M-1H):354.9.
1H NMR(400MHz,DMSO-d6)δ:11.03(s,1H),8.69(d,1H,J=8.3Hz),7.86(d,1H,J=2.1Hz),7.69(m,3H),7.54(s,1H),7.47(dd,1H,J=8.5Hz,2.5Hz),6.98(d,2H,J=8.6Hz),4.24(m,1H),4.13(m,1H),4.06(m,1H),1.75(m,1H),1.62(m,1H),0.93(t,3H,J=7.3Hz).EM(計算値):402;MS(ES1)m/e(M+1H)+:403.0,(M-1H)-:400.9.
1H NMR(400MHz,DMSO-d6)δ:11.02(s,1H),9.00(t,1H,J=5.8Hz),7.85(d,1H,J=1.9Hz),7.68(m,3H),7.52(s,1H),7.46(dd,1H,J=8.5Hz,1.9Hz),7.03(d,2H,J=8.5Hz),4.69(m,1H),3.57(m,1H),3.40(m,1H),1.32(d,3H,J=5.9Hz).EM(計算値):388;MS(ESI)m/e(M+1H)+:389.1,(M-1H)-:387.0.
1H NMR(400MHz,DMSO-d6)δ:11.05(brs,1H),8.96(t,1H,J=5.6Hz),8.80(d,1H,J=2.0Hz),8.75(dd,1H,J=5.6,0.8Hz),8.35,(d,1H,J=8.0Hz),7.87(dd,1H,J=7.6,5.6Hz),7.71(m,3H),7.61(d,1H,J=8.0Hz),7.45(t,1H,J=6.8Hz),7.34(d,1H,J=7.2Hz),7.00(m,2H),4.91(s,2H),4.75(s,2H),4.18(t,2H,J=5.6Hz),3.66(q,2H,J=6.0Hz).EM(計算値):461;MS(ESI)m/e(M+1H)+:462.2,(M-1H)-:460.3.
1H NMR(400MHz,DMSO-d6)δ:11.00(s,1H),8.82(m,1H),8.37(s,1H),7.67(dd,2H,J=6.8,1.6Hz),7.32-7.24(m,2H),7.01(d,2H,J=9.6Hz),6.90(d,1H,J=8.0Hz),4.17(t,2H,J=5.2Hz),3.89(s,3H),3.69(m,2H).EM(計算値):370;MS(ESI)m/e(M+1H)+:371.2,(M-1H)-:369.1.
1H NMR(400MHz,DMSO-d6)δ:11.04(s,1H),8.96(t,1H,J=5.6Hz),8.45(s,1H),7.70(d,2H,J=8.4Hz),7.37-7.30(m,2H),7.02(d,2H,J=8.4Hz),6.98(dd,1H,J=7.6,0.8Hz),4.37(m,2H),4.17(t,2H,J=5.6Hz),3.82(m,2H),3.69(q,2H,J=6.0Hz),3.34(s,3H).EM(計算値):414;MS(ESI)m/e(M+1H)+:415.2,(M-1H)-:413.3.
1H NMR(400MHz,DMSO-d6)δ:11.04(brs,1H),8.86(m,1H),8.65(t,1H,5.6Hz),8.61(dd,1H,J=4.8,1.6Hz),8.37(s,1H),8.13(m,1H),7.67(m,2H),7.54(m,1H),7.38-7.31(m,2H),7.07(dd,1H,J=7.6,0.8Hz),6.88(m,2H),5.40(s,2H),3.91(t,2H,J=6.0Hz),3.40(m,2H).EM(計算値):447;MS(ESI)m/e(M+1H)+:448.2,(M-1H)-:446.1.
1H NMR(400MHz,DMSO-d6)δ:11.57(s,1H),8.65(t,1H,J=4.5Hz),7.69(d,2H,J=8.5Hz),7.20(s,1H),7.09-6.98(m,4H),6.48(d,1H,J=7.9Hz),4.17(m,2H),3.85(s,3H),3.65(m,2H).EM(計算値):369;MS(ESI)m/e(M+1H)+:370.1,(M-1H)-:368.2.
1H NMR(400MHz,DMSO-d6)δ:11.06(s,1H),8.62(d,1H,J=8.7Hz),7.88(d,1H,J=7.6Hz),7.72(d,2H,J=8.5Hz),7.65(d,1H,J=8.5Hz),7.50(t,1H,J=8.5Hz),7.36(t,1H,J=8.5Hz),7.02(d,2H,J=8.5Hz),5.08(s,2H),4.29(m,1H),4.18(m,1H),4.10(m,1H),3.62(m,2H),3.51(m,2H),3.26(s,3H),1.77(m,1H),1.67(m,1H),0.97(t,3H,J=7.3Hz).EM(計算値):456;MS(ESI)m/e(M+1H)+:457.1,(M-1H)-:455.2.
1H NMR(400MHz,DMSO-d6)δ:11.05(s,1H),8.91(t,1H,J=6.1Hz),7.88(d,1H,J=7.5Hz),7.72(d,2H,J=8.4Hz),7.63(d,1H,J=8.4Hz),7.50(t,1H,J=8.5Hz),7.36(t,1H,J=8.5Hz),7.07(d,2H,J=8.4Hz),5.07(s,2H),4.74(q,1H,J=6.0Hz),3.60(m,2H),3.50(m,2H),3.45(m,2H),3.26(s,3H),1.32(d,3H,J=6.1Hz).EM(計算値):442;MS(ESI)m/e(M+1H)+:443.1,(M-1H)-:441.5.
1H NMR(400MHz,DMSO-d6)δ:11.09(s,1H),9.54(s,1H),9.40(t,1H,J=5.6Hz),8.04(d,1H,J=7.8Hz),7.74(d,2H,J=8.3Hz),7.61(t,1H,J=7.3Hz),7.49(t,1H,J=7.3Hz),7.03(d,2H,J=8.5Hz),4.82(s,2H),4.26(t,2H,J=5.6Hz),3.75(q,2H,J=5.6Hz),3.50(m,2H),3.25(m,4H),1.32(t,6H,J=7.4Hz).EM(計算値):425;MS(ESI)m/e(M+1H)+:426.1,(M-1H)-:424.2.
1H NMR(DMSO-d6):1.95(2H,m);2.05(3H,s);2.48-2.62(2H,m);4.08(1H,dd,11,6Hz);4.16(1h,dd,11,7Hz);4.45(1H,m);6.99(2H,d,9Hz);7.32(1H,t,7Hz);7.45(1H,td,8,1Hz);7.55(1H,d,1Hz);7.64(1H,d,8Hz);7.69(2H,d,9Hz);7.76(1H,d,8Hz);8.7(1H,d,8Hz);8.87(1H,s).MS(M+1):415.
1H NMR(DMSO-d6):2.03-2.21(2H,m);2.99(1H,s,3H);3.22(2H,t,7Hz);4.12(1H,dd,11,6Hz);4.19(1h,dd,11,7Hz);4.46(1H,m);7.00(2H,d,9Hz);7.33(1H,t,7Hz);7.46(1H,td,8,1Hz);7.57(1H,d,1Hz);7.64(1H,d,8Hz);7.70(2H,d,9Hz);7.77(1H,d,8Hz);8.79(1H,d,8Hz);8.88(1H,s).MS(M+1):447.
化合物.1
EM(計算値):381.13;MS(ESI)m/e(M+1H)+:382.3,(M-1H)-:380.2.
EM(計算値):395.15;MS(ESI)m/e(M+1H)+:396.1,(M-1H)-:394.2.
EM(計算値):331.08;MS(ESI)m/e(M+1H)+:331.7,(M-1H)-:330.1.
EM(計算値):317.10;MS(ESI)m/e(M+1H)+:318.10,(M-1H)-:315.9.
EM(計算値):425.2;MS(ESI)m/e(M+1)+:426.1,(M-1)-:424.1.
EM(計算値):381.1;MS(ESI)m/e(M+1)+:382.0,(M-1)-:380.1.
EM(計算値):381.1;MS(ESI)m/e(M+1)+:382.0,(M-1)-:380.2.
EM(計算値):341.1;MS(ESI)m/e(M+1)+:341.9,(M-1)-:340.1.
EM(計算値):381.1;MS(ESI)m/e(M+1)+:381.8,(M-1)-:380.0.
EM(計算値):411.1;MS(ESI)m/e(M+1)+:412.0,(M-1)-:410.3.
EM(計算値):395.2;MS(ESI)m/e(M+1)+:396.0,(M-1)-:394.2.
EM(計算値):388.1;MS(ESI)m/e(M+1)+:389.1,(M-1)-:387.0.
EM(計算値):355.12;MS(ESI)m/e(M+1)+:355.9,(M-1)-:354.1.
EM(計算値):355.1;MS(ESI)m/e(M+1)+:355.9,(M-1)-:353.8.
EM(計算値):409.2;MS(ESI)m/e(M+1)+:410.2,(M-1)-:408.3.
EM(計算値):341.1;MS(ESI)m/e(M+1)+:341.8,(M-1)-:340.2.
1H NMR(400MHz,DMSO-d6)δ11.64(s,1H),8.66(d,J=8.0Hz,1H),7.76(d,J=8.0Hz,1H),7.64(d,J=8.0Hz,1H),7.55(s,1H),7.46(t,J=8.4Hz,1H),7.32(t,J=8.0Hz,1H),6.72(s,1H),4.30(m,3H),1.67(m,2H),0.92(t,J=7.2Hz,3H).EM(計算値):359.1;MS(ESI)m/e:(M+1H):359.8,(M-1H):358.1.
1H NMR(400MHz,DMSO-d6)δ11.64(s,1H),9.48(s,1H),8.47(d,J=8.0Hz,1H),8.09(m,1H),7.82(m,2H),7.71(m,2H),7.55(t,J=8.0Hz,1H),7.49(m,2H),7.39(m,1H),4.30(m,3H),1.69(m,2H),0.94(t,J=7.2Hz,3H).EM(計算値):395.2;MS(ESI)m/e:(M+1H)+:395.8,(M-1H)-:394.0.
1H NMR(400MHz,DMSO-d6)δ11.63(s,1H),8.93(t,J=5.6Hz,1H),7.75(d,J=7.6Hz,1H),7.63(d,J=7.6Hz,1H),7.54(s,1H),7.45(t,J=7.6Hz,1H),7.32(t,J=7.6Hz,1H),6.72(s,1H),4.90(m,1H),3.56(m,2H),0.35(d,J=7.2Hz,3H).EM(計算値):345.1;MS(ESI)m/e:(M+1H)+:345.8,(M-1H)-:344.0.
1H NMR(400MHz,DMSO-d6)δ11.64(s,1H),9.480(s,1H),8.83(t,J=5.6Hz,1H),7.07(m,1H),7.80(d,J=7.6Hz,1H),7.70(d,J=7.6Hz,1H),7.53(t,J=7.6Hz,1H),7.48(m,2H),7.39(m,1H),6.72(s,1H),4.91(m,1H),3.58(m,2H),1.36(d,J=7.0Hz,3H).EM(計算値):381.1;MS(ESI)m/e:(M+1H)+:382.0,(M-1H)-:380.0.
EM(計算値):367.1;MS(ESI)m/e(M+1)+:367.8,(M-1)-:366.2.
EM(計算値):367.12;MS(ESI)m/e(M+1H)+:368.0,(M-1H)-:366.1.
EM(計算値):374.0;MS(ESI)m/e(M+1)+:374.7,(M-1)-:372.9.
EM(計算値):395.2;MS(ESI)m/e(M+1)+:396.1.(M-1)-:394.1
EM(計算値):367.1;MS(ESI)m/e(M+1)+:368.1,(M-1)-:366.2.
EM(計算値):381.1;MS(ESI)m/e(M+1)+:382.0,(M-1)-:380.1.
1H NMR(400MHz,DMSO-d6)δ11.62(s,1H),9.45(s,1H),8.54(d,J=7.6Hz,1H),8.43(s,1H),7.97(m,4H),7.60(m,2H),6.73(s,1H),4.33(m,3H),1.70(m,2H),0.96(t,J=7.6Hz,3H).EM(計算値):369.1;MS(ESI)m/e:(M+1H)+:369.9,(M-1H)-:368.0.
1H NMR(400MHz,DMSO-d6)δ11.66(s,1H),9.50(s,1H),8.53(d,J=7.6Hz,1H),8.11(m,1H),7.96(m,2H),7.55(m,4H),6.78(s,1H),4.33(m,3H),1.68(m,2H),1.01(t,J=7.2Hz,3H).EM(計算値):369.1;MS(ESI)m/e:(M+1H)+:370.0,(M-1H)-:368.2.
1H NMR(400MHz,DMSO-d6)δ11.64(s,1H),8.86(t,J=5.6Hz,1H),8.40(s,1H),7.90(m,4H),7.59(m,2H),6.73(s,1H),4.94(m,1H),3.60(m,2H),1.38(d,J=6.0Hz,3H).EM(計算値):355.1;MS(ESI)m/e:(M+1H)+:355.9,(M-1H)-:353.9.
1H NMR(400MHz,DMSO-d6)δ11.66(s,1H),8.78(t,J=5.6Hz,1H),8.09(d,J=7.6Hz,1H),7.96(m,2H),7.50(m,4H),6.74(s,1H),4.97(m,1H),3.61(m,2H),1.41(d,J=6.4Hz,3H).EM(計算値):355.1;MS(ESI)m/e:(M+1H)+:356.1,(M-1H)-:353.9.
EM(計算値):345.1;MS(ESI)m/e(M+1)+:345.8,(M-1)-:344.0.
EM(計算値):331.1;MS(ESI)m/e(M+1)+:331.9,(M-1)-:330.2.
EM(計算値):437.12;MS(ESI)m/e(M+1H)+:438.0,(M-1H)-:436.2.
アセチル-Gly-Ala-(N-アセチル-Lys)-AMCの合成
tert-Boc(N-アセチル-Lys)-AMC(445mg、1mmol、Bachemから購入した)をジオキサン中4MのHCLに溶かし、H-(N-アセチル-Lys)-AMCを白色固体として獲得した。DMF(5ml)中のH-(N-アセチル-Lys)-AMCの溶液に対して、PyBOP(520mg、1mmol)、HOBt(135mg、1mmol)、及びNMM(0.296ml、2mmol)を使用することでAc-Gly-Ala-OH(188mg、1mmol)を加えた。この反応混合物を1時間に渡り撹拌し、そしてH-(N-アセチル-Lys)-AMCの存在についてMS/LCによってモニタリングした。更なる量のPyBOP(260mg、0.5mmol)、HOBt(70mg、0.5mmol)、及びNMM(0.146ml、1mmol)を加え、撹拌をさらに4時間に渡り続けた。その後、産物を定量できる収量において単離した。
実施例1
invitroでのHDACの阻害
本発明の化合物のinvitroでのHDAC阻害活性を次のように特定した。
invitro細胞増殖アッセイ
式(I)の化合物がin vitroで細胞の増殖を阻害する能力を以下のようにして測定した。
以下は式(I)の化合物を含む代表的な医薬組成物である。
以下の成分を十分に混合しそして単一核の錠剤へと圧縮している。
以下の成分を十分に混合しそして硬殻ゼラチンカプセルへと圧縮している。
以下の成分を十分に混合しそして経口投与のための懸濁を形成した
以下の成分を十分に混合しそして注射可能製剤を形成した。
総重量2.5gの座薬製剤を、本発明の化合物とWitepsol H-15(飽和植物性脂肪酸のトリグリセリド;Riches-Nelson, Inc., New York)を混合することによって調製した。以下の組成を有する。
本発明の化合物500mg
Witepsol(登録商標)H-15のこり
Claims (16)
- 式(I) :
R1は水素又はアルキルであり;
Xは-O-、-NR2-、又は-S(O)n-であり、ここでnは0〜2でありそしてR2は水素又はアルキルであり;
Yは、シクロアルキル、任意に置換されたフェニル、アルキルチオ、アルキルスルフィニル、アルキルスルホニル、任意に置換されたフェニルアルキルチオ、任意に置換されたフェニルアルキルスルホニル、ヒドロキシ、又は任意に置換されたフェノキシにより任意に置換された2又は3個の炭素原子アルキレンであり;
R3は、水素、アルキル、ヒドロキシアルキル、又は任意に置換されたフェニルであり;そして
Ar 2はアリール、アラルキル、アラルケニル、ヘテロアリール、ヘテロアラルキル、ヘテロアラルケニル、シクロアルキル、シクロアルキルアルキル、ヘテロシクロアルキル、又はヘテロシクロアルキルアルキルである)
の化合物;又は医薬的に許容できるその塩。 - Xが-O-であり、そしてR1及びR3が水素である、請求項1に記載の化合物。
- Xが-S(O)n-であり、そしてR1及びR3が水素である、請求項1に記載の化合物。
- Yが置換されていない2又は3個の炭素原子アルキレンである、請求項1に記載の化合物。
- Ar 2がアリール又はアラルケニルである、請求項2〜4のいずれか1項に記載の化合物。
- Ar 2が1又は2個の置換基により任意に置換されているへテロアリールであり、当該置換基は独立してアルキル、ハロ、ハロアルキル、アルコキシ、アルコキシアルキル、ヒドロキシアルコキシ、ヒドロキシアルコキシアルキル、アルコキシアルキルオキシ、アルコキシアルキルオキシアルキル、アミノアルキル、アミノアルコキシ、ハロアルコキシ、ハロアルコキシアルキル、任意に置換されたフェニルアルキル、任意に置換されたフェニルオキシアルキル、任意に置換されたヘテロアリール、任意に置換されたヘテロアラルキルオキシ、任意に置換されたヘテロアリールオキシアルキル、任意に置換されたヘテロシクロアルキルアルキル、任意に置換されたヘテロシクロアルキルオキシ、任意に置換されたヘテロシクロアルキルアルキルオキシ、-アルキレン-S(O)n-Ra(ここで、nは0〜2であり、そしてRaはヒドロキシアルキル又は任意に置換されたフェニルである)、-アルキレン-NRe-アルキレンCONRCRd(ここで、Rcはヒドロキシルであり、そしてRd及びReは独立して水素又はアルキルである)、又はカルボキシアルキルアミノアルキルから選択されている、請求項2〜4のいずれか1項に記載の化合物。
- Ar 2がベンゾフラン-2-イルであり、そして当該ベンゾフラン2-イル環の3-位において一置換されており、当該置換基は、N,N-ジメチルアミノメチル、N,N-ジエチルアミノメチル、2-フルオロフェノキシメチル、3-フルオロフェノキシメチル、4-フルオロフェノキシメチル、ヒドロキシル-4-イルオキシメチル、2,4,6-トリフルオロフェノキシ-メチル、2-オキソピリジン-1-イルメチル、2,2,2-トリフルオロエトキシ-メチル、4-イミダゾール-1-イルフェノキシ-メチル、4-[1.2.4]-トリアジン-1-イル-フェノキシメチル、2-フェニルエチル、3-ヒドロキシプロピルオキシメチル、2-メトキシエチルオキシメチル、ピロリジン-1-イルメチル、ピペリジン-1-イルメチル、4-トリフルオロメチルピペリジン-1-イルメチル、4-メチルピペラジン-1-イルメチル、3,3,3-トリフルオロプロピルオキシメチル、4-フルオロフェニルチオメチル、4-フルオロフェニルスルフィニルメチル、4-フルオロフェニルスルホニルメチル、2-(3-トリフルオロメトキシフェニルエチル)、N-メチル-N-ベンジル-アミノメチル、N-メチル-N-2-フェニルエチルアミノメチル、3-ヒドロキシプロピル-チオメチル、3-ヒドロキシプロピルスルフィニル-メチル、3-ヒドロキシプロピルスルホニルメチル、N-メチル-N-2-インドール-3-イルエチルアミノメチル、2-(4-トリフルオロメチルフェニル)エチル、N-ヒドロキシアミノカルボニル-メチルアミノメチル、又は2-カルボキシエチルアミノ-メチルである請求項6に記載の化合物。
- Ar 2がベンゾフラン-2-イルであり、そして当該ベンゾフラン-2-イル環の5-位において一置換されている、請求項6に記載の化合物。
- 前記置換基が、シクロプロピルピペリジン-4-イルオキシ、ピペリジン-4-イルオキシ、テトラヒドロピラン-4-イルオキシ、2,2,2-トリフルオロエトキシ、2-ピロリジン-1-イルエチルオキシ、又は1-(2,2,2-トリフルオロエチル)ピペリジン-4-イルオキシである、請求項8に記載の化合物。
- Ar 2がアラルケニルである、請求項5に記載の化合物。
- Ar 2がトランスフェニルCH=CH-であり、ここで当該フェニルは、アルキル、アルコキシ、メチレンジオキシ、又はヒドロキシルから独立して選択された1又は2個の置換基により任意に置換されている、請求項10に記載の化合物。
- N-ヒドロキシ-4-(2-ベンゼンカルボニルアミノ-エトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-トランス-シンナモイルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-トランス-2-フェニルシクロプロピルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-トランス-4-メトキシシンナモイルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(2-フェニルエチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-3-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-(2-チオフェン-2-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-ピリジン-3-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-ビフェン-4-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-ビフェン-3-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(5-フェニルチオフェン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(チオフェン-2-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ナフタ-2-イルカルボニルアミノ)エトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-6-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-tert-ブチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-ピリジン-3-イルアクリロイルアミノ)エトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピロール-1-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-シクロヘキセン-3-オキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチアゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾオキサゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(オクタヒドロイソキノリン-2-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-4-イルピペラジン-1-イルメチルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(フラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-3-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-2-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾイミダゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-ピロール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ベンゾイルアミノフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-4-イルチアゾール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(アドマンタン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,4-ジフルオロフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-トランス-3,4-メレンジオキシフェニルアクリロイルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(3,4-メチレンジオキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3,4-ジメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3,5-ジメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3,4-ジフルオロフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,5-ジメチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,3-ジクロロフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2,3-ジメチルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-クロロ-2-メトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-エトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシ-2-メチルフェニルカルボニルアミノ)エトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(3-フルオロ-4-メトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-チオフェン-2-イルメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-チオフェン-2-イルメトキシフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ビフェン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-5-イルカルボニルアミノ)エトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-3-イルカルボニルアミノ)エトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-8-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インダゾール-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1H-ベンゾトリアゾール-5-イオカルボニルアミノ)エトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(イソキノリン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(イソキノリン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノキサリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ナフタ-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-ピロール-1-イルフェニルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-フルオロナフタ-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(H-ベンゾイミダゾール-5-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1-メチルインドール-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシキノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-メトキシナフタ-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-メトキシナフタ-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(キノリン-4-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-メチルシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(2-N,N-ジメチルアミノメチルベンゾフラン-5-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-(2-インドリン-1-イルカルボニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(1,2,3,4-テトラヒドロキノリン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2S-[トランス-3-(5-ヒドロキシベンゾフラン-2-イル)ブト-2-エノイルアミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[トランス-3-(5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イル)ブタ-2-エノイル-アミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)-4-フェニルブトキシ)ベンズアミド;
N-ヒドロキシ-4-{2-[5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(1-シクロプロピルピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(1-(2,2,2-トリフルオロエチル)ピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニル-アミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2R-(ベンゾフラン-2-イルカルボニルアミノ)-3-ベンジルスルホニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(ベンゾフラン-2-イルカルボニルアミノ)-3-ベンジルチオプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-(5-メトキシベンゾフラン-2-イル)ブト-2-エノイルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1,2,3,4-テトラヒドロイソキノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(イソインドリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(モルホリン-4-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ベンジルピペラジン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3(R)-ヒドロキシピロリジン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ピペリジン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-メチル-1,2,3,4-テトラヒドロキノリン-1-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(2-メチルインドリン-1-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-フルオロ-2-メチル-1,2,3,4-テトラヒドロキノリン-1-イルカルボニルアミノ)-エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(イソインドリン-1-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[3-(トランス-シンナモイルアミノ)プロポキシ]ベンズアミド;
N-ヒドロキシ-4-[3-(トランス-4-メトキシシンナモイルアミノ) プロポキシ]ベンズアミド;
N-ヒドロキシ-4-[3-(4-フェニルチアゾール-2-イルカルボニルアミノ)プロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)プロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)プロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-4-メチルペントキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-シクロヘキシルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-メチルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-フェニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-フェニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-4-メチルペントキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-メチルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2RS-(トランス-シンナモイルアミノ)ヘキシルオキシ]ベンズアミド;
N-ヒドロキシ-4-[2RS-(トランス-シンナモイルアミノ)-3-(4-クロロフェニル)プロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-4-メチルチオブトキシ)ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-4-メチルチオブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-2-フェニルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-2-フェニルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-4-メチルスルホニルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-4-メチルスルホニルブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-ベンジルスルホニルプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(チオフェン-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ビフェン-4-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ナフタ-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2R-(トランス-シンナモイルアミノ)-3-ベンジルチオプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゼンカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンジルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(2-フェニルエチルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-シンナモイルアミノ)-3-ヒドロキシプロポキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(4-フェニルチアゾール-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(トランス-4-メトキシシンナモイルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(2-N,N-ジメチルアミノメチルベンゾフラン-5-イルカルボニルアミノ)ブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-シンナモイルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-シンナモイルアミノ)-1S-メチルエトキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)-1R-メチルエトキシ] ベンズアミド;
N-ヒドロキシ-4-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)-1S-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(ビフェン-4-イルカルボニルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-4-メトキシシンナモイルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-ピリジン-2-イルチアゾール-5-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(7-クロロ-4-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-(4-メチルピペラジン-1-イル)チアゾール-5-イル)フェニルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-ピリジン-4-イルアミノチアゾール-5-イル)フェニルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(4-メチルピペラジン-1-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(4-ヒドロキシピペリジン-1-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(4-モルホリン-4-イルメチルチアゾール-5-イル)フェニルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(7-フルオロ-4-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[7-フルオロ-4-(2-メトキシエトキシメチル)ベンゾフラン-2-イルカルボニルアミノ)-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(4-ヒドロキシキノリン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(7-フルオロ-4-フェノキシメチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-(4-メチルピペラジン-1-イルメチル)チアゾール-5-イル)フェニルカルボニル-アミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(ピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(3-ヒドロキシピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-ヒドロキシピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[6-(4-ニトロフェノキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-メトキシエトキシ)キノリン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-N,N-ジメチルアミノエトキシ)キノリン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(6-ブロモピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(5-ブロモピリジン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(4-メトキシキノリン-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(1-メトキシナフタ-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシキノリン-2-イルカルボニルアミノ)-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(5-フェニルピリジン-3-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(6-ベンジルオキシピリジン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-メチルプロピルオキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-フェニルエチルオキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[4-(3,3,3-トリフルオロプロピルオキシ)キノリン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[4- (3,3,3-トリフルオロプロピルオキシ)キノリン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[4-(3,3,3-トリフルオロプロピルオキシ)キノリン-2-イルカルボニルアミノ]-1R-メチル-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-ヒドロキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-4-ヒドロキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[3'-(2-ヒドロキシエチル)ビフェン-4-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3'-(2-ヒドロキシエチル)ビフェン-3-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[2'-(2-ヒドロキシエチル)ビフェン-4-イルカルボニルアミン]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-ベンゾフラン-2-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[2'-(2-ヒドロキシエチル)ビフェン-3-イルカルボニルアミノ]エトキシ}ベンズアミド ;
N-ヒドロキシ-4-{2-[5-(チオフェン-3-イル)ピリジン-3-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[6-(4-アセチルアミノフェノキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(4-アミノフェノキシ)ピリジン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-メトキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-メトキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[5-(4-ジメチルアミノフェニル)ピリジン-3-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-(5-ブロモチオフェン-2-イル)アクリロイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-フラン-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-チオフェン-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-チオフェン-2-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-メチルシンナモイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-4-メチルシンナモイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-3-(ベンゾフラン-2-イル)ブタ-2-エノイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[シス-3-(ベンゾフラン-2-イル)ブタ-2-エノイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-4-ジメチルアミノシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-([2-(トランス-3-インドール-3-イルアクリロイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[トランス-2-メチルシンナモイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-2-ヒドロキシシンナモイルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2- [トランス-3- (7-メトキシベンゾフラン-2-イル)アクリロイルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2R-[トランス-3-(7-メトキシベンゾフラン-2-イル)アクリロイルアミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[トランス-3-(5-メトキシベンゾフラン-2-イル)ブタ-2-エノイルアミノ]ブトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(トランス-3-フラン-2-イルアクリロイルアミノ)エトキシ]ベンズアミド;及び
N-ヒドロキシ-4-{2-[4-(4-(2-モルホリン-4-イルエチル)チアゾール-2-イル)フェニルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-ヒドロキシエチルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-フェニルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-メチルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-ベンゾチオフェン-2-イル-N-イソプロピルアミノエトキシ)ベンズアミド;
N-ヒドロキシ-4-(2-N-トランス-シンナモイル-N-イソプロピルアミノエトキシ)ベンズアミド;及び
N-ヒドロキシ-4-(3-N-トランス-シンナモイル-N-メチルアミノプロポキシ)ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(1H-インドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(1-メチルインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[3-(ベンゾチオフェン-2-イルカルボニルアミノ)プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[3-(ベンゾフラン-2-イルカルボニルアミノ)プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾチオフェン-2-イルカルボニルアミノ)-3-メチルブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾチオフェン-2-イルカルボニルアミノ)ブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾチオフェン-2-イルカルボニルアミノ)-プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[2R-(ベンゾチオフェン-2-イルカルボニルアミノ)-プロポキシ]-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)ブトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イルカルボニルアミノ)-1R-メチルエトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾチオフェン-2-イルカルボニルアミノ)-1S-メチルエトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)-1R-メチルエトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(6-メトキシベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メチルベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(3-クロロベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(6-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(4-トリフルオロメチルベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-フルオロベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メトキシベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-クロロベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(7-メトキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メトキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-メトキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-モルホリン-4-イルエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ)-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(ピリジン-3-イルメトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(3-メチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(3-メチルベンゾチオフェン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-ヒドロキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-N,N-ジメチルアミノエトキシ)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-メトキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(2-モルホリン-4-イルエトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[6-(ピリジン-3-イルメトキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(3-エチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-フルオロインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-[2-(5-メトキシインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(メトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(フェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(5,6-ジメトキシインドール-2-イルカルボニルアミノ)エトキシ]-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(モルホリン-4-イルメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N, N-ジメチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(i-プロポキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(フェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(メトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[7-(モルホリン-4-イルメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ} ベンズアミド;
N-ヒドロキシ-4-{2-[7-(N,N-ジメチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{3-[5-(メチル)ベンゾチオフェン-2-イルカルボニルアミノ]プロポキシ}-ベンズアミド;
N-ヒドロキシ-4-{3-[6-(メトキシ)ベンゾチオフェン-2-イルカルボニルアミノ]プロポキシ}-ベンズアミド;
N-ヒドロキシ-4-{3-[7-(メトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]プロポキシ)-ベンズアミド;
N-ヒドロキシ-4-{3-[7-(フェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]プロポキシ}-ベンズアミド;及び
N-ヒドロキシ-4-{2-[5-(2-メトキシエトキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ}ベンズアミド;
N-ヒドロキシ-4-(2R-ベンゾフラン-2-イルカルボニルアミノ-3-メチルチオプロポキシ)ベンズアミド;
N-ヒドロキシ-4-(2R-ベンゾフラン-2-イルカルボニルアミノ-3-メチルスルホニルプロポキシ)ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-フェニルエチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-メチル-N-ベンジルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-メチル-N-2-フェニルエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロピルチオメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロピルスルフィニルメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロピルスルホニルメチル)ベンゾフラン-2-イルカルボニルアミノ-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-メチル-N-2-インドール-3-イルエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-(3-トリフルオロメチルフェニル)エチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-(3-トリフルオロメトキシフェニル)エチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N-ヒドロキシアミノカルボニルメチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-カルボキシエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(ベンゾフラン-2-イルカルボニルアミノ)-1RS-フェノキシメチルエトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-ヒドロキシプロポキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-フルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3-フルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-メトキシエチルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ)-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(ピリジン-4-イルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2,4,6-トリフルオロフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-オキソピリジン-1-イルメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-イミダゾール-1-イルフェノキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-[1.2.4]-トリアジン-1-イルフェノキシメチル)ベンゾフラン-2-イルカルボニル-アミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(ピロリジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(ピペリジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-トリフルオロメチルピペリジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-メチルピペラジン-1-メチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(3,3,3-トリフルオロプロピルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}ベンズアミド;
N-ヒドロキシ-4-[2-(4-メチルベンゾフラン-2-イルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェニルチオメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェニルスルフィニルメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[3-(4-フルオロフェニルスルホニルメチル)ベンゾフラン-2-イルカルボニルアミノ]-エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[3-(2,2,2-トリフルオロエトキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(4-ヒドロキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(5-クロロベンゾフラン-2-イルカルボニルアミノ)ブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(5-クロロベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-3-イルメチルオキシメチルベンゾフラン-2-イルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシベンゾフラン-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2-[4-(2-メトキシエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ)エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2-(4-ピリジン-3-イルメチルオキシベンゾフラン-2-イルカルボニルアミノ)-エトキシ]ベンズアミド;
N-ヒドロキシ-4-[2-(4-メトキシインドール-2-イルカルボニルアミノ)エトキシ]ベンズアミド;
N-ヒドロキシ-4-{2S-[3-(2-メトキシエチルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-ブトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(2-メトキシエチルオキシメチル)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[3-(N,N-ジエチルアミノメチル)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(2-メトキシエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(テトラヒドロピラン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(テトラヒドロピラン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(テトラヒドロピラン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチル-エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2,2,2-トリフルオロエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-{5-(2-ピロリドン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}ベンズアミド;
N-ヒドロキシ-4-{2S-[5-(2-ピロリジン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]ブトキシ}-ベンズアミド;
N-ヒドロキシ-4-{2-[5-(2-ピロリジン-1-イルエチルオキシ)ベンゾフラン-2-イルカルボニルアミノ]-1R-メチルエトキシ}ベンズアミド;
N-ヒドロキシ-4-{2-[5-(ピペリジン-4-イルオキシ)ベンゾフラン-2-イルカルボニルアミノ]エトキシ}-ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)-4-メチルチオブトキシ]ベンズアミド;
N-ヒドロキシ-4-[2S-(ベンゾフラン-2-イルカルボニルアミノ)-4-メチルスルホニルブトキシ]ベンズアミド;
N-ヒドロキシ-3-[2-(ビフェン-4-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ビフェン-4-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ベンゾフラン-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(トランス-シンナモイルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(4-(2-エトキシフェニル) フェニルカルボニルアミノ) プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ビフェン-3-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ビフェン-4-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(3-メチルビフェン-4-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-[2'-エトキシルビフェン-4-イルカルボニルアミノ)エトキシ]イソオキゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(3-メチルビフェン-4-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(4-フェニルチアゾール-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ナフタ-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ナフタ-1-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-{3-[2-(2-フェニルエチル)フェニルカルボニルアミノ]プロポキシ}イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-1-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ベンゾフラン-2-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ビフェン-3-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ベンゾフラン-2-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-3-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-3-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-4-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(4-フェニルチアゾール-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-{2-[2-(2-フェニルエチル)フェニルカルボニルアミノ]エトキシ}イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ビフェン-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ビフェン-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ナフタ-2-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2S-(ナフタ-1-イルカルボニルアミノ)ブトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-2-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[2-(ナフタ-1-イルカルボニルアミノ)-1R-メチルエトキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(ベンゾフラン-2-イルカルボニルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;
N-ヒドロキシ-3-[3-(トランス-シンナモイルアミノ)プロポキシ]イソオキサゾール-5-イルカルボキサミド;及び
N-ヒドロキシ-3-[2-(3-フェノキシメチルベンゾフラン-2-イルカルボニルアミノ)エトキシ]イソオキサゾール-5-イル-カルボキサミド;
からなる群から選択された化合物又は医薬的に許用できるその塩。
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PCT/US2004/010549 WO2004092115A2 (en) | 2003-04-07 | 2004-04-06 | Hydroxamates as therapeutic agents |
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OA12790A (en) | 2002-03-13 | 2006-07-10 | Janssen Pharmaceutica Nv | New inhibitors of histone deacetylase. |
MXPA04007776A (es) | 2002-03-13 | 2004-10-15 | Janssen Pharmaceutica Nv | Derivados de sulfonilamino como nuevos inhibidores de histona deacetilasa. |
ES2306858T3 (es) | 2002-03-13 | 2008-11-16 | Janssen Pharmaceutica Nv | Derivados de carbonilamino como nuevos inhibidores de las histonadesacetilasas. |
ATE398615T1 (de) | 2002-03-13 | 2008-07-15 | Janssen Pharmaceutica Nv | Piperazinyl-, piperidinyl- und morpholinylderivate als neue inhibitoren von histon-deacetylase |
SI1611088T1 (sl) | 2003-04-07 | 2009-12-31 | Pharmacyclics Inc | Hidroksamati kot terapevtska sredstva |
WO2005011598A2 (en) * | 2003-07-31 | 2005-02-10 | University Of South Florida | Leukemia treatment method and composition |
BRPI0413439A (pt) * | 2003-08-08 | 2006-10-17 | Novartis Ag | combinações compreendendo estaurosporinas |
GB2427405A (en) * | 2004-04-07 | 2006-12-27 | Pharmacyclics Inc | Novel hydroxamates as therapeutic agents |
ITMI20041347A1 (it) * | 2004-07-05 | 2004-10-05 | Italfarmaco Spa | Derivati di alfa-amminoacidi ad attivita'antiinfiammatoria |
WO2006010750A1 (en) | 2004-07-28 | 2006-02-02 | Janssen Pharmaceutica N.V. | Substituted indolyl alkyl amino derivatives as novel inhibitors of histone deacetylase |
RS51189B (sr) | 2004-07-28 | 2010-10-31 | Janssen Pharmaceutica N.V. | Supstituisani derivati propenil piperazina kao novi inhibitori histonske deacetilaze |
WO2006042035A2 (en) * | 2004-10-07 | 2006-04-20 | Pharmacyclics, Inc. | Method of monitoring anti-tumor activity of an hdac inhibitor |
WO2006054793A1 (ja) * | 2004-11-19 | 2006-05-26 | The New Industry Research Organization | ベンゾフラン化合物、およびそれを含有してなる医薬組成物 |
EP2500063A1 (en) | 2005-02-03 | 2012-09-19 | TopoTarget UK Limited | Combination therapy using HDAC inhibitors and melphalan for treating cancer |
AU2006214319A1 (en) | 2005-02-14 | 2006-08-24 | Miikana Therapeutics, Inc. | Fused heterocyclic compounds useful as inhibitors of histone deacetylase |
GB0509223D0 (en) | 2005-05-05 | 2005-06-15 | Chroma Therapeutics Ltd | Enzyme inhibitors |
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