JP2011500603A5

JP2011500603A5 -

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Publication number: JP2011500603A5
Authority: JP; Japan
Prior art keywords: isopropyl; tetrazol; methoxy; diol; biphenyl
Prior art date: 2008-10-14
Legal status : Granted

Application number

JP2010529145A

Other languages

English (en)

Japanese (ja)

Other versions

JP2011500603A (ja

JP4792128B2 (ja

Filing date

2008-10-14

Publication date

2011-04-21

2008-10-14 Application filed filed Critical

2008-10-14 Priority claimed from PCT/US2008/079755 external-priority patent/WO2009049305A2/en

2011-01-06 Publication of JP2011500603A publication Critical patent/JP2011500603A/ja

2011-04-21 Publication of JP2011500603A5 publication Critical patent/JP2011500603A5/ja

2011-10-12 Application granted granted Critical

2011-10-12 Publication of JP4792128B2 publication Critical patent/JP4792128B2/ja

Status Expired - Fee Related legal-status Critical Current

2028-10-14 Anticipated expiration legal-status Critical

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150000001875 compounds Chemical class 0.000 claims description 123
-1 CH 3 Inorganic materials 0.000 claims description 90
229910052739 hydrogen Inorganic materials 0.000 claims description 50
239000001257 hydrogen Substances 0.000 claims description 50
125000003118 aryl group Chemical group 0.000 claims description 48
125000000623 heterocyclic group Chemical group 0.000 claims description 44
125000001072 heteroaryl group Chemical group 0.000 claims description 41
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 35
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
150000003839 salts Chemical class 0.000 claims description 23
125000000547 substituted alkyl group Chemical group 0.000 claims description 23
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 21
125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 19
150000002431 hydrogen Chemical class 0.000 claims description 19
239000008194 pharmaceutical composition Substances 0.000 claims description 16
239000002246 antineoplastic agent Substances 0.000 claims description 11
229910052794 bromium Inorganic materials 0.000 claims description 11
229910052801 chlorine Inorganic materials 0.000 claims description 11
239000003937 drug carrier Substances 0.000 claims description 11
229910052731 fluorine Inorganic materials 0.000 claims description 11
229910052740 iodine Inorganic materials 0.000 claims description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 10
229940127089 cytotoxic agent Drugs 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 9
229960004397 cyclophosphamide Drugs 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 8
229960002949 fluorouracil Drugs 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
125000003107 substituted aryl group Chemical group 0.000 claims description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 6
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 6
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 6
229960000485 methotrexate Drugs 0.000 claims description 6
239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
CSUYJYHMSVADNP-UHFFFAOYSA-N 3-[5-[2,4-dihydroxy-5-(2-methoxy-5-propan-2-ylphenyl)phenyl]tetrazol-1-yl]oxolan-2-one Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)C2C(OCC2)=O)=C(O)C=C1O CSUYJYHMSVADNP-UHFFFAOYSA-N 0.000 claims description 4
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 4
XAVVXZPRLKCUGN-UHFFFAOYSA-N 4-(1-cyclohexyltetrazol-5-yl)-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)C2CCCCC2)=C(O)C=C1O XAVVXZPRLKCUGN-UHFFFAOYSA-N 0.000 claims description 4
XBGRTKOSKOLVTB-UHFFFAOYSA-N 4-(2-methoxy-5-propan-2-ylphenyl)-6-(1-piperidin-4-yltetrazol-5-yl)benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)C2CCNCC2)=C(O)C=C1O XBGRTKOSKOLVTB-UHFFFAOYSA-N 0.000 claims description 4
FJHOZNUNSIJGJM-UHFFFAOYSA-N 4-(2-methoxy-5-propan-2-ylphenyl)-6-(1-propan-2-yltetrazol-5-yl)benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)C(C)C)=C(O)C=C1O FJHOZNUNSIJGJM-UHFFFAOYSA-N 0.000 claims description 4
CQEHQAFCLGCBFL-UHFFFAOYSA-N 4-(2-methoxy-5-propan-2-ylphenyl)-6-[1-(2-methylpropyl)tetrazol-5-yl]benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)CC(C)C)=C(O)C=C1O CQEHQAFCLGCBFL-UHFFFAOYSA-N 0.000 claims description 4
FDCHOCJMFUIDQE-UHFFFAOYSA-N 4-(2-methoxy-5-propan-2-ylphenyl)-6-[1-(oxolan-2-ylmethyl)tetrazol-5-yl]benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)CC2OCCC2)=C(O)C=C1O FDCHOCJMFUIDQE-UHFFFAOYSA-N 0.000 claims description 4
STGCXYLBJMIFPE-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)tetrazol-5-yl]-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)C=2C=CC(F)=CC=2)=C(O)C=C1O STGCXYLBJMIFPE-UHFFFAOYSA-N 0.000 claims description 4
HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 4
BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims description 4
108010069236 Goserelin Proteins 0.000 claims description 4
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
229930012538 Paclitaxel Natural products 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
229960001904 epirubicin Drugs 0.000 claims description 4
229960001433 erlotinib Drugs 0.000 claims description 4
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
229960001592 paclitaxel Drugs 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
229960004641 rituximab Drugs 0.000 claims description 4
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
PRRDVCMTUYSYTG-UHFFFAOYSA-N 3-[5-(1-butyltetrazol-5-yl)-2,4-dihydroxyphenyl]benzoic acid Chemical compound CCCCN1N=NN=C1C1=CC(C=2C=C(C=CC=2)C(O)=O)=C(O)C=C1O PRRDVCMTUYSYTG-UHFFFAOYSA-N 0.000 claims description 3
XNLWJFYYOIRPIO-UHFFFAOYSA-N 3-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=CC=CC=2)=C1 XNLWJFYYOIRPIO-UHFFFAOYSA-N 0.000 claims description 3
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
GHSDAIFRAMFILB-UHFFFAOYSA-N 4-(1-butyltetrazol-5-yl)-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound CCCCN1N=NN=C1C1=CC(C=2C(=CC=C(C=2)C(C)C)OC)=C(O)C=C1O GHSDAIFRAMFILB-UHFFFAOYSA-N 0.000 claims description 3
GQWSQQNQNYJJFX-UHFFFAOYSA-N 4-(1-ethyltetrazol-5-yl)-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound CCN1N=NN=C1C1=CC(C=2C(=CC=C(C=2)C(C)C)OC)=C(O)C=C1O GQWSQQNQNYJJFX-UHFFFAOYSA-N 0.000 claims description 3
ZPSNRIRIDAIZKA-UHFFFAOYSA-N 4-(2-methoxy-5-propan-2-ylphenyl)-6-(1-propyltetrazol-5-yl)benzene-1,3-diol Chemical compound CCCN1N=NN=C1C1=CC(C=2C(=CC=C(C=2)C(C)C)OC)=C(O)C=C1O ZPSNRIRIDAIZKA-UHFFFAOYSA-N 0.000 claims description 3
SGUFIGIAFHGKQG-UHFFFAOYSA-N 4-[1-(1-ethylpiperidin-4-yl)tetrazol-5-yl]-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound C1CN(CC)CCC1N1C(C=2C(=CC(O)=C(C=2)C=2C(=CC=C(C=2)C(C)C)OC)O)=NN=N1 SGUFIGIAFHGKQG-UHFFFAOYSA-N 0.000 claims description 3
JDFHSCGYBIPHSB-UHFFFAOYSA-N 4-[1-(2-methoxyethyl)tetrazol-5-yl]-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound COCCN1N=NN=C1C1=CC(C=2C(=CC=C(C=2)C(C)C)OC)=C(O)C=C1O JDFHSCGYBIPHSB-UHFFFAOYSA-N 0.000 claims description 3
CAZLYPHIUHRCTE-UHFFFAOYSA-N 4-[1-(cyclopropylmethyl)tetrazol-5-yl]-6-(2-methoxy-5-propan-2-ylphenyl)benzene-1,3-diol Chemical compound COC1=CC=C(C(C)C)C=C1C1=CC(C=2N(N=NN=2)CC2CC2)=C(O)C=C1O CAZLYPHIUHRCTE-UHFFFAOYSA-N 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 claims description 3
MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 3
101100002068 Bacillus subtilis (strain 168) araR gene Proteins 0.000 claims description 3
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 3
108010092160 Dactinomycin Proteins 0.000 claims description 3
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PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 3
KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 claims description 3
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 3
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 3
229960002932 anastrozole Drugs 0.000 claims description 3
YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 3
101150044616 araC gene Proteins 0.000 claims description 3
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 3
VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 3
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125000001309 chloro group Chemical group Cl* 0.000 claims description 3
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
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125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
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STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
229960000975 daunorubicin Drugs 0.000 claims description 3
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KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 3
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GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 3
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JP2010529145A 2007-10-12 2008-10-14 癌に対するｈｓｐ９０阻害剤としての５−（２−ヒドロキシフェニル）テトラゾール Expired - Fee Related JP4792128B2 (ja)