JP5342142B2 - 12−アリールプロスタグランジンアナログ - Google Patents
12−アリールプロスタグランジンアナログ Download PDFInfo
- Publication number
- JP5342142B2 JP5342142B2 JP2007545643A JP2007545643A JP5342142B2 JP 5342142 B2 JP5342142 B2 JP 5342142B2 JP 2007545643 A JP2007545643 A JP 2007545643A JP 2007545643 A JP2007545643 A JP 2007545643A JP 5342142 B2 JP5342142 B2 JP 5342142B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- cyclopentyl
- phenyl
- chloro
- methyl ester
- 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.)
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- 150000001875 compounds Chemical class 0.000 claims abstract description 165
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims description 95
- 150000004702 methyl esters Chemical class 0.000 claims description 38
- -1 2-hydroxy-1,1-dimethyl-ethyl Chemical group 0.000 claims description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 230000004410 intraocular pressure Effects 0.000 claims description 15
- 208000010412 Glaucoma Diseases 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 150000001408 amides Chemical class 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- HVQPCSIKQMRYAQ-HBLLDXLXSA-N methyl (z)-7-[(1r,2s,3r)-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(C(O)C2CCCCC2)C=C1 HVQPCSIKQMRYAQ-HBLLDXLXSA-N 0.000 claims description 6
- XWMXWKGOQYWZNY-JMWRMVSPSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C2CCCCC2)C=C1 XWMXWKGOQYWZNY-JMWRMVSPSA-N 0.000 claims description 6
- SNNNCRUILASWAJ-DEOIKXTHSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]hept-5-enoic acid Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(O)=O)C=CC=1C(O)C1CCCCC1 SNNNCRUILASWAJ-DEOIKXTHSA-N 0.000 claims description 5
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- AETUZWCDUUSBRC-NEXMAASUSA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(C2(O)CCC2)C=C1 AETUZWCDUUSBRC-NEXMAASUSA-N 0.000 claims description 5
- NTUILXJVELUSRZ-RPEOMIDLSA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(C(O)CC2)C2=C1 NTUILXJVELUSRZ-RPEOMIDLSA-N 0.000 claims description 5
- NKLFEKONSITWAH-ILZDJORESA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-[4-(hydroxymethyl)phenyl]-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(CO)C=C1 NKLFEKONSITWAH-ILZDJORESA-N 0.000 claims description 5
- BELBFBSHUITIAA-POMLREGLSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-2-[4-(cyclohexylmethyl)phenyl]-3-hydroxycyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C(C=C1)=CC=C1CC1CCCCC1 BELBFBSHUITIAA-POMLREGLSA-N 0.000 claims description 5
- JHUZQUMJNPQVQM-IQLLUQGCSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C2CCCCC2)C=C1 JHUZQUMJNPQVQM-IQLLUQGCSA-N 0.000 claims description 5
- MYYLZOGRCGVWSF-GDXPKGJTSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2)C2=C1 MYYLZOGRCGVWSF-GDXPKGJTSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- QKZVCUBCHFTZNL-IRNVDABOSA-N propan-2-yl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]hept-5-enoate Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2)C2=C1 QKZVCUBCHFTZNL-IRNVDABOSA-N 0.000 claims description 5
- SCBQUKWWTNGHNE-NAENYJNXSA-N (z)-7-[(1r,2s,3r)-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C=1C=CC([C@@H]2[C@H](C(=O)C[C@H]2O)C\C=C/CCCC(O)=O)=CC=1C(O)C1(CCC)CCC1 SCBQUKWWTNGHNE-NAENYJNXSA-N 0.000 claims description 4
- SNBKHQKOJMMUPT-PKENTYADSA-N (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-(hydroxymethyl)phenyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C1=CC(CO)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)C(=O)C[C@H]1O SNBKHQKOJMMUPT-PKENTYADSA-N 0.000 claims description 4
- XQMVWUPVNFAGKL-GDSIGRTQSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2,2-dimethylpropyl)phenyl]cyclopentyl]hept-5-enoic acid Chemical compound C1=CC(C(O)C(C)(C)C)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@H](Cl)C[C@H]1O XQMVWUPVNFAGKL-GDSIGRTQSA-N 0.000 claims description 4
- CFCKBYKCOVVZRP-HRGNYIASSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropyl)phenyl]cyclopentyl]hept-5-enoic acid Chemical compound C1=CC(C(O)C(C)C)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@H](Cl)C[C@H]1O CFCKBYKCOVVZRP-HRGNYIASSA-N 0.000 claims description 4
- SERARKCJMHKXJN-MLMRMRFMSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(hydroxymethyl)phenyl]cyclopentyl]hept-5-enoic acid Chemical compound C1=CC(CO)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@H](Cl)C[C@H]1O SERARKCJMHKXJN-MLMRMRFMSA-N 0.000 claims description 4
- LJMMSVVQMJQKGD-BMJBQGFASA-N 2-[3-[[(1r,2s,3r)-3-hydroxy-2-[3-[(s)-hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]methyl]phenoxy]acetic acid Chemical compound CCCC1([C@H](O)C=2C=C(C=CC=2)[C@@H]2[C@H](C(=O)C[C@H]2O)CC=2C=C(OCC(O)=O)C=CC=2)CCC1 LJMMSVVQMJQKGD-BMJBQGFASA-N 0.000 claims description 4
- LFURQAOXCGLIRL-KZDJQDIGSA-N 2-[3-[[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-[(s)-hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]methyl]phenoxy]acetic acid Chemical compound CCCC1([C@H](O)C=2C=C(C=CC=2)[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CC=2C=C(OCC(O)=O)C=CC=2)CCC1 LFURQAOXCGLIRL-KZDJQDIGSA-N 0.000 claims description 4
- ZHSBXMHCTCKQQU-NTXCDXHRSA-N 2-[4-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]butoxy]acetic acid Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCCOCC(O)=O)C=CC=1C(O)C1CCCCC1 ZHSBXMHCTCKQQU-NTXCDXHRSA-N 0.000 claims description 4
- JPCYMKKZFAJAIW-FBBABVLZSA-N 7-[(1r,2s,3r)-2-(2,3-dihydro-1h-inden-5-yl)-3-hydroxy-5-oxocyclopentyl]heptanoic acid Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(CCC2)C2=C1 JPCYMKKZFAJAIW-FBBABVLZSA-N 0.000 claims description 4
- IWSXNGMJGVZSIZ-QYJPUHJCSA-N 7-[(1r,2s,3r)-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxy-5-oxocyclopentyl]heptanoic acid Chemical compound C=1C=C([C@@H]2[C@H](C(=O)C[C@H]2O)CCCCCCC(O)=O)C=CC=1C(O)C1CCCCC1 IWSXNGMJGVZSIZ-QYJPUHJCSA-N 0.000 claims description 4
- WXDRQRFIODIFPC-MDYPYWROSA-N 7-[(1r,2s,3r)-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)-5-oxocyclopentyl]heptanoic acid Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(C(O)CC2)C2=C1 WXDRQRFIODIFPC-MDYPYWROSA-N 0.000 claims description 4
- HQESDFOICQWKKP-YELUUFJXSA-N 7-[(1r,2s,3r)-5-fluoro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]heptanoic acid Chemical compound O[C@@H]1CC(F)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(C(O)CC2)C2=C1 HQESDFOICQWKKP-YELUUFJXSA-N 0.000 claims description 4
- AMMUDLZBSSMGFI-QEUVDIPISA-N 7-[(1r,2s,3r,5r)-5-chloro-2-(2,3-dihydro-1h-inden-5-yl)-3-hydroxycyclopentyl]heptanoic acid Chemical compound O[C@@H]1C[C@@H](Cl)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(CCC2)C2=C1 AMMUDLZBSSMGFI-QEUVDIPISA-N 0.000 claims description 4
- XVJWBTBYXGKBDM-XJTUCQONSA-N 7-[(1r,2s,3r,5r)-5-chloro-2-[4-(cyclohexylmethyl)phenyl]-3-hydroxycyclopentyl]heptanoic acid Chemical compound O[C@@H]1C[C@@H](Cl)[C@H](CCCCCCC(O)=O)[C@H]1C(C=C1)=CC=C1CC1CCCCC1 XVJWBTBYXGKBDM-XJTUCQONSA-N 0.000 claims description 4
- RRVFTYQAYUKSPL-BBPSQCEISA-N 7-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]heptanoic acid Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCCCCC(O)=O)C=CC=1C(O)C1CCCCC1 RRVFTYQAYUKSPL-BBPSQCEISA-N 0.000 claims description 4
- DJFDILBLNQVKDN-HWYLODKRSA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]heptanoic acid Chemical compound O[C@@H]1C[C@@H](Cl)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(C(O)CC2)C2=C1 DJFDILBLNQVKDN-HWYLODKRSA-N 0.000 claims description 4
- JKTGWXLVQIWUCS-ISXLOPNHSA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2,2-dimethylpropyl)phenyl]cyclopentyl]heptanoic acid Chemical compound C1=CC(C(O)C(C)(C)C)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)[C@H](Cl)C[C@H]1O JKTGWXLVQIWUCS-ISXLOPNHSA-N 0.000 claims description 4
- OJIHIXUIWYZIKX-DODZYUBVSA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(hydroxymethyl)phenyl]cyclopentyl]heptanoic acid Chemical compound C1=CC(CO)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)[C@H](Cl)C[C@H]1O OJIHIXUIWYZIKX-DODZYUBVSA-N 0.000 claims description 4
- KZQQQASYBXZUMD-XBLXZFMMSA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(C(O)CC2)C2=C1 KZQQQASYBXZUMD-XBLXZFMMSA-N 0.000 claims description 4
- CWMCJSUKXSOXHF-UKZBHSNASA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-(hydroxymethyl)phenyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(CO)C=C1 CWMCJSUKXSOXHF-UKZBHSNASA-N 0.000 claims description 4
- UMGJHGOSNMTDSC-ROBUQXGOSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2)C2=C1 UMGJHGOSNMTDSC-ROBUQXGOSA-N 0.000 claims description 4
- HINYBJRUVOVRJC-XWNLZDBOSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C(C)C)C=C1 HINYBJRUVOVRJC-XWNLZDBOSA-N 0.000 claims description 4
- VHEHTZLUALNHCY-LPWJOBEDSA-N methyl 2-[3-[[(1r,2s,3r)-3-hydroxy-2-[3-[(s)-hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]methyl]phenoxy]acetate Chemical compound CCCC1([C@H](O)C=2C=C(C=CC=2)[C@@H]2[C@H](C(=O)C[C@H]2O)CC=2C=C(OCC(=O)OC)C=CC=2)CCC1 VHEHTZLUALNHCY-LPWJOBEDSA-N 0.000 claims description 4
- KVYBNNFCMIKGKE-GVLJIQMASA-N methyl 2-[3-[[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-[(s)-hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]methyl]phenoxy]acetate Chemical compound CCCC1([C@H](O)C=2C=C(C=CC=2)[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CC=2C=C(OCC(=O)OC)C=CC=2)CCC1 KVYBNNFCMIKGKE-GVLJIQMASA-N 0.000 claims description 4
- IAYIDTHYSFIKFX-CZTZKLFOSA-N methyl 7-[(1r,2s,3r)-2-(2,3-dihydro-1h-inden-5-yl)-3-hydroxy-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(CCC2)C2=C1 IAYIDTHYSFIKFX-CZTZKLFOSA-N 0.000 claims description 4
- PVXQLGVDQMQKID-ILZDJORESA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-(4-methylphenyl)-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(C)C=C1 PVXQLGVDQMQKID-ILZDJORESA-N 0.000 claims description 4
- VLGQBBOMXRICBE-IGKLCKLNSA-N methyl 7-[(1r,2s,3r)-5-fluoro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1C(F)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2)C2=C1 VLGQBBOMXRICBE-IGKLCKLNSA-N 0.000 claims description 4
- OQYUUCYOTLSMRU-GPQLQYNLSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-2-(2,3-dihydro-1h-inden-5-yl)-3-hydroxycyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(CCC2)C2=C1 OQYUUCYOTLSMRU-GPQLQYNLSA-N 0.000 claims description 4
- BEWXXKHHJWEQTD-ALMFXJGDSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2,2-dimethylpropyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C(C)(C)C)C=C1 BEWXXKHHJWEQTD-ALMFXJGDSA-N 0.000 claims description 4
- RCZYVQXXLLDIQH-ALMFXJGDSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C(C)C)C=C1 RCZYVQXXLLDIQH-ALMFXJGDSA-N 0.000 claims description 4
- RSIIKWFUMMKNRU-JRBPQWBISA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(hydroxymethyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(CO)C=C1 RSIIKWFUMMKNRU-JRBPQWBISA-N 0.000 claims description 4
- MJSOWZQIYLGSHR-VISJXMKQSA-N propan-2-yl (z)-7-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]hept-5-enoate Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C2CCCCC2)C=C1 MJSOWZQIYLGSHR-VISJXMKQSA-N 0.000 claims description 4
- 230000009467 reduction Effects 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
- NZCDHAXKMOJPJV-FUVOQIETSA-N (z)-7-[(1r,2s,3r)-2-(4-tert-butylphenyl)-3-hydroxy-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)C(=O)C[C@H]1O NZCDHAXKMOJPJV-FUVOQIETSA-N 0.000 claims description 3
- JFCUIZFHNHUFLO-BUYFTJNASA-N (z)-7-[(1r,2s,3r)-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C=1C=C([C@@H]2[C@H](C(=O)C[C@H]2O)C\C=C/CCCC(O)=O)C=CC=1C(O)C1CCCCC1 JFCUIZFHNHUFLO-BUYFTJNASA-N 0.000 claims description 3
- KARPJTLGVFQYJV-MMJXDPMESA-N (z)-7-[(1r,2s,3r)-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)-5-oxocyclopentyl]hept-5-enoic acid Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(O)=O)[C@H]1C1=CC=C(C(O)CC2)C2=C1 KARPJTLGVFQYJV-MMJXDPMESA-N 0.000 claims description 3
- XDQPTOUZKUXHDR-BKLNIUGLSA-N (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C1=CC(C(C)(CO)C)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)C(=O)C[C@H]1O XDQPTOUZKUXHDR-BKLNIUGLSA-N 0.000 claims description 3
- DDARURYBMDCOMC-NAENYJNXSA-N (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]hept-5-enoic acid Chemical compound C=1C=C([C@@H]2[C@H](C(=O)C[C@H]2O)C\C=C/CCCC(O)=O)C=CC=1C(O)C1(CCC)CCC1 DDARURYBMDCOMC-NAENYJNXSA-N 0.000 claims description 3
- XOBLUXQJETUBPH-BWJIKEEOSA-N (z)-7-[(1r,2s,3r)-5-fluoro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]hept-5-enoic acid Chemical compound O[C@@H]1CC(F)[C@H](C\C=C/CCCC(O)=O)[C@H]1C1=CC=C(C(O)CC2)C2=C1 XOBLUXQJETUBPH-BWJIKEEOSA-N 0.000 claims description 3
- FLIRCOOFHPQNCZ-KDNUDLGWSA-N (z)-7-[(1r,2s,3r,5r)-2-(4-tert-butylphenyl)-5-chloro-3-hydroxycyclopentyl]hept-5-enoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@H](Cl)C[C@H]1O FLIRCOOFHPQNCZ-KDNUDLGWSA-N 0.000 claims description 3
- GZOYDZXHUXHYPQ-ABEOENOBSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]hept-5-enoic acid Chemical compound O[C@@H]1C[C@@H](Cl)[C@H](C\C=C/CCCC(O)=O)[C@H]1C1=CC=C(C(O)CC2)C2=C1 GZOYDZXHUXHYPQ-ABEOENOBSA-N 0.000 claims description 3
- SEKQEASNUGOUOU-OGYBNYPZSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]cyclopentyl]hept-5-enoic acid Chemical compound O[C@@H]1C[C@@H](Cl)[C@H](C\C=C/CCCC(O)=O)[C@H]1C1=CC=C(C2(O)CCC2)C=C1 SEKQEASNUGOUOU-OGYBNYPZSA-N 0.000 claims description 3
- PCQSXENKHCECGM-NTXCDXHRSA-N 2-[4-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]but-2-ynoxy]acetic acid Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CC#CCOCC(O)=O)C=CC=1C(O)C1CCCCC1 PCQSXENKHCECGM-NTXCDXHRSA-N 0.000 claims description 3
- NQRVJJNFNBPWHN-FBBABVLZSA-N 7-[(1r,2s,3r)-2-(4-tert-butylphenyl)-3-hydroxy-5-oxocyclopentyl]heptanoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]1O NQRVJJNFNBPWHN-FBBABVLZSA-N 0.000 claims description 3
- NVDLIRUYYFEISR-QYJPUHJCSA-N 7-[(1r,2s,3r)-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C=1C=CC([C@@H]2[C@H](C(=O)C[C@H]2O)CCCCCCC(O)=O)=CC=1C(O)C1(CCC)CCC1 NVDLIRUYYFEISR-QYJPUHJCSA-N 0.000 claims description 3
- HNJALCPDBOOKTH-FBBABVLZSA-N 7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C1=CC(C(C)(CO)C)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]1O HNJALCPDBOOKTH-FBBABVLZSA-N 0.000 claims description 3
- LYIOFXTXACPEFA-FBBABVLZSA-N 7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(C2(O)CCC2)C=C1 LYIOFXTXACPEFA-FBBABVLZSA-N 0.000 claims description 3
- SAGFSXDZSAWPFP-QYJPUHJCSA-N 7-[(1r,2s,3r)-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C=1C=C([C@@H]2[C@H](C(=O)C[C@H]2O)CCCCCCC(O)=O)C=CC=1C(O)C1(CCC)CCC1 SAGFSXDZSAWPFP-QYJPUHJCSA-N 0.000 claims description 3
- VUABBZYGIWUQLU-QEUVDIPISA-N 7-[(1r,2s,3r,5r)-2-(4-tert-butylphenyl)-5-chloro-3-hydroxycyclopentyl]heptanoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)[C@H](Cl)C[C@H]1O VUABBZYGIWUQLU-QEUVDIPISA-N 0.000 claims description 3
- QJVZVQODDFMWMY-BBPSQCEISA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]heptanoic acid Chemical compound C=1C=CC([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCCCCC(O)=O)=CC=1C(O)C1(CCC)CCC1 QJVZVQODDFMWMY-BBPSQCEISA-N 0.000 claims description 3
- IQEMGHAXYOTQHG-QEUVDIPISA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]cyclopentyl]heptanoic acid Chemical compound C1=CC(C(C)(CO)C)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)[C@H](Cl)C[C@H]1O IQEMGHAXYOTQHG-QEUVDIPISA-N 0.000 claims description 3
- OPLWXPAXAJYKRO-ISXLOPNHSA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropyl)phenyl]cyclopentyl]heptanoic acid Chemical compound C1=CC(C(O)C(C)C)=CC=C1[C@@H]1[C@@H](CCCCCCC(O)=O)[C@H](Cl)C[C@H]1O OPLWXPAXAJYKRO-ISXLOPNHSA-N 0.000 claims description 3
- LHWZYGSXSIGZAW-QEUVDIPISA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]cyclopentyl]heptanoic acid Chemical compound O[C@@H]1C[C@@H](Cl)[C@H](CCCCCCC(O)=O)[C@H]1C1=CC=C(C2(O)CCC2)C=C1 LHWZYGSXSIGZAW-QEUVDIPISA-N 0.000 claims description 3
- CTEIQPNPVYCXAG-BBPSQCEISA-N 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]heptanoic acid Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCCCCC(O)=O)C=CC=1C(O)C1(CCC)CCC1 CTEIQPNPVYCXAG-BBPSQCEISA-N 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QODUKAICOKXMSX-ZLVOKCHPSA-N methyl (z)-7-[(1r,2s,3r)-2-(4-tert-butylphenyl)-3-hydroxy-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(C(C)(C)C)C=C1 QODUKAICOKXMSX-ZLVOKCHPSA-N 0.000 claims description 3
- HAOFKXXCXDQHEZ-TZTOVLLNSA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C=1C=CC([C@@H]2[C@H](C(=O)C[C@H]2O)C\C=C/CCCC(=O)OC)=CC=1C(O)C1(CCC)CCC1 HAOFKXXCXDQHEZ-TZTOVLLNSA-N 0.000 claims description 3
- UGPPNXNMAOIIJK-ZZJJKNIKSA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(C(C)(C)CO)C=C1 UGPPNXNMAOIIJK-ZZJJKNIKSA-N 0.000 claims description 3
- YSAJKYSBSUZZJF-TZTOVLLNSA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C=1C=C([C@@H]2[C@H](C(=O)C[C@H]2O)C\C=C/CCCC(=O)OC)C=CC=1C(O)C1(CCC)CCC1 YSAJKYSBSUZZJF-TZTOVLLNSA-N 0.000 claims description 3
- VRZLWCZDEDTXOI-KQPRDRKMSA-N methyl (z)-7-[(1r,2s,3r)-5-fluoro-3-hydroxy-2-(1-hydroxy-2,3-dihydro-1h-inden-5-yl)cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1C(F)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2)C2=C1 VRZLWCZDEDTXOI-KQPRDRKMSA-N 0.000 claims description 3
- JVJSZVIWJDEHTQ-CQJJLBMOSA-N methyl (z)-7-[(1r,2s,3r,5r)-2-(4-tert-butylphenyl)-5-chloro-3-hydroxycyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(C)(C)C)C=C1 JVJSZVIWJDEHTQ-CQJJLBMOSA-N 0.000 claims description 3
- ZDYORXDJNMUWCL-BCMUVELESA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C2(O)CCC2)C=C1 ZDYORXDJNMUWCL-BCMUVELESA-N 0.000 claims description 3
- ZZYCFRJEFHHTSN-IFXLXSALSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(hydroxymethyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(CO)C=C1 ZZYCFRJEFHHTSN-IFXLXSALSA-N 0.000 claims description 3
- ZBRPQKZIVPCWJY-BBPSQCEISA-N methyl 2-[4-[(1r,2s,3r,5r)-5-chloro-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxycyclopentyl]butoxy]acetate Chemical compound COC(=O)COCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C2CCCCC2)C=C1 ZBRPQKZIVPCWJY-BBPSQCEISA-N 0.000 claims description 3
- IRVWZTVUXFVHPI-CZTZKLFOSA-N methyl 7-[(1r,2s,3r)-2-(4-tert-butylphenyl)-3-hydroxy-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(C(C)(C)C)C=C1 IRVWZTVUXFVHPI-CZTZKLFOSA-N 0.000 claims description 3
- PWDCKKKZECYAPI-YBRKRNMPSA-N methyl 7-[(1r,2s,3r)-2-[4-[cyclohexyl(hydroxy)methyl]phenyl]-3-hydroxy-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(C(O)C2CCCCC2)C=C1 PWDCKKKZECYAPI-YBRKRNMPSA-N 0.000 claims description 3
- HGVQTLDTGTVRFU-YBRKRNMPSA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]heptanoate Chemical compound C=1C=CC([C@@H]2[C@H](C(=O)C[C@H]2O)CCCCCCC(=O)OC)=CC=1C(O)C1(CCC)CCC1 HGVQTLDTGTVRFU-YBRKRNMPSA-N 0.000 claims description 3
- ZZGDTQRJWZRPGV-CZTZKLFOSA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(C(C)(C)CO)C=C1 ZZGDTQRJWZRPGV-CZTZKLFOSA-N 0.000 claims description 3
- UQNJSTMIKPRSSG-CZTZKLFOSA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]-5-oxocyclopentyl]heptanoate Chemical compound O[C@@H]1CC(=O)[C@H](CCCCCCC(=O)OC)[C@H]1C1=CC=C(C2(O)CCC2)C=C1 UQNJSTMIKPRSSG-CZTZKLFOSA-N 0.000 claims description 3
- UKCUBAMARYVDPD-YBRKRNMPSA-N methyl 7-[(1r,2s,3r)-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]heptanoate Chemical compound C=1C=C([C@@H]2[C@H](C(=O)C[C@H]2O)CCCCCCC(=O)OC)C=CC=1C(O)C1(CCC)CCC1 UKCUBAMARYVDPD-YBRKRNMPSA-N 0.000 claims description 3
- DKFBAFOHUJCIPJ-GPQLQYNLSA-N methyl 7-[(1r,2s,3r,5r)-2-(4-tert-butylphenyl)-5-chloro-3-hydroxycyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(C)(C)C)C=C1 DKFBAFOHUJCIPJ-GPQLQYNLSA-N 0.000 claims description 3
- PAZBGXZBOAQSBR-IQLLUQGCSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]heptanoate Chemical compound C=1C=CC([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCCCCC(=O)OC)=CC=1C(O)C1(CCC)CCC1 PAZBGXZBOAQSBR-IQLLUQGCSA-N 0.000 claims description 3
- HAADWBSFVMKLLN-GPQLQYNLSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(C)(C)CO)C=C1 HAADWBSFVMKLLN-GPQLQYNLSA-N 0.000 claims description 3
- VTASWXKZFIHLTQ-GPQLQYNLSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxycyclobutyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C2(O)CCC2)C=C1 VTASWXKZFIHLTQ-GPQLQYNLSA-N 0.000 claims description 3
- JIGKFIDMOFKHFK-IQLLUQGCSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]heptanoate Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCCCCC(=O)OC)C=CC=1C(O)C1(CCC)CCC1 JIGKFIDMOFKHFK-IQLLUQGCSA-N 0.000 claims description 3
- SAOVVWSFMVXSDI-ULHQQPNYSA-N propan-2-yl (z)-7-[(1r,2s,3r,5r)-2-(4-tert-butylphenyl)-5-chloro-3-hydroxycyclopentyl]hept-5-enoate Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(C)(C)C)C=C1 SAOVVWSFMVXSDI-ULHQQPNYSA-N 0.000 claims description 3
- NJOXKYGJCYOIRG-PBNZNZKVSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]hept-5-enoic acid Chemical compound C=1C=CC([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(O)=O)=CC=1C(O)C1(CCC)CCC1 NJOXKYGJCYOIRG-PBNZNZKVSA-N 0.000 claims description 2
- QKCBLYQALCVPFG-QUUVRLJHSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]cyclopentyl]hept-5-enoic acid Chemical compound C1=CC(C(C)(CO)C)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@H](Cl)C[C@H]1O QKCBLYQALCVPFG-QUUVRLJHSA-N 0.000 claims description 2
- ILHOKXFOVAGWCG-PBNZNZKVSA-N (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]hept-5-enoic acid Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(O)=O)C=CC=1C(O)C1(CCC)CCC1 ILHOKXFOVAGWCG-PBNZNZKVSA-N 0.000 claims description 2
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims description 2
- MLIBRBNKZWETMV-JVNMPXIPSA-N propan-2-yl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]cyclopentyl]heptanoate Chemical compound CC(C)OC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(C)(C)CO)C=C1 MLIBRBNKZWETMV-JVNMPXIPSA-N 0.000 claims description 2
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- UFIBIOWDGWGAKB-BZGQIJLNSA-N methyl (z)-7-[(1r,2s,3r)-3-hydroxy-2-[1-[(4-methoxyphenyl)methoxy]-2,3-dihydro-1h-inden-5-yl]-5-oxocyclopentyl]hept-5-enoate Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)OC)[C@H]1C1=CC=C(C(CC2)OCC=3C=CC(OC)=CC=3)C2=C1 UFIBIOWDGWGAKB-BZGQIJLNSA-N 0.000 description 1
- JIFZFFHFAIHMDF-JTJRSPNGSA-N methyl (z)-7-[(1r,2s,3r,5r)-2-[4-(1-acetyloxyhexyl)phenyl]-3-[tert-butyl(dimethyl)silyl]oxy-5-chlorocyclopentyl]hept-5-enoate Chemical compound C1=CC(C(OC(C)=O)CCCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](Cl)C[C@H]1O[Si](C)(C)C(C)(C)C JIFZFFHFAIHMDF-JTJRSPNGSA-N 0.000 description 1
- MDKYMWDYNIPYHQ-ZAKVNNCQSA-N methyl (z)-7-[(1r,2s,3r,5r)-2-[4-(1-acetyloxyhexyl)phenyl]-5-chloro-3-hydroxycyclopentyl]hept-5-enoate Chemical compound C1=CC(C(OC(C)=O)CCCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](Cl)C[C@H]1O MDKYMWDYNIPYHQ-ZAKVNNCQSA-N 0.000 description 1
- GRAMJSJDNBNXSP-IQLDPICRSA-N methyl (z)-7-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[1-[tert-butyl(dimethyl)silyl]oxyhexyl]phenyl]-5-fluorocyclopentyl]hept-5-enoate Chemical compound C1=CC(C(O[Si](C)(C)C(C)(C)C)CCCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](F)C[C@H]1O[Si](C)(C)C(C)(C)C GRAMJSJDNBNXSP-IQLDPICRSA-N 0.000 description 1
- GALPRVSRJHYDGG-IQLDPICRSA-N methyl (z)-7-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[1-[tert-butyl(dimethyl)silyl]oxyhexyl]phenyl]-5-hydroxycyclopentyl]hept-5-enoate Chemical compound C1=CC(C(O[Si](C)(C)C(C)(C)C)CCCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](O)C[C@H]1O[Si](C)(C)C(C)(C)C GALPRVSRJHYDGG-IQLDPICRSA-N 0.000 description 1
- OUVSGWDILIYKLQ-OQARILPGSA-N methyl (z)-7-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[[tert-butyl(dimethyl)silyl]oxy-cyclohexylmethyl]phenyl]-5-chlorocyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(O[Si](C)(C)C(C)(C)C)C2CCCCC2)C=C1 OUVSGWDILIYKLQ-OQARILPGSA-N 0.000 description 1
- AEAZJTPMURMQIV-CAFLSVRGSA-N methyl (z)-7-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-5-chloro-2-[1-[(4-methoxyphenyl)methoxy]-2,3-dihydro-1h-inden-5-yl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(CC2)OCC=3C=CC(OC)=CC=3)C2=C1 AEAZJTPMURMQIV-CAFLSVRGSA-N 0.000 description 1
- MWKKDIUCMATTJZ-XKGIYNKYSA-N methyl (z)-7-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-5-chloro-2-[4-(1-hydroxy-2-methylpropyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(O)C(C)C)C=C1 MWKKDIUCMATTJZ-XKGIYNKYSA-N 0.000 description 1
- PCDPPZGSJIJFBJ-VZPDAMIGSA-N methyl (z)-7-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-5-chloro-2-[4-(hydroxymethyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(CO)C=C1 PCDPPZGSJIJFBJ-VZPDAMIGSA-N 0.000 description 1
- CNXXZAQYLKOVOZ-VKALJCJESA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-2-[4-(2-cyclohexyl-1-hydroxyethyl)phenyl]-3-hydroxycyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2CCCCC2)C=C1 CNXXZAQYLKOVOZ-VKALJCJESA-N 0.000 description 1
- OQNRFIPAIFYNQV-OZBWURBHSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-2-[4-(3-cyclohexyl-1-hydroxypropyl)phenyl]-3-hydroxycyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CCC2CCCCC2)C=C1 OQNRFIPAIFYNQV-OZBWURBHSA-N 0.000 description 1
- CFTWLLPZJGZGRO-ZXWKARSNSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[1-[(4-methoxyphenyl)methoxy]-2,3-dihydro-1h-inden-5-yl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(CC2)OCC=3C=CC(OC)=CC=3)C2=C1 CFTWLLPZJGZGRO-ZXWKARSNSA-N 0.000 description 1
- RUOPLBVXTRYTJQ-SRKXXCEFSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-(1-hydroxyhexyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound CCCCCC(O)C1=CC=CC([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(=O)OC)=C1 RUOPLBVXTRYTJQ-SRKXXCEFSA-N 0.000 description 1
- RKTMUCONKYIHOW-MXFHKUQTSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-(1-hydroxypentyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound CCCCC(O)C1=CC=CC([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(=O)OC)=C1 RKTMUCONKYIHOW-MXFHKUQTSA-N 0.000 description 1
- AMSYNEAWRKZFHZ-UPBVYHFLSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[3-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]hept-5-enoate Chemical compound C=1C=CC([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(=O)OC)=CC=1C(O)C1(CCC)CCC1 AMSYNEAWRKZFHZ-UPBVYHFLSA-N 0.000 description 1
- NYJDESYPAZHHAC-FZXGYTRFSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2,2-dimethylpropyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C(C)(C)C)C=C1 NYJDESYPAZHHAC-FZXGYTRFSA-N 0.000 description 1
- FTZLQTVABVUGQA-RUJXCBFBSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(C)(C)CO)C=C1 FTZLQTVABVUGQA-RUJXCBFBSA-N 0.000 description 1
- LSZRIGGDBCTFNU-VKALJCJESA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-phenylethyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC=2C=CC=CC=2)C=C1 LSZRIGGDBCTFNU-VKALJCJESA-N 0.000 description 1
- XNUCZXFBMVUNFX-OZBWURBHSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-3-phenylpropyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CCC=2C=CC=CC=2)C=C1 XNUCZXFBMVUNFX-OZBWURBHSA-N 0.000 description 1
- RHWUVRPWPRGPCY-ZJUKYYLBSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxybutyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound C1=CC(C(O)CCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](Cl)C[C@H]1O RHWUVRPWPRGPCY-ZJUKYYLBSA-N 0.000 description 1
- IGSBGIVLYZHQNY-BTROZPGGSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxyheptyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound C1=CC(C(O)CCCCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](Cl)C[C@H]1O IGSBGIVLYZHQNY-BTROZPGGSA-N 0.000 description 1
- HLOSWLMISVDLKU-MXFHKUQTSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxypentyl)phenyl]cyclopentyl]hept-5-enoate Chemical compound C1=CC(C(O)CCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@H](Cl)C[C@H]1O HLOSWLMISVDLKU-MXFHKUQTSA-N 0.000 description 1
- AHHCOBVSDPNNAY-QEMOYHHTSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-[(4-methoxyphenyl)methoxymethyl]phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C(C=C1)=CC=C1COCC1=CC=C(OC)C=C1 AHHCOBVSDPNNAY-QEMOYHHTSA-N 0.000 description 1
- FNPLOLLSWQKVIM-JMWRMVSPSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-[hydroxy(phenyl)methyl]phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)C=2C=CC=CC=2)C=C1 FNPLOLLSWQKVIM-JMWRMVSPSA-N 0.000 description 1
- ZVCNJHXASNRNKY-UPBVYHFLSA-N methyl (z)-7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-[hydroxy-(1-propylcyclobutyl)methyl]phenyl]cyclopentyl]hept-5-enoate Chemical compound C=1C=C([C@@H]2[C@H]([C@H](Cl)C[C@H]2O)C\C=C/CCCC(=O)OC)C=CC=1C(O)C1(CCC)CCC1 ZVCNJHXASNRNKY-UPBVYHFLSA-N 0.000 description 1
- OZJADAACJSBZAI-TZYDCJQVSA-N methyl (z)-7-[(1r,2s,3r,5s)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[1-[tert-butyl(dimethyl)silyl]oxyhexyl]phenyl]-5-chlorocyclopentyl]hept-5-enoate Chemical compound C1=CC(C(O[Si](C)(C)C(C)(C)C)CCCCC)=CC=C1[C@@H]1[C@@H](C\C=C/CCCC(=O)OC)[C@@H](Cl)C[C@H]1O[Si](C)(C)C(C)(C)C OZJADAACJSBZAI-TZYDCJQVSA-N 0.000 description 1
- UVFYHJIASOCMAX-FIDDLHAVSA-N methyl (z)-7-[(1r,2s,3r,5s)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[[tert-butyl(dimethyl)silyl]oxy-cyclohexylmethyl]phenyl]-5-hydroxycyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(O[Si](C)(C)C(C)(C)C)C2CCCCC2)C=C1 UVFYHJIASOCMAX-FIDDLHAVSA-N 0.000 description 1
- YXGXQMJEQLCVCJ-KKKSCNFHSA-N methyl (z)-7-[(1r,2s,3r,5s)-3-[tert-butyl(dimethyl)silyl]oxy-5-hydroxy-2-[1-[(4-methoxyphenyl)methoxy]-2,3-dihydro-1h-inden-5-yl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(CC2)OCC=3C=CC(OC)=CC=3)C2=C1 YXGXQMJEQLCVCJ-KKKSCNFHSA-N 0.000 description 1
- RHIOPTMWFJERTK-YRSCLOHMSA-N methyl (z)-7-[(1r,2s,3r,5s)-3-[tert-butyl(dimethyl)silyl]oxy-5-hydroxy-2-[4-[(4-methoxyphenyl)methoxymethyl]phenyl]cyclopentyl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C(C=C1)=CC=C1COCC1=CC=C(OC)C=C1 RHIOPTMWFJERTK-YRSCLOHMSA-N 0.000 description 1
- DYTLLXFKOGFFFL-DSSIUBFHSA-N methyl (z)-7-[(4r,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-[1-[(4-methoxyphenyl)methoxy]-2,3-dihydro-1h-inden-5-yl]cyclopenten-1-yl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/CC1=CC[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C1=CC=C(C(CC2)OCC=3C=CC(OC)=CC=3)C2=C1 DYTLLXFKOGFFFL-DSSIUBFHSA-N 0.000 description 1
- TXJGBHZYTUCOCA-UHFFFAOYSA-N methyl 1-propylcyclobutane-1-carboxylate Chemical compound CCCC1(C(=O)OC)CCC1 TXJGBHZYTUCOCA-UHFFFAOYSA-N 0.000 description 1
- PXGGYWKCASWNEC-UHFFFAOYSA-N methyl 2-[3-(hydroxymethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(CO)=C1 PXGGYWKCASWNEC-UHFFFAOYSA-N 0.000 description 1
- BNYUAUDBQADFNN-UHFFFAOYSA-N methyl 2-[3-(iodomethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(CI)=C1 BNYUAUDBQADFNN-UHFFFAOYSA-N 0.000 description 1
- LRURUFDVXJMCNI-BJJNPZJTSA-N methyl 2-[3-[[(1r,2s,3r)-3-[tert-butyl(dimethyl)silyl]oxy-2-[3-[[tert-butyl(dimethyl)silyl]oxy-(1-propylcyclobutyl)methyl]phenyl]-5-oxocyclopentyl]methyl]phenoxy]acetate Chemical compound C=1C=CC([C@@H]2[C@H](C(=O)C[C@H]2O[Si](C)(C)C(C)(C)C)CC=2C=C(OCC(=O)OC)C=CC=2)=CC=1C(O[Si](C)(C)C(C)(C)C)C1(CCC)CCC1 LRURUFDVXJMCNI-BJJNPZJTSA-N 0.000 description 1
- DRLZTIAELKYRDB-XDPZQGNMSA-N methyl 2-[4-[(1r,2s,3r,5r)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[[tert-butyl(dimethyl)silyl]oxy-cyclohexylmethyl]phenyl]-5-chlorocyclopentyl]but-2-ynoxy]acetate Chemical compound COC(=O)COCC#CC[C@H]1[C@H](Cl)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(O[Si](C)(C)C(C)(C)C)C2CCCCC2)C=C1 DRLZTIAELKYRDB-XDPZQGNMSA-N 0.000 description 1
- GBWBCBXUORYSGK-GRVANCTKSA-N methyl 2-[4-[(1r,2s,3r,5s)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[[tert-butyl(dimethyl)silyl]oxy-cyclohexylmethyl]phenyl]-5-hydroxycyclopentyl]but-2-ynoxy]acetate Chemical compound COC(=O)COCC#CC[C@H]1[C@@H](O)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1=CC=C(C(O[Si](C)(C)C(C)(C)C)C2CCCCC2)C=C1 GBWBCBXUORYSGK-GRVANCTKSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- ROOBRIVWRSZZNR-UHFFFAOYSA-N methyl 3-[3-(hydroxymethyl)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CO)=C1 ROOBRIVWRSZZNR-UHFFFAOYSA-N 0.000 description 1
- IZLNNMOKRWMENT-UHFFFAOYSA-N methyl 3-[3-(iodomethyl)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CI)=C1 IZLNNMOKRWMENT-UHFFFAOYSA-N 0.000 description 1
- SDILNRZQFQQLIR-JZCQAGPTSA-N methyl 3-[3-[[(1r,2s,3r)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[1-[tert-butyl(dimethyl)silyl]oxyhexyl]phenyl]-5-oxocyclopentyl]methyl]phenyl]propanoate Chemical compound C1=CC(C(O[Si](C)(C)C(C)(C)C)CCCCC)=CC=C1[C@@H]1[C@@H](CC=2C=C(CCC(=O)OC)C=CC=2)C(=O)C[C@H]1O[Si](C)(C)C(C)(C)C SDILNRZQFQQLIR-JZCQAGPTSA-N 0.000 description 1
- VTSBASYAYRVCFE-BTZUXBTFSA-N methyl 3-[3-[[(1r,2s,3r,5s)-3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[1-[tert-butyl(dimethyl)silyl]oxyhexyl]phenyl]-5-hydroxycyclopentyl]methyl]phenyl]propanoate Chemical compound C1=CC(C(O[Si](C)(C)C(C)(C)C)CCCCC)=CC=C1[C@@H]1[C@@H](CC=2C=C(CCC(=O)OC)C=CC=2)[C@@H](O)C[C@H]1O[Si](C)(C)C(C)(C)C VTSBASYAYRVCFE-BTZUXBTFSA-N 0.000 description 1
- QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-UHFFFAOYSA-N 0.000 description 1
- FXXRTAJANAWNEQ-ORMYUUTLSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-2-[4-(2-cyclohexyl-1-hydroxyethyl)phenyl]-3-hydroxycyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC2CCCCC2)C=C1 FXXRTAJANAWNEQ-ORMYUUTLSA-N 0.000 description 1
- MGURSTWEYHFDOC-PCQPPPAVSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-2-[4-(3-cyclohexyl-1-hydroxypropyl)phenyl]-3-hydroxycyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CCC2CCCCC2)C=C1 MGURSTWEYHFDOC-PCQPPPAVSA-N 0.000 description 1
- TVWSVUITCQZHLR-ORMYUUTLSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-2-phenylethyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CC=2C=CC=CC=2)C=C1 TVWSVUITCQZHLR-ORMYUUTLSA-N 0.000 description 1
- SWJYMHQRZZOELG-PCQPPPAVSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-3-phenylpropyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CCC=2C=CC=CC=2)C=C1 SWJYMHQRZZOELG-PCQPPPAVSA-N 0.000 description 1
- DVQPOEKOSVBFPK-JNGBSPTRSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxy-5,5-dimethylhexyl)phenyl]cyclopentyl]heptanoate Chemical compound COC(=O)CCCCCC[C@H]1[C@H](Cl)C[C@@H](O)[C@@H]1C1=CC=C(C(O)CCCC(C)(C)C)C=C1 DVQPOEKOSVBFPK-JNGBSPTRSA-N 0.000 description 1
- BHTIRFDIBMYOKU-YVHFYUGVSA-N methyl 7-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[4-(1-hydroxyhexyl)phenyl]cyclopentyl]heptanoate Chemical compound C1=CC(C(O)CCCCC)=CC=C1[C@@H]1[C@@H](CCCCCCC(=O)OC)[C@H](Cl)C[C@H]1O BHTIRFDIBMYOKU-YVHFYUGVSA-N 0.000 description 1
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- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 1
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- 201000000484 premenstrual tension Diseases 0.000 description 1
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- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Description
降眼圧薬は、外科的およびレーザーによる線維柱帯切除術後の高眼圧発症、緑内障のようなあらゆる高眼圧状態の治療、ならびに手術の補助療法として、有用である。
本明細書で以下を含む化合物を開示する;
破線は、共有結合の有無を表し、;
Yは、カルボン酸、スルホン酸、またはホスホン酸; または0から12の炭素原子を含むそのアミドまたはエステル; またはYは、ヒドロキシメチル、またはテトラゾリル官能基であり;
Aは、-(CH2)6-、シス-CH2CH=CH-(CH2)3-、または-CH2C≡C-(CH2)3-であり、その1または2の炭素原子はSまたはOで置換されていてもよく; またはAは、-(CH2)m-Ar-(CH2)o-であり、Arは、置換フェニルまたは非置換フェニルまたは単環ヘテロアリールであり、mとoの和は1から4であり、およびそのCH2の1つは、SまたはOで置換していてもよい;
Xは、C=O、CHF、CF2、CHCl、またはCHOHであり、; XがCHOHであるとき、OHはβ-立体配置にある;
Rは、1から12の炭素原子をふくむ、ヒドロカルビルまたはヒドロキシヒドロカルビル基であり、;
Dは、独立して1から6の非-水素原子の基であり、;および
nは、0から4の整数である。
これらの化合物のいくつかの炭素原子はキラル中心である。いずれも本発明の範囲を制限するものではなく、または決して説に縛らることを意図しないが、以下に示される立体化学を有する多くの化合物および医薬的に活性な塩またはそのプロドラッグは、特に有用と考えられている。
テトラゾリル-R3; R3は非依存的にH、C1-C6アルキル、フェニル、またはビフェニルである、からなる群から選ばれる。
Aは、O、0から3のCH2部分、およびArを含み、例えば、-O-Ar-、Ar-CH2-O-、-O-Ar-(CH2)2-、-O-CH2-Ar-、-O-CH2-Ar-(CH2)2、および同類のものであり、; または、
Aは、S、0から3のCH2部分、およびArを含み、例えば、-S-Ar-、Ar-CH2-S-、-S-Ar-(CH2)2-、-S-CH2-Ar-、-S-CH2-Ar-(CH2)2、および同類のものである。
a)メチル、エチル、プロピル、n-ブチル、n-ペンチル、n-ヘキシル、および同類のものの、ような直鎖アルキル;
b)イソプロピル、分岐ブチル異性体(すなわち、sec-ブチル、tert-ブチル等)、分岐ペンチル異性体(すなわち、イソペンチル等)、分岐ヘキシル異性体、および高級分岐アルキルフラグメント、のような分岐アルキル;
c)シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチルなど、のようなシクロアルキル;および
d)直鎖であろう分岐であろうと、該分子の残りの部分の末端、内部、または環の炭素原子を含む可能な位置に結合する、環状および非環状部分の両方で構成されるアルキルフラグメント
を含む。アルキルの類似においては、直鎖、分岐、シクロアルキル、およびヒドロカルビルの組み合わせがある。
(Z)-7-{(1R,2S,3R)-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-5-オキソ-シクロペンチル}-ヘプト-5-エン酸メチルエステル(5-4);
(Z)-7-{(1R,2S,3R)-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-5-オキソ-シクロペンチル}-ヘプト-5-エン酸(5-5);
7-{(1R,2S,3R)-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-5-オキソ-シクロペンチル}-ヘプタン酸メチルエステル(5-7);
7-{(1R,2S,3R)-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-5-オキソ-シクロペンチル}-ヘプタン酸(5-8);
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸メチルエステル;
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸;
7-((1R,2S,3R)-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプタン酸メチルエステル;
7-((1R,2S,3R)-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプタン酸;
(Z)-7-[(1R,2S,3R)-2-(4-tert-ブチル-フェニル)-3-ヒドロキシ-5-オキソ-シクロペンチル]-ヘプト-5-エン酸メチルエステル;
(Z)-7-[(1R,2S,3R)-2-(4-tert-ブチル-フェニル)-3-ヒドロキシ-5-オキソ-シクロペンチル]-ヘプト-5-エン酸;
7-[(1R,2S,3R)-2-(4-tert-ブチル-フェニル)-3-ヒドロキシ-5-オキソ-シクロペンチル]-ヘプタン酸メチルエステル;
7-[(1R,2S,3R)-2-(4-tert-ブチル-フェニル)-3-ヒドロキシ-5-オキソ-シクロペンチル]-ヘプタン酸;
(Z)-7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプト-5-エン酸;
7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプタン酸;
(Z)-7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプト-5-エン酸メチルエステル(e1-2);
7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R)-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-5-オキソ-シクロペンチル}-ヘプタン酸;
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸メチルエステル;
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸(e2-1);
7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプタン酸メチルエステル;
7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプタン酸;
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸(2-ヒドロキシ-エチル)-アミド(e2-2, R= 2-ヒドロキシエチル);
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸エチルアミド(e2-2, R=エチル);
(Z)-7-((1R,2S,3R)-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチル)-ヘプト-5-エン酸エチルアミド(e2-2, R=H);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸メチルエステル(6-3);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸(6-4);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸イソプロピルエステル(6-5);
7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプタン酸メチルエステル(6-6);
7-[(1R,2S,3R,5R)-5-クロロ-2-(4-シクロヘキシルメチル-フェニル)-3-ヒドロキシ-シクロペンチル]-ヘプタン酸メチルエステル(6-8);
7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプタン酸(6-7);
7-[(1R,2S,3R,5R)-5-クロロ-2-(4-シクロヘキシルメチル-フェニル)-3-ヒドロキシ-シクロペンチル]-ヘプタン酸(6-9);
(Z)-7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプト-5-エン酸メチルエステル;
(Z)-7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプト-5-エン酸;
7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプタン酸メチルエステル;
7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプタン酸;
(Z)-7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプト-5-エン酸メチルエステル;
(Z)-7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプト-5-エン酸;
7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプタン酸メチルエステル;
7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{4-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチル)-ヘプタン酸;
(Z)-7-[(1R,2S,3R,5R)-2-(4-tert-ブチル-フェニル)-5-クロロ-3-ヒドロキシ-シクロペンチル]-ヘプト-5-エン酸メチルエステル;
(Z)-7-[(1R,2S,3R,5R)-2-(4-tert-ブチル-フェニル)-5-クロロ-3-ヒドロキシ-シクロペンチル]-ヘプト-5-エン酸;
7-[(1R,2S,3R,5R)-2-(4-tert-ブチル-フェニル)-5-クロロ-3-ヒドロキシ-シクロペンチル]-ヘプタン酸メチルエステル;
7-[(1R,2S,3R,5R)-2-(4-tert-ブチル-フェニル)-5-クロロ-3-ヒドロキシ-シクロペンチル]-ヘプタン酸;
(Z)-7-[(1R,2S,3R,5R)-2-(4-tert-ブチル-フェニル)-5-クロロ-3-ヒドロキシ-シクロペンチル]-ヘプト-5-エン酸イソプロピルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-シクロブチル)-フェニル]-シクロペンチル}-ヘプタン酸;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-シクロペンチル}-ヘプタン酸;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-エチル)-フェニル]-シクロペンチル}-ヘプタン酸イソプロピルエステル;
(Z)-7-[(1R,2S,3R)-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-5-オキソ-シクロペンチル]-ヘプト-5-エン酸メチルエステル(7-5);
(Z)-7-[(1R,2S,3R)-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-5-オキソ-シクロペンチル]-ヘプト-5-エン酸(7-6);
7-[(1R,2S,3R)-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-5-オキソ-シクロペンチル]-ヘプタン酸メチルエステル(7-7);
7-((1R,2S,3R)-3-ヒドロキシ-5-オキソ-2-p-トリル-シクロペンチル)-ヘプタン酸メチルエステル(7-9);
7-[(1R,2S,3R)-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-5-オキソ-シクロペンチル]-ヘプタン酸(7-8);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-シクロペンチル]-ヘプト-5-エン酸メチルエステル(8-4);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-シクロペンチル]-ヘプト-5-エン酸(8-5);
7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-シクロペンチル]-ヘプタン酸メチルエステル(8-6);
7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(4-ヒドロキシメチル-フェニル)-シクロペンチル]-ヘプタン酸(8-7);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-メチル-プロピル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル(9-5);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2,2-ジメチル-プロピル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル(9-6);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-メチル-プロピル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(9-7);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2,2-ジメチル-プロピル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(9-8);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-メチル-プロピル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル(9-9);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2,2-ジメチル-プロピル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル(9-10);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-メチル-プロピル)-フェニル]-シクロペンチル}-ヘプタン酸(9-11);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2,2-ジメチル-プロピル)-フェニル]-シクロペンチル}-ヘプタン酸(9-12);
(4-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ブタ-2-イニルオキシ)-酢酸メチルエステル(10-6);
(4-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ブタ-2-イニルオキシ)-酢酸(10-7);
((Z)-4-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ブタ-2-エニルオキシ)-酢酸メチルエステル(11-1);
((Z)-4-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ブタ-2-エニルオキシ)-酢酸(11-2);
(4-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ブトキシ)-酢酸メチルエステル(11-3);
(4-{(1R,2S,3R,5R)-5-クロロ-2-[4-(シクロヘキシル-ヒドロキシ-メチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ブトキシ)-酢酸(11-4);
[3-((1R,2S,3R)-3-ヒドロキシ-2-{3-[(S)-ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチルメチル)-フェノキシ]-酢酸メチルエステル(13-3);
[3-((1R,2S,3R)-3-ヒドロキシ-2-{3-[(S)-ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-5-オキソ-シクロペンチルメチル)-フェノキシ]-酢酸(13-4);
[3-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[(S)-ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチルメチル)-フェノキシ]-酢酸メチルエステル(14-3);
[3-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[(S)-ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチルメチル)-フェノキシ]-酢酸(14-4);
(Z)-7-[(1R,2S,3R)-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-5-オキソ-シクロペンチル]-ヘプト-5-エン酸メチルエステル(15-6);
(Z)-7-[(1R,2S,3R)-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-5-オキソ-シクロペンチル]-ヘプト-5-エン酸(15-7);
(Z)-7-[(1R,2S,3R)-3-ヒドロキシ-5-オキソ-2-(1-オキソ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸メチルエステル(15-8);
(Z)-7-[(1R,2S,3R)-3-ヒドロキシ-5-オキソ-2-(1-オキソ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸(15-9);
7-[(1R,2S,3R)-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-5-オキソ-シクロペンチル]-ヘプタン酸メチルエステル(15-10);
7-((1R,2S,3R)-3-ヒドロキシ-2-インダン-5-イル-5-オキソ-シクロペンチル)-ヘプタン酸メチルエステル(15-12);
7-[(1R,2S,3R)-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-5-オキソ-シクロペンチル]-ヘプタン酸(15-11);
7-((1R,2S,3R)-3-ヒドロキシ-2-インダン-5-イル-5-オキソ-シクロペンチル)-ヘプタン酸(15-13);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸メチルエステル(16-4);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸(16-5);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸イソプロピルエステル(16-6);
7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプタン酸メチルエステル(16-7);
7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-インダン-5-イル-シクロペンチル)-ヘプタン酸メチルエステル(16-9);
7-[(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプタン酸(16-8);
7-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-インダン-5-イル-シクロペンチル)-ヘプタン酸(16-10);
7-[(1R,2S,3R)-5-フルオロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプタン酸メチルエステル(17-3);
7-[(1R,2S,3R)-5-フルオロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプタン酸(17-4);
(Z)-7-[(1R,2S,3R)-5-フルオロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸メチルエステル(17-5);
(Z)-7-[(1R,2S,3R)-5-フルオロ-3-ヒドロキシ-2-(1-ヒドロキシ-インダン-5-イル)-シクロペンチル]-ヘプト-5-エン酸(17-6);
3-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-安息香酸(18-13);
3-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-安息香酸エチルエステル;
5-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-チオフェン-2-カルボン酸(102);
5-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-チオフェン-2-カルボン酸メチルエステル;
5-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-チオフェン-2-カルボン酸イソプロピルエステル;
3-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチルメチル}-フェニル)-プロピオン酸(20-5);
3-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチルメチル}-フェニル)-プロピオン酸メチルエステル;
3-[3-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチルメチル)-フェニル]-プロピオン酸(104);
3-[3-((1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-{3-[ヒドロキシ-(1-プロピル-シクロブチル)-メチル]-フェニル}-シクロペンチルメチル)-フェニル]-プロピオン酸メチルエステル;
2-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-チアゾール-5-カルボン酸(21-7);
2-(3-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-プロピル)-チアゾール-5-カルボン酸エチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-フルオロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(22-3);
(Z)-7-{(1R,2S,3R,5R)-5-フルオロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5S)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(23-5);
(Z)-7-{(1R,2S,3R,5S)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル(110);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(24-4);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸イソプロピルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプタン酸(114);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(3-シクロヘキシル-1-ヒドロキシ-プロピル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸(115);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(3-シクロヘキシル-1-ヒドロキシ-プロピル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(3-シクロヘキシル-1-ヒドロキシ-プロピル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプタン酸(116);
7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(3-シクロヘキシル-1-ヒドロキシ-プロピル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプタン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(2-シクロヘキシル-1-ヒドロキシ-エチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸(117);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(2-シクロヘキシル-1-ヒドロキシ-エチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(2-シクロヘキシル-1-ヒドロキシ-エチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプタン酸(118);
7-{(1R,2S,3R,5R)-5-クロロ-2-[4-(2-シクロヘキシル-1-ヒドロキシ-エチル)-フェニル]-3-ヒドロキシ-シクロペンチル}-ヘプタン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-5,5-ジメチル-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-5,5-ジメチル-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(119);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-5,5-ジメチル-ヘキシル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-5,5-ジメチル-ヘキシル)-フェニル]-シクロペンチル}-ヘプタン酸(120);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-フェニル-エチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-フェニル-エチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸イソプロピルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-フェニル-エチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(121);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-フェニル-エチル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-2-フェニル-エチル)-フェニル]-シクロペンチル}-ヘプタン酸(122);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-3-フェニル-プロピル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-3-フェニル-プロピル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(123);
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-3-フェニル-プロピル)-フェニル]-シクロペンチル}-ヘプタン酸メチルエステル;
7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-3-フェニル-プロピル)-フェニル]-シクロペンチル}-ヘプタン酸(124);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘプチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘプチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(125);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ブチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ブチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(126);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ブチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸イソプロピルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ペンチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ペンチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(127);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(ヒドロキシ-フェニル-メチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(ヒドロキシ-フェニル-メチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(128);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[3-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[3-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(129);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[3-(1-ヒドロキシ-ペンチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[3-(1-ヒドロキシ-ペンチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(130);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-ヘプチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-ヘプチル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(131);
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸メチルエステル;
(Z)-7-{(1R,2S,3R,5R)-5-クロロ-3-ヒドロキシ-2-[4-(2-ヒドロキシ-1,1-ジメチル-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(132);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-2-(4-ヘキシル-フェニル)-3-ヒドロキシ-シクロペンチル]-ヘプト-5-エン酸(26-2);
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-2-(4-ヘキシル-フェニル)-3-ヒドロキシ-シクロペンチル]-ヘプト-5-エン酸メチルエステル;
(Z)-7-[(1R,2S,3R,5R)-5-クロロ-2-(4-ヘキシル-フェニル)-3-ヒドロキシ-シクロペンチル]-ヘプト-5-エン酸イソプロピルエステル; および
(Z)-7-{(1R,2S,3S,5R)-5-クロロ-3-ヒドロキシ-2-[4-(1-ヒドロキシ-ヘキシル)-フェニル]-シクロペンチル}-ヘプト-5-エン酸(211217)。
(R)-4-(tert-ブチル-ジメチル-シラニルオキシ)-2-ヨード-シクロペンタ-2-エノン(18-2)。(A.G. Myers and P. S. Dragovich J. Am. Chem. Soc. 1993,115,7021)に記載の方法と同様の方法に従った。0℃のエノン10-1(3.163g、14.9mmol,Evotec OAI, 151 Milton Park, Abington, Oxon, OX 14 4SD, UK)およびピリジン(5mL)のジクロロメタン(5mL)中溶液を、I2(6.511g、25.7mmol)のピリジン(12mL)/ジクロロメタン(12mL)中溶液と反応させた。該反応物を室温に加温し、2時間後1M HCl(60mL)を加えた。生じた混合物を100mLの1M HClに注ぎ入れ、その後ジクロロメタン(3×60mL)で抽出した。混合ジクロロメタン溶液を、飽和NaHSO3溶液およびブラインで洗浄し、その後乾燥し(Na2SO4)、ろ過し、および濃縮した。シリカゲルのフラッシュクロマトグラフィー(5%酢酸エチル/ヘキサン)により精製して、標記の化合物(4.600g、91%)を得た。
Ki
EP1、EP2、EP4およびFP受容体を安定発現する細胞
ヒトまたはネコFP受容体、またはEP1、EP2、またはEP4受容体を安定発現するHEK-293細胞を、TME緩衝液で洗浄し、該フラスコの底からすくい取り、Brinkman PT 10/35 polytronを用いて、30秒間ホモジナイズした。遠心分離管中、TME緩衝液を加えて、最終体積40mLとした(TMEの組成は、100mM トリス塩基、20mMmgCl2、2M EDTA; 10N HClを加えてpHを7.4とする)。
(a)細胞培養
組み換えヒトプロスタグランジン受容体(プロスタグランジン受容体発現: hDP/Gqs5; hEP1; hEP2/Gqs5; hEP3A/Gqi5; hEP4/Gqs5; hFP; hIP; hTP)の1つのタイプまたはサブタイプを安定発現するHEK-293(EBNA)細胞を、10%ウシ胎仔血清、2mM l-グルタミン、選択マーカーとして250μg/mlのジェネテシン(G418)および200μg/mlのハイグロマイシンB、ならびに100ユニット/mlのペニシリンG、100μg/mlのストレプトマイシンおよび0.25μg/mlのアンホテリシンBを含む、高-グルコースDMEM培地の100mmの培養皿で培養した。
細胞をBiocoat登録商標 ポリ-D-リジン-コート黒色-壁、透明-底、96-ウェルプレート(Becton-Dickinson)のウェルにつき、濃度5×104細胞でシーズし、37℃のインキュベーターに一晩設置した。細胞を、その後HBSS-HEPES緩衝液(炭酸水素塩およびフェノールレッドなしのハンクス平衡塩溶液、20mM HEPES、pH7.4)で、Denley Cellwash plate washer(Labsystems)を用いて2回洗浄した。色素をローディングし、暗所で45分後、最終濃度2μMでカルシウム-感受性色素Fluo-4 AMを使用して、プレートをHBSS-HEPES緩衝液で4回洗浄して過剰の色素を取り除き、各ウェルに100μLを残した。プレートを37℃で数分間、再平衡化した。
384-ウェル薬剤プレートを、16段階希釈、3通りに、6試験化合物、PGE2およびcAMPを含むよう、Biomek stationを使用して、調製した。標的PG受容体サブタイプ(EP2またはEP4)を発現するHEK-EBNA細胞を、刺激緩衝液(HBSS、0.1%BSA、0.5mM IBMXおよび5mM HEPES、pH7.4)で濃度104細胞/5μlに懸濁した。該反応を5μlの薬剤希釈液と5μlのHEK-EBNA細胞をウェル中で混ぜて、開始し、30分間室温で行い、続いて、Tween-20(25mM NaCl、0.03%Tween-20、5mM HEPES、pH7.4)を含むコントロール緩衝液中の抗-cAMPアクセプタービーズを5μl添加した。後暗所、室温で30分、該混合物を、溶解/検出緩衝液(0.1%BSA、0.3%Tween-20および5mM HEPES、pH7.4)中のビオチン化-cAMP/ストレパビジン(strepavidin)ドナービーズの15μlと共に、45分間、室温でインキュベートした。蛍光変化を、Fusion-アルファHTマイクロプレートリーダー使用して測定した。
眼圧(IOP)
イヌにおける眼圧試験には、意識のあるビーグル犬の両方の性(10-15kg)で行われたニューマトノメトリイ(pneumatonometry)が含まれる。該動物は試験の間ずっと意識はあり、手で優しく押さえた。薬剤を体積25μLの滴として、一方の眼に局所投与し、コントロールとして、他方の眼に25μLの賦形剤(0.1%ポリソルベート80:10mM トリス)を投与した。プロパラカイン(0.1%)を、眼圧測定の間、角膜の麻酔として使用した。5日間の試験の各日に、薬剤投与の直前、その2、4および6時間後、眼圧を測定した。薬剤を最初のIOP測定の後、直ちに投与した。
Claims (45)
-
Yは、カルボン酸、スルホン酸、またはホスホン酸; または0から12の炭素原子を含むそのアミドまたはエステルであり、; またはYは、ヒドロキシメチル、またはテトラゾリル官能基であり、ただし、XがC=Oである場合、Yはアミドではない;
Aは、−(CH2)6−、シス−CH2CH=CH−(CH2)3−、または−CH2C≡C−(CH2)3−であり、1または2の炭素原子はSまたはOで置換していてもよく、; またはAは、−(CH2)m−Ar−(CH2)o−であり、Arは、置換または非置換フェニルまたは単環ヘテロアリールであり、mとoの和は1から4であり、およびCH2の1つはSまたはOで置換していてもよく、;
Xは、C=O、CHF、CF2、CHCl、またはCHOHであり、; XがCHOHであるとき、OHはβ−立体配置にあり、;
Rは、ヒドロカルビル部分が1から5の炭素原子からなるヒドロカルビルまたはヒドロキシヒドロカルビル基、または、Rは、ヒドロカルビル部分が6から9の炭素原子からなり、かつ環状構造を有するヒドロカルビルまたはヒドロキシヒドロカルビル基、であり、;
Dは、独立して、1から6の非−水素原子の基であり、;および
nは、0から4の整数である、
で示される化合物、またはその医薬的に許容しうる塩。 - nが0である、請求項1に記載の化合物。
- Rが1−ヒドロキシヒドロカルビル基である、請求項1に記載の化合物。
- Rがt−ブチルである、請求項1に記載の化合物。
- (Z)−7−{(1R,2S,3R)−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−5−オキソ−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
(Z)−7−{(1R,2S,3R)−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−5−オキソ−シクロペンチル}−ヘプト−5−エン酸;
7−{(1R,2S,3R)−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−5−オキソ−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R)−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−5−オキソ−シクロペンチル}−ヘプタン酸;
(Z)−7−((1R,2S,3R)−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプト−5−エン酸メチルエステル;
(Z)−7−((1R,2S,3R)−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプト−5−エン酸;
7−((1R,2S,3R)−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプタン酸メチルエステル;
7−((1R,2S,3R)−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプタン酸;
(Z)−7−[(1R,2S,3R)−2−(4−tert−ブチル−フェニル)−3−ヒドロキシ−5−オキソ−シクロペンチル]−ヘプト−5−エン酸メチルエステル;
(Z)−7−[(1R,2S,3R)−2−(4−tert−ブチル−フェニル)−3−ヒドロキシ−5−オキソ−シクロペンチル]−ヘプト−5−エン酸;
7−[(1R,2S,3R)−2−(4−tert−ブチル−フェニル)−3−ヒドロキシ−5−オキソ−シクロペンチル]−ヘプタン酸メチルエステル;
7−[(1R,2S,3R)−2−(4−tert−ブチル−フェニル)−3−ヒドロキシ−5−オキソ−シクロペンチル]−ヘプタン酸;
(Z)−7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
(Z)−7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプト−5−エン酸;
7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプタン酸;
(Z)−7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R)−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−5−オキソ−シクロペンチル}−ヘプタン酸;
(Z)−7−((1R,2S,3R)−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプト−5−エン酸メチルエステル;
(Z)−7−((1R,2S,3R)−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプト−5−エン酸;
7−((1R,2S,3R)−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプタン酸メチルエステル;
7−((1R,2S,3R)−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチル)−ヘプタン酸;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ヘプト−5−エン酸;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ヘプト−5−エン酸イソプロピルエステル;
7−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ヘプタン酸メチルエステル;
7−[(1R,2S,3R,5R)−5−クロロ−2−(4−シクロヘキシルメチル−フェニル)−3−ヒドロキシ−シクロペンチル]−ヘプタン酸メチルエステル;
7−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ヘプタン酸;
7−[(1R,2S,3R,5R)−5−クロロ−2−(4−シクロヘキシルメチル−フェニル)−3−ヒドロキシ−シクロペンチル]−ヘプタン酸;
(Z)−7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプト−5−エン酸メチルエステル;
(Z)−7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプト−5−エン酸;
7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプタン酸メチルエステル;
7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{3−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプタン酸;
(Z)−7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプト−5−エン酸メチルエステル;
(Z)−7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプト−5−エン酸;
7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプタン酸メチルエステル;
7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{4−[ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチル)−ヘプタン酸;
(Z)−7−[(1R,2S,3R,5R)−2−(4−tert−ブチル−フェニル)−5−クロロ−3−ヒドロキシ−シクロペンチル]−ヘプト−5−エン酸メチルエステル;
(Z)−7−[(1R,2S,3R,5R)−2−(4−tert−ブチル−フェニル)−5−クロロ−3−ヒドロキシ−シクロペンチル]−ヘプト−5−エン酸;
7−[(1R,2S,3R,5R)−2−(4−tert−ブチル−フェニル)−5−クロロ−3−ヒドロキシ−シクロペンチル]−ヘプタン酸メチルエステル;
7−[(1R,2S,3R,5R)−2−(4−tert−ブチル−フェニル)−5−クロロ−3−ヒドロキシ−シクロペンチル]−ヘプタン酸;
(Z)−7−[(1R,2S,3R,5R)−2−(4−tert−ブチル−フェニル)−5−クロロ−3−ヒドロキシ−シクロペンチル]−ヘプト−5−エン酸イソプロピルエステル;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸メチルエステル;(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−シクロブチル)−フェニル]−シクロペンチル}−ヘプタン酸;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−シクロペンチル}−ヘプタン酸;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(2−ヒドロキシ−1,1−ジメチル−エチル)−フェニル]−シクロペンチル}−ヘプタン酸イソプロピルエステル;(Z)−7−[(1R,2S,3R)−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−5−オキソ−シクロペンチル]−ヘプト−5−エン酸メチルエステル;
(Z)−7−[(1R,2S,3R)−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−5−オキソ−シクロペンチル]−ヘプト−5−エン酸;
7−[(1R,2S,3R)−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−5−オキソ−シクロペンチル]−ヘプタン酸メチルエステル;
7−((1R,2S,3R)−3−ヒドロキシ−5−オキソ−2−p−トリル−シクロペンチル)−ヘプタン酸メチルエステル;
7−[(1R,2S,3R)−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−5−オキソ−シクロペンチル]−ヘプタン酸;
(Z)−7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−シクロペンチル]−ヘプト−5−エン酸メチルエステル;
(Z)−7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−シクロペンチル]−ヘプト−5−エン酸;
7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−シクロペンチル]−ヘプタン酸メチルエステル;
7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(4−ヒドロキシメチル−フェニル)−シクロペンチル]−ヘプタン酸;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2−メチル−プロピル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2,2−ジメチル−プロピル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸メチルエステル;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2−メチル−プロピル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸;
(Z)−7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2,2−ジメチル−プロピル)−フェニル]−シクロペンチル}−ヘプト−5−エン酸;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2−メチル−プロピル)−フェニル]−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2,2−ジメチル−プロピル)−フェニル]−シクロペンチル}−ヘプタン酸メチルエステル;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2−メチル−プロピル)−フェニル]−シクロペンチル}−ヘプタン酸;
7−{(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−[4−(1−ヒドロキシ−2,2−ジメチル−プロピル)−フェニル]−シクロペンチル}−ヘプタン酸;
(4−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ブタ−2−イニルオキシ)−酢酸メチルエステル;
(4−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ブタ−2−イニルオキシ)−酢酸;((Z)−4−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ブタ−2−エニルオキシ)−酢酸メチルエステル;
((Z)−4−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ブタ−2−エニルオキシ)−酢酸;
(4−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ブトキシ)−酢酸メチルエステル;
(4−{(1R,2S,3R,5R)−5−クロロ−2−[4−(シクロヘキシル−ヒドロキシ−メチル)−フェニル]−3−ヒドロキシ−シクロペンチル}−ブトキシ)−酢酸;
[3−((1R,2S,3R)−3−ヒドロキシ−2−{3−[(S)−ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチルメチル)−フェノキシ]−酢酸メチルエステル;
[3−((1R,2S,3R)−3−ヒドロキシ−2−{3−[(S)−ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−5−オキソ−シクロペンチルメチル)−フェノキシ]−酢酸;
[3−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{3−[(S)−ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチルメチル)−フェノキシ]−酢酸メチルエステル;[3−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−{3−[(S)−ヒドロキシ−(1−プロピル−シクロブチル)−メチル]−フェニル}−シクロペンチルメチル)−フェノキシ]−酢酸;
(Z)−7−[(1R,2S,3R)−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−5−オキソ−シクロペンチル]−ヘプト−5−エン酸メチルエステル;
(Z)−7−[(1R,2S,3R)−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−5−オキソ−シクロペンチル]−ヘプト−5−エン酸;
7−[(1R,2S,3R)−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−5−オキソ−シクロペンチル]−ヘプタン酸メチルエステル;
7−((1R,2S,3R)−3−ヒドロキシ−2−インダン−5−イル−5−オキソ−シクロペンチル)−ヘプタン酸メチルエステル;
7−[(1R,2S,3R)−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−5−オキソ−シクロペンチル]−ヘプタン酸;
7−((1R,2S,3R)−3−ヒドロキシ−2−インダン−5−イル−5−オキソ−シクロペンチル)−ヘプタン酸;
(Z)−7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプト−5−エン酸メチルエステル;
(Z)−7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプト−5−エン酸;
(Z)−7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプト−5−エン酸イソプロピルエステル;
7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプタン酸メチルエステル;
7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−インダン−5−イル−シクロペンチル)−ヘプタン酸メチルエステル;
7−[(1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプタン酸;
7−((1R,2S,3R,5R)−5−クロロ−3−ヒドロキシ−2−インダン−5−イル−シクロペンチル)−ヘプタン酸;
7−[(1R,2S,3R)−5−フルオロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプタン酸メチルエステル;
7−[(1R,2S,3R)−5−フルオロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプタン酸;
(Z)−7−[(1R,2S,3R)−5−フルオロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプト−5−エン酸メチルエステル; 及び
(Z)−7−[(1R,2S,3R)−5−フルオロ−3−ヒドロキシ−2−(1−ヒドロキシ−インダン−5−イル)−シクロペンチル]−ヘプト−5−エン酸
からなる群より選択される、請求項1に記載の化合物。 - Aが−(CH2)6−、シス−CH2CH=CH−(CH2)3−、または−CH2C≡C−(CH2)3−である、請求項25に記載の化合物。
- Rが1から5の炭素原子からなる1−ヒドロキシアルキルである、請求項1に記載の化合物。
- Yが、CO2(R3)、CON(R3)2、CON(OR3)R3、CON(CH2CH2OH)2、CONH(CH2CH2OH)、CH2OH、P(O)(OH)2、CONHSO2R3、SO2N(R3)2、SO2NHR3、およびテトラゾリル−R3(R3は独立してH、C1−C6アルキル、フェニル、またはビフェニルである)からなる群から選ばれる、請求項1に記載の化合物。
- Rが、2−ヒドロキシヒドロカルビルである請求項1に記載の化合物。
- R4およびR5がメチルである、請求項33に記載の化合物。
- Aが−(CH2)m−Ar−(CH2)o−であり、Arがフェニルであり、mとoの和が1から4であり、CH2の1つはSまたはOで置換してもよい、請求項1に記載の化合物。
- Aが−CH2−Ar−O−CH2−である、請求項36に記載の化合物。
-
からなる群より選択される化合物であって、
式中、Yは、カルボン酸、スルホン酸、またはホスホン酸; または0から12の炭素原子を含むそのアミドまたはエステルであり、; またはYは、ヒドロキシメチル、またはテトラゾリル官能基であり;
Aは、−(CH 2 ) 6 −、シス−CH 2 CH=CH−(CH 2 ) 3 −、または−CH 2 C≡C−(CH 2 ) 3 −であり、1または2の炭素原子はSまたはOで置換していてもよく、; またはAは、−(CH 2 ) m −Ar−(CH 2 ) o −であり、Arは、置換または非置換フェニルまたは単環ヘテロアリールであり、mとoの和は1から4であり、CH 2 はCH 2 SまたはOで置換していてもよい;
である上記化合物。 - 請求項1−43のいずれかに記載の化合物の緑内障の治療または眼圧の低下のための医薬の製造のための使用。
- 請求項1−43のいずれかに記載の化合物を含む眼科的に許容される液体。
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