CA2692572A1 - Cyclopentanes therapeutiques substitues pour reduire la pression intraoculaire - Google Patents
Cyclopentanes therapeutiques substitues pour reduire la pression intraoculaire Download PDFInfo
- Publication number
- CA2692572A1 CA2692572A1 CA 2692572 CA2692572A CA2692572A1 CA 2692572 A1 CA2692572 A1 CA 2692572A1 CA 2692572 CA2692572 CA 2692572 CA 2692572 A CA2692572 A CA 2692572A CA 2692572 A1 CA2692572 A1 CA 2692572A1
- Authority
- CA
- Canada
- Prior art keywords
- chloro
- carboxylic acid
- thiophene
- propyl
- mmol
- 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.)
- Abandoned
Links
- 230000004410 intraocular pressure Effects 0.000 title claims description 4
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 150000001940 cyclopentanes Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 150000002148 esters Chemical class 0.000 claims abstract description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 23
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 18
- 150000001408 amides Chemical class 0.000 claims abstract description 14
- 125000000524 functional group Chemical group 0.000 claims abstract description 14
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 14
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 13
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 13
- 150000007524 organic acids Chemical group 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 101
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 6
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- ZHNPIGCMDFFPSX-NCXUSEDFSA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-phenylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)CCC1=CC=C(C(O)=O)S1 ZHNPIGCMDFFPSX-NCXUSEDFSA-N 0.000 claims description 3
- FIVUYQLAXMGLDM-YQVWRLOYSA-N 5-[3-[(1s,2s,3r)-3-hydroxy-5-oxo-2-(2-phenylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@@H]1C(=O)C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)CCC1=CC=C(C(O)=O)S1 FIVUYQLAXMGLDM-YQVWRLOYSA-N 0.000 claims description 3
- UDJNEXIKFLPQPN-IJXRJRJASA-N 5-[3-[(1s,2s,3r,5r)-5-cyano-3-hydroxy-2-(2-phenylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](C#N)C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)CCC1=CC=C(C(O)=O)S1 UDJNEXIKFLPQPN-IJXRJRJASA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- YDWDIWNFBPTJFF-GXRSIYKFSA-N propan-2-yl 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-phenylethynyl)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC(C)C)=CC=C1CCC[C@@H]1[C@@H](C#CC=2C=CC=CC=2)[C@H](O)C[C@H]1Cl YDWDIWNFBPTJFF-GXRSIYKFSA-N 0.000 claims description 3
- MAOFDTVJZGIUOB-XGNHVKOBSA-N 5-[3-[(1r,2s,3r)-3-hydroxy-2-(2-phenylethynyl)-5-(trifluoromethyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1C(C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)C(F)(F)F)CCC1=CC=C(C(O)=O)S1 MAOFDTVJZGIUOB-XGNHVKOBSA-N 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- PJGFZUBLJSMVLV-JKOPJJFASA-N 2-[2-[(1r,2r,3r,5r)-2-[(e)-2-(3-but-3-enyl-5-chlorophenyl)ethenyl]-5-chloro-3-hydroxycyclopentyl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C\C=1C=C(CCC=C)C=C(Cl)C=1)O)CSC1=NC(C(O)=O)=CS1 PJGFZUBLJSMVLV-JKOPJJFASA-N 0.000 claims 1
- PJGFZUBLJSMVLV-DLSAWSQDSA-N 2-[2-[(1r,2r,3r,5r)-2-[(z)-2-(3-but-3-enyl-5-chlorophenyl)ethenyl]-5-chloro-3-hydroxycyclopentyl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C/C=1C=C(CCC=C)C=C(Cl)C=1)O)CSC1=NC(C(O)=O)=CS1 PJGFZUBLJSMVLV-DLSAWSQDSA-N 0.000 claims 1
- ABGOBDXEJASGNN-KCYZZUKISA-N 2-[2-[(1r,2r,3r,5r)-5-chloro-2-[2-(3,5-dichlorophenyl)ethenyl]-3-hydroxycyclopentyl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C=CC=1C=C(Cl)C=C(Cl)C=1)O)CSC1=NC(C(O)=O)=CS1 ABGOBDXEJASGNN-KCYZZUKISA-N 0.000 claims 1
- VGQVVKIOZYQLPT-KCYZZUKISA-N 2-[2-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-phenylethynyl)cyclopentyl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)CSC1=NC(C(O)=O)=CS1 VGQVVKIOZYQLPT-KCYZZUKISA-N 0.000 claims 1
- LASWCVMLRMFKLM-SSGKUCQKSA-N 5-[3-[(1r,2r,3r,5r)-2-[2-(3-but-3-enylphenyl)ethenyl]-5-chloro-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C=CC=1C=C(CCC=C)C=CC=1)O)CCC1=CC=C(C(O)=O)S1 LASWCVMLRMFKLM-SSGKUCQKSA-N 0.000 claims 1
- SOPHKEPUTWPCEL-FQRLNYBZSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e)-2-(2,6-dichloropyridin-4-yl)ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C\C=1C=C(Cl)N=C(Cl)C=1)O)CCC1=CC=C(C(O)=O)S1 SOPHKEPUTWPCEL-FQRLNYBZSA-N 0.000 claims 1
- PEBZVFPSFALNKS-AQWMBLLYSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e)-2-(3,5-difluorophenyl)ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C\C=1C=C(F)C=C(F)C=1)O)CCC1=CC=C(C(O)=O)S1 PEBZVFPSFALNKS-AQWMBLLYSA-N 0.000 claims 1
- CZHYKYWDRJHXPF-OLMDXKKMSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e)-2-(5-chloropyridin-3-yl)ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C\C=1C=C(Cl)C=NC=1)O)CCC1=CC=C(C(O)=O)S1 CZHYKYWDRJHXPF-OLMDXKKMSA-N 0.000 claims 1
- LFMZZLKLKPJYQR-CXEXCLRBSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e)-2-[3-chloro-5-[(e)-prop-1-enyl]phenyl]ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C\C=C\C1=CC(Cl)=CC(\C=C\[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 LFMZZLKLKPJYQR-CXEXCLRBSA-N 0.000 claims 1
- SOPHKEPUTWPCEL-ASAKMOIOSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(z)-2-(2,6-dichloropyridin-4-yl)ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C/C=1C=C(Cl)N=C(Cl)C=1)O)CCC1=CC=C(C(O)=O)S1 SOPHKEPUTWPCEL-ASAKMOIOSA-N 0.000 claims 1
- PEBZVFPSFALNKS-CLCQPTCASA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(z)-2-(3,5-difluorophenyl)ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1\C=C/C=1C=C(F)C=C(F)C=1)O)CCC1=CC=C(C(O)=O)S1 PEBZVFPSFALNKS-CLCQPTCASA-N 0.000 claims 1
- LFMZZLKLKPJYQR-OQYPPDPBSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(z)-2-[3-chloro-5-[(e)-prop-1-enyl]phenyl]ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C\C=C\C1=CC(Cl)=CC(\C=C/[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 LFMZZLKLKPJYQR-OQYPPDPBSA-N 0.000 claims 1
- AFYXHGFPTHLXOO-NCXUSEDFSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[2-(3,5-dichlorophenyl)ethenyl]-3-hydroxycyclopentyl]prop-1-enyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C=CC=1C=C(Cl)C=C(Cl)C=1)O)C=CC1=CC=C(C(O)=O)S1 AFYXHGFPTHLXOO-NCXUSEDFSA-N 0.000 claims 1
- QHCLGDFRJRXXHG-XRXFAXGQSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[2-(3,5-dimethylphenyl)ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound CC1=CC(C)=CC(C=C[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 QHCLGDFRJRXXHG-XRXFAXGQSA-N 0.000 claims 1
- KUOBGHVIANMHER-UAFMIMERSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[2-[3-chloro-5-(hydroxymethyl)phenyl]ethenyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound OCC1=CC(Cl)=CC(C=C[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 KUOBGHVIANMHER-UAFMIMERSA-N 0.000 claims 1
- UXVFOUCAAHXZKV-ZLTFGEGPSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-3-hydroxy-2-[(e)-2-(2-propylpyridin-4-yl)ethenyl]cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C1=NC(CCC)=CC(\C=C\[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 UXVFOUCAAHXZKV-ZLTFGEGPSA-N 0.000 claims 1
- QNFADXKJITUROP-UAFMIMERSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-3-hydroxy-2-[2-(3-methylphenyl)ethenyl]cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound CC1=CC=CC(C=C[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 QNFADXKJITUROP-UAFMIMERSA-N 0.000 claims 1
- FIVUYQLAXMGLDM-ZHALLVOQSA-N 5-[3-[(1r,2s,3r)-3-hydroxy-5-oxo-2-(2-phenylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1C(=O)C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)CCC1=CC=C(C(O)=O)S1 FIVUYQLAXMGLDM-ZHALLVOQSA-N 0.000 claims 1
- RXGDMTUMEHYFIW-SSGKUCQKSA-N 5-[3-[(1r,2s,3r,5r)-2-[2-(3-but-3-enylphenyl)ethynyl]-5-chloro-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1C=C(CCC=C)C=CC=1)O)CCC1=CC=C(C(O)=O)S1 RXGDMTUMEHYFIW-SSGKUCQKSA-N 0.000 claims 1
- VDGLHJDYWSNCPH-NCXUSEDFSA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-2-[2-(3,5-dichlorophenyl)ethynyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1C=C(Cl)C=C(Cl)C=1)O)CCC1=CC=C(C(O)=O)S1 VDGLHJDYWSNCPH-NCXUSEDFSA-N 0.000 claims 1
- ZSRDESZSQMSFML-XRXFAXGQSA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-2-[2-(3-ethylphenyl)ethynyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound CCC1=CC=CC(C#C[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 ZSRDESZSQMSFML-XRXFAXGQSA-N 0.000 claims 1
- JGJUWDVADPDGBR-BRSBDYLESA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-pyridin-2-ylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1N=CC=CC=1)O)CCC1=CC=C(C(O)=O)S1 JGJUWDVADPDGBR-BRSBDYLESA-N 0.000 claims 1
- KCIQLMFPXGVODC-BRSBDYLESA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-pyridin-3-ylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1C=NC=CC=1)O)CCC1=CC=C(C(O)=O)S1 KCIQLMFPXGVODC-BRSBDYLESA-N 0.000 claims 1
- VZACPPDKNVXDRD-BRSBDYLESA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-pyridin-4-ylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1C=CN=CC=1)O)CCC1=CC=C(C(O)=O)S1 VZACPPDKNVXDRD-BRSBDYLESA-N 0.000 claims 1
- PVDNYUSNELXNOS-QBPKDAKJSA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-thiophen-2-ylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC=1SC=CC=1)O)CCC1=CC=C(C(O)=O)S1 PVDNYUSNELXNOS-QBPKDAKJSA-N 0.000 claims 1
- TUZDLGRNKRUHGC-QBPKDAKJSA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-(2-thiophen-3-ylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](Cl)C[C@H]([C@@H]1C#CC1=CSC=C1)O)CCC1=CC=C(C(O)=O)S1 TUZDLGRNKRUHGC-QBPKDAKJSA-N 0.000 claims 1
- XYTWIQSLLRKJRM-GXRSIYKFSA-N 5-[3-[(1r,2s,3r,5r)-5-chloro-3-hydroxy-2-[2-[3-(3-hydroxypropyl)phenyl]ethynyl]cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound OCCCC1=CC=CC(C#C[C@@H]2[C@H]([C@H](Cl)C[C@H]2O)CCCC=2SC(=CC=2)C(O)=O)=C1 XYTWIQSLLRKJRM-GXRSIYKFSA-N 0.000 claims 1
- HIPOZNRDSBNERQ-NCXUSEDFSA-N 5-[3-[(1r,2s,3r,5r)-5-fluoro-3-hydroxy-2-(2-phenylethynyl)cyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H]1[C@H](F)C[C@H]([C@@H]1C#CC=1C=CC=CC=1)O)CCC1=CC=C(C(O)=O)S1 HIPOZNRDSBNERQ-NCXUSEDFSA-N 0.000 claims 1
- 239000002220 antihypertensive agent Substances 0.000 abstract description 2
- 229940112258 acular Drugs 0.000 abstract 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000243 solution Substances 0.000 description 72
- 239000000203 mixture Substances 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- 238000000746 purification Methods 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
- 239000012074 organic phase Substances 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 45
- -1 hydride ion Chemical class 0.000 description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- 238000004587 chromatography analysis Methods 0.000 description 35
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
- 238000010511 deprotection reaction Methods 0.000 description 31
- 238000002360 preparation method Methods 0.000 description 31
- 150000001336 alkenes Chemical class 0.000 description 30
- 238000007127 saponification reaction Methods 0.000 description 29
- 239000012267 brine Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 22
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 150000001299 aldehydes Chemical class 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 17
- 102100034195 Thrombopoietin Human genes 0.000 description 17
- 238000010438 heat treatment Methods 0.000 description 16
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 15
- AVCVDUDESCZFHJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound [Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 AVCVDUDESCZFHJ-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- 208000010412 Glaucoma Diseases 0.000 description 13
- 101710129069 Serine/threonine-protein phosphatase 5 Proteins 0.000 description 13
- 101710199542 Serine/threonine-protein phosphatase T Proteins 0.000 description 13
- 239000008346 aqueous phase Substances 0.000 description 13
- 125000001309 chloro group Chemical group Cl* 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 229920000470 poly(p-phenylene terephthalate) polymer Polymers 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 description 12
- 238000007239 Wittig reaction Methods 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 238000006254 arylation reaction Methods 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D409/08—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 linked by a carbon chain containing alicyclic rings
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- A47—FURNITURE; DOMESTIC ARTICLES OR APPLIANCES; COFFEE MILLS; SPICE MILLS; SUCTION CLEANERS IN GENERAL
- A47G—HOUSEHOLD OR TABLE EQUIPMENT
- A47G19/00—Table service
- A47G19/02—Plates, dishes or the like
- A47G19/06—Plates with integral holders for spoons, glasses, or the like
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- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/559—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing hetero atoms other than oxygen
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- 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
- C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/08—Hydrogen atoms or radicals containing only hydrogen and carbon atoms
- C07D333/10—Thiophene
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- 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
- C07D333/40—Thiophene-2-carboxylic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94790407P | 2007-07-03 | 2007-07-03 | |
| US60/947,904 | 2007-07-03 | ||
| PCT/US2008/068716 WO2009006370A1 (fr) | 2007-07-03 | 2008-06-30 | Cyclopentanes thérapeutiques substitués pour réduire la pression intraoculaire |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2692572A1 true CA2692572A1 (fr) | 2009-01-08 |
Family
ID=39941423
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2692572 Abandoned CA2692572A1 (fr) | 2007-07-03 | 2008-06-30 | Cyclopentanes therapeutiques substitues pour reduire la pression intraoculaire |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US9591935B2 (fr) |
| EP (1) | EP2170345B1 (fr) |
| JP (1) | JP5453254B2 (fr) |
| KR (1) | KR20100051803A (fr) |
| CN (1) | CN101795692B (fr) |
| AU (2) | AU2008269965A1 (fr) |
| CA (1) | CA2692572A1 (fr) |
| DK (1) | DK2170345T3 (fr) |
| ES (1) | ES2401920T3 (fr) |
| NZ (1) | NZ582705A (fr) |
| RU (2) | RU2010103149A (fr) |
| WO (1) | WO2009006370A1 (fr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010093945A2 (fr) | 2009-02-13 | 2010-08-19 | Glaukos Corporation | Implant médicamenteux uvéoscléral et ses procédés d'implantation |
| WO2012071476A2 (fr) | 2010-11-24 | 2012-05-31 | David Haffner | Implant oculaire à élution de médicament |
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| US8299068B2 (en) * | 2010-01-29 | 2012-10-30 | Allergan, Inc. | Therapeutically active cyclopentanes |
| US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
| US9890146B2 (en) | 2014-02-27 | 2018-02-13 | Ono Pharmaceutical Co., Ltd. | Compound having selective EP2 agonist activity |
| EP3327018B1 (fr) | 2015-07-23 | 2020-11-25 | ONO Pharmaceutical Co., Ltd. | Dérivés du acide carboxylique 2-(octahydrocyclopenta[b]pyran-2-yl)1,3-thiazole-4- et composés similaires en tant qu'agonists du ep2 a activité abaissant la pression intraoculaire |
| US11497759B2 (en) | 2017-12-01 | 2022-11-15 | Lunella Biotech, Inc. | Repurposcins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2307882A (en) * | 1939-12-04 | 1943-01-12 | Freud Joseph | Combined food and beverage server |
| US3980700A (en) | 1971-10-07 | 1976-09-14 | G. D. Searle & Co. | Prostaglandin intermediates and optically active isomers thereof |
| US4149007A (en) * | 1977-06-23 | 1979-04-10 | Miles Laboratories, Inc. | C14 Phenyl-substituted derivatives of prostaglandin analogues |
| US5390798A (en) * | 1991-11-07 | 1995-02-21 | G'-Ka International, Inc. | Food and beverage support tray with beverage vessel cutout |
| US5323910A (en) * | 1992-08-07 | 1994-06-28 | Van De Graaf Jr Pieter A | Party plate |
| US5352708A (en) * | 1992-09-21 | 1994-10-04 | Allergan, Inc. | Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| US5688819A (en) * | 1992-09-21 | 1997-11-18 | Allergan | Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| US5536725A (en) | 1993-08-25 | 1996-07-16 | Fmc Corporation | Insecticidal substituted-2,4-diamino-5,6,7,8-tetrahydroquinazolines |
| US5593062A (en) * | 1995-10-10 | 1997-01-14 | Martin; Melvin E. | Social serving plate |
| US5727678A (en) * | 1996-06-12 | 1998-03-17 | Chen; Chin Chen | Two-in-one paper dish and cup holder |
| US6264026B1 (en) * | 1997-04-15 | 2001-07-24 | Vincent H. Bradley | Food, beverage and utility tray |
| US5950856A (en) * | 1997-04-15 | 1999-09-14 | Cinque; Richard | Plate and cup holder |
| WO1998058911A2 (fr) * | 1997-06-23 | 1998-12-30 | Pfizer Inc. | Agonistes de prostaglandines |
| IL139941A0 (en) | 1999-12-02 | 2002-02-10 | Pfizer Prod Inc | Use of prostaglandin agonists to treat erectile dysfunction or impotence |
| BR0211545A (pt) * | 2001-07-31 | 2004-07-13 | Sucampo Ag | Método e composição para tratamento de hipertensão ocular e glaucoma |
| US6651836B1 (en) * | 2002-07-03 | 2003-11-25 | Leonard L. Hofheins | Hand-held plate for holding a beverage container and food |
| EP1846354B1 (fr) * | 2005-01-14 | 2010-04-28 | Allergan, Inc. | Cyclopentanes ou cyclopentanones substitues utilises pour traiter l'hypertension oculaire |
| BRPI0713587A2 (pt) | 2006-06-20 | 2012-10-23 | Allergan Inc | descrição de compostos terapêuticos da invenção |
| JP5532302B2 (ja) * | 2006-07-10 | 2014-06-25 | アラーガン インコーポレイテッド | 治療化合物 |
| US20080015219A1 (en) * | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Therapeutic compounds |
| CA2657719C (fr) * | 2006-07-11 | 2015-12-29 | Allergan, Inc. | Derives de cyclopentane en tant qu'agents contre le glaucome |
-
2008
- 2008-06-30 WO PCT/US2008/068716 patent/WO2009006370A1/fr active Application Filing
- 2008-06-30 NZ NZ582705A patent/NZ582705A/en not_active IP Right Cessation
- 2008-06-30 CN CN2008801052735A patent/CN101795692B/zh not_active Expired - Fee Related
- 2008-06-30 EP EP08781152A patent/EP2170345B1/fr active Active
- 2008-06-30 JP JP2010515212A patent/JP5453254B2/ja not_active Expired - Fee Related
- 2008-06-30 RU RU2010103149/15A patent/RU2010103149A/ru unknown
- 2008-06-30 DK DK08781152.7T patent/DK2170345T3/da active
- 2008-06-30 KR KR1020107002370A patent/KR20100051803A/ko not_active Application Discontinuation
- 2008-06-30 CA CA 2692572 patent/CA2692572A1/fr not_active Abandoned
- 2008-06-30 AU AU2008269965A patent/AU2008269965A1/en not_active Abandoned
- 2008-06-30 ES ES08781152T patent/ES2401920T3/es active Active
- 2008-06-30 US US12/667,197 patent/US9591935B2/en active Active
-
2014
- 2014-02-19 RU RU2014105895/15A patent/RU2014105895A/ru not_active Application Discontinuation
- 2014-07-01 AU AU2014203599A patent/AU2014203599A1/en not_active Abandoned
-
2017
- 2017-02-06 US US15/425,470 patent/US9765065B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2170345A1 (fr) | 2010-04-07 |
| US9591935B2 (en) | 2017-03-14 |
| RU2010103149A (ru) | 2011-08-10 |
| WO2009006370A1 (fr) | 2009-01-08 |
| DK2170345T3 (da) | 2013-05-13 |
| AU2008269965A1 (en) | 2009-01-08 |
| AU2014203599A1 (en) | 2014-07-17 |
| ES2401920T3 (es) | 2013-04-25 |
| EP2170345B1 (fr) | 2013-03-06 |
| JP2010532379A (ja) | 2010-10-07 |
| RU2014105895A (ru) | 2015-08-27 |
| KR20100051803A (ko) | 2010-05-18 |
| US20110062165A1 (en) | 2011-03-17 |
| US20170144999A1 (en) | 2017-05-25 |
| JP5453254B2 (ja) | 2014-03-26 |
| NZ582705A (en) | 2012-06-29 |
| CN101795692A (zh) | 2010-08-04 |
| CN101795692B (zh) | 2013-06-12 |
| US9765065B2 (en) | 2017-09-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20130611 |
|
| FZDE | Discontinued |
Effective date: 20160428 |