AU2008331597B2 - Substituted cyclopentanes having prostaglandin activity - Google Patents
Substituted cyclopentanes having prostaglandin activity Download PDFInfo
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- AU2008331597B2 AU2008331597B2 AU2008331597A AU2008331597A AU2008331597B2 AU 2008331597 B2 AU2008331597 B2 AU 2008331597B2 AU 2008331597 A AU2008331597 A AU 2008331597A AU 2008331597 A AU2008331597 A AU 2008331597A AU 2008331597 B2 AU2008331597 B2 AU 2008331597B2
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- Prior art keywords
- compound according
- alkyl
- formula
- represented
- carbon atoms
- Prior art date
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- 150000003180 prostaglandins Chemical class 0.000 title description 8
- 150000001940 cyclopentanes Chemical class 0.000 title description 2
- 230000000694 effects Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 239000003814 drug Substances 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 208000010412 Glaucoma Diseases 0.000 claims description 16
- 125000001475 halogen functional group Chemical group 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 8
- 230000004410 intraocular pressure Effects 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 150000007524 organic acids Chemical group 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 18
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 7
- 102100034195 Thrombopoietin Human genes 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 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 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 229910000085 borane Inorganic materials 0.000 description 5
- -1 hydride ion Chemical class 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- LNZGYNQGYGWHEC-ZDUSSCGKSA-N (6s)-6-[tert-butyl(dimethyl)silyl]oxy-1-dimethoxyphosphorylheptan-2-one Chemical compound COP(=O)(OC)CC(=O)CCC[C@H](C)O[Si](C)(C)C(C)(C)C LNZGYNQGYGWHEC-ZDUSSCGKSA-N 0.000 description 3
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 3
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000002159 anterior chamber Anatomy 0.000 description 3
- 210000001742 aqueous humor Anatomy 0.000 description 3
- 239000013626 chemical specie Substances 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 201000004569 Blindness Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101710129069 Serine/threonine-protein phosphatase 5 Proteins 0.000 description 2
- 101710199542 Serine/threonine-protein phosphatase T Proteins 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 201000001326 acute closed-angle glaucoma Diseases 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- YSVULBSRVGBTQG-GFCCVEGCSA-N ethyl (5r)-5-[tert-butyl(dimethyl)silyl]oxyhexanoate Chemical compound CCOC(=O)CCC[C@@H](C)O[Si](C)(C)C(C)(C)C YSVULBSRVGBTQG-GFCCVEGCSA-N 0.000 description 2
- YUQVKXFPYUHIIF-SSDOTTSWSA-N ethyl (5r)-5-hydroxyhexanoate Chemical compound CCOC(=O)CCC[C@@H](C)O YUQVKXFPYUHIIF-SSDOTTSWSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000004533 oil dispersion Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 229920000470 poly(p-phenylene terephthalate) polymer Polymers 0.000 description 2
- 201000006366 primary open angle glaucoma Diseases 0.000 description 2
- WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical class CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- LNZGYNQGYGWHEC-CYBMUJFWSA-N (6r)-6-[tert-butyl(dimethyl)silyl]oxy-1-dimethoxyphosphorylheptan-2-one Chemical compound COP(=O)(OC)CC(=O)CCC[C@@H](C)O[Si](C)(C)C(C)(C)C LNZGYNQGYGWHEC-CYBMUJFWSA-N 0.000 description 1
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
- VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical compound C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 description 1
- VMKAFJQFKBASMU-UHFFFAOYSA-N 1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C12CCCN2B(C)OC1(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-UHFFFAOYSA-N 0.000 description 1
- VXSRPAQNHPYETH-OSMZHDNNSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e,3s,7r)-3,7-dihydroxyoct-1-enyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C[C@@H](O)CCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@@H](Cl)[C@@H]1CCCC1=CC=C(C(O)=O)S1 VXSRPAQNHPYETH-OSMZHDNNSA-N 0.000 description 1
- VXSRPAQNHPYETH-STUYAHHDSA-N 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e,3s,7s)-3,7-dihydroxyoct-1-enyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylic acid Chemical compound C[C@H](O)CCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@@H](Cl)[C@@H]1CCCC1=CC=C(C(O)=O)S1 VXSRPAQNHPYETH-STUYAHHDSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 206010018325 Congenital glaucomas Diseases 0.000 description 1
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- 206010068960 Narrow anterior chamber angle Diseases 0.000 description 1
- NMNFDTCOWIDEAV-UHFFFAOYSA-N OP(O)=O.OP(O)=O Chemical compound OP(O)=O.OP(O)=O NMNFDTCOWIDEAV-UHFFFAOYSA-N 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 201000005667 central retinal vein occlusion Diseases 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
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- 201000005682 chronic closed-angle glaucoma Diseases 0.000 description 1
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- 229940125898 compound 5 Drugs 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
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- 125000004185 ester group Chemical group 0.000 description 1
- MGPSIDGTLFKDEY-UHFFFAOYSA-N ethyl 5-oxohexanoate Chemical compound CCOC(=O)CCCC(C)=O MGPSIDGTLFKDEY-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
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- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 1
- JMSYRGOMOGSYDO-VWTNDGODSA-N methyl 5-[3-[(1r,2r,3r,5r)-2-[(e,3s,7r)-7-[tert-butyl(dimethyl)silyl]oxy-3-hydroxyoct-1-enyl]-5-chloro-3-(oxan-2-yloxy)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\[C@@H](O)CCC[C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H](OC2OCCCC2)C[C@H]1Cl JMSYRGOMOGSYDO-VWTNDGODSA-N 0.000 description 1
- JMSYRGOMOGSYDO-CDQLLSSVSA-N methyl 5-[3-[(1r,2r,3r,5r)-2-[(e,3s,7s)-7-[tert-butyl(dimethyl)silyl]oxy-3-hydroxyoct-1-enyl]-5-chloro-3-(oxan-2-yloxy)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\[C@@H](O)CCC[C@H](C)O[Si](C)(C)C(C)(C)C)[C@H](OC2OCCCC2)C[C@H]1Cl JMSYRGOMOGSYDO-CDQLLSSVSA-N 0.000 description 1
- LHKRTASKXZCULX-OLAKJOHKSA-N methyl 5-[3-[(1r,2r,3r,5r)-2-[(e,7r)-7-[tert-butyl(dimethyl)silyl]oxy-3-oxooct-1-enyl]-5-chloro-3-(oxan-2-yloxy)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\C(=O)CCC[C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H](OC2OCCCC2)C[C@H]1Cl LHKRTASKXZCULX-OLAKJOHKSA-N 0.000 description 1
- LHKRTASKXZCULX-WBBPHZFKSA-N methyl 5-[3-[(1r,2r,3r,5r)-2-[(e,7s)-7-[tert-butyl(dimethyl)silyl]oxy-3-oxooct-1-enyl]-5-chloro-3-(oxan-2-yloxy)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\C(=O)CCC[C@H](C)O[Si](C)(C)C(C)(C)C)[C@H](OC2OCCCC2)C[C@H]1Cl LHKRTASKXZCULX-WBBPHZFKSA-N 0.000 description 1
- FLBNTWPFLSSWDA-ZUEFNXKHSA-N methyl 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e,3s,7r)-3,7-dihydroxyoct-1-enyl]-3-(oxan-2-yloxy)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\[C@@H](O)CCC[C@@H](C)O)[C@H](OC2OCCCC2)C[C@H]1Cl FLBNTWPFLSSWDA-ZUEFNXKHSA-N 0.000 description 1
- IBBYOXWYNOMKHJ-PNWHWVHWSA-N methyl 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e,3s,7r)-3,7-dihydroxyoct-1-enyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\[C@@H](O)CCC[C@@H](C)O)[C@H](O)C[C@H]1Cl IBBYOXWYNOMKHJ-PNWHWVHWSA-N 0.000 description 1
- IBBYOXWYNOMKHJ-NMALZKOJSA-N methyl 5-[3-[(1r,2r,3r,5r)-5-chloro-2-[(e,3s,7s)-3,7-dihydroxyoct-1-enyl]-3-hydroxycyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](\C=C\[C@@H](O)CCC[C@H](C)O)[C@H](O)C[C@H]1Cl IBBYOXWYNOMKHJ-NMALZKOJSA-N 0.000 description 1
- YLYLAMFRJDFZBH-ROYKXYEVSA-N methyl 5-[3-[(1r,2r,3r,5r)-5-chloro-2-formyl-3-(oxan-2-yloxy)cyclopentyl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCC[C@@H]1[C@@H](C=O)[C@H](OC2OCCCC2)C[C@H]1Cl YLYLAMFRJDFZBH-ROYKXYEVSA-N 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical compound B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99100307P | 2007-11-29 | 2007-11-29 | |
| US60/991,003 | 2007-11-29 | ||
| PCT/US2008/084495 WO2009073432A1 (en) | 2007-11-29 | 2008-11-24 | Substituted cyclopentanes having prostaglandin activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2008331597A1 AU2008331597A1 (en) | 2009-06-11 |
| AU2008331597B2 true AU2008331597B2 (en) | 2013-11-28 |
Family
ID=40456785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008331597A Ceased AU2008331597B2 (en) | 2007-11-29 | 2008-11-24 | Substituted cyclopentanes having prostaglandin activity |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US8158676B2 (enExample) |
| EP (1) | EP2231162A1 (enExample) |
| JP (2) | JP5566902B2 (enExample) |
| AU (1) | AU2008331597B2 (enExample) |
| BR (1) | BRPI0819707A2 (enExample) |
| CA (1) | CA2706879A1 (enExample) |
| WO (1) | WO2009073432A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9315486B2 (en) | 2013-10-29 | 2016-04-19 | Allergan, Inc. | Therapeutic cyclopentanols, compositions thereof, and methods for use thereof |
| CN109072186B (zh) | 2016-03-04 | 2023-06-23 | 莱兰斯坦福初级大学评议会 | 利用前列腺素e2进行肌肉再生的组合物和方法 |
| WO2018227134A1 (en) | 2017-06-09 | 2018-12-13 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for preventing or treating muscle conditions |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006063179A1 (en) * | 2004-12-10 | 2006-06-15 | Allergan, Inc. | 12-aryl prostaglandin analogs |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4259516A (en) * | 1979-04-02 | 1981-03-31 | The Upjohn Company | 19-Hydroxy-inter-oxa-13,14-dihydro-PG1 compounds |
| US20020013304A1 (en) * | 1997-10-28 | 2002-01-31 | Wilson Leland F. | As-needed administration of an androgenic agent to enhance female sexual desire and responsiveness |
| US5877211A (en) * | 1997-11-21 | 1999-03-02 | Allergan | EP2 receptor agonists as neuroprotective agents for the eye |
| US6090847A (en) * | 1997-11-21 | 2000-07-18 | Allergan Sales, Inc. | EP2 -receptor agonists as neuroprotective agents for the eye |
| BRPI0605926A2 (pt) * | 2005-01-14 | 2009-05-26 | Allergan Inc | ciclopentanos substituìdos ou ciclopentanonas como agentes terapêuticos |
| US7427685B2 (en) * | 2005-12-06 | 2008-09-23 | Allergan, Inc. | Therapeutic substituted cyclopentanes |
| US7476755B2 (en) * | 2006-05-04 | 2009-01-13 | Allergan, Inc. | Therapeutic compounds |
| US20080015219A1 (en) * | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Therapeutic compounds |
| EP2288385A2 (en) * | 2008-04-16 | 2011-03-02 | Allergan, Inc. | Combination therapy for glaucoma |
-
2008
- 2008-11-24 BR BRPI0819707-5A patent/BRPI0819707A2/pt not_active IP Right Cessation
- 2008-11-24 EP EP08858242A patent/EP2231162A1/en not_active Withdrawn
- 2008-11-24 WO PCT/US2008/084495 patent/WO2009073432A1/en not_active Ceased
- 2008-11-24 JP JP2010536091A patent/JP5566902B2/ja not_active Expired - Fee Related
- 2008-11-24 CA CA2706879A patent/CA2706879A1/en not_active Abandoned
- 2008-11-24 AU AU2008331597A patent/AU2008331597B2/en not_active Ceased
- 2008-11-24 US US12/276,491 patent/US8158676B2/en active Active
-
2012
- 2012-03-19 US US13/423,500 patent/US8546603B2/en active Active
-
2014
- 2014-06-18 JP JP2014125190A patent/JP2014221776A/ja not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006063179A1 (en) * | 2004-12-10 | 2006-06-15 | Allergan, Inc. | 12-aryl prostaglandin analogs |
Also Published As
| Publication number | Publication date |
|---|---|
| US20120178798A1 (en) | 2012-07-12 |
| WO2009073432A1 (en) | 2009-06-11 |
| US20090143461A1 (en) | 2009-06-04 |
| EP2231162A1 (en) | 2010-09-29 |
| BRPI0819707A2 (pt) | 2015-06-16 |
| AU2008331597A1 (en) | 2009-06-11 |
| JP2011505361A (ja) | 2011-02-24 |
| JP5566902B2 (ja) | 2014-08-06 |
| CA2706879A1 (en) | 2009-06-11 |
| US8158676B2 (en) | 2012-04-17 |
| JP2014221776A (ja) | 2014-11-27 |
| US8546603B2 (en) | 2013-10-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |