TWI646074B - 用於製備無異構體的前列腺素的方法和中間體 - Google Patents
用於製備無異構體的前列腺素的方法和中間體 Download PDFInfo
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- TWI646074B TWI646074B TW103122576A TW103122576A TWI646074B TW I646074 B TWI646074 B TW I646074B TW 103122576 A TW103122576 A TW 103122576A TW 103122576 A TW103122576 A TW 103122576A TW I646074 B TWI646074 B TW I646074B
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- alkyl
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- 238000000034 method Methods 0.000 title claims abstract description 60
- 150000003180 prostaglandins Chemical class 0.000 title abstract description 20
- 229940094443 oxytocics prostaglandins Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 239000000543 intermediate Substances 0.000 claims abstract description 16
- -1 alkoxide salt Chemical class 0.000 claims description 119
- 238000006243 chemical reaction Methods 0.000 claims description 99
- 239000000203 mixture Substances 0.000 claims description 95
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 49
- 125000006239 protecting group Chemical group 0.000 claims description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 229960002368 travoprost Drugs 0.000 claims description 33
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 claims description 33
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 claims description 32
- 229960001160 latanoprost Drugs 0.000 claims description 32
- 229960004458 tafluprost Drugs 0.000 claims description 28
- WSNODXPBBALQOF-VEJSHDCNSA-N tafluprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\C(F)(F)COC1=CC=CC=C1 WSNODXPBBALQOF-VEJSHDCNSA-N 0.000 claims description 28
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 20
- 229960002470 bimatoprost Drugs 0.000 claims description 19
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000006243 carbonyl protecting group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- XXUPXHKCPIKWLR-JHUOEJJVSA-N isopropyl unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C XXUPXHKCPIKWLR-JHUOEJJVSA-N 0.000 claims description 18
- 238000005809 transesterification reaction Methods 0.000 claims description 18
- 229950008081 unoprostone isopropyl Drugs 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 239000012535 impurity Substances 0.000 claims description 12
- 238000006460 hydrolysis reaction Methods 0.000 claims description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
- HNPFPERDNWXAGS-LZCJLJQNSA-N (e)-7-[3,5-dihydroxy-2-(3-hydroxy-5-phenylpentyl)cyclopentyl]hept-5-enoic acid Chemical compound C=1C=CC=CC=1CCC(O)CCC1C(O)CC(O)C1C\C=C\CCCC(O)=O HNPFPERDNWXAGS-LZCJLJQNSA-N 0.000 claims description 9
- KIQXRQVVYTYYAZ-VKVYFNERSA-N (z)-7-[(1r,2r,3r,5s)-2-[(e)-3,3-difluoro-4-phenoxybut-1-enyl]-3,5-dihydroxycyclopentyl]hept-5-enoic acid Chemical compound OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\C(F)(F)COC1=CC=CC=C1 KIQXRQVVYTYYAZ-VKVYFNERSA-N 0.000 claims description 8
- 229960004317 unoprostone Drugs 0.000 claims description 8
- TVHAZVBUYQMHBC-SNHXEXRGSA-N unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O TVHAZVBUYQMHBC-SNHXEXRGSA-N 0.000 claims description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical group C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 7
- 230000003301 hydrolyzing effect Effects 0.000 claims description 7
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 claims description 6
- 238000007273 lactonization reaction Methods 0.000 claims description 6
- 239000012038 nucleophile Substances 0.000 claims description 6
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- WWSWYXNVCBLWNZ-QIZQQNKQSA-N fluprostenol Chemical compound C([C@H](O)\C=C\[C@@H]1[C@H]([C@@H](O)C[C@H]1O)C\C=C/CCCC(O)=O)OC1=CC=CC(C(F)(F)F)=C1 WWSWYXNVCBLWNZ-QIZQQNKQSA-N 0.000 claims description 5
- 125000000468 ketone group Chemical group 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- HNPFPERDNWXAGS-NFVOFSAMSA-N latanoprost free acid Chemical compound C([C@@H](O)CCC=1C=CC=CC=1)C[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O HNPFPERDNWXAGS-NFVOFSAMSA-N 0.000 claims description 4
- 150000004703 alkoxides Chemical class 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000007112 amidation reaction Methods 0.000 claims description 3
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 claims description 3
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 3
- 229930194542 Keto Natural products 0.000 claims description 2
- KIQXRQVVYTYYAZ-MTNCBHNASA-N Tafluprost free acid Chemical compound OC(=O)CCC\C=C/CC1C(O)CC(O)C1\C=C\C(F)(F)COC1=CC=CC=C1 KIQXRQVVYTYYAZ-MTNCBHNASA-N 0.000 claims description 2
- MXOSTENCGSDMRE-UHFFFAOYSA-N butyl-chloro-dimethylsilane Chemical group CCCC[Si](C)(C)Cl MXOSTENCGSDMRE-UHFFFAOYSA-N 0.000 claims description 2
- DBKNGKYVNBJWHL-UHFFFAOYSA-N chloro-dimethyl-octylsilane Chemical compound CCCCCCCC[Si](C)(C)Cl DBKNGKYVNBJWHL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 230000009435 amidation Effects 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 2
- 230000007062 hydrolysis Effects 0.000 claims 2
- 230000006651 lactation Effects 0.000 claims 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 321
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 81
- 239000012044 organic layer Substances 0.000 description 75
- 239000000243 solution Substances 0.000 description 74
- 239000012043 crude product Substances 0.000 description 73
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- 239000010410 layer Substances 0.000 description 57
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 51
- 238000005160 1H NMR spectroscopy Methods 0.000 description 49
- 239000000047 product Substances 0.000 description 47
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 43
- 229920006395 saturated elastomer Polymers 0.000 description 41
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 238000004458 analytical method Methods 0.000 description 32
- 239000007787 solid Substances 0.000 description 32
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
- 235000019341 magnesium sulphate Nutrition 0.000 description 31
- 239000007864 aqueous solution Substances 0.000 description 30
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 30
- KPSZWAJWFMFMFF-UHFFFAOYSA-N hept-5-enoic acid Chemical compound CC=CCCCC(O)=O KPSZWAJWFMFMFF-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 description 24
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 18
- 239000003960 organic solvent Substances 0.000 description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 17
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000012544 monitoring process Methods 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 238000005886 esterification reaction Methods 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 238000005191 phase separation Methods 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 150000002596 lactones Chemical class 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 9
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 9
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- LMPPOYVKJVJRTH-UHFFFAOYSA-N propan-2-yl hept-5-enoate Chemical compound C(C)(C)OC(CCCC=CC)=O LMPPOYVKJVJRTH-UHFFFAOYSA-N 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 230000032050 esterification Effects 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- IFUYEJWYVORTEU-UHFFFAOYSA-N 3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]furan-2-ol Chemical compound C1CCC2OC(O)CC21 IFUYEJWYVORTEU-UHFFFAOYSA-N 0.000 description 6
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 4
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 4
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 4
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 4
- MXVMRHIWTSFDPU-UHFFFAOYSA-N 2-chlorobenzenecarboximidamide Chemical compound NC(=N)C1=CC=CC=C1Cl MXVMRHIWTSFDPU-UHFFFAOYSA-N 0.000 description 4
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 4
- 239000004367 Lipase Substances 0.000 description 4
- 102000004882 Lipase Human genes 0.000 description 4
- 108090001060 Lipase Proteins 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 238000005828 desilylation reaction Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 235000019421 lipase Nutrition 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 229940041033 macrolides Drugs 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000000634 powder X-ray diffraction Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000007142 ring opening reaction Methods 0.000 description 3
- 238000006884 silylation reaction Methods 0.000 description 3
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- BNGPVKSKKYIJCR-UHFFFAOYSA-N 2-chloro-1,3-dimethylimidazolidine;hydrochloride Chemical compound [Cl-].CN1CC[NH+](C)C1Cl BNGPVKSKKYIJCR-UHFFFAOYSA-N 0.000 description 1
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- IJBSTWJYAQXFIX-UHFFFAOYSA-N 2-chlorobutanoyl 2-chlorobutanoate Chemical compound CCC(Cl)C(=O)OC(=O)C(Cl)CC IJBSTWJYAQXFIX-UHFFFAOYSA-N 0.000 description 1
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- CQZYOCXYDKXQSI-ROQOMYSCSA-N C(/[C@@H]1[C@H]([C@H](C[C@H]1OC1OCCCC1)O)C\C=C/CCCC(O)=O)=C\C(F)(F)COc1ccccc1 Chemical compound C(/[C@@H]1[C@H]([C@H](C[C@H]1OC1OCCCC1)O)C\C=C/CCCC(O)=O)=C\C(F)(F)COc1ccccc1 CQZYOCXYDKXQSI-ROQOMYSCSA-N 0.000 description 1
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- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
- TUIAGKJNVWZBOW-UHFFFAOYSA-N [O-][N+](=O)c1cccc(c1C(=O)OC(=O)c1c(cccc1[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O Chemical compound [O-][N+](=O)c1cccc(c1C(=O)OC(=O)c1c(cccc1[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O TUIAGKJNVWZBOW-UHFFFAOYSA-N 0.000 description 1
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- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XUDOZULIAWNMIU-UHFFFAOYSA-N delta-hexenoic acid Chemical compound OC(=O)CCCC=C XUDOZULIAWNMIU-UHFFFAOYSA-N 0.000 description 1
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- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- PQRCENWIXBYZEW-UHFFFAOYSA-N hept-5-en-1-amine Chemical compound CC=CCCCCN PQRCENWIXBYZEW-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 150000002678 macrocyclic compounds Chemical class 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- ARLQDYZAXIPMJQ-UHFFFAOYSA-N methyl hept-5-enoate Chemical compound COC(=O)CCCC=CC ARLQDYZAXIPMJQ-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- FWICBZQTZDXXOL-UHFFFAOYSA-N oxecane Chemical compound C1CCCCOCCCC1 FWICBZQTZDXXOL-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- OCNSAYQJDKJOLH-AHTXBMBWSA-N propan-2-yl (z)-7-[(1r,2r,3r,5s)-2-[(e,3r)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]hept-5-enoate Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(Cl)=C1 OCNSAYQJDKJOLH-AHTXBMBWSA-N 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- KAFAIALSGSIJFN-UHFFFAOYSA-N s-pyridin-2-yl chloromethanethioate Chemical compound ClC(=O)SC1=CC=CC=N1 KAFAIALSGSIJFN-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- DEIYFTQMQPDXOT-UHFFFAOYSA-N sildenafil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 DEIYFTQMQPDXOT-UHFFFAOYSA-N 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940094720 viagra Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/02—Preparation of carboxylic acid esters by interreacting ester groups, i.e. transesterification
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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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- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
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- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
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- C07C59/40—Unsaturated compounds
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- C—CHEMISTRY; METALLURGY
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- C07C2601/00—Systems containing only non-condensed rings
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- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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| US13/967,473 | 2013-08-15 |
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| US9115109B2 (en) * | 2013-08-15 | 2015-08-25 | Chirogate International Inc. | Processes and intermediates for the preparations of isomer free prostaglandins |
| CN106467465A (zh) * | 2015-08-17 | 2017-03-01 | 上海天伟生物制药有限公司 | 一种高纯度拉坦前列素及其制备方法和用途 |
| WO2017062770A1 (en) | 2015-10-08 | 2017-04-13 | Silverberg Noah | Punctal plug and bioadhesives |
| CN107226790A (zh) * | 2016-03-25 | 2017-10-03 | 苏州朗科生物技术有限公司 | 一种高纯度他氟前列素及其类似化合物的制备方法及中间体化合物 |
| US10106499B1 (en) * | 2017-11-10 | 2018-10-23 | Chirogate International Inc. | Processes for preparing cyclopenta[b]naphthalenol derivatives and intermediates thereof |
| CN108084073B (zh) * | 2017-12-05 | 2019-10-29 | 重庆药友制药有限责任公司 | 一种纯化贝美前列素的方法 |
| WO2019222244A1 (en) * | 2018-05-15 | 2019-11-21 | California Institute Of Technology | Total synthesis of prostaglandin j natural products by stereoretentive metathesis |
| CN109053452B (zh) * | 2018-08-23 | 2021-11-19 | 扬子江药业集团有限公司 | 一种他氟前列素原料药的制备方法 |
| US20220169600A1 (en) | 2019-03-27 | 2022-06-02 | Kyowa Pharma Chemical Co., Ltd. | Method for producing pkrostaglandin |
| US12509469B2 (en) | 2019-08-07 | 2025-12-30 | Ripple Therapeutics Corporation | Compositions and methods for the treatment of pain and dependence disorders |
| CN115066232B (zh) | 2020-02-06 | 2024-12-10 | 视尔普斯眼科公司 | 用于治疗眼病的组合物和方法 |
| EP4142664A4 (en) | 2020-04-27 | 2024-05-29 | Ocular Therapeutix, Inc. | METHODS FOR TREATING ALLERGIC CONJUNCTIVITIS |
| US11332433B2 (en) | 2020-07-24 | 2022-05-17 | Chirogate International Inc. | Process for the preparation of latanoprostene bunod and intermediate thereof and compositions comprising the same |
| CN112457277B (zh) * | 2020-12-16 | 2022-06-28 | 西安国康瑞金制药有限公司 | 一种他氟前列腺素的制备方法 |
| JP7686673B2 (ja) * | 2020-12-23 | 2025-06-02 | 協和ファーマケミカル株式会社 | 幾何異性体の分離方法 |
| CN114671906B (zh) * | 2020-12-24 | 2024-03-15 | 武汉武药制药有限公司 | 制备曲伏前列素中间体的方法 |
| CN112851510B (zh) | 2021-01-27 | 2022-07-19 | Ａｇｃ株式会社 | 他氟前列素的纯化方法 |
| US12565468B2 (en) * | 2021-08-23 | 2026-03-03 | Chirogate International Inc. | Processes and intermediates for the preparations of Carboprost and Carboprost Tromethamine, and Carboprost Tromethamine prepared therefrom |
| CN115010692A (zh) * | 2022-05-21 | 2022-09-06 | 上海彩迩文生化科技有限公司 | 一类新颖大环内酯的设计、制备及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010104344A2 (en) * | 2009-03-11 | 2010-09-16 | Yonsung Fine Chemical Co., Ltd. | Process for preparing prostaglandin derivatives |
| WO2011008756A1 (en) * | 2009-07-13 | 2011-01-20 | Irix Pharmaceuticals | Synthesis of prostanoids |
| WO2013093528A1 (en) * | 2011-12-21 | 2013-06-27 | CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt. | Process for the preparation of travoprost |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1432950A (en) * | 1972-11-10 | 1976-04-22 | Ici Ltd | Cyclopentane aldehydes as chemical intermediates |
| US4049648A (en) * | 1975-06-23 | 1977-09-20 | The Upjohn Company | PG-type, 1,9-lactones |
| JP2746800B2 (ja) * | 1991-09-03 | 1998-05-06 | 株式会社アールテック・ウエノ | プロスタグランジン中間体の製法 |
| WO2000018316A2 (en) | 1998-09-25 | 2000-04-06 | Alcon Laboratories, Inc. | Sustained release, and comfortable ophthalmic composition and method for ocular therapy |
| US7166730B2 (en) * | 2000-01-27 | 2007-01-23 | Fine Tech Laboratories, Ltd | Process for the preparation of prostaglandin derivatives |
| IL134241A (en) * | 2000-01-27 | 2006-06-11 | Finetech Pharmaceutical Ltd | Process for the preparation of latanoprost |
| KR100437873B1 (ko) | 2001-05-08 | 2004-06-26 | 연성정밀화학(주) | 프로스타글란딘 유도체의 제조방법 및 그의 입체특이적출발물질 |
| GB0112699D0 (en) | 2001-05-24 | 2001-07-18 | Resolution Chemicals Ltd | Process for the preparation of prostglandins and analogues thereof |
| US6864282B2 (en) * | 2002-08-05 | 2005-03-08 | Allergan, Inc. | 9,11-cycloendoperoxide pro-drugs of prostaglandin analogues for treatment of ocular hypertension and glaucoma |
| JP2009500315A (ja) * | 2005-06-29 | 2009-01-08 | ファイザー・インク | フルオロプロスタグランジンのニトロ誘導体 |
| US7511168B2 (en) | 2006-01-18 | 2009-03-31 | Shih-Yi Wei | Processes and intermediates for the preparations of prostaglandins |
| JP2008037782A (ja) | 2006-08-04 | 2008-02-21 | Daiichi Fine Chemical Co Ltd | プロスタグランジン誘導体の製造方法 |
| US7642370B2 (en) | 2006-08-07 | 2010-01-05 | Daiichi Fine Chemical Co., Ltd. | Method for preparing prostaglandin derivative |
| AR071312A1 (es) | 2008-04-09 | 2010-06-09 | Scinopharm Taiwan Ltd | Proceso para la preparacion de analogos de prostaglandina y sus intermediarios |
| EP2143712A1 (en) | 2008-07-10 | 2010-01-13 | Sandoz AG | Improved Process for the Production of Prostaglandins and Prostaglandin Analogs |
| WO2010096123A2 (en) * | 2008-10-29 | 2010-08-26 | Aerie Pharmaceuticals, Inc. | Amino acid salts of prostaglandins |
| IT1393112B1 (it) | 2009-02-27 | 2012-04-11 | Sifavitor S R L | Procedimento per la preparazione di derivati di prostaglandine |
| US8519178B2 (en) * | 2009-06-22 | 2013-08-27 | Johnson Matthey Public Limited Company | Method for the purification of prostaglandins |
| DE202009010329U1 (de) | 2009-07-23 | 2009-10-01 | Vogelgesang Ag | Mobile Reinigungsvorrichtung |
| WO2011095990A2 (en) * | 2010-02-03 | 2011-08-11 | Fdc Limited | Process for the purification of prostaglandins and analogues thereof |
| FR2961694B1 (fr) * | 2010-06-29 | 2013-01-25 | Thea Lab | Systeme de delivrance polymerique d'une solution non visqueuse a base de prostaglandine sans conservateur |
| EP2567689A1 (en) * | 2011-09-12 | 2013-03-13 | Visiotact Pharma | Ophthtalmic compositions comprising prostaglandin F2 alpha derivatives and hyaluronic acid |
| JP2012246301A (ja) | 2012-08-10 | 2012-12-13 | Cayman Chemical Co Inc | Ｆ系プロスタグランジン類を調製する方法 |
| US9115109B2 (en) * | 2013-08-15 | 2015-08-25 | Chirogate International Inc. | Processes and intermediates for the preparations of isomer free prostaglandins |
| WO2015048736A1 (en) * | 2013-09-30 | 2015-04-02 | Irix Pharmaceuticals, Inc. | Novel synthesis routes for prostaglandins and prostaglandin intermediates using metathesis |
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2013
- 2013-08-15 US US13/967,473 patent/US9115109B2/en active Active
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2014
- 2014-06-30 TW TW103122576A patent/TWI646074B/zh active
- 2014-08-13 HU HUE14180866A patent/HUE047688T2/hu unknown
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- 2014-08-13 EP EP14180866.7A patent/EP2837621B1/en active Active
- 2014-08-14 CN CN201410400057.0A patent/CN104370786B/zh active Active
- 2014-08-14 CN CN201910505100.2A patent/CN110172033A/zh active Pending
- 2014-08-14 KR KR1020140106008A patent/KR101732477B1/ko active Active
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2015
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2016
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2017
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2018
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2020
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- 2021-06-07 KR KR1020210073326A patent/KR102417861B1/ko active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010104344A2 (en) * | 2009-03-11 | 2010-09-16 | Yonsung Fine Chemical Co., Ltd. | Process for preparing prostaglandin derivatives |
| WO2011008756A1 (en) * | 2009-07-13 | 2011-01-20 | Irix Pharmaceuticals | Synthesis of prostanoids |
| WO2013093528A1 (en) * | 2011-12-21 | 2013-06-27 | CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt. | Process for the preparation of travoprost |
Non-Patent Citations (1)
| Title |
|---|
| Bundy G. L. et al., J. Med. Chem., 1983, 26(8): 1089-1099 * |
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