TWI805692B - 製備一氧化氮供體型前列腺素類似物之方法 - Google Patents
製備一氧化氮供體型前列腺素類似物之方法 Download PDFInfo
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- TWI805692B TWI805692B TW108105320A TW108105320A TWI805692B TW I805692 B TWI805692 B TW I805692B TW 108105320 A TW108105320 A TW 108105320A TW 108105320 A TW108105320 A TW 108105320A TW I805692 B TWI805692 B TW I805692B
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- Prior art keywords
- formula
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- nitroxy
- chloride
- ester
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- 238000000034 method Methods 0.000 title claims description 46
- 238000002360 preparation method Methods 0.000 title claims description 11
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title 2
- 150000003180 prostaglandins Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 60
- 239000000203 mixture Substances 0.000 claims abstract description 34
- 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 abstract description 33
- 229960002470 bimatoprost Drugs 0.000 claims abstract description 31
- OBRMAFMGLBADSZ-UHFFFAOYSA-N (6-chloro-6-oxohexyl) nitrate Chemical compound [O-][N+](=O)OCCCCCC(Cl)=O OBRMAFMGLBADSZ-UHFFFAOYSA-N 0.000 claims abstract description 21
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims abstract description 14
- -1 6-(nitrooxy)- Chemical compound 0.000 claims abstract description 13
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims abstract description 12
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims abstract description 12
- FYGFQAJDFJYPLK-UHFFFAOYSA-N 3-butyloxiran-2-one Chemical compound CCCCC1OC1=O FYGFQAJDFJYPLK-UHFFFAOYSA-N 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical group COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 36
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 35
- 150000002148 esters Chemical group 0.000 claims description 26
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 22
- CBSFPBTYVIYRQZ-UHFFFAOYSA-N 6-nitrooxyhexanoic acid Chemical compound OC(=O)CCCCCO[N+]([O-])=O CBSFPBTYVIYRQZ-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 238000000746 purification Methods 0.000 claims description 12
- NAHLTKBFPWKXMI-UHFFFAOYSA-N C(CCCCl)CCO[N+](=O)[O-] Chemical compound C(CCCCl)CCO[N+](=O)[O-] NAHLTKBFPWKXMI-UHFFFAOYSA-N 0.000 claims description 11
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 4
- 238000005660 chlorination reaction Methods 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- XWWKSLXUVZVGSP-UHFFFAOYSA-N 6-chlorohexanoic acid Chemical compound OC(=O)CCCCCCl XWWKSLXUVZVGSP-UHFFFAOYSA-N 0.000 claims description 2
- IWHLYPDWHHPVAA-UHFFFAOYSA-N 6-hydroxyhexanoic acid Chemical compound OCCCCCC(O)=O IWHLYPDWHHPVAA-UHFFFAOYSA-N 0.000 claims description 2
- 238000004458 analytical method Methods 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 230000000802 nitrating effect Effects 0.000 claims 1
- PMNSIPXEFSYNKZ-UHFFFAOYSA-M potassium;6-hydroxyhexanoate Chemical compound [K+].OCCCCCC([O-])=O PMNSIPXEFSYNKZ-UHFFFAOYSA-M 0.000 abstract description 16
- 238000006396 nitration reaction Methods 0.000 abstract description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 abstract description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 229910017604 nitric acid Inorganic materials 0.000 abstract description 3
- 238000007142 ring opening reaction Methods 0.000 abstract description 3
- 125000005621 boronate group Chemical group 0.000 abstract 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 abstract 1
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 17
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000012535 impurity Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 8
- 229910021641 deionized water Inorganic materials 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229910001961 silver nitrate Inorganic materials 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-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
- 239000010410 layer Substances 0.000 description 6
- 238000012544 monitoring process Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- JTYUIAOHIYZBPB-UHFFFAOYSA-N 1-bromo-6-chlorohexane Chemical compound ClCCCCCCBr JTYUIAOHIYZBPB-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000005886 esterification reaction Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000010533 azeotropic distillation Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 231100000243 mutagenic effect Toxicity 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- MKPLKVHSHYCHOC-JPVYXPJZSA-N propan-2-yl (e)-7-[(1r,2r,3r,5s)-3,5-dihydroxy-2-[(e,3r)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]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(C(F)(F)F)=C1 MKPLKVHSHYCHOC-JPVYXPJZSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- JEDGAPUZBUOYQF-UHFFFAOYSA-N 2-nitrooxyhexanoic acid Chemical compound CCCCC(C(O)=O)O[N+]([O-])=O JEDGAPUZBUOYQF-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HBPVGJGBRWIVSX-UHFFFAOYSA-N 6-bromohexanoyl chloride Chemical compound ClC(=O)CCCCCBr HBPVGJGBRWIVSX-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- RCHYDUJNMUGDSI-LZVOYVEMSA-N CCCCB(OC(C1)[C@@H]2C/C=C\CCCC(NCC)=O)OC1[C@@H]2/C=C/[C@H](CCC1=CC=CC=C1)C(CCCCO[N+]([O-])=O)C(O)=O Chemical compound CCCCB(OC(C1)[C@@H]2C/C=C\CCCC(NCC)=O)OC1[C@@H]2/C=C/[C@H](CCC1=CC=CC=C1)C(CCCCO[N+]([O-])=O)C(O)=O RCHYDUJNMUGDSI-LZVOYVEMSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000004155 Chlorine dioxide Substances 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- BQMGULZBNNQXCI-TZDNYGFYSA-N [(E,3S)-1-[(6R,7R)-3-butyl-7-[(Z)-7-(ethylamino)-7-oxohept-2-enyl]-2,4-dioxa-3-borabicyclo[3.2.1]octan-6-yl]-5-phenylpent-1-en-3-yl] 6-nitrooxyhexanoate Chemical compound [N+](=O)([O-])OCCCCCC(=O)O[C@H](\C=C\[C@H]1C2OB(OC([C@@H]1C\C=C/CCCC(=O)NCC)C2)CCCC)CCC1=CC=CC=C1 BQMGULZBNNQXCI-TZDNYGFYSA-N 0.000 description 1
- OJIKUUOKTOAPIO-UHFFFAOYSA-N [N+](=O)([O-])OCCCCCC(=O)OC1=CC=C(C=C1)[N+](=O)[O-] Chemical compound [N+](=O)([O-])OCCCCCC(=O)OC1=CC=C(C=C1)[N+](=O)[O-] OJIKUUOKTOAPIO-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- CKLORIIGDPMMDW-UHFFFAOYSA-N bromo hexanoate Chemical compound CCCCCC(=O)OBr CKLORIIGDPMMDW-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000019398 chlorine dioxide Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000005610 enamide group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- WWSWYXNVCBLWNZ-QIZQQNKQSA-N fluprostenol Chemical class 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 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- NNRDTRXBVBOCAG-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine;hydrochloride Chemical compound Cl.CN(C)C1=CC=NC=C1 NNRDTRXBVBOCAG-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
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
- C07C405/0041—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/02—Preparation of esters of nitric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C203/00—Esters of nitric or nitrous acid
- C07C203/02—Esters of nitric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C291/00—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00
- C07C291/02—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18157888.1 | 2018-02-21 | ||
| EP18157888.1A EP3530649B1 (en) | 2018-02-21 | 2018-02-21 | Process for the preparation of a nitric oxide donating prostaglandin analogue |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202000643A TW202000643A (zh) | 2020-01-01 |
| TWI805692B true TWI805692B (zh) | 2023-06-21 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108105320A TWI805692B (zh) | 2018-02-21 | 2019-02-18 | 製備一氧化氮供體型前列腺素類似物之方法 |
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| US (1) | US10988438B2 (https=) |
| EP (2) | EP3757089B1 (https=) |
| JP (2) | JP7365349B2 (https=) |
| KR (1) | KR102945338B1 (https=) |
| CN (1) | CN111757868B (https=) |
| AR (1) | AR114262A1 (https=) |
| CA (1) | CA3089530A1 (https=) |
| ES (2) | ES2923623T3 (https=) |
| HU (1) | HUE052204T2 (https=) |
| MY (1) | MY201321A (https=) |
| PH (1) | PH12020551320A1 (https=) |
| PT (1) | PT3530649T (https=) |
| SG (1) | SG11202007113XA (https=) |
| TW (1) | TWI805692B (https=) |
| WO (1) | WO2019162149A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3772511B1 (en) * | 2019-08-05 | 2023-11-08 | Nicox S.A. | Process for the preparation of a nitric oxide donating prostaglandin analogue |
| ES3017242T3 (en) | 2021-02-03 | 2025-05-12 | Nicox Sa | Process for the preparation of a nitric oxide donating prostaglandin analogue |
| EP4404936A1 (en) | 2021-09-20 | 2024-07-31 | Nicox SA | Nitric oxide releasing prostamide as neuroprotective agent |
| LT4303211T (lt) | 2022-07-07 | 2024-11-25 | Nicox S.A. | Pramoninis procesas, skirtas heksano rūgšties, 6-(nitrooksi)-, (1s,2e)-3- [(1r,2r,3s,5r)-2-[(2z)-7-(etilamino)-7-okso-2-hepten-1-il]-3,5- dihidroksiciklopentil]-1-(2-feniletil)-2-propen-1-ilo esterio ir aukšto grynumo produkto gamybai |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009136281A1 (en) * | 2008-05-09 | 2009-11-12 | Nicox S.A. | Nitric oxide donating prostamides |
| WO2016155906A1 (en) * | 2015-03-31 | 2016-10-06 | Nicox S.A. | Nitric oxide donating derivatives of fluprostenol |
Family Cites Families (2)
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|---|---|---|---|---|
| CN103288698A (zh) * | 2013-05-07 | 2013-09-11 | 北京洛斯顿精细化工有限公司 | 一种合成前列素类似物的新方法 |
| JP6279409B2 (ja) | 2014-06-02 | 2018-02-14 | 株式会社ダイセル | ポスト処理を行ったスズ置換ゼオライト・ベータを用いたケトン類のエステル類への酸化 |
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2018
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- 2018-02-21 EP EP20185329.8A patent/EP3757089B1/en active Active
- 2018-02-21 EP EP18157888.1A patent/EP3530649B1/en active Active
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- 2018-02-21 HU HUE18157888A patent/HUE052204T2/hu unknown
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2019
- 2019-02-12 US US16/967,057 patent/US10988438B2/en active Active
- 2019-02-12 SG SG11202007113XA patent/SG11202007113XA/en unknown
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- 2019-02-12 JP JP2020544224A patent/JP7365349B2/ja active Active
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2020
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009136281A1 (en) * | 2008-05-09 | 2009-11-12 | Nicox S.A. | Nitric oxide donating prostamides |
| WO2016155906A1 (en) * | 2015-03-31 | 2016-10-06 | Nicox S.A. | Nitric oxide donating derivatives of fluprostenol |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2923623T3 (es) | 2022-09-29 |
| CN111757868A (zh) | 2020-10-09 |
| ES2836118T3 (es) | 2021-06-24 |
| JP7661437B2 (ja) | 2025-04-14 |
| HUE052204T2 (hu) | 2021-04-28 |
| TW202000643A (zh) | 2020-01-01 |
| MY201321A (en) | 2024-02-16 |
| CA3089530A1 (en) | 2019-08-29 |
| US20210040032A1 (en) | 2021-02-11 |
| JP2024009896A (ja) | 2024-01-23 |
| KR102945338B1 (ko) | 2026-03-26 |
| AR114262A1 (es) | 2020-08-12 |
| EP3757089A1 (en) | 2020-12-30 |
| EP3530649A1 (en) | 2019-08-28 |
| PT3530649T (pt) | 2020-12-04 |
| US10988438B2 (en) | 2021-04-27 |
| EP3757089B1 (en) | 2022-05-11 |
| PH12020551320A1 (en) | 2021-04-26 |
| KR20200123151A (ko) | 2020-10-28 |
| CN111757868B (zh) | 2023-03-14 |
| JP2021514371A (ja) | 2021-06-10 |
| WO2019162149A1 (en) | 2019-08-29 |
| JP7365349B2 (ja) | 2023-10-19 |
| SG11202007113XA (en) | 2020-09-29 |
| EP3530649B1 (en) | 2020-09-30 |
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