ES2310056T3 - Sintesis de dihidrocloruro de histamina. - Google Patents
Sintesis de dihidrocloruro de histamina. Download PDFInfo
- Publication number
- ES2310056T3 ES2310056T3 ES99968148T ES99968148T ES2310056T3 ES 2310056 T3 ES2310056 T3 ES 2310056T3 ES 99968148 T ES99968148 T ES 99968148T ES 99968148 T ES99968148 T ES 99968148T ES 2310056 T3 ES2310056 T3 ES 2310056T3
- Authority
- ES
- Spain
- Prior art keywords
- histamine
- dihydrochloride
- methanol
- impurities
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 27
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 19
- 229960004931 histamine dihydrochloride Drugs 0.000 claims abstract description 63
- 239000012535 impurity Substances 0.000 claims abstract description 48
- 150000003839 salts Chemical group 0.000 claims abstract description 20
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 117
- 238000000034 method Methods 0.000 claims description 75
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 63
- 229960001340 histamine Drugs 0.000 claims description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 31
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 229960002885 histidine Drugs 0.000 claims description 24
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 22
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- IVCJGQQPPHYHBS-UHFFFAOYSA-N 2-(1h-imidazol-5-yl)ethanamine;hydrochloride Chemical compound Cl.NCCC1=CN=CN1 IVCJGQQPPHYHBS-UHFFFAOYSA-N 0.000 claims description 14
- 239000012458 free base Substances 0.000 claims description 13
- 238000001953 recrystallisation Methods 0.000 claims description 12
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 10
- 239000006184 cosolvent Substances 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 7
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 6
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 150000004682 monohydrates Chemical class 0.000 claims description 4
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 claims description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 3
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 claims description 2
- YQYGPGKTNQNXMH-UHFFFAOYSA-N 4-nitroacetophenone Chemical compound CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YQYGPGKTNQNXMH-UHFFFAOYSA-N 0.000 claims description 2
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 claims description 2
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
- 229940008309 acetone / ethanol Drugs 0.000 claims description 2
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012965 benzophenone Substances 0.000 claims description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 claims 1
- MKUWVMRNQOOSAT-UHFFFAOYSA-N but-3-en-2-ol Chemical compound CC(O)C=C MKUWVMRNQOOSAT-UHFFFAOYSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 36
- 238000006114 decarboxylation reaction Methods 0.000 abstract description 26
- 239000012467 final product Substances 0.000 abstract description 26
- 238000006243 chemical reaction Methods 0.000 abstract description 25
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 abstract description 13
- 238000002360 preparation method Methods 0.000 abstract description 13
- 230000002255 enzymatic effect Effects 0.000 abstract description 4
- 238000010189 synthetic method Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 55
- 239000000725 suspension Substances 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 29
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 21
- 239000012065 filter cake Substances 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- -1 histidine HCl monohydrate Chemical class 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 239000000356 contaminant Substances 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000010926 purge Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 231100000027 toxicology Toxicity 0.000 description 3
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000000911 decarboxylating effect Effects 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- AKRQHOWXVSDJEF-UHFFFAOYSA-N heptane-1-sulfonic acid Chemical compound CCCCCCCS(O)(=O)=O AKRQHOWXVSDJEF-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 231100000719 pollutant Toxicity 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- CMXXUDSWGMGYLZ-XRIGFGBMSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride;hydrate Chemical compound O.Cl.OC(=O)[C@@H](N)CC1=CN=CN1 CMXXUDSWGMGYLZ-XRIGFGBMSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- QZNNVYOVQUKYSC-UHFFFAOYSA-N L-hystidine hydrochloride Chemical compound [Cl-].OC(=O)C([NH3+])CC1=CN=CN1 QZNNVYOVQUKYSC-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000008380 degradant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/147777—Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11393398P | 1998-12-23 | 1998-12-23 | |
| US113933P | 1998-12-23 | ||
| US09/467,652 US6403806B1 (en) | 1998-12-23 | 1999-12-20 | Synthesis of histamine dihydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2310056T3 true ES2310056T3 (es) | 2008-12-16 |
Family
ID=26811642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99968148T Expired - Lifetime ES2310056T3 (es) | 1998-12-23 | 1999-12-20 | Sintesis de dihidrocloruro de histamina. |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US6403806B1 (https=) |
| EP (1) | EP1140857B1 (https=) |
| JP (1) | JP4139082B2 (https=) |
| CN (1) | CN1155579C (https=) |
| AT (1) | ATE399769T1 (https=) |
| AU (1) | AU763523B2 (https=) |
| CA (1) | CA2356871C (https=) |
| DE (1) | DE69939027D1 (https=) |
| DK (1) | DK1140857T3 (https=) |
| ES (1) | ES2310056T3 (https=) |
| HK (1) | HK1040998B (https=) |
| IL (2) | IL143570A0 (https=) |
| NZ (1) | NZ512935A (https=) |
| PT (1) | PT1140857E (https=) |
| TW (1) | TWI243166B (https=) |
| WO (1) | WO2000039098A1 (https=) |
| ZA (1) | ZA200104552B (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6590106B2 (en) * | 1997-05-09 | 2003-07-08 | Pharm-Eco Laboratories, Inc. | Amino acid derivatives and methods of making the same |
| US20080051440A1 (en) * | 2004-04-22 | 2008-02-28 | Mor Research Applications Ltd. | Compositions for weight management |
| BRPI0506807A (pt) * | 2004-04-22 | 2007-05-29 | Mor Research Applic Ltd | método de gerenciamento de consumo de alimento e composição farmacológica |
| US7728015B2 (en) * | 2004-04-22 | 2010-06-01 | Mor Research Applications Ltd. | Compositions for weight management |
| US20060188528A1 (en) * | 2005-02-23 | 2006-08-24 | Ansell Healthcare Products Llc | Spreadable warming lubricant |
| US7709428B2 (en) * | 2005-02-23 | 2010-05-04 | Ansell Healthcare Products Llc | Thickened spreadable warming lubricant |
| DE102006060908A1 (de) | 2006-12-20 | 2008-07-03 | Evonik Degussa Gmbh | Kontinuierliches Verfahren zur Decarboxylierung von Carbonsäuren |
| US8770201B2 (en) * | 2007-10-26 | 2014-07-08 | Glycobiosciences Inc. | Condom with multifunctional coating |
| CN102477014B (zh) * | 2010-11-27 | 2015-08-19 | 山东新时代药业有限公司 | 二盐酸组胺的制备方法 |
| ITMI20110379A1 (it) * | 2011-03-10 | 2012-09-11 | Erregierre Spa | Procedimento per la preparazione di istamina dicloridrato con elevato grado di purezza |
| US9452954B2 (en) | 2013-03-14 | 2016-09-27 | University Of Georgia Research Foundation, Inc. | Method for decarboxylation of amino acids via imine formation |
| US10118898B2 (en) | 2013-03-14 | 2018-11-06 | University Of Georgia Research Foundation, Inc. | Method for decarboxylation of amino acids via imine formation |
| US10487042B2 (en) | 2013-03-14 | 2019-11-26 | University Of Georgia Research Foundation, Inc. | Method for solvent-free decarboxylation of amino acids via imine formation |
| CN103288742A (zh) * | 2013-06-04 | 2013-09-11 | 四川百利药业有限责任公司 | 一种高纯度英加韦林原料的制备方法 |
| CN103739551B (zh) * | 2013-09-24 | 2016-03-23 | 国药一心制药有限公司 | 一种二盐酸组胺的纯化方法 |
| MX390861B (es) * | 2013-12-17 | 2025-03-21 | Univ Fraser Simon | Compuestos, composiciones y metodos para atraer y/o detener chinches. |
| CN103739552B (zh) * | 2014-01-24 | 2015-08-26 | 国药一心制药有限公司 | 二盐酸组胺的制备方法 |
| CN104402825B (zh) * | 2014-12-13 | 2017-03-15 | 济南诚汇双达化工有限公司 | 一种组胺二盐酸盐的合成方法 |
| CN106432089B (zh) * | 2016-09-12 | 2018-09-07 | 开封制药(集团)有限公司 | 二盐酸组胺的合成方法 |
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| WO2019008594A1 (en) * | 2017-07-03 | 2019-01-10 | Jubilant Generics Limited | CONTINUOUS PROCESS FOR THE PREPARATION OF 2- (1H-IMIDAZOL-4-YL) ETHANAMINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS |
| CN112266360B (zh) * | 2020-10-26 | 2022-06-10 | 武汉桀升生物科技有限公司 | 一种高纯度组胺二盐酸盐的合成方法 |
| CN113045500A (zh) * | 2021-03-31 | 2021-06-29 | 苏州园方生物科技有限公司 | 一种组胺二盐酸盐的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE57638C (de) | O. ECKARDT in Berlin j N.W., Bandelslr. 14 | Verfahren zur Herstellung von Steinkohlenbriquettes auf kaltem Wege | ||
| GB430108A (en) * | 1934-02-23 | 1935-06-13 | Boot S Pure Drug Company Ltd | Improvements relating to the preparation of histamine and its derivatives |
| GB1008594A (en) | 1963-07-03 | 1965-10-27 | Nat Res Dev | Process for the production of amines |
| SU557755A3 (ru) * | 1968-08-19 | 1977-05-05 | Янссен Фармасьютика Н.В. (Фирма) | Способ получени производных имидазола |
| DE3322117A1 (de) * | 1983-06-20 | 1984-12-20 | Diamalt AG, 8000 München | Verfahren zur herstellung von n(pfeil hoch)(tau)(pfeil hoch)-substituierten histidinderivaten, n(pfeil hoch)(tau)(pfeil hoch)-substituierten histidinderivate und ihre verwendung |
| NL8800998A (nl) * | 1988-04-18 | 1989-11-16 | Cedona Pharm Bv | Werkwijze voor het bereiden van een al of niet gesubstitueerd 4(5)-(omega-aminoalkyl) imidazool. |
| JPH05255204A (ja) | 1992-03-11 | 1993-10-05 | Kanegafuchi Chem Ind Co Ltd | アミン類の製造法 |
| SE513429C2 (sv) | 1992-06-03 | 2000-09-11 | Syntello Inc | Preparat för aktivering av naturliga mördarceller, vilket preparat innehåller interferon alfa och biogena aminer |
-
1999
- 1999-12-20 DE DE69939027T patent/DE69939027D1/de not_active Expired - Lifetime
- 1999-12-20 WO PCT/US1999/030379 patent/WO2000039098A1/en not_active Ceased
- 1999-12-20 HK HK02102715.8A patent/HK1040998B/en not_active IP Right Cessation
- 1999-12-20 DK DK99968148T patent/DK1140857T3/da active
- 1999-12-20 AT AT99968148T patent/ATE399769T1/de active
- 1999-12-20 ES ES99968148T patent/ES2310056T3/es not_active Expired - Lifetime
- 1999-12-20 AU AU24825/00A patent/AU763523B2/en not_active Expired
- 1999-12-20 CN CNB998149063A patent/CN1155579C/zh not_active Expired - Lifetime
- 1999-12-20 CA CA2356871A patent/CA2356871C/en not_active Expired - Lifetime
- 1999-12-20 PT PT99968148T patent/PT1140857E/pt unknown
- 1999-12-20 JP JP2000591009A patent/JP4139082B2/ja not_active Expired - Fee Related
- 1999-12-20 IL IL14357099A patent/IL143570A0/xx active IP Right Grant
- 1999-12-20 US US09/467,652 patent/US6403806B1/en not_active Expired - Fee Related
- 1999-12-20 EP EP99968148A patent/EP1140857B1/en not_active Expired - Lifetime
- 1999-12-20 NZ NZ512935A patent/NZ512935A/en not_active IP Right Cessation
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2000
- 2000-02-14 TW TW088122820A patent/TWI243166B/zh not_active IP Right Cessation
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2001
- 2001-06-04 ZA ZA200104552A patent/ZA200104552B/en unknown
- 2001-06-05 IL IL143570A patent/IL143570A/en not_active IP Right Cessation
- 2001-10-09 US US09/974,469 patent/US6528654B2/en not_active Expired - Fee Related
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Also Published As
| Publication number | Publication date |
|---|---|
| PT1140857E (pt) | 2008-10-06 |
| IL143570A (en) | 2006-08-20 |
| WO2000039098A1 (en) | 2000-07-06 |
| EP1140857A1 (en) | 2001-10-10 |
| NZ512935A (en) | 2003-08-29 |
| EP1140857B1 (en) | 2008-07-02 |
| CA2356871C (en) | 2010-09-14 |
| WO2000039098A9 (en) | 2001-05-17 |
| JP4139082B2 (ja) | 2008-08-27 |
| US6528654B2 (en) | 2003-03-04 |
| DK1140857T3 (da) | 2008-10-20 |
| US6620942B2 (en) | 2003-09-16 |
| AU2482500A (en) | 2000-07-31 |
| CN1155579C (zh) | 2004-06-30 |
| JP2002533445A (ja) | 2002-10-08 |
| DE69939027D1 (de) | 2008-08-14 |
| US20020035268A1 (en) | 2002-03-21 |
| IL143570A0 (en) | 2002-04-21 |
| CN1331681A (zh) | 2002-01-16 |
| HK1040998B (en) | 2009-04-24 |
| US20030138964A1 (en) | 2003-07-24 |
| US6403806B1 (en) | 2002-06-11 |
| ZA200104552B (en) | 2002-01-16 |
| CA2356871A1 (en) | 2000-07-06 |
| AU763523B2 (en) | 2003-07-24 |
| ATE399769T1 (de) | 2008-07-15 |
| HK1040998A1 (en) | 2002-06-28 |
| TWI243166B (en) | 2005-11-11 |
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