JP4495465B2 - オメプラゾール及びエソメプラゾールのアルキルアンモニウム塩 - Google Patents
オメプラゾール及びエソメプラゾールのアルキルアンモニウム塩 Download PDFInfo
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- JP4495465B2 JP4495465B2 JP2003572982A JP2003572982A JP4495465B2 JP 4495465 B2 JP4495465 B2 JP 4495465B2 JP 2003572982 A JP2003572982 A JP 2003572982A JP 2003572982 A JP2003572982 A JP 2003572982A JP 4495465 B2 JP4495465 B2 JP 4495465B2
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- omeprazole
- esomeprazole
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- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical class N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229960000381 omeprazole Drugs 0.000 title claims abstract description 43
- 229960004770 esomeprazole Drugs 0.000 title claims abstract description 41
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical class C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 title claims abstract description 37
- 125000005210 alkyl ammonium group Chemical group 0.000 title abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- YBRBMKDOPFTVDT-UHFFFAOYSA-O tert-butylammonium Chemical class CC(C)(C)[NH3+] YBRBMKDOPFTVDT-UHFFFAOYSA-O 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 6
- 210000004211 gastric acid Anatomy 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 abstract description 22
- 150000003973 alkyl amines Chemical class 0.000 abstract description 12
- -1 4-methoxy-3,5-dimethyl-2-pyridinyl Chemical group 0.000 abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 239000001257 hydrogen Substances 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 230000002496 gastric effect Effects 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 12
- 159000000003 magnesium salts Chemical class 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 125000006165 cyclic alkyl group Chemical group 0.000 description 9
- 238000000634 powder X-ray diffraction Methods 0.000 description 9
- 239000008186 active pharmaceutical agent Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000010936 titanium Substances 0.000 description 4
- 229910052719 titanium Inorganic materials 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000002050 diffraction method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UCORZVXJQDKVAC-UHFFFAOYSA-N 6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1H-benzimidazole 2-methylpropan-2-amine Chemical compound CC(C)(C)N.N1C2=CC(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C UCORZVXJQDKVAC-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010019375 Helicobacter infections Diseases 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 239000003699 antiulcer agent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- KWORUUGOSLYAGD-YPPDDXJESA-N esomeprazole magnesium Chemical compound [Mg+2].C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C.C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-YPPDDXJESA-N 0.000 description 2
- 201000000052 gastrinoma Diseases 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229940112641 nexium Drugs 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 150000003608 titanium Chemical class 0.000 description 2
- SUBDBMMJDZJVOS-XMMPIXPASA-N (R)-omeprazole Chemical compound C([S@@](=O)C=1NC2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-XMMPIXPASA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000028861 Helicobacter pylori infectious disease Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 206010042220 Stress ulcer Diseases 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 206010046274 Upper gastrointestinal haemorrhage Diseases 0.000 description 1
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 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
- 239000003085 diluting agent Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 150000002357 guanidines Chemical class 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
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 239000011872 intimate mixture Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([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])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Ceramic Engineering (AREA)
- Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Paper (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
式Ib:オメプラゾールの(S)−鏡像異性体アルキルアンモニウム塩
式Ic:オメプラゾールの(R)−鏡像異性体アルキルアンモニウム塩
ム塩は2つのベンズイミダゾール部分のメトキシ基が必ず5位にあるということを意味するのではなく6位にも同様にあり得るのであり、又は2つの混合物もあり得る。
a)R1は直鎖、分枝鎖C2−C11−アルキル基、又は環状C3−C11−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−C6−アルキル若しくはアルキレン基により又はフェニル若しくはフェニレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル若しくはアルキレン基又は前記フェニル若しくはフェニレン基は更に0、1、2、3個のメチル基により置換されている:
b)R1は直鎖、分枝鎖又は環状C3−C10−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−C6−アルキル若しくはアルキレン基により又はフェニル若しくはフェニレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル若しくはアルキレン基又は前記フェニル若しくはフェニレン基は更に0、1、2、3個のメチル基により置換されている:
c)R1は直鎖、分枝鎖又は環状C4−C9−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−C6−アルキル若しくはアルキレン基により又はフェニル若しくはフェニレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル若しくはアルキレン基又は前記フェニル若しくはフェニレン基は更に0、1、2、3個のメチル基により置換されている:
d)R1は直鎖、分枝鎖又は環状C4−C8−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−C6−アルキル若しくはアルキレン基により又はフェニル若しくはフェニレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル若しくはアルキレン基又は前記フェニル若しくはフェニレン基は更に0、1、2、3個のメチル基により置換されている:
e)R1は直鎖、分枝鎖又は環状C4−C7−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−C6−アルキル若しくはアルキレン基により又はフェニル若しくはフェニレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル若しくはアルキレン基又は前記フェニル若しくはフェニレン基は更に0、1、2、3個のメチル基により置換されている:
f)R1は直鎖、分枝鎖又は環状C1−C6−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−C5−アルキル若しくはアルキレン基により又はフェニル若しくはフェニレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル若しくはアルキレン基又は前記フェニル若しくはフェニレン基は更に0、1、2、3個のメチル基により置換されている:
g)R1は直鎖、分枝鎖又は環状C4−アルキル基であり、この場合前記直鎖又は分枝鎖アルキル基は環状C3−アルキル又はアルキレン基により置換されるか又は介入されることがあり、そしてこの場合前記環状アルキル又はアルキレン基は更に0、1、2、3個のメチル基により置換されている。
。
25−100 vs(極めて強い)
10−25 s(強い)
3−10 m(中位の)
1−3 w(弱い)
* 相対強度は可変スリットを用いて測定した回折図から得られる。XRPD距離値は最後の小数位で±2の範囲で変動し得る。
ぞれ、結晶形体である。それらは化学的及び固体状態安定性のみならず取扱いに好都合と云った有利な性質を示す。本発明により得られる生成物は明確な結晶生成物である。そのような結晶生成物は適当な投薬形体の製造の間に容易な加工可能性を示す。結晶生成物は摩砕、濾過及び打錠の間取扱いが容易である。操作は高い再現性を有する。又、化合物の明確な結晶形体が得られる場合安定性も改良される。これらの性質は例えば錠剤のような投薬形体を考慮する場合大きな価値ある性質である。
オメプラゾール(1.0g,2.9mmol)を第三級ブチルメチルエーテル(10ml)に60〜70℃で溶解した。第三級ブチルアミン(0.60g,8.1mmol)を添加しそして次に混合物を室温に冷却すると製造物が結晶化した。形成された沈殿を濾別しそして第三級ブチルメチルエーテルで洗浄した。表題化合物を白色固体として収得した。
1H-NMR (500 MHz, CDC13) : 1.2 (s, 9H), 2.2, (s, 3H), 2.3, (s, 3H), 3.6 (s, 3H), 3.8 (s, 3H), 4.5 (bs, 3H), 4.7 (m, 2H), 6.9 (m, 1H), 7.0 (d, 1H), 7.5 (d, 1H), 8.2 (s, 1H)。
製造した化合物をXRPDにより分析した結果図1に示す回折図を得た。
エソメプラゾール ナトリウム塩を水に溶解しそしてエソメプラゾールを二酸化炭素の添加により沈殿させた。
エソメプラゾール(1.0g,2.9mmol)をアセトニトリル(10ml)に室温で溶解した。第三級ブチルアミン(0.42g,5.7mmol)を添加しそして混合物を室温で2時間撹拌した。形成された沈殿を濾別しそしてアセトニトリル(5ml)で洗浄した。714mg(59%)の表題化合物を収得した。旋光度[α]D 20+26.1(水中1%溶液)
1H-NMR (500 MHz, CDC13) : 1.15 (s, 9H), 2.20 (s, 3H), 2.22 (s, 3H), 3.68 (s, 3H), 3.83 (s, 3H), 3.14 (bs, 3H), 4.69-4.80 (m, 2H), 6.90-6.94 (m, 1H), 7.01 (d, 1H), 7.52 (d, 1H), 8.20 (s, 1H)。
製造した化合物をXRPDにより分析した結果図2に示す回折図を得た。
Claims (8)
- オメプラゾール又はエソメプラゾールの第三級ブチルアンモニウム塩。
- 化合物は結晶であることを特徴とする請求項1に記載のオメプラゾール又はエソメプラゾールの第三級ブチルアンモニウム塩。
- 以下の工程:
a)オメプラゾール又はエソメプラゾールを有機溶媒に溶解する;
b)第三級ブチルアミンを添加しそして所望の塩を沈殿させる;
c)オメプラゾール又はエソメプラゾールの得られた塩を単離しそして乾燥させることを含む請求項1〜2のいずれかに記載のオメプラゾール又はエソメプラゾールの第三級ブチルアンモニウム塩の製造方法。 - 有機溶媒はアセトニトリル又は第三級ブチルメチルエーテルである請求項3に記載の方法。
- オメプラゾールの第三級ブチルアンモニウム塩が得られる請求項3又は4に記載の方法。
- エソメプラゾールの第三級ブチルアンモニウム塩が得られる請求項3又は4に記載の方法。
- 医薬的に受け入れられる賦形剤及び場合により他の治療用成分と配合した活性成分として請求項1〜2のいずれかに記載のオメプラゾール又はエソメプラゾールの第三級ブチルアンモニウム塩を含む医薬組成物。
- 胃酸が関連する疾患の治療における使用のための薬物の製造のための請求項1〜2のいずれかに記載のオメプラゾール又はエソメプラゾールの第三級ブチルアンモニウム塩の使用。
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US36218702P | 2002-03-05 | 2002-03-05 | |
PCT/SE2003/000378 WO2003074514A1 (en) | 2002-03-05 | 2003-03-04 | Alkylammonium salts of omeprazole and esomeprazole |
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EP1633736A1 (en) | 2003-05-05 | 2006-03-15 | Ranbaxy Laboratories Limited | Barium salt of benzimidazole derivative |
SE0302381D0 (sv) | 2003-09-04 | 2003-09-04 | Astrazeneca Ab | New salts I |
SE0302382D0 (sv) | 2003-09-04 | 2003-09-04 | Astrazeneca Ab | New salts II |
WO2006013960A1 (ja) | 2004-08-06 | 2006-02-09 | Eisai R & D Management Co., Ltd. | ベンズイミダゾール誘導体とアミンとの塩およびその製造方法 |
US7576219B2 (en) | 2005-10-26 | 2009-08-18 | Hanmi Pharm. Co., Ltd | Crystalline S-omeprazole strontium hydrate, method for preparing same, and pharmaceutical composition containing same |
EP1801110A1 (en) | 2005-12-22 | 2007-06-27 | KRKA, tovarna zdravil, d.d., Novo mesto | Esomeprazole arginine salt |
JP2009539830A (ja) * | 2006-06-07 | 2009-11-19 | アストラゼネカ・アクチエボラーグ | エソメプラゾールのアンモニウム塩の新規な製造方法 |
EA200900985A1 (ru) | 2007-01-31 | 2009-12-30 | Крка, Товарна Здравил, Д. Д., Ново Место | Способ получения оптически чистого омепразола |
AU2008277446A1 (en) | 2007-07-16 | 2009-01-22 | Astrazeneca Ab | Pyrimidine derivatives 934 |
EP2222663A1 (en) * | 2007-12-18 | 2010-09-01 | Watson Pharma Private Limited | A process for preparation of stable amorphous r-lansoprazole |
AU2009336561A1 (en) * | 2008-05-14 | 2010-07-15 | Watson Pharma Private Limited | Stable R-(+)-lansoprazole amine salt and a process for preparing the same |
WO2011058569A1 (en) * | 2009-11-12 | 2011-05-19 | Hetero Research Foundation | Process for the resolution of omeprazole |
CN110935190A (zh) * | 2019-12-20 | 2020-03-31 | 达州瓮福蓝剑化工有限责任公司 | 一种铵盐连续结晶工艺及装置 |
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SE7804231L (sv) * | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
SE8301182D0 (sv) * | 1983-03-04 | 1983-03-04 | Haessle Ab | Novel compounds |
GB2189698A (en) | 1986-04-30 | 1987-11-04 | Haessle Ab | Coated omeprazole tablets |
FR2692146B1 (fr) * | 1992-06-16 | 1995-06-02 | Ethypharm Sa | Compositions stables de microgranules d'omeprazole gastro-protégés et leur procédé d'obtention. |
SE9301830D0 (sv) * | 1993-05-28 | 1993-05-28 | Ab Astra | New compounds |
JP3350054B2 (ja) | 1994-07-08 | 2002-11-25 | アストラゼネカ・アクチエボラーグ | 複数単位の錠剤化された剤形▲i▼ |
SE504459C2 (sv) | 1994-07-15 | 1997-02-17 | Astra Ab | Förfarande för framställning av substituerade sulfoxider |
SE508669C2 (sv) * | 1996-04-26 | 1998-10-26 | Astra Ab | Nytt förfarande |
SE510650C2 (sv) * | 1997-05-30 | 1999-06-14 | Astra Ab | Ny förening |
US6048981A (en) * | 1998-04-22 | 2000-04-11 | Torcan Chemical Ltd. | Magnesium omeprazole and process for its preparation |
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EP1487818B1 (en) | 2007-05-30 |
AU2003208686A1 (en) | 2003-09-16 |
DE60314105T2 (de) | 2008-01-24 |
JP2005521693A (ja) | 2005-07-21 |
WO2003074514A1 (en) | 2003-09-12 |
ATE363480T1 (de) | 2007-06-15 |
DE60314105D1 (de) | 2007-07-12 |
PT1487818E (pt) | 2007-07-18 |
HK1070886A1 (en) | 2005-06-30 |
CA2474246A1 (en) | 2003-09-12 |
CY1108024T1 (el) | 2013-09-04 |
DK1487818T3 (da) | 2007-08-20 |
US7345061B2 (en) | 2008-03-18 |
CA2474246C (en) | 2010-06-29 |
EP1487818A1 (en) | 2004-12-22 |
US20050182099A1 (en) | 2005-08-18 |
ES2286408T3 (es) | 2007-12-01 |
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