LV12313B - Process for the preparation of leukotriene antagonists - Google Patents
Process for the preparation of leukotriene antagonists Download PDFInfo
- Publication number
- LV12313B LV12313B LVP-99-73A LV990073A LV12313B LV 12313 B LV12313 B LV 12313B LV 990073 A LV990073 A LV 990073A LV 12313 B LV12313 B LV 12313B
- Authority
- LV
- Latvia
- Prior art keywords
- compound
- acid
- formula
- solution
- phenyl
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 102
- 238000000034 method Methods 0.000 claims abstract description 47
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims abstract description 38
- -1 7-chloroquinolin-2-yl Chemical group 0.000 claims abstract description 33
- 159000000000 sodium salts Chemical class 0.000 claims abstract description 29
- VFAXPOVKNPTBTM-UHFFFAOYSA-N 2-[1-(sulfanylmethyl)cyclopropyl]acetic acid Chemical compound OC(=O)CC1(CS)CC1 VFAXPOVKNPTBTM-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 213
- 239000000243 solution Substances 0.000 claims description 112
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 29
- 239000003960 organic solvent Substances 0.000 claims description 19
- 238000002425 crystallisation Methods 0.000 claims description 14
- 230000008025 crystallization Effects 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 13
- UTKQJRWEYCKICG-UHFFFAOYSA-N s-[[1-(cyanomethyl)cyclopropyl]methyl] ethanethioate Chemical compound CC(=O)SCC1(CC#N)CC1 UTKQJRWEYCKICG-UHFFFAOYSA-N 0.000 claims description 13
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 7
- 230000002051 biphasic effect Effects 0.000 claims description 7
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000011975 tartaric acid Substances 0.000 claims description 7
- 235000002906 tartaric acid Nutrition 0.000 claims description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 229910001415 sodium ion Inorganic materials 0.000 claims description 4
- 235000011054 acetic acid Nutrition 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 4
- WMGVPDQNPUQRND-UHFFFAOYSA-N (2-methylphenyl)acetonitrile Chemical compound CC1=CC=CC=C1CC#N WMGVPDQNPUQRND-UHFFFAOYSA-N 0.000 claims 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical compound [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 abstract description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 72
- 238000006243 chemical reaction Methods 0.000 description 51
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- 229910052757 nitrogen Inorganic materials 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000002002 slurry Substances 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 239000010410 layer Substances 0.000 description 23
- 238000004821 distillation Methods 0.000 description 19
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 13
- 229910001868 water Inorganic materials 0.000 description 13
- 230000015572 biosynthetic process Effects 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 11
- 150000002009 diols Chemical class 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 125000004122 cyclic group Chemical group 0.000 description 10
- 150000002617 leukotrienes Chemical class 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 8
- YAINYZJQSQEGND-UHFFFAOYSA-N [1-(hydroxymethyl)cyclopropyl]methanol Chemical compound OCC1(CO)CC1 YAINYZJQSQEGND-UHFFFAOYSA-N 0.000 description 8
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
- 238000000386 microscopy Methods 0.000 description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
- 229940086542 triethylamine Drugs 0.000 description 8
- 238000000113 differential scanning calorimetry Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 229960004592 isopropanol Drugs 0.000 description 7
- 229940011051 isopropyl acetate Drugs 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 6
- 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 6
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- 238000003756 stirring Methods 0.000 description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 6
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- 239000012267 brine Substances 0.000 description 5
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- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 3
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 1
- OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- HIFGQTSRSNYUFC-YCBFMBTMSA-N methyl 2-[(3s)-3-[3-[2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-hydroxypropyl]benzoate;hydrate Chemical compound O.COC(=O)C1=CC=CC=C1CC[C@H](O)C1=CC=CC(C=CC=2N=C3C=C(Cl)C=CC3=CC=2)=C1 HIFGQTSRSNYUFC-YCBFMBTMSA-N 0.000 description 1
- JRHLVNAWLWIHDN-UHFFFAOYSA-N methyl 2-[1-(sulfanylmethyl)cyclopropyl]acetate Chemical compound COC(=O)CC1(CS)CC1 JRHLVNAWLWIHDN-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SMZMHUCIDGHERP-UHFFFAOYSA-N thieno[2,3-b]pyridine Chemical compound C1=CN=C2SC=CC2=C1 SMZMHUCIDGHERP-UHFFFAOYSA-N 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/53—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Pulmonology (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17493193A | 1993-12-28 | 1993-12-28 | |
| US35042894A | 1994-12-09 | 1994-12-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LV12313A LV12313A (lv) | 1999-07-20 |
| LV12313B true LV12313B (en) | 1999-11-20 |
Family
ID=26870681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LVP-99-73A LV12313B (en) | 1993-12-28 | 1999-04-27 | Process for the preparation of leukotriene antagonists |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US5614632A (cs) |
| EP (1) | EP0737186B1 (cs) |
| JP (1) | JP3640962B2 (cs) |
| KR (1) | KR100319336B1 (cs) |
| CN (3) | CN1046712C (cs) |
| AT (1) | ATE169906T1 (cs) |
| AU (1) | AU686303B2 (cs) |
| BG (1) | BG62850B1 (cs) |
| BR (1) | BR9408452A (cs) |
| CA (1) | CA2179407C (cs) |
| CY (1) | CY2104B1 (cs) |
| CZ (1) | CZ286079B6 (cs) |
| DE (1) | DE69412644T2 (cs) |
| DK (1) | DK0737186T3 (cs) |
| ES (1) | ES2122534T3 (cs) |
| FI (1) | FI113045B (cs) |
| GE (1) | GEP20012387B (cs) |
| HR (1) | HRP941022B1 (cs) |
| HU (1) | HU226394B1 (cs) |
| LV (1) | LV12313B (cs) |
| NZ (1) | NZ278263A (cs) |
| PL (1) | PL178671B1 (cs) |
| RO (1) | RO119018B1 (cs) |
| RU (2) | RU2225398C2 (cs) |
| TW (2) | TW416948B (cs) |
| UA (1) | UA44724C2 (cs) |
| WO (1) | WO1995018107A1 (cs) |
| YU (1) | YU49412B (cs) |
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| EP1474386B1 (en) * | 2002-02-06 | 2006-12-27 | Delmar Chemicals Inc. | Process for the preparation of 1-(mercaptomethyl)-cyclopropaneacetic acid |
| WO2003066598A1 (en) * | 2002-02-07 | 2003-08-14 | Dr. Reddy's Laboratories Ltd. | Novel anhydrous amorphous forms of montelukast sodium salt |
| US20050107612A1 (en) * | 2002-12-30 | 2005-05-19 | Dr. Reddy's Laboratories Limited | Process for preparation of montelukast and its salts |
| AU2004229507B2 (en) * | 2003-04-15 | 2008-12-18 | Merck Frosst Canada & Co. | Polymorphic form of montelukast sodium |
| WO2004096785A1 (ja) | 2003-04-25 | 2004-11-11 | Nippon Chemiphar Co., Ltd. | （２s，３s）－３－［［（１s）－１－イソブトキシメチル－３－メチルブチル］カルバモイル］オキシラン－２－カルボン酸の塩 |
| AU2003253247A1 (en) * | 2003-06-06 | 2005-01-04 | Morepen Laboratories Limited | An improved method for the preparation of montelukast acid and sodium salt thereof in amorphous form |
| WO2005040123A1 (en) | 2003-10-10 | 2005-05-06 | Synhton B. V. | Solid-state montelukast |
| EP1760077A1 (en) * | 2004-01-30 | 2007-03-07 | Teva Pharmaceutical Industries Ltd. | Montelukast free acid polymorphs |
| US20050187244A1 (en) * | 2004-01-30 | 2005-08-25 | Entire Interest. | Montelukast sodium polymorphs |
| WO2005074935A1 (en) * | 2004-01-30 | 2005-08-18 | Teva Pharmaceutical Industries Ltd. | Montelukast free acid polymorphs |
| NZ548873A (en) | 2004-02-03 | 2010-04-30 | Chemagis Ltd | Stable amorphous forms of montelukast sodium |
| US7189853B2 (en) * | 2004-04-15 | 2007-03-13 | Dr. Reddy's Laboratories Limited | Process for the preparation of [R-(E)-1-[[[1-[3-[2-[7-chloro-2-quinolinyl]ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (Montelukast) and its pharmaceutically acceptable salts |
| EP1646612B1 (en) * | 2004-04-21 | 2009-07-01 | Teva Pharmaceutical Industries Ltd | Processes for preparing montelukast sodium |
| US7501517B2 (en) | 2004-04-30 | 2009-03-10 | Synthon Ip, Inc. | Process for making montelukast and intermediates therefor |
| US7829716B2 (en) | 2004-04-30 | 2010-11-09 | Synthon Pharmaceuticals, Inc. | Process for making montelukast and intermediates therefor |
| ATE539061T1 (de) * | 2004-07-19 | 2012-01-15 | Matrix Lab Ltd | 2-ä(3s)-ä3-ä(2e)-(7-chlorchinolin-2- yl)ethenylüphenylü-3- halogenpropylübenzoesäuremethylester |
| EP1812394B1 (en) * | 2004-07-19 | 2011-03-02 | Matrix Laboratories Ltd | Process for the preparation of montelukast and its salts |
| WO2006021974A1 (en) * | 2004-08-23 | 2006-03-02 | Morepen Laboratories Limited | A process for synthesizing diol (viii)-an intermediate of montelukast sodium |
| PL205637B1 (pl) * | 2004-10-22 | 2010-05-31 | Inst Farmaceutyczny | Sposób wytwarzania kwasu (R,E)-(1-{1-{3-[2-(7-chlorochinolin-2-ylo)etenylo]fenylo}-3-[2-(1-hydroksy-1-metyloetylo)fenylo] propylosulfanylometylo}cyklopropylo)octowego i/lub jego farmaceutycznie dopuszczalnych soli |
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| EP1817289A1 (en) * | 2004-11-30 | 2007-08-15 | Medichem, S.A. | New process for the preparation of a leukotriene antagonist |
| ITMI20050247A1 (it) * | 2005-02-18 | 2006-08-19 | Chemi Spa | Processo per la preparazione di montelukast |
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| EP1783117A1 (en) * | 2005-11-04 | 2007-05-09 | Esteve Quimica, S.A. | Process for the preparation of a leukotriene antagonist and intermediates thereof |
| WO2007059325A2 (en) * | 2005-11-16 | 2007-05-24 | Teva Pharmaceutical Industries Ltd. | Drying methods of montelukast sodium by azeotropic removal of the solvent |
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| EP1968943B1 (en) * | 2005-12-13 | 2013-01-23 | MSN Laboratories Limited | An improved process for the preparation of montelukast and its pharmaceutically acceptable salts |
| CA2632954A1 (en) * | 2005-12-23 | 2007-06-28 | Glade Organics Private Limited | An improved process for the manufacture of montelukast sodium |
| ES2426443T3 (es) | 2005-12-30 | 2013-10-23 | Krka Tovarna Zdravil, D.D., Novo Mesto | Composición farmacéutica que contiene montelukast |
| US7572930B2 (en) * | 2006-02-02 | 2009-08-11 | Chemagis Ltd. | Process for preparing 1-(mercaptomethyl)cyclopropaneacetic acid, a useful intermediate in the preparation of montelukast and salts thereof |
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| EP1986649A4 (en) * | 2006-02-21 | 2010-03-31 | Chemagis Ltd | NOVEL MONTELUKAST AMMONIUM SALT POLYMORPHS AND METHODS FOR PREPARING THE SAME |
| IL181607A0 (en) * | 2006-02-27 | 2007-07-04 | Chemagis Ltd | Novel process for preparing montelukast and salts thereof |
| WO2007107297A1 (en) | 2006-03-17 | 2007-09-27 | Synthon B.V. | Montelukast amantadine salt |
| ATE524444T1 (de) * | 2006-04-12 | 2011-09-15 | Glade Organics Private Ltd | Verbessertes verfahren zur herstellung von montelukast-natrium |
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| JP2017503814A (ja) | 2014-01-22 | 2017-02-02 | タケダ ゲー・エム・ベー・ハーＴａｋｅｄａ ＧｍｂＨ | 部分的コントロール状態の重症喘息またはコントロール不良状態の重症喘息のｐｄｅ４インヒビターを用いた（およびロイコトリエン調節薬と組み合わせて用いた）治療 |
| CN104119270A (zh) * | 2014-08-12 | 2014-10-29 | 牡丹江恒远药业有限公司 | 一种孟鲁司特钠的制备方法 |
| CN105085391B (zh) | 2015-06-10 | 2017-08-22 | 广东默泰同创医药科技有限公司 | 用作白三烯受体拮抗剂的环丙基不饱和喹啉化合物及应用 |
| CN105541786B (zh) * | 2016-01-06 | 2017-08-08 | 鲁南贝特制药有限公司 | 一种孟鲁司特钠侧链中间体及其制备方法 |
| CN109503476A (zh) * | 2018-12-26 | 2019-03-22 | 哈尔滨珍宝制药有限公司 | 一种孟鲁司特钠的合成工艺 |
| CN111170939A (zh) * | 2019-12-20 | 2020-05-19 | 牡丹江恒远药业股份有限公司 | 一种高纯度孟鲁司特钠及其中间体的制备方法 |
| CN117024340A (zh) * | 2023-07-27 | 2023-11-10 | 迪嘉药业集团股份有限公司 | 一种孟鲁司特钠的合成方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| HU188235B (en) * | 1982-12-11 | 1986-03-28 | Alkaloida Vegyeszeti Gyar,Hu | Process for producing fluoro-methyl-quinoline derivatives |
| EP0133244B1 (en) * | 1983-07-22 | 1990-12-05 | E.I. Du Pont De Nemours And Company | Phenylquinolinecarboxylic acids and derivatives as antitumor agents |
| US5256675A (en) * | 1989-08-07 | 1993-10-26 | Fujisawa Pharmaceutical Co., Ltd. | Thiazole derivatives, processes for production thereof and pharmaceutical compositions comprising the same |
| FR2665159B1 (fr) * | 1990-07-24 | 1992-11-13 | Rhone Poulenc Sante | Nouveaux derives de la pyridine et de la quinoleine, leur preparation et les compositions pharmaceutiques qui les contiennent. |
| CA2053209C (en) * | 1990-10-12 | 1998-12-08 | Michel L. Belley | Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists |
| US5428033A (en) * | 1990-10-12 | 1995-06-27 | Merck Frosst Canada, Inc. | Saturated hydroxyalkylquinoline acids as leukotriene antagonists |
| US5270324A (en) * | 1992-04-10 | 1993-12-14 | Merck Frosst Canada, Inc. | Fluorinated hydroxyalkylquinoline acids as leukotriene antagonists |
| US5358946A (en) * | 1992-05-29 | 1994-10-25 | The Du Pont Merck Pharmaceutical Company | Heterocycle-substituted amides, carbamates and ureas as agents for the treatment of atherosclerosis |
| US5270234A (en) * | 1992-10-30 | 1993-12-14 | International Business Machines Corporation | Deep submicron transistor fabrication method |
| CA2111372C (en) * | 1992-12-22 | 2007-01-16 | Robert N. Young | Diaryl 5,6-fusedheterocyclic acids as leukotriene antagonists |
| US5371096A (en) * | 1993-08-27 | 1994-12-06 | Ciba-Geigy Corporation | (3-pyridyl)tetrafuran-2-yl substituted carboxylic acids |
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