CS272767B2 - Method of benzimidazole derivatives production - Google Patents
Method of benzimidazole derivatives production Download PDFInfo
- Publication number
- CS272767B2 CS272767B2 CS782686A CS782686A CS272767B2 CS 272767 B2 CS272767 B2 CS 272767B2 CS 782686 A CS782686 A CS 782686A CS 782686 A CS782686 A CS 782686A CS 272767 B2 CS272767 B2 CS 272767B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- group
- substituted
- formula
- alkyl
- carbon atoms
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 26
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 9
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 113
- 125000000217 alkyl group Chemical group 0.000 claims description 68
- 125000004432 carbon atom Chemical group C* 0.000 claims description 68
- 150000003839 salts Chemical class 0.000 claims description 58
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- -1 hydrochloride Chemical class 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 7
- 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 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 230000027119 gastric acid secretion Effects 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000007903 gelatin capsule Substances 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 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 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000002702 enteric coating Substances 0.000 description 3
- 238000009505 enteric coating Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 235000019204 saccharin Nutrition 0.000 description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 3
- 229940081974 saccharin Drugs 0.000 description 3
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical class O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Chemical class OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
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- 208000035944 Duodenal fistula Diseases 0.000 description 2
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- 241001465754 Metazoa Species 0.000 description 2
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
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- 230000010933 acylation Effects 0.000 description 2
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- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
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- SCCCIUGOOQLDGW-UHFFFAOYSA-N 1,1-dicyclohexylurea Chemical compound C1CCCCC1N(C(=O)N)C1CCCCC1 SCCCIUGOOQLDGW-UHFFFAOYSA-N 0.000 description 1
- WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
- LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
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- OKDQKPLMQBXTNH-UHFFFAOYSA-N n,n-dimethyl-2h-pyridin-1-amine Chemical compound CN(C)N1CC=CC=C1 OKDQKPLMQBXTNH-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-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
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- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
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- 125000006233 propoxy propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
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Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
Claims (8)
- PŘEDMĚT VYNÁLEZU1, Způsob výroby benzimidazolových derivátů obecného vzorce I kde12 3 4R , R , R a R , které jsou stejné nebo rozdílné, znamenaj ia) atom vodíku,b) alkylovou skupinu obsahující 1 až 6 atomů uhlíku,c) cykloalkylovou skupinu obsahující 3 až 7 atomů uhlíku,d) alkoxyskupinu obsahující 1 až 6 atomů uhlíku,e) alkoxyalkylovou skupinu obsahující 1 až 3 atomy uhlíku v každé alkylové části,f) alkoxyalkoxyskupinu obsahující 1 až 3 atomy uhlíku v každé alkoxylové části, ag) atom halogenu,CS 272 767 B2R5 představujea) alkylovou skupinu obsahující 1 až 6 atomů uhlíku,b) monohydroxysubstituovanou nebo dihydroxysubstituovanou alkylovou skupinu obsahující 1 až 6 atomů uhlíku,c) alkylovou skupinu obsahující 1 až 6 atomů uhlíku substituovanou aminoskupinou, monoalkylaminoskupínou obsahující 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsahující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu,d) alkylovou skupinu s I až 7 atomy uhlíku substituovanou karboxyskupínou, popřípadě ve formě soli, jako soli sodné nebo draselné,e) cykloalkylovou skupinu obsahující 3 až 7 atomů uhlíku,f) alkoxyskupinu obsahující 1 až 6 atomů uhlíku,g) monohydroxysubstituovanou nebo dihydroxysubstituovanou alkoxyskupinu obsahující 1 až 6 atomů uhlíku,Oh) alkoxyskupinu obsahující 1 až 6 atomů uhlíku, substituovanou aminoskupinou, monoalkylaminoskupínou obsahující 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsahující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu,i) alkoxyskupinu s 1 až 7 atomy uhlíku substituovanou karboxyskupínou, popřípadě ve formě soli, jako soli sodné nebo draselné,j) alkoxyalkoxyskupinu obsahující 1 až 3 atomy uhlíku v každé alkylové části,k) alkylaminoskupinu obsahující 1 až 6 atomů uhlíku,l) dialkylaminoskupinu obsahující 1 až 4 atomy uhlíku v každé alkylové části,m) monokarboxysubstituovanou nebo dikarboxysubstituovanou alkylaminoskupinu obsahující 1 až 4 atomy uhlíku v alkylové části, která je popřípadě ve formě soli nebo která je popřípadě v esterifikované formě,n) fenylovou skupinu, která je popřípadě substituována alkylovou skupinou obsahující 1 až 4 atomy uhlíku, alkoxyskupinůu obsahující I až 4 atomy uhlíku, alkoxykarbonylovou skupinou obsahující 2 až 5 atomů uhlíku nebo karboxyskupínou, přičemž karboxyskupina je popřípadě ve formě soli, jako například soli sodné,o) fenoxyskupinu, která je popřípadě substituována alkylovou skupinou obsahující1 až 4 atomy uhlíku, alkoxyskupínou obsahující 1 až 4 atomy uhlíku, alkoxykarbonylovou skupinou obsahující 2 až 5 atomů uhlíku nebo karboxyskupínou, přičemž karboxyskupina je popřípadě ve formě soli, jako soli sodné,p) fenylalkoxyskupinu obsahující 1 až 6 atomů uhlíku a alkoxylové části, přičemž fenylová část je popřípadě substituována alkylovou skupinou obsahující 1 až 6 atomů uhlíku a/nebo alkoxyskupínou obsahující 1 až 6 atomů uhlíku, fi RR a R , které jsou stejné nebo rozdílné, znamenají skupinu vybranou ze souboru zahrnuj ícíhoa) atom vodíku ab) alkylovou skupinu obsahující 1 až 6 atomů uhlíku,R7 představujea) atom vodíku,h) alkylovou skupinu obsahující 1 až 7 atomů uhlíku,c) alkoxyskupinu obsahující 1 až 7 atomů uhlíku, neboCS 272 767 B2d) fenylovou skupinu,R9 znamenáa) atom vodíku nebob) alkylovou skupinu obsahující 1 až 4 atomy uhlíku,X znamená atom síry nebo skupinu vzorce -S0-, s podmínkou, žea) R představuje atom vodíku, alkylovou skupinu nebo fenylovou skupinu, pokud jsou současně naplněny tyto podmínky:al) r1 a R4 oba znamenají atom vodíku,
- 2 3 a2) R a R jsou zvoleny ze souboru zahrnujícího atom vodíku, alkylovou skupinu nebo alkoxyskupinu aK a3) R představuje alkylovou skupinu, karboxysubstituovanou alkylovou skupinu, která 5 je v kyselé formě, aminosubstituovanou alkylovou skupinu nebo R představuje fenylovou skupinu substituovanou alkylovou skupinou nebo alkoxyskupinou,b) r5 neznamená 2-methylpropoxyskupinu, pokud R^, R2, R3, R4, r6, r7, r8 a R9 znamenají atom vodíku a X představuje atom síry, a jejich fyziologicky přijatelných solí a jejich optických isomerů, vyznačující se tím, že se nechá reagovat sloučenina obecného vzorce IV kde r\ R2, R3, R4, R6, R7, R8 a X mají významy uvedené pod obecným vzorcem I, se sloučeninou obecného vzorce VR5COOH ( V ) kdeR má význam uvedený pod obecným vzorcem I, nebo jejím aktivním derivátem, získaná sloučenina se popřípadě alkyluje za vzniku sloučeniny obecného vzorce Ϊ, kde. R9 znamená alkylovou skupinu s 1 až 4 atomy uhlíku, a potom, je-li to žádoucí, chránící skupiny se odstraní a takto získaná sloučenina obecného vzorce I se podle potřeby převede na fyziologicky přijatelnou sůl nebo svůj optický isomer.CS 272 767 B22. Způsob podle bodu 1, vyznačující se tím, že se nechá reagovat odpovídající sloučenina obecného vzorce IV s příslušnou sloučeninou obecného vzorce V za vzniku sloučeniny obecného vzorce I, ve kterém X znamená skupinu vzorce SO a ostatní substituenty mají význam uvedený v bodě 1.
- 3. Způsob podle bodu I, vyznačující se tím, že se nechá reagovat odpovídající sloučenina obecného vzorce IV s příslušnou sloučeninou obecného vzorce V za vzniku sloučeniny obecného vzorce I, ve kterém X znamená atom síry a ostatní substituenty mají význam uvedený v bodč 1,
- 4. Způsob podle bodu 1, vyznačující se tím, že se nechá reagovat odpovídající sloučenina obecného vzorce IV s příslušnou sloučeninou obecného vzorce V za vzniku sloučeniny obecného vzorce I, ve kterém R , R , R a R které jsou stejné nebo rozdílné, znamenají atom vodíku, alkylovou skupinu obsahující 1 až 6 atomů uhlíku nebo alkoxyskupinu obsahující 1 až 6 atomů uhlíku a ostatní substituenty mají význam uvedený v bodě 1.
- 5. Způsob podle bodu 1, vyznačující se tím, že se nechá reagovat odpovídající sloučenina obecného vzorce IV s příslušnou sloučeninou obecného vzorce V za vzniku sloučeniny obecného vzorce I, ve kterém R znamená alkylovou skupinu obsahující 1 až 6 atomů uhlíku, zvláště methylovou skupinu, alkoxyskupinu obsahující 1 až 6 atomů uhlíku, fenylovou skupinu, která není substituována nebo je substituována karboxyskupinou, s výhodou ve formě soli, monohydroxysubstituovanou nebo dihydroxysubstituovanou alkylovou skupinu obsahující 1 až 6 atomů uhlíku, monohydroxysubstituovanou nebo dihydroxysubstituovanou alkoxyskupinu obsahující 1 až 6 atomů uhlíku, karboxysubstituovanou alkylovou skupinu obsahující 1 až 7 atomů uhlíku, ve které je karboxyskupina popřípadě ve formě soli, karboxysubstituovanou alkoxyskupinu obsahující 1 až 7 atomů uhlíku, ve které je karboxyskupina popřípadě ve formě soli, monokarboxysubstituovanou nebo dikarboxysubstituovanou alkylaminoskupinu obsahující 1 až 4 atomy uhlíku v alkylové části, alkylovou skupinu obsahující 1 až 6 atomů uhlíku, která je popřípadě substituována aminoskupinou, monoalkylaminoskupinou s 1 až 3 atomy uhlíku nebo dialkylaminoskupinou s 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu nebo znamená alkoxyskupinu obsahující 1 až 6 atomů uhlíku substituovanou aminoskupinou, monoalkylaminoskupinou s 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsahující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu, a ostatní substituenty mají význam uvedený v bodě I.
- 6. Způsob podle bodu 1, vyznačující se tím, že se nechá reagovat odpovídající sloučenina obecného vzorce IV s příslušnou sloučeninou obecného vzorce V za vzniku sloučen.iny obecného vzorce I, ve kterém R představuje fenylovou skupinu substituovanou karboxyskupinou, přičemž karboxyskupina je s výhodou v poloze 4 fenylového kruhu, a ostatní substituenty mají význam uvedený v bodě 1.
- 7. Způsob podle bodu 1, pro výrobu benzimidazolových derivátů obecného vozorce I, ve kterémX, R1, R2, R3, R4, R6, R7, R8 a R9 mají význam uvedený v bodě 1 a cR představujea) alkylovou skupinu obsahující 1 až 6 atomů uhlíku,b) monohydroxysubstituovanou nebo dihydroxysubstituovanou alkylovou skupinu obsahující 1 až 6 atomů uhlíku,c) alkylovou skupinu obsahující 1 až 6 atomů uhlíku substituovanou aminoskupinou, monoalkylaminoskupinou obsahující 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsahující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu,d) alkylovou skupinu obsahující 1 až 7 atomů uhlíku substituovanou karboxyskupinou,CS 272 767 B2 která je popřípadě ve formě soli, jako sodné nebo draselné soli,e) cykloalkylovou skupinu obsahující 3 až 7 atomů uhlíku,f) alkoxyskupinu obsahující 1 až 6 atomů uhlíku,g) monohydroxysubstituovanou nebo dihydroxysubstituovanou alkoxyskupinu obsahující 1 až 6 atomů uhlíku,h) alkoxyskupinu obsahující 1 až 6 atomů uhlíku substituovanou aminoskupinou, monoalkylaminoskupinou obsahující 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsa hující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu,i) alkoxyskupinu obsahující 1 až 7 atomů uhlíku substituovanou karboxyskupinou, popřípadě ve formě soli, jako sodné nebo draselné soli,j) alkoxyalkoxyskupinu obsahující 1 až 3 atomy uhlíku v každé alkylové části,k) alkylaminoskupinu obsahující 1 až 6 atomů uhlíku nebol) dialkylaminoskupinu obsahující 1 až 4 atomy uhlíku v každé alkylové části, aniž by platily podmínky uvedené v závěru předvýznakové části bodu 1, a jejich fyziologicky přijatelných solí a jejich optických isomerů, vyznačující se tím, že se nechá reagovat sloučenina obecného vzorce IV, kde všechny substituenty mají význam uvedený v bodě 1, se sloučeninou obecného vzorce V, kdeR má význam uvedený v tomto bodě, získaná sloučenina se popřípadě alkyluje za vzniku sloučeniny obecného vzorce I, ve 9 kterém R znamená alkylovou skupinu obsahující 1 až 4 atomy uhlíku, a potom, je-li to žádodbí, chránící skupiny se odstraní a takto získaná sloučenina obecného vzorce I se podle potřeby převede na fyziologicky přijatelnou sůl nebo optický isomer.
- 8. Způsob podle bodu 7, vyznačující se tím, že se nechá reagovat odpovídající sloučenina obecného vzorce IV s příslušnou sloučeninou obecného vzorce V za vzniku sloučeniny obecného vzorce I, ve kterém R znamená alkylovou skupinu obsahující 1 až 6 atomů uhlíku, zvláště methylovou skupinu, alkoxyskupinu obsahující 1 až 6 atomů uhlíku, fenylovou skupinu, která není substituována nebo je substituována karboxyskupinou, s výhodou ve formě soli, monohydroxysubstituovanou nebo dihydroxysubstituovanou alkylovou skupinu obsahující 1 až 6 atomů uhlíku, monohydroxysubstituovanou nebo dihydroxysubstituovanou alkoxyskupinu obsahující 1 až 6 atomů uhlíku, alkylovou skupinu obsahující 1 až 7 atomů uhlíku substituovanou karboxyskupinou, přičemž karboxyskupina je ve formě soli, alkoxyskupinu obsahující 1 až 7 atomů uhlíku substituovanou karboxyskupinou, přičemž karboxyskupina je popřípadě ve formě soli, alkylovou skupinu obsahující 1 až 6 atomů uhlíku substituovanou aminoskupinou, monoalkylaminoskupinou obsahující 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsahující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu nebo alkoxyskupinu obsahující 1 až 6 atomů uhlíku substituovanou aminoskupinou, monoalkylaminoskupinou obsahující 1 až 3 atomy uhlíku nebo dialkylaminoskupinou obsahující 1 až 3 atomy uhlíku v každé alkylové části, popřípadě ve formě soli, jako hydrochloridu, a ostatní substituenty mají význam uvedený v bodě 1.
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| US4026776A (en) * | 1970-12-02 | 1977-05-31 | Mitsui Mining & Smelting Co., Ltd. | Method for producing high purity lead |
| US4045564A (en) * | 1974-02-18 | 1977-08-30 | Ab Hassle | Benzimidazole derivatives useful as gastric acid secretion inhibitors |
| SE418966B (sv) * | 1974-02-18 | 1981-07-06 | Haessle Ab | Analogiforfarande for framstellning av foreningar med magsyrasekretionsinhiberande verkan |
| US3960681A (en) * | 1974-02-21 | 1976-06-01 | Mitsui Mining & Smelting Co., Ltd. | Method for producing electrolytic high purity lead using large-sized electrodes |
| SE416649B (sv) * | 1974-05-16 | 1981-01-26 | Haessle Ab | Forfarande for framstellning av foreningar som paverkar magsyrasekretionen |
| NZ181123A (en) * | 1975-06-30 | 1979-12-11 | Univ Melbourne | Treatment of mineralcontaining materials with an acid in the presence of fluoride ion |
| US3972790A (en) * | 1975-09-26 | 1976-08-03 | Uop Inc. | Production of metallic lead |
| IN148930B (cs) * | 1977-09-19 | 1981-07-25 | Hoffmann La Roche | |
| US4189461A (en) * | 1977-11-30 | 1980-02-19 | Kennecott Copper Corporation | Metal leaching from concentrates using nitrogen dioxide in acids |
| SE7804231L (sv) * | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
| FR2446863A1 (fr) * | 1979-01-22 | 1980-08-14 | Uop Inc | Procede perfectionne de recuperation de plomb |
| FR2453906A1 (fr) * | 1979-04-12 | 1980-11-07 | Uop Inc | Procede de preparation hydrometallurgique de plomb a l'aide d'une extraction par voie electrochimique |
| US4229271A (en) * | 1979-05-24 | 1980-10-21 | Rsr Corporation | Method of recovering lead values from battery sludge |
| US4359465A (en) * | 1980-07-28 | 1982-11-16 | The Upjohn Company | Methods for treating gastrointestinal inflammation |
| CH644116A5 (de) * | 1980-08-21 | 1984-07-13 | Hoffmann La Roche | Imidazolderivate. |
| FR2505876A1 (en) * | 1981-05-12 | 1982-11-19 | Noual Patrick | Selective winning of lead from sulphide ores - by leaching with hot aq. hydro:fluorosilicic acid soln. contg. hydrogen peroxide and air so only lead is dissolved |
| SE8300736D0 (sv) * | 1983-02-11 | 1983-02-11 | Haessle Ab | Novel pharmacologically active compounds |
| IL75400A (en) * | 1984-06-16 | 1988-10-31 | Byk Gulden Lomberg Chem Fab | Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same |
| US4500398A (en) * | 1984-06-20 | 1985-02-19 | The United States Of America As Represented By The Secretary Of The Interior | Production of lead from sulfides |
| ZA856671B (en) * | 1984-09-24 | 1986-04-30 | Upjohn Co | N-substituted derivatives of 2-(pyridylaklenesulfinyl)benzimidazoles as gastric antisecretory agents |
| AU568441B2 (en) * | 1984-09-24 | 1987-12-24 | Upjohn Company, The | 2-(pyridylalkenesulfinyl) benzimidazole derivatives |
-
1985
- 1985-10-29 SE SE8505112A patent/SE8505112D0/xx unknown
-
1986
- 1986-10-09 ZA ZA867716A patent/ZA867716B/xx unknown
- 1986-10-22 NZ NZ218028A patent/NZ218028A/xx unknown
- 1986-10-22 EG EG661/86A patent/EG17753A/xx active
- 1986-10-23 IE IE280586A patent/IE59167B1/en not_active IP Right Cessation
- 1986-10-24 PH PH34408A patent/PH25319A/en unknown
- 1986-10-27 JO JO19861502A patent/JO1502B1/en active
- 1986-10-27 MY MYPI86000038A patent/MY101791A/en unknown
- 1986-10-27 DD DD86295633A patent/DD252375A5/de not_active IP Right Cessation
- 1986-10-28 JP JP61505700A patent/JPH0780874B2/ja not_active Expired - Lifetime
- 1986-10-28 EP EP86906498A patent/EP0233284B1/en not_active Expired - Lifetime
- 1986-10-28 IL IL80437A patent/IL80437A0/xx not_active IP Right Cessation
- 1986-10-28 IS IS3156A patent/IS1564B/is unknown
- 1986-10-28 AT AT86906498T patent/ATE79619T1/de not_active IP Right Cessation
- 1986-10-28 WO PCT/SE1986/000493 patent/WO1987002668A1/en active IP Right Grant
- 1986-10-28 HU HU865443A patent/HU198474B/hu not_active IP Right Cessation
- 1986-10-28 EP EP86850378A patent/EP0221041A3/en active Pending
- 1986-10-28 KR KR1019870700555A patent/KR950009858B1/ko active IP Right Grant
- 1986-10-28 DE DE8686906498T patent/DE3686483T2/de not_active Expired - Fee Related
- 1986-10-28 AU AU65429/86A patent/AU598491B2/en not_active Ceased
- 1986-10-28 ES ES86906498T patent/ES2051696T3/es not_active Expired - Lifetime
- 1986-10-29 CS CS782686A patent/CS272767B2/cs unknown
- 1986-10-29 PT PT83647A patent/PT83647B/pt not_active IP Right Cessation
- 1986-10-29 PL PL1986262105A patent/PL150240B1/pl unknown
- 1986-10-29 CN CN86107595A patent/CN1022487C/zh not_active Expired - Lifetime
-
1987
- 1987-06-24 DK DK320587A patent/DK320587A/da not_active Application Discontinuation
- 1987-06-26 NO NO872686A patent/NO171365C/no unknown
- 1987-06-29 FI FI872864A patent/FI91151C/sv not_active IP Right Cessation
-
1988
- 1988-05-12 US US07/195,343 patent/US5021433A/en not_active Expired - Fee Related
-
1992
- 1992-11-05 GR GR920402498T patent/GR3006177T3/el unknown
-
1993
- 1993-06-30 LV LVP-93-856A patent/LV10270B/xx unknown
- 1993-12-28 LT LTIP1681A patent/LTIP1681A/xx not_active Application Discontinuation
-
1994
- 1994-12-21 JP JP6318132A patent/JPH0826014B2/ja not_active Expired - Lifetime
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