NO301229B1 - Analogifremgangsmåte for fremstilling av terapeutisk aktive benzimidazolderivater, samt mellomproduktforbindelser - Google Patents
Analogifremgangsmåte for fremstilling av terapeutisk aktive benzimidazolderivater, samt mellomproduktforbindelser Download PDFInfo
- Publication number
- NO301229B1 NO301229B1 NO930499A NO930499A NO301229B1 NO 301229 B1 NO301229 B1 NO 301229B1 NO 930499 A NO930499 A NO 930499A NO 930499 A NO930499 A NO 930499A NO 301229 B1 NO301229 B1 NO 301229B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- general formula
- benzenesulfonamide
- methyl
- isobutyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 77
- 238000000034 method Methods 0.000 title claims description 68
- 238000002360 preparation method Methods 0.000 title claims description 28
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 797
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 145
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000012312 sodium hydride Substances 0.000 claims description 10
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 150000002460 imidazoles Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 2
- 229910000105 potassium hydride Inorganic materials 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 abstract description 37
- 108010003541 Platelet Activating Factor Proteins 0.000 abstract description 37
- 239000005557 antagonist Substances 0.000 abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000035475 disorder Diseases 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 150000004677 hydrates Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 136
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 136
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 128
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- 239000000377 silicon dioxide Substances 0.000 description 66
- 238000004587 chromatography analysis Methods 0.000 description 63
- 239000000243 solution Substances 0.000 description 62
- -1 2-methyl-2-propynyl Chemical group 0.000 description 56
- 239000007787 solid Substances 0.000 description 55
- 239000000203 mixture Substances 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 46
- 229910001868 water Inorganic materials 0.000 description 44
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 42
- 239000003921 oil Substances 0.000 description 40
- 235000019198 oils Nutrition 0.000 description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 238000004458 analytical method Methods 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000012230 colorless oil Substances 0.000 description 27
- 239000002904 solvent Substances 0.000 description 24
- 229910052786 argon Inorganic materials 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 10
- 210000001772 blood platelet Anatomy 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- LDZYRENCLPUXAX-UHFFFAOYSA-N 2-methyl-1h-benzimidazole Chemical compound C1=CC=C2NC(C)=NC2=C1 LDZYRENCLPUXAX-UHFFFAOYSA-N 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- VSRBKQFNFZQRBM-UHFFFAOYSA-N tuaminoheptane Chemical compound CCCCCC(C)N VSRBKQFNFZQRBM-UHFFFAOYSA-N 0.000 description 7
- JWQVOMJORQXNME-UHFFFAOYSA-N 2-methyl-3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC(C)=NC2=C1 JWQVOMJORQXNME-UHFFFAOYSA-N 0.000 description 6
- ZFBQCMXJHJDUQC-UHFFFAOYSA-N 4-(bromomethyl)-n-(1,2-diphenylethyl)benzenesulfonamide Chemical compound C1=CC(CBr)=CC=C1S(=O)(=O)NC(C=1C=CC=CC=1)CC1=CC=CC=C1 ZFBQCMXJHJDUQC-UHFFFAOYSA-N 0.000 description 6
- FXSNYMOVKVRYLI-UHFFFAOYSA-N 4-(bromomethyl)-n-heptan-2-ylbenzenesulfonamide Chemical compound CCCCCC(C)NS(=O)(=O)C1=CC=C(CBr)C=C1 FXSNYMOVKVRYLI-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 239000007900 aqueous suspension Substances 0.000 description 6
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- QXTQWYZHHMQSQH-UHFFFAOYSA-N 4-(bromomethyl)benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(CBr)C=C1 QXTQWYZHHMQSQH-UHFFFAOYSA-N 0.000 description 5
- 208000001953 Hypotension Diseases 0.000 description 5
- 235000019502 Orange oil Nutrition 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 150000008065 acid anhydrides Chemical class 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
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- 229910052740 iodine Inorganic materials 0.000 description 5
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- 239000010502 orange oil Substances 0.000 description 5
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- ICSKJDZASFIJQK-UHFFFAOYSA-N 2-Methyloctan-4-one Chemical compound CCCCC(=O)CC(C)C ICSKJDZASFIJQK-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000006196 drop Substances 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 230000036543 hypotension Effects 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
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- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
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- NNHPQZVYKCAOCM-UHFFFAOYSA-N 2-methyloctan-4-amine Chemical compound CCCCC(N)CC(C)C NNHPQZVYKCAOCM-UHFFFAOYSA-N 0.000 description 3
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
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- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000004079 stearyl 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])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])[H] 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- QOUMJXYJNQUGAT-UHFFFAOYSA-N tert-butyl n-(1-bromo-4-methylpentan-2-yl)carbamate Chemical compound CC(C)CC(CBr)NC(=O)OC(C)(C)C QOUMJXYJNQUGAT-UHFFFAOYSA-N 0.000 description 1
- GCBVZHIDLDHLOF-UHFFFAOYSA-N tert-butyl n-(1-hydroxypentan-2-yl)carbamate Chemical compound CCCC(CO)NC(=O)OC(C)(C)C GCBVZHIDLDHLOF-UHFFFAOYSA-N 0.000 description 1
- QOUMJXYJNQUGAT-VIFPVBQESA-N tert-butyl n-[(2s)-1-bromo-4-methylpentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](CBr)NC(=O)OC(C)(C)C QOUMJXYJNQUGAT-VIFPVBQESA-N 0.000 description 1
- LDKDMDVMMCXTMO-LBPRGKRZSA-N tert-butyl n-[(2s)-1-hydroxy-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)CC1=CC=CC=C1 LDKDMDVMMCXTMO-LBPRGKRZSA-N 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229960003279 thiopental Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Developing Agents For Electrophotography (AREA)
- Phenolic Resins Or Amino Resins (AREA)
- Polyesters Or Polycarbonates (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909017878A GB9017878D0 (en) | 1990-08-15 | 1990-08-15 | Compounds |
| GB909018040A GB9018040D0 (en) | 1990-08-16 | 1990-08-16 | Compounds |
| GB919112857A GB9112857D0 (en) | 1991-06-14 | 1991-06-14 | Compounds |
| PCT/GB1991/001391 WO1992003422A1 (fr) | 1990-08-15 | 1991-08-15 | Derives benzimidazoliques, procede de preparation et applications |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO930499D0 NO930499D0 (no) | 1993-02-12 |
| NO930499L NO930499L (no) | 1993-04-14 |
| NO301229B1 true NO301229B1 (no) | 1997-09-29 |
Family
ID=27265234
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO930499A NO301229B1 (no) | 1990-08-15 | 1993-02-12 | Analogifremgangsmåte for fremstilling av terapeutisk aktive benzimidazolderivater, samt mellomproduktforbindelser |
| NO973981A NO973981D0 (no) | 1990-08-15 | 1997-08-29 | Benzimidazolderivater |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO973981A NO973981D0 (no) | 1990-08-15 | 1997-08-29 | Benzimidazolderivater |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US5200412A (fr) |
| EP (1) | EP0543861B1 (fr) |
| JP (1) | JP3218243B2 (fr) |
| KR (1) | KR930701412A (fr) |
| AT (1) | ATE172195T1 (fr) |
| AU (1) | AU657920B2 (fr) |
| CA (1) | CA2088742C (fr) |
| DE (1) | DE69130362T2 (fr) |
| ES (1) | ES2123511T3 (fr) |
| FI (1) | FI930633A (fr) |
| HU (2) | HUT65983A (fr) |
| IE (1) | IE912874A1 (fr) |
| NO (2) | NO301229B1 (fr) |
| NZ (1) | NZ239408A (fr) |
| PT (1) | PT98674B (fr) |
| TW (1) | TW199860B (fr) |
| WO (1) | WO1992003422A1 (fr) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE70217B1 (en) * | 1990-08-15 | 1996-10-30 | British Bio Technology | Benzimidazole derivatives process for their preparation and application |
| US5466704A (en) * | 1991-02-26 | 1995-11-14 | E. R. Squibb & Sons, Inc. | N-substituted imidazole and benzimidazole derivatives useful as angiotenson II antagonists |
| GB9122308D0 (en) * | 1991-10-21 | 1991-12-04 | British Bio Technology | Compounds |
| GB9200209D0 (en) * | 1992-01-07 | 1992-02-26 | British Bio Technology | Compounds |
| GB9200245D0 (en) * | 1992-01-07 | 1992-02-26 | British Bio Technology | Compounds |
| GB9201755D0 (en) * | 1992-01-28 | 1992-03-11 | British Bio Technology | Compounds |
| GB9202791D0 (en) * | 1992-02-11 | 1992-03-25 | British Bio Technology | Compounds |
| IL111785A0 (en) * | 1993-12-03 | 1995-01-24 | Ferring Bv | Dp-iv inhibitors and pharmaceutical compositions containing them |
| WO1996004270A1 (fr) | 1994-08-04 | 1996-02-15 | Synaptic Pharmaceutical Corporation | Nouveaux derives de benzimidazole |
| GB9508748D0 (en) * | 1995-04-28 | 1995-06-14 | British Biotech Pharm | Benzimidazole derivatives |
| US6495583B1 (en) | 1997-03-25 | 2002-12-17 | Synaptic Pharmaceutical Corporation | Benzimidazole derivatives |
| FR2776925B3 (fr) * | 1998-04-07 | 2000-05-26 | Sanofi Sa | Utilisation de derives d'aminothiazole pour la preparation de medicaments pour le traitement des maladies entrainant une demyelinisation |
| ATE373660T1 (de) * | 2002-03-25 | 2007-10-15 | Merck & Co Inc | Heterocyclische beta-aminoverbindungen als inhibitoren der dipeptidylpeptidase zur behandlung bzw. prävention von diabetes |
| GB201321735D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| CN113292873B (zh) * | 2021-05-11 | 2022-03-08 | 重庆工程职业技术学院 | 一种煤矿矿井巷道喷涂材料及其制备方法 |
| MX2024009216A (es) * | 2022-01-28 | 2024-08-06 | Insilico Medicine Ip Ltd | Inhibidores de ectonucleotido pirofosfatasa-fosfodiesterasa 1 (enpp1) y usos de los mismos. |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6715600A (fr) * | 1966-12-02 | 1968-06-04 | ||
| US4612323A (en) * | 1983-06-27 | 1986-09-16 | Sumitomo Chemical Company, Limited | Insecticidal and acaricidal derivatives of 1-benzylbenzimidazole |
| US4539332A (en) * | 1983-11-14 | 1985-09-03 | Merck & Co., Inc. | 2,5-Diaryl tetrahydrofurans and analogs thereof as PAF-antagonists |
| JP2556849B2 (ja) * | 1986-02-13 | 1996-11-27 | 三共株式会社 | グリセリン誘導体 |
| US4804658A (en) * | 1986-09-15 | 1989-02-14 | G. D. Searle & Co. | Imidazopyridine derivatives and pharmaceutical compositions |
| US4914108A (en) * | 1988-03-14 | 1990-04-03 | G. D. Searle & Co. | 5-substituted(4,5-c)imidazopyridine compounds which have useful platelet activating factor antagonistic activity |
| AU616508B2 (en) * | 1988-03-15 | 1991-10-31 | G.D. Searle & Co. | Benzyl-imidazo (4,5-c) pyridines |
| GB8904174D0 (en) * | 1989-02-23 | 1989-04-05 | British Bio Technology | Compounds |
| US5157026A (en) * | 1989-05-30 | 1992-10-20 | Merck & Co., Inc. | Oxo-purines as angiotensin II antagonists |
| IL94390A (en) * | 1989-05-30 | 1996-03-31 | Merck & Co Inc | The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them |
| IE70217B1 (en) * | 1990-08-15 | 1996-10-30 | British Bio Technology | Benzimidazole derivatives process for their preparation and application |
-
1991
- 1991-08-14 PT PT98674A patent/PT98674B/pt not_active IP Right Cessation
- 1991-08-14 IE IE287491A patent/IE912874A1/en not_active IP Right Cessation
- 1991-08-15 ES ES91914362T patent/ES2123511T3/es not_active Expired - Lifetime
- 1991-08-15 AU AU84216/91A patent/AU657920B2/en not_active Ceased
- 1991-08-15 JP JP51367591A patent/JP3218243B2/ja not_active Expired - Fee Related
- 1991-08-15 DE DE69130362T patent/DE69130362T2/de not_active Expired - Fee Related
- 1991-08-15 EP EP91914362A patent/EP0543861B1/fr not_active Expired - Lifetime
- 1991-08-15 NZ NZ239408A patent/NZ239408A/en unknown
- 1991-08-15 HU HU9300390A patent/HUT65983A/hu unknown
- 1991-08-15 CA CA002088742A patent/CA2088742C/fr not_active Expired - Fee Related
- 1991-08-15 WO PCT/GB1991/001391 patent/WO1992003422A1/fr active IP Right Grant
- 1991-08-15 US US07/745,471 patent/US5200412A/en not_active Expired - Lifetime
- 1991-08-15 AT AT91914362T patent/ATE172195T1/de active
- 1991-08-15 KR KR1019930700436A patent/KR930701412A/ko not_active Application Discontinuation
- 1991-08-31 TW TW080106909A patent/TW199860B/zh active
-
1992
- 1992-12-14 US US07/990,273 patent/US5276153A/en not_active Expired - Fee Related
-
1993
- 1993-02-12 FI FI930633A patent/FI930633A/fi not_active Application Discontinuation
- 1993-02-12 NO NO930499A patent/NO301229B1/no unknown
-
1994
- 1994-07-01 HU HU94P/P00003P patent/HU210218A9/hu unknown
-
1997
- 1997-08-29 NO NO973981A patent/NO973981D0/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI930633A0 (fi) | 1993-02-12 |
| PT98674B (pt) | 1999-01-29 |
| CA2088742C (fr) | 2002-02-12 |
| EP0543861A1 (fr) | 1993-06-02 |
| JPH06500085A (ja) | 1994-01-06 |
| NO973981D0 (no) | 1997-08-29 |
| HU210218A9 (en) | 1995-02-28 |
| US5276153A (en) | 1994-01-04 |
| ATE172195T1 (de) | 1998-10-15 |
| ES2123511T3 (es) | 1999-01-16 |
| US5200412A (en) | 1993-04-06 |
| FI930633A (fi) | 1993-04-07 |
| KR930701412A (ko) | 1993-06-11 |
| EP0543861B1 (fr) | 1998-10-14 |
| HU9300390D0 (en) | 1993-04-28 |
| NO930499L (no) | 1993-04-14 |
| NO930499D0 (no) | 1993-02-12 |
| HUT65983A (en) | 1994-08-29 |
| AU657920B2 (en) | 1995-03-30 |
| PT98674A (pt) | 1992-07-31 |
| IE912874A1 (en) | 1992-02-26 |
| NZ239408A (en) | 1993-12-23 |
| CA2088742A1 (fr) | 1992-02-16 |
| DE69130362T2 (de) | 1999-04-01 |
| AU8421691A (en) | 1992-03-17 |
| WO1992003422A1 (fr) | 1992-03-05 |
| NO973981L (no) | 1993-04-14 |
| TW199860B (fr) | 1993-02-11 |
| JP3218243B2 (ja) | 2001-10-15 |
| DE69130362D1 (de) | 1998-11-19 |
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