FI95252B - Förfarande för framställning av som läkemedel användbara dihydrotianaftalenföreningar - Google Patents
Förfarande för framställning av som läkemedel användbara dihydrotianaftalenföreningar Download PDFInfo
- Publication number
- FI95252B FI95252B FI870373A FI870373A FI95252B FI 95252 B FI95252 B FI 95252B FI 870373 A FI870373 A FI 870373A FI 870373 A FI870373 A FI 870373A FI 95252 B FI95252 B FI 95252B
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- Finland
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- compound
- methyl
- singlet
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 341
- 238000002360 preparation method Methods 0.000 title claims description 121
- 238000000034 method Methods 0.000 title claims description 108
- 230000008569 process Effects 0.000 title claims description 13
- 239000003814 drug Substances 0.000 title claims description 5
- 229940079593 drug Drugs 0.000 title 1
- 150000002148 esters Chemical class 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 14
- 150000001408 amides Chemical class 0.000 claims abstract description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 11
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 7
- -1 methylene, ethylene- Chemical class 0.000 claims description 132
- 238000006243 chemical reaction Methods 0.000 claims description 130
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 65
- 239000002253 acid Substances 0.000 claims description 28
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims description 9
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 abstract description 17
- 230000015572 biosynthetic process Effects 0.000 abstract description 15
- 125000000217 alkyl group Chemical group 0.000 abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 11
- 238000011282 treatment Methods 0.000 abstract description 8
- 239000001257 hydrogen Substances 0.000 abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 125000004450 alkenylene group Chemical group 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 230000001732 thrombotic effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 216
- 239000000243 solution Substances 0.000 description 153
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 148
- 239000000203 mixture Substances 0.000 description 124
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 104
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 70
- 239000000126 substance Substances 0.000 description 70
- 239000011541 reaction mixture Substances 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 64
- 238000001704 evaporation Methods 0.000 description 58
- 230000008020 evaporation Effects 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 48
- 239000002904 solvent Substances 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000011780 sodium chloride Substances 0.000 description 32
- 239000003480 eluent Substances 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 238000010898 silica gel chromatography Methods 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 25
- 229920006395 saturated elastomer Polymers 0.000 description 25
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 238000000921 elemental analysis Methods 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 20
- 239000000843 powder Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
- 229960000583 acetic acid Drugs 0.000 description 17
- 238000000862 absorption spectrum Methods 0.000 description 16
- 239000005457 ice water Substances 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- 239000012279 sodium borohydride Substances 0.000 description 16
- 229910000033 sodium borohydride Inorganic materials 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- 229910052708 sodium Inorganic materials 0.000 description 15
- 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 14
- 238000004440 column chromatography Methods 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000007796 conventional method Methods 0.000 description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 10
- 150000002170 ethers Chemical class 0.000 description 10
- 150000002642 lithium compounds Chemical class 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- 150000007942 carboxylates Chemical class 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- 150000004795 grignard reagents Chemical class 0.000 description 9
- 230000003301 hydrolyzing effect Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 229910052721 tungsten Inorganic materials 0.000 description 9
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 231100000989 no adverse effect Toxicity 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 7
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 7
- 229910003446 platinum oxide Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000007818 Grignard reagent Substances 0.000 description 6
- 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 6
- 238000009835 boiling Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- 238000007239 Wittig reaction Methods 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- XQGZSYKGWHUSDH-UHFFFAOYSA-N dazoxiben Chemical compound C1=CC(C(=O)O)=CC=C1OCCN1C=NC=C1 XQGZSYKGWHUSDH-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
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- 238000010438 heat treatment Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
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- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 5
- 229960002218 sodium chlorite Drugs 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 229910052727 yttrium Inorganic materials 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 4
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 4
- 102000003960 Ligases Human genes 0.000 description 4
- 108090000364 Ligases Proteins 0.000 description 4
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- 208000007536 Thrombosis Diseases 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 238000010533 azeotropic distillation Methods 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 4
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- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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- 150000003855 acyl compounds Chemical class 0.000 description 3
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- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 3
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- 150000004678 hydrides Chemical class 0.000 description 3
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- 150000003180 prostaglandins Chemical class 0.000 description 3
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- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 2
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
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- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
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- 241000124008 Mammalia Species 0.000 description 2
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 102200043753 rs104893640 Human genes 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- XNRNNGPBEPRNAR-JQBLCGNGSA-N thromboxane B2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1OC(O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O XNRNNGPBEPRNAR-JQBLCGNGSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000012991 xanthate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (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)
- Hematology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Liquid Crystal Substances (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (4)
1. Förfarande för framställning av som läkemedel användbara dihydrotia-naftenföreningar med formeln (I) : 5 » 10 där: den ena av grupperna A1 och A2 avser en grupp med formeln -Z-Y där Y 15 avser en imidazolyl- eller pyridylgrupp och Z avser en metylen-, etylen-, trimetylen- eller vinylengrupp eller en metylen-, etylen-, trimetylen- eller vinylengrupp med ätminstone en substituent som är vald frän en grupp som bestär av -C4 alkylgrupper, C3-C6 cykloalkylgrupper, fenyl- eller naftylgrupper, substituerade fenylgrupper med ätminstone en 20 substituent som är en C1-C<) alkylgrupp, C1-C4 alkoxigrupp, en halogen-atom, nitrogrupp, cyanogrupp eller aminogrupp; och tienylgrupper; den andra av grupperna A1 och A2 avser en grupp med formeln -W-C00H, där W avser en direkt bindning, en metylengrupp, en metingrupp, med den 25 förutsättningen att W endast avser nämnda metingrupp dä A1 avser nämnda grupp med formeln -Z-Y; A2 är vid 5- eller 6-positionen i tianaftensystemet; 30 varje bruten linje avser en enkel eller dubbel kol-kolbindning mellan 4-och 5- eller 6- och 7-positionerna, med den förutsättningen att, dä A2 är vid 5-positionen, finns det en enkelbindning mellan 6- och 7-positionerna, och att, dä A2 är vid 6-positionen, finns det en enkelbindning mellan 4- och 5-positionerna; 35 och farmaceutiskt acceptabla salter, amider och estrar därav, k ä n -* netecknat av att man läter en förening med formeln (II): 95252 "" 7 (där de brutna linjerna är definierade som ovan; den ena av grupperna B1 10 och B2 avser gruppen med formeln -W-C00H som representeras av A1 och A2 eller en sadan grupp där karboxigruppen är skyddad; och den andra av grupperna B1 och B2 avser en reaktiv grupp säsom hydroxi-, halogen-, lägre alkansulfonyloxi- eller arylsulfonyloxigrupp eller är ett karbo-nylderivat av Z, där Z är definierad som ovan) reagera med en 15 imidazolyl- eller pyridylförening för att introducera imidazolyl- eller pyridylgruppen som representeras av Y tili nämnda förening och, om nöd-vändigt, den resulterande föreningen utsätts för reduktion och/eller hydrolys och/eller avlägsnande av skyddet, och salterna framställs, da sä önskas, pä känt sätt genom att bringa i kontakt med en lämplig syra 20 eller bas.
2. Förfarande enligt patentkrav 1, kännetecknat därav, att reagenterna och reaktionsförhällandena väljes för att framställa: « I. 25 4,5,6,7-tetrahydro-2-(1-imidazolyl)metyltianaften-6-karboxylsyra eller ett farmaceutiskt acceptabelt salt, ester eller amid därav.
3. Förfarande enligt patentkrav 1, kännetecknat därav, att reagenterna och reaktionsförhällandena väljes för att framställa: 30 4,5-dihydro-2 -(1-imidazolyl)metyltianaften-6-karboxylsyra eller ett farmaceutiskt acceptabelt salt, ester eller amid därav.
4. Förfarande enligt patentkrav 1, kännetecknat därav, att 35 reagenterna och reaktionsförhällandena väljes för att framställa: il 95252 4,5,6,7-tetrahydro-2-(1-imidazolyl)metyltianaften-5-karboxylsyra eller ett farmaceutiskt acceptabelt salt, ester eller amid därav. » » t
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1650186 | 1986-01-28 | ||
| JP1650186 | 1986-01-28 | ||
| JP61228769A JPH0696577B2 (ja) | 1986-09-27 | 1986-09-27 | チアナフテン誘導体およびその製造法 |
| JP22876986 | 1986-09-27 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI870373A0 FI870373A0 (sv) | 1987-01-28 |
| FI870373A FI870373A (sv) | 1987-07-29 |
| FI95252B true FI95252B (sv) | 1995-09-29 |
| FI95252C FI95252C (sv) | 1996-01-10 |
Family
ID=26352848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI870373A FI95252C (sv) | 1986-01-28 | 1987-01-28 | Förfarande för framställning av som läkemedel användbara dihydrotianaftalenföreningar |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US4847272A (sv) |
| EP (1) | EP0240107B1 (sv) |
| KR (1) | KR920002129B1 (sv) |
| CN (1) | CN1023013C (sv) |
| AT (1) | ATE66476T1 (sv) |
| AU (1) | AU591750B2 (sv) |
| CA (1) | CA1301172C (sv) |
| DE (1) | DE3772235D1 (sv) |
| DK (1) | DK45987A (sv) |
| ES (1) | ES2038654T3 (sv) |
| FI (1) | FI95252C (sv) |
| HU (1) | HU207313B (sv) |
| IE (1) | IE59655B1 (sv) |
| NO (1) | NO166644C (sv) |
| SU (1) | SU1739848A3 (sv) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2990563A (en) * | 1958-12-03 | 1961-07-04 | Guild Molders | Applicator device |
| EP0347378A1 (de) * | 1988-06-13 | 1989-12-20 | Ciba-Geigy Ag | Imidazol-Derivate |
| EP0457716A1 (de) * | 1990-04-20 | 1991-11-21 | Ciba-Geigy Ag | Naphthalinderivate |
| TW224461B (sv) * | 1990-09-18 | 1994-06-01 | Ciba Geigy Ag | |
| US5364869A (en) * | 1992-03-09 | 1994-11-15 | Abbott Laboratories | Heterocycle-substituted benzyaminopyridine angiotensin II receptor antagonists |
| DE69528860T2 (de) * | 1994-06-30 | 2003-07-10 | Kuraray Co., Ltd | 1-Amino-2-Cyclohexenderivate und Verfahren zu ihrer Herstellung |
| WO1999064425A1 (en) * | 1998-06-09 | 1999-12-16 | Neurogen Corporation | Substituted thienocycloalkylpyrazoles: dopamine receptor subtype specific ligands |
| CN1089122C (zh) * | 1999-09-03 | 2002-08-14 | 杨继玉 | 一种制冷机芯钢管内壁表面处理方法 |
| WO2009105140A2 (en) | 2007-12-11 | 2009-08-27 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties |
| WO2010025425A1 (en) * | 2008-08-29 | 2010-03-04 | Angros Lee H | Multiplexed microscope slide staining apparatus |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK471479A (da) | 1978-12-13 | 1980-06-14 | Pfizer | Fremgangsmaade til fremstilling af imidazolderivater og salte deraf |
| GR75101B (sv) * | 1980-10-23 | 1984-07-13 | Pfizer | |
| ZA825413B (en) * | 1981-08-26 | 1983-06-29 | Pfizer | Thromboxane synthetase inhibitors, processes for their production, and pharmaceutical compositions comprising them |
| US4611059A (en) * | 1982-10-12 | 1986-09-09 | The Upjohn Company | Pyridyl-substituted benzothiophenes |
-
1987
- 1987-01-27 SU SU874028995A patent/SU1739848A3/ru active
- 1987-01-27 US US07/007,375 patent/US4847272A/en not_active Expired - Lifetime
- 1987-01-27 NO NO870319A patent/NO166644C/no not_active IP Right Cessation
- 1987-01-27 KR KR1019870000639A patent/KR920002129B1/ko not_active IP Right Cessation
- 1987-01-28 EP EP87300759A patent/EP0240107B1/en not_active Expired - Lifetime
- 1987-01-28 DK DK045987A patent/DK45987A/da not_active Application Discontinuation
- 1987-01-28 IE IE21787A patent/IE59655B1/en not_active IP Right Cessation
- 1987-01-28 AT AT87300759T patent/ATE66476T1/de not_active IP Right Cessation
- 1987-01-28 AU AU68114/87A patent/AU591750B2/en not_active Ceased
- 1987-01-28 CN CN87102672A patent/CN1023013C/zh not_active Expired - Fee Related
- 1987-01-28 HU HU87258A patent/HU207313B/hu not_active IP Right Cessation
- 1987-01-28 ES ES198787300759T patent/ES2038654T3/es not_active Expired - Lifetime
- 1987-01-28 DE DE8787300759T patent/DE3772235D1/de not_active Expired - Fee Related
- 1987-01-28 FI FI870373A patent/FI95252C/sv not_active IP Right Cessation
- 1987-01-28 CA CA000528417A patent/CA1301172C/en not_active Expired - Fee Related
-
1989
- 1989-05-19 US US07/354,984 patent/US5021444A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2038654T3 (es) | 1993-08-01 |
| FI870373A (sv) | 1987-07-29 |
| FI95252C (sv) | 1996-01-10 |
| CN1023013C (zh) | 1993-12-08 |
| NO166644C (no) | 1991-08-21 |
| EP0240107B1 (en) | 1991-08-21 |
| CN87102672A (zh) | 1987-11-04 |
| IE59655B1 (en) | 1994-03-09 |
| AU6811487A (en) | 1987-07-30 |
| ATE66476T1 (de) | 1991-09-15 |
| IE870217L (en) | 1987-07-28 |
| DE3772235D1 (de) | 1991-09-26 |
| HU207313B (en) | 1993-03-29 |
| FI870373A0 (sv) | 1987-01-28 |
| CA1301172C (en) | 1992-05-19 |
| KR870007153A (ko) | 1987-08-17 |
| DK45987D0 (da) | 1987-01-28 |
| US4847272A (en) | 1989-07-11 |
| EP0240107A1 (en) | 1987-10-07 |
| NO870319D0 (no) | 1987-01-27 |
| KR920002129B1 (ko) | 1992-03-12 |
| NO870319L (no) | 1987-07-29 |
| AU591750B2 (en) | 1989-12-14 |
| HUT43593A (en) | 1987-11-30 |
| NO166644B (no) | 1991-05-13 |
| SU1739848A3 (ru) | 1992-06-07 |
| DK45987A (da) | 1987-07-29 |
| US5021444A (en) | 1991-06-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB | Publication of examined application | ||
| MM | Patent lapsed |
Owner name: SANKYO COMPANY LIMITED |