IE58359B1 - New phenol derivatives, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions - Google Patents

New phenol derivatives, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions

Info

Publication number: IE58359B1
Authority: IE; Ireland
Prior art keywords: formula; group; same meaning; compound; radical
Prior art date: 1985-05-23

Application number

IE74586A

Other languages

English (en)

Other versions

IE860745L (en

Original Assignee

Gruenenthal Chemie

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1985-05-23

Filing date

1986-03-21

Publication date

1993-09-08

1986-03-21 Application filed by Gruenenthal Chemie filed Critical Gruenenthal Chemie

1986-11-24 Publication of IE860745L publication Critical patent/IE860745L/en

1993-09-08 Publication of IE58359B1 publication Critical patent/IE58359B1/en

Links

150000001875 compounds Chemical class 0.000 title claims description 203
238000000034 method Methods 0.000 title claims description 65
239000000203 mixture Substances 0.000 title claims description 54
150000002989 phenols Chemical class 0.000 title claims description 21
230000008569 process Effects 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title claims description 13
239000008194 pharmaceutical composition Substances 0.000 title description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
-1 alkyl radical Chemical class 0.000 claims description 44
238000006243 chemical reaction Methods 0.000 claims description 42
229910052739 hydrogen Inorganic materials 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 32
150000003254 radicals Chemical class 0.000 claims description 31
150000003839 salts Chemical class 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 23
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 19
125000006239 protecting group Chemical group 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
230000015572 biosynthetic process Effects 0.000 claims description 16
150000002431 hydrogen Chemical class 0.000 claims description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 14
230000009471 action Effects 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 11
239000002904 solvent Substances 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
230000003197 catalytic effect Effects 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 10
150000007513 acids Chemical class 0.000 claims description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
150000001768 cations Chemical class 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
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
239000003054 catalyst Substances 0.000 claims description 7
229910052763 palladium Inorganic materials 0.000 claims description 7
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 7
229910052708 sodium Inorganic materials 0.000 claims description 7
239000011734 sodium Substances 0.000 claims description 7
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
229910052744 lithium Inorganic materials 0.000 claims description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 5
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 5
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 5
239000007788 liquid Substances 0.000 claims description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
238000009835 boiling Methods 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 4
230000009467 reduction Effects 0.000 claims description 4
150000003512 tertiary amines Chemical class 0.000 claims description 4
238000011282 treatment Methods 0.000 claims description 4
239000011230 binding agent Substances 0.000 claims description 3
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
238000007911 parenteral administration Methods 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000005270 trialkylamine group Chemical group 0.000 claims description 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
239000002775 capsule Substances 0.000 claims description 2
239000007795 chemical reaction product Substances 0.000 claims description 2
150000001879 copper Chemical class 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
230000003111 delayed effect Effects 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
229910052751 metal Inorganic materials 0.000 claims description 2
239000002184 metal Substances 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
230000035515 penetration Effects 0.000 claims description 2
239000007921 spray Substances 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 4
239000004480 active ingredient Substances 0.000 claims 3
239000000010 aprotic solvent Substances 0.000 claims 2
VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical class [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
239000000463 material Substances 0.000 claims 1
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
229910052700 potassium Inorganic materials 0.000 claims 1
239000011591 potassium Substances 0.000 claims 1
125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
238000002156 mixing Methods 0.000 abstract description 2
230000001105 regulatory effect Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 288
239000000243 solution Substances 0.000 description 87
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
239000000047 product Substances 0.000 description 66
238000005160 1H NMR spectroscopy Methods 0.000 description 65
239000003208 petroleum Substances 0.000 description 65
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 61
238000004440 column chromatography Methods 0.000 description 60
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
229910052757 nitrogen Inorganic materials 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
238000003756 stirring Methods 0.000 description 18
239000013078 crystal Substances 0.000 description 17
239000000126 substance Substances 0.000 description 17
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
239000012043 crude product Substances 0.000 description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 12
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 12
238000004809 thin layer chromatography Methods 0.000 description 12
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 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
230000005764 inhibitory process Effects 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
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 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 9
239000007858 starting material Substances 0.000 description 9
102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 8
108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
238000009472 formulation Methods 0.000 description 8
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
238000005481 NMR spectroscopy Methods 0.000 description 7
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
239000002585 base Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
206010030113 Oedema Diseases 0.000 description 6
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 6
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
229960001760 dimethyl sulfoxide Drugs 0.000 description 6
238000012360 testing method Methods 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
150000002617 leukotrienes Chemical class 0.000 description 5
239000012071 phase Substances 0.000 description 5
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
150000003180 prostaglandins Chemical class 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
229940114079 arachidonic acid Drugs 0.000 description 4
235000021342 arachidonic acid Nutrition 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 3
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
SXYFAZGVNNYGJQ-UHFFFAOYSA-M chloromethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCl)C1=CC=CC=C1 SXYFAZGVNNYGJQ-UHFFFAOYSA-M 0.000 description 3
238000001816 cooling Methods 0.000 description 3
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000005457 ice water Substances 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
WMWSRIHFAVOHSW-UHFFFAOYSA-N lithium;ethane-1,2-diamine;ethyne Chemical compound [Li+].[C-]#C.NCCN WMWSRIHFAVOHSW-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
229940094443 oxytocics prostaglandins Drugs 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
LVWSZGCVEZRFBT-UHFFFAOYSA-N 1,7-dibromoheptane Chemical compound BrCCCCCCCBr LVWSZGCVEZRFBT-UHFFFAOYSA-N 0.000 description 2
AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
OPHQOIGEOHXOGX-UHFFFAOYSA-N 3,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC OPHQOIGEOHXOGX-UHFFFAOYSA-N 0.000 description 2
PCYGLFXKCBFGPC-UHFFFAOYSA-N 3,4-Dihydroxy hydroxymethyl benzene Natural products OCC1=CC=C(O)C(O)=C1 PCYGLFXKCBFGPC-UHFFFAOYSA-N 0.000 description 2
239000005995 Aluminium silicate Substances 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
229910052684 Cerium Inorganic materials 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
230000005526 G1 to G0 transition Effects 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
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239000011981 lindlar catalyst Substances 0.000 description 1
150000002641 lithium Chemical group 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000000155 melt Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
238000012544 monitoring process Methods 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
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
229960004838 phosphoric acid Drugs 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
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RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
PDFGPBXCEASWLG-UHFFFAOYSA-N propyl 2-hydroxy-5-iodobenzoate Chemical compound CCCOC(=O)C1=CC(I)=CC=C1O PDFGPBXCEASWLG-UHFFFAOYSA-N 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
210000001625 seminal vesicle Anatomy 0.000 description 1
229910000077 silane Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
201000010653 vesiculitis Diseases 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
- G05D23/00—Control of temperature
- G05D23/01—Control of temperature without auxiliary power
- G05D23/13—Control of temperature without auxiliary power by varying the mixing ratio of two fluids having different temperatures
- G05D23/1393—Control of temperature without auxiliary power by varying the mixing ratio of two fluids having different temperatures characterised by the use of electric means
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
- G05D23/00—Control of temperature
- G05D23/185—Control of temperature with auxiliary non-electric power
- G05D23/1858—Control of temperature with auxiliary non-electric power by varying the mixing ratio of fluids having different temperatures

Landscapes

Engineering & Computer Science (AREA)
Physics & Mathematics (AREA)
General Physics & Mathematics (AREA)
Automation & Control Theory (AREA)
Power Engineering (AREA)
Multiple-Way Valves (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Domestic Plumbing Installations (AREA)
Control Of Temperature (AREA)
Domestic Hot-Water Supply Systems And Details Of Heating Systems (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Bidet-Like Cleaning Device And Other Flush Toilet Accessories (AREA)

IE74586A 1985-05-23 1986-03-21 New phenol derivatives, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions IE58359B1 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19853518644 DE3518644A1 (de)	1985-05-23	1985-05-23	Sanitaer-mischarmatur

Publications (2)

Publication Number	Publication Date
IE860745L IE860745L (en)	1986-11-24
IE58359B1 true IE58359B1 (en)	1993-09-08

Family

ID=6271497

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE74586A IE58359B1 (en)	1985-05-23	1986-03-21	New phenol derivatives, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions

Country Status (8)

Country	Link
BE (1)	BE904792A (de)
DE (1)	DE3518644A1 (de)
DK (1)	DK162794C (de)
FI (1)	FI82298C (de)
FR (1)	FR2582418B1 (de)
IE (1)	IE58359B1 (de)
IT (1)	IT1188686B (de)
NL (1)	NL8601310A (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8720431D0 (en) *	1987-08-28	1987-10-07	Armitage Shanks Ltd	Valves for controlling water supply
DE19961183A1 (de)	1999-12-18	2001-07-26	Innotech Electronic Gmbh	Elektronischer Mischwasserbereiter und Verfahren zur Mischwasserbereitung
GB2405224B (en) *	2001-01-30	2005-05-25	Aqualisa Products Ltd	Water mixing valve apparatus
DE102018104571A1 (de)	2018-02-28	2019-08-29	Schell Gmbh & Co. Kg	Mischarmatur

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3482624A (en) *	1967-01-13	1969-12-09	Itt	Three-way valves
DE2323841C3 (de) *	1973-05-11	1978-08-24	Heinrich 6508 Alzey Arndt	Mischventil mit je einem elektromechanisch betätigten Zuflußventil in der Kalt- und in der Heißwasserzufuhrleitung
DE2836698A1 (de) *	1978-08-22	1980-03-06	Hansa Metallwerke Ag	Elektronisch gesteuerte mischarmatur, insbesondere im sanitaerbereich
DE3030765C2 (de) *	1980-08-14	1985-09-26	Friedrich Grohe Armaturenfabrik Gmbh & Co, 5870 Hemer	Elektronisch geregeltes Mischventil
GB2143343A (en) *	1983-07-13	1985-02-06	Standard Telephones Cables Ltd	Thermostatically controlled mixer
DE3430176A1 (de) *	1983-08-25	1985-03-21	Harley Glen Iris Victoria Pizzey	Vorrichtung zum mischen von heissem und kaltem wasser

1985
- 1985-05-23 DE DE19853518644 patent/DE3518644A1/de active Granted
1986
- 1986-03-21 IE IE74586A patent/IE58359B1/en not_active IP Right Cessation
- 1986-05-19 FI FI862072A patent/FI82298C/fi not_active IP Right Cessation
- 1986-05-20 BE BE0/216682A patent/BE904792A/fr not_active IP Right Cessation
- 1986-05-21 FR FR8607238A patent/FR2582418B1/fr not_active Expired - Fee Related
- 1986-05-22 NL NL8601310A patent/NL8601310A/nl not_active Application Discontinuation
- 1986-05-22 DK DK238686A patent/DK162794C/da not_active IP Right Cessation
- 1986-05-22 IT IT20518/86A patent/IT1188686B/it active

Also Published As

Publication number	Publication date
FI862072A0 (fi)	1986-05-19
DK162794C (da)	1992-04-27
FI862072A (fi)	1986-11-24
IT1188686B (it)	1988-01-20
FR2582418A1 (fr)	1986-11-28
FI82298C (fi)	1991-02-11
IE860745L (en)	1986-11-24
IT8620518A0 (it)	1986-05-22
BE904792A (fr)	1986-09-15
NL8601310A (nl)	1986-12-16
DE3518644A1 (de)	1986-11-27
FI82298B (fi)	1990-10-31
DK238686D0 (da)	1986-05-22
DK238686A (da)	1986-11-24
DK162794B (da)	1991-12-09
FR2582418B1 (fr)	1995-04-14
IT8620518A1 (it)	1987-11-22
DE3518644C2 (de)	1989-01-26

Legal Events

Date	Code	Title	Description
1996-12-11	MM4A	Patent lapsed

Publication	Publication Date	Title
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US4751240A (en)	1988-06-14	Phenol derivatives
EP0106565A1 (de)	1984-04-25	Leukotrienantagonisten, deren Herstellung und diese enthaltende Zusammensetzungen
FI85368B (fi)	1991-12-31	Foerfarande foer framstaellning av terapeutiskt anvaendbara syklopentyletrar.
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EP0107618B1 (de)	1986-07-16	N-substituierte-2-(1-Imidazolyl)-Indole
IE58359B1 (en)	1993-09-08	New phenol derivatives, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions
JPH029031B2 (de)	1990-02-28
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HU196163B (en)	1988-10-28	Process for production of derivatives of bensoic acid and medical preparatives containing them as active substance
US4094896A (en)	1978-06-13	1-Alkoximino-2-(ω-substituted-alkyl)-2-cyclopentenes