PL80550B1 - 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] - Google Patents
1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] Download PDFInfo
- Publication number
- PL80550B1 PL80550B1 PL1970142704A PL14270470A PL80550B1 PL 80550 B1 PL80550 B1 PL 80550B1 PL 1970142704 A PL1970142704 A PL 1970142704A PL 14270470 A PL14270470 A PL 14270470A PL 80550 B1 PL80550 B1 PL 80550B1
- Authority
- PL
- Poland
- Prior art keywords
- formula
- hydroxy
- cyanophenoxy
- compound
- salts
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 title claims description 7
- MAXGKGLXEAPYGY-UHFFFAOYSA-N 2-[3-(ethylamino)-2-hydroxypropoxy]benzonitrile Chemical compound CCNCC(O)COC1=CC=CC=C1C#N MAXGKGLXEAPYGY-UHFFFAOYSA-N 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 7
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000013543 active substance Substances 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- -1 epoxide compound Chemical class 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- TUMNHQRORINJKE-UHFFFAOYSA-N 1,1-diethylurea Chemical compound CCN(CC)C(N)=O TUMNHQRORINJKE-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000005662 Paraffin oil Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- MUFFOLPYTIIKNT-UHFFFAOYSA-N 2-(3-chloro-2-hydroxypropoxy)benzonitrile Chemical compound ClCC(O)COC1=CC=CC=C1C#N MUFFOLPYTIIKNT-UHFFFAOYSA-N 0.000 description 1
- BIJYXIOVXFBJEP-UHFFFAOYSA-N 2-(oxiran-2-ylmethoxy)benzonitrile Chemical compound N#CC1=CC=CC=C1OCC1OC1 BIJYXIOVXFBJEP-UHFFFAOYSA-N 0.000 description 1
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- DFJAVDXYHCJASO-UHFFFAOYSA-N Cl.C(#N)C1=C(OCC(CNCC)O)C=CC=C1 Chemical compound Cl.C(#N)C1=C(OCC(CNCC)O)C=CC=C1 DFJAVDXYHCJASO-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000008753 Papaver somniferum Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000003944 halohydrins Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012731 long-acting form Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000012749 thinning agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 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
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 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
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/275—Nitriles; Isonitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/53—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Uprawniony z patentu: C. H. Boehringer Sohn, Ingelheim n. Renem (Republika Federalna Niemiec) Sposób wytwarzania l-/2-cyjanofenoksy/-2-hydroksy-3-etyloaminopropanu Przedmiotem wynalazku jest sposób wytwarza¬ nia nowego zwiazku l-/2-cyjanofenoksy/-2-hydro- ksy-3-etyloaminopropanu o wzorze 1 i jego soli addycyjnych z kwasami, o wlasciwosciach farma¬ kologicznych.Wedlug wynalazku nowy zwiazek wytwarza sie przez reakcje zwiazku o wzorze 2, w którym Z oznacza grupe o wzorze 2a lub grupe o wzorze -CHOH-CH£-Hal, w którym Hal oznacza atom chlo¬ rowca, z N,N-dwuetylomocznika o wzorze 3. Po¬ wstaje przy tym bezposrednio w jednym etapie po¬ zadany zwiazek. Reakcje prowadzi sie korzystnie w wysokowrzacym, obojetnym rozpuszczalniku organicznym, takim jak tetralina, dekalina, benzo- nitryl, olej parafinowy lub chlorowane zwiazki aro- ifiatyczne, albo tez przez stopienie w temperatu¬ rze 150—220°C, korzystnie w temperaturze 180— —200°C.Zwiazki wyjsciowe sa czesciowo juz znane, cze¬ sciowo zas moga byc uzyskane znanymi sposoba¬ mi, przy czym najczesciej wychodzi sie z 1-/2- -cyjanofenoksy/ - 2,3 - epoksypropanu. Ten zwiazek epoksydowy odpowiadajacy wzorowi ogólnemu 2 mozna wytwarzac droga reakcji 2-hydroksy-benzo- nitrylu z epichlorohydryna w obecnosci wodoro¬ tlenku sodowego i przeksztalcenie w chlorowco- hydryne o wzorze 2 przez poddanie reakcji z od¬ powiednim kwasem chlorowcowodorowym.Zwiazek wytworzony sposobem wedlug wyna¬ lazku ma w grupie -CHOH- asymetryczny atom 10 15 20 25 30 wegla i dlatego wystepuje w postaci racematu, jak równiez optycznie aktywnych antypodów. Optycznie aktywne zwiazki mozna otrzymac w ten sposób, ze albo wychodzi sie z optycznie aktywnych zwiazków wyjsciowych, albo tez otrzymany racemat racemat rozszczepia sie na antypody optyczne w znany spo¬ sób, np. za pomoca kwasu dwubenzoilowinowego lub bromokamforosulfonowego.Zwiazek wytworzony sposobem wedlug wynalaz¬ ku mozna przeprowadzac w znany sposób w jego fizjologicznie dopuszczalne sole addycyjne z kwa¬ sami. Odpowiednimi kwasami sa np. kwas solny, kwas bromowodorowy, kwas siarkowy, kwas me- tanosulfonowy, kwas maleinowy, kwas octowy, kwas szczawiowy, kwas mlekowy, kwas winowy lub 8-chloroteofilina.Zwiazek o wzorze 1 wytworzony sposobem we¬ dlug wynalazku, ewentualnie jego fizjologicznie dopuszczalne sole addycyjne z kwasami maja cenne wlasciwosci terapeutyczne, zwlaszcza dzialanie 0- -adrenolityczne i w zwiazku z tym moga byc sto¬ sowane np. w leczeniu lub zapobieganiu schorzen naczyn wiencowych serca i w leczeniu arytmii serca u ludzi, w szczególnosci tachykardii czyli czestoskurczu. W doswiadczeniach na zwierzetach, swinkach morskich, odnosnie dzialania na zwolnie¬ nie czynnosci serca i odnosnie dzialania antagoni- styczego aludryny czyli l-/3,4-dwuhydroksyfenyk/- -l-hydroksy-2-izopropyloaminoetanu, nowy zwiazek okazal sie znacznie bardziej skuteczny, a przy tym 80 5503 równiez mniej toksyczny, niz znany l-/l-naftoksy/- -2-hydroksy-3-izopropyloaminopropan.Dawka jednostkowa zwiazku otrzymanego sposo¬ bem wedlug wjrnalazku wynosi 1—150 mg; ko¬ rzystnie 5—50 mg doustnie lub 1—20 mg pozaje- litowo.Preparaty galenowe zawierajace zwiazki wytwo¬ rzone sposobem wedlug wynalazku maja postacie takie, jak roztwory, emulsje, tabletki, drazetki lub postacie o przedluzonym dzialaniu i sporzadza sie je w znany sposób przy uzyciu srodków pomocni¬ czych, nosników, srodków rozsadzajacych, wiaza¬ cych, pokrywajacych lub poslizgowych, substancji nadajacych «mak, srodków slodzacych, srodków dla uzyakarria efektu przedluzonego dzialania lub srod¬ ków (ulatwiajacych rozpuszczanie. Zwiazek otrzy¬ many sposobem wedlug wynalazku moze byc rów¬ niez stosowany w polaczeniu z innymi farmako- dyiiftffliicenie aktywnymi substancjami, takimi jak srodki rozszerzajace naczynia wiencowe, sympa- tykom(imetyka, glukozydy nasercowe lub srodki uspokajajace.Odpowiednio tabletki otrzymuje sie np. przez zmieszanie substancji aktywnych ze znanymi sub¬ stancjami pomocniczymi, np. obojetnymi srodka¬ mi rozcienczajacymi, takimi jak weglan wapnio¬ wy, fosforan wapniowy lub cukier mleczny, srod¬ kami rozsadzajacymi, takimi jak skrobia kukury¬ dziana lub kwas alginowy, srodkami wiazacymi, takimi jak skrobia lub zelatyna, srodkami poslizgo¬ wymi, takimi jak stearynian magnezowy lub talk i/lub srodkami wywolujacymi efekt przedluzonego dzialania, takimi jak karboksypolimetylen, karbo- ksymetyloceluloza, ftalan acetylocelulozy lub octan poliwinylu.Tabletki moga sie równiez skladac z kilku warstw. Odpowiednio moga byc wytworzone dra¬ zetki przez powleczenie rdzeni wytworzonych ana¬ logicznie do tabletek za pomoca srodków zwykle stosowanych w powlokach drazetkarskich, np. ko- lidonu lub szelaku, gumy arabskiej, talku, dwu¬ tlenku tytanu lub cukru. W celu uzyskania efektu przedluzonego dzialania lub dla unikniecia nie¬ zgodnosci rdzen moze sie równiez skladac z kilku warstw. Podobnie takze powloka drazetki, w celu uzyskania efektu przedluzonego dzialania, moze sie skladac z kilku warstw, przy czym moga byc sto¬ sowane substancje pomocnicze wymienione wyzej przy tabletkach.W celu wytworzenia miekkich kapsulek zelaty¬ nowych lub podobnych zamknietych kapsulek, sub¬ stancje aktywna mozna zmieszac z olejem roslin¬ nym. Twarde kapsulki zelatynowe moga zawierac granulaty substancji aktywnej w polaczeniu ze sta lymi sproszowanymi substancjami nosnikowymi, ta¬ kimi jak cukier mleczny, sacharoza, sorbit, mannit, skrobia, np. skrobia ziemniaczana, skrobia kuku¬ rydziana lub amylopektyna, pochodne celulozy lub zelatyna.Syropy z substancjami aktywnymi, otrzymany¬ mi sposobem wedlug wynalazku lub z kombinacji substancji aktywnych, moga jeszcze dodatkowo za wierac srodek slodzacy, taki jak sacharyna, cy- klaminian, gliceryna lub cukier, jak równiez srod- I 550 4 lei poprawiajace smak, np. substancje zapachowe, •takie, jak wanilina lub ekstrakt pomaranczowy.Ponadto moga one zawierac substancje ulatwia¬ jace powstawanie zawiesin lub srodki zageszcza- 5 jace, tkie jak np. sól sodowa karboksymetyloce- lulozy, srodki zwilzajace, np. produkty kondensacji alkoholi tluszczowych z tlenkiem etylenu lub sub¬ stancje konserwujace, takie jak np. p-hydroksy- benzoesany. 10 Roztwory injekcyjne wytwarza sie w znany spo¬ sób, np. przy dodaniu srodków konserwujacych, takich jak p-hydroksybenzoesany, lub stabilizato¬ rów, takich jak kompleksony, po czym napelnia sie nimi fiolki injekcyjne lub ampulki. Roztwory 15 moga równiez zawierac srodki stabilizujace i/lub substancje buforujace.Odpowiednie czopki wytwarza sie np. przez zmie¬ szanie przeznaczonych do tego substancji aktyw¬ nych lub kombinacji substancji aktywnych ze 20 zwyklymi srodkami nosnikowymi, takimi jak obo¬ jetne tluszcze lub glikol polietylenowy ewentu¬ alnie jego pochodne. Mozna równiez wytwarzac doodbytnicze kapsulki zelatynowe, zawierajace aktywna substancje w mieszaninie z olejem roslin- 25 nym lub olejem parafinowym.Nastepujacy przyklad wyjasnia wynalazek nie ograniczajac jego zakresu.Przyklad. Chlorowodorek l-/2-cyjanofenoksy/- -2-hydroksy-3-etyloaminopropanu. 30 Mieszanine 4,23 g (0,02 mola) l-/2-cyjanofenoksy/- -2-hydroksy-3-chloropropanu, 4,6 g (0,04 mola) N.N^dwuetylomocznika i 20 ml tetraliny ogrze¬ wa sie w ciagu 30 minut w temperaturze 195— —200°C. Po oziebieniu rozciencza sie eterem i wy- 35 trzasa dwukrotnie z 10 ml In roztworu HC1. Po¬ laczone fazy HC1 przemywa sie jeden raz eterem i alkalizuje za pomoca NaOH. Wydzielajacy sie olej rozpuszcza sie w eterze. Roztwór eterowy prze¬ mywa sie H20, osusza MgS04 i zageszcza. Pozosta- 40 losc przekrystalizowuje sie z mieszaniny octan etylu/eter naftowy i zasade wytraca sie w postaci chlorowodorku przez dodanie eterowego roztworu HC1. Temperatura topnienia: 132—134°C, po prze- krystalizowaniu z mieszaniny etanol/eter. 45 PL PL PL PL PL PL PL PL PL
Claims (2)
1. Zastrzezenia patentowe 1. Sposób wytwarzania l-/2-cyjanofenoksy/-2-hy- droksy-3-etyloaminopropanu o wzorze 1, w postaci racemicznej lub optycznie czynnej, znamienny tym, 50 ze zwiazek o wzorze ogólnym 2, w którym Z ozna¬ cza grupe o wzorze 2a lub grupe o wzorze -CHOH- -CH2-Hal, w którym Hal oznacza atom chlorowca, poddaje sie reakcji z NjN^dwuetylomocznikiem o wzorze 3 i ewentualnie uzyskany racemat ewen- S5 tualnie rozszczepia sie na postacie optycznie czynne i/lub zwiazek o wzorze 1 przeprowadza sie w fi¬ zjologicznie dopuszczalne sole addycyjne z kwa¬ sami.
2. Sposób wedlug zastrz. 1, znamienny tym, ze 60 w przypadku wytwarzania optycznie czynnego 1- -/2-cyjanofenoksy/-2-hydroksy-3 - etyloaminopropa- nu i jego soli, racemiczny l-/2-cyjanofenoksy/-2- -hydroksy-3-etyloaminopropan za pomoca kwasów pomocniczych przeprowadza sie w sole diastereo- 65 metryczne, które rozklada sie w znany sposób. \80 550 CN £3-OCH2-CHOH -CH2-NHC2H5 Wzór 1 CN « ^0CH2-Z Wzór 2 CH - CH9 0 Wzór 2a C2H5-NH-C-NHC2H5 0 Wzór 3 PL PL PL PL PL PL PL PL PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1940566A DE1940566C3 (de) | 1969-08-08 | 1969-08-08 | 1- (2-Nitrilophenoxy)-2-hydroxy-3äthylaminopropan, Verfahren zu dessen Herstellung und dieses enthaltende Arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL80550B1 true PL80550B1 (en) | 1975-08-30 |
Family
ID=5742361
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1970174660A PL84519B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174661A PL86937B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174658A PL84398B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174657A PL84339B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174659A PL84520B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174662A PL84357B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174656A PL84341B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970142704A PL80550B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
Family Applications Before (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1970174660A PL84519B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174661A PL86937B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174658A PL84398B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174657A PL84339B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174659A PL84520B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174662A PL84357B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
| PL1970174656A PL84341B1 (en) | 1969-08-08 | 1970-08-07 | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US3732277A (pl) |
| AT (9) | AT303013B (pl) |
| BE (1) | BE754604A (pl) |
| BG (8) | BG16739A3 (pl) |
| CH (1) | CH546223A (pl) |
| CS (8) | CS166734B2 (pl) |
| DE (1) | DE1940566C3 (pl) |
| DK (1) | DK125639B (pl) |
| ES (8) | ES382497A1 (pl) |
| FR (1) | FR2068479B1 (pl) |
| NL (1) | NL171702C (pl) |
| PL (8) | PL84519B1 (pl) |
| RO (8) | RO60083A (pl) |
| SE (1) | SE375303B (pl) |
| SU (1) | SU386506A3 (pl) |
| YU (1) | YU34515B (pl) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT323132B (de) * | 1935-11-15 | 1975-06-25 | Boehringer Sohn Ingelheim | Verfahren zur herstellung von neuen racemischen oder optisch aktiven n,n'-bis-(3-subst.phenoxy-2-hydroxy-1-propyl)-alpha,omega-diaminoalkanen sowie deren saureadditionssalzen |
| GB1231783A (en) * | 1967-05-16 | 1971-05-12 | May & Baker Ltd | Benzene derivatives |
| GB1415505A (en) * | 1972-06-01 | 1975-11-26 | Ici Ltd | Alkanolamine derivatives |
| US4171374A (en) * | 1972-12-15 | 1979-10-16 | Imperial Chemical Industries Limited | Alkanolamine derivatives |
| GB1455116A (en) * | 1972-12-15 | 1976-11-10 | Ici Ltd | Pharmaceutical compositions |
| US4167581A (en) * | 1972-12-15 | 1979-09-11 | Imperial Chemical Industries Limited | Alkanolamine derivatives and pharmaceutical compositions and uses thereof |
| US4083992A (en) * | 1972-12-15 | 1978-04-11 | Imperial Chemical Industries Limited | Alkanolamine derivatives |
| US4131685A (en) * | 1972-12-15 | 1978-12-26 | Imperial Chemical Industries Limited | Pharmaceutical compositions and uses of alkanolamine derivatives |
| GB1509527A (en) * | 1974-06-05 | 1978-05-04 | Ici Ltd | 1-(aryl-or heteroaryl)oxy-3-(substituted-amino)propan-2-ol derivatives processes for their manufacture and pharmaceutical compositions containing them |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL144926B (nl) * | 1963-08-26 | 1975-02-17 | Boehringer Sohn Ingelheim | Werkwijze ter bereiding van een beta-adrenolytisch werkzaam 1-(cyaanfenoxy)-2-hydroxy-3-isopropylaminopropaan en zouten daarvan. |
-
0
- BE BE754604D patent/BE754604A/xx not_active IP Right Cessation
-
1969
- 1969-08-08 DE DE1940566A patent/DE1940566C3/de not_active Expired
-
1970
- 1970-07-30 SU SU701469623D patent/SU386506A3/ru active
- 1970-08-03 US US00060749A patent/US3732277A/en not_active Expired - Lifetime
- 1970-08-04 CS CS703685A patent/CS166734B2/cs unknown
- 1970-08-04 CS CS3686*[A patent/CS166735B2/cs unknown
- 1970-08-04 CS CS3688*[A patent/CS166737B2/cs unknown
- 1970-08-04 CS CS5440A patent/CS166731B2/cs unknown
- 1970-08-04 CS CS3683*[A patent/CS166732B2/cs unknown
- 1970-08-04 CS CS3687*[A patent/CS166736B2/cs unknown
- 1970-08-04 CS CS3689*[A patent/CS166738B2/cs unknown
- 1970-08-04 CS CS3684*[A patent/CS166733B2/cs unknown
- 1970-08-05 BG BG18257A patent/BG16739A3/xx unknown
- 1970-08-05 CH CH1180070A patent/CH546223A/xx not_active IP Right Cessation
- 1970-08-06 RO RO69112A patent/RO60083A/ro unknown
- 1970-08-06 RO RO69108A patent/RO60644A/ro unknown
- 1970-08-06 SE SE7010830A patent/SE375303B/xx unknown
- 1970-08-06 RO RO69110A patent/RO60746A/ro unknown
- 1970-08-06 RO RO69109A patent/RO60645A/ro unknown
- 1970-08-06 RO RO64160A patent/RO55805A/ro unknown
- 1970-08-06 RO RO69115A patent/RO61039A/ro unknown
- 1970-08-06 RO RO69111A patent/RO60082A/ro unknown
- 1970-08-06 ES ES382497A patent/ES382497A1/es not_active Expired
- 1970-08-06 YU YU2007/70A patent/YU34515B/xx unknown
- 1970-08-06 RO RO69113A patent/RO60084A/ro unknown
- 1970-08-07 BG BG18258A patent/BG17762A3/xx unknown
- 1970-08-07 PL PL1970174660A patent/PL84519B1/pl unknown
- 1970-08-07 DK DK407670AA patent/DK125639B/da not_active IP Right Cessation
- 1970-08-07 PL PL1970174661A patent/PL86937B1/pl unknown
- 1970-08-07 PL PL1970174658A patent/PL84398B1/pl unknown
- 1970-08-07 BG BG18256A patent/BG18179A3/xx unknown
- 1970-08-07 BG BG18253A patent/BG17759A3/xx unknown
- 1970-08-07 AT AT1108071A patent/AT303013B/de not_active IP Right Cessation
- 1970-08-07 AT AT1107671A patent/AT302996B/de not_active IP Right Cessation
- 1970-08-07 PL PL1970174657A patent/PL84339B1/pl unknown
- 1970-08-07 AT AT1108171A patent/AT303014B/de not_active IP Right Cessation
- 1970-08-07 PL PL1970174659A patent/PL84520B1/pl unknown
- 1970-08-07 PL PL1970174662A patent/PL84357B1/pl unknown
- 1970-08-07 BG BG18255A patent/BG17761A3/xx unknown
- 1970-08-07 FR FR7029317A patent/FR2068479B1/fr not_active Expired
- 1970-08-07 BG BG15431A patent/BG18178A3/xx unknown
- 1970-08-07 AT AT723670A patent/AT303006B/de not_active IP Right Cessation
- 1970-08-07 BG BG18259A patent/BG17955A3/xx unknown
- 1970-08-07 AT AT1107771A patent/AT303010B/de not_active IP Right Cessation
- 1970-08-07 AT AT1107971A patent/AT303012B/de not_active IP Right Cessation
- 1970-08-07 AT AT1107471A patent/AT303008B/de not_active IP Right Cessation
- 1970-08-07 PL PL1970174656A patent/PL84341B1/pl unknown
- 1970-08-07 NL NLAANVRAGE7011735,A patent/NL171702C/xx not_active IP Right Cessation
- 1970-08-07 AT AT1107571A patent/AT303009B/de not_active IP Right Cessation
- 1970-08-07 AT AT1107871A patent/AT303011B/de not_active IP Right Cessation
- 1970-08-07 BG BG18254A patent/BG17760A3/xx unknown
- 1970-08-07 PL PL1970142704A patent/PL80550B1/pl unknown
-
1971
- 1971-03-04 ES ES388884A patent/ES388884A1/es not_active Expired
- 1971-03-04 ES ES388881A patent/ES388881A1/es not_active Expired
- 1971-03-04 ES ES388885A patent/ES388885A1/es not_active Expired
- 1971-03-04 ES ES388880A patent/ES388880A1/es not_active Expired
- 1971-03-04 ES ES388883A patent/ES388883A1/es not_active Expired
- 1971-03-04 ES ES388882A patent/ES388882A1/es not_active Expired
- 1971-03-04 ES ES388879A patent/ES388879A1/es not_active Expired
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PL80550B1 (en) | 1-(2'-cyano-phenoxy)-2-hydroxy-3-ethylamino-propane and salts thereof[us3732277a] | |
| IE70070B1 (en) | Aryloxyphenylpropylamines their preparation and use | |
| EP0558487B1 (en) | Piperidine compounds, their preparation and use | |
| CA2004986A1 (en) | Piperidine derivatives | |
| AU626549B2 (en) | Chroman derivatives | |
| JPH02502725A (ja) | 新規な抗不整脈剤ι | |
| CH645371A5 (de) | Isochromane, isothiochromane, 2-benzoxepine und 2-benzothiepine. | |
| US3542874A (en) | 1 - (2 - methylthiophenoxy) - 2 - hydroxy - 3-isopropylaminopropane and the salts thereof | |
| JPS6350353B2 (pl) | ||
| US3706755A (en) | Certain 4(3-(4-(phenyl)-3,6-dihydro-1(2h)pyridyl)-2 - hydroxy-propoxy)-benzophenones | |
| PT95526A (pt) | Processo para a preparacao de derivados de 10,5-(iminometano)-5h-dibenzo{a,d}ciclo-hepteno uteis como agentes neuroprotectores | |
| EP0011747B1 (de) | Aminopropanolderivate des 6-Hydroxy-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ons, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen | |
| FI61484C (fi) | Foerfarande foer framstaellning av z-3-(4-bromfenyl)-n-metyl-3-(3-pyridyl)-allylamin med antidepressiv och aongestdaempande verkan | |
| US5102894A (en) | Substituted piperidine compounds and their use | |
| US3959338A (en) | 1-(Cyano-phenoxy)-2-hydroxy-3-hydroxyalkylamino-propanes and salts thereof | |
| US3950335A (en) | 1-(3'-trifluoromethyl-4'-chloro-phenyl)-2-amino-propanes and salts thereof | |
| US3928613A (en) | Compounds useful as antidepressive agents | |
| US3796715A (en) | 8-alkoxy-3,4-dihydroisoquinolines | |
| US3853882A (en) | 2,9-DIHYDRO-{8 c,f{9 -S-TRIAZOLO{8 4,3-a{9 AZEPIN-3-ONES | |
| IE50100B1 (en) | 3-amino-1-benzoxepine derivatives and their salts;processes for their preparation and pharmaceutical composition containing these compounds | |
| PL84226B1 (pl) | ||
| JP2002517392A (ja) | ５ｈｔレセプターに対して親和性を有するｎ−ベンゾジオキサニルメチル−１−ピペリジル−メチルアミン化合物 | |
| US3575983A (en) | Substituted 1,2,3,4-tetrahydroisoquinolines | |
| DE2116213A1 (de) | Piperazinderivate | |
| US3300497A (en) | 2-aryl-2-piperazinylacetophenones |