CH622491A5 - Process for the preparation of novel hydroxypropylamines - Google Patents
Process for the preparation of novel hydroxypropylamines Download PDFInfo
- Publication number
- CH622491A5 CH622491A5 CH781079A CH781079A CH622491A5 CH 622491 A5 CH622491 A5 CH 622491A5 CH 781079 A CH781079 A CH 781079A CH 781079 A CH781079 A CH 781079A CH 622491 A5 CH622491 A5 CH 622491A5
- Authority
- CH
- Switzerland
- Prior art keywords
- propanol
- ethylamino
- formula
- carbamylphenoxy
- methyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical class NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 239000002585 base Substances 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052783 alkali metal Chemical group 0.000 claims abstract 2
- 150000001340 alkali metals Chemical group 0.000 claims abstract 2
- -1 4-carbamylphenoxy Chemical group 0.000 claims description 29
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 239000007858 starting material Substances 0.000 abstract description 5
- 102000012740 beta Adrenergic Receptors Human genes 0.000 abstract description 3
- 108010079452 beta Adrenergic Receptors Proteins 0.000 abstract description 3
- 230000000903 blocking effect Effects 0.000 abstract description 2
- 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- FZKCAHQKNJXICB-UHFFFAOYSA-N 2,1-benzoxazole Chemical compound C1=CC=CC2=CON=C21 FZKCAHQKNJXICB-UHFFFAOYSA-N 0.000 description 1
- LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- JWZZKOKVBUJMES-LLVKDONJSA-N 4-[(1S)-1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol Chemical compound CC(C)NC[C@@H](O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-LLVKDONJSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-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
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- JWZZKOKVBUJMES-NSHDSACASA-N L-isoprenaline Chemical compound CC(C)NC[C@H](O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-NSHDSACASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000019255 Menstrual disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012459 cleaning 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
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229950008384 levisoprenaline Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
- 230000002792 vascular Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft ein Verfahren zur Her- rer Erkrankungen dienen können. Die neuen Verbindungen Stellung neuer Hydroxypropylamine mit blockierender Wir- 50 haben die Formel (I) The present invention relates to a method for the use of menstrual disorders. The new compounds position of new hydroxypropylamines with blocking agents have the formula (I)
kung auf die ß -Rezeptoren, die zur Behandlung kardiovaskulä- on the ß -receptors used to treat cardiovascular
,5 , 5th
HO HO
R~ R ~
(R1) (R1)
(R' (R '
)Ar0CHoCHCHoNH-CH-(CH_) -Y « fc ^ n ) Ar0CHoCHCHoNH-CH- (CH_) -Y «fc ^ n
(i) (i)
worin R1 in 2- oder 3-Stellung die Gruppe -CH2CH=CH2, -OCH2CH=CH2, -OCH2OCH, Alkoxyalkyl, H0CH2CH2NHC0CH20, CH30CH2CH2NHC0CH20- oder -CH=NOR mit R Wasserstoff oder Alkyl mit 1 bis 6 Kohlenstoffatomen ist, R2 Wasserstoff, Halogen, Alkyl oder Alkoxy, Rs Wasserstoff oder Methyl und R9 Wasserstoff oder -CONH2, Y -O- oder -CH2-, n eine ganze Zahl von 0 bis 5, m eine ganze Zahl von 0 bis 2 und Ar die Phenylgruppe bedeuten. wherein R1 in the 2- or 3-position is the group -CH2CH = CH2, -OCH2CH = CH2, -OCH2OCH, alkoxyalkyl, H0CH2CH2NHC0CH20, CH30CH2CH2NHC0CH20- or -CH = NOR with R hydrogen or alkyl with 1 to 6 carbon atoms, R2 is hydrogen, Halogen, alkyl or alkoxy, Rs is hydrogen or methyl and R9 is hydrogen or -CONH2, Y -O- or -CH2-, n is an integer from 0 to 5, m is an integer from 0 to 2 and Ar is the phenyl group.
60 R1 als Alkoxyalkyl hat bis zu 7 Kohlenstoffatome, vorzugsweise bis zu 4 Kohlenstoffatome in jeder Alkylkette, und jedes Alkyl kann geradkettig oder verzweigt sein. Alkoxyalkyl R1 ist daher beispielsweise Methoxymethyl, Methoxyäthyl, Äthoxyäthyl, Isopropoxyäthyl, n-Propoxymethyl oder 65 tert.-Butyloxymethyl. 60 R1 as alkoxyalkyl has up to 7 carbon atoms, preferably up to 4 carbon atoms in each alkyl chain, and each alkyl can be straight or branched. Alkoxyalkyl R1 is therefore, for example, methoxymethyl, methoxyethyl, ethoxyethyl, isopropoxyethyl, n-propoxymethyl or 65 tert-butyloxymethyl.
R1 kann -CH=NOR sein, worin R Wasserstoff oder eine Alkylgruppe mit 1 bis 6 Kohlenstoffatomen bedeutet, beispielsweise Isonitrosomethyl, Methylisonitrosomethyl, Äthyl- R1 can be -CH = NOR, where R is hydrogen or an alkyl group having 1 to 6 carbon atoms, for example isonitrosomethyl, methylisonitrosomethyl, ethyl
3 3rd
622 491 622 491
isonitrosomethyl, n-Propylisonitrosomethyl, Isopropylisonitro-somethyl. isonitrosomethyl, n-propylisonitrosomethyl, isopropylisonitro-somethyl.
R2 als Halogen ist beispielsweise Chlor, Fluor oder Brom. R2 als Alkyl hat bis zu 7, vorzugsweise bis zu 4 Kohlenstoffatome und ist geradkettig oder verzweigt und kann beispielsweise Methyl, Äthyl, n-Propyl, Isopropyl, n-Butyl, sec.-Butyl oder tert.-Butyl sein. R2 as halogen is, for example, chlorine, fluorine or bromine. R2 as alkyl has up to 7, preferably up to 4 carbon atoms and is straight-chain or branched and can be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl.
R2 als Alkoxy hat bis zu 7 Kohlenstoffatome, vorzugsweise bis zu 4 Kohlenstoffatome und ist geradkettig oder verzweigt und kann beispielsweise Methoxy, Äthoxy, n-Propoxy, Isoprop-oxy, n-Butoxy oder tert.-Butoxy sein. R2 as alkoxy has up to 7 carbon atoms, preferably up to 4 carbon atoms and is straight-chain or branched and can be, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or tert-butoxy.
m ist vorzugsweise 0 oder 1. m is preferably 0 or 1.
n ist vorzugsweise 1 oder 2. n is preferably 1 or 2.
Den Stand der Technik beschreiben beispielsweise die BE-Patentschrift Nr. 750 430, das NL-Patentgesuch Nr. 7 106 642 sowie die DE-Offenlegungsschriften 2 135 678 und 2 357 849. The state of the art is described, for example, by BE patent specification No. 750 430, NL patent application no. 7 106 642 and DE laid-open specifications 2 135 678 and 2 357 849.
In diesen Veröffentlichungen werden ß-Rezeptor blockierende Verbindungen beschrieben, die eine carbamylsubstituierte Phenoxyäthylaminogruppe aufweisen. In these publications, ß-receptor blocking compounds are described which have a carbamyl-substituted phenoxyethylamino group.
Das erfindungsgemässe Verfahren zur Herstellung von neuen Hydroxypropylaminen der Formel I ist im Patentanspruch 1 definiert. The process according to the invention for the preparation of new hydroxypropylamines of the formula I is defined in patent claim 1.
Die neuen, erfindungsgemäss erhältlichen Verbindungen haben wertvolle pharmakologische Eigenschaften. So blockieren sie beispielsweise die Herz-/?-Rezeptoren, was durch die Bestimmung des Antagonismus der Tachycardie nach intravenöser Injektion von 0,5 /<g/kg von d/l-lsoproterenolsulfat an einer anästhesierten Katze bei einer intravenösen Dosis von The new compounds obtainable according to the invention have valuable pharmacological properties. For example, they block the heart /?
0.002.bis 2 mg/kg gezeigt werden kann. Ferner blockieren sie die vaskulären /?-Rezeptoren, was durch die Bestimmung des Antagonismus der Vasodilatation nach intravenöser Injektion von 0,5 /ig/kg von d/l-Isoproterenolsulfat an einer anästhesierten Katze bei einer intravenösen Dosis von 3 mg/kg oder mehr gezeigt werden kann. Sie sind daher selektiv für das Herz. 0.002 to 2 mg / kg can be shown. They also block the vascular /? - receptors, which is determined by determining the antagonism of vasodilation after intravenous injection of 0.5 / ig / kg of d / l-isoproterenol sulfate in an anesthetized cat at an intravenous dose of 3 mg / kg or more can be shown. They are therefore selective for the heart.
Die neuen, erfindungsgemäss erhältlichen Verbindungen können als kardioselektive Antagonisten von adrenergischen /3-Rezeptorstimulatoren verwendet werden, beispielsweise zur Behandlung von Exogen oder Endogen verursachten Arryth-mien und Angina pectoris. Man kann sie auch als Zwischenprodukte zur Herstellung anderer, wertvoller pharmakologisch wirksamer Verbindungen verwenden. The new compounds obtainable according to the invention can be used as cardioselective antagonists of adrenergic / 3-receptor stimulators, for example for the treatment of exogenous or endogenous arrhythmias and angina pectoris. They can also be used as intermediates for the preparation of other valuable pharmacologically active compounds.
Die folgenden Verbindungen werden besonders bevorzugt: The following compounds are particularly preferred:
1. l-[2-(4-Carbamylphenoxy)-äthylamino]-3-(2-allyl-phenoxy)-propanol-(2), 1. l- [2- (4-carbamylphenoxy) ethylamino] -3- (2-allylphenoxy) propanol- (2),
2. l-[2-(4-Carbamylphenoxy)-äthylamino]-3-(2-methoxy-äthyl)-phenoxy-propanol-(2), 2. l- [2- (4-carbamylphenoxy) ethylamino] -3- (2-methoxyethyl) phenoxy propanol (2),
3. l-[l-Methyl-2-(4-carbamylphenoxy)-äthylamino]-3-(2-allylphenoxy)-propanol-(2), 3. l- [l-methyl-2- (4-carbamylphenoxy) ethylamino] -3- (2-allylphenoxy) propanol- (2),
4. l-[l-Methyl-2-(2-methylphenoxy)-äthylamino]-3-(2-allylphenoxy)-propanol-(2), 4. l- [l-methyl-2- (2-methylphenoxy) ethylamino] -3- (2-allylphenoxy) propanol- (2),
5. l-[l-Methyl-2-(4-methylphenoxy)-äthylamino]-3-(2-allylphenoxy)-propanol-(2), 5. l- [l-methyl-2- (4-methylphenoxy) ethylamino] -3- (2-allylphenoxy) propanol- (2),
6. 1 -[1 -Methyl-2-(4-carbamylphenoxy)-äthylamino]-3-(2-methylisonitrosomethylphenoxy)-propanol-(2), 6. 1 - [1-methyl-2- (4-carbamylphenoxy) ethylamino] -3- (2-methylisonitrosomethylphenoxy) propanol- (2),
7. 1 -[2 -(4-Carbamylphenoxy)-äthylamino] -3 -(3 -allyl-phenoxy)-propanol-(2). 7. 1 - [2 - (4-Carbamylphenoxy) ethylamino] -3 - (3 -allyl-phenoxy) propanol- (2).
Die Umsetzungen können in an sich bekannter Weise in Abwesenheit oder in Gegenwart von Verdünnungsmitteln und/oder Kondensationsmitteln und/oder Katalysatoren, bei Zimmertemperatur oder bei einer erhöhten Temperatur möglicherweise in einem geschlossenen Gefäss durchgeführt werden. The reactions can possibly be carried out in a manner known per se in the absence or in the presence of diluents and / or condensing agents and / or catalysts, at room temperature or at an elevated temperature in a closed vessel.
Je nach den Verfahrensbedingungen und den verwendeten Ausgangsmaterialien wird das Endprodukt entweder in freier Form oder in Form seines Säureadditionssalzes, das in den Schutzumfang der vorliegenden Erfindung eingezogen ist, erhalten. Depending on the process conditions and the starting materials used, the end product is obtained either in free form or in the form of its acid addition salt, which is within the scope of the present invention.
So können beispielsweise basische, neutrale oder gemischte Salze sowie Hemiamino, Sesqui- oder Polyhydrate erhalten werden. Die Säureadditionssalze der erfindungsgemäss erhaltenen Verbindungen können in an sich bekannter Weise in die freien Verbindungen übergeführt werden, indem z. B. basische Mittel wie Alkalien, oder Ionenaustauscher verwendet werden. Anderseits können erhaltene freie Basen Salze mit organischen oder anorganischen Säuren bilden. Bei der Herstellung von Säureadditionssalzen werden nur solche Säuren verwendet, die geeignete therapeutisch zulässige Salze bilden. Solche Säuren sind beispielsweise Chlorwasserstoffsäuren, Schwefelsäure, Phosphorsäure, Salpetersäure, Perchlorsäure, aliphatische, alicyclische, aromatische oder heterocyclische Carbon- oder Sulfonsäuren, wie beispielsweise Ameisen-, Essig-, Propion-, Bernstein-, Glycol-, Milch-, Äpfel-, Wein-, Citronen-, Ascor-bin-, Malein-, Hydroxymalein-, Brenztrauben-, Phenylessig-, Benzoe-, p-Aminobenzoe, Anthranil-, p-Hydroxybenzoe-, Salicyl-, p-Aminosalicyl- oder Embonsäure, Methansulfon-, Äthansulfon-, Hydroxyäthansulfon- oder Äthylensulfonsäuren, Halogenbenzolsulfon-, Toluolsulfon- oder Naphthylsulfonsäu-ren oder Sulfanilsäure, Methionin, Tryptophan, Lysin oder Arginin. For example, basic, neutral or mixed salts and hemiamino, sesqui or polyhydrates can be obtained. The acid addition salts of the compounds obtained according to the invention can be converted into the free compounds in a manner known per se by, for. B. basic agents such as alkalis, or ion exchangers can be used. On the other hand, free bases obtained can form salts with organic or inorganic acids. Only acids which form suitable therapeutically permissible salts are used in the production of acid addition salts. Such acids are, for example, hydrochloric acids, sulfuric acid, phosphoric acid, nitric acid, perchloric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as, for example, formic, acetic, propionic, amber, glycolic, lactic, apple, wine -, Lemon-, Ascor-bin-, Maleic-, Hydroxymalein-, Brenztrauben-, Phenylacetic-, Benzoe-, p-Aminobenzoe, Anthranil-, p-Hydroxybenzoe-, Salicyl-, p-Aminosalicyl- or Embonic Acid, Methanesulfon-, Ethanesulfonic, hydroxyethanesulfonic or ethylenesulfonic acids, halobenzenesulfonic, toluenesulfonic or naphthylsulfonic acids or sulfanilic acid, methionine, tryptophan, lysine or arginine.
Diese oder andere Salze der neuen erfindungsgemäss erhältlichen Verbindungen wie beispielsweise Picrate, können als Reinigungsmittel für die erhaltenen freien Basen dienen, These or other salts of the new compounds obtainable according to the invention, such as picrates, can serve as cleaning agents for the free bases obtained.
indem die freien Basen in Salze übergeführt werden, indem diese abgetrennt und dann aus diesen Salzen die Basen wiederum in Freiheit gesetzt werden. Zufolge der engen Beziehung zwischen den neuen Verbindungen in freier Form und in Form ihrer Salze versteht es sich, dass - falls möglich - die entsprechenden Salze anstelle der freien Verbindungen verwendet werden können. by converting the free bases into salts, separating them and then releasing the bases from these salts. Due to the close relationship between the new compounds in free form and in the form of their salts, it is understood that the corresponding salts can be used instead of the free compounds if possible.
Die neuen erfindungsgemäss erhältlichen Verbindungen können je nach der Wahl der Ausgangsmaterialien und der Verfahren in Form von optischen Antipoden oder Racematen vorliegen, oder sie können, falls sie mindestens ein asymmetrisches Kohlenstoffatom enthalten, als ein Isomerengemisch (Racematgemisch) vorliegen. Depending on the choice of the starting materials and the processes, the new compounds obtainable according to the invention can be in the form of optical antipodes or racemates or, if they contain at least one asymmetric carbon atom, they can be present as a mixture of isomers (racemate mixture).
Die isomeren Mischungen (Racematgemische), die erhalten werden, können je nach den physikalisch-chemischen Unterschieden zwischen den Komponenten in die beiden stereoisomeren (diastereomeren) Formen getrennt werden, beispielsweise durch Chromatographie und/oder fraktionierte Kristallisation. The isomeric mixtures (racemate mixtures) that are obtained can be separated into the two stereoisomeric (diastereomeric) forms, for example by chromatography and / or fractional crystallization, depending on the physico-chemical differences between the components.
Die erhaltenen Racemate können nach an sich bekannten Methoden getrennt werden, beispielsweise durch Umkristalli-sation aus einem optisch aktiven Lösungsmittel, mittels Mikroorganismen oder durch Umsetzung mit optisch aktiven Säuren, wobei die Salze der Verbindung gebildet werden, die dann beispielsweise aufgrund ihrer unterschiedlichen Löslichkeit in die Diastereomeren getrennt werden, aus denen mit geeigneten Mitteln die Antipoden freigesetzt werden. Geeignete optisch aktive Säuren sind z. B. die L- und D-Formen der Weinsäure, Di-o-tolylweinsäure, Apfelsäure, Mandelsäure, Kampfersulfonsäure oder Chinasäure. Vorzugsweise wird der aktivere Teil der beiden Antipoden isoliert. The racemates obtained can be separated by methods known per se, for example by recrystallization from an optically active solvent, by means of microorganisms or by reaction with optically active acids, the salts of the compound being formed, which then, for example, owing to their different solubility in the Diastereomers are separated, from which the antipodes are released by suitable means. Suitable optically active acids are e.g. B. the L and D forms of tartaric acid, di-o-tolyltartaric acid, malic acid, mandelic acid, camphor sulfonic acid or quinic acid. The more active part of the two antipodes is preferably isolated.
Zur Durchführung des erfindungsgemässen Verfahrens werden vorzugsweise solche Ausgangsmaterialien verwendet, die zu Gruppen in den Endstoffen führen, die in erster Linie besonders erwünscht sind und insbesondere zu den speziell beschriebenen und bevorzugten Endprodukten führen. To carry out the process according to the invention, preference is given to using starting materials which lead to groups in the end products which are primarily particularly desirable and in particular lead to the specifically described and preferred end products.
Die Ausgangsmaterialien sind an sich bekannt oder können, falls sie neu sein sollten, nach an sich bekannten Verfahren erhalten werden. The starting materials are known per se or, if they are new, can be obtained by methods known per se.
Bei der klinischen Anwendung können die erfindungsgemäss erhältlichen Verbindungen normalerweise oral, rektal oder durch Injektion in Form eines pharmazeutischen Präparats, das eine aktive Verbindung entweder als freie Base oder In clinical use, the compounds obtainable according to the invention can normally be administered orally, rectally or by injection in the form of a pharmaceutical preparation which is an active compound either as a free base or
5 5
10 10th
15 15
20 20th
25 25th
30 30th
35 35
40 40
45 45
50 50
55 55
60 60
65 65
622 491 622 491
4 4th
als pharmazeutisch zulässiges, nichttoxisches Säureadditionssalz, z. B. das Hydrochlorid, Lactat, Acetat, Sulfamat oder dergleichen, in Kombination mit einem pharmazeutisch zulässigen Trägerstoff enthält, angewendet werden. Die Erwähnung der neuen erfindungsgemäss erhältlichen Verbindungen bezieht sich entweder auf die freie Aminbasis oder die Säureadditionssalze dieser Basen, auch wenn die Verbindungen allgemein erwähnt oder speziell beschrieben werden, vorausgesetzt, dass der Zusammenhang, in dem diese Ausdrücke verwendet werden, z. B. in den Beispielen, mit dieser breiten Auslegung übereinstimmt. Der Trägerstoff kann ein festes, halbfestes oder flüssiges Verdünnungsmittel oder eine Kapsel sein. Üblicherweise trägt die Menge an wirksamer Verbindung von 0,1 bis 95% des Gewichtes des Präparates, vorzugsweise von 0,5 bis 20 Gew.% bei Präparaten zur Injektion und 2 bis 50 Gew. % bei Präparaten für orale Verabreichung. as a pharmaceutically acceptable, non-toxic acid addition salt, e.g. B. contains the hydrochloride, lactate, acetate, sulfamate or the like, in combination with a pharmaceutically acceptable carrier. The mention of the new compounds obtainable according to the invention relates either to the free amine base or the acid addition salts of these bases, even if the compounds are generally mentioned or specifically described, provided that the context in which these terms are used, e.g. B. in the examples, agrees with this broad interpretation. The carrier can be a solid, semi-solid or liquid diluent or a capsule. Usually the amount of active compound is from 0.1 to 95% by weight of the preparation, preferably from 0.5 to 20% by weight in the case of preparations for injection and 2 to 50% by weight in the case of preparations for oral administration.
Beispiel example
3 g Natrium wurden in 100 ml Äthanol aufgelöst. In die Lösung wurden anschliessend 19,5 g 2-[N-(2-Hydroxyäthyl)-carbamyl(methoxy)-phenol] und 19 g l-[2-(4-Carbamyl-phenoxy)-äthylamino]-3-chlorpropanol-2 gegeben. Die Reaktionsmischung wurde nun in einem Autoklav auf siedendem Wasserbad 15 Stunden lang erwärmt. Anschliessend wurde der in der Reaktionsmischung ausgefallene Feststoff abfiltriert und das Filtrat zur Trockne eingedampft. Der Rückstand wurde mit 2n HCl angesäuert und mit Äther extrahiert. Die erhaltene wässrige Phase wurde mittels 2n NaOH-Lösung alkalisiert und mit Äther extrahiert. Nachdem die abgetrennte Ätherphase über K2C03 getrocknet worden war, wurde das Cyclamat des l-[2-(4-Carbamylphenoxy)-äthylamino]-3-[2-(N-(2-hydroxy-äthyl)-carbamylmethoxy)-phenoxy]-propanoI-2 ausgefällt, s Der Schmelzpunkt der erhaltenen Verbindung lag bei 146 bis 155° C. 3 g of sodium was dissolved in 100 ml of ethanol. 19.5 g of 2- [N- (2-hydroxyethyl) carbamyl (methoxy) phenol] and 19 g of l- [2- (4-carbamylphenoxy) ethylamino] -3-chloropropanol were then added to the solution. 2 given. The reaction mixture was then heated in an autoclave on a boiling water bath for 15 hours. The solid which had precipitated out in the reaction mixture was then filtered off and the filtrate was evaporated to dryness. The residue was acidified with 2N HCl and extracted with ether. The aqueous phase obtained was alkalized using 2N NaOH solution and extracted with ether. After the separated ether phase was dried over K2C03, the cyclamate of 1- [2- (4-carbamylphenoxy) ethylamino] -3- [2- (N- (2-hydroxyethyl) carbamylmethoxy) phenoxy] - propanoI-2 precipitated, s The melting point of the compound obtained was 146 to 155 ° C.
Mittels des gleichen Verfahrens wurden die folgenden Verbindungen erhalten: The following compounds were obtained by the same method:
io l-[2-(4-Carbamylphenoxy)-äthylamino]-3-(2-allylphenoxy)-propanol-(2), io l- [2- (4-carbamylphenoxy) ethylamino] -3- (2-allylphenoxy) propanol- (2),
l-[4-Carbamylphenoxy)-äthylamino]-3-(2-chlor-5-methyl- l- [4-carbamylphenoxy) ethylamino] -3- (2-chloro-5-methyl-
phenoxy)-propanol-(2), l-[2-(4-Carbamylphenoxy)-äthylamino]-3-(2-methoxyäthyl)-15 phenoxy-propanol-(2), phenoxy) propanol- (2), l- [2- (4-carbamylphenoxy) ethylamino] -3- (2-methoxyethyl) -15 phenoxypropanol- (2),
l-[l-Methyl-2-(4-carbamylphenoxy)-äthylamino]-3- l- [l-methyl-2- (4-carbamylphenoxy) ethylamino] -3-
(2-allylphenoxy)-propanol-(2), (2-allylphenoxy) propanol (2),
1 -[ 1 -Methyl-2-(2 -methylphenoxy ) -äthylamino] -3 -(2-aIlylphenoxy)-propanol-(2), 20 l-[l-Methyl-2-(4-methylphenoxy)-äthyIaminoj-3-(2-allylphenöxy)-propanol-(2), l-[l-MethyI-2-(4-carbamylphenoxy)-äthylamino]-3-(2-methyIisonitrosomethylphenoxy)-propanol-(2), 1 -[2 -(4-Carbamylphenoxy)-äthyIamino]-3 -(3 -allyl-25 phenoxy)-propanol-(2) und l-[2-(4-Carbamoyl-phenoxy)-äthylamino]-3-(2-chlor- 1 - [1-Methyl-2- (2-methylphenoxy) ethylamino] -3 - (2-alylphenoxy) propanol- (2), 20 l- [l-methyl-2- (4-methylphenoxy) ethylamine- 3- (2-allylphenoxy) -propanol- (2), l- [l-methyl-2- (4-carbamylphenoxy) ethylamino] -3- (2-methylisonitrosomethylphenoxy) propanol- (2), 1 - [2 - (4-carbamylphenoxy) ethylamino] -3 - (3-allyl-25 phenoxy) propanol (2) and l- [2- (4-carbamoyl-phenoxy) ethylamino] -3- (2-chloro
phenoxy)-propanol-(2) phenoxy) propanol (2)
sowie die Verbindungen der Formel I mit as well as the compounds of formula I with
Ar Ar
R1 R1
R2 R2
Rs n Rs n
m m
R9 R9
Schmelzpunkt (°C) Melting point (° C)
Phenyl Phenyl
2-CH2=CH-CH20- 2-CH2 = CH-CH20-
H H
H H
1 1
0 0
4-NH2CO- 4-NH2CO-
136-7 (HCl) 136-7 (HCl)
Phenyl Phenyl
2-CH2=C—CH20— 2-CH2 = C — CH20—
H H
H H
1 1
0 0
4-NH2CO- 4-NH2CO-
215 (HCl) 215 (HCl)
Phenyl Phenyl
2-NH2COCH2- 2-NH2COCH2-
H H
H H
1 1
0 0
4-NH2CO— 4-NH2CO—
176 (HCl) 176 (HCl)
Phenyl Phenyl
2-H0CH2CH2NHC0CH20- 2-H0CH2CH2NHC0CH20-
H H
H H
1 1
0 0
4-NH2CO— 4-NH2CO—
66 (p-OH- 66 (p-OH-
Benzoat) Benzoate)
Phenyl Phenyl
2-CH2=CH-CH20— 2-CH2 = CH-CH20—
H H
H H
2 2nd
0 0
4-NH2CO— 4-NH2CO—
200 (HCl) 200 (HCl)
Phenyl Phenyl
2-CH2=CH-CH20 2-CH2 = CH-CH20
H H
H H
4 4th
0 0
4-NH2CO— 4-NH2CO—
öl (HCl) oil (HCl)
1,2,5-Thiadiazolyl 1,2,5-thiadiazolyl
4-C1 4-C1
H H
1 1
0 . 0.
4-NH2CO— 4-NH2CO—
>250 (HCl) > 250 (HCl)
Claims (7)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7413789A SE422052B (en) | 1974-11-01 | 1974-11-01 | PROCEDURE FOR PREPARING CERTAIN STATED 1-PHENOXY-2-HYDROXY-3-AMINOPHENYL PROPYL DERIVATIVES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH622491A5 true CH622491A5 (en) | 1981-04-15 |
Family
ID=20322597
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1196775A CH618417A5 (en) | 1974-11-01 | 1975-09-16 | Process for the preparation of novel hydroxyamines |
| CH781079A CH622491A5 (en) | 1974-11-01 | 1979-08-28 | Process for the preparation of novel hydroxypropylamines |
| CH780979A CH622490A5 (en) | 1974-11-01 | 1979-08-28 | Process for the preparation of novel hydroxypropylamines |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1196775A CH618417A5 (en) | 1974-11-01 | 1975-09-16 | Process for the preparation of novel hydroxyamines |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH780979A CH622490A5 (en) | 1974-11-01 | 1979-08-28 | Process for the preparation of novel hydroxypropylamines |
Country Status (24)
| Country | Link |
|---|---|
| JP (1) | JPS51131839A (en) |
| AT (1) | AT344142B (en) |
| AU (1) | AU498770B2 (en) |
| BE (2) | BE835090A (en) |
| CA (1) | CA1093095A (en) |
| CH (3) | CH618417A5 (en) |
| CS (1) | CS189726B2 (en) |
| DD (1) | DD119207A5 (en) |
| DE (1) | DE2531312A1 (en) |
| DK (1) | DK444475A (en) |
| FI (1) | FI752201A (en) |
| FR (1) | FR2289172A1 (en) |
| GB (1) | GB1524036A (en) |
| HK (1) | HK36081A (en) |
| HU (1) | HU172652B (en) |
| IE (1) | IE41652B1 (en) |
| LU (1) | LU73703A1 (en) |
| MY (1) | MY8200085A (en) |
| NL (1) | NL7509548A (en) |
| NO (1) | NO144773C (en) |
| NZ (1) | NZ178313A (en) |
| SE (1) | SE422052B (en) |
| SU (3) | SU906368A3 (en) |
| ZA (2) | ZA754241B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3433616A1 (en) * | 1984-08-08 | 1986-02-20 | BBC Aktiengesellschaft Brown, Boveri & Cie., Baden, Aargau | PROTECTIVE DEVICE FOR AN ELECTRICAL NET |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4119718A (en) * | 1977-05-02 | 1978-10-10 | Merck & Co., Inc. | 3-Amino-2-oxy-propoxy-substituted isothiazoles |
| SE7807408L (en) * | 1978-06-30 | 1979-12-31 | Haessle Ab | HEART ACTIVE ASSOCIATIONS |
| DD150456A5 (en) * | 1979-03-01 | 1981-09-02 | Ciba Geigy Ag | PROCESS FOR THE PREPARATION OF DERIVATIVES OF 3-AMINO-1,2-PROPANDIOL |
| US4410548A (en) * | 1980-07-09 | 1983-10-18 | Reckitt & Colman Products Limited | Propanolamine derivatives |
| DE3125870C2 (en) * | 1980-07-09 | 1994-09-15 | William John Louis | 3-aminopropoxyphenyl derivatives, their preparation and medicaments containing them |
| FR2508032A1 (en) * | 1981-06-17 | 1982-12-24 | Delalande Sa | 3-Amino-2-aryloxy-methyl-1-propanol derivs. - are used to treat cardiovascular troubles, esp. angina esp 3-tri:methoxy-cinnamoyl-piperazino- 2-1,4-benzodioxan-5-yl-oxy-methyl cpds. |
| DE3151201A1 (en) * | 1981-12-23 | 1983-07-28 | Beiersdorf Ag, 2000 Hamburg | SUBSTITUTED PHENOXYALKANOLAMINE AND PHENOXYALKANOL-CYCLOALKYLAMINE, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATIONS CONTAINING THESE COMPOUNDS AND INTERMEDIATE PRODUCTS |
| SE457505B (en) * | 1984-01-10 | 1989-01-09 | Lejus Medical Ab | LAMINATED ORAL PHARMACEUTICAL COMPOSITION AND PROCEDURES FOR ITS PREPARATION |
| JPS6341451A (en) * | 1986-08-06 | 1988-02-22 | Nippon Kayaku Co Ltd | Ether derivative and miticidal and insecticidal composition containing said derivative as active component |
| US5321036A (en) * | 1993-02-10 | 1994-06-14 | Bristol-Myers Squibb Company | Thiazole and oxazole-based β3 adrenergic receptor agonists |
-
1974
- 1974-07-02 ZA ZA00754241A patent/ZA754241B/en unknown
- 1974-11-01 SE SE7413789A patent/SE422052B/en unknown
-
1975
- 1975-07-02 ZA ZA00754240A patent/ZA754240B/en unknown
- 1975-07-12 DE DE19752531312 patent/DE2531312A1/en not_active Ceased
- 1975-07-31 FI FI752201A patent/FI752201A/fi not_active Application Discontinuation
- 1975-07-31 AT AT592975A patent/AT344142B/en not_active IP Right Cessation
- 1975-08-04 AU AU83637/75A patent/AU498770B2/en not_active Expired
- 1975-08-06 NZ NZ178313A patent/NZ178313A/en unknown
- 1975-08-06 NO NO752765A patent/NO144773C/en unknown
- 1975-08-08 SU SU752163123A patent/SU906368A3/en active
- 1975-08-08 DD DD187775A patent/DD119207A5/xx unknown
- 1975-08-11 NL NL7509548A patent/NL7509548A/en not_active Application Discontinuation
- 1975-08-14 IE IE1809/75A patent/IE41652B1/en unknown
- 1975-09-09 GB GB37073/75A patent/GB1524036A/en not_active Expired
- 1975-09-16 CH CH1196775A patent/CH618417A5/en not_active IP Right Cessation
- 1975-10-02 DK DK444475A patent/DK444475A/en unknown
- 1975-10-21 FR FR7532204A patent/FR2289172A1/en active Granted
- 1975-10-30 HU HU75HE694A patent/HU172652B/en unknown
- 1975-10-30 CS CS757328A patent/CS189726B2/en unknown
- 1975-10-31 CA CA238,763A patent/CA1093095A/en not_active Expired
- 1975-10-31 JP JP50131345A patent/JPS51131839A/en active Pending
- 1975-10-31 BE BE161438A patent/BE835090A/en unknown
- 1975-10-31 LU LU73703A patent/LU73703A1/xx unknown
- 1975-10-31 BE BE161439A patent/BE835091A/en unknown
-
1976
- 1976-09-03 SU SU762393516A patent/SU625599A3/en active
- 1976-09-03 SU SU762393515A patent/SU637078A3/en active
-
1979
- 1979-08-28 CH CH781079A patent/CH622491A5/en not_active IP Right Cessation
- 1979-08-28 CH CH780979A patent/CH622490A5/en not_active IP Right Cessation
-
1981
- 1981-07-31 HK HK360/81A patent/HK36081A/en unknown
-
1982
- 1982-12-30 MY MY85/82A patent/MY8200085A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3433616A1 (en) * | 1984-08-08 | 1986-02-20 | BBC Aktiengesellschaft Brown, Boveri & Cie., Baden, Aargau | PROTECTIVE DEVICE FOR AN ELECTRICAL NET |
Also Published As
| Publication number | Publication date |
|---|---|
| FI752201A (en) | 1976-05-02 |
| AU498770B2 (en) | 1979-03-22 |
| CH618417A5 (en) | 1980-07-31 |
| GB1524036A (en) | 1978-09-06 |
| CS189726B2 (en) | 1979-04-30 |
| BE835091A (en) | 1976-04-30 |
| LU73703A1 (en) | 1976-08-13 |
| FR2289172B1 (en) | 1980-11-21 |
| ATA592975A (en) | 1977-11-15 |
| NO144773B (en) | 1981-07-27 |
| IE41652L (en) | 1976-05-01 |
| ZA754241B (en) | 1976-06-30 |
| IE41652B1 (en) | 1980-02-27 |
| HU172652B (en) | 1977-11-28 |
| SE422052B (en) | 1982-02-15 |
| HK36081A (en) | 1981-07-31 |
| NO144773C (en) | 1981-11-04 |
| NL7509548A (en) | 1976-05-04 |
| DK444475A (en) | 1976-05-02 |
| ZA754240B (en) | 1976-06-30 |
| DD119207A5 (en) | 1976-04-12 |
| JPS51131839A (en) | 1976-11-16 |
| BE835090A (en) | 1976-04-30 |
| SE7413789L (en) | 1976-05-03 |
| NO752765L (en) | 1976-05-04 |
| CH622490A5 (en) | 1981-04-15 |
| SU906368A3 (en) | 1982-02-15 |
| AU8363775A (en) | 1977-02-10 |
| NZ178313A (en) | 1978-06-02 |
| FR2289172A1 (en) | 1976-05-28 |
| DE2531312A1 (en) | 1976-05-06 |
| AT344142B (en) | 1978-07-10 |
| SU625599A3 (en) | 1978-09-25 |
| CA1093095A (en) | 1981-01-06 |
| SU637078A3 (en) | 1978-12-05 |
| MY8200085A (en) | 1982-12-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |
