CA1129416A - Carbazolyl-(4)-oxypropanolamine derivatives - Google Patents
Carbazolyl-(4)-oxypropanolamine derivativesInfo
- Publication number
- CA1129416A CA1129416A CA324,667A CA324667A CA1129416A CA 1129416 A CA1129416 A CA 1129416A CA 324667 A CA324667 A CA 324667A CA 1129416 A CA1129416 A CA 1129416A
- Authority
- CA
- Canada
- Prior art keywords
- oxy
- propan
- carbazolyl
- ethylamino
- process according
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 claims abstract description 118
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 7
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 4
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- BQIKRTGTPBOIMK-UHFFFAOYSA-N [O]C[O] Chemical compound [O]C[O] BQIKRTGTPBOIMK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- 239000001301 oxygen Substances 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 69
- SVWKIGRDISDRLO-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)-9h-carbazole Chemical compound C=1C=CC=2NC3=CC=CC=C3C=2C=1OCC1CO1 SVWKIGRDISDRLO-UHFFFAOYSA-N 0.000 claims description 66
- 239000000126 substance Substances 0.000 claims description 49
- -1 pivalolyl Chemical group 0.000 claims description 41
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 13
- KDKGUNGYIFBNPP-UHFFFAOYSA-N 2-(2-methylphenyl)sulfanylethanamine Chemical compound CC1=CC=CC=C1SCCN KDKGUNGYIFBNPP-UHFFFAOYSA-N 0.000 claims description 5
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- GBBBWTDKOLEAOC-UHFFFAOYSA-N 1-(2-methoxyphenoxy)propan-2-one Chemical compound COC1=CC=CC=C1OCC(C)=O GBBBWTDKOLEAOC-UHFFFAOYSA-N 0.000 claims description 3
- QFFKNTCASXEPOQ-UHFFFAOYSA-N 2-(2,3-dimethylphenoxy)ethanamine Chemical compound CC1=CC=CC(OCCN)=C1C QFFKNTCASXEPOQ-UHFFFAOYSA-N 0.000 claims description 3
- BDOKKFIYLQAJOF-UHFFFAOYSA-N 2-(2,6-dimethoxyphenoxy)ethanamine Chemical compound COC1=CC=CC(OC)=C1OCCN BDOKKFIYLQAJOF-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims description 2
- JHNURUNMNRSGRO-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-3-ylmethanamine Chemical compound C1=CC=C2OC(CN)COC2=C1 JHNURUNMNRSGRO-UHFFFAOYSA-N 0.000 claims description 2
- ZMEQUDXFAHZUPR-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yloxy)ethanamine Chemical compound NCCOC1=CC=C2OCOC2=C1 ZMEQUDXFAHZUPR-UHFFFAOYSA-N 0.000 claims description 2
- NAPNYPMMDVRKGM-UHFFFAOYSA-N 2-(2-chlorophenoxy)ethanamine Chemical compound NCCOC1=CC=CC=C1Cl NAPNYPMMDVRKGM-UHFFFAOYSA-N 0.000 claims description 2
- OOKCBENPEIHOJG-UHFFFAOYSA-N 2-(2-ethoxyphenoxy)ethanamine Chemical compound CCOC1=CC=CC=C1OCCN OOKCBENPEIHOJG-UHFFFAOYSA-N 0.000 claims description 2
- VOIPEKOXTFLQNY-UHFFFAOYSA-N 2-(2-methoxyphenoxy)-n-methylethanamine Chemical compound CNCCOC1=CC=CC=C1OC VOIPEKOXTFLQNY-UHFFFAOYSA-N 0.000 claims description 2
- CKJRKLKVCHMWLV-UHFFFAOYSA-N 2-(2-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC=C1OCCN CKJRKLKVCHMWLV-UHFFFAOYSA-N 0.000 claims description 2
- BIWHLVXMIXGLJA-UHFFFAOYSA-N 2-(2-methoxyphenoxy)propan-1-amine Chemical compound COC1=CC=CC=C1OC(C)CN BIWHLVXMIXGLJA-UHFFFAOYSA-N 0.000 claims description 2
- WSWPCNMLEVZGSM-UHFFFAOYSA-N 2-(2-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC=C1CCN WSWPCNMLEVZGSM-UHFFFAOYSA-N 0.000 claims description 2
- DXYUDCFZHJXQQR-UHFFFAOYSA-N 2-(2-methylphenoxy)ethanamine Chemical compound CC1=CC=CC=C1OCCN DXYUDCFZHJXQQR-UHFFFAOYSA-N 0.000 claims description 2
- RTRHUTMJBNRFOL-UHFFFAOYSA-N 2-(2-methylsulfinylphenoxy)ethanamine Chemical compound CS(=O)C1=CC=CC=C1OCCN RTRHUTMJBNRFOL-UHFFFAOYSA-N 0.000 claims description 2
- IYVSABAGVFWSNU-UHFFFAOYSA-N 2-(2-phenylmethoxyphenoxy)ethanamine Chemical compound NCCOC1=CC=CC=C1OCC1=CC=CC=C1 IYVSABAGVFWSNU-UHFFFAOYSA-N 0.000 claims description 2
- MWOLPDQWBBJNJU-UHFFFAOYSA-N 2-(3-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC(OCCN)=C1 MWOLPDQWBBJNJU-UHFFFAOYSA-N 0.000 claims description 2
- IGGVZLIHUYNMNQ-UHFFFAOYSA-N 2-(3-methylphenoxy)ethanamine Chemical compound CC1=CC=CC(OCCN)=C1 IGGVZLIHUYNMNQ-UHFFFAOYSA-N 0.000 claims description 2
- HTMIRIIZZGJJBK-UHFFFAOYSA-N 2-(4-fluorophenoxy)ethanamine Chemical compound NCCOC1=CC=C(F)C=C1 HTMIRIIZZGJJBK-UHFFFAOYSA-N 0.000 claims description 2
- YXRCDWIZAGWUBL-UHFFFAOYSA-N 2-(4-methoxyphenoxy)ethanamine Chemical compound COC1=CC=C(OCCN)C=C1 YXRCDWIZAGWUBL-UHFFFAOYSA-N 0.000 claims description 2
- IMLAIXAZMVDRGA-UHFFFAOYSA-N 2-phenoxyethanamine Chemical compound NCCOC1=CC=CC=C1 IMLAIXAZMVDRGA-UHFFFAOYSA-N 0.000 claims description 2
- IDLHTECVNDEOIY-UHFFFAOYSA-N 2-pyridin-4-ylethanamine Chemical compound NCCC1=CC=NC=C1 IDLHTECVNDEOIY-UHFFFAOYSA-N 0.000 claims description 2
- XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 claims description 2
- YEGXZBYGDXGWJU-UHFFFAOYSA-N 3-(2-methoxyphenyl)propanoyl chloride Chemical compound COC1=CC=CC=C1CCC(Cl)=O YEGXZBYGDXGWJU-UHFFFAOYSA-N 0.000 claims description 2
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 claims description 2
- MHIAMONBYDFGFO-UHFFFAOYSA-N 4-(2-aminoethoxy)benzamide Chemical compound NCCOC1=CC=C(C(N)=O)C=C1 MHIAMONBYDFGFO-UHFFFAOYSA-N 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- JWQOQWYYUBHJFI-UHFFFAOYSA-N n-[2-(2-methoxyphenoxy)ethyl]butan-1-amine Chemical compound CCCCNCCOC1=CC=CC=C1OC JWQOQWYYUBHJFI-UHFFFAOYSA-N 0.000 claims description 2
- SZDYRZVWNVIYGO-UHFFFAOYSA-N n-benzyl-2-(2-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC=C1OCCNCC1=CC=CC=C1 SZDYRZVWNVIYGO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 230000001590 oxidative effect Effects 0.000 claims 2
- SXQSTYXLCULOEC-UHFFFAOYSA-N 2-(5-fluoro-2-methoxyphenoxy)ethyl 4-methylbenzenesulfonate Chemical compound COC1=CC=C(F)C=C1OCCOS(=O)(=O)C1=CC=C(C)C=C1 SXQSTYXLCULOEC-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 11
- 238000011282 treatment Methods 0.000 abstract description 7
- 230000000304 vasodilatating effect Effects 0.000 abstract description 6
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 3
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 235000005985 organic acids Nutrition 0.000 abstract description 3
- 208000019622 heart disease Diseases 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000013078 crystal Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 239000003610 charcoal Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000008298 dragée Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 description 4
- 229960001317 isoprenaline Drugs 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 3
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
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- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- QWBBPBRQALCEIZ-UHFFFAOYSA-N 2,3-dimethylphenol Chemical compound CC1=CC=CC(O)=C1C QWBBPBRQALCEIZ-UHFFFAOYSA-N 0.000 description 2
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- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
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- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Chemical compound OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 description 2
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- 239000011230 binding agent Substances 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
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- 239000000706 filtrate Substances 0.000 description 2
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- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000004780 naphthols Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
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- 150000005840 aryl radicals Chemical class 0.000 description 1
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- 235000010233 benzoic acid Nutrition 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 238000006480 benzoylation reaction Methods 0.000 description 1
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- 238000009835 boiling Methods 0.000 description 1
- 125000003865 brosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)S(*)(=O)=O 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
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- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000001716 carbazoles Chemical class 0.000 description 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 238000004519 manufacturing process Methods 0.000 description 1
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- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 150000002825 nitriles Chemical class 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- FZJCXIDLUFPGPP-UHFFFAOYSA-N propan-2-ol;toluene Chemical compound CC(C)O.CC1=CC=CC=C1 FZJCXIDLUFPGPP-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000005624 silicic acid group Chemical class 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 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
- 238000001665 trituration Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/64—Oxygen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782815926 DE2815926A1 (de) | 1978-04-13 | 1978-04-13 | Neue carbazolyl-(4)-oxy-propanolamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DEP2815926.4 | 1978-04-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1129416A true CA1129416A (en) | 1982-08-10 |
Family
ID=6036838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA324,667A Expired CA1129416A (en) | 1978-04-13 | 1979-04-02 | Carbazolyl-(4)-oxypropanolamine derivatives |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4503067A (Direct) |
| EP (1) | EP0004920B1 (Direct) |
| JP (2) | JPS54157558A (Direct) |
| AT (1) | AT375639B (Direct) |
| AU (1) | AU522975B2 (Direct) |
| BG (1) | BG61419B2 (Direct) |
| CA (1) | CA1129416A (Direct) |
| CS (2) | CS227007B2 (Direct) |
| DD (1) | DD143607A5 (Direct) |
| DE (2) | DE2815926A1 (Direct) |
| DK (1) | DK154555C (Direct) |
| ES (1) | ES479396A1 (Direct) |
| FI (1) | FI70406C (Direct) |
| HK (1) | HK2385A (Direct) |
| HU (1) | HU179433B (Direct) |
| IL (1) | IL57020A (Direct) |
| LT (1) | LT2628B (Direct) |
| LU (1) | LU88320I2 (Direct) |
| MX (1) | MX9203380A (Direct) |
| NL (1) | NL930110I2 (Direct) |
| SG (1) | SG52284G (Direct) |
| SU (1) | SU810079A3 (Direct) |
| ZA (1) | ZA791732B (Direct) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007144785A3 (en) * | 2006-03-26 | 2008-04-17 | Uti Limited Partnership | Ryanodine receptor inhibitors and methods relating thereto |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3131146A1 (de) * | 1981-08-06 | 1983-02-24 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue heteroaryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3300933A1 (de) * | 1983-01-13 | 1984-07-19 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verwendung von d,l- und d-carazolol als antiglaukommittel sowie arzneimittel, die diese stoffe enthalten |
| DE3319027A1 (de) * | 1983-05-26 | 1984-11-29 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verfahren zur herstellung von optisch aktiven carbazol-derivaten, neue r- und s-carbazol-derivate, sowie arzneimittel, die diese verbindungen enthalten |
| GB9113802D0 (en) * | 1991-06-26 | 1991-08-14 | Smithkline Beecham Plc | Medicaments |
| US5405863A (en) * | 1992-12-01 | 1995-04-11 | Smithkline Beecham Corporation | Antioxidant cardioprotective use of, and method of treatment using, hydroxycarbazole compounds |
| ZA938897B (en) * | 1992-12-01 | 1994-08-01 | Smithkline Beecham Corp | Antioxidant neuroprotective use of and method of treatment using hydroxycarbazole compounds |
| US5308862A (en) * | 1993-03-05 | 1994-05-03 | Boehringer Mannheim Pharmaceuticals Corporation - Smithkline Beecham Corp., Ltd. Partnership No. 1 | Use of, and method of treatment using, carbazolyl-(4)-oxypropanolamine compounds for inhibition of smooth muscle cell proliferation |
| WO1994020096A1 (en) * | 1993-03-05 | 1994-09-15 | Boehringer Mannheim Pharmaceuticals Corporation - Smithkline Beckman Corporation Limited | Method of employing carbazolyl-(4)-oxypropanolamine compounds for inhibition of smooth muscle cell proliferation |
| US5393772A (en) * | 1993-11-24 | 1995-02-28 | Boehringer Mannheim Pharmaceuticals Corporation | Use of, and method of treatment using, hydroxycarbazole compounds for inhibition of smooth muscle migration and proliferation |
| US5760069A (en) * | 1995-02-08 | 1998-06-02 | Boehringer Mannheim Pharmaceuticals Corporation-Smithkline Beecham Corporation Limited Partnership #1 | Method of treatment for decreasing mortality resulting from congestive heart failure |
| ZA967892B (en) * | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
| US6177430B1 (en) | 1997-03-27 | 2001-01-23 | Pfizer Inc | Use of α1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia |
| DE19628335A1 (de) * | 1996-07-13 | 1998-01-15 | Boehringer Mannheim Gmbh | Verwendung von Carbazolyl-(4)-oxy-propanolamin-Derivaten zur topischen Behandlung von peripheren Durchblutungsstörungen |
| AU4083097A (en) * | 1996-08-23 | 1998-03-06 | Boehringer Mannheim Pharmaceuticals Corporation-Smithkline Beecham Corporation Limited Partnership No. 1 | Method for inhibiting the expression of fas |
| DE69711519T2 (de) * | 1996-09-05 | 2002-10-31 | Eli Lilly And Co., Indianapolis | Carbazolanaloge als selektive beta3-adrenergische Agonisten |
| US5808080A (en) | 1996-09-05 | 1998-09-15 | Eli Lilly And Company | Selective β3 adrenergic agonists |
| TR199900762T2 (xx) * | 1996-10-09 | 1999-07-21 | Boehringer Mannheim Pharmaceuticals Cor.Smithkline Beecham | Stresle aktifle�tirilen protein kinazlar�n�n engellenme y�ntemi. |
| EP0893440A1 (en) * | 1997-07-22 | 1999-01-27 | Roche Diagnostics GmbH | Thermodynamically stable modification of 1-(4-carbazolyloxy)-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanole, process for its preparation and pharmaceutical compositions containing it |
| US6730326B2 (en) | 1997-07-22 | 2004-05-04 | Roche Diagnostics Gmbh | Thermodynamically stable modification of 1-(4-carbazolyl-oxy-3[2-(2-methoxyphenoxy)-ethylamino]-2-propanol process for its preparation and pharmaceutical compositions containing it |
| ZA989365B (en) * | 1997-10-15 | 1999-04-15 | Boehringer Mannheim Pharm Corp | Preparation for treating alzheimer's disease |
| CA2309542A1 (en) * | 1997-11-12 | 1999-05-20 | Boehringer Mannheim Pharmaceuticals Corp. - Smithkline Beecham Corporati On Limited Partnership No.1 | Novel oral dosage form for carvedilol |
| HU9702209D0 (en) * | 1997-11-24 | 1998-01-28 | Egyt Gyogyszervegyeszeti Gyar | Process for producing pharmaceutical product |
| HU227441B1 (en) * | 1997-11-24 | 2011-06-28 | Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag | Process for producing carvedilol, enantiomers and salts thereof |
| CO5011072A1 (es) * | 1997-12-05 | 2001-02-28 | Lilly Co Eli | Etanolaminas pirazinil substituidas como agfonistas de los receptores |
| CN1151788C (zh) * | 1998-04-09 | 2004-06-02 | 罗切诊断学有限公司 | 卡维地洛-盖仑制剂 |
| EP0968714A1 (de) * | 1998-07-02 | 2000-01-05 | Roche Diagnostics GmbH | Verfahren zur Herstellung schnellauflösender pharmazeutischer Zubereitungen von schwerlöslichen Wirkstoffen |
| US6664284B2 (en) | 1998-07-23 | 2003-12-16 | Roche Diagnostics Gmbh | Stabilized carvedilol injection solution |
| DE19833119A1 (de) * | 1998-07-23 | 2000-01-27 | Roche Diagnostics Gmbh | Spritzfertige Injektionslösungen enthaltend Carvedilol |
| AU5251999A (en) | 1998-08-04 | 2000-02-28 | Wisconsin Alumni Research Foundation | Method of reducing retinal ganglion cell degeneration |
| PE20001302A1 (es) | 1998-11-27 | 2000-11-30 | Hoffmann La Roche | Preparaciones de una combinacion farmaceutica que contiene carvedilol e hidroclorotiazida |
| MY125942A (en) | 1999-09-07 | 2006-09-29 | Upjohn Co | Aminoalkoxy carbazoles for the treatment of cns diseases |
| CA2392085A1 (en) * | 1999-11-15 | 2001-05-25 | Smithkline Beecham Corporation | Carvedilol methanesulfonate |
| US20010036959A1 (en) * | 2000-04-03 | 2001-11-01 | Gabel Rolf Dieter | Carvedilol-hydrophilic solutions |
| JP2003528914A (ja) * | 2000-04-03 | 2003-09-30 | エフ．ホフマン−ラ ロシュ アーゲー | カルベジロールの濃縮溶液 |
| DK174645B1 (da) * | 2000-05-18 | 2003-08-04 | Gea Farmaceutisk Fabrik As | Fremgangsmåde og mellemprodukter til fremstillingen af 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxy-phenoxy)-ethylamino]-propan-2-ol, carvedilol og syreadditionssalte deraf |
| EP1299101A4 (en) * | 2000-06-28 | 2004-06-16 | Teva Pharma | CARVEDILOL |
| EP1655285A1 (en) * | 2000-06-28 | 2006-05-10 | Teva Pharmaceutical Industries Ltd. | Method for preparation of a crystalline form of carvedilol (form II) |
| GB0106953D0 (en) * | 2001-03-20 | 2001-05-09 | Univ Aberdeen | Neufofibrillary labels |
| WO2002078692A1 (en) * | 2001-04-02 | 2002-10-10 | Smithkline Beecham Corporation | Method of treatment |
| IN191028B (Direct) * | 2001-05-17 | 2003-09-13 | Sun Pharmaceutical Ind Ltd | |
| DE60212130D1 (en) * | 2001-07-13 | 2006-07-20 | Smithkline Beecham Corp | Carvedilolpolymorph |
| WO2003017046A2 (en) * | 2001-08-14 | 2003-02-27 | Variant Holdings, Llc. | System for marketing goods and services utilizing computerized central and remote facilities |
| EP1429744A1 (en) | 2001-09-21 | 2004-06-23 | Egalet A/S | Morphine polymer release system |
| EP1429739A1 (en) | 2001-09-21 | 2004-06-23 | Egalet A/S | Polymer release system |
| WO2003029214A1 (en) * | 2001-09-28 | 2003-04-10 | F. Hoffmann-La Roche Ag | Pseudopolymorphic forms of carvedilol |
| WO2003028718A1 (en) * | 2001-10-01 | 2003-04-10 | Smithkline Beecham Corporation | Novel formulations of carvedilol |
| US8101209B2 (en) * | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
| US6710184B2 (en) * | 2002-01-15 | 2004-03-23 | Teva Pharmaceutical Industries Ltd. | Crystalline solids of carvedilol and processes for their preparation |
| KR20040088519A (ko) | 2002-02-22 | 2004-10-16 | 뉴 리버 파마슈티칼스, 인크. | 활성 제제 전달 시스템 및 활성 제제의 보호 및 투여 방법 |
| WO2003092622A2 (en) * | 2002-04-30 | 2003-11-13 | Sb Pharmco Puerto Rico Inc. | Carvedilol monocitrate monohydrate |
| US20060094771A1 (en) * | 2002-05-03 | 2006-05-04 | Wei Chen | Carvedilol pharmasolve solvate |
| JP2005524701A (ja) * | 2002-05-03 | 2005-08-18 | エスビー・ファルムコ・プエルト・リコ・インコーポレイテッド | カルベジロール処方 |
| US20050261355A1 (en) * | 2002-06-27 | 2005-11-24 | Sb Pharmco Puerto Rico Inc., | Carvedilol hydobromide |
| CN103288714A (zh) * | 2002-06-27 | 2013-09-11 | 史密斯克莱.比奇曼（科克）有限公司 | 卡维地洛磷酸盐和/或其溶剂合物相应的组合物和/或治疗方法 |
| US20040152756A1 (en) * | 2002-07-15 | 2004-08-05 | Wei Chen | Carvedilol polymorph |
| EP1542728A4 (en) * | 2002-07-22 | 2005-09-21 | Nanohybrid Co Ltd | HYBRID OF ITRACONAZOLE, CYCLOSPORINE OR CARVEDILOL WITH A LAYERED SILICATE AND PROCESS FOR PREPARING THE SAME |
| DE60336485D1 (de) | 2002-08-19 | 2011-05-05 | Pfizer | Kombinationstherapie gegen hyperproliferative erkrankungen |
| US6632832B1 (en) | 2002-09-10 | 2003-10-14 | Dabur Research Foundation | Anti-cancer activity of carvedilol and its isomers |
| WO2004041252A1 (en) * | 2002-11-08 | 2004-05-21 | Egalet A/S | Controlled release carvedilol compositions |
| SK285547B6 (sk) * | 2002-11-08 | 2007-03-01 | Zentiva, A. S. | Spôsob prípravy Carvedilolu |
| WO2004094378A1 (en) * | 2003-04-21 | 2004-11-04 | Matrix Laboratories Ltd | Process for the preparation of carvedilol form-ii |
| RS20050890A (sr) * | 2003-05-30 | 2007-12-31 | Ranbaxy Laboratories Limited, | Supstituisani pirol derivati |
| WO2004113296A1 (en) * | 2003-06-20 | 2004-12-29 | Sun Pharmaceutical Industries Limited | A process for preparation of 1-[9h-carbazol-4-yloxy]- 3-[{2-(2-(-(methoxy)phenoxy)-ethyl}-amino]-propan-2-ol |
| US20050037063A1 (en) * | 2003-07-21 | 2005-02-17 | Bolton Anthony E. | Combined therapies |
| JP2007512372A (ja) * | 2003-11-25 | 2007-05-17 | エスビー・ファルムコ・プエルト・リコ・インコーポレイテッド | カルベジロール塩、対応する組成物、送達および／または治療方法 |
| ES2662903T3 (es) | 2003-11-25 | 2018-04-10 | Smithkline Beecham (Cork) Limited | Base libre de carvedilol, sales, formas anhidras o solvato de la misma, composiciones farmacéuticas correspondientes, formulaciones de liberación controlada, y procedimientos de tratamiento o administración |
| WO2005051325A2 (en) * | 2003-11-25 | 2005-06-09 | Sb Pharmco Puerto Rico Inc. | Carvedilol compositions methods of treatment and delivery |
| WO2005115981A2 (en) * | 2004-04-22 | 2005-12-08 | Usv Limited | A process for the preparation of 1-(9h-carbazol-4-yloxy)-3-2-(-methoxyphenoxy)-ethyl amino-propan-2-ol |
| GB0411273D0 (en) * | 2004-05-20 | 2004-06-23 | Cipla Ltd | Process and product |
| JP2008521805A (ja) * | 2004-11-30 | 2008-06-26 | アーテシアン セラピューティクス， インコーポレイテッド | β−アドレナリン作用性受容体およびホスホジエステラーゼに対する阻害活性を有する強心性化合物 |
| PL1838670T3 (pl) * | 2004-12-09 | 2010-03-31 | Zach System Spa | Sposób wytwarzania karwedilolu i jego enancjomerów |
| US20070027202A1 (en) * | 2005-06-07 | 2007-02-01 | Ashok Kumar | Process for the preparation of carvedilol and its salts |
| WO2006135757A1 (en) * | 2005-06-09 | 2006-12-21 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of carvedilol and processes for their preparation |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| WO2007042912A2 (en) * | 2005-10-13 | 2007-04-19 | Orchid Research Laboratories Limited | Heterocyclic compounds as pstat3/il-6 inhibitors |
| US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
| JP2009514851A (ja) * | 2005-11-08 | 2009-04-09 | ランバクシー ラボラトリーズ リミテッド | （３ｒ，５ｒ）−７−［２−（４−フルオロフェニル）−５−イソプロピル−３−フェニル−４−［（４−ヒドロキシメチルフェニルアミノ）カルボニル］−ピロール−１−イル］−３，５−ジヒドロキシ−ヘプタン酸ヘミカルシウム塩の製法 |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| US8367112B2 (en) * | 2006-02-28 | 2013-02-05 | Alkermes Pharma Ireland Limited | Nanoparticulate carverdilol formulations |
| TW200744583A (en) * | 2006-03-14 | 2007-12-16 | Ranbaxy Lab Ltd | Statin stabilizing dosage formulations |
| EP1991527A2 (en) * | 2006-06-28 | 2008-11-19 | Teva Pharmaceutical Industries Ltd | Polymorphous forms of carvedilol phosphate |
| TW200811101A (en) * | 2006-07-14 | 2008-03-01 | Ranbaxy Lab Ltd | Polymorphic forms of an HMG-CoA reductase inhibitor and uses thereof |
| WO2008038301A1 (en) * | 2006-09-26 | 2008-04-03 | Morepen Laboratories Limited | A process for the preparation of carvedilol |
| WO2008070496A2 (en) | 2006-12-01 | 2008-06-12 | Bristol-Myers Squibb Company | N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases |
| US20090028935A1 (en) * | 2006-12-01 | 2009-01-29 | Kristin Arnold | Carvedilol forms, compositions, and methods of preparation thereof |
| US20080292695A1 (en) * | 2006-12-01 | 2008-11-27 | Kristin Arnold | Carvedilol forms, compositions, and methods of preparation thereof |
| WO2008084494A1 (en) * | 2007-01-08 | 2008-07-17 | Matrix Laboratories Limited | Novel polymorphic forms of carvedilol dihydrogen phosphate and process for preparing the same |
| NZ577560A (en) * | 2007-01-16 | 2012-01-12 | Egalet Ltd | Use of i) a polyglycol and ii) an active drug substance for the preparation of a pharmaceutical composition for i) mitigating the risk of alcohol induced dose dumping and/or ii) reducing the risk of drug abuse |
| CZ302357B6 (cs) * | 2007-01-26 | 2011-03-30 | Zentiva, A. S. | Zpusob cištení Carvedilolu |
| WO2008105794A1 (en) * | 2007-02-26 | 2008-09-04 | Teva Pharmaceutical Industries Ltd. | Process for the purification of carvedilol or its salts thereof |
| US20080249317A1 (en) * | 2007-04-04 | 2008-10-09 | Apotex Inc. | Novel amorphous form of carvedilol phosphate and processes for the preparation thereof |
| WO2008142703A1 (en) * | 2007-05-17 | 2008-11-27 | Wanbury Limited | A novel cost effective process for production of carvedilol phosphate |
| NZ580972A (en) | 2007-06-04 | 2012-02-24 | Egalet Ltd | Controlled release pharmaceutical compositions for prolonged effect |
| WO2009024997A1 (en) * | 2007-08-21 | 2009-02-26 | Lupin Limited | Stable amorphous form of carvedilol dihydrogen phosphate with stabilizer |
| WO2009035535A2 (en) * | 2007-09-07 | 2009-03-19 | Scinopharm Taiwan Ltd. | Method of crystallizing carvedilol phosphate and the product thereof |
| US20090076116A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched carvediolo |
| US20090111998A1 (en) * | 2007-10-25 | 2009-04-30 | Srinivas Reddy Gade | Process for the preparation of carvedilol dihydrogen phosphate hemihydrate and pharmaceutical compositions thereof |
| ATE539769T1 (de) * | 2008-03-04 | 2012-01-15 | Lupin Ltd | Stabile pharmazeutische zusammensetzungen mit carvedilol |
| WO2009115906A2 (en) * | 2008-03-19 | 2009-09-24 | Cadila Pharmaceuticals Ltd. | An improved process for preparation of carvedilol involving halohydrin derivative |
| WO2009115902A1 (en) * | 2008-03-19 | 2009-09-24 | Cadila Pharmaceuticals Ltd. | Process for the preparation of carvedilol via silyl protection of substituted amine |
| WO2009122425A1 (en) * | 2008-04-04 | 2009-10-08 | Shodhana Laboratories Limited | Novel crystalline form of carvedilol dihydrogen phosphate and related processes |
| US7763645B2 (en) * | 2008-05-23 | 2010-07-27 | Wanbury Limited | Carvedilol dihydrogen phosphate monohydrate |
| WO2010092589A2 (en) * | 2008-05-26 | 2010-08-19 | Alkem Laboratories Ltd. | Process for preparation of amorphous carvedilol phosphate |
| US9005660B2 (en) | 2009-02-06 | 2015-04-14 | Egalet Ltd. | Immediate release composition resistant to abuse by intake of alcohol |
| WO2010149169A2 (en) | 2009-06-24 | 2010-12-29 | Egalet A/S | Controlled release formulations |
| TWI415604B (zh) | 2009-09-29 | 2013-11-21 | Tsh Biopharm Corp Ltd | 調控釋放卡菲蒂羅劑型 |
| US20110229564A1 (en) * | 2010-03-22 | 2011-09-22 | Amneal Pharmaceuticals, L.L.C. | Pharmaceutical Compositions Of Carvedilol Salts And Process For Preparation Thereof |
| WO2013090136A2 (en) | 2011-12-16 | 2013-06-20 | 3M Innovative Properties Company | Oxirane-containing bisanhydrohexitol derivatives and uses thereof |
| EP2877161A1 (en) | 2012-07-06 | 2015-06-03 | Egalet Ltd. | Abuse deterrent pharmaceutical compositions for controlled release |
| US8492426B1 (en) | 2012-07-12 | 2013-07-23 | Anis Ahmad | Use of carvedilol for treatment of diabetes mellitus |
| JP2016516804A (ja) | 2013-04-17 | 2016-06-09 | ファイザー・インク | 心血管疾患を治療するためのｎ−ピペリジン−３−イルベンズアミド誘導体 |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
| US10357476B1 (en) | 2018-10-30 | 2019-07-23 | Anis Ahmad | Method for treating coronary artery disease |
| PE20220138A1 (es) | 2019-01-18 | 2022-01-27 | Astrazeneca Ab | Inhibidores de la pcsk9 y metodos de uso de los mismos |
| CN111170997A (zh) * | 2019-12-31 | 2020-05-19 | 广州医科大学 | 咔唑类化合物及其制备方法和应用 |
| CN113372260A (zh) * | 2021-07-05 | 2021-09-10 | 大连蒙迪科技有限公司 | 一种卡维地洛杂质的合成方法 |
| CN115960032A (zh) * | 2021-10-08 | 2023-04-14 | 复旦大学 | 具有β-arrestin偏向性激动活性的芳氧丙醇胺类β-肾上腺素受体配基及其用途 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1834015A (en) * | 1929-06-29 | 1931-12-01 | Gen Aniline Works Inc | Manufacture of hydroxy carbazoles |
| DE1152107B (de) * | 1956-06-27 | 1963-08-01 | Chem Fab Promonta G M B H | Verfahren zur Herstellung von basisch substituierten Carbazolderivaten und deren Salzen |
| US3932424A (en) * | 1970-06-15 | 1976-01-13 | Richardson-Merrell Inc. | Bis-basic ethers of carbazole |
| BE789072A (fr) * | 1971-09-23 | 1973-03-21 | Astra Laekemedel Ab | Composes abaissant le taux de lipides du serum et leur obtention |
| AT336176B (de) * | 1971-12-10 | 1977-04-25 | Sandoz Ag | Verfahren zur herstellung eines pharmazeutischen praparates |
| US3975398A (en) * | 1973-08-01 | 1976-08-17 | Boehringer Mannheim G.M.B.H. | 9-Substituted 3-aminocarbazole compounds |
| DE2339396C2 (de) * | 1973-08-03 | 1984-06-28 | Boehringer Mannheim Gmbh, 6800 Mannheim | N-substituierte 1-Amino-3-phenoxypropan-2-ole, deren Salze, Verfahren zu deren Herstellung sowie Arzneimittel, die diese Verbindungen enthalten |
| DE2424523A1 (de) * | 1974-05-21 | 1975-12-11 | Boehringer Mannheim Gmbh | Neue 1,2,3,4-tetrahydrocarbazol-derivate und verfahren zu deren herstellung |
| US4076829A (en) * | 1974-11-16 | 1978-02-28 | Boehringer Mannheim Gmbh | Aminopropanol compounds and compositions for the treatment of cardiac and circulatory diseases |
| US4152446A (en) * | 1974-11-16 | 1979-05-01 | Boehringer Mannheim Gmbh | Aminopropanol compounds and compositions for the treatment of cardiac and circulatory diseases |
| DE2454406A1 (de) * | 1974-11-16 | 1976-05-20 | Boehringer Mannheim Gmbh | Neue aminopropanol-derivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| GB1508208A (en) * | 1975-12-05 | 1978-04-19 | Ici Ltd | Amide derivatives |
| US4115409A (en) * | 1975-12-05 | 1978-09-19 | Imperial Chemical Industries Limited | Alkanolamine derivatives |
-
1978
- 1978-04-13 DE DE19782815926 patent/DE2815926A1/de not_active Withdrawn
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1979
- 1979-04-02 CA CA324,667A patent/CA1129416A/en not_active Expired
- 1979-04-06 SU SU792745301A patent/SU810079A3/ru active
- 1979-04-06 ES ES479396A patent/ES479396A1/es not_active Expired
- 1979-04-06 FI FI791142A patent/FI70406C/fi not_active IP Right Cessation
- 1979-04-06 AU AU45820/79A patent/AU522975B2/en not_active Expired
- 1979-04-06 DK DK141979A patent/DK154555C/da not_active IP Right Cessation
- 1979-04-07 DE DE7979101063T patent/DE2960553D1/de not_active Expired
- 1979-04-07 EP EP79101063A patent/EP0004920B1/de not_active Expired
- 1979-04-08 IL IL57020A patent/IL57020A/xx unknown
- 1979-04-09 DD DD79212096A patent/DD143607A5/de not_active IP Right Cessation
- 1979-04-10 CS CS792434A patent/CS227007B2/cs unknown
- 1979-04-11 JP JP4311979A patent/JPS54157558A/ja active Granted
- 1979-04-11 ZA ZA791732A patent/ZA791732B/xx unknown
- 1979-04-12 HU HU79BO1774A patent/HU179433B/hu unknown
- 1979-04-12 AT AT0276279A patent/AT375639B/de not_active IP Right Cessation
-
1983
- 1983-04-04 US US06/479,921 patent/US4503067A/en not_active Expired - Lifetime
-
1984
- 1984-07-20 SG SG52284A patent/SG52284G/en unknown
-
1985
- 1985-01-10 HK HK23/85A patent/HK2385A/xx not_active IP Right Cessation
-
1987
- 1987-03-31 JP JP62076548A patent/JPS63258416A/ja active Pending
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1991
- 1991-12-31 CS CS914200A patent/CS420091A3/cs unknown
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1992
- 1992-06-25 MX MX9203380A patent/MX9203380A/es unknown
-
1993
- 1993-06-22 LU LU88320C patent/LU88320I2/de unknown
- 1993-06-29 NL NL930110C patent/NL930110I2/nl unknown
- 1993-09-27 LT LTRP1124A patent/LT2628B/xx unknown
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1994
- 1994-02-28 BG BG098612A patent/BG61419B2/bg unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007144785A3 (en) * | 2006-03-26 | 2008-04-17 | Uti Limited Partnership | Ryanodine receptor inhibitors and methods relating thereto |
| US8703804B2 (en) | 2006-03-26 | 2014-04-22 | Uti Limited Partnership | Ryanodine receptor inhibitors and methods relating thereto |
Also Published As
| Publication number | Publication date |
|---|---|
| DD143607A5 (de) | 1980-09-03 |
| AU4582079A (en) | 1979-10-18 |
| JPS63258416A (ja) | 1988-10-25 |
| JPS54157558A (en) | 1979-12-12 |
| IL57020A0 (en) | 1979-07-25 |
| US4503067A (en) | 1985-03-05 |
| AT375639B (de) | 1984-08-27 |
| JPH0123462B2 (Direct) | 1989-05-02 |
| FI70406B (fi) | 1986-03-27 |
| IL57020A (en) | 1982-07-30 |
| ATA276279A (de) | 1984-01-15 |
| FI791142A7 (fi) | 1979-10-14 |
| NL930110I1 (nl) | 1993-10-18 |
| DK141979A (da) | 1979-10-14 |
| ZA791732B (en) | 1980-05-28 |
| DE2815926A1 (de) | 1979-10-18 |
| EP0004920A1 (de) | 1979-10-31 |
| DE2960553D1 (en) | 1981-11-05 |
| EP0004920B1 (de) | 1981-08-05 |
| DK154555C (da) | 1989-06-19 |
| HK2385A (en) | 1985-01-18 |
| FI70406C (fi) | 1986-09-19 |
| SG52284G (en) | 1985-03-29 |
| CS420091A3 (en) | 1992-04-15 |
| AU522975B2 (en) | 1982-07-08 |
| CS227007B2 (en) | 1984-04-16 |
| DK154555B (da) | 1988-11-28 |
| HU179433B (en) | 1982-10-28 |
| ES479396A1 (es) | 1980-04-16 |
| SU810079A3 (ru) | 1981-02-28 |
| BG61419B2 (bg) | 1997-07-31 |
| NL930110I2 (nl) | 1994-12-01 |
| MX9203380A (es) | 1992-09-01 |
| LU88320I2 (de) | 1994-05-04 |
| LT2628B (lt) | 1994-04-25 |
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