FI63224C - Foerfarande foer framstaellning av medicinskt anvaendbara 5-(3-amino-2-hydroxipropoxi)-karbostyrilderivat - Google Patents
Foerfarande foer framstaellning av medicinskt anvaendbara 5-(3-amino-2-hydroxipropoxi)-karbostyrilderivat Download PDFInfo
- Publication number
- FI63224C FI63224C FI770827A FI770827A FI63224C FI 63224 C FI63224 C FI 63224C FI 770827 A FI770827 A FI 770827A FI 770827 A FI770827 A FI 770827A FI 63224 C FI63224 C FI 63224C
- Authority
- FI
- Finland
- Prior art keywords
- group
- alkyl
- carbon atoms
- cholatomers
- moiety
- Prior art date
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- 235000013399 edible fruits Nutrition 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 79
- -1 piperidino, pyrrolidino, piperazino, morpholino Chemical group 0.000 claims description 75
- 125000004432 carbon atom Chemical group C* 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 54
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- ZFXJRLUYIMXSLK-UHFFFAOYSA-N 5-(3-amino-2-hydroxypropoxy)-1H-quinolin-2-one Chemical class NCC(O)COC1=C2C=CC(=O)NC2=CC=C1 ZFXJRLUYIMXSLK-UHFFFAOYSA-N 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 4
- 206010008631 Cholera Diseases 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- OANCNKPXGDDPQS-UHFFFAOYSA-N [C].C=CC1=CC=CC=C1 Chemical group [C].C=CC1=CC=CC=C1 OANCNKPXGDDPQS-UHFFFAOYSA-N 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical group C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 142
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 140
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 72
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 239000000243 solution Substances 0.000 description 60
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- 239000002904 solvent Substances 0.000 description 37
- 230000002829 reductive effect Effects 0.000 description 36
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 238000003756 stirring Methods 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
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- ZKUQQILIPICYQD-UHFFFAOYSA-N 5-(oxan-2-yloxy)-8-phenylmethoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(OCC=2C=CC=CC=2)=C2NC(=O)CCC2=C1OC1CCCCO1 ZKUQQILIPICYQD-UHFFFAOYSA-N 0.000 description 18
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- 239000002585 base Substances 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
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- 230000000052 comparative effect Effects 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
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- 238000001953 recrystallisation Methods 0.000 description 10
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- 238000010992 reflux Methods 0.000 description 9
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- 230000000903 blocking effect Effects 0.000 description 8
- 150000004820 halides Chemical class 0.000 description 8
- 239000012456 homogeneous solution Substances 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
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- 229920006395 saturated elastomer Polymers 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical group C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 5
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- TVZJLAKRXHGVOK-UHFFFAOYSA-N 8-Hydroxycarteolol Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2OCC(O)CNC(C)(C)C TVZJLAKRXHGVOK-UHFFFAOYSA-N 0.000 description 4
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- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000001339 alkali metal compounds Chemical class 0.000 description 2
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- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
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- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
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- 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- XYSGBFRCBYEBRU-UHFFFAOYSA-N 1-benzyl-5-(oxan-2-yloxy)-8-phenylmethoxy-3,4-dihydroquinolin-2-one Chemical compound C1=CC(OCC=2C=CC=CC=2)=C2N(CC=3C=CC=CC=3)C(=O)CCC2=C1OC1CCCCO1 XYSGBFRCBYEBRU-UHFFFAOYSA-N 0.000 description 1
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- RYMVEKOKZTZGFN-UHFFFAOYSA-N 2-(3,5-dimethoxyphenoxy)ethanamine Chemical compound COC1=CC(OC)=CC(OCCN)=C1 RYMVEKOKZTZGFN-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- DVAXCYOGICFKQM-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=CC=C2NC(=O)CCC2=C1 DVAXCYOGICFKQM-UHFFFAOYSA-N 0.000 description 1
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- FSQRRLALKOLFLY-UHFFFAOYSA-N 5,8-dihydroxy-1h-quinolin-2-one Chemical class N1C(=O)C=CC2=C1C(O)=CC=C2O FSQRRLALKOLFLY-UHFFFAOYSA-N 0.000 description 1
- SZTHWBGTQITKOR-UHFFFAOYSA-N 5-(2-hydroxy-3-pyrrolidin-1-ylpropoxy)-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C=1C=C(OCC#C)C=2NC(=O)CCC=2C=1OCC(O)CN1CCCC1 SZTHWBGTQITKOR-UHFFFAOYSA-N 0.000 description 1
- WMBNSMKKEDQBNK-UHFFFAOYSA-N 5-(3-amino-2-hydroxypropoxy)-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)CCC2=C1C(OCC#C)=CC=C2OCC(O)CN WMBNSMKKEDQBNK-UHFFFAOYSA-N 0.000 description 1
- FTOLVSJSPXVSGL-UHFFFAOYSA-N 5-(oxiran-2-ylmethoxy)-8-phenylmethoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(OCC=2C=CC=CC=2)=C2NC(=O)CCC2=C1OCC1CO1 FTOLVSJSPXVSGL-UHFFFAOYSA-N 0.000 description 1
- NRIYKJPFJRDPCZ-UHFFFAOYSA-N 5-[2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]propoxy]-8-(2-methoxyethoxy)-3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=2CCC(=O)NC=2C(OCCOC)=CC=C1OCC(O)CNCCOC1=CC=C(OC)C=C1 NRIYKJPFJRDPCZ-UHFFFAOYSA-N 0.000 description 1
- XIFMJPRVQJSJSL-UHFFFAOYSA-N 5-[3-(benzylamino)-2-hydroxypropoxy]-1-methyl-8-phenylmethoxy-3,4-dihydroquinolin-2-one;hydrochloride Chemical compound Cl.C1=CC(OCC=2C=CC=CC=2)=C2N(C)C(=O)CCC2=C1OCC(O)CNCC1=CC=CC=C1 XIFMJPRVQJSJSL-UHFFFAOYSA-N 0.000 description 1
- WBMNPAPTOXJWKH-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-phenylmethoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC(C=1CCC(=O)NC=11)=CC=C1OCC1=CC=CC=C1 WBMNPAPTOXJWKH-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RLBUDOGTAJQTMS-UHFFFAOYSA-N 8-(2-hydroxyethoxy)-5-(oxiran-2-ylmethoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCO)=CC=C1OCC1CO1 RLBUDOGTAJQTMS-UHFFFAOYSA-N 0.000 description 1
- GMZIYNSIZFOLGW-UHFFFAOYSA-N 8-(2-methoxyethoxy)-5-(oxiran-2-ylmethoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCOC)=CC=C1OCC1CO1 GMZIYNSIZFOLGW-UHFFFAOYSA-N 0.000 description 1
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical group OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001590997 Moolgarda engeli Species 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-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
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- SGNKUUILPUFRBR-UHFFFAOYSA-N [5-[3-(tert-butylamino)-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] acetate;hydrochloride Chemical compound Cl.C1CC(=O)NC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2OC(=O)C SGNKUUILPUFRBR-UHFFFAOYSA-N 0.000 description 1
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- 230000007059 acute toxicity Effects 0.000 description 1
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- 125000002252 acyl group Chemical group 0.000 description 1
- 239000003513 alkali Substances 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
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- 238000010171 animal model Methods 0.000 description 1
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- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- ICLWTJIMXVISSR-UHFFFAOYSA-N gallamine Chemical compound CCN(CC)CCOC1=CC=CC(OCCN(CC)CC)=C1OCCN(CC)CC ICLWTJIMXVISSR-UHFFFAOYSA-N 0.000 description 1
- 229960003054 gallamine Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002506 iron compounds Chemical class 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- XVDBWWRIXBMVJV-UHFFFAOYSA-N n-[bis(dimethylamino)phosphanyl]-n-methylmethanamine Chemical compound CN(C)P(N(C)C)N(C)C XVDBWWRIXBMVJV-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
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N phenyl propionaldehyde Natural products CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
- C07D215/32—Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2895776 | 1976-03-17 | ||
| JP51028957A JPS5919541B2 (ja) | 1976-03-17 | 1976-03-17 | 新規３，４−ジヒドロカルボスチリル誘導体 |
| JP51052498A JPS609501B2 (ja) | 1976-05-07 | 1976-05-07 | 新規３，４−ジヒドロカルボスチリル誘導体 |
| JP5249876 | 1976-05-07 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI770827A7 FI770827A7 (en, 2012) | 1977-09-18 |
| FI63224B FI63224B (fi) | 1983-01-31 |
| FI63224C true FI63224C (fi) | 1983-05-10 |
Family
ID=26367107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI770827A FI63224C (fi) | 1976-03-17 | 1977-03-15 | Foerfarande foer framstaellning av medicinskt anvaendbara 5-(3-amino-2-hydroxipropoxi)-karbostyrilderivat |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US4289883A (en, 2012) |
| AR (1) | AR211570A1 (en, 2012) |
| AT (1) | AT363474B (en, 2012) |
| AU (1) | AU513950B2 (en, 2012) |
| CA (1) | CA1081232A (en, 2012) |
| CH (1) | CH619453A5 (en, 2012) |
| DE (1) | DE2711719C2 (en, 2012) |
| DK (1) | DK154970C (en, 2012) |
| ES (1) | ES456963A1 (en, 2012) |
| FI (1) | FI63224C (en, 2012) |
| FR (1) | FR2344538A1 (en, 2012) |
| GB (2) | GB1578972A (en, 2012) |
| IE (1) | IE45269B1 (en, 2012) |
| LU (1) | LU76957A1 (en, 2012) |
| MX (1) | MX4808E (en, 2012) |
| NL (1) | NL179816C (en, 2012) |
| NO (1) | NO149388C (en, 2012) |
| PH (1) | PH15115A (en, 2012) |
| PT (1) | PT66312B (en, 2012) |
| SE (1) | SE443140B (en, 2012) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54130587A (en) * | 1978-03-30 | 1979-10-09 | Otsuka Pharmaceut Co Ltd | Carbostyryl derivative |
| DE2901336A1 (de) * | 1979-01-15 | 1980-07-24 | Boehringer Mannheim Gmbh | Neue arylether, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| AU518814B2 (en) * | 1979-01-30 | 1981-10-22 | Otsuka Pharamaceutical Co. | Glaucoma treatment |
| DE3034237A1 (de) * | 1979-09-18 | 1981-04-16 | Otsuka Pharmaceutical Co. Ltd., Tokyo | Carbostyrilderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende, antihistaminisch wirkende mittel |
| FR2539413A1 (fr) * | 1983-01-17 | 1984-07-20 | Pos Lab | Carbostyriloximinopropanolamines utiles comme medicaments et procede pour leur preparation |
| US5541204A (en) * | 1994-12-02 | 1996-07-30 | Bristol-Myers Squibb Company | Aryloxypropanolamine β 3 adrenergic agonists |
| NZ332068A (en) * | 1996-04-09 | 2001-03-30 | Smithkline Beecham | Alpha, alpha-disubstituted arylalkylamine derivatives as calcilytic compounds |
| US6818660B2 (en) | 1996-04-09 | 2004-11-16 | Nps Pharmaceuticals, Inc. | Calcilytic compounds |
| US7202261B2 (en) | 1996-12-03 | 2007-04-10 | Nps Pharmaceuticals, Inc. | Calcilytic compounds |
| TW483881B (en) | 1996-12-03 | 2002-04-21 | Nps Pharma Inc | Calcilytic compounds |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3910924A (en) * | 1972-04-13 | 1975-10-07 | Otsuka Pharma Co Ltd | 3,4-Dihydrocarbostyril derivatives and a process for preparing the same |
| JPS48103590A (en, 2012) * | 1972-04-13 | 1973-12-25 | ||
| JPS5239035B2 (en, 2012) * | 1972-12-14 | 1977-10-03 | ||
| US3975391A (en) * | 1973-12-26 | 1976-08-17 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]ethyl-8-hydroxy-3,4-dihydrocarbostyril derivatives |
| JPS5082218A (en, 2012) * | 1973-11-10 | 1975-07-03 | ||
| DK138890C (da) * | 1973-12-26 | 1979-04-30 | Otsuka Pharma Co Ltd | Analogifremgangsmaade til fremstilling af et carbostyril- eller 3,4-dihydrocarbostyrilderivat eller syreadditionssalte deraf |
| US4026897A (en) * | 1974-01-31 | 1977-05-31 | Otsuka Pharmaceutical Company | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-hydroxycarbostyril derivatives |
| US3994901A (en) * | 1974-06-13 | 1976-11-30 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-hydroxy-3,4-dihydrocarbostyril derivatives |
| FI58329C (fi) * | 1974-11-08 | 1981-01-12 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av i 8-staellning substituerade 5-(3'-alkylamino-2'-hydroxi)propoxi-3,4-dihydrokarbostyrilderivat |
| US4081447A (en) * | 1975-04-09 | 1978-03-28 | Abbott Laboratories | 5-[2-Hydroxy-3-(3,4-dimethoxy phenethylamino)]-propoxy-3,4-dihydro carbostyril and pharmaceutically acceptable salts thereof |
| US4210753A (en) * | 1976-03-17 | 1980-07-01 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril compounds |
-
1977
- 1977-03-11 CH CH308777A patent/CH619453A5/fr not_active IP Right Cessation
- 1977-03-15 FI FI770827A patent/FI63224C/fi not_active IP Right Cessation
- 1977-03-15 IE IE563/77A patent/IE45269B1/en not_active IP Right Cessation
- 1977-03-16 LU LU76957A patent/LU76957A1/xx unknown
- 1977-03-16 NO NO770940A patent/NO149388C/no unknown
- 1977-03-16 MX MX775546U patent/MX4808E/es unknown
- 1977-03-16 DK DK115677A patent/DK154970C/da not_active IP Right Cessation
- 1977-03-16 SE SE7703000A patent/SE443140B/xx not_active IP Right Cessation
- 1977-03-16 PT PT66312A patent/PT66312B/pt unknown
- 1977-03-16 AU AU23299/77A patent/AU513950B2/en not_active Expired
- 1977-03-17 NL NLAANVRAGE7702896,A patent/NL179816C/xx not_active IP Right Cessation
- 1977-03-17 GB GB27038/79A patent/GB1578972A/en not_active Expired
- 1977-03-17 PH PH19562A patent/PH15115A/en unknown
- 1977-03-17 AT AT0181577A patent/AT363474B/de active
- 1977-03-17 AR AR266891A patent/AR211570A1/es active
- 1977-03-17 FR FR7708041A patent/FR2344538A1/fr active Granted
- 1977-03-17 CA CA274,453A patent/CA1081232A/en not_active Expired
- 1977-03-17 ES ES456963A patent/ES456963A1/es not_active Expired
- 1977-03-17 DE DE2711719A patent/DE2711719C2/de not_active Expired
- 1977-03-17 GB GB11461/77A patent/GB1578971A/en not_active Expired
-
1978
- 1978-11-30 US US05/965,535 patent/US4289883A/en not_active Expired - Lifetime
- 1978-11-30 US US05/965,469 patent/US4302588A/en not_active Expired - Lifetime
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: OTSUKA PHARMACEUTICAL CO. LTD. |