CA1081232A - 5-(3-substituted-2-hydroxypropoxy)-8-substituted-carbostyril and 3,4-dihydrocarbostyril compounds - Google Patents
5-(3-substituted-2-hydroxypropoxy)-8-substituted-carbostyril and 3,4-dihydrocarbostyril compoundsInfo
- Publication number
- CA1081232A CA1081232A CA274,453A CA274453A CA1081232A CA 1081232 A CA1081232 A CA 1081232A CA 274453 A CA274453 A CA 274453A CA 1081232 A CA1081232 A CA 1081232A
- Authority
- CA
- Canada
- Prior art keywords
- hydroxypropoxy
- dihydrocarbostyril
- group
- carbon atoms
- acid addition
- 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
- -1 5-(3-substituted-2-hydroxypropoxy)-8-substituted-carbostyril Chemical class 0.000 title claims description 153
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical class C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 title description 11
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims abstract description 125
- 239000002253 acid Substances 0.000 claims abstract description 54
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims abstract description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 5
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims abstract description 5
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims abstract description 5
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims abstract description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 78
- 125000004432 carbon atom Chemical group C* 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 55
- 239000000126 substance Substances 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 30
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 claims description 28
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 5
- AAXABQXZMJFUBP-UHFFFAOYSA-N 5-(oxiran-2-ylmethoxy)-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(OCC#C)=C2NC(=O)CCC2=C1OCC1CO1 AAXABQXZMJFUBP-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- CHTDYLDTHBWBFD-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(O)C2=C1CCC(=O)N2 CHTDYLDTHBWBFD-UHFFFAOYSA-N 0.000 claims description 3
- MFBPDWKSBUXIMP-UHFFFAOYSA-N 8-hydroxy-5-[2-hydroxy-3-(propan-2-ylamino)propoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2OCC(O)CNC(C)C MFBPDWKSBUXIMP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- RHUPWMLNRRXWPP-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(2-methoxyethoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCOC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 RHUPWMLNRRXWPP-UHFFFAOYSA-N 0.000 claims description 2
- IXJJPGSXJXQFGI-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(2-oxopropoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC(C)=O)C2=C1CCC(=O)N2 IXJJPGSXJXQFGI-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- IYAKIYAMPHNHLX-UHFFFAOYSA-N 2-[[5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl]oxy]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC(N)=O)C2=C1CCC(=O)N2 IYAKIYAMPHNHLX-UHFFFAOYSA-N 0.000 claims 2
- GGDRYRVQUYFTCF-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(5-methylhex-2-ynoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC#CCC(C)C)C2=C1CCC(=O)N2 GGDRYRVQUYFTCF-UHFFFAOYSA-N 0.000 claims 2
- ZEOYAMIVUXMZDO-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-hept-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCC#CCCCC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 ZEOYAMIVUXMZDO-UHFFFAOYSA-N 0.000 claims 2
- IECHFDQQFHBVTC-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC#C)C2=C1CCC(=O)N2 IECHFDQQFHBVTC-UHFFFAOYSA-N 0.000 claims 2
- DPXHJDPJXUDQID-UHFFFAOYSA-N [5-[2-hydroxy-3-(propan-2-ylamino)propoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] cyclohexanecarboxylate Chemical compound C1=2NC(=O)CCC=2C(OCC(O)CNC(C)C)=CC=C1OC(=O)C1CCCCC1 DPXHJDPJXUDQID-UHFFFAOYSA-N 0.000 claims 2
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 claims 2
- RXMTUVIKZRXSSM-UHFFFAOYSA-N 2,2-diphenylethanamine Chemical compound C=1C=CC=CC=1C(CN)C1=CC=CC=C1 RXMTUVIKZRXSSM-UHFFFAOYSA-N 0.000 claims 1
- HIYCLSOMRAVSMQ-UHFFFAOYSA-N 2-[[5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl]oxy]acetic acid Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC(O)=O)C2=C1CCC(=O)N2 HIYCLSOMRAVSMQ-UHFFFAOYSA-N 0.000 claims 1
- WAEDDRVLABSYBI-UHFFFAOYSA-N 5-(3-chloro-2-hydroxypropoxy)-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(OCC#C)=CC=C2OCC(CCl)O WAEDDRVLABSYBI-UHFFFAOYSA-N 0.000 claims 1
- ZVNWMAIALLVRMX-UHFFFAOYSA-N 5-[3-(tert-butylamino)-2-hydroxypropoxy]-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(OCC#C)=CC=C2OCC(O)CNC(C)(C)C ZVNWMAIALLVRMX-UHFFFAOYSA-N 0.000 claims 1
- NBSGLYCBXPDCCD-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(2-hydroxyethoxy)-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCCO)C2=C1C=CC(=O)N2 NBSGLYCBXPDCCD-UHFFFAOYSA-N 0.000 claims 1
- HVMSPULUWUSUHU-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-prop-2-ynoxy-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC#C)C2=C1C=CC(=O)N2 HVMSPULUWUSUHU-UHFFFAOYSA-N 0.000 claims 1
- XILBEXXPWNQODR-UHFFFAOYSA-N ethyl 2-[[5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl]oxy]acetate Chemical compound C1=2CCC(=O)NC=2C(OCC(=O)OCC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 XILBEXXPWNQODR-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 6
- 125000005842 heteroatom Chemical group 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 154
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 120
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- 229960001701 chloroform Drugs 0.000 description 60
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 239000000203 mixture Substances 0.000 description 37
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 238000002844 melting Methods 0.000 description 26
- 230000008018 melting Effects 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000013078 crystal Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 235000011121 sodium hydroxide Nutrition 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 229940083608 sodium hydroxide Drugs 0.000 description 19
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
- PXSBSBDNZRLRLK-UHFFFAOYSA-N 2-(2h-pyran-2-yloxy)-2h-pyran Chemical compound O1C=CC=CC1OC1OC=CC=C1 PXSBSBDNZRLRLK-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- 235000011167 hydrochloric acid Nutrition 0.000 description 16
- 229960000443 hydrochloric acid Drugs 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 150000004820 halides Chemical class 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000012456 homogeneous solution Substances 0.000 description 9
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 8
- 229960004592 isopropanol Drugs 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000008096 xylene Substances 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 239000012346 acetyl chloride Substances 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 238000010531 catalytic reduction reaction Methods 0.000 description 4
- 230000035487 diastolic blood pressure Effects 0.000 description 4
- 229910000039 hydrogen halide Inorganic materials 0.000 description 4
- 239000012433 hydrogen halide Substances 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
- 125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229960001317 isoprenaline Drugs 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 2
- YXRCDWIZAGWUBL-UHFFFAOYSA-N 2-(4-methoxyphenoxy)ethanamine Chemical compound COC1=CC=C(OCCN)C=C1 YXRCDWIZAGWUBL-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- FVXYRXMYPXVHNY-UHFFFAOYSA-N 3-propoxy-3,4-dihydro-1H-quinolin-2-one Chemical compound C(CC)OC1C(NC2=CC=CC=C2C1)=O FVXYRXMYPXVHNY-UHFFFAOYSA-N 0.000 description 2
- UHLHIYJDIQPKOU-UHFFFAOYSA-N 5,8-Dihydroxy-3,4-dihydrocarbostyril Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2O UHLHIYJDIQPKOU-UHFFFAOYSA-N 0.000 description 2
- QRXBEYORZJAXKA-UHFFFAOYSA-N 5-hydroxy-8-(2-methoxyethoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1CC(=O)NC2=C1C(O)=CC=C2OCCOC QRXBEYORZJAXKA-UHFFFAOYSA-N 0.000 description 2
- LEMGZJIEPSVWRS-UHFFFAOYSA-N 5-hydroxy-8-phenylmethoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2NC(=O)CCC=2C(O)=CC=C1OCC1=CC=CC=C1 LEMGZJIEPSVWRS-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000020446 Cardiac disease Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920006383 Tyril Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000001339 alkali metal compounds Chemical class 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000003849 aromatic solvent Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 229960002274 atenolol Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000036647 reaction Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-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
- NENBPJPXCKNIEJ-UHFFFAOYSA-N 1-benzyl-5-(oxiran-2-ylmethoxy)-8-phenylmethoxy-3,4-dihydroquinolin-2-one Chemical compound O=C1CCC2=C(OCC3CO3)C=CC(OCC3=CC=CC=C3)=C2N1CC1=CC=CC=C1 NENBPJPXCKNIEJ-UHFFFAOYSA-N 0.000 description 1
- DMPAWEHPKQFAGW-UHFFFAOYSA-N 1-benzyl-5-[3-(tert-butylamino)-2-hydroxypropoxy]-8-phenylmethoxy-3,4-dihydroquinolin-2-one hydrochloride Chemical compound Cl.CC(C)(C)NCC(O)COC1=C2CCC(=O)N(CC3=CC=CC=C3)C2=C(OCC2=CC=CC=C2)C=C1 DMPAWEHPKQFAGW-UHFFFAOYSA-N 0.000 description 1
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 1
- DPDHHHQSUFHCLJ-UHFFFAOYSA-N 1-methyl-5-(oxan-2-yloxy)-8-phenylmethoxy-3,4-dihydroquinolin-2-one Chemical compound C1=CC(OCC=2C=CC=CC=2)=C2N(C)C(=O)CCC2=C1OC1CCCCO1 DPDHHHQSUFHCLJ-UHFFFAOYSA-N 0.000 description 1
- HNNIFJFBHHKZOG-UHFFFAOYSA-N 1-methyl-5-(oxiran-2-ylmethoxy)-8-phenylmethoxy-3,4-dihydroquinolin-2-one Chemical compound C1=CC(OCC=2C=CC=CC=2)=C2N(C)C(=O)CCC2=C1OCC1CO1 HNNIFJFBHHKZOG-UHFFFAOYSA-N 0.000 description 1
- ZUGRYLJRHKHZLR-UHFFFAOYSA-N 1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=CC=C2NC(=O)C=CC2=C1 ZUGRYLJRHKHZLR-UHFFFAOYSA-N 0.000 description 1
- 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
- RYMVEKOKZTZGFN-UHFFFAOYSA-N 2-(3,5-dimethoxyphenoxy)ethanamine Chemical compound COC1=CC(OC)=CC(OCCN)=C1 RYMVEKOKZTZGFN-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- AGIBHMPYXXPGAX-UHFFFAOYSA-N 2-(iodomethyl)oxirane Chemical compound ICC1CO1 AGIBHMPYXXPGAX-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- FGXGCGSTPUEGIK-UHFFFAOYSA-N 2-[[5-[3-(2-ethoxyethylamino)-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl]oxy]acetic acid Chemical compound N1C(=O)CCC2=C1C(OCC(O)=O)=CC=C2OCC(O)CNCCOCC FGXGCGSTPUEGIK-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 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
- KUVIIUITMVVSSQ-UHFFFAOYSA-N 3-(2-hydroxypropoxy)-3,4-dihydro-1H-quinolin-2-one Chemical compound OC(COC1C(NC2=CC=CC=C2C1)=O)C KUVIIUITMVVSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- NCJRORHASCFLBI-UHFFFAOYSA-N 4-[2-[[2-hydroxy-3-[(8-hydroxy-2-oxo-1h-quinolin-5-yl)oxy]propyl]amino]ethyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1CCNCC(O)COC1=CC=C(O)C2=C1C=CC(=O)N2 NCJRORHASCFLBI-UHFFFAOYSA-N 0.000 description 1
- QMJYWVJNEVRYNU-UHFFFAOYSA-N 4-[2-[[2-hydroxy-3-[(8-hydroxy-2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]propyl]amino]ethoxy]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1OCCNCC(O)COC1=CC=C(O)C2=C1CCC(=O)N2 QMJYWVJNEVRYNU-UHFFFAOYSA-N 0.000 description 1
- SOPFBBXTMJPGBE-UHFFFAOYSA-N 4-[2-[[2-hydroxy-3-[(8-hydroxy-2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]propyl]amino]ethyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1CCNCC(O)COC1=CC=C(O)C2=C1CCC(=O)N2 SOPFBBXTMJPGBE-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-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
- LWZZNZMSEIWCDM-UHFFFAOYSA-N 5-(2-hydroxy-3-morpholin-4-ylpropoxy)-8-prop-2-ynoxy-1h-quinolin-2-one Chemical compound C=1C=C(OCC#C)C=2NC(=O)C=CC=2C=1OCC(O)CN1CCOCC1 LWZZNZMSEIWCDM-UHFFFAOYSA-N 0.000 description 1
- ILMYPIYQKZSQLF-UHFFFAOYSA-N 5-(2-hydroxy-3-morpholin-4-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)CN1CCOCC1 ILMYPIYQKZSQLF-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
- 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 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
- AXOSOURXATYIQE-UHFFFAOYSA-N 5-[2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]propoxy]-8-phenylmethoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(OC)=CC=C1OCCNCC(O)COC(C=1CCC(=O)NC=11)=CC=C1OCC1=CC=CC=C1 AXOSOURXATYIQE-UHFFFAOYSA-N 0.000 description 1
- OTVGFHDSIRKRQA-UHFFFAOYSA-N 5-[2-hydroxy-3-[4-(2-methylphenyl)piperazin-1-yl]propoxy]-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound CC1=CC=CC=C1N1CCN(CC(O)COC=2C=3CCC(=O)NC=3C(OCC#C)=CC=2)CC1 OTVGFHDSIRKRQA-UHFFFAOYSA-N 0.000 description 1
- HRIZGKKYJHKUKQ-UHFFFAOYSA-N 5-[3-(benzhydrylamino)-2-hydroxypropoxy]-8-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C=1C=C(O)C=2NC(=O)CCC=2C=1OCC(O)CNC(C=1C=CC=CC=1)C1=CC=CC=C1 HRIZGKKYJHKUKQ-UHFFFAOYSA-N 0.000 description 1
- XYAOTRBAXYLURO-UHFFFAOYSA-N 5-[3-(cyclohexylamino)-2-hydroxypropoxy]-8-(3-hydroxypropoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCCO)=CC=C1OCC(O)CNC1CCCCC1 XYAOTRBAXYLURO-UHFFFAOYSA-N 0.000 description 1
- NJFPDQRJLVPTGF-UHFFFAOYSA-N 5-[3-(tert-butylamino)-2-hydroxypropoxy]-8-(2-hydroxyethoxy)-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(OCCO)=CC=C2OCC(O)CNC(C)(C)C NJFPDQRJLVPTGF-UHFFFAOYSA-N 0.000 description 1
- KRHYRXWVJTUFFL-UHFFFAOYSA-N 5-[3-(tert-butylamino)-2-hydroxypropoxy]-8-(2-oxopropoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1CC(=O)NC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2OCC(=O)C KRHYRXWVJTUFFL-UHFFFAOYSA-N 0.000 description 1
- GJVXUKACOOZZKP-UHFFFAOYSA-N 5-[3-(tert-butylamino)-2-hydroxypropoxy]-8-(5-hydroxypentoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(OCCCCCO)=CC=C2OCC(O)CNC(C)(C)C GJVXUKACOOZZKP-UHFFFAOYSA-N 0.000 description 1
- XEWKMOFHRYRPMK-UHFFFAOYSA-N 5-[3-(tert-butylamino)-2-hydroxypropoxy]-8-pent-4-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(OCCCC#C)=CC=C2OCC(O)CNC(C)(C)C XEWKMOFHRYRPMK-UHFFFAOYSA-N 0.000 description 1
- HJEJOYSZGHHFRR-UHFFFAOYSA-N 5-[3-[2-(1,3-benzodioxol-5-yl)ethylamino]-2-hydroxypropoxy]-8-(6-methyl-5-oxoheptoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1CC(=O)NC2=C1C(OCC(O)CNCCC=1C=C3OCOC3=CC=1)=CC=C2OCCCCC(=O)C(C)C HJEJOYSZGHHFRR-UHFFFAOYSA-N 0.000 description 1
- HSATZPUNDYVWBH-UHFFFAOYSA-N 5-[3-[2-(1,3-benzodioxol-5-yloxy)ethylamino]-2-hydroxypropoxy]-8-hydroxy-3,4-dihydro-1H-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2OCC(O)CNCCOC1=CC=C(OCO2)C2=C1 HSATZPUNDYVWBH-UHFFFAOYSA-N 0.000 description 1
- JTCZXHLUBNRAJN-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenoxy)ethylamino]-2-hydroxypropoxy]-8-prop-2-ynoxy-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1OCCNCC(O)COC1=CC=C(OCC#C)C2=C1C=CC(=O)N2 JTCZXHLUBNRAJN-UHFFFAOYSA-N 0.000 description 1
- UKISVRGQBSBXDI-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-1-ethyl-8-prop-1-ynoxy-3,4-dihydroquinolin-2-one Chemical compound C1=CC(OC#CC)=C2N(CC)C(=O)CCC2=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 UKISVRGQBSBXDI-UHFFFAOYSA-N 0.000 description 1
- LAWNIAMGJUBQIU-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(1-hydroxypropan-2-yloxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OC(C)CO)C2=C1CCC(=O)N2 LAWNIAMGJUBQIU-UHFFFAOYSA-N 0.000 description 1
- FMYIAXKFYIDGCQ-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(2-hydroxyethoxy)-3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCCO)C2=C1CCC(=O)N2 FMYIAXKFYIDGCQ-UHFFFAOYSA-N 0.000 description 1
- IFFZZDMWQUBTSD-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(2-methoxyethoxy)-1h-quinolin-2-one Chemical compound C1=2C=CC(=O)NC=2C(OCCOC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 IFFZZDMWQUBTSD-UHFFFAOYSA-N 0.000 description 1
- ZSHZVWXZNAUEFY-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(3-hydroxybutoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCCC(C)O)C2=C1CCC(=O)N2 ZSHZVWXZNAUEFY-UHFFFAOYSA-N 0.000 description 1
- TVDWBMOUDIUYHB-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(5-hydroxypentoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCCCCCO)C2=C1CCC(=O)N2 TVDWBMOUDIUYHB-UHFFFAOYSA-N 0.000 description 1
- RDHMWWYMCRPBKM-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-(6-hydroxyhexoxy)-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCCCCCCO)C2=C1C=CC(=O)N2 RDHMWWYMCRPBKM-UHFFFAOYSA-N 0.000 description 1
- ONRIRMKMGFXDRT-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-hydroxy-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(O)C2=C1C=CC(=O)N2 ONRIRMKMGFXDRT-UHFFFAOYSA-N 0.000 description 1
- MOZYNPVNFGHRGA-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-hydroxy-3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(O)C2=C1CCC(=O)N2 MOZYNPVNFGHRGA-UHFFFAOYSA-N 0.000 description 1
- WBIXVRIQDSYQSB-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-pent-3-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCCC#CC)C2=C1CCC(=O)N2 WBIXVRIQDSYQSB-UHFFFAOYSA-N 0.000 description 1
- QZBUAULGUQDFLN-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-propoxy-1h-quinolin-2-one Chemical compound C1=2C=CC(=O)NC=2C(OCCC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 QZBUAULGUQDFLN-UHFFFAOYSA-N 0.000 description 1
- OEZMBOXVKMRLCV-UHFFFAOYSA-N 5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-propoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 OEZMBOXVKMRLCV-UHFFFAOYSA-N 0.000 description 1
- OKWHZWIEMYVALF-UHFFFAOYSA-N 5-[3-[2-(3,5-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-8-hex-5-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound COC1=CC(OC)=CC(CCNCC(O)COC=2C=3CCC(=O)NC=3C(OCCCCC#C)=CC=2)=C1 OKWHZWIEMYVALF-UHFFFAOYSA-N 0.000 description 1
- VCHZOBQWEWEGHX-UHFFFAOYSA-N 5-[3-[4-(4-chlorophenyl)piperazin-1-yl]-2-hydroxypropoxy]-8-(2-hydroxyethoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCO)=CC=C1OCC(O)CN(CC1)CCN1C1=CC=C(Cl)C=C1 VCHZOBQWEWEGHX-UHFFFAOYSA-N 0.000 description 1
- HDIGMAUTCNRFOA-UHFFFAOYSA-N 5-hydroxy-1-methyl-8-phenylmethoxy-3,4-dihydroquinolin-2-one Chemical compound C=12N(C)C(=O)CCC2=C(O)C=CC=1OCC1=CC=CC=C1 HDIGMAUTCNRFOA-UHFFFAOYSA-N 0.000 description 1
- UTTJAIFHRUAFED-UHFFFAOYSA-N 5-hydroxy-3,4-dihydro-2(1h)-quinolinone Chemical compound N1C(=O)CCC2=C1C=CC=C2O UTTJAIFHRUAFED-UHFFFAOYSA-N 0.000 description 1
- JUDPUVVHQWZKNL-UHFFFAOYSA-N 5-hydroxy-8-prop-2-ynoxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(OCC#C)=CC=C2O JUDPUVVHQWZKNL-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
- HQDPFAPOLQZWQK-UHFFFAOYSA-N 8-(2-hydroxyethoxy)-5-[2-hydroxy-3-(propan-2-ylamino)propoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(OCCO)=CC=C2OCC(O)CNC(C)C HQDPFAPOLQZWQK-UHFFFAOYSA-N 0.000 description 1
- RWABARSHZDKKOW-UHFFFAOYSA-N 8-(3-hydroxypropoxy)-5-[2-hydroxy-3-(3-pyrrolidin-1-ylpropylamino)propoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCCCO)=CC=C1OCC(O)CNCCCN1CCCC1 RWABARSHZDKKOW-UHFFFAOYSA-N 0.000 description 1
- ZIDRUJJSXICGEU-UHFFFAOYSA-N 8-(4-hydroxy-2-methylbutoxy)-5-[2-hydroxy-3-(4-phenylpiperazin-1-yl)propoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCC(CCO)C)=CC=C1OCC(O)CN(CC1)CCN1C1=CC=CC=C1 ZIDRUJJSXICGEU-UHFFFAOYSA-N 0.000 description 1
- BVZNSNVSZYKGEK-UHFFFAOYSA-N 8-(butoxymethoxy)-1-butyl-5-[2-hydroxy-3-(propan-2-ylamino)propoxy]-3,4-dihydroquinolin-2-one Chemical compound C1CC(=O)N(CCCC)C2=C1C(OCC(O)CNC(C)C)=CC=C2OCOCCCC BVZNSNVSZYKGEK-UHFFFAOYSA-N 0.000 description 1
- JBBRBOJFUICMLH-UHFFFAOYSA-N 8-but-2-ynoxy-5-[3-(cyclohexylamino)-2-hydroxypropoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=2CCC(=O)NC=2C(OCC#CC)=CC=C1OCC(O)CNC1CCCCC1 JBBRBOJFUICMLH-UHFFFAOYSA-N 0.000 description 1
- KFBREGGOQAZINJ-UHFFFAOYSA-N 8-but-2-ynoxy-5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-1h-quinolin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OCC#CC)C2=C1C=CC(=O)N2 KFBREGGOQAZINJ-UHFFFAOYSA-N 0.000 description 1
- IOLWUGUIRGLFJT-UHFFFAOYSA-N 8-hydroxy-5-[2-hydroxy-3-(2-phenoxyethylamino)propoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C=1C=C(O)C=2NC(=O)CCC=2C=1OCC(O)CNCCOC1=CC=CC=C1 IOLWUGUIRGLFJT-UHFFFAOYSA-N 0.000 description 1
- VFXNBAFVMSRFQZ-UHFFFAOYSA-N 8-hydroxy-5-[2-hydroxy-3-(2-phenylethylamino)propoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C=1C=C(O)C=2NC(=O)CCC=2C=1OCC(O)CNCCC1=CC=CC=C1 VFXNBAFVMSRFQZ-UHFFFAOYSA-N 0.000 description 1
- DHNVEJYKTXYCTH-UHFFFAOYSA-N 8-phenylmethoxy-3-propoxy-3,4-dihydro-1H-quinolin-2-one Chemical compound C(CC)OC1C(NC2=C(C=CC=C2C1)OCC1=CC=CC=C1)=O DHNVEJYKTXYCTH-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
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound 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
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100038239 Protein Churchill Human genes 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
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- KNEZKGHTWDMDCW-UHFFFAOYSA-N [5-[2-hydroxy-3-(propan-2-ylamino)propoxy]-2-oxo-1h-quinolin-8-yl] cyclohexanecarboxylate Chemical compound C1=2NC(=O)C=CC=2C(OCC(O)CNC(C)C)=CC=C1OC(=O)C1CCCCC1 KNEZKGHTWDMDCW-UHFFFAOYSA-N 0.000 description 1
- LUUITJPNULRFGN-UHFFFAOYSA-N [5-[3-(tert-butylamino)-2-hydroxypropoxy]-2-oxo-1h-quinolin-8-yl] acetate Chemical compound C1=CC(=O)NC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2OC(=O)C LUUITJPNULRFGN-UHFFFAOYSA-N 0.000 description 1
- WSDDNDNILNCLPG-UHFFFAOYSA-N [5-[3-(tert-butylamino)-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] acetate Chemical compound C1CC(=O)NC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2OC(=O)C WSDDNDNILNCLPG-UHFFFAOYSA-N 0.000 description 1
- NEYSKIMFOKBKAP-UHFFFAOYSA-N [5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-1h-quinolin-8-yl] 2-methylpropanoate Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OC(=O)C(C)C)C2=C1C=CC(=O)N2 NEYSKIMFOKBKAP-UHFFFAOYSA-N 0.000 description 1
- PGTPXGMPDQICER-UHFFFAOYSA-N [5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-1h-quinolin-8-yl] acetate Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OC(C)=O)C2=C1C=CC(=O)N2 PGTPXGMPDQICER-UHFFFAOYSA-N 0.000 description 1
- MJTPZYSBXLKGPC-UHFFFAOYSA-N [5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] 2-methylpropanoate Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OC(=O)C(C)C)C2=C1CCC(=O)N2 MJTPZYSBXLKGPC-UHFFFAOYSA-N 0.000 description 1
- IBMSTKQMGVUTMX-UHFFFAOYSA-N [5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] acetate Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(O)COC1=CC=C(OC(C)=O)C2=C1CCC(=O)N2 IBMSTKQMGVUTMX-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl 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
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000006640 cycloheptyl carbonyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- DATRMGMTYKBDGA-UHFFFAOYSA-N ethyl 2-[[5-[3-(tert-butylamino)-2-hydroxypropoxy]-2-oxo-1h-quinolin-8-yl]oxy]acetate Chemical compound C1=CC(=O)NC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2OCC(=O)OCC DATRMGMTYKBDGA-UHFFFAOYSA-N 0.000 description 1
- OFEVSVMSMVCHAH-UHFFFAOYSA-N ethyl 2-[[5-[3-(tert-butylamino)-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl]oxy]acetate Chemical compound C1CC(=O)NC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2OCC(=O)OCC OFEVSVMSMVCHAH-UHFFFAOYSA-N 0.000 description 1
- 125000005469 ethylenyl group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 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
- 239000000499 gel Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 108010052322 limitin Proteins 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium 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
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- XNDUFMGXKDZGDZ-UHFFFAOYSA-N methyl 2-[[5-[3-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypropoxy]-2-oxo-3,4-dihydro-1h-quinolin-8-yl]oxy]acetate Chemical compound C1=2CCC(=O)NC=2C(OCC(=O)OC)=CC=C1OCC(O)CNCCC1=CC=C(OC)C(OC)=C1 XNDUFMGXKDZGDZ-UHFFFAOYSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 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
- 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
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910052763 palladium Inorganic materials 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
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient 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
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium 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
- 238000002360 preparation method Methods 0.000 description 1
- TURAMGVWNUTQKH-UHFFFAOYSA-N propa-1,2-dien-1-one Chemical group C=C=C=O TURAMGVWNUTQKH-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 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
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 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
- 210000003437 trachea Anatomy 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- ULIAPOFMBCCSPE-UHFFFAOYSA-N tridecan-7-one Chemical group CCCCCCC(=O)CCCCCC ULIAPOFMBCCSPE-UHFFFAOYSA-N 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1081232A true CA1081232A (en) | 1980-07-08 |
Family
ID=26367107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA274,453A Expired CA1081232A (en) | 1976-03-17 | 1977-03-17 | 5-(3-substituted-2-hydroxypropoxy)-8-substituted-carbostyril and 3,4-dihydrocarbostyril compounds |
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
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1074801A (en) | 5,8-disubstituted quinolic derivatives and processes for preparing same | |
| KR970002876B1 (ko) | 피리다지논 유도체 | |
| CA1081232A (en) | 5-(3-substituted-2-hydroxypropoxy)-8-substituted-carbostyril and 3,4-dihydrocarbostyril compounds | |
| US4210753A (en) | Carbostyril compounds | |
| GB2127402A (en) | Pharmaceutically active carbostyril derivatives | |
| CA1157474A (en) | Aromatic aminoethanol compounds, process for production thereof, and utilization thereof | |
| US4216314A (en) | N-Aryloxypropyl-N'-dioxopyrimidyl-α,ω-alkylenediamines | |
| US4264613A (en) | Piperidylbenzimidazolinone compounds | |
| US5403857A (en) | Benzenesulphonamide derivatives having 5-lipoxygenase inhibitory activity | |
| JPS6215062B2 (en, 2012) | ||
| CA1185240A (en) | Alkylenedioxybenzene derivatives and acid addition salts thereof | |
| EP0054304B1 (en) | Alkylenedioxybenzene derivatives, acid addition salts thereof and a method for their preparation | |
| US4363808A (en) | N-(3-Phenoxy-2-hydroxypropyl)benzimidazole-1-alkanamines | |
| US4147869A (en) | 3,4-Dihydrocarbostyril derivatives and process for preparing the same | |
| HU176895B (en) | Process for preparing new aminoalkoxy-phenyl-derivatives | |
| GB1566491A (en) | Substituted pyranones and their preparation | |
| US4092416A (en) | Benzopyrone derivatives exhibiting anti-allergic activity | |
| CA2015730C (en) | Esters of phenylalkanoic acid | |
| US4808618A (en) | Substituted 1,3-dialkylpyrido[4,3-d]pyrimidine-2,4-diones | |
| CA1192198A (en) | Quinolylacetic acid compounds, process for producing thereof and pharmaceutical compositions containing them | |
| CA1247116A (en) | 7,8,9,10-tetrahydro-6-oxo-6h-dibenzo/b,d/pyranyloxy- propanes | |
| EP0097202B1 (en) | Hydrazinopyridazine compound, process for production thereof, and use thereof as medicament | |
| EP0116268A1 (en) | Novel quinazolinone derivative, a process for preparing the same and a pharmaceutical composition | |
| EP0419286A2 (en) | Pyridone nitriles useful in treating cardiovascular disease | |
| BE852556A (fr) | Derives de carbostyrile et leur procede de preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |