DE2825048C2 - - Google Patents
Info
- Publication number
- DE2825048C2 DE2825048C2 DE2825048A DE2825048A DE2825048C2 DE 2825048 C2 DE2825048 C2 DE 2825048C2 DE 2825048 A DE2825048 A DE 2825048A DE 2825048 A DE2825048 A DE 2825048A DE 2825048 C2 DE2825048 C2 DE 2825048C2
- Authority
- DE
- Germany
- Prior art keywords
- group
- carbostyril
- propoxy
- methyl
- carbon atoms
- 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 - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 claims description 116
- -1 2- (3,4-dimethoxyphenyl) ethyl group Chemical group 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 45
- 150000001412 amines Chemical class 0.000 claims description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 150000001447 alkali salts Chemical class 0.000 claims description 5
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000008043 acidic salts Chemical class 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000005529 alkyleneoxy group Chemical group 0.000 claims 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims 1
- 229940000425 combination drug Drugs 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 106
- 239000000243 solution Substances 0.000 description 92
- 239000013078 crystal Substances 0.000 description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- 239000002904 solvent Substances 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 230000008018 melting Effects 0.000 description 35
- 238000002844 melting Methods 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- 238000003756 stirring Methods 0.000 description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- 239000003054 catalyst Substances 0.000 description 28
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 16
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- 230000002401 inhibitory effect Effects 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 239000007832 Na2SO4 Substances 0.000 description 15
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 13
- 150000007514 bases Chemical class 0.000 description 13
- 229940095074 cyclic amp Drugs 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 235000011121 sodium hydroxide Nutrition 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 239000012452 mother liquor Substances 0.000 description 11
- 235000015320 potassium carbonate Nutrition 0.000 description 11
- 229940086542 triethylamine Drugs 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 210000004623 platelet-rich plasma Anatomy 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102000008186 Collagen Human genes 0.000 description 9
- 108010035532 Collagen Proteins 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 230000002776 aggregation Effects 0.000 description 9
- 238000004220 aggregation Methods 0.000 description 9
- 229920001436 collagen Polymers 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 235000002639 sodium chloride Nutrition 0.000 description 9
- 235000009518 sodium iodide Nutrition 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 8
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 8
- UIAYVIIHMORPSJ-UHFFFAOYSA-N N-cyclohexyl-N-methyl-4-[(2-oxo-1H-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C)C1CCCCC1 UIAYVIIHMORPSJ-UHFFFAOYSA-N 0.000 description 8
- 150000008065 acid anhydrides Chemical class 0.000 description 8
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 8
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 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 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000002140 halogenating effect Effects 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 235000011118 potassium hydroxide Nutrition 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 229910052722 tritium Inorganic materials 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical class C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 5
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 229910017052 cobalt Inorganic materials 0.000 description 5
- 239000010941 cobalt Substances 0.000 description 5
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 230000035699 permeability Effects 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- 239000002798 polar solvent Substances 0.000 description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- FHJRNXFGMHYZDW-UHFFFAOYSA-N 4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoic acid Chemical compound N1C(=O)C=CC2=CC(OCCCC(=O)O)=CC=C21 FHJRNXFGMHYZDW-UHFFFAOYSA-N 0.000 description 4
- HQWFWBNJUPPCDU-UHFFFAOYSA-N 4-chloro-n-cyclohexyl-n-methylbutanamide Chemical compound ClCCCC(=O)N(C)C1CCCCC1 HQWFWBNJUPPCDU-UHFFFAOYSA-N 0.000 description 4
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- BBQQLBGXIDYZRE-UHFFFAOYSA-N [4-[methyl-[4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoyl]amino]cyclohexyl] acetate Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C)C1CCC(OC(C)=O)CC1 BBQQLBGXIDYZRE-UHFFFAOYSA-N 0.000 description 4
- 229960005305 adenosine Drugs 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 229910052759 nickel Inorganic materials 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
- 239000011736 potassium bicarbonate Substances 0.000 description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 4
- AQLYZDRHNHZHIS-UHFFFAOYSA-N quinoline-2,6-diol Chemical compound N1C(=O)C=CC2=CC(O)=CC=C21 AQLYZDRHNHZHIS-UHFFFAOYSA-N 0.000 description 4
- 229910052703 rhodium Inorganic materials 0.000 description 4
- 239000010948 rhodium Substances 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 3
- LHSYLPPPCKSEOW-UHFFFAOYSA-N 4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanoic acid Chemical compound N1C(=O)CCC2=CC(OCCCC(=O)O)=CC=C21 LHSYLPPPCKSEOW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229920002261 Corn starch Polymers 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 238000003436 Schotten-Baumann reaction Methods 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 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
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 210000003298 dental enamel Anatomy 0.000 description 3
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000005658 halogenation reaction Methods 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
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- QQHNGZNHRRLNKI-UHFFFAOYSA-N methyl carbonobromidate Chemical compound COC(Br)=O QQHNGZNHRRLNKI-UHFFFAOYSA-N 0.000 description 3
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- HMDSHIZGTPRJHT-UHFFFAOYSA-N n,2-dimethylcyclohexan-1-amine Chemical compound CNC1CCCCC1C HMDSHIZGTPRJHT-UHFFFAOYSA-N 0.000 description 3
- IKZRDLOFEKQEPJ-UHFFFAOYSA-N n,3-dimethyl-n-(2-methylcyclohexyl)-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCC(C)CC(=O)N(C)C1CCCCC1C IKZRDLOFEKQEPJ-UHFFFAOYSA-N 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
- 229940001584 sodium metabisulfite Drugs 0.000 description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- SMXSSIWOLSYXGA-UHFFFAOYSA-N 3-methyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoic acid Chemical compound N1C(=O)C=CC2=CC(OCC(C)CC(O)=O)=CC=C21 SMXSSIWOLSYXGA-UHFFFAOYSA-N 0.000 description 2
- UVSKBQACCRVBTH-UHFFFAOYSA-N 3-methyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]butanoic acid Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(C)CC(O)=O UVSKBQACCRVBTH-UHFFFAOYSA-N 0.000 description 2
- OYUIUMREMKVLBL-UHFFFAOYSA-N 4-chloro-n-ethyl-3-methyl-n-(2-methylcyclohexyl)butanamide Chemical compound ClCC(C)CC(=O)N(CC)C1CCCCC1C OYUIUMREMKVLBL-UHFFFAOYSA-N 0.000 description 2
- XCXDDKNPUFGHKD-UHFFFAOYSA-N 6-hydroxy-1-methyl-3,4-dihydroquinolin-2-one Chemical compound OC1=CC=C2N(C)C(=O)CCC2=C1 XCXDDKNPUFGHKD-UHFFFAOYSA-N 0.000 description 2
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CBWUNQZJGJFJLZ-UHFFFAOYSA-N [Cl].Cl Chemical compound [Cl].Cl CBWUNQZJGJFJLZ-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 239000010425 asbestos Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 description 2
- 150000001555 benzenes Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000000035 biogenic effect Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 150000001924 cycloalkanes Chemical class 0.000 description 2
- 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 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 150000002168 ethanoic acid esters Chemical class 0.000 description 2
- SNBIRWAABSXIMA-UHFFFAOYSA-N ethyl 2-[(8-bromo-2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]acetate Chemical compound N1C(=O)CCC2=C1C(Br)=CC=C2OCC(=O)OCC SNBIRWAABSXIMA-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 150000002366 halogen compounds Chemical class 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000003112 inhibitor Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- RQGJDYPBBZGUKL-UHFFFAOYSA-N n-cyclohexyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)NC1CCCCC1 RQGJDYPBBZGUKL-UHFFFAOYSA-N 0.000 description 2
- NYTVEEANUQPCMO-UHFFFAOYSA-N n-cyclohexyl-n,3-dimethyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCC(C)CC(=O)N(C)C1CCCCC1 NYTVEEANUQPCMO-UHFFFAOYSA-N 0.000 description 2
- QEOVZKKLVAZJGC-UHFFFAOYSA-N n-cyclohexyl-n-ethyl-3-methyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]butanamide Chemical compound C=1C=CC=2NC(=O)CCC=2C=1OCC(C)CC(=O)N(CC)C1CCCCC1 QEOVZKKLVAZJGC-UHFFFAOYSA-N 0.000 description 2
- HHWYQEJEFUHTPT-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-(1-methyl-2-oxoquinolin-6-yl)oxybutanamide Chemical compound C=1C=C2N(C)C(=O)C=CC2=CC=1OCCCC(=O)N(C)C1CCCCC1 HHWYQEJEFUHTPT-UHFFFAOYSA-N 0.000 description 2
- MAIPUMHMEHYUGW-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]butanamide Chemical compound C=1C=CC=2NC(=O)CCC=2C=1OCCCC(=O)N(C)C1CCCCC1 MAIPUMHMEHYUGW-UHFFFAOYSA-N 0.000 description 2
- AGVKXDPPPSLISR-UHFFFAOYSA-N n-ethylcyclohexanamine Chemical compound CCNC1CCCCC1 AGVKXDPPPSLISR-UHFFFAOYSA-N 0.000 description 2
- 229910000480 nickel oxide Inorganic materials 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 description 2
- 229960001789 papaverine Drugs 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229910052895 riebeckite Inorganic materials 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- WYNJLBDOYKQQTE-UHFFFAOYSA-N (4-nitrophenyl) 3-methyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoate Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCC(C)CC(=O)OC1=CC=C([N+]([O-])=O)C=C1 WYNJLBDOYKQQTE-UHFFFAOYSA-N 0.000 description 1
- ZVMLBJUTFOGOAM-UHFFFAOYSA-N (4-nitrophenyl) 4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)CCCOC1=CC=C(NC(=O)C=C2)C2=C1 ZVMLBJUTFOGOAM-UHFFFAOYSA-N 0.000 description 1
- SJQBHNHASPQACB-ONEGZZNKSA-N (e)-1,2-dimethoxyethene Chemical group CO\C=C\OC SJQBHNHASPQACB-ONEGZZNKSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- BLIQUJLAJXRXSG-UHFFFAOYSA-N 1-benzyl-3-(trifluoromethyl)pyrrolidin-1-ium-3-carboxylate Chemical compound C1C(C(=O)O)(C(F)(F)F)CCN1CC1=CC=CC=C1 BLIQUJLAJXRXSG-UHFFFAOYSA-N 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- ANPXPHDDYSTTKQ-UHFFFAOYSA-N 1-methyl-3-(2-methylpropyl)-9h-xanthene Chemical compound C1=CC=C2OC3=CC(CC(C)C)=CC(C)=C3CC2=C1 ANPXPHDDYSTTKQ-UHFFFAOYSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005976 1-phenylethyloxy group Chemical group 0.000 description 1
- NXBJSUOOKXVSFX-UHFFFAOYSA-N 2-(propan-2-ylamino)cyclohexan-1-ol Chemical compound CC(C)NC1CCCCC1O NXBJSUOOKXVSFX-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- ITLOWEUCMKICEF-UHFFFAOYSA-N 2-[(8-bromo-2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]acetic acid Chemical compound N1C(=O)CCC2=C1C(Br)=CC=C2OCC(=O)O ITLOWEUCMKICEF-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical class 0.000 description 1
- PQMCFTMVQORYJC-UHFFFAOYSA-N 2-aminocyclohexan-1-ol Chemical compound NC1CCCCC1O PQMCFTMVQORYJC-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- FWJSWOKMWDIRJA-UHFFFAOYSA-N 2-methyl-2-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]propanoic acid Chemical compound N1C(=O)CCC2=CC(OC(C)(C)C(O)=O)=CC=C21 FWJSWOKMWDIRJA-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 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
- 125000005975 2-phenylethyloxy group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- LQIMKAYQADIOHA-UHFFFAOYSA-N 3-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]-n-propan-2-ylpropanamide Chemical compound N1C(=O)CCC2=CC(OCCC(=O)NC(C)C)=CC=C21 LQIMKAYQADIOHA-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WZWIHIXOELFINB-UHFFFAOYSA-N 3-methyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]-n-propylbutanamide Chemical compound N1C(=O)CCC2=CC(OCC(C)CC(=O)NCCC)=CC=C21 WZWIHIXOELFINB-UHFFFAOYSA-N 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005977 3-phenylpropyloxy group Chemical group 0.000 description 1
- OMJKFWFDNIIACS-UHFFFAOYSA-N 4-(methylamino)cyclohexan-1-ol Chemical compound CNC1CCC(O)CC1 OMJKFWFDNIIACS-UHFFFAOYSA-N 0.000 description 1
- PWCABTKLGNWKKO-UHFFFAOYSA-N 4-[(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)oxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=C2N(C)C(=O)CCC2=C1 PWCABTKLGNWKKO-UHFFFAOYSA-N 0.000 description 1
- CVTSMAOVTVKGJQ-UHFFFAOYSA-N 4-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]butanoic acid Chemical compound N1C(=O)CCC2=C1C=CC=C2OCCCC(=O)O CVTSMAOVTVKGJQ-UHFFFAOYSA-N 0.000 description 1
- LRRQYOXJIZKCQD-UHFFFAOYSA-N 4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]-n,n-diphenylbutanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 LRRQYOXJIZKCQD-UHFFFAOYSA-N 0.000 description 1
- AWDIMEMWBBWIFF-UHFFFAOYSA-N 4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]-n-phenylbutanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)NC1=CC=CC=C1 AWDIMEMWBBWIFF-UHFFFAOYSA-N 0.000 description 1
- OJIPCLUWCYVOAQ-UHFFFAOYSA-N 4-[(5-chloro-2-oxo-1h-quinolin-6-yl)oxy]-n-cyclohexyl-n-methylbutanamide Chemical compound C=1C=C2NC(=O)C=CC2=C(Cl)C=1OCCCC(=O)N(C)C1CCCCC1 OJIPCLUWCYVOAQ-UHFFFAOYSA-N 0.000 description 1
- HYSNAKBSWGQEAV-UHFFFAOYSA-N 4-[(6,8-dichloro-2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]-n-ethyl-n-phenylbutanamide Chemical compound ClC=1C=C(Cl)C=2NC(=O)CCC=2C=1OCCCC(=O)N(CC)C1=CC=CC=C1 HYSNAKBSWGQEAV-UHFFFAOYSA-N 0.000 description 1
- PBSUVEWLDXZWHD-UHFFFAOYSA-N 4-chloro-n-cyclohexyl-n-ethyl-3-methylbutanamide Chemical compound ClCC(C)CC(=O)N(CC)C1CCCCC1 PBSUVEWLDXZWHD-UHFFFAOYSA-N 0.000 description 1
- ONFLCMFDSFTMPA-UHFFFAOYSA-N 4-chloro-n-methyl-n-phenylbutanamide Chemical compound ClCCCC(=O)N(C)C1=CC=CC=C1 ONFLCMFDSFTMPA-UHFFFAOYSA-N 0.000 description 1
- ZFIQGRISGKSVAG-UHFFFAOYSA-N 4-methylaminophenol Chemical compound CNC1=CC=C(O)C=C1 ZFIQGRISGKSVAG-UHFFFAOYSA-N 0.000 description 1
- 125000003836 4-phenylbutoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 102000004008 5'-Nucleotidase Human genes 0.000 description 1
- FBFZNNSQKCCHAO-UHFFFAOYSA-N 5,6,7-trichloro-8-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1CC(=O)NC2=C1C(Cl)=C(Cl)C(Cl)=C2O FBFZNNSQKCCHAO-UHFFFAOYSA-N 0.000 description 1
- NXGYIDNFNINXDO-UHFFFAOYSA-N 5,7,8-trichloro-6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C(Cl)C(O)=C(Cl)C(Cl)=C21 NXGYIDNFNINXDO-UHFFFAOYSA-N 0.000 description 1
- OGHVHWURQPBPBZ-UHFFFAOYSA-N 6,8-dichloro-5-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(Cl)=CC(Cl)=C2O OGHVHWURQPBPBZ-UHFFFAOYSA-N 0.000 description 1
- KLQUAIPDEJVPEG-UHFFFAOYSA-N 6-(2-morpholin-4-yl-2-oxoethoxy)-3,4-dihydro-1h-quinolin-2-one Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCC(=O)N1CCOCC1 KLQUAIPDEJVPEG-UHFFFAOYSA-N 0.000 description 1
- NOIQPNXLNANOPX-UHFFFAOYSA-N 6-hydroxy-1-methylquinolin-2-one Chemical compound C1=C(O)C=C2C=CC(=O)N(C)C2=C1 NOIQPNXLNANOPX-UHFFFAOYSA-N 0.000 description 1
- CBTAWFFEPGSZNS-UHFFFAOYSA-N 7-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]heptanoic acid Chemical compound N1C(=O)CCC2=C1C=CC=C2OCCCCCCC(=O)O CBTAWFFEPGSZNS-UHFFFAOYSA-N 0.000 description 1
- DQJZKRKTOJJCCO-UHFFFAOYSA-N 7-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]heptanoic acid Chemical compound N1C(=O)CCC2=CC(OCCCCCCC(=O)O)=CC=C21 DQJZKRKTOJJCCO-UHFFFAOYSA-N 0.000 description 1
- CUIKMKFHNHPLPY-UHFFFAOYSA-N 8-bromo-5-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(Br)=CC=C2O CUIKMKFHNHPLPY-UHFFFAOYSA-N 0.000 description 1
- UDKMDIKMJWOSJP-UHFFFAOYSA-N 8-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound C1CC(=O)NC2=C1C=CC=C2O UDKMDIKMJWOSJP-UHFFFAOYSA-N 0.000 description 1
- AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- SNGWPOZURCAELA-UHFFFAOYSA-N ClC1=C2CCC(N=C2C(=CC1(OCCCC(=O)N(C1CCC(CC1)OC(C)=O)C)Cl)Cl)=O Chemical compound ClC1=C2CCC(N=C2C(=CC1(OCCCC(=O)N(C1CCC(CC1)OC(C)=O)C)Cl)Cl)=O SNGWPOZURCAELA-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 244000292411 Excoecaria agallocha Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- HAWJJTBWFDGAJQ-UHFFFAOYSA-N N-butyl-4-[(5-chloro-2-oxo-1H-quinolin-6-yl)oxy]-N-cyclohexylbutanamide Chemical compound ClC1=C2C=CC(NC2=CC=C1OCCCC(=O)N(CCCC)C1CCCCC1)=O HAWJJTBWFDGAJQ-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029216 Nervousness Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- BERPCVULMUPOER-UHFFFAOYSA-N Quinolinediol Chemical class C1=CC=C2NC(=O)C(O)=CC2=C1 BERPCVULMUPOER-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DQMDZQHIHGAMRK-UHFFFAOYSA-N [(4-acetyloxycyclohexyl)-methylamino] 4-[(2-oxo-1H-quinolin-6-yl)oxy]butanoate Chemical compound CN(C1CCC(CC1)OC(C)=O)OC(=O)CCCOC=1C=C2C=CC(NC2=CC=1)=O DQMDZQHIHGAMRK-UHFFFAOYSA-N 0.000 description 1
- SKAJFTMILLERCB-UHFFFAOYSA-M [Na+].CC(O)=O.CC(O)=O.CC(O)=O.CC([O-])=O Chemical compound [Na+].CC(O)=O.CC(O)=O.CC(O)=O.CC([O-])=O SKAJFTMILLERCB-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- LRHVEGCJASOOIG-UHFFFAOYSA-N acetic acid;bromoethane Chemical compound CCBr.CC(O)=O LRHVEGCJASOOIG-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000004054 benzoquinones Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 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
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000004122 cyclic 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
- 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
- FQROBSPJQAMMPA-UHFFFAOYSA-N cyclohexyl 4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanoate Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)OC1CCCCC1 FQROBSPJQAMMPA-UHFFFAOYSA-N 0.000 description 1
- 150000003946 cyclohexylamines Chemical class 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- OCDXZFSOHJRGIL-UHFFFAOYSA-N cyclohexyloxycyclohexane Chemical compound C1CCCCC1OC1CCCCC1 OCDXZFSOHJRGIL-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- OKQSSSVVBOUMNZ-UHFFFAOYSA-N diminazene diaceturate Chemical compound CC(=O)NCC(O)=O.CC(=O)NCC(O)=O.C1=CC(C(=N)N)=CC=C1NN=NC1=CC=C(C(N)=N)C=C1 OKQSSSVVBOUMNZ-UHFFFAOYSA-N 0.000 description 1
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- WCTMRZGBQOAJNP-UHFFFAOYSA-N ethyl 2-[(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)oxy]propanoate Chemical compound CN1C(=O)CCC2=CC(OC(C)C(=O)OCC)=CC=C21 WCTMRZGBQOAJNP-UHFFFAOYSA-N 0.000 description 1
- ORTHSJDDYKIPFJ-UHFFFAOYSA-N ethyl 2-[(2-oxo-1h-quinolin-6-yl)oxy]propanoate Chemical compound N1C(=O)C=CC2=CC(OC(C)C(=O)OCC)=CC=C21 ORTHSJDDYKIPFJ-UHFFFAOYSA-N 0.000 description 1
- HFUIGOFKSVEFSI-UHFFFAOYSA-N ethyl 2-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]propanoate Chemical compound N1C(=O)CCC2=CC(OC(C)C(=O)OCC)=CC=C21 HFUIGOFKSVEFSI-UHFFFAOYSA-N 0.000 description 1
- YCLBWBPKRSBGEB-UHFFFAOYSA-N ethyl 2-[(2-oxo-3,4-dihydro-1h-quinolin-7-yl)oxy]propanoate Chemical compound C1CC(=O)NC2=CC(OC(C)C(=O)OCC)=CC=C21 YCLBWBPKRSBGEB-UHFFFAOYSA-N 0.000 description 1
- ZXCQOWHICBYYQD-UHFFFAOYSA-N ethyl 2-[(2-oxo-3,4-dihydro-1h-quinolin-8-yl)oxy]propanoate Chemical compound C1CC(=O)NC2=C1C=CC=C2OC(C)C(=O)OCC ZXCQOWHICBYYQD-UHFFFAOYSA-N 0.000 description 1
- MVUIGVBMKMEMIP-UHFFFAOYSA-N ethyl 3-methyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoate Chemical compound N1C(=O)C=CC2=CC(OCC(C)CC(=O)OCC)=CC=C21 MVUIGVBMKMEMIP-UHFFFAOYSA-N 0.000 description 1
- HFNZBYCSGWOSSC-UHFFFAOYSA-N ethyl 4-[(2-oxo-1h-quinolin-6-yl)oxy]butanoate Chemical compound N1C(=O)C=CC2=CC(OCCCC(=O)OCC)=CC=C21 HFNZBYCSGWOSSC-UHFFFAOYSA-N 0.000 description 1
- JAQRBXZYBPDYJA-UHFFFAOYSA-N ethyl 4-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]butanoate Chemical compound N1C(=O)CCC2=C1C=CC=C2OCCCC(=O)OCC JAQRBXZYBPDYJA-UHFFFAOYSA-N 0.000 description 1
- QOQVKCLJMBKWCA-UHFFFAOYSA-N ethyl 4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanoate Chemical compound N1C(=O)CCC2=CC(OCCCC(=O)OCC)=CC=C21 QOQVKCLJMBKWCA-UHFFFAOYSA-N 0.000 description 1
- ROMUOLIBKWIVQG-UHFFFAOYSA-N ethyl 7-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]heptanoate Chemical compound N1C(=O)CCC2=CC(OCCCCCCC(=O)OCC)=CC=C21 ROMUOLIBKWIVQG-UHFFFAOYSA-N 0.000 description 1
- XCPXPFNKTCFWTA-UHFFFAOYSA-N ethyl carbonobromidate Chemical compound CCOC(Br)=O XCPXPFNKTCFWTA-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000003977 halocarboxylic acids Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- QTBFPMKWQKYFLR-UHFFFAOYSA-N isobutyl chloride Chemical compound CC(C)CCl QTBFPMKWQKYFLR-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 1
- FEQYITXCOLIQRI-UHFFFAOYSA-N n,3-dimethyl-n-(2-methylcyclohexyl)-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCC(C)CC(=O)N(C)C1CCCCC1C FEQYITXCOLIQRI-UHFFFAOYSA-N 0.000 description 1
- ZQVOIVLHTTWANF-UHFFFAOYSA-N n,n-dicyclohexyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)N(C1CCCCC1)C1CCCCC1 ZQVOIVLHTTWANF-UHFFFAOYSA-N 0.000 description 1
- ULZFIGHUHPVTHP-UHFFFAOYSA-N n,n-dimethyl-2-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]acetamide Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(=O)N(C)C ULZFIGHUHPVTHP-UHFFFAOYSA-N 0.000 description 1
- GNPIAQKLWNSYIN-UHFFFAOYSA-N n-(2-chlorocyclohexyl)-n-cyclohexyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound ClC1CCCCC1N(C(=O)CCCOC=1C=C2CCC(=O)NC2=CC=1)C1CCCCC1 GNPIAQKLWNSYIN-UHFFFAOYSA-N 0.000 description 1
- PYDXJQWWXPSIHY-UHFFFAOYSA-N n-(4-hydroxycyclohexyl)-n-methyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C)C1CCC(O)CC1 PYDXJQWWXPSIHY-UHFFFAOYSA-N 0.000 description 1
- BRKAZJSNXFCALC-UHFFFAOYSA-N n-(cyclohexylmethyl)-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)NCC1CCCCC1 BRKAZJSNXFCALC-UHFFFAOYSA-N 0.000 description 1
- KVZYKYUSNOBGTM-UHFFFAOYSA-N n-benzyl-4-[(1-ethyl-2-oxo-3,4-dihydroquinolin-5-yl)oxy]butanamide Chemical compound C1=CC=C2N(CC)C(=O)CCC2=C1OCCCC(=O)NCC1=CC=CC=C1 KVZYKYUSNOBGTM-UHFFFAOYSA-N 0.000 description 1
- OOOWCHQFULPVTF-UHFFFAOYSA-N n-benzyl-n-cyclohexyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C1CCCCC1)CC1=CC=CC=C1 OOOWCHQFULPVTF-UHFFFAOYSA-N 0.000 description 1
- ZUYNBXWHCMZZIE-UHFFFAOYSA-N n-benzyl-n-cyclohexyl-7-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]heptanamide Chemical compound C=1C=CC=2NC(=O)CCC=2C=1OCCCCCCC(=O)N(C1CCCCC1)CC1=CC=CC=C1 ZUYNBXWHCMZZIE-UHFFFAOYSA-N 0.000 description 1
- IYWYMFZAZUYNLC-UHFFFAOYSA-N n-benzylcyclohexanamine Chemical compound C=1C=CC=CC=1CNC1CCCCC1 IYWYMFZAZUYNLC-UHFFFAOYSA-N 0.000 description 1
- LOHRHKXCMFGXCM-UHFFFAOYSA-N n-butyl-n-cyclohexyl-5-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]pentanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC(=O)N(CCCC)C1CCCCC1 LOHRHKXCMFGXCM-UHFFFAOYSA-N 0.000 description 1
- VXXLEXCQCSPKFI-UHFFFAOYSA-N n-butylcyclohexanamine Chemical compound CCCCNC1CCCCC1 VXXLEXCQCSPKFI-UHFFFAOYSA-N 0.000 description 1
- IAVMSZUTKWUMCA-UHFFFAOYSA-N n-cycloheptyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)NC1CCCCCC1 IAVMSZUTKWUMCA-UHFFFAOYSA-N 0.000 description 1
- UFPVSNJQXZJXSF-UHFFFAOYSA-N n-cyclohexyl-3-hydroxy-n-methyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCC(O)CC(=O)N(C)C1CCCCC1 UFPVSNJQXZJXSF-UHFFFAOYSA-N 0.000 description 1
- KLCAQUFEGKILBV-UHFFFAOYSA-N n-cyclohexyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]-n-phenylbutanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C=1C=CC=CC=1)C1CCCCC1 KLCAQUFEGKILBV-UHFFFAOYSA-N 0.000 description 1
- HMFXIDNJCWANQB-UHFFFAOYSA-N n-cyclohexyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)NC1CCCCC1 HMFXIDNJCWANQB-UHFFFAOYSA-N 0.000 description 1
- LQOZPHGENDQTNS-UHFFFAOYSA-N n-cyclohexyl-4-[(8-hydroxy-2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]-n-methylbutanamide Chemical compound C=1C=C(O)C=2NC(=O)CCC=2C=1OCCCC(=O)N(C)C1CCCCC1 LQOZPHGENDQTNS-UHFFFAOYSA-N 0.000 description 1
- WJPDPBXURRIOFG-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-[(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2N(C)C(=O)CCC2=CC=1OCCCC(=O)N(C)C1CCCCC1 WJPDPBXURRIOFG-UHFFFAOYSA-N 0.000 description 1
- XSUBCFUQNASGMT-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)N(C)C1CCCCC1 XSUBCFUQNASGMT-UHFFFAOYSA-N 0.000 description 1
- MLVYGERFZRVATE-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-[(5,7,8-trichloro-2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound ClC=1C(Cl)=C2NC(=O)C=CC2=C(Cl)C=1OCCCC(=O)N(C)C1CCCCC1 MLVYGERFZRVATE-UHFFFAOYSA-N 0.000 description 1
- PMWNKFSLBFEUKO-UHFFFAOYSA-N n-cyclohexyl-n-methyl-7-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]heptanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCCCC(=O)N(C)C1CCCCC1 PMWNKFSLBFEUKO-UHFFFAOYSA-N 0.000 description 1
- XPRXUARMKOMPCN-UHFFFAOYSA-N n-ethyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]-n-phenylbutanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(CC)C1=CC=CC=C1 XPRXUARMKOMPCN-UHFFFAOYSA-N 0.000 description 1
- GTHUFXHESVDRBB-UHFFFAOYSA-N n-ethyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-5-yl)oxy]-n-phenylbutanamide Chemical compound C=1C=CC=2NC(=O)CCC=2C=1OCCCC(=O)N(CC)C1=CC=CC=C1 GTHUFXHESVDRBB-UHFFFAOYSA-N 0.000 description 1
- OVIZUAPOIAVILA-UHFFFAOYSA-N n-methyl-4-[(2-oxo-1h-quinolin-6-yl)oxy]-n-phenylbutanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C)C1=CC=CC=C1 OVIZUAPOIAVILA-UHFFFAOYSA-N 0.000 description 1
- JREJXTLTNVFDGX-UHFFFAOYSA-N n-methyl-4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]-n-phenylbutanamide Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCC(=O)N(C)C1=CC=CC=C1 JREJXTLTNVFDGX-UHFFFAOYSA-N 0.000 description 1
- LCUCBBNKAFTMEG-UHFFFAOYSA-N n-methyl-n-(2-methylcyclohexyl)-4-[(2-oxo-1h-quinolin-6-yl)oxy]butanamide Chemical compound CC1CCCCC1N(C)C(=O)CCCOC1=CC=C(NC(=O)C=C2)C2=C1 LCUCBBNKAFTMEG-UHFFFAOYSA-N 0.000 description 1
- SQGBZKZDUMBTIJ-UHFFFAOYSA-N n-prop-2-enylcyclohexanamine Chemical compound C=CCNC1CCCCC1 SQGBZKZDUMBTIJ-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- HZPNKQREYVVATQ-UHFFFAOYSA-L nickel(2+);diformate Chemical group [Ni+2].[O-]C=O.[O-]C=O HZPNKQREYVVATQ-UHFFFAOYSA-L 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- TWVXKHLXVRWAAP-UHFFFAOYSA-N pentyl 2-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]propanoate Chemical compound N1C(=O)CCC2=CC(OC(C)C(=O)OCCCCC)=CC=C21 TWVXKHLXVRWAAP-UHFFFAOYSA-N 0.000 description 1
- CQPOKUTXQWMNDQ-UHFFFAOYSA-N pentyl 4-[(2-oxo-3,4-dihydro-1h-quinolin-6-yl)oxy]butanoate Chemical compound N1C(=O)CCC2=CC(OCCCC(=O)OCCCCC)=CC=C21 CQPOKUTXQWMNDQ-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 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
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- LOSADGOBZWIIFQ-UHFFFAOYSA-N propan-2-yl 2-[(2-oxo-1h-quinolin-6-yl)oxy]propanoate Chemical compound N1C(=O)C=CC2=CC(OC(C)C(=O)OC(C)C)=CC=C21 LOSADGOBZWIIFQ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000012000 urushibara nickel Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- 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)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6931977A JPS545981A (en) | 1977-06-10 | 1977-06-10 | Carbostyryl derivatives |
| JP7586377A JPS5412385A (en) | 1977-06-24 | 1977-06-24 | Carbostyril derivative |
| JP53023012A JPS6059912B2 (ja) | 1978-02-28 | 1978-02-28 | カルボスチリル誘導体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2825048A1 DE2825048A1 (de) | 1978-12-14 |
| DE2825048C2 true DE2825048C2 (OSRAM) | 1991-05-08 |
Family
ID=27284068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19782825048 Granted DE2825048A1 (de) | 1977-06-10 | 1978-06-07 | Neue carbostyrilderivate und verfahren zu deren herstellung |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4298739A (OSRAM) |
| AR (2) | AR224345A1 (OSRAM) |
| AT (1) | AT367038B (OSRAM) |
| AU (1) | AU510138B2 (OSRAM) |
| CA (1) | CA1098907A (OSRAM) |
| CH (1) | CH636087A5 (OSRAM) |
| DE (1) | DE2825048A1 (OSRAM) |
| DK (1) | DK149449C (OSRAM) |
| ES (2) | ES470690A1 (OSRAM) |
| FI (1) | FI69300C (OSRAM) |
| FR (1) | FR2393795B1 (OSRAM) |
| GB (1) | GB2002745B (OSRAM) |
| IE (1) | IE46852B1 (OSRAM) |
| IT (1) | IT1108326B (OSRAM) |
| MX (1) | MX5527E (OSRAM) |
| NL (1) | NL178074C (OSRAM) |
| NO (1) | NO148813C (OSRAM) |
| NZ (1) | NZ187452A (OSRAM) |
| PH (1) | PH14670A (OSRAM) |
| PT (1) | PT68157A (OSRAM) |
| SE (1) | SE444562B (OSRAM) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU843739A3 (ru) * | 1978-02-17 | 1981-06-30 | Карл Томэ Гмбх (Фирма) | Способ получени карбостириловыхили ОКСиНдОлОВыХ пРОизВОдНыХ |
| JPS56122356A (en) | 1980-02-29 | 1981-09-25 | Otsuka Pharmaceut Co Ltd | Carbostyril derivative |
| AT383594B (de) * | 1980-02-29 | 1987-07-27 | Otsuka Pharma Co Ltd | Verfahren zum herstellen von neuen carbostyrilderivaten und ihren salzen |
| FI77852C (fi) * | 1981-02-17 | 1989-05-10 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av nya, saosom hjaertmediciner anvaendbara substituerade amid- och (maettad heterocykel)karbonylkarbostyrilderivat. |
| US4442111A (en) * | 1981-07-25 | 1984-04-10 | Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung | Antithrombotic sulfimino and sulfoximino indolinones-2 |
| FI80022C (fi) * | 1982-07-05 | 1990-04-10 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av ett nytt, terapeutiskt anvaendbart karbostyrilderivat. |
| CH655110A5 (de) * | 1982-09-03 | 1986-03-27 | Otsuka Pharma Co Ltd | Carbostyrilderivate, verfahren zu deren herstellung und arzneimittel, welche diese enthalten. |
| US4490371A (en) * | 1983-02-16 | 1984-12-25 | Syntex (U.S.A.) Inc. | N,N-Disubstituted-(2-oxo-1,2,3,5-tetrahydroimidazo-[2,1-B]quinazolinyl)oxyalkylamides |
| US4663320A (en) * | 1983-02-16 | 1987-05-05 | Syntex (U.S.A.) Inc. | (2-oxo-1,2,3,5-tetrahydroimidazo[2,1-b]quinoazolinyl)oxyalkylamides, compositions and the use thereof |
| IL74349A (en) * | 1984-02-15 | 1988-07-31 | Syntex Inc | (2-oxo-1,2,3,5-tetrahydroimidazo(2,1-b)quinazolinyl)-oxyalkylamides,their preparation and pharmaceutical compositions containing them |
| US4670434A (en) * | 1985-11-14 | 1987-06-02 | Syntex (U.S.A.) Inc. | (2-oxo-3-methylene-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolinyl)oxyalkylamides useful as cyclic AMP phosphodiesterase inhibitors |
| US5227381A (en) * | 1988-05-02 | 1993-07-13 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivative |
| JP2753622B2 (ja) | 1988-05-02 | 1998-05-20 | 大塚製薬株式会社 | カルボスチリル誘導体 |
| TW201305B (OSRAM) * | 1991-04-03 | 1993-03-01 | Otsuka Pharma Co Ltd | |
| KR930702307A (ko) * | 1991-08-23 | 1993-09-08 | 오오쓰까 아끼히꼬 | 카르보스티릴 유도체 및 혈소판 응집 억제제 |
| US5958926A (en) * | 1996-11-01 | 1999-09-28 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1956906A4 (en) | 2005-11-09 | 2009-12-30 | Combinatorx Inc | METHODS, COMPOSITIONS AND KITS FOR THE TREATMENT OF PATHOLOGIES |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| MX2009013293A (es) | 2007-06-04 | 2010-02-15 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos. |
| DE102008022221A1 (de) | 2008-05-06 | 2009-11-12 | Universität des Saarlandes | Inhibitoren der humanen Aldosteronsynthase CYP11B2 |
| ES2522968T3 (es) | 2008-06-04 | 2014-11-19 | Synergy Pharmaceuticals Inc. | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| CA2730603C (en) | 2008-07-16 | 2019-09-24 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2196453A1 (en) * | 2008-12-10 | 2010-06-16 | Cellvir | Novel substituted aryl derivatives, their process of preparation and their therapeutical uses as anti-HIV agents |
| US8796447B2 (en) | 2009-08-21 | 2014-08-05 | Otsuka Pharmaceutical Co., Ltd. | Process for producing benzo[B][1,4]diazepine-2,4-dione compound |
| TWI481601B (zh) | 2009-08-21 | 2015-04-21 | Otsuka Pharma Co Ltd | 含氮化合物及藥學組成物 |
| US8541404B2 (en) | 2009-11-09 | 2013-09-24 | Elexopharm Gmbh | Inhibitors of the human aldosterone synthase CYP11B2 |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| ES2664873T3 (es) | 2011-03-01 | 2018-04-23 | Synergy Pharmaceuticals Inc. | Proceso de preparación de agonistas de guanilato ciclasa C |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| EP3718557A3 (en) | 2013-02-25 | 2020-10-21 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonist sp-333 for use in colonic cleansing |
| HK1220696A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 鸟苷酸环化酶激动剂及其用途 |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| KR102272746B1 (ko) | 2013-06-05 | 2021-07-08 | 보슈 헬스 아일랜드 리미티드 | 구아닐레이트 사이클라제 c의 초순수 작용제, 및 이의 제조 및 사용 방법 |
| AU2014305843B2 (en) | 2013-08-09 | 2019-08-29 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| US20200368223A1 (en) | 2019-05-21 | 2020-11-26 | Ardelyx, Inc. | Methods for inhibiting phosphate transport |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR207554A1 (es) * | 1972-12-02 | 1976-10-15 | Otsuka Pharma Co Ltd | Procedimiento para producir derivados de 3-alquil-5-((3,4-dihidro-5-carbostiril)oximetil)-oxazolidinona-(2) |
| JPS5239035B2 (OSRAM) * | 1972-12-14 | 1977-10-03 | ||
| JPS5234629B2 (OSRAM) * | 1973-02-03 | 1977-09-05 | ||
| NL179275C (nl) * | 1973-10-24 | 1986-08-18 | Otsuka Pharma Co Ltd | Werkwijze voor de bereiding van farmacologisch werkzame glycerol-derivaten en werkwijze voor de bereiding van preparaten die ze bevatten. |
| US4022784A (en) * | 1974-01-31 | 1977-05-10 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-substituted-carbostyril and -3,4-dihydrocarbostyril derivatives |
| US4070470A (en) * | 1974-06-24 | 1978-01-24 | Otsuka Pharmaceutical Co., Ltd. | Platelet aggregation inhibiting carbostyrils, their compositions and method of use |
| JPS54119478A (en) * | 1978-03-06 | 1979-09-17 | Otsuka Pharmaceut Co Ltd | Carbostyril derivative |
-
1978
- 1978-06-01 NZ NZ187452A patent/NZ187452A/xx unknown
- 1978-06-01 IE IE1104/78A patent/IE46852B1/en unknown
- 1978-06-06 AU AU36866/78A patent/AU510138B2/en not_active Expired
- 1978-06-07 FI FI781811A patent/FI69300C/fi not_active IP Right Cessation
- 1978-06-07 DE DE19782825048 patent/DE2825048A1/de active Granted
- 1978-06-08 NL NLAANVRAGE7806245,A patent/NL178074C/xx not_active IP Right Cessation
- 1978-06-08 FR FR7817167A patent/FR2393795B1/fr not_active Expired
- 1978-06-08 DK DK254878A patent/DK149449C/da not_active IP Right Cessation
- 1978-06-09 PH PH21245A patent/PH14670A/en unknown
- 1978-06-09 AR AR272511A patent/AR224345A1/es active
- 1978-06-09 ES ES470690A patent/ES470690A1/es not_active Expired
- 1978-06-09 AT AT0421378A patent/AT367038B/de not_active IP Right Cessation
- 1978-06-09 IT IT68355/78A patent/IT1108326B/it active
- 1978-06-09 GB GB7826613A patent/GB2002745B/en not_active Expired
- 1978-06-09 PT PT68157A patent/PT68157A/pt unknown
- 1978-06-09 CH CH632578A patent/CH636087A5/de not_active IP Right Cessation
- 1978-06-09 NO NO782022A patent/NO148813C/no unknown
- 1978-06-09 MX MX787136U patent/MX5527E/es unknown
- 1978-06-09 SE SE7806710A patent/SE444562B/sv not_active IP Right Cessation
- 1978-06-09 CA CA305,102A patent/CA1098907A/en not_active Expired
-
1979
- 1979-03-30 ES ES479138A patent/ES479138A1/es not_active Expired
-
1980
- 1980-02-05 AR AR279858A patent/AR225755A1/es active
- 1980-04-21 US US06/142,057 patent/US4298739A/en not_active Expired - Lifetime
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2825048C2 (OSRAM) | ||
| DE2934747C2 (OSRAM) | ||
| DE3142982C2 (de) | Carbostyrilverbindungen, Verfahren zu deren Herstellung und Arzneimittel, welche diese enthalten | |
| AT363096B (de) | Verfahren zur herstellung von neuen phthalazinderivaten und deren salzen | |
| AT390732B (de) | Pharmazeutika enthaltend pyrazole | |
| DE60013859T2 (de) | Indolderivate und deren verwendung zur behandlung von u.a. osteoporosis | |
| EP0207331A1 (de) | Neue feste Formen von 2-Äthoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl]-benzoesäure, diese Formen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
| CH626612A5 (OSRAM) | ||
| DE3023626A1 (de) | 1,9-dihydroxyoctahydrobenzo eckige klammer auf c eckige klammer zu chinoline und 1-hydroxyhexahydrobenzo eckige klammer auf c eckige klammer zu chinolin-9 (8h)- one als antiemetika | |
| CH645892A5 (de) | Carbostyrilderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende, antihistaminisch wirkende mittel. | |
| DE2537070C2 (OSRAM) | ||
| DE3230209C2 (de) | Carbostyrilderivate, Verfahren zu deren Herstellung und diese enthaltende kardiotonische Mittel | |
| DE3715779A1 (de) | Flavon-3-carbonsaeure-verbindungen sowie verfahren, zwischenprodukte zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE69126978T2 (de) | Derivate des 6-amino-octahydro-indolizintriols | |
| DE3049959C2 (OSRAM) | ||
| EP0250361B1 (de) | Disubstituierte Piperazine | |
| DE3880953T2 (de) | Chinolinderivate, Verfahren zur Herstellung davon und diese enthaltendes antibakterielles Mittel. | |
| DE3784835T2 (de) | Chinoxalinon-derivate. | |
| DE3813531A1 (de) | Neue 2-aminoalkyl-4-benzyl-1-(2h)-phthalazinon-derivate | |
| DE3427985A1 (de) | Neue 2h-l-benzopyran-2-on-derivate, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten | |
| DE69200739T2 (de) | Carbostyrilderivate und diese enthaltende pharmazeutische Zusammensetzungen zur Verwendung als Mittel zur Verbesserung der Störung des Bewusstseinszustandes, ZNS-Stimulans oder Sigma-Rezeptor-Agonist. | |
| DE69614553T2 (de) | Aromatische carbonsaürediamide mit antigastrin wirkung, ihre herstellung und pharmazeutische verwendung | |
| DE69800092T2 (de) | Substituierte 4-(6-fluor-[1H]-indol-3-yl)1,2,3,6-Tetrahydropyridin-Derivate für die Behandlung von ZNS-Störungen | |
| DE3874465T2 (de) | 1,2,3,4-tetrahydroisochonoline als antiarrhythmische mittel. | |
| DE3223877C2 (OSRAM) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OAP | Request for examination filed | ||
| OD | Request for examination | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |