BG61519B2 - Нови производни на фенилоцетната киселина, лекарствени средства,съдържащи тези съединения и методи за тяхното получаване - Google Patents
Нови производни на фенилоцетната киселина, лекарствени средства,съдържащи тези съединения и методи за тяхното получаване Download PDFInfo
- Publication number
- BG61519B2 BG61519B2 BG098407A BG9840794A BG61519B2 BG 61519 B2 BG61519 B2 BG 61519B2 BG 098407 A BG098407 A BG 098407A BG 9840794 A BG9840794 A BG 9840794A BG 61519 B2 BG61519 B2 BG 61519B2
- Authority
- BG
- Bulgaria
- Prior art keywords
- group
- general formula
- methyl
- compound
- benzoic acid
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 94
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title claims abstract description 11
- 239000000203 mixture Substances 0.000 title abstract description 13
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical class O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 title 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960003424 phenylacetic acid Drugs 0.000 claims abstract description 4
- 239000003279 phenylacetic acid Substances 0.000 claims abstract description 4
- -1 hexamethyleneimino- Chemical class 0.000 claims description 117
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 238000003776 cleavage reaction Methods 0.000 claims description 15
- 230000007017 scission Effects 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 235000005985 organic acids Nutrition 0.000 claims description 5
- 230000001681 protective effect Effects 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 238000005695 dehalogenation reaction Methods 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 238000007323 disproportionation reaction Methods 0.000 claims description 2
- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 238000001149 thermolysis Methods 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 claims 1
- 102100023132 Transcription factor Jun Human genes 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 39
- 239000008280 blood Substances 0.000 abstract description 8
- 210000004369 blood Anatomy 0.000 abstract description 8
- 230000001729 effect on metabolism Effects 0.000 abstract description 2
- 238000002844 melting Methods 0.000 description 88
- 230000008018 melting Effects 0.000 description 88
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 67
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000005711 Benzoic acid Substances 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 35
- 235000010233 benzoic acid Nutrition 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- OTGSESBEJUHCES-UHFFFAOYSA-N 2-(3-ethoxy-4-ethoxycarbonylphenyl)acetic acid Chemical compound CCOC(=O)C1=CC=C(CC(O)=O)C=C1OCC OTGSESBEJUHCES-UHFFFAOYSA-N 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000008298 dragée Substances 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- ISDXXLAJBAYROO-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=CC=CC=C1N1CCCCC1 ISDXXLAJBAYROO-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
- FAEKWTJYAYMJKF-UHFFFAOYSA-N 2-ethoxy-4-[2-[[3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)NC(CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 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 3
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- YWJWVSXLNSOMOM-UHFFFAOYSA-N ethyl 2-hydroxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)butylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(O)=C1 YWJWVSXLNSOMOM-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 3
- 150000004658 ketimines Chemical class 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- XRPRMKLRYZRKLP-UHFFFAOYSA-N methyl 4-(cyanomethyl)-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CC#N)C=C1OC XRPRMKLRYZRKLP-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- MTKOJRYAEWHRNC-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)ethanamine Chemical compound CC(N)C1=CC=CC=C1N1CCCCC1 MTKOJRYAEWHRNC-UHFFFAOYSA-N 0.000 description 2
- NRDNCDNXOHBIBS-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)ethanol Chemical compound CC(O)C1=CC=CC=C1N1CCCCC1 NRDNCDNXOHBIBS-UHFFFAOYSA-N 0.000 description 2
- KFIKFFKIHJWNMP-UHFFFAOYSA-N 2-(3-methoxy-4-methoxycarbonylphenyl)acetic acid Chemical compound COC(=O)C1=CC=C(CC(O)=O)C=C1OC KFIKFFKIHJWNMP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- BPMPFKUUFWRFKB-UHFFFAOYSA-N 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)butylamino]ethyl]benzoic acid Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 BPMPFKUUFWRFKB-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229950005499 carbon tetrachloride Drugs 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000005661 deetherification reaction Methods 0.000 description 2
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- LYZRNZVPFGOZAK-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[1-(2-methyl-6-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound CC=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 LYZRNZVPFGOZAK-UHFFFAOYSA-N 0.000 description 1
- ADEGIKPUTAZTJE-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[1-(5-methoxy-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C(OC)=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 ADEGIKPUTAZTJE-UHFFFAOYSA-N 0.000 description 1
- YNSUZPUSZZOPJI-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[[(4-methyl-2-piperidin-1-ylphenyl)-phenylmethyl]amino]-2-oxoethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC(C)=CC=1)N1CCCCC1)C1=CC=CC=C1 YNSUZPUSZZOPJI-UHFFFAOYSA-N 0.000 description 1
- RZTULGXPQDQICH-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[(2-piperidin-1-ylphenyl)methylamino]ethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NCC1=CC=CC=C1N1CCCCC1 RZTULGXPQDQICH-UHFFFAOYSA-N 0.000 description 1
- PNMSEZJAQNRHIJ-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)butylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 PNMSEZJAQNRHIJ-UHFFFAOYSA-N 0.000 description 1
- UFYJOMHZXOAMFT-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)ethylamino]ethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C)C1=CC=CC=C1N1CCCCC1 UFYJOMHZXOAMFT-UHFFFAOYSA-N 0.000 description 1
- NWXSBWUGALCNNY-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)hexylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCCCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 NWXSBWUGALCNNY-UHFFFAOYSA-N 0.000 description 1
- FVUANQUTNIPIHR-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-pyrrolidin-1-ylphenyl)butylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 FVUANQUTNIPIHR-UHFFFAOYSA-N 0.000 description 1
- NMMZVDHTRGGUMX-UHFFFAOYSA-N ethyl 2-hydroxy-4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1 NMMZVDHTRGGUMX-UHFFFAOYSA-N 0.000 description 1
- CFGAAVLKBXSSRX-UHFFFAOYSA-N ethyl 3-carbamoyl-2-methylbenzoate Chemical compound C(C)OC(C1=C(C(=CC=C1)C(=O)N)C)=O CFGAAVLKBXSSRX-UHFFFAOYSA-N 0.000 description 1
- SCCDVNMYOZUNPU-UHFFFAOYSA-N ethyl 4-(cyanomethyl)-2-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(CC#N)C=C1O SCCDVNMYOZUNPU-UHFFFAOYSA-N 0.000 description 1
- LQTPFMBRYDMVFU-UHFFFAOYSA-N ethyl 4-[2-[(5-chloro-2-piperidin-1-ylphenyl)methylamino]-2-oxoethyl]-2-ethoxybenzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NCC1=CC(Cl)=CC=C1N1CCCCC1 LQTPFMBRYDMVFU-UHFFFAOYSA-N 0.000 description 1
- WYUJYUWIOITEMM-UHFFFAOYSA-N ethyl 4-[2-[1-(2-chloro-6-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]-2-ethoxybenzoate Chemical compound ClC=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 WYUJYUWIOITEMM-UHFFFAOYSA-N 0.000 description 1
- BCPVEVPBKGGITC-UHFFFAOYSA-N ethyl 4-[2-[1-(5-chloro-2-piperidin-1-ylphenyl)propylamino]-2-oxoethyl]-2-ethoxybenzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(CC)C1=CC(Cl)=CC=C1N1CCCCC1 BCPVEVPBKGGITC-UHFFFAOYSA-N 0.000 description 1
- GMMMMCYQGNQOIS-UHFFFAOYSA-N ethyl 4-[2-[1-[2-(azepan-1-yl)phenyl]butylamino]-2-oxoethyl]-2-ethoxybenzoate Chemical compound C=1C=CC=C(N2CCCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 GMMMMCYQGNQOIS-UHFFFAOYSA-N 0.000 description 1
- JFWFVSQWOHOMLQ-UHFFFAOYSA-N ethyl 4-[2-[[[2-(azepan-1-yl)phenyl]-phenylmethyl]amino]-2-oxoethyl]-2-ethoxybenzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCCC1)C1=CC=CC=C1 JFWFVSQWOHOMLQ-UHFFFAOYSA-N 0.000 description 1
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000013563 matrix tablet Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- PLAUNGJHAKRSPI-UHFFFAOYSA-N methyl 2-methoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)butylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OC)C(OC)=C1 PLAUNGJHAKRSPI-UHFFFAOYSA-N 0.000 description 1
- NWKAFEGKHLVWHL-UHFFFAOYSA-N methyl 2-methoxy-4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1 NWKAFEGKHLVWHL-UHFFFAOYSA-N 0.000 description 1
- KBPROMPXFOKGMJ-UHFFFAOYSA-N methyl 4-[2-[[[2-(azepan-1-yl)phenyl]-phenylmethyl]amino]-2-oxoethyl]-2-methoxybenzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCCC1)C1=CC=CC=C1 KBPROMPXFOKGMJ-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015145 nougat Nutrition 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- SMPAPEKFGLKOIC-UHFFFAOYSA-N oxolane;hydrochloride Chemical compound Cl.C1CCOC1 SMPAPEKFGLKOIC-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 229940031826 phenolate Drugs 0.000 description 1
- CVWKHDGZSCEBQU-UHFFFAOYSA-N phenyl-(2-piperidin-1-ylphenyl)methanamine Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(N)C1=CC=CC=C1 CVWKHDGZSCEBQU-UHFFFAOYSA-N 0.000 description 1
- JWBVHEWXPDFVTR-UHFFFAOYSA-N phenyl-(2-pyrrolidin-1-ylphenyl)methanamine Chemical compound C=1C=CC=C(N2CCCC2)C=1C(N)C1=CC=CC=C1 JWBVHEWXPDFVTR-UHFFFAOYSA-N 0.000 description 1
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 101150076714 stambp gene Proteins 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Superconductors And Manufacturing Methods Therefor (AREA)
- Lubricants (AREA)
- Glass Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833347565 DE3347565A1 (de) | 1983-12-30 | 1983-12-30 | Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE19853522604 DE3522604A1 (de) | 1983-12-30 | 1985-06-25 | Neue feste formen von 2-(gamma)thoxy-4-(n-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl)-benzoesaeure, diese formen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG61519B2 true BG61519B2 (bg) | 1997-10-31 |
Family
ID=37847099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG098407A BG61519B2 (bg) | 1983-12-30 | 1994-01-24 | Нови производни на фенилоцетната киселина, лекарствени средства,съдържащи тези съединения и методи за тяхното получаване |
Country Status (26)
| Country | Link |
|---|---|
| EP (2) | EP0147850B1 (xx) |
| JP (2) | JPH0623200B2 (xx) |
| KR (1) | KR900005320B1 (xx) |
| AT (1) | ATE44027T1 (xx) |
| AU (2) | AU577815B2 (xx) |
| BG (1) | BG61519B2 (xx) |
| CA (2) | CA1225398A (xx) |
| CS (1) | CS409791A3 (xx) |
| DD (1) | DD231348A5 (xx) |
| DE (4) | DE3347565A1 (xx) |
| DK (2) | DK167439B1 (xx) |
| ES (7) | ES8605500A1 (xx) |
| FI (2) | FI80447C (xx) |
| GR (2) | GR82614B (xx) |
| HK (1) | HK87492A (xx) |
| HU (1) | HU194548B (xx) |
| IE (1) | IE57700B1 (xx) |
| IL (2) | IL73963A (xx) |
| LU (1) | LU90301I2 (xx) |
| MX (1) | MX9202772A (xx) |
| NL (1) | NL980034I1 (xx) |
| NO (3) | NO162819C (xx) |
| NZ (2) | NZ210657A (xx) |
| PT (2) | PT79772B (xx) |
| SG (1) | SG55492G (xx) |
| ZA (2) | ZA8410103B (xx) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3347565A1 (de) * | 1983-12-30 | 1985-07-11 | Thomae Gmbh Dr K | Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3523466A1 (de) * | 1985-07-01 | 1987-01-08 | Thomae Gmbh Dr K | Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| EP0589874B1 (de) * | 1991-06-21 | 1999-09-08 | Boehringer Ingelheim Pharma KG | Verwendung von (s)(+)-2-äthoxy-4-[n-[1-(2-piperidino-phenyl)-3-methyl-1-butyl]aminocarbonylmethyl]-benzoesäure zur herstellung eines langzeitantidiabetikums |
| ATE184279T1 (de) * | 1991-06-21 | 1999-09-15 | Boehringer Ingelheim Pharma | Verwendung von (s)(+)-2-äthoxy-4-(n-(1-(2- piperidino-phenyl)-3-methyl-1- butyl>aminocarbonylmethyl>-benzoesäure zur herstellung eines langzeitantidiabetikums |
| FR2763590B1 (fr) * | 1997-05-22 | 2000-03-24 | Synthelabo | Derives d'acides[[[(arylmethyl)amino]carbonyl] alkyl]- aromatiques, leur preparation et leur application en therapeutique |
| BRPI0107715B8 (pt) | 2000-01-21 | 2021-05-25 | Novartis Ag | produto farmacêutico compreendendo um inibidor de dipeptidilpeptidase-iv e metformina, bem como usos do dito produto farmacêutico e do inibidor de dipeptidilpeptidase-iv |
| WO2004018442A1 (en) * | 2002-08-23 | 2004-03-04 | Dr. Reddy's Laboratories Limited | Crystalline and amorphous forms of (s) -repaglinide and the processes for preparation thereof |
| US7915421B2 (en) | 2003-05-14 | 2011-03-29 | Cilag Ltd. | Method for preparing phenyl acetic acid derivatives |
| AU2003237595A1 (en) * | 2003-05-26 | 2004-12-13 | Biocon Limited | Process for the preparation of s(+)-2-ethoxy-4-(n-{1-(2-piperidinophelyl)-3-methyl-1- butyl} aminocarbonylmethyl)benzoic acid derivatives |
| JP4550811B2 (ja) * | 2003-06-09 | 2010-09-22 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | パピローマウイルスのインヒビター |
| FR2875805B1 (fr) * | 2004-09-27 | 2006-12-29 | Genfit S A | Composes derives de n-(benzyl) phenylacetamide substitues, preparation et utilisations |
| CN1305863C (zh) * | 2004-12-27 | 2007-03-21 | 浙江大学 | (s)－异丙基－(2－哌啶)苯基－甲基胺的合成方法 |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| CN102908351B (zh) | 2005-09-14 | 2014-07-23 | 武田药品工业株式会社 | 用于治疗糖尿病的二肽基肽酶抑制剂 |
| EP2177221A1 (en) | 2008-10-20 | 2010-04-21 | Krka Tovarna Zdravil, D.D., Novo Mesto | Process for the preparation of substantially optically pure Repaglinide and precursors thereof |
| CN102459247B (zh) | 2009-05-15 | 2014-09-17 | 诺华股份有限公司 | 作为醛固酮合酶抑制剂的苯并噁唑酮衍生物 |
| BRPI1010600A2 (pt) | 2009-05-15 | 2016-03-15 | Novartis Ag | aril piridina como inibidores de aldosterona sintase |
| KR101442897B1 (ko) | 2009-05-28 | 2014-09-23 | 노파르티스 아게 | 네프릴리신 억제제로서의 치환된 아미노프로피온산 유도체 |
| SG176010A1 (en) | 2009-05-28 | 2011-12-29 | Novartis Ag | Substituted aminobutyric derivatives as neprilysin inhibitors |
| WO2011041293A1 (en) | 2009-09-30 | 2011-04-07 | Takeda Pharmaceutical Company Limited | Pyrazolo [1, 5-a] pyrimidine derivatives as apoptosis signal-regulating kinase 1 inhibitors |
| US8519134B2 (en) | 2009-11-17 | 2013-08-27 | Novartis Ag | Aryl-pyridine derivatives as aldosterone synthase inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| WO2011064376A1 (en) | 2009-11-30 | 2011-06-03 | Novartis Ag | Imidazole derivatives as aldosterone synthase inhibitors |
| RS53176B (en) | 2010-02-03 | 2014-06-30 | Takeda Pharmaceutical Company Limited | KINASE INHIBITORS 1 REGULATING SIGNALS IN APOPTOSIS |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
| WO2012095548A2 (es) | 2011-01-13 | 2012-07-19 | Centro De Investigación Biomédica En Red De Enfermedades Neurodegenerativas (Ciberned) | Compuestos para el tratamiento de enfermedades neurodegenerativas |
| UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
| NZ710574A (en) | 2013-02-14 | 2017-11-24 | Novartis Ag | Substituted bisphenyl butanoic phosphonic acid derivatives as nep (neutral endopeptidase) inhibitors |
| US9340582B2 (en) | 2013-07-25 | 2016-05-17 | Novartis Ag | Bioconjugates of synthetic apelin polypeptides |
| WO2015013168A1 (en) | 2013-07-25 | 2015-01-29 | Novartis Ag | Cyclic polypeptides for the treatment of heart failure |
| CA2972871A1 (en) | 2015-01-23 | 2016-07-28 | Novartis Ag | Synthetic apelin fatty acid conjugates with improved half-life |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3100535A1 (de) * | 1981-01-10 | 1982-08-12 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue carbonsaeure-derivate, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3100575A1 (de) * | 1981-01-10 | 1982-09-02 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue benzoesaeuren, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3375783D1 (en) * | 1982-07-06 | 1988-04-07 | Thomae Gmbh Dr K | Phenyl-acetic-acid derivatives, their preparation and pharmaceutical compostions containing them |
| FR2554875B1 (fr) * | 1983-11-10 | 1986-02-28 | Dba | Amplificateur hydraulique de freinage |
| DE3347565A1 (de) * | 1983-12-30 | 1985-07-11 | Thomae Gmbh Dr K | Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3523466A1 (de) * | 1985-07-01 | 1987-01-08 | Thomae Gmbh Dr K | Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
-
1983
- 1983-12-30 DE DE19833347565 patent/DE3347565A1/de not_active Withdrawn
-
1984
- 1984-12-20 NZ NZ210657A patent/NZ210657A/xx unknown
- 1984-12-20 DK DK613184A patent/DK167439B1/da active Protection Beyond IP Right Term
- 1984-12-24 JP JP59272685A patent/JPH0623200B2/ja not_active Expired - Lifetime
- 1984-12-27 DE DE8484116359T patent/DE3478682D1/de not_active Expired
- 1984-12-27 ES ES539078A patent/ES8605500A1/es not_active Expired
- 1984-12-27 AT AT84116359T patent/ATE44027T1/de active
- 1984-12-27 DE DE1998175044 patent/DE19875044I2/de active Active
- 1984-12-27 EP EP84116359A patent/EP0147850B1/de not_active Expired
- 1984-12-28 IL IL73963A patent/IL73963A/xx not_active IP Right Cessation
- 1984-12-28 PT PT79772A patent/PT79772B/pt unknown
- 1984-12-28 NO NO845282A patent/NO162819C/no not_active IP Right Cessation
- 1984-12-28 IE IE3349/84A patent/IE57700B1/en not_active IP Right Cessation
- 1984-12-28 DD DD84272061A patent/DD231348A5/de not_active IP Right Cessation
- 1984-12-28 HU HU844870A patent/HU194548B/hu unknown
- 1984-12-28 AU AU37210/84A patent/AU577815B2/en not_active Expired
- 1984-12-28 KR KR1019840008504A patent/KR900005320B1/ko not_active IP Right Cessation
- 1984-12-28 FI FI845145A patent/FI80447C/fi active IP Right Grant
- 1984-12-28 GR GR82614A patent/GR82614B/el unknown
- 1984-12-28 ZA ZA8410103A patent/ZA8410103B/xx unknown
- 1984-12-28 CA CA000471120A patent/CA1225398A/en not_active Expired
-
1985
- 1985-06-25 DE DE19853522604 patent/DE3522604A1/de not_active Withdrawn
- 1985-08-05 ES ES545879A patent/ES8604544A1/es not_active Expired
- 1985-08-05 ES ES545881A patent/ES8604546A1/es not_active Expired
- 1985-08-05 ES ES545882A patent/ES8604547A1/es not_active Expired
- 1985-08-05 ES ES545883A patent/ES8604548A1/es not_active Expired
- 1985-08-05 ES ES545880A patent/ES8604545A1/es not_active Expired
-
1986
- 1986-06-10 EP EP86107890A patent/EP0207331B1/de not_active Expired - Lifetime
- 1986-06-16 GR GR861558A patent/GR861558B/el unknown
- 1986-06-23 FI FI862650A patent/FI82689C/fi not_active IP Right Cessation
- 1986-06-24 ZA ZA864695A patent/ZA864695B/xx unknown
- 1986-06-24 NZ NZ216640A patent/NZ216640A/xx unknown
- 1986-06-24 CA CA000512269A patent/CA1292000C/en not_active Expired - Lifetime
- 1986-06-24 JP JP61148027A patent/JPH0739405B2/ja not_active Expired - Lifetime
- 1986-06-24 NO NO862532A patent/NO168302C/no not_active IP Right Cessation
- 1986-06-24 ES ES556495A patent/ES8802145A1/es not_active Expired
- 1986-06-24 AU AU59139/86A patent/AU583631B2/en not_active Expired
- 1986-06-24 DK DK296686A patent/DK167573B1/da not_active IP Right Cessation
- 1986-06-24 IL IL79217A patent/IL79217A/xx not_active IP Right Cessation
- 1986-06-24 PT PT82832A patent/PT82832B/pt unknown
-
1991
- 1991-12-27 CS CS914097A patent/CS409791A3/cs unknown
-
1992
- 1992-05-25 SG SG554/92A patent/SG55492G/en unknown
- 1992-06-10 MX MX9202772A patent/MX9202772A/es unknown
- 1992-11-05 HK HK874/92A patent/HK87492A/xx not_active IP Right Cessation
-
1994
- 1994-01-24 BG BG098407A patent/BG61519B2/bg unknown
-
1998
- 1998-10-21 LU LU90301C patent/LU90301I2/fr unknown
- 1998-11-18 NL NL980034C patent/NL980034I1/nl unknown
-
1999
- 1999-07-20 NO NO1999016C patent/NO1999016I1/no unknown
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