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 PDF

Info

Publication number: BG61519B2
Authority: BG; Bulgaria
Prior art keywords: group; general formula; methyl; compound; benzoic acid
Prior art date: 1983-12-30

Application number

BG098407A

Other languages

Bulgarian (bg)

English (en)

Inventor

Wolfgang Grell

Rudolf Hurnaus

Gerhart Griss

Robert Sauter

Eckhard Rupprecht

Original Assignee

Dr. Karl Thomae Gmbh

Priority date (The priority date 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 date listed.)

1983-12-30

Filing date

1994-01-24

Publication date

1997-10-31

1994-01-24 Application filed by Dr. Karl Thomae Gmbh filed Critical Dr. Karl Thomae Gmbh

1997-10-31 Publication of BG61519B2 publication Critical patent/BG61519B2/bg

Links

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
239000003480 eluent Substances 0.000 description 2
OYNXWMZSJQWQNM-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[1-(4-methyl-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C=C(C)C=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 OYNXWMZSJQWQNM-UHFFFAOYSA-N 0.000 description 2
WLWARXSSESCKKM-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1 WLWARXSSESCKKM-UHFFFAOYSA-N 0.000 description 2
SWWOAPXYEOXWIA-UHFFFAOYSA-N ethyl 4-(cyanomethyl)-2-ethoxybenzoate Chemical compound CCOC(=O)C1=CC=C(CC#N)C=C1OCC SWWOAPXYEOXWIA-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
150000002642 lithium compounds Chemical class 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
229910052987 metal hydride Inorganic materials 0.000 description 2
150000004681 metal hydrides Chemical class 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
229920000137 polyphosphoric acid Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000047 product Substances 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
150000007970 thio esters Chemical class 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
YTXAXEOTXYNECW-UHFFFAOYSA-N (4-methylphenyl)-(2-piperidin-1-ylphenyl)methanamine Chemical compound C1=CC(C)=CC=C1C(N)C1=CC=CC=C1N1CCCCC1 YTXAXEOTXYNECW-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
BNOGFVPTZLWIGZ-UHFFFAOYSA-N 1-(2-chloro-6-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=C(Cl)C=CC=C1N1CCCCC1 BNOGFVPTZLWIGZ-UHFFFAOYSA-N 0.000 description 1
ILWIUPCJTDPJGJ-UHFFFAOYSA-N 1-(2-methyl-6-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=C(C)C=CC=C1N1CCCCC1 ILWIUPCJTDPJGJ-UHFFFAOYSA-N 0.000 description 1
SUTMRHSHRQPPSM-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)pentan-1-amine Chemical compound CCCCC(N)C1=CC=CC=C1N1CCCCC1 SUTMRHSHRQPPSM-UHFFFAOYSA-N 0.000 description 1
RUMUAMGOPNPMFE-UHFFFAOYSA-N 1-(2-pyrrolidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=CC=CC=C1N1CCCC1 RUMUAMGOPNPMFE-UHFFFAOYSA-N 0.000 description 1
MMPHOXNVZGOXJE-UHFFFAOYSA-N 1-(4-methoxy-2-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=CC=C(OC)C=C1N1CCCCC1 MMPHOXNVZGOXJE-UHFFFAOYSA-N 0.000 description 1
ZTXBOPBBDVABHE-UHFFFAOYSA-N 1-(5-chloro-2-piperidin-1-ylphenyl)propan-1-amine Chemical compound CCC(N)C1=CC(Cl)=CC=C1N1CCCCC1 ZTXBOPBBDVABHE-UHFFFAOYSA-N 0.000 description 1
UATRMJQIJMZYTC-UHFFFAOYSA-N 1-(5-methoxy-2-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=CC(OC)=CC=C1N1CCCCC1 UATRMJQIJMZYTC-UHFFFAOYSA-N 0.000 description 1
WKJGCCQAQKFJBF-UHFFFAOYSA-N 1-[2-(4-methylpiperidin-1-yl)phenyl]butan-1-amine Chemical compound CCCC(N)C1=CC=CC=C1N1CCC(C)CC1 WKJGCCQAQKFJBF-UHFFFAOYSA-N 0.000 description 1
AQJISIWVGGUWCH-UHFFFAOYSA-N 1-[2-(azepan-1-yl)phenyl]butan-1-amine Chemical compound CCCC(N)C1=CC=CC=C1N1CCCCCC1 AQJISIWVGGUWCH-UHFFFAOYSA-N 0.000 description 1
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-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
HYHYNFMBVHFVMZ-UHFFFAOYSA-N 2-(3-ethoxy-4-methylphenyl)acetic acid Chemical compound CCOC1=CC(CC(O)=O)=CC=C1C HYHYNFMBVHFVMZ-UHFFFAOYSA-N 0.000 description 1
NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
GKAFSANXAZVZGG-UHFFFAOYSA-N 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)hexylamino]ethyl]benzoic acid Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCCCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 GKAFSANXAZVZGG-UHFFFAOYSA-N 0.000 description 1
DMSQLCXIZHIPHK-UHFFFAOYSA-N 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)propylamino]ethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)NC(CC)C=2C(=CC=CC=2)N2CCCCC2)=C1 DMSQLCXIZHIPHK-UHFFFAOYSA-N 0.000 description 1
LPNZWRTVUHLPRS-UHFFFAOYSA-N 2-ethoxy-4-[2-oxo-2-[1-(2-pyrrolidin-1-ylphenyl)butylamino]ethyl]benzoic acid Chemical compound C=1C=CC=C(N2CCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 LPNZWRTVUHLPRS-UHFFFAOYSA-N 0.000 description 1
DEXKSFLYVXFCLF-UHFFFAOYSA-N 2-ethoxy-4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)NC(C=2C=CC=CC=2)C=2C(=CC=CC=2)N2CCCCC2)=C1 DEXKSFLYVXFCLF-UHFFFAOYSA-N 0.000 description 1
QLQBJLOVOBRJFZ-UHFFFAOYSA-N 2-methoxy-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(OC)=C1 QLQBJLOVOBRJFZ-UHFFFAOYSA-N 0.000 description 1
ZHRXLVWBPNOSTO-UHFFFAOYSA-N 2-methoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)ethylamino]ethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(CC(=O)NC(C)C=2C(=CC=CC=2)N2CCCCC2)=C1 ZHRXLVWBPNOSTO-UHFFFAOYSA-N 0.000 description 1
IIVWHGMLFGNMOW-UHFFFAOYSA-N 2-methylpropane Chemical compound C[C](C)C IIVWHGMLFGNMOW-UHFFFAOYSA-N 0.000 description 1
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
INQWZSLKTMTMSK-UHFFFAOYSA-N 3-ethoxy-3-oxo-2-phenylpropanoic acid Chemical compound CCOC(=O)C(C(O)=O)C1=CC=CC=C1 INQWZSLKTMTMSK-UHFFFAOYSA-N 0.000 description 1
SWABGGMYKWYBGR-UHFFFAOYSA-N 4-(cyanomethyl)-2-ethoxybenzoic acid Chemical compound CCOC1=CC(CC#N)=CC=C1C(O)=O SWABGGMYKWYBGR-UHFFFAOYSA-N 0.000 description 1
SHWHMQDCKXTDDM-UHFFFAOYSA-N 4-(cyanomethyl)-2-methoxybenzoic acid Chemical compound COC1=CC(CC#N)=CC=C1C(O)=O SHWHMQDCKXTDDM-UHFFFAOYSA-N 0.000 description 1
NPNRECLLBPOODU-UHFFFAOYSA-N 4-[2-[(5-chloro-2-piperidin-1-ylphenyl)methylamino]-2-oxoethyl]-2-ethoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)NCC=2C(=CC=C(Cl)C=2)N2CCCCC2)=C1 NPNRECLLBPOODU-UHFFFAOYSA-N 0.000 description 1
CMPNHZQHOGLUBO-UHFFFAOYSA-N 4-[2-[1-(2-chloro-6-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]-2-ethoxybenzoic acid Chemical compound ClC=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 CMPNHZQHOGLUBO-UHFFFAOYSA-N 0.000 description 1
QWEGUBJSHDNARK-UHFFFAOYSA-N 4-[2-[1-[2-(azepan-1-yl)phenyl]butylamino]-2-oxoethyl]-2-ethoxybenzoic acid Chemical compound C=1C=CC=C(N2CCCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 QWEGUBJSHDNARK-UHFFFAOYSA-N 0.000 description 1
ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
101150105875 AZIN1 gene Proteins 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
229910000951 Aluminide Inorganic materials 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
MIPAFBGLVDGHBF-UHFFFAOYSA-N C(C)C1=C(C(=O)O)C=CC(=C1)CC(=O)NC(CCC)C1=C(C=CC=C1)N1CCCCC1 Chemical compound C(C)C1=C(C(=O)O)C=CC(=C1)CC(=O)NC(CCC)C1=C(C=CC=C1)N1CCCCC1 MIPAFBGLVDGHBF-UHFFFAOYSA-N 0.000 description 1
206010007134 Candida infections Diseases 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
241000283153 Cetacea Species 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
101100257999 Danio rerio stambpa gene Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
102000005548 Hexokinase Human genes 0.000 description 1
108700040460 Hexokinases Proteins 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
208000007027 Oral Candidiasis Diseases 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
AYUNIORJHRXIBJ-HTLBVUBBSA-N [(3r,5s,6r,7s,8e,10s,11s,12e,14e)-6-hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-21-(prop-2-enylamino)-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate Chemical compound N1C(=O)\C(C)=C\C=C\[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-HTLBVUBBSA-N 0.000 description 1
PCADECJZNDDUOH-UHFFFAOYSA-N [2-(azepan-1-yl)phenyl]-phenylmethanamine Chemical compound C=1C=CC=C(N2CCCCCC2)C=1C(N)C1=CC=CC=C1 PCADECJZNDDUOH-UHFFFAOYSA-N 0.000 description 1
JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
OADIJYCFJDBFNR-UHFFFAOYSA-M [Na+].C(C)OC1=C(C(=O)[O-])C=CC(=C1)CC(=O)NC(CCC)C1=C(C=CC=C1C)N1CCCCC1 Chemical compound [Na+].C(C)OC1=C(C(=O)[O-])C=CC(=C1)CC(=O)NC(CCC)C1=C(C=CC=C1C)N1CCCCC1 OADIJYCFJDBFNR-UHFFFAOYSA-M 0.000 description 1
239000006096 absorbing agent Substances 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000004705 aldimines Chemical class 0.000 description 1
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001409 amidines Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
239000002585 base Substances 0.000 description 1
229940095076 benzaldehyde Drugs 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
QNHCWLYFWBZVOM-UHFFFAOYSA-N benzoic acid;hydrate Chemical compound O.OC(=O)C1=CC=CC=C1 QNHCWLYFWBZVOM-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 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
239000004305 biphenyl Substances 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
125000004799 bromophenyl group Chemical group 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
201000003984 candidiasis Diseases 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
150000004650 carbonic acid diesters Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
125000000068 chlorophenyl group Chemical group 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
239000013078 crystal Substances 0.000 description 1
OCDXZFSOHJRGIL-UHFFFAOYSA-N cyclohexyloxycyclohexane Chemical compound C1CCCCC1OC1CCCCC1 OCDXZFSOHJRGIL-UHFFFAOYSA-N 0.000 description 1
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000007257 deesterification reaction Methods 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000011917 diastereoselective reduction Methods 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
HZBLLTXMVMMHRJ-UHFFFAOYSA-L disodium;sulfidosulfanylmethanedithioate Chemical compound [Na+].[Na+].[S-]SC([S-])=S HZBLLTXMVMMHRJ-UHFFFAOYSA-L 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
125000005610 enamide group Chemical group 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
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)

BG098407A 1983-12-30 1994-01-24 Нови производни на фенилоцетната киселина, лекарствени средства,съдържащи тези съединения и методи за тяхното получаване BG61519B2 (bg)

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 (cs)
JP (2)	JPH0623200B2 (cs)
KR (1)	KR900005320B1 (cs)
AT (1)	ATE44027T1 (cs)
AU (2)	AU577815B2 (cs)
BG (1)	BG61519B2 (cs)
CA (2)	CA1225398A (cs)
CS (1)	CS409791A3 (cs)
DD (1)	DD231348A5 (cs)
DE (4)	DE3347565A1 (cs)
DK (2)	DK167439B1 (cs)
ES (7)	ES8605500A1 (cs)
FI (2)	FI80447C (cs)
GR (2)	GR82614B (cs)
HK (1)	HK87492A (cs)
HU (1)	HU194548B (cs)
IE (1)	IE57700B1 (cs)
IL (2)	IL73963A (cs)
LU (1)	LU90301I2 (cs)
MX (1)	MX9202772A (cs)
NL (1)	NL980034I1 (cs)
NO (3)	NO162819C (cs)
NZ (2)	NZ210657A (cs)
PT (2)	PT79772B (cs)
SG (1)	SG55492G (cs)
ZA (2)	ZA8410103B (cs)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3523466A1 (de) *	1985-07-01	1987-01-08	Thomae Gmbh Dr K	Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
DE3347565A1 (de) *	1983-12-30	1985-07-11	Thomae Gmbh Dr K	Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
DE59109240D1 (de) *	1991-06-21	2002-10-10	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von (S)-3-Methyl-1-(2-piperidino-phenyl)-1-butylamin
JP2921982B2 (ja) *	1991-06-21	1999-07-19	ドクトルカルルトーマエゲゼルシャフトミットベシュレンクテルハフツング	（ｓ）（＋）−２−エトキシ−４−［ｎ−［１−（２−ピペリジノ−フェニル）−３−メチル−１−ブチル〕アミノカルボニルメチル〕−安息香酸、この化合物を含む医薬組成物及びその調製方法
FR2763590B1 (fr) *	1997-05-22	2000-03-24	Synthelabo	Derives d'acides[[[(arylmethyl)amino]carbonyl] alkyl]- aromatiques, leur preparation et leur application en therapeutique
EP1741445B1 (en)	2000-01-21	2013-08-14	Novartis AG	Combinations comprising dipeptidylpeptidase-IV inhibitors and antidiabetic agents
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
WO2004101540A2 (de) *	2003-05-14	2004-11-25	Cilag Ag	Verfahren zur herstellung von phenylessigsäurederivaten
WO2004103983A1 (en) *	2003-05-26	2004-12-02	Biocon Limited	Process for the preparation of s(+)-2-ethoxy-4-[n-{1-(2-piperidinophelyl)-3-methyl-1- butyl} aminocarbonylmethyl]benzoic acid derivatives
EP1636200A2 (en) *	2003-06-09	2006-03-22	Boehringer Ingelheim International GmbH	Inhibitors of papilloma virus
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
CA2622608C (en)	2005-09-14	2014-08-19	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors for treating diabetes
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
US8455522B2 (en)	2009-05-15	2013-06-04	Novartis Ag	Benzoxazolone derivatives as aldosterone synthase inhibitors
JP5659224B2 (ja)	2009-05-15	2015-01-28	ノバルティスアーゲー	アルドステロンシンターゼ阻害剤としてのアリールピリジン
ES2582395T3 (es)	2009-05-28	2016-09-12	Novartis Ag	Derivados aminobutíricos sustituidos como inhibidores de neprilisina
MX2011012628A (es)	2009-05-28	2011-12-14	Novartis Ag	Derivados amino-propionicos sustituidos como inhibidores de neprilisina.
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
CN102712589B (zh)	2009-11-17	2015-05-13	诺华股份有限公司	作为醛固酮合酶抑制剂的芳基-吡啶衍生物
JO2967B1 (en)	2009-11-20	2016-03-15	نوفارتس ايه جي	Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
CN102666535B (zh)	2009-11-30	2015-02-25	诺华股份有限公司	作为醛固酮合酶抑制剂的咪唑衍生物
SI2531501T1 (sl)	2010-02-03	2014-04-30	Takeda Pharmaceutical Company Limited	Inhibitorji kinaze-1, ki regulirajo signal apoptoze
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
JP6295277B2 (ja)	2013-02-14	2018-03-14	ノバルティスアーゲー	Ｎｅｐ（中性エンドペプチダーゼ）阻害剤としての置換ビスフェニルブタン酸ホスホン酸誘導体
PE20160991A1 (es)	2013-07-25	2016-10-15	Novartis Ag	Bioconjugados de polipeptidos de apelina sintetica
TW201536814A (zh)	2013-07-25	2015-10-01	Novartis Ag	用於治療心臟衰竭之合成環狀多肽
WO2016116842A1 (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)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3100575A1 (de) *	1981-01-10	1982-09-02	Dr. Karl Thomae Gmbh, 7950 Biberach	"neue benzoesaeuren, ihre herstellung und ihre verwendung als arzneimittel"
DE3100535A1 (de) *	1981-01-10	1982-08-12	Dr. Karl Thomae Gmbh, 7950 Biberach	"neue carbonsaeure-derivate, ihre herstellung und ihre verwendung als arzneimittel"
EP0099017B1 (de) *	1982-07-06	1988-03-02	Dr. Karl Thomae GmbH	Neue Phenylessigsäure-Derivate, ihre Herstellung und diese Verbindungen enthaltende Arzneimittel
FR2554875B1 (fr) *	1983-11-10	1986-02-28	Dba	Amplificateur hydraulique de freinage
DE3523466A1 (de) *	1985-07-01	1987-01-08	Thomae Gmbh Dr K	Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
DE3347565A1 (de) *	1983-12-30	1985-07-11	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 DK DK613184A patent/DK167439B1/da active Protection Beyond IP Right Term
- 1984-12-20 NZ NZ210657A patent/NZ210657A/xx unknown
- 1984-12-24 JP JP59272685A patent/JPH0623200B2/ja not_active Expired - Lifetime
- 1984-12-27 DE DE1998175044 patent/DE19875044I2/de active Active
- 1984-12-27 ES ES539078A patent/ES8605500A1/es not_active Expired
- 1984-12-27 DE DE8484116359T patent/DE3478682D1/de not_active Expired
- 1984-12-27 AT AT84116359T patent/ATE44027T1/de active
- 1984-12-27 EP EP84116359A patent/EP0147850B1/de not_active Expired
- 1984-12-28 DD DD84272061A patent/DD231348A5/de 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 IL IL73963A patent/IL73963A/xx not_active IP Right Cessation
- 1984-12-28 ZA ZA8410103A patent/ZA8410103B/xx unknown
- 1984-12-28 CA CA000471120A patent/CA1225398A/en not_active Expired
- 1984-12-28 AU AU37210/84A patent/AU577815B2/en not_active Expired
- 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 KR KR1019840008504A patent/KR900005320B1/ko not_active Expired
- 1984-12-28 HU HU844870A patent/HU194548B/hu unknown
1985
- 1985-06-25 DE DE19853522604 patent/DE3522604A1/de not_active Withdrawn
- 1985-08-05 ES ES545883A patent/ES8604548A1/es not_active Expired
- 1985-08-05 ES ES545880A patent/ES8604545A1/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 ES545879A patent/ES8604544A1/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 NZ NZ216640A patent/NZ216640A/xx unknown
- 1986-06-24 IL IL79217A patent/IL79217A/xx not_active IP Right Cessation
- 1986-06-24 PT PT82832A patent/PT82832B/pt unknown
- 1986-06-24 JP JP61148027A patent/JPH0739405B2/ja not_active Expired - Lifetime
- 1986-06-24 DK DK296686A patent/DK167573B1/da not_active IP Right Cessation
- 1986-06-24 AU AU59139/86A patent/AU583631B2/en not_active Expired
- 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 ZA ZA864695A patent/ZA864695B/xx unknown
- 1986-06-24 CA CA000512269A patent/CA1292000C/en not_active Expired - Lifetime
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

Also Published As

Publication number	Publication date
PT79772B (de)	1987-01-05
ES545882A0 (es)	1986-02-01
IL73963A (en)	1989-01-31
IL79217A0 (en)	1986-09-30
ES545883A0 (es)	1986-02-01
LU90301I2 (fr)	1998-12-21
ES8604545A1 (es)	1986-02-01
FI845145A0 (fi)	1984-12-28
ES8604547A1 (es)	1986-02-01
AU577815B2 (en)	1988-10-06
DE3478682D1 (en)	1989-07-20
ES556495A0 (es)	1988-04-01
CA1292000C (en)	1991-11-12
FI80447C (fi)	1990-06-11
AU583631B2 (en)	1989-05-04
NL980034I1 (nl)	1999-02-01
FI862650L (fi)	1986-12-26
FI82689B (fi)	1990-12-31
NO845282L (no)	1985-07-01
ES8604546A1 (es)	1986-02-01
FI862650A0 (fi)	1986-06-23
EP0207331A1 (de)	1987-01-07
DK296686D0 (da)	1986-06-24
SG55492G (en)	1992-10-02
GR861558B (en)	1986-10-17
NO862532D0 (no)	1986-06-24
ES545879A0 (es)	1986-02-01
AU5913986A (en)	1987-01-08
NO162819C (no)	1990-02-21
EP0147850A2 (de)	1985-07-10
ES8802145A1 (es)	1988-04-01
DE3522604A1 (de)	1987-01-08
NZ216640A (en)	1989-02-24
NO168302C (no)	1992-02-05
MX9202772A (es)	1992-06-30
JPS60158171A (ja)	1985-08-19
ES545880A0 (es)	1986-02-01
FI80447B (fi)	1990-02-28
KR900005320B1 (ko)	1990-07-27
PT79772A (de)	1985-01-01
GR82614B (en)	1985-05-02
PT82832B (pt)	1988-12-15
ES545881A0 (es)	1986-02-01
HK87492A (en)	1992-11-13
FI82689C (fi)	1991-04-10
NO162819B (no)	1989-11-13
EP0147850A3 (en)	1985-08-07
HU194548B (en)	1988-02-29
CA1225398A (en)	1987-08-11
NO862532L (no)	1986-12-29
DD231348A5 (de)	1985-12-24
ES8605500A1 (es)	1986-03-16
JPH0739405B2 (ja)	1995-05-01
ZA8410103B (en)	1986-09-24
ES8604544A1 (es)	1986-02-01
DK167573B1 (da)	1993-11-22
ZA864695B (en)	1988-02-24
AU3721084A (en)	1985-08-01
FI845145L (fi)	1985-07-01
HUT37773A (en)	1986-02-28
EP0147850B1 (de)	1989-06-14
IE843349L (en)	1985-06-30
ES8604548A1 (es)	1986-02-01
DK296686A (da)	1986-12-26
IL73963A0 (en)	1985-03-31
JPH0623200B2 (ja)	1994-03-30
DK613184D0 (da)	1984-12-20
ES539078A0 (es)	1986-03-16
IL79217A (en)	1991-01-31
DE19875044I2 (de)	2002-07-18
NO168302B (no)	1991-10-28
EP0207331B1 (de)	1990-05-23
DK167439B1 (da)	1993-11-01
PT82832A (de)	1986-07-01
KR850004590A (ko)	1985-07-25
ATE44027T1 (de)	1989-06-15
DK613184A (da)	1985-07-01
CS409791A3 (en)	1992-07-15
DE3347565A1 (de)	1985-07-11
NO1999016I1 (no)	1999-07-20
JPS62474A (ja)	1987-01-06
IE57700B1 (en)	1993-03-10
NZ210657A (en)	1988-10-28

Publication	Publication Date	Title
BG61519B2 (bg)	1997-10-31	Нови производни на фенилоцетната киселина, лекарствени средства,съдържащи тези съединения и методи за тяхното получаване
US8158673B2 (en)	2012-04-17	Histamine-3 receptor antagonists
US6143769A (en)	2000-11-07	Phenylacetic acid benzylamides
US5883096A (en)	1999-03-16	Muscarinic antagonists
Chen et al.	2006	The synthesis of L-carvone and limonene derivatives with increased antiproliferative effect and activation of ERK pathway in prostate cancer cells
RU2351596C2 (ru)	2009-04-10	Производные n-[гетероарил(пиперидин-2-ил)метил]бензамида и их применение в терапии
JP4488891B2 (ja)	2010-06-23	Ｎ−［フェニル（ピペリジン−２−イル）メチル］ベンズアミド誘導体、その製造法、およびその治療用途
US5922887A (en)	1999-07-13	Diaryldiamine derivatives and their use as delta opiod (ANT)-agonists
JP3176935B2 (ja)	2001-06-18	ドーパミンリセプタサプタイプ特異性リガンドとしてのｎ―アミノアルキルジベンゾフランカルボキサミド
Wyatt et al.	1995	Benzophenone derivatives: a novel series of potent and selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase
JPH021442A (ja)	1990-01-05	２―（２‐ヒドロキシ‐３‐フエノキシプロピルアミノ）エチルフエノキシアセトアミド化合物、その製法、この化合物を含む肥満症及び関連症治療剤並びに中間体
JP2002509918A (ja)	2002-04-02	ムスカリン性レセプタに活性を有する化合物
SK188399A3 (en)	2000-07-11	Substituted 1,2,3,4-tetrahydronaphthalene derivatives
JP5250627B2 (ja)	2013-07-31	新規化合物
Yang et al.	2020	Synthesis and glycosidase inhibition of N-substituted derivatives of 1, 4-dideoxy-1, 4-imino-d-mannitol (DIM)
US5216167A (en)	1993-06-01	Phenylacetic acid benzylamides
PL199351B1 (pl)	2008-09-30	Związki pochodne fenylopiperazyny, zawierająca je kompozycja farmaceutyczna i ich zastosowanie
CS228910B2 (en)	1984-05-14	Method of preparing new substituted alkyleneiminophenylalkyl amides of phenylalkane carboxylic acids
JP2000086603A (ja)	2000-03-28	桂皮酸アミド誘導体および３―フェニルプロピオン酸アミド誘導体
KR20100096222A (ko)	2010-09-01	피페라진 유도체 및 렙틴 수용체 조절물질로서 그 유도체의 용도
KR20100132553A (ko)	2010-12-17	신규한 ｎ-(2-아미노-페닐)-아크릴아미드
US4282223A (en)	1981-08-04	Isoquinoline derivatives, processes for their manufacture and their use for the manufacture of medicaments
JP2009526844A (ja)	2009-07-23	ピペラジン誘導体
JP5152995B2 (ja)	2013-02-27	ピペリジン誘導体及びピペラジン誘導体
HU195651B (en)	1988-06-28	Process for production of new derivatives of phenil acetic acid and medical compounds containing them