DK167439B1 - Phenyleddikesyrederivater eller salte deraf, laegemidler indeholdende disse forbindelser, anvendelse af forbindelserne til fremstilling af et laegemiddel, fremgangsmaade til fremstilling af et laegemiddel samt en fremgangsmaade til fremstilling af phenyleddikesyrederivaterne - Google Patents

Phenyleddikesyrederivater eller salte deraf, laegemidler indeholdende disse forbindelser, anvendelse af forbindelserne til fremstilling af et laegemiddel, fremgangsmaade til fremstilling af et laegemiddel samt en fremgangsmaade til fremstilling af phenyleddikesyrederivaterne Download PDF

Info

Publication number: DK167439B1
Authority: DK; Denmark
Prior art keywords: group; phenyl; piperidino; general formula; compound
Prior art date: 1983-12-30

Application number

DK613184A

Other languages

Danish (da)

English (en)

Other versions

DK613184D0 (da

DK613184A (da

Inventor

Eckhard Rupprecht

Gerhart Griss

Rudolf Hurnaus

Wolfgang Grell

Robert Sauter

Original Assignee

Thomae Gmbh Dr K

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

1984-12-20

Publication date

1993-11-01

1984-12-20 Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K

1984-12-20 Publication of DK613184D0 publication Critical patent/DK613184D0/da

1985-07-01 Publication of DK613184A publication Critical patent/DK613184A/da

1993-11-01 Application granted granted Critical

1993-11-01 Publication of DK167439B1 publication Critical patent/DK167439B1/da

Links

150000001875 compounds Chemical class 0.000 title claims description 93
238000000034 method Methods 0.000 title claims description 13
238000002360 preparation method Methods 0.000 title claims description 12
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 title claims description 9
239000003814 drug Substances 0.000 title claims description 8
239000000825 pharmaceutical preparation Substances 0.000 title 1
229940127557 pharmaceutical product Drugs 0.000 title 1
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 claims abstract description 4
-1 pyrrolidino, piperidino, hexamethylenimino, methylpyrrolidino, dimethylpyrrolidino, 2-methylpiperidino, 3-methylpiperidino, 4-methylpiperidino, 3,3-dimethylpiperidino Chemical group 0.000 claims description 102
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 20
239000001257 hydrogen Substances 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
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 claims description 12
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 12
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 11
150000007522 mineralic acids Chemical class 0.000 claims description 11
150000007524 organic acids Chemical class 0.000 claims description 11
235000005985 organic acids Nutrition 0.000 claims description 11
230000007062 hydrolysis Effects 0.000 claims description 10
238000006460 hydrolysis reaction Methods 0.000 claims description 10
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
125000006239 protecting group Chemical group 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 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
238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
239000011541 reaction mixture Substances 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
238000004587 chromatography analysis Methods 0.000 claims description 3
238000005695 dehalogenation reaction Methods 0.000 claims description 3
206010012601 diabetes mellitus Diseases 0.000 claims description 3
230000032050 esterification Effects 0.000 claims description 3
238000005886 esterification reaction Methods 0.000 claims description 3
229910052736 halogen Inorganic materials 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
238000004519 manufacturing process Methods 0.000 claims description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
230000003647 oxidation Effects 0.000 claims description 3
238000007254 oxidation reaction Methods 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000001118 alkylidene group Chemical group 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
230000000269 nucleophilic effect Effects 0.000 claims description 2
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 claims description 2
238000001149 thermolysis Methods 0.000 claims description 2
239000000969 carrier Substances 0.000 claims 2
239000003085 diluting agent Substances 0.000 claims 2
235000013312 flour Nutrition 0.000 claims 1
239000000126 substance Substances 0.000 claims 1
230000008018 melting Effects 0.000 abstract 2
238000002844 melting Methods 0.000 abstract 2
238000001228 spectrum Methods 0.000 abstract 2
239000007787 solid Substances 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
239000005711 Benzoic acid Substances 0.000 description 31
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
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 22
239000002904 solvent Substances 0.000 description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Substances OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 14
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
229960004217 benzyl alcohol Drugs 0.000 description 12
238000003776 cleavage reaction Methods 0.000 description 12
239000000203 mixture Substances 0.000 description 12
230000007017 scission Effects 0.000 description 12
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 11
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000008280 blood Substances 0.000 description 10
210000004369 blood Anatomy 0.000 description 10
238000004440 column chromatography Methods 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000006722 reduction reaction Methods 0.000 description 9
239000003826 tablet Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
238000009835 boiling Methods 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
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 8
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 7
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
239000013543 active substance Substances 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
239000008298 dragée Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000000284 extract Substances 0.000 description 7
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RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000001267 polyvinylpyrrolidone Substances 0.000 description 6
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235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
238000010992 reflux Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
241000282461 Canis lupus Species 0.000 description 5
229910000147 aluminium phosphate Inorganic materials 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
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 4
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 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000012280 lithium aluminium hydride Substances 0.000 description 4
229910052987 metal hydride Inorganic materials 0.000 description 4
150000004681 metal hydrides Chemical class 0.000 description 4
230000000144 pharmacologic effect Effects 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
239000007858 starting material Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
PZXZXTRTZSZKIN-UHFFFAOYSA-N 2-ethoxy-4-[2-[[(4-methyl-2-piperidin-1-ylphenyl)-phenylmethyl]amino]-2-oxoethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)NC(C=2C=CC=CC=2)C=2C(=CC(C)=CC=2)N2CCCCC2)=C1 PZXZXTRTZSZKIN-UHFFFAOYSA-N 0.000 description 3
239000005909 Kieselgur Substances 0.000 description 3
239000012448 Lithium borohydride Substances 0.000 description 3
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
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 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
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 3
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 3
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 3
238000001704 evaporation Methods 0.000 description 3
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150000002431 hydrogen Chemical class 0.000 description 3
150000004658 ketimines Chemical class 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
239000012071 phase Substances 0.000 description 3
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 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000003756 stirring Methods 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000012360 testing method Methods 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
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
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 2
XHMBLERZKDDZHV-UHFFFAOYSA-N 2-methoxy-4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(CC(=O)NC(C=2C=CC=CC=2)C=2C(=CC=CC=2)N2CCCCC2)=C1 XHMBLERZKDDZHV-UHFFFAOYSA-N 0.000 description 2
SHWHMQDCKXTDDM-UHFFFAOYSA-N 4-(cyanomethyl)-2-methoxybenzoic acid Chemical compound COC1=CC(CC#N)=CC=C1C(O)=O SHWHMQDCKXTDDM-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
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
RGBGOAYEKVNHOA-UHFFFAOYSA-M [Na+].C(C)OC1=C(C(=O)[O-])C=CC(=C1)CC(=O)NC(C)C1=C(C=CC=C1)N1CCCCC1 Chemical compound [Na+].C(C)OC1=C(C(=O)[O-])C=CC(=C1)CC(=O)NC(C)C1=C(C=CC=C1)N1CCCCC1 RGBGOAYEKVNHOA-UHFFFAOYSA-M 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
229910052796 boron Inorganic materials 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 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
150000001728 carbonyl compounds Chemical class 0.000 description 2
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
238000007323 disproportionation reaction Methods 0.000 description 2
230000001729 effect on metabolism Effects 0.000 description 2
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 2
VKLQNXVEXFHQLY-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[1-(4-methoxy-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C=C(OC)C=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 VKLQNXVEXFHQLY-UHFFFAOYSA-N 0.000 description 2
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 2
VHUHDYTUTAIAQU-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[[(2-methyl-6-piperidin-1-ylphenyl)-phenylmethyl]amino]-2-oxoethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1C)N1CCCCC1)C1=CC=CC=C1 VHUHDYTUTAIAQU-UHFFFAOYSA-N 0.000 description 2
HBEKQCYFHNPXLE-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[[(4-methylphenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=C(C)C=C1 HBEKQCYFHNPXLE-UHFFFAOYSA-N 0.000 description 2
FVAWUMZKHUNZAU-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[[3-methyl-1-(2-piperidin-1-ylphenyl)but-1-enyl]amino]-2-oxoethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(=CC(C)C)C1=CC=CC=C1N1CCCCC1 FVAWUMZKHUNZAU-UHFFFAOYSA-N 0.000 description 2
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 2
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 2
AJRNGKBQRDDNKV-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)heptylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCCCCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 AJRNGKBQRDDNKV-UHFFFAOYSA-N 0.000 description 2
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 2
XZSWPDMDXFPUHO-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)propylamino]ethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(CC)C1=CC=CC=C1N1CCCCC1 XZSWPDMDXFPUHO-UHFFFAOYSA-N 0.000 description 2
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 2
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 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
230000010030 glucose lowering effect Effects 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
150000002642 lithium compounds Chemical class 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
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 2
QCZLKGODWGTKCC-UHFFFAOYSA-N methyl 2-methoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)ethylamino]ethyl]benzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC=C1CC(=O)NC(C)C1=CC=CC=C1N1CCCCC1 QCZLKGODWGTKCC-UHFFFAOYSA-N 0.000 description 2
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 2
LIUUVPBPQMVIER-UHFFFAOYSA-N methyl 4-[2-[[(4-chlorophenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]-2-methoxybenzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=C(Cl)C=C1 LIUUVPBPQMVIER-UHFFFAOYSA-N 0.000 description 2
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 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
238000002156 mixing Methods 0.000 description 2
229910052757 nitrogen 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
239000000843 powder Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
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LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
150000007970 thio esters Chemical class 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
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
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ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
LZLNARHIRUKNFV-UHFFFAOYSA-N (2-methylphenyl)-phenylmethanamine Chemical compound CC1=CC=CC=C1C(N)C1=CC=CC=C1 LZLNARHIRUKNFV-UHFFFAOYSA-N 0.000 description 1
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
VYZAEIKBLFDHLW-UHFFFAOYSA-N (5-chloro-2-piperidin-1-ylphenyl)methanamine Chemical compound NCC1=CC(Cl)=CC=C1N1CCCCC1 VYZAEIKBLFDHLW-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
239000004912 1,5-cyclooctadiene Substances 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
ISLJAJXNWNYTAB-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)butan-1-ol Chemical compound CCCC(O)C1=CC=CC=C1N1CCCCC1 ISLJAJXNWNYTAB-UHFFFAOYSA-N 0.000 description 1
NRDNCDNXOHBIBS-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)ethanol Chemical compound CC(O)C1=CC=CC=C1N1CCCCC1 NRDNCDNXOHBIBS-UHFFFAOYSA-N 0.000 description 1
QGYZQNBRZAUNNK-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)heptan-1-amine Chemical compound CCCCCCC(N)C1=CC=CC=C1N1CCCCC1 QGYZQNBRZAUNNK-UHFFFAOYSA-N 0.000 description 1
QDQQTIBXASOWJQ-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)hexan-1-amine Chemical compound CCCCCC(N)C1=CC=CC=C1N1CCCCC1 QDQQTIBXASOWJQ-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
OXPWGWUSFMXACD-UHFFFAOYSA-N 1-(4-methyl-2-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=CC=C(C)C=C1N1CCCCC1 OXPWGWUSFMXACD-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
FIZIOFRNPVCSBL-UHFFFAOYSA-N 2-(3-ethoxy-4-formylphenyl)-n-[1-(2-piperidin-1-ylphenyl)butyl]acetamide Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C=O)C(OCC)=C1 FIZIOFRNPVCSBL-UHFFFAOYSA-N 0.000 description 1
XMGPSGJQXWINIB-UHFFFAOYSA-N 2-(3-ethoxy-4-formylphenyl)-n-[phenyl-(2-piperidin-1-ylphenyl)methyl]acetamide Chemical compound C1=C(C=O)C(OCC)=CC(CC(=O)NC(C=2C=CC=CC=2)C=2C(=CC=CC=2)N2CCCCC2)=C1 XMGPSGJQXWINIB-UHFFFAOYSA-N 0.000 description 1
XMEZPNMVQGZEAT-UHFFFAOYSA-N 2-(3-ethoxy-4-methylphenyl)-n-[1-(2-piperidin-1-ylphenyl)butyl]acetamide Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C)C(OCC)=C1 XMEZPNMVQGZEAT-UHFFFAOYSA-N 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
YJIVFNMAZMHQJY-UHFFFAOYSA-N 2-(3-propoxy-4-propoxycarbonylphenyl)acetic acid Chemical compound CCCOC(=O)C1=CC=C(CC(O)=O)C=C1OCCC YJIVFNMAZMHQJY-UHFFFAOYSA-N 0.000 description 1
ILRWWRMCQDIMIP-UHFFFAOYSA-N 2-(4-ethoxycarbonyl-3-hydroxyphenyl)acetic acid Chemical compound CCOC(=O)C1=CC=C(CC(O)=O)C=C1O ILRWWRMCQDIMIP-UHFFFAOYSA-N 0.000 description 1
MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-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
RNWXYAXCNBEZNM-UHFFFAOYSA-N 2-[4-(chloromethyl)-3-ethoxyphenyl]-n-[1-(2-piperidin-1-ylphenyl)butyl]acetamide Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(CCl)C(OCC)=C1 RNWXYAXCNBEZNM-UHFFFAOYSA-N 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
IDOWYUMXSQCDEB-UHFFFAOYSA-N 2-ethoxy-4-[2-[1-(4-methoxy-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoic acid Chemical compound C=1C=C(OC)C=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 IDOWYUMXSQCDEB-UHFFFAOYSA-N 0.000 description 1
RCYJFAQNRZCAIY-UHFFFAOYSA-N 2-ethoxy-4-[2-[1-(5-methoxy-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoic acid Chemical compound C=1C(OC)=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 RCYJFAQNRZCAIY-UHFFFAOYSA-N 0.000 description 1
LWXMXQSEEARGAZ-UHFFFAOYSA-N 2-ethoxy-4-[2-[[(4-methylphenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)NC(C=2C=CC(C)=CC=2)C=2C(=CC=CC=2)N2CCCCC2)=C1 LWXMXQSEEARGAZ-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
IGFJWEWLOMWYDK-UHFFFAOYSA-N 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)pentylamino]ethyl]benzoic acid Chemical group C=1C=CC=C(N2CCCCC2)C=1C(CCCC)NC(=O)CC1=CC=C(C(O)=O)C(OCC)=C1 IGFJWEWLOMWYDK-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
VQOQJWWSLIZTCE-UHFFFAOYSA-N 2-hydroxy-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(O)=C1 VQOQJWWSLIZTCE-UHFFFAOYSA-N 0.000 description 1
IXODCENSEOJTCJ-UHFFFAOYSA-N 2-hydroxy-4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1 IXODCENSEOJTCJ-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
LJZLMLIHYFGJIZ-UHFFFAOYSA-N 3-ethoxy-4-methyl-n-[1-(2-piperidin-1-ylphenyl)butyl]benzamide Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)C1=CC=C(C)C(OCC)=C1 LJZLMLIHYFGJIZ-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
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
IMUZAPGTNXIVGM-UHFFFAOYSA-N 4-[2-[[(4-chlorophenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(CC(=O)NC(C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)N2CCCCC2)=C1 IMUZAPGTNXIVGM-UHFFFAOYSA-N 0.000 description 1
CNDVUWOSGNHGCG-UHFFFAOYSA-N 4-[2-[[[2-(azepan-1-yl)phenyl]-phenylmethyl]amino]-2-oxoethyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(CC(=O)NC(C=2C=CC=CC=2)C=2C(=CC=CC=2)N2CCCCCC2)=C1 CNDVUWOSGNHGCG-UHFFFAOYSA-N 0.000 description 1
FZOSSMRFMRLQEU-UHFFFAOYSA-N 4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)butylamino]ethyl]benzoic acid Chemical group C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(O)=O)C=C1 FZOSSMRFMRLQEU-UHFFFAOYSA-N 0.000 description 1
FCZXMKQGPJNSOM-UHFFFAOYSA-N 4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)propylamino]ethyl]benzoic acid Chemical group C=1C=CC=C(N2CCCCC2)C=1C(CC)NC(=O)CC1=CC=C(C(O)=O)C=C1 FCZXMKQGPJNSOM-UHFFFAOYSA-N 0.000 description 1
KLYSDWDGUUKBSX-UHFFFAOYSA-N 4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoic acid Chemical group C1=CC(C(=O)O)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1 KLYSDWDGUUKBSX-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ROYLVXPKXJTTPC-UHFFFAOYSA-N C(C)OC(C1=C(C=CC=C1)CC(=O)N)=O Chemical compound C(C)OC(C1=C(C=CC=C1)CC(=O)N)=O ROYLVXPKXJTTPC-UHFFFAOYSA-N 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-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
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 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
238000006434 Ritter amidation reaction Methods 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
244000269722 Thea sinensis Species 0.000 description 1
101150046432 Tril gene Proteins 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
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
150000004705 aldimines Chemical class 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
150000003868 ammonium compounds Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
125000004799 bromophenyl group Chemical group 0.000 description 1
239000001273 butane Substances 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
239000002775 capsule Substances 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
150000004650 carbonic acid diesters Chemical class 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000000068 chlorophenyl group Chemical group 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
239000003245 coal Substances 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
239000013078 crystal Substances 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
238000010918 diastereoselective addition Methods 0.000 description 1
238000011917 diastereoselective reduction Methods 0.000 description 1
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
229940008406 diethyl sulfate Drugs 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
235000014103 egg white Nutrition 0.000 description 1
210000000969 egg white Anatomy 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
125000005610 enamide group Chemical group 0.000 description 1
AINBZKYUNWUTRE-UHFFFAOYSA-N ethanol;propan-2-ol Chemical compound CCO.CC(C)O AINBZKYUNWUTRE-UHFFFAOYSA-N 0.000 description 1
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 1
AVVLGZPLSMJXCG-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[1-[2-(4-methylpiperidin-1-yl)phenyl]butylamino]-2-oxoethyl]benzoate Chemical compound C=1C=CC=C(N2CCC(C)CC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 AVVLGZPLSMJXCG-UHFFFAOYSA-N 0.000 description 1
FTCMVLQJMIXDSI-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-[[3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(CC(C)C)C1=CC=CC=C1N1CCCCC1 FTCMVLQJMIXDSI-UHFFFAOYSA-N 0.000 description 1
ZFDSQWINFFBCRS-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)pentylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCCC)NC(=O)CC1=CC=C(C(=O)OCC)C(OCC)=C1 ZFDSQWINFFBCRS-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
LDIMIOSWXWXKBG-UHFFFAOYSA-N ethyl 2-ethoxy-4-[2-oxo-2-[[phenyl-(2-pyrrolidin-1-ylphenyl)methyl]amino]ethyl]benzoate Chemical compound C1=C(OCC)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCC1)C1=CC=CC=C1 LDIMIOSWXWXKBG-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
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
HMXLIEMJCUHJRD-UHFFFAOYSA-N ethyl 4-[2-oxo-2-[[phenyl-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]-2-phenylmethoxybenzoate Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1 HMXLIEMJCUHJRD-UHFFFAOYSA-N 0.000 description 1
VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
150000002238 fumaric acids Chemical class 0.000 description 1
239000008103 glucose Substances 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000004970 halomethyl group Chemical group 0.000 description 1
125000005059 halophenyl group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
150000002463 imidates Chemical class 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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000003446 ligand 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
150000002689 maleic acids Chemical class 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 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
150000002905 orthoesters Chemical class 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000005192 partition Methods 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
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
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-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
239000011148 porous material Substances 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
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
SWWHCQCMVCPLEQ-UHFFFAOYSA-N propan-2-yl methanesulfonate Chemical compound CC(C)OS(C)(=O)=O SWWHCQCMVCPLEQ-UHFFFAOYSA-N 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000007127 saponification reaction Methods 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
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
150000003444 succinic acids Chemical class 0.000 description 1
150000003459 sulfonic acid esters Chemical class 0.000 description 1
MQTBXFQVMCDOKP-UHFFFAOYSA-N tert-butyl 2-ethoxy-4-[1-(2-piperidin-1-ylphenyl)butylcarbamoyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)C1=CC=C(C(=O)OC(C)(C)C)C(OCC)=C1 MQTBXFQVMCDOKP-UHFFFAOYSA-N 0.000 description 1
FMFLQMYDIBELEE-UHFFFAOYSA-N tert-butyl 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)OC(C)(C)C)C(OCC)=C1 FMFLQMYDIBELEE-UHFFFAOYSA-N 0.000 description 1
150000003509 tertiary alcohols Chemical class 0.000 description 1
125000003831 tetrazolyl group 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
238000005809 transesterification reaction Methods 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
238000005303 weighing Methods 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)
Glass Compositions (AREA)
Superconductors And Manufacturing Methods Therefor (AREA)
Lubricants (AREA)

DK613184A 1983-12-30 1984-12-20 Phenyleddikesyrederivater eller salte deraf, laegemidler indeholdende disse forbindelser, anvendelse af forbindelserne til fremstilling af et laegemiddel, fremgangsmaade til fremstilling af et laegemiddel samt en fremgangsmaade til fremstilling af phenyleddikesyrederivaterne DK167439B1 (da)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE3347565		1983-12-30
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
DE3522604		1985-06-25

Publications (3)

Publication Number	Publication Date
DK613184D0 DK613184D0 (da)	1984-12-20
DK613184A DK613184A (da)	1985-07-01
DK167439B1 true DK167439B1 (da)	1993-11-01

Family

ID=37847099

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
DK613184A DK167439B1 (da)	1983-12-30	1984-12-20	Phenyleddikesyrederivater eller salte deraf, laegemidler indeholdende disse forbindelser, anvendelse af forbindelserne til fremstilling af et laegemiddel, fremgangsmaade til fremstilling af et laegemiddel samt en fremgangsmaade til fremstilling af phenyleddikesyrederivaterne
DK296686A DK167573B1 (da)	1983-12-30	1986-06-24	Faste former af 2-ethoxy-4-oen-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethylaa-benzoesyre, laegemidler indeholdende disse former, fremgangsmaade til fremstilling af de faste former, samt fremgangsmaade til fremstilling af et laegemiddel

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
DK296686A DK167573B1 (da)	1983-12-30	1986-06-24	Faste former af 2-ethoxy-4-oen-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethylaa-benzoesyre, laegemidler indeholdende disse former, fremgangsmaade til fremstilling af de faste former, samt fremgangsmaade til fremstilling af et laegemiddel

Country Status (26)

Country	Link
EP (2)	EP0147850B1 (es)
JP (2)	JPH0623200B2 (es)
KR (1)	KR900005320B1 (es)
AT (1)	ATE44027T1 (es)
AU (2)	AU577815B2 (es)
BG (1)	BG61519B2 (es)
CA (2)	CA1225398A (es)
CS (1)	CS409791A3 (es)
DD (1)	DD231348A5 (es)
DE (4)	DE3347565A1 (es)
DK (2)	DK167439B1 (es)
ES (7)	ES8605500A1 (es)
FI (2)	FI80447C (es)
GR (2)	GR82614B (es)
HK (1)	HK87492A (es)
HU (1)	HU194548B (es)
IE (1)	IE57700B1 (es)
IL (2)	IL73963A (es)
LU (1)	LU90301I2 (es)
MX (1)	MX9202772A (es)
NL (1)	NL980034I1 (es)
NO (3)	NO162819C (es)
NZ (2)	NZ210657A (es)
PT (2)	PT79772B (es)
SG (1)	SG55492G (es)
ZA (2)	ZA8410103B (es)

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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
SG43036A1 (en) *	1991-06-21	1997-10-17	Thomae Gmbh Dr K	(S) (+) -2-ethoxy-4-[N-[1-(2-piperidino-phenyl)-3-methyl- 1-buthyl]aminocarbony methyl] - benzoic a cid
EP0965591B1 (de) *	1991-06-21	2002-09-04	Boehringer Ingelheim Pharma KG	Verfahren zur Herstellung von (S)-3-Methyl-1-(2-piperidino-phenyl)-1-butylamin
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
US20040102477A1 (en) *	2002-08-23	2004-05-27	Dr. Reddy's Laboratories Limited	Polymorphic 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
WO2004108673A2 (en) *	2003-06-09	2004-12-16	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
EA015735B1 (ru)	2005-09-14	2011-10-31	Такеда Фармасьютикал Компани Лимитед	Фармацевтические композиции на основе 2-[[6-[(3r)-3-амино-1-пиперидинил]-3,4-дигидро-3-метил-2,4-диоксо-1(2н)-пиримидинил]метил]бензонитрила
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
EA201101621A1 (ru)	2009-05-15	2012-05-30	Новартис Аг	Производные бензоксазолона в качестве ингибиторов альдостеронсинтазы
SG175925A1 (en)	2009-05-15	2011-12-29	Novartis Ag	Aryl pyridine as aldosterone synthase inhibitors
SI2435409T1 (sl)	2009-05-28	2014-12-31	Novartis Ag	Substituirani aminopropionski derivati kot inhibitorji neprilizina
EA201101672A1 (ru)	2009-05-28	2012-06-29	Новартис Аг	Замещенные производные аминомасляной кислоты в качестве ингибиторов неприлизина
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
WO2011061168A1 (en)	2009-11-17	2011-05-26	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
US8575160B2 (en)	2009-11-30	2013-11-05	Novartis Ag	Imidazole derivatives as aldosterone synthase inhibitors
CN102834393B (zh)	2010-02-03	2015-07-22	武田药品工业株式会社	细胞凋亡信号调节激酶1抑制剂
US8877815B2 (en)	2010-11-16	2014-11-04	Novartis Ag	Substituted carbamoylcycloalkyl acetic acid derivatives as NEP
US8673974B2 (en)	2010-11-16	2014-03-18	Novartis Ag	Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
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
JP2016527249A (ja)	2013-07-25	2016-09-08	ノバルティスアーゲー	合成アペリンポリペプチドのバイオコンジュゲート
AU2014293386B2 (en)	2013-07-25	2016-11-17	Novartis Ag	Cyclic polypeptides for the treatment of heart failure
BR112017014194A2 (pt)	2015-01-23	2018-01-09	Novartis Ag	conjugados de ácido graxo de apelina sintéticos com meia-vida melhorada
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"
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 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 EP EP84116359A patent/EP0147850B1/de not_active Expired
- 1984-12-27 DE DE1998175044 patent/DE19875044I2/de active Active
- 1984-12-27 AT AT84116359T patent/ATE44027T1/de active
- 1984-12-27 ES ES539078A patent/ES8605500A1/es not_active Expired
- 1984-12-27 DE DE8484116359T patent/DE3478682D1/de not_active Expired
- 1984-12-28 IL IL73963A patent/IL73963A/xx not_active IP Right Cessation
- 1984-12-28 KR KR1019840008504A patent/KR900005320B1/ko not_active Expired
- 1984-12-28 FI FI845145A patent/FI80447C/fi active IP Right Grant
- 1984-12-28 DD DD84272061A patent/DD231348A5/de not_active IP Right Cessation
- 1984-12-28 GR GR82614A patent/GR82614B/el unknown
- 1984-12-28 AU AU37210/84A patent/AU577815B2/en not_active Expired
- 1984-12-28 PT PT79772A patent/PT79772B/pt unknown
- 1984-12-28 CA CA000471120A patent/CA1225398A/en not_active Expired
- 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 HU HU844870A patent/HU194548B/hu unknown
- 1984-12-28 ZA ZA8410103A patent/ZA8410103B/xx unknown
1985
- 1985-06-25 DE DE19853522604 patent/DE3522604A1/de not_active Withdrawn
- 1985-08-05 ES ES545881A patent/ES8604546A1/es not_active Expired
- 1985-08-05 ES ES545879A patent/ES8604544A1/es not_active Expired
- 1985-08-05 ES ES545883A patent/ES8604548A1/es not_active Expired
- 1985-08-05 ES ES545882A patent/ES8604547A1/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 NO NO862532A patent/NO168302C/no not_active IP Right Cessation
- 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 ES ES556495A patent/ES8802145A1/es not_active Expired
- 1986-06-24 JP JP61148027A patent/JPH0739405B2/ja not_active Expired - Lifetime
- 1986-06-24 NZ NZ216640A patent/NZ216640A/xx unknown
- 1986-06-24 PT PT82832A patent/PT82832B/pt unknown
- 1986-06-24 CA CA000512269A patent/CA1292000C/en not_active Expired - Lifetime
- 1986-06-24 ZA ZA864695A patent/ZA864695B/xx unknown
- 1986-06-24 IL IL79217A patent/IL79217A/xx not_active IP Right Cessation
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
IL79217A0 (en)	1986-09-30
NL980034I1 (nl)	1999-02-01
FI862650L (fi)	1986-12-26
KR900005320B1 (ko)	1990-07-27
AU577815B2 (en)	1988-10-06
FI80447C (fi)	1990-06-11
FI82689B (fi)	1990-12-31
EP0207331A1 (de)	1987-01-07
HUT37773A (en)	1986-02-28
NO862532L (no)	1986-12-29
EP0147850A2 (de)	1985-07-10
IL73963A0 (en)	1985-03-31
JPH0739405B2 (ja)	1995-05-01
DD231348A5 (de)	1985-12-24
FI862650A0 (fi)	1986-06-23
EP0147850B1 (de)	1989-06-14
MX9202772A (es)	1992-06-30
PT82832A (de)	1986-07-01
KR850004590A (ko)	1985-07-25
JPS62474A (ja)	1987-01-06
HK87492A (en)	1992-11-13
NO845282L (no)	1985-07-01
NO168302B (no)	1991-10-28
DK167573B1 (da)	1993-11-22
IE843349L (en)	1985-06-30
ES556495A0 (es)	1988-04-01
LU90301I2 (fr)	1998-12-21
PT82832B (pt)	1988-12-15
ES545882A0 (es)	1986-02-01
ES8604545A1 (es)	1986-02-01
ES8802145A1 (es)	1988-04-01
JPH0623200B2 (ja)	1994-03-30
SG55492G (en)	1992-10-02
NO168302C (no)	1992-02-05
ES545880A0 (es)	1986-02-01
ES545879A0 (es)	1986-02-01
DE3522604A1 (de)	1987-01-08
CS409791A3 (en)	1992-07-15
NO162819B (no)	1989-11-13
EP0147850A3 (en)	1985-08-07
FI845145L (fi)	1985-07-01
DE19875044I2 (de)	2002-07-18
FI82689C (fi)	1991-04-10
HU194548B (en)	1988-02-29
ZA8410103B (en)	1986-09-24
GR82614B (en)	1985-05-02
ES8604547A1 (es)	1986-02-01
IE57700B1 (en)	1993-03-10
FI845145A0 (fi)	1984-12-28
ES8604546A1 (es)	1986-02-01
ZA864695B (en)	1988-02-24
CA1292000C (en)	1991-11-12
AU5913986A (en)	1987-01-08
ATE44027T1 (de)	1989-06-15
NZ216640A (en)	1989-02-24
NO1999016I1 (no)	1999-07-20
ES8605500A1 (es)	1986-03-16
CA1225398A (en)	1987-08-11
JPS60158171A (ja)	1985-08-19
ES539078A0 (es)	1986-03-16
IL79217A (en)	1991-01-31
PT79772B (de)	1987-01-05
DE3347565A1 (de)	1985-07-11
NO862532D0 (no)	1986-06-24
DK613184D0 (da)	1984-12-20
AU583631B2 (en)	1989-05-04
DK613184A (da)	1985-07-01
NZ210657A (en)	1988-10-28
BG61519B2 (bg)	1997-10-31
DK296686D0 (da)	1986-06-24
ES8604548A1 (es)	1986-02-01
FI80447B (fi)	1990-02-28
DK296686A (da)	1986-12-26
PT79772A (de)	1985-01-01
EP0207331B1 (de)	1990-05-23
ES8604544A1 (es)	1986-02-01
IL73963A (en)	1989-01-31
ES545881A0 (es)	1986-02-01
AU3721084A (en)	1985-08-01
NO162819C (no)	1990-02-21
ES545883A0 (es)	1986-02-01
GR861558B (en)	1986-10-17
DE3478682D1 (en)	1989-07-20

Publication	Publication Date	Title
DK167439B1 (da)	1993-11-01	Phenyleddikesyrederivater eller salte deraf, laegemidler indeholdende disse forbindelser, anvendelse af forbindelserne til fremstilling af et laegemiddel, fremgangsmaade til fremstilling af et laegemiddel samt en fremgangsmaade til fremstilling af phenyleddikesyrederivaterne
US6143769A (en)	2000-11-07	Phenylacetic acid benzylamides
US20070078120A1 (en)	2007-04-05	Novel piperidine derivative
JPH06502183A (ja)	1994-03-10	新規な４−アリールピペラジン類および４−アリールピペリジン類
CA2059127A1 (en)	1990-12-20	Medicaments useful in cancer therapy and having antihistaminic properties
EP0085959B1 (en)	1989-04-19	Aromatic compounds
NO820047L (no)	1982-07-12	Analogifremgangsmaate for fremstilling av terapeutisk aktive karboksylsyreamider
NO311515B1 (no)	2001-12-03	Tetrahydrobenzindolforbindelser, og farmasöytiske preparater inneholdende slike forbindelser
DK165741B (da)	1993-01-11	Analogifremgangsmaade til fremstilling af 3-phenoxy-1-azetidincarboxamider
HU202508B (en)	1991-03-28	Process for producing new 1,4-disubstituted piperazine derivatives and pharmaceutical compositions containing them as active components
US4442102A (en)	1984-04-10	1,5-Diphenylpyrazolin-3-one compounds, process and intermediates for preparation thereof and pharmaceutical compositions containing same
AU600378B2 (en)	1990-08-09	Piperidine derivatives, their preparation and their application in therapy
US5177077A (en)	1993-01-05	1,4-disubstituted piperazines
DK168741B1 (da)	1994-05-30	Phenyleddikesyrederivater, lægemiddel indeholdende et sådant derivat, anvendelse af et sådant derivat til fremstilling af et lægemiddel, fremgangsmåde til fremstilling af lægemidlet samt analogifremgangsmåde til fremstilling af phenyleddikesyrederivaterne
NO159590B (no)	1988-10-10	Analogifremgangsm te for fremstilling av terapeutisk aktive fenyleddiksyre-derivater.
JPH037280A (ja)	1991-01-14	新規ベンゾチオピラニルアミン
US5166157A (en)	1992-11-24	Naphthyl piperazines useful as 5-HT1A receptor ligands
DK153843B (da)	1988-09-12	Analogifremgangsmaade til fremstilling af 5-substituerede 10,11-dihydro-5h-dibenzooea,daacyclohepten-5,10-iminer eller salte deraf
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2005-06-20	CTFG	Supplementary protection certificate (spc) issued	Free format text: PRODUCT NAME: REPAGLINIDE Spc suppl protection certif: CA 1999 00005 Filing date: 19990215

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1993-11-01

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2000-04-03

CTFF

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Free format text: CA 1999 00005, 19990215, EXPIRES: 20091220

2005-06-20

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