CH591415A5 - 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder - Google Patents
3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladderInfo
- Publication number
- CH591415A5 CH591415A5 CH1030276A CH1030276A CH591415A5 CH 591415 A5 CH591415 A5 CH 591415A5 CH 1030276 A CH1030276 A CH 1030276A CH 1030276 A CH1030276 A CH 1030276A CH 591415 A5 CH591415 A5 CH 591415A5
- Authority
- CH
- Switzerland
- Prior art keywords
- group
- alkoxy
- carbon atoms
- acid
- alkyl
- Prior art date
Links
- 235000019260 propionic acid Nutrition 0.000 title description 5
- 210000000232 gallbladder Anatomy 0.000 title description 4
- 230000002048 spasmolytic effect Effects 0.000 title description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 title description 3
- 150000004672 propanoic acids Chemical class 0.000 title description 2
- 239000002249 anxiolytic agent Substances 0.000 title 1
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 24
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 11
- 125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 229910000497 Amalgam Inorganic materials 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000005661 deetherification reaction Methods 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 claims description 2
- 238000006722 reduction reaction Methods 0.000 claims description 2
- 229910001023 sodium amalgam Inorganic materials 0.000 claims description 2
- 239000011135 tin Substances 0.000 claims description 2
- 229910052718 tin Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 3
- MTXHYYFYFLXUEN-UHFFFAOYSA-N 1,2,4-triethoxybenzene Chemical compound CCOC1=CC=C(OCC)C(OCC)=C1 MTXHYYFYFLXUEN-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 2
- 150000002825 nitriles Chemical class 0.000 abstract 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 abstract 2
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 abstract 1
- 150000005690 diesters Chemical class 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- 239000001384 succinic acid Substances 0.000 abstract 1
- 229940014800 succinic anhydride Drugs 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- -1 methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy Chemical group 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 210000000013 bile duct Anatomy 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 229940124571 cholagogue Drugs 0.000 description 3
- 239000000812 cholinergic antagonist Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 230000002040 relaxant effect Effects 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-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
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- YPTFHLJNWSJXKG-UHFFFAOYSA-N Trepibutone Chemical compound CCOC1=CC(OCC)=C(C(=O)CCC(O)=O)C=C1OCC YPTFHLJNWSJXKG-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000008845 cholagoga Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XXWOUXPBGGXXJW-BQYQJAHWSA-N (e)-4-oxo-4-(2,4,5-triethoxyphenyl)but-2-enoic acid Chemical compound CCOC1=CC(OCC)=C(C(=O)\C=C\C(O)=O)C=C1OCC XXWOUXPBGGXXJW-BQYQJAHWSA-N 0.000 description 1
- VNCQTTDYACAVDT-UHFFFAOYSA-N 2-methyl-3-oxo-3-phenylpropanoic acid Chemical class OC(=O)C(C)C(=O)C1=CC=CC=C1 VNCQTTDYACAVDT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- GXKHBRVNRGJYLK-UHFFFAOYSA-N 4-(2-ethoxy-4,5-dimethylphenyl)-4-sulfanylidenebutanoic acid Chemical compound CCOC1=CC(C)=C(C)C=C1C(=S)CCC(O)=O GXKHBRVNRGJYLK-UHFFFAOYSA-N 0.000 description 1
- GJWRJEMLJOEDFP-UHFFFAOYSA-N 4-(2-hydroxy-4,5-dimethoxyphenyl)-4-oxobutanoic acid Chemical compound COC1=CC(O)=C(C(=O)CCC(O)=O)C=C1OC GJWRJEMLJOEDFP-UHFFFAOYSA-N 0.000 description 1
- DQYHRNYKHCEMSZ-UHFFFAOYSA-N 4-(4,5-diethoxy-2-hydroxyphenyl)-4-oxobutanoic acid Chemical compound CCOC1=CC(O)=C(C(=O)CCC(O)=O)C=C1OCC DQYHRNYKHCEMSZ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 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 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
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 208000003770 biliary dyskinesia Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 210000004514 sphincter of oddi Anatomy 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Cpds (I) and their salts. (where R1 is 1-4C alkyl or alkoxy or OH, R2 and R3 are such 1-4C alkyl or alkoxy OH, halogen 1-4C alkylthio, or R2+R3 is 1-3C alkylenedioxy provided that when R1 is alkoxy >=1 of R2 and R3 is alkoxy or alkylthio or R2+R3 is alkylenedioxy, when R1 is alkyl or OH, R2 and R3 are alkoxy or alkylthio or R2+R3 is alkylenedioxy; when R2 and R3 are MeO, R1 is 2-3 C alkyl, 2-4C alkoxy or OH and when R2 is Me and R3 is MeO, R1 is 2-4C alkoxy) are prepd by reacting a trisubstd benzene with a reactive ester of succinic acid or its nitrile and opt. hydrolysing the product to give free COOH hydrogenating the corresponding alpa beta-unsatd acid, hydrolysing the corresponding mono- or di-ester or nitrile and cleaving a gp R1=ether to give R1=OH. Thus, 1,2,4-triethoxybenzene with succinic anhydride in the presence of AlCl3 gave (I, R1=R2=R3=EtO).
Description
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von neuen, in 3-Stellung durch trisubstituiertes Benzoyl substituierten Propionsäuren.
Bisher wurde noch nicht berichtet, dass Benzoylpropionsäurederivate spasmolytische oder entspannende Wirkung auf die Gallenblase, den Hauptgallengang und insbesondere den Sphincter Oddi haben.
Es wurde nun gefunden, dass Verbindungen der weiter unten angegebenen Formel I eine starke spasmolytische oder entspannende Wirkung auf die Gallenblase, den Hauptgallengang und insbesondere den Sphincter Oddi sowie eine starke gallentreibende Wirkung und eine geringe Toxizität haben:
EMI1.1
worin R1 eine Alkyl- oder Alkoxygruppe mit je 1 bis 4 Kohlenstoffatomen oder Hydroxyl darstellt, R2 eine Methylgruppe, eine Alkoxy- oder Alkylthiogruppe mit je 1 bis 4 Kohlenstoffatomen oder eine Hydroxylgruppe oder ein Halogenatom bedeutet und R3 eine Alkyl-, Alkoxy- oder Alkylthiogruppe mit je 1 bis 4 Kohlenstoffatomen oder eine Hydroxylgruppe oder ein Halogenatom bedeutet oder R2 und R3 miteinander zu einer Alkylendioxygruppe mit 1 bis 3 Kohlenstoffatomen verbunden sind, wobei, falls R1 eine C1-C4 Alkoxygruppe darstellt,
mindestens eines der Symbole R2 und R3 eine C1-C4-Alkoxygruppe oder eine C1-C4-Alkylthiogruppe darstellt oder R2 und R3 miteinander zu einer C1-C3 Alkylendioxygruppe verbunden sind; falls R1 eine C1-C4 Alkylgruppe oder Hydroxyl darstellt, R2 und R3, die gleich oder verschieden sein können, C1-C4-Alkoxygruppen oder oder C1-C4-Alkylthiogruppen bedeuten oder miteinander zu einer C1-C3-Alkylendioxygruppe verbunden sind; falls R2 und R3 Methoxy darstellen, R1 eine Alkoxygruppe mit 2 bis 4 Kohlenstoffatomen oder Hydroxyl darstellt; und falls R2 eine Methylgruppe und R3 Methoxy ist, R1 eine Alkoxygruppe mit 2 bis 4 Kohlenstoffatomen bedeutet.
Die aus dem Schutzumfang ausgeschlossenen Verbindungen haben sich bei der pharmakologischen Untersuchung als wenig wirksam erwiesen.
Beispiele von Alkylgruppen, die R1 und R3 in Formel I dar stellen können, sind Methyl, Äthyl, n-Propyl, Isopropyl, n-Butyl, sek.-Butyl und tert.-Butyl; Beispiele von Alkoxygruppen, die R1, R2 oder R3 darstellen können, sind Methoxy, Äthoxy, n-Propoxy, Isopropoxy, n-Butoxy, sek.-Butoxy und tert.-Butoxy; Beispiele von Halogenatomen, die R2 oder R3 darstellen können, sind Brom, Jod und Fluor; Beispiele von Alkylthiogruppen, die R2 oder R3 darstellen können, sind Methylthio, Äthylthio, n-Propylthio, Isopropylthio, n-Butylthio, sek.-Butylthio und tert.-Butylthio; und Beispiele von Alkylendioxygruppen, die R2 und R3 zusammen darstellen können, sind Methylendioxy, Äthylendioxy und Propylendioxy.
Das erfindungsgemässe Verfahren besteht darin, dass man eine Verbindung der Formel:
EMI1.2
worin Rl, R2 und R3 die obigen Bedeutungen haben, hydriert.
Zur Herstellung von Verbindungen der Formel I, worin Rl Hydroxyl darstellt, nämlich Verbindungen der Formel:
EMI1.3
worin R8 und Rg, die gleich oder verschieden sein können, Alkoxygruppen mit 1 bis 4 Kohlenstoffatomen oder Alkylthiogruppen mit 1 bis 4 Kohlenstoffatomen bedeuten oder miteinander zu einer Alkylendioxygruppe mit 1 bis 3 Kohlenstoffatomen verbunden sind, kann man auch eine erhaltene Verbindung der Formel:
EMI1.4
worin R7 eine Alkoxygruppe bedeutet und R8 und R9 die obigen Bedeutungen haben, einer Ätherspaltungsreaktion durch Behandlung mit einer Säure unterwerfen.
R7, R8 und Rg können die gleichen Alkoxygruppen und R8 und Rg können die gleichen Alkylthiogruppen und die gleichen Alkylendioxygruppen darstellen wie R1, R2 und R3.
Die Hydrierung kann in üblicher Weise ausgeführt werden, beispielsweise durch katalytische Reduktion, Reduktion unter Verwendung einer Säure und eines Metalls, wie Zink, Eisen oder Zinn, oder eines Amalgams, wie Natriumamalgam.
Die katalytische Reduktion wird im allgemeinen in einem geeigneten Lösungsmittel, wie einem niederen Alkohol (z. B.
Methanol, Äthanol), einem Äther (z. B. Dioxan, Tetrahydrofuran, Isopropyläther), Essigsäure, Äthylacetat oder Wasser oder einem Gemisch aus zwei oder mehr dieser Lösungsmittel in Gegenwart eines Katalysators, wie Palladium, Platin, Rhodium und Nickel, ausgeführt.
Die Verbindungen der Formel III sind neue Verbindungen und können hergestellt werden, indem man eine Verbindung der Formel II:
EMI2.1
worin R1, R2 und R3 die obigen Bedeutungen haben, mit einem funktionellen reaktionsfähigen Derivat der Maleinsäure oder Fumarsäure, wie Maleinsäureanhydrid, umsetzt.
Die Ätherspaltung einer Verbindung der Formel VI wird mit Vorteil in Gegenwart einer anorganischen Säure, z. B.
Jodwasserstoffsäure, Bromwasserstoffsäure, Salzsäure, einem Gemisch aus Kaliumjodid und Polyphosphorsäure, oder einer organischen Säure, wie Ameisensäure, Essigsäure, Trifluoressigsäure, oder einem Gemisch aus einer organischen Säure und Natriumjodid oder Kaliumjodid ausgeführt. In Kombination mit der Säure kann ein geeignetes Lösungsmittel, wie Wasser, ein niederer Alkohol, ein Phenol, eine organische Säure, ein Äther, wie Dioxan oder Tetrahydrofuran, verwendet werden. Die Reaktionstemperatur liegt im allgemeinen im Bereich von 0 bis 200 C, vorzugsweise 70 bis 160"C.
Um die gewünschten Verbindungen der Formel I aus irgendeinem der oben beschriebenen Reaktionsgemische zu isolieren, können herkömmliche Verfahren angewandt werden. Beispielsweise können vorteilhaft die Wasserdampfdestillation, die Extraktion mit einem Lösungsmittel oder einer alkalischen Lösung, die Destillation oder die Chromatographie angewandt werden.
Die Verbindungen der Formel I können in Form von pharmazeutisch unbedenklichen Salzen, wie Metallsalzen mit z. B. Natrium, Calcium, Magnesium, Lithium, oder Ammonium- oder Aminsalzen, erhalten werden.
Die so hergestellten Verbindungen der Formel I sind neu und haben eine starke spasmolytische oder entspannende Wirkung auf die glatten Muskeln der Gallenblase, des Hauptgallenganges und insbesondere auf den Oddischen Muskel sowie eine starke gallentreibende Wirkung und eine geringe Toxizität; daher sind sie sehr nützlich als therapeutische Mittel für Gallenblasenleiden, insbesondere Gallendyskinesie und Gallensteinkrankheit, oder als gallentreibende Mittel.
Die Verbindungen der Formel I können oral in Form von Tabletten, Granulaten, Pulvern oder durch Injektion verabreicht werden.
Typische wirksame tägliche Dosen der Verbindungen der Formel I sind gewöhnlich ca. 20 bis 1000 mg, vorzugsweise 50 bis 300 mg, wenn sie erwachsenen Menschen intravenös verabreicht werden. Natürlich kann je nach Art der Symptome auch eine höhere oder niedrigere Dosis wirksam sein.
In den folgenden Beispielen verhalten sich Gewichtsteile zu Volumteilen wie g zu ml.
Beispiel 1
Ein Gemisch aus 2,1 Gew.-Teilen 1,2,4-Triäthoxybenzol, 1,2 Gew.-Teilen Maleinsäureanhydrid und 30 Vol.-Teilen Tetrachlorkohlenstoff wird mit 5,2 Gew.-Teilen wasserfreiem Aluminiumchlorid versetzt. Das Gemisch wird eine Stunde lang gerührt und eine weitere Stunde lang auf 50 C erhitzt.
Nach dem Abkühlen wird das Gemisch mit konzentrierter Salzsäure und Eis versetzt. Das Gemisch wird mit Methylenchlorid extrahiert, die Methylenchloridschicht mit Wasser gewaschen und über wasserfreiem Natriumsulfat getrocknet.
Nach Entfernen des Lösungsmittels durch Destillation wird 3-(2',4' ,5'-Triäthoxybenzoyl-trans-acrylsäure in Form von Kristallen erhalten. Durch Umkristallisation aus einem Gemisch aus Äthanol und Benzol erhält man gelbe Nadeln vom Schmelzpunkt 192 bis 194" C.
Ein Gemisch aus 1,0 Gew.-Teil 3-(2',4' ,5'-Triäthoxy- benzoyl)-trans-acrylsäure, 50 Vol.-Teilen Methanol und 0,2 Gew.-Teil 50 %igem Palladium-auf-Kohle wird bei 25 C unter Atmosphärendruck eine Stunde lang katalytisch reduziert.
Nach Abfiltrieren des Katalysators wird das Filtrat eingedampft und der Rückstand aus wässrigem Äthanol umkristallisiert, wobei man 0,85 Gew.-Teil 3-(2',4',5'-Triäthoxybenzoyl)-propionsäure als blassgelbe Nadeln vom Schmelzpunkt 150 bis 151" C erhält.
Beispiele 2 bis 5
In ähnlicher Weise wie in Beispiel 1 werden die in der folgenden Tabelle angegebenen Acrylsäure-Ausgangsmaterialien in die entsprechenden Propionsäureprodukte übergeführt.
Beispiel Ausgangsverbindung Katalysator Produkt Nr. Name Smp. ("C) Name Smp. ("C) 2 3-(2'-Methyl-4',5'-di- 126-127,5 Pd-C 3-(2'-Methyl-4',5'-di- 116-117 äthoxybenzoyl)-trans- äthoxybenzoyl)-propion acrylsäure säure 3 3-(2',4'-Diäthoxy-5'- 198 Na-Amalgam 3-(2',4'-Diäthoxy-5'- 172-173 chlorbenzoyl)-trans- chlor-benzoyl)-propion acrylsäure säure 4 3-(2'-n-Propyl-4'- 91-93 Pd-C 3-(2'-n-Propyl-4'- 85-86 methoxy-5' -n-butoxy- methoxy-5 -n-butoxy- benzoyl)-trans-acrylsäure benzoyl)-propionsäure 5 3-(2'-n-Propyl-4'- 103-106 Pd-C 3-(2'-n-Propyl-4'- 85-86 methoxy-5'-n-butoxy- methoxy-5'-n-butoxy benzoyl)-cis-acrylsäure benzoyl)-propionsäure
Beispiel 6
Ein Gemisch von 0,06 Gew.-Teil 3-(2'-Äthoxy-4'methyl-5'-methylthiobenzoyl)-trans-acrylsäure,
6 Vol.-Teile Essigsäure und 0,3 Gew.-Teil Zinkstaub wird während 15 Minuten bei 70" C gerührt. Nach dem Abkühlen wird das Reaktionsgemisch filtriert und das Filtrat eingedampft, wobei rohe Kristalle erhalten werden. Die Kristalle werden mit 30 Scigem wässrigem Äthanol gewaschen. Man erhält 0,04 Gew.-Teil 3-(2'-Äthoxy-4'-methyl-5-methylthiobenzoyl)propionsäure in Form von Kristallen von Smp. 117 bis 118" C.
Beispiel 7
Ein Gemisch aus 2 Gew.-Teilen 3-(2',4',5'-Triäthoxybenzoyl)-propionsäure, 12 Gew.-Teilen Kaliumjodid und 60 Vol.-Teilen Ameisensäure wird 3 Stunden lang zum Rückfluss erhitzt, worauf das Lösungsmittel abdestilliert wird. Der Rückstand wird mit 50 Vol.-Teilen Wasser gemischt und eine Weile gerührt, worauf eine unlösliche Substanz abfiltriert wird. Die Substanz wird mit Wasser gewaschen und aus wässrigem Äthanol umkristallisiert, wodurch man 1,2 Gew.-Teile 3-(2'-Hydroxy-4',5'-diäthoxybenzoyl)-propionsäure in Form farbloser Kristalle vom Schmelzpunkt 142 bis 144 C erhält.
Beispiele 8 bis 10 Ähnlich wie in Beispiel 7 werden die folgenden Verbindungen erhalten: Beispiel Verbindung Smp. ( C)
8 3-(2'-Hydroxy-4',5'-dimethoxy benzoyl)-propionsäure 162-163
9 3-(2'-Hydroxy-4' ,5'-methylendioxy benzoyl)-propionsäure 180-182 10 3-(2'-Hydroxy-4' ,5'-n-butoxy- benzoyl)-propionsäure 127
The present invention relates to a process for the preparation of new propionic acids substituted in the 3-position by trisubstituted benzoyl.
So far it has not been reported that benzoylpropionic acid derivatives have spasmolytic or relaxing effects on the gall bladder, the main bile duct and in particular the sphincter of Oddi.
It has now been found that compounds of the formula I given below have a strong spasmolytic or relaxing effect on the gall bladder, the main bile duct and in particular the sphincter Oddi as well as a strong cholagogue and low toxicity:
EMI1.1
where R1 is an alkyl or alkoxy group with 1 to 4 carbon atoms or hydroxyl, R2 is a methyl group, an alkoxy or alkylthio group with 1 to 4 carbon atoms or a hydroxyl group or a halogen atom and R3 is an alkyl, alkoxy or alkylthio group with each denotes 1 to 4 carbon atoms or a hydroxyl group or a halogen atom or R2 and R3 are connected to one another to form an alkylenedioxy group with 1 to 3 carbon atoms, where, if R1 represents a C1-C4 alkoxy group,
at least one of the symbols R2 and R3 represents a C1-C4-alkoxy group or a C1-C4-alkylthio group or R2 and R3 are connected to one another to form a C1-C3 alkylenedioxy group; if R1 represents a C1-C4 alkyl group or hydroxyl, R2 and R3, which can be identical or different, represent C1-C4-alkoxy groups or or C1-C4-alkylthio groups or are connected to one another to form a C1-C3-alkylenedioxy group; if R2 and R3 represent methoxy, R1 represents an alkoxy group having 2 to 4 carbon atoms or hydroxyl; and if R2 is a methyl group and R3 is methoxy, R1 is an alkoxy group having 2 to 4 carbon atoms.
The compounds excluded from the scope of protection have proven to be ineffective in pharmacological testing.
Examples of alkyl groups which R1 and R3 in formula I can represent are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl; Examples of alkoxy groups which R1, R2 or R3 can represent are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy and tert-butoxy; Examples of halogen atoms which R2 or R3 can represent are bromine, iodine and fluorine; Examples of alkylthio groups which R2 or R3 can represent are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, sec-butylthio and tert-butylthio; and examples of alkylenedioxy groups which R2 and R3 can represent together are methylenedioxy, ethylenedioxy and propylenedioxy.
The process according to the invention consists in that a compound of the formula:
EMI1.2
wherein R1, R2 and R3 have the above meanings, hydrogenated.
For the preparation of compounds of the formula I in which Rl is hydroxyl, namely compounds of the formula:
EMI1.3
in which R8 and Rg, which can be identical or different, denote alkoxy groups with 1 to 4 carbon atoms or alkylthio groups with 1 to 4 carbon atoms or are connected to one another to form an alkylenedioxy group with 1 to 3 carbon atoms, a compound of the formula obtained can also be obtained:
EMI1.4
wherein R7 is an alkoxy group and R8 and R9 have the above meanings, subject to an ether cleavage reaction by treatment with an acid.
R7, R8 and Rg can represent the same alkoxy groups and R8 and Rg can represent the same alkylthio groups and the same alkylenedioxy groups as R1, R2 and R3.
The hydrogenation can be carried out in a conventional manner, for example by catalytic reduction, reduction using an acid and a metal such as zinc, iron or tin, or an amalgam such as sodium amalgam.
The catalytic reduction is generally carried out in a suitable solvent such as a lower alcohol (e.g.
Methanol, ethanol), an ether (e.g. dioxane, tetrahydrofuran, isopropyl ether), acetic acid, ethyl acetate or water or a mixture of two or more of these solvents in the presence of a catalyst such as palladium, platinum, rhodium and nickel.
The compounds of Formula III are new compounds and can be prepared by adding a compound of Formula II:
EMI2.1
wherein R1, R2 and R3 have the above meanings, with a functional reactive derivative of maleic acid or fumaric acid, such as maleic anhydride.
The ether cleavage of a compound of formula VI is advantageously carried out in the presence of an inorganic acid, e.g. B.
Hydroiodic acid, hydrobromic acid, hydrochloric acid, a mixture of potassium iodide and polyphosphoric acid, or an organic acid such as formic acid, acetic acid, trifluoroacetic acid, or a mixture of an organic acid and sodium iodide or potassium iodide. In combination with the acid, a suitable solvent such as water, a lower alcohol, a phenol, an organic acid, an ether such as dioxane or tetrahydrofuran can be used. The reaction temperature is generally in the range from 0 to 200.degree. C., preferably from 70 to 160.degree.
Conventional methods can be used to isolate the desired compounds of Formula I from any of the reaction mixtures described above. For example, steam distillation, extraction with a solvent or an alkaline solution, distillation or chromatography can advantageously be used.
The compounds of formula I can be in the form of pharmaceutically acceptable salts, such as metal salts with z. B. sodium, calcium, magnesium, lithium, or ammonium or amine salts can be obtained.
The compounds of formula I prepared in this way are new and have a strong spasmolytic or relaxing effect on the smooth muscles of the gallbladder, the main bile duct and in particular on the Oddic muscle as well as a strong cholagogue effect and a low toxicity; therefore, they are very useful as therapeutic agents for gallbladder diseases, particularly biliary dyskinesia and gallstone disease, or as cholagogues.
The compounds of the formula I can be administered orally in the form of tablets, granules, powders or by injection.
Typical effective daily doses of the compounds of Formula I are usually about 20 to 1000 mg, preferably 50 to 300 mg, when administered intravenously to adult humans. Of course, depending on the nature of the symptoms, a higher or lower dose may also be effective.
In the following examples, parts by weight are related to parts by volume as g to ml.
example 1
A mixture of 2.1 parts by weight of 1,2,4-triethoxybenzene, 1.2 parts by weight of maleic anhydride and 30 parts by volume of carbon tetrachloride is mixed with 5.2 parts by weight of anhydrous aluminum chloride. The mixture is stirred for one hour and heated to 50 ° C. for an additional hour.
After cooling, the mixture is treated with concentrated hydrochloric acid and ice. The mixture is extracted with methylene chloride, the methylene chloride layer is washed with water and dried over anhydrous sodium sulfate.
After removing the solvent by distillation, 3- (2 ', 4', 5'-triethoxybenzoyl-trans-acrylic acid is obtained in the form of crystals. Recrystallization from a mixture of ethanol and benzene gives yellow needles with a melting point of 192 to 194 "C .
A mixture of 1.0 part by weight of 3- (2 ', 4', 5'-triethoxybenzoyl) trans-acrylic acid, 50 parts by volume of methanol and 0.2 part by weight of 50% palladium on carbon is catalytically reduced at 25 C under atmospheric pressure for one hour.
After filtering off the catalyst, the filtrate is evaporated and the residue is recrystallized from aqueous ethanol, giving 0.85 part by weight of 3- (2 ', 4', 5'-triethoxybenzoyl) propionic acid as pale yellow needles with a melting point of 150 to 151 " C receives.
Examples 2 to 5
In a manner similar to Example 1, the acrylic acid starting materials given in the table below are converted into the corresponding propionic acid products.
Example starting compound catalyst Product No. Name m.p. ("C) Name m.p. (" C) 2 3- (2'-methyl-4 ', 5'-di-126-127.5 Pd-C 3- (2' -Methyl-4 ', 5'-di- 116-117 ethoxybenzoyl) -trans- ethoxybenzoyl) propionic acrylic acid 3 3- (2', 4'-diethoxy-5'-198 Na amalgam 3- (2 ', 4'-diethoxy-5'- 172-173 chlorobenzoyl) -trans- chloro-benzoyl) -propion acrylic acid 4 3- (2'-n-propyl-4'- 91-93 Pd-C 3- (2'- n-Propyl-4'- 85-86 methoxy-5 '-n-butoxy-methoxy-5 -n-butoxy-benzoyl) -trans-acrylic acid benzoyl) -propionic acid 5 3- (2'-n-propyl-4' 103-106 Pd-C 3- (2'-n-propyl-4'- 85-86 methoxy-5'-n-butoxy-methoxy-5'-n-butoxy benzoyl) -cis-acrylic acid benzoyl) -propionic acid
Example 6
A mixture of 0.06 part by weight of 3- (2'-ethoxy-4'methyl-5'-methylthiobenzoyl) -trans-acrylic acid,
6 parts by volume of acetic acid and 0.3 part by weight of zinc dust are stirred for 15 minutes at 70 ° C. After cooling, the reaction mixture is filtered and the filtrate is evaporated to give crude crystals. The crystals are mixed with 30% aqueous 0.04 part by weight of 3- (2'-ethoxy-4'-methyl-5-methylthiobenzoyl) propionic acid is obtained in the form of crystals with a melting point of 117 to 118 "C.
Example 7
A mixture of 2 parts by weight of 3- (2 ', 4', 5'-triethoxybenzoyl) propionic acid, 12 parts by weight of potassium iodide and 60 parts by volume of formic acid is refluxed for 3 hours, after which the solvent is distilled off becomes. The residue is mixed with 50 parts by volume of water and stirred for a while, after which an insoluble substance is filtered off. The substance is washed with water and recrystallized from aqueous ethanol, giving 1.2 parts by weight of 3- (2'-hydroxy-4 ', 5'-diethoxybenzoyl) propionic acid in the form of colorless crystals with a melting point of 142 to 144 ° C .
Examples 8 to 10 Similar to Example 7, the following compounds are obtained: Example Compound m.p. (C)
8 3- (2'-Hydroxy-4 ', 5'-dimethoxy benzoyl) propionic acid 162-163
9 3- (2'-Hydroxy-4 ', 5'-methylenedioxy benzoyl) propionic acid 180-182 10 3- (2'-Hydroxy-4', 5'-n-butoxy-benzoyl) propionic acid 127
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1030276A CH591415A5 (en) | 1972-09-13 | 1972-09-13 | 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1030276A CH591415A5 (en) | 1972-09-13 | 1972-09-13 | 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH591415A5 true CH591415A5 (en) | 1977-09-15 |
Family
ID=4361726
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1030276A CH591415A5 (en) | 1972-09-13 | 1972-09-13 | 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH591415A5 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2481118A1 (en) * | 1980-04-24 | 1981-10-30 | Roussel Uclaf | APPLICATION AS MEDICAMENTS OF DERIVATIVES SUBSTITUTED WITH PHENYL-4-OXO-2-BUTENOIC ACID |
| US4402978A (en) | 1980-04-24 | 1983-09-06 | Roussel-Uclaf | Gastro-protecting activity of substituted derivatives of 4-phenyl-4-oxo-2-hydroxy-butanoic acid |
| US4454155A (en) * | 1981-10-22 | 1984-06-12 | Roussel Uclaf | Pharmaceutical compositions containing a mono-substituted derivative of 4-phenyl-4-oxobuten-2-oic acid, and methods of using them in treating gastric and gastroduodenal ailments |
| US4473583A (en) * | 1981-10-22 | 1984-09-25 | Roussel Uclaf | Compositions containing certain derivatives of 4-phenyl-4-oxobuten-2-oic acid and methods of treatment using them |
| US4486429A (en) * | 1981-10-22 | 1984-12-04 | Roussel Uclaf | Amino derivatives of 4-phenyl 4-oxobuten-2-oic acid, pharmaceutical compositions containing them, and methods for preparing and therapeutically using them |
| US4814348A (en) * | 1983-01-24 | 1989-03-21 | Roussel Uclaf | Therapeutic compositions containing derivatives of acrylic acid having an oxygen-containing heterocycle, therapeutic treatment therewith and new compounds |
| AT391689B (en) * | 1981-10-22 | 1990-11-12 | Roussel Uclaf | METHOD FOR PRODUCING NEW 4-PHENYL-4-OXO-2-BUTENIC ACID DERIVATIVES AND THEIR SALTS |
-
1972
- 1972-09-13 CH CH1030276A patent/CH591415A5/en not_active IP Right Cessation
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2481118A1 (en) * | 1980-04-24 | 1981-10-30 | Roussel Uclaf | APPLICATION AS MEDICAMENTS OF DERIVATIVES SUBSTITUTED WITH PHENYL-4-OXO-2-BUTENOIC ACID |
| US4402978A (en) | 1980-04-24 | 1983-09-06 | Roussel-Uclaf | Gastro-protecting activity of substituted derivatives of 4-phenyl-4-oxo-2-hydroxy-butanoic acid |
| US4483868A (en) * | 1980-04-24 | 1984-11-20 | Roussel Uclaf | Gastro-protecting activity |
| US4454155A (en) * | 1981-10-22 | 1984-06-12 | Roussel Uclaf | Pharmaceutical compositions containing a mono-substituted derivative of 4-phenyl-4-oxobuten-2-oic acid, and methods of using them in treating gastric and gastroduodenal ailments |
| US4473583A (en) * | 1981-10-22 | 1984-09-25 | Roussel Uclaf | Compositions containing certain derivatives of 4-phenyl-4-oxobuten-2-oic acid and methods of treatment using them |
| US4486429A (en) * | 1981-10-22 | 1984-12-04 | Roussel Uclaf | Amino derivatives of 4-phenyl 4-oxobuten-2-oic acid, pharmaceutical compositions containing them, and methods for preparing and therapeutically using them |
| AT391689B (en) * | 1981-10-22 | 1990-11-12 | Roussel Uclaf | METHOD FOR PRODUCING NEW 4-PHENYL-4-OXO-2-BUTENIC ACID DERIVATIVES AND THEIR SALTS |
| US4814348A (en) * | 1983-01-24 | 1989-03-21 | Roussel Uclaf | Therapeutic compositions containing derivatives of acrylic acid having an oxygen-containing heterocycle, therapeutic treatment therewith and new compounds |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1543427C3 (en) | ||
| DE2244324A1 (en) | NEW 3-BENZOYLPROPIONIC ACID WITH TRIPLE SUBSTITUTED BENZYL RESIDUE AND PROCESS FOR THEIR PRODUCTION | |
| DE2651500A1 (en) | DI (PHENOXY-2 ALKANCARBONIC ACIDS), THE PROCESS FOR THEIR MANUFACTURING AND THE MEDICINAL PRODUCTS CONTAINING THESE | |
| DE2314636C2 (en) | Indane derivatives, their production and pharmaceutical compositions containing them | |
| DE2439294A1 (en) | NEW PHENYL ALKENOLS AND ALCANOLS AND PROCESS FOR THEIR PRODUCTION | |
| CH642077A5 (en) | 3-FLUOR-10-PIPERAZINO-8-SUBSTITUTED 10,11-DIHYDRODIBENZO- (B, F) -THIEPINE, THEIR ACID ADDITIONAL SALTS, METHOD FOR PRODUCING THE SAME AND PREPARATIONS THEREOF. | |
| CH591415A5 (en) | 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder | |
| EP0003825A1 (en) | Process for the preparation of 4-hydroxyphenylacetic acid | |
| DE2629752A1 (en) | NEW CARBONIC ACID DERIVATIVES AND THE PROCESS FOR THEIR PRODUCTION | |
| DE2729817C2 (en) | Process for the preparation of dl-6a-10a-cis-1-hydroxy-3-alkyl-substituted-6,6-dimethyl-6,6a, 7,8,10,10a-hexahydro-9H-dibenzo [b, d] -pyran -9-ones | |
| DE1493323B2 (en) | 1- (P-HYDROXYPHENYL) -2-PHENYL-6METHOXY-3,4-DIHYDRONAPHTHALIN, ITS PHARMACOLOGICALLY APPROPRIATE SALT AND METHOD FOR PREPARING THESE COMPOUNDS | |
| DE2051012A1 (en) | 1,6-methano-(10)-annulenes - with anti-inflammatory analgesic antipyr hypocholesterolaemic and fibrinolytic activity | |
| DE2157694C3 (en) | Phenylacetic acid derivatives, processes for their preparation and pharmaceutical preparations containing phenylacetic acid derivatives | |
| DE1950012C2 (en) | New tricyclic compounds and their preparation | |
| DE2104871A1 (en) | ||
| DE934103C (en) | Process for the production of cyclooctylated alkyl acetic acids with a strong cholagogue effect | |
| AT200136B (en) | Process for the preparation of new tertiary amines of the tetrahydrofuran series | |
| CH455777A (en) | Process for the production of new indole derivatives | |
| DE2243305C3 (en) | New derivatives of phenylacetic acid, processes for their production and pharmaceutical preparations containing the derivatives as an active ingredient | |
| DE818937C (en) | Process for the synthesis of oestrone and its degradation products as well as their derivatives and isomers | |
| DE1593644C3 (en) | ||
| CH591416A5 (en) | 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder | |
| AT162906B (en) | Process for the preparation of derivatives of the cyclopentano-polyhydro-phenantren- or the polyhydro-chrysen series | |
| DE2135711A1 (en) | ||
| AT256844B (en) | Process for the preparation of new 6,11-dihydrodibenzo- [b, e] -thiepinen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |