FI61479C - Foerfarande foer framstaellning av spasmolytiska nya d,l-tyrosinderivat - Google Patents
Foerfarande foer framstaellning av spasmolytiska nya d,l-tyrosinderivat Download PDFInfo
- Publication number
- FI61479C FI61479C FI750255A FI750255A FI61479C FI 61479 C FI61479 C FI 61479C FI 750255 A FI750255 A FI 750255A FI 750255 A FI750255 A FI 750255A FI 61479 C FI61479 C FI 61479C
- Authority
- FI
- Finland
- Prior art keywords
- group
- formula
- yield
- tyrosyl
- alk
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 claims description 50
- 150000001875 compounds Chemical class 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 229960004441 tyrosine Drugs 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 14
- -1 pyrrolidino, piperidino Chemical group 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical compound OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 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 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 238000003436 Schotten-Baumann reaction Methods 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 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 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000013522 chelant Substances 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 229930195729 fatty acid Natural products 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 150000004665 fatty acids Chemical class 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 88
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 75
- 238000002425 crystallisation Methods 0.000 description 45
- 230000008025 crystallization Effects 0.000 description 45
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 241000700159 Rattus Species 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 229960001789 papaverine Drugs 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000001663 anti-spastic effect Effects 0.000 description 6
- 239000001961 anticonvulsive agent Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000003610 charcoal Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- 230000001773 anti-convulsant effect Effects 0.000 description 4
- 229960003965 antiepileptics Drugs 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 210000003405 ileum Anatomy 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229940076279 serotonin Drugs 0.000 description 4
- LFNRYYJKYBWVAN-UHFFFAOYSA-N 4-chloro-n-[1-(dipropylamino)-3-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]-1-oxopropan-2-yl]benzamide;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)N(CCC)CCC)CC(C=C1)=CC=C1OCCCN1CCN(C)CC1 LFNRYYJKYBWVAN-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- WUKJETKICHNKHZ-UHFFFAOYSA-N N-[1-(4-hydroxyphenyl)-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 WUKJETKICHNKHZ-UHFFFAOYSA-N 0.000 description 3
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 3
- 101800000989 Oxytocin Proteins 0.000 description 3
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 3
- 229960001723 oxytocin Drugs 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000000626 ureter Anatomy 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- YLDQIABNRZYWAP-UHFFFAOYSA-N 4-bromo-n-[3-[4-[2-(diethylamino)ethoxy]phenyl]-1-(dipropylamino)-1-oxopropan-2-yl]benzamide Chemical compound C=1C=C(Br)C=CC=1C(=O)NC(C(=O)N(CCC)CCC)CC1=CC=C(OCCN(CC)CC)C=C1 YLDQIABNRZYWAP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 230000000794 anti-serotonin Effects 0.000 description 2
- 229940125681 anticonvulsant agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000003420 antiserotonin agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 2
- 229960000396 atropine Drugs 0.000 description 2
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical group C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- HOZOZZFCZRXYEK-GSWUYBTGSA-M butylscopolamine bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CCCC)=CC=CC=C1 HOZOZZFCZRXYEK-GSWUYBTGSA-M 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- GMAQGZBMSCEZAL-UHFFFAOYSA-N n-[1-(butylamino)-1-oxo-3-[4-(2-pyrrolidin-1-ylethoxy)phenyl]propan-2-yl]-4-chlorobenzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)NCCCC)CC(C=C1)=CC=C1OCCN1CCCC1 GMAQGZBMSCEZAL-UHFFFAOYSA-N 0.000 description 2
- IUJWBGUKNJQHCH-UHFFFAOYSA-N n-[1-(butylamino)-3-[4-[2-(diethylamino)ethoxy]phenyl]-1-oxopropan-2-yl]-4-chlorobenzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)NCCCC)CC1=CC=C(OCCN(CC)CC)C=C1 IUJWBGUKNJQHCH-UHFFFAOYSA-N 0.000 description 2
- QUIWYJNJVWDLQV-UHFFFAOYSA-N n-[1-(butylamino)-3-[4-[2-(diethylamino)ethoxy]phenyl]-1-oxopropan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)NCCCC)CC1=CC=C(OCCN(CC)CC)C=C1 QUIWYJNJVWDLQV-UHFFFAOYSA-N 0.000 description 2
- QYBPBEKJXBRSGI-UHFFFAOYSA-N n-[1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)N)CC1=CC=C(O)C=C1 QYBPBEKJXBRSGI-UHFFFAOYSA-N 0.000 description 2
- PCIUIOOWSCCVDJ-UHFFFAOYSA-N n-[1-amino-3-[4-[2-(diethylamino)ethoxy]phenyl]-1-oxopropan-2-yl]benzamide Chemical compound C1=CC(OCCN(CC)CC)=CC=C1CC(C(N)=O)NC(=O)C1=CC=CC=C1 PCIUIOOWSCCVDJ-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 230000001148 spastic effect Effects 0.000 description 2
- 210000005070 sphincter Anatomy 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- IJGUGRDWHORRQH-NSHDSACASA-N (2s)-2-amino-3-(4-hydroxyphenyl)-n-propylpropanamide Chemical compound CCCNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 IJGUGRDWHORRQH-NSHDSACASA-N 0.000 description 1
- URHADIBOYNHFGM-LBPRGKRZSA-N (2s)-2-amino-n-butyl-3-(4-hydroxyphenyl)propanamide Chemical compound CCCCNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 URHADIBOYNHFGM-LBPRGKRZSA-N 0.000 description 1
- KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- ILLUNETYZYIYAH-UHFFFAOYSA-N 4-bromo-N-[1-(4-hydroxyphenyl)-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=C(Br)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 ILLUNETYZYIYAH-UHFFFAOYSA-N 0.000 description 1
- PIILQJQLIVQTOW-UHFFFAOYSA-N 4-chloro-N-[1-(4-hydroxyphenyl)-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 PIILQJQLIVQTOW-UHFFFAOYSA-N 0.000 description 1
- PZBRCQWMAIRLFK-UHFFFAOYSA-N 4-chloro-N-[1-[4-[2-(diethylamino)ethoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(CC)CC)C=C1 PZBRCQWMAIRLFK-UHFFFAOYSA-N 0.000 description 1
- VGVLFWGODCGJHX-UHFFFAOYSA-N 4-chloro-n-[1-(dipropylamino)-3-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-1-oxopropan-2-yl]benzamide;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)N(CCC)CCC)CC(C=C1)=CC=C1OCCN1CCN(C)CC1 VGVLFWGODCGJHX-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- VCCNKWWXYVWTLT-CYZBKYQRSA-N 7-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCCNKWWXYVWTLT-CYZBKYQRSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- ONOCVFQUJLSIOC-UHFFFAOYSA-N C=1C=C([N+]([O-])=O)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 ONOCVFQUJLSIOC-UHFFFAOYSA-N 0.000 description 1
- LPGGSTXPIBYXEL-UHFFFAOYSA-N C=1C=C([N+]([O-])=O)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(C)C)C=C1 Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(C)C)C=C1 LPGGSTXPIBYXEL-UHFFFAOYSA-N 0.000 description 1
- GGQAFLRAMIQTNT-UHFFFAOYSA-N CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(C(C)C)C(C)C)NC(=O)C2=CC=C(C=C2)Cl Chemical compound CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(C(C)C)C(C)C)NC(=O)C2=CC=C(C=C2)Cl GGQAFLRAMIQTNT-UHFFFAOYSA-N 0.000 description 1
- YKEYHKWZBDXXJC-UHFFFAOYSA-N CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(C)C)NC2=CC=CC=C2C Chemical compound CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(C)C)NC2=CC=CC=C2C YKEYHKWZBDXXJC-UHFFFAOYSA-N 0.000 description 1
- LEBOFLQWUXKGRH-UHFFFAOYSA-N CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(CC)CC)NC2=CC=CC=C2C Chemical compound CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(CC)CC)NC2=CC=CC=C2C LEBOFLQWUXKGRH-UHFFFAOYSA-N 0.000 description 1
- OETXFYFNWDXAOR-UHFFFAOYSA-N CCCNCCCC(C(CC(C=C1)=CC=C1O)NC1=C(C)C=CC=C1)=O Chemical compound CCCNCCCC(C(CC(C=C1)=CC=C1O)NC1=C(C)C=CC=C1)=O OETXFYFNWDXAOR-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- XJODKSPXAKFJHU-UHFFFAOYSA-N N-[1-(4-hydroxyphenyl)-3-oxo-6-(propylamino)hexan-2-yl]-3,4-dimethylbenzamide Chemical compound C=1C=C(C)C(C)=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 XJODKSPXAKFJHU-UHFFFAOYSA-N 0.000 description 1
- DPKYOXGEKJLXBA-UHFFFAOYSA-N N-[1-(4-hydroxyphenyl)-3-oxo-6-(propylamino)hexan-2-yl]-4-methoxybenzamide Chemical compound C=1C=C(OC)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(O)C=C1 DPKYOXGEKJLXBA-UHFFFAOYSA-N 0.000 description 1
- MZEQPIRJYDCWAI-UHFFFAOYSA-N N-[1-(4-hydroxyphenyl)-4-(methylamino)-3-oxobutan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CNC)CC1=CC=C(O)C=C1 MZEQPIRJYDCWAI-UHFFFAOYSA-N 0.000 description 1
- KPKUWCJCOAACPQ-UHFFFAOYSA-N N-[1-(butylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-4-chlorobenzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)NC(C(=O)NCCCC)CC1=CC=C(O)C=C1 KPKUWCJCOAACPQ-UHFFFAOYSA-N 0.000 description 1
- RFLKDXAKGKLDEA-UHFFFAOYSA-N N-[1-[4-[2-(diethylamino)ethoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]-4-methoxybenzamide Chemical compound C=1C=C(OC)C=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(CC)CC)C=C1 RFLKDXAKGKLDEA-UHFFFAOYSA-N 0.000 description 1
- XTBLRXZFSNMMKP-UHFFFAOYSA-N N-[1-[4-[2-(diethylamino)ethoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(CC)CC)C=C1 XTBLRXZFSNMMKP-UHFFFAOYSA-N 0.000 description 1
- XTBBJGUYGNTWDP-UHFFFAOYSA-N N-[1-[4-[2-(diethylamino)ethoxy]phenyl]-4-(methylamino)-3-oxobutan-2-yl]benzamide Chemical compound C1=CC(OCCN(CC)CC)=CC=C1CC(C(=O)CNC)NC(=O)C1=CC=CC=C1 XTBBJGUYGNTWDP-UHFFFAOYSA-N 0.000 description 1
- KRBKUVLVQATIEV-UHFFFAOYSA-N N-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound CCCNCCCC(=O)C(CC1=CC=C(C=C1)OCCN(C)C)NC(=O)C2=CC=CC=C2 KRBKUVLVQATIEV-UHFFFAOYSA-N 0.000 description 1
- SJYXAZSHQVTXNQ-UHFFFAOYSA-N N-[1-[4-[2-(dipropylamino)ethoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(CCC)CCC)C=C1 SJYXAZSHQVTXNQ-UHFFFAOYSA-N 0.000 description 1
- KZIALMFBNCGOPV-UHFFFAOYSA-N N-[1-[4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCN(C(C)C)C(C)C)C=C1 KZIALMFBNCGOPV-UHFFFAOYSA-N 0.000 description 1
- AHFKFQBCRHYLEK-UHFFFAOYSA-N N-[1-[4-[3-(diethylamino)propoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCCN(CC)CC)C=C1 AHFKFQBCRHYLEK-UHFFFAOYSA-N 0.000 description 1
- SURCOZULKHIZID-UHFFFAOYSA-N N-[1-[4-[3-(dimethylamino)propoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCCN(C)C)C=C1 SURCOZULKHIZID-UHFFFAOYSA-N 0.000 description 1
- OWYHOTGPGQJECW-UHFFFAOYSA-N N-[1-[4-[4-(diethylamino)-3-methylbutan-2-yl]oxyphenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OC(C)C(C)CN(CC)CC)C=C1 OWYHOTGPGQJECW-UHFFFAOYSA-N 0.000 description 1
- CHJKQETVTBFFDL-UHFFFAOYSA-N N-[1-[4-[4-(diethylamino)butoxy]phenyl]-3-oxo-6-(propylamino)hexan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)CCCNCCC)CC1=CC=C(OCCCCN(CC)CC)C=C1 CHJKQETVTBFFDL-UHFFFAOYSA-N 0.000 description 1
- RWZBUNSUROYJJI-UHFFFAOYSA-N N-[3-[4-[2-(diethylamino)ethoxy]phenyl]-1-oxo-1-(pyrrolidin-1-ylamino)propan-2-yl]benzamide Chemical compound CCN(CC)CCOC1=CC=C(C=C1)CC(C(=O)NN2CCCC2)NC(=O)C3=CC=CC=C3 RWZBUNSUROYJJI-UHFFFAOYSA-N 0.000 description 1
- HPLMCDUMPUKVNW-UHFFFAOYSA-N N-butyl-3-(4-hydroxyphenyl)-2-(2-methylanilino)propanamide Chemical compound CCCCNC(=O)C(CC1=CC=C(C=C1)O)NC2=CC=CC=C2C HPLMCDUMPUKVNW-UHFFFAOYSA-N 0.000 description 1
- DTAFLBZLAZYRDX-UHFFFAOYSA-N OOOOOO Chemical compound OOOOOO DTAFLBZLAZYRDX-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229940059260 amidate Drugs 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
- 229910001626 barium chloride Inorganic materials 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960001903 ergotamine tartrate Drugs 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 229960001186 methysergide Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- BWIGKFXJUIEFON-UHFFFAOYSA-N n-[1-(benzylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]benzamide Chemical compound C1=CC(O)=CC=C1CC(C(=O)NCC=1C=CC=CC=1)NC(=O)C1=CC=CC=C1 BWIGKFXJUIEFON-UHFFFAOYSA-N 0.000 description 1
- JOBYHDSHMVTOBW-UHFFFAOYSA-N n-[1-(benzylamino)-3-[4-[2-(dimethylamino)ethoxy]phenyl]-1-oxopropan-2-yl]benzamide Chemical compound C1=CC(OCCN(C)C)=CC=C1CC(C(=O)NCC=1C=CC=CC=1)NC(=O)C1=CC=CC=C1 JOBYHDSHMVTOBW-UHFFFAOYSA-N 0.000 description 1
- FBQIPWVDKIXRLF-UHFFFAOYSA-N n-[1-(butylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)NCCCC)CC1=CC=C(O)C=C1 FBQIPWVDKIXRLF-UHFFFAOYSA-N 0.000 description 1
- GKAKYWQREHNALZ-UHFFFAOYSA-N n-[1-(dipropylamino)-3-[4-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy]phenyl]-1-oxopropan-2-yl]benzamide;oxalic acid Chemical compound OC(=O)C(O)=O.C=1C=CC=CC=1C(=O)NC(C(=O)N(CCC)CCC)CC(C=C1)=CC=C1OCCCN1CCN(CCO)CC1 GKAKYWQREHNALZ-UHFFFAOYSA-N 0.000 description 1
- PHSNFVDDUQJFBI-UHFFFAOYSA-N n-[3-(4-hydroxyphenyl)-1-oxo-1-(propylamino)propan-2-yl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C(=O)NCCC)CC1=CC=C(O)C=C1 PHSNFVDDUQJFBI-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003667 tyrosine derivatives Chemical class 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
Classifications
-
- 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/18—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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- 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
- C07D295/08—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 bound oxygen or sulfur atoms
- C07D295/084—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/18—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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT67286/74A IT1062206B (it) | 1974-02-01 | 1974-02-01 | Derivati della tirosina attivi sulla muscolatura liscia |
| IT6728674 | 1974-02-01 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI750255A7 FI750255A7 (forum.php) | 1975-08-02 |
| FI61479B FI61479B (fi) | 1982-04-30 |
| FI61479C true FI61479C (fi) | 1982-08-10 |
Family
ID=11301149
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI750255A FI61479C (fi) | 1974-02-01 | 1975-01-30 | Foerfarande foer framstaellning av spasmolytiska nya d,l-tyrosinderivat |
| FI750256A FI63744C (fi) | 1974-02-01 | 1975-01-30 | Foerfarande foer framstaellning av nya spasmolytiska tyrosinderivat |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI750256A FI63744C (fi) | 1974-02-01 | 1975-01-30 | Foerfarande foer framstaellning av nya spasmolytiska tyrosinderivat |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4004008A (forum.php) |
| JP (2) | JPS5417729B2 (forum.php) |
| AT (2) | AT343632B (forum.php) |
| BE (1) | BE824995A (forum.php) |
| CA (2) | CA1047498A (forum.php) |
| CH (2) | CH605657A5 (forum.php) |
| DE (1) | DE2503992C2 (forum.php) |
| ES (1) | ES434323A1 (forum.php) |
| FI (2) | FI61479C (forum.php) |
| FR (1) | FR2259592B1 (forum.php) |
| GB (1) | GB1467927A (forum.php) |
| HK (1) | HK38979A (forum.php) |
| HU (2) | HU174825B (forum.php) |
| IN (1) | IN139364B (forum.php) |
| IT (1) | IT1062206B (forum.php) |
| NL (1) | NL167683C (forum.php) |
| NO (2) | NO144211C (forum.php) |
| SE (2) | SE413094B (forum.php) |
| ZA (1) | ZA75530B (forum.php) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5225243A (en) * | 1975-08-20 | 1977-02-25 | Toshiba Electric Equip Corp | Distributing panel |
| US4579866A (en) * | 1984-05-29 | 1986-04-01 | Usv Pharmaceutical Corp. | Phenylacetamides as anti-allergy, anti-asthma and anti-inflammatory agents |
| CA1320734C (en) * | 1986-02-04 | 1993-07-27 | Suntory Limited | Pyrrolidineamide derivative of acylamino acid and pharmaceutical composition containing the same |
| US5198458A (en) * | 1986-02-04 | 1993-03-30 | Suntory Limited | Pyrrolidineamide derivatives of acylamino acid and pharmaceutical composition containing the same |
| IL99537A (en) * | 1990-09-27 | 1995-11-27 | Merck & Co Inc | Fibrinogen receptor antagonists and pharmaceutical compositions containing them |
| NZ239846A (en) * | 1990-09-27 | 1994-11-25 | Merck & Co Inc | Sulphonamide derivatives and pharmaceutical compositions thereof |
| US5258407A (en) * | 1991-12-31 | 1993-11-02 | Sterling Winthrop Inc. | 3,4-disubstituted phenols-immunomodulating agents |
| US5206373A (en) * | 1992-02-28 | 1993-04-27 | Merck & Co., Inc. | Process for preparing fibrinogen receptor antagonists |
| DE10204951A1 (de) * | 2002-02-06 | 2003-08-14 | Basf Ag | Phenylalaninderivate als Herbizide |
| MXPA06005989A (es) * | 2003-12-19 | 2006-08-23 | Basf Ag | Fenilalanina-amidas sustituidas por benzoilo. |
| MX2008000971A (es) | 2005-07-19 | 2008-03-27 | Daiichi Sankyo Co Ltd | Derivado de propanamida sustituida y composicion farmaceutica que comprende al mismo. |
| WO2011094890A1 (en) | 2010-02-02 | 2011-08-11 | Argusina Inc. | Phenylalanine derivatives and their use as non-peptide glp-1 receptor modulators |
| WO2011156655A2 (en) | 2010-06-09 | 2011-12-15 | Receptos, Inc. | Novel glp-1 receptor stabilizers and modulators |
| EP2713722B1 (en) | 2011-05-31 | 2017-03-15 | Receptos, LLC | Novel glp-1 receptor stabilizers and modulators |
| MX365923B (es) | 2011-12-12 | 2019-06-20 | Celgene Int Ii Sarl | Derivados de acido carboxilico que comprenden cuatro ciclos, que actuan como moduladores del receptor del peptido 1 similar al glucagon (glp-1) para terapia de enfermedades como la diabetes. |
| CN102659619A (zh) * | 2012-04-18 | 2012-09-12 | 上海骏捷生化科技有限公司 | 一种合成酪氨酸衍生物的方法 |
| CN103508920B (zh) * | 2012-06-21 | 2016-03-02 | 贵州百灵企业集团制药股份有限公司 | 一种苯丙氨醇化合物的光学异构体的制备方法及其用途 |
| CN103508921B (zh) * | 2012-06-21 | 2015-09-30 | 贵州百灵企业集团制药股份有限公司 | 一种苯丙氨醇化合物的制备方法 |
| KR102271179B1 (ko) | 2013-06-11 | 2021-07-01 | 셀진 인터내셔널 Ii 에스에이알엘 | 신규의 glp-1 수용체 조절제 |
| AU2015292356B2 (en) | 2014-07-25 | 2020-02-06 | Receptos Llc | Novel GLP-1 receptor modulators |
| WO2016094729A1 (en) | 2014-12-10 | 2016-06-16 | Celgene International Ii Sarl | Glp-1 receptor modulators |
| CN107417560B (zh) * | 2017-03-30 | 2020-05-22 | 上海常丰生物医药科技有限公司 | 一种合成盐酸替罗酰胺的方法 |
| CN110015978B (zh) * | 2019-04-29 | 2021-03-19 | 康化（上海）新药研发有限公司 | O-[2-[[叔丁氧羰基]氨基]乙基]-n-[芴甲氧羰基]-l-酪氨酸的合成方法 |
| CN115850107B (zh) * | 2022-11-30 | 2024-11-12 | 苏州诚和医药化学有限公司 | 一种工业化合成盐酸替罗酰胺的方法 |
-
1974
- 1974-02-01 IT IT67286/74A patent/IT1062206B/it active Protection Beyond IP Right Term
-
1975
- 1975-01-22 GB GB287875A patent/GB1467927A/en not_active Expired
- 1975-01-24 ZA ZA00750530A patent/ZA75530B/xx unknown
- 1975-01-29 IN IN179/CAL/75A patent/IN139364B/en unknown
- 1975-01-30 FI FI750255A patent/FI61479C/fi not_active IP Right Cessation
- 1975-01-30 CH CH110875A patent/CH605657A5/xx not_active IP Right Cessation
- 1975-01-30 CA CA219,027A patent/CA1047498A/en not_active Expired
- 1975-01-30 FI FI750256A patent/FI63744C/fi not_active IP Right Cessation
- 1975-01-30 CH CH110975A patent/CH605658A5/xx not_active IP Right Cessation
- 1975-01-30 NO NO750288A patent/NO144211C/no unknown
- 1975-01-30 NO NO750287A patent/NO144210C/no unknown
- 1975-01-30 BE BE152889A patent/BE824995A/xx not_active IP Right Cessation
- 1975-01-30 CA CA75219028A patent/CA1048503A/en not_active Expired
- 1975-01-31 JP JP1328575A patent/JPS5417729B2/ja not_active Expired
- 1975-01-31 JP JP1326675A patent/JPS5417728B2/ja not_active Expired
- 1975-01-31 SE SE7501115A patent/SE413094B/xx unknown
- 1975-01-31 SE SE7501114A patent/SE410850B/xx not_active IP Right Cessation
- 1975-01-31 AT AT74675A patent/AT343632B/de not_active IP Right Cessation
- 1975-01-31 HU HU75RO820A patent/HU174825B/hu unknown
- 1975-01-31 ES ES434323A patent/ES434323A1/es not_active Expired
- 1975-01-31 NL NL7501193A patent/NL167683C/xx not_active IP Right Cessation
- 1975-01-31 HU HU75RO821A patent/HU175156B/hu unknown
- 1975-01-31 DE DE2503992A patent/DE2503992C2/de not_active Expired
- 1975-01-31 AT AT74575A patent/AT342026B/de not_active IP Right Cessation
- 1975-01-31 FR FR7503079A patent/FR2259592B1/fr not_active Expired
- 1975-02-03 US US05/546,481 patent/US4004008A/en not_active Expired - Lifetime
-
1979
- 1979-06-14 HK HK389/79A patent/HK38979A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI61479C (fi) | Foerfarande foer framstaellning av spasmolytiska nya d,l-tyrosinderivat | |
| DE69907476T2 (de) | Dibenzothiophene derivate und ihre verwendung | |
| Ducrocq et al. | Structure-activity relationship in a series of newly synthesized 1-amino-substituted ellipticine derivatives | |
| PL116103B1 (en) | Process for preparing novel derivatives of 3,4-cycloalkyltriazoles | |
| MX2007004489A (es) | Analogos de 17-hidroxiwortamina como inhibidores pi3k. | |
| CN103781753B (zh) | 用于治疗ape1介导的疾病的醌化合物 | |
| JPH0386887A (ja) | 含硫黄縮合ピリミジン誘導体 | |
| AU1915200A (en) | Nitrosated and nitrosylated h2 receptor antagonist compounds, compositions and methods of use | |
| WO2024008129A1 (zh) | 作为kat6抑制剂的化合物 | |
| JPS6330309B2 (forum.php) | ||
| TW202334148A (zh) | 用於治療弗里德希氏共濟失調（ｆｒｉｅｄｒｅｉｃｈ＇ｓ ａｔａｘｉａ）之化合物及方法 | |
| FI66002B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara substituerade 9,10-dihydro-4h-tieno(3,4-b)(1,5)bensodiazepin-10-oner samt deras syraadditionssalter | |
| SU1574177A3 (ru) | Способ получени производных 4,5-дигидрооксазолов | |
| CN118852216A (zh) | 一种金(i)配合物及其制备方法和应用 | |
| JP3575610B2 (ja) | 新規ベンゾピラノン、それらの製造方法およびそれらの使用 | |
| EP0548177B1 (en) | 5-aminosalicylic acid derivatives for the therapy of chronic inflammatory bowel diseases | |
| ES2222988T3 (es) | Formas de sal especificas de derivados de trifeniletileno como moduladores selectivos de los receptores de estrogenos. | |
| CN115974855A (zh) | Ezh2和hdac双靶点抑制剂、其药物组合物及其制备方法和用途 | |
| ES2347681T3 (es) | Agentes para tratar el herpes genital despues de su aparicion. | |
| US4364867A (en) | N-(1-Methyl-2-pyrrolidinylmethyl)-2,3-dimethoxy-5-methylsulfamoyl benzamide and its derivatives | |
| JPH03258770A (ja) | ベンズアゾール誘導体、その製法及びその合成中間体 | |
| FI60863B (fi) | Foerfarande foer framstaellning av nya bentshydryloxialkylaminderivat med foerlaengd antihistamineffekt | |
| FI62531B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbart 3-yan-n-(n n-dimetylamino-propyl)-iminobensyl och syraaddit iossalter daerav | |
| CA3093196A1 (en) | Methods and compositions of isoindoline-1,3-dione and isoindole prodrugs useful for treating cancer, ulcerative colitis and related inflammatory diseases | |
| FR2846330A1 (fr) | Derives de pyridoindolone substitues en -3 par groupe heterocyclique, leur preparation et leur application en therapeutique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: ROTTA RESEARCH LABORATORIUM S.P.A. |