FI67846C - Foerfarande foer framstaellning av nya terapeutiskt aktiva 3-(4-(dialkylaminoalkyl)-oxi-bensoyl)-indolizinderivat - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt aktiva 3-(4-(dialkylaminoalkyl)-oxi-bensoyl)-indolizinderivat Download PDFInfo
- Publication number
- FI67846C FI67846C FI803792A FI803792A FI67846C FI 67846 C FI67846 C FI 67846C FI 803792 A FI803792 A FI 803792A FI 803792 A FI803792 A FI 803792A FI 67846 C FI67846 C FI 67846C
- Authority
- FI
- Finland
- Prior art keywords
- oxy
- indolizine
- acid
- oxalate
- ethyl
- Prior art date
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- 230000001225 therapeutic effect Effects 0.000 title description 4
- 230000004913 activation Effects 0.000 title 1
- 239000002253 acid Substances 0.000 claims description 146
- -1 alkali metal salt Chemical class 0.000 claims description 146
- 239000000460 chlorine Substances 0.000 claims description 80
- 150000001875 compounds Chemical class 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 22
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 15
- 150000002478 indolizines Chemical class 0.000 claims description 15
- 239000011630 iodine Substances 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000012458 free base Substances 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- YDOAQLOTLLFWEM-UHFFFAOYSA-N 3-(dibutylamino)propyl 4-methylbenzenesulfonate Chemical compound S(=O)(=O)(C1=CC=C(C)C=C1)OCCCN(CCCC)CCCC YDOAQLOTLLFWEM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- ANLMKUQEPXRMGV-UHFFFAOYSA-N n-butyl-n-(3-chloropropyl)butan-1-amine Chemical compound CCCCN(CCCC)CCCCl ANLMKUQEPXRMGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- SOIREJVRGZZKLI-UHFFFAOYSA-N [3-bromo-4-(3-bromopropoxy)phenyl]-(2-butylindolizin-3-yl)methanone Chemical compound C(CCC)C=1C=C2C=CC=CN2C=1C(C1=CC(=C(C=C1)OCCCBr)Br)=O SOIREJVRGZZKLI-UHFFFAOYSA-N 0.000 claims 1
- NWIHDMKHSNEADJ-UHFFFAOYSA-N [3-bromo-4-[3-(dibutylamino)propoxy]phenyl]-(2-butylindolizin-3-yl)methanone Chemical compound C1=C(Br)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CCCC)C=C2N1C=CC=C2 NWIHDMKHSNEADJ-UHFFFAOYSA-N 0.000 claims 1
- KURZCZMGELAPSV-UHFFFAOYSA-N [Br].[I] Chemical group [Br].[I] KURZCZMGELAPSV-UHFFFAOYSA-N 0.000 claims 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 97
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
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- 239000000203 mixture Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 206010002383 Angina Pectoris Diseases 0.000 description 11
- KVRGDVMQISBTKV-UHFFFAOYSA-N acetic acid;oxalic acid Chemical compound CC(O)=O.OC(=O)C(O)=O KVRGDVMQISBTKV-UHFFFAOYSA-N 0.000 description 11
- OZHOHTGAQOJLCS-UHFFFAOYSA-N oxalic acid;propanoic acid Chemical compound CCC(O)=O.OC(=O)C(O)=O OZHOHTGAQOJLCS-UHFFFAOYSA-N 0.000 description 11
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 11
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 10
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 10
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 10
- ROCHZUNCIZLTRQ-UHFFFAOYSA-N oxalic acid;propan-2-ol Chemical compound CC(C)O.OC(=O)C(O)=O ROCHZUNCIZLTRQ-UHFFFAOYSA-N 0.000 description 10
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical group CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 9
- 229930182837 (R)-adrenaline Natural products 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- SMTNXTHHYPIVQU-UHFFFAOYSA-N butanoic acid;oxalic acid Chemical compound CCCC(O)=O.OC(=O)C(O)=O SMTNXTHHYPIVQU-UHFFFAOYSA-N 0.000 description 9
- 229960005139 epinephrine Drugs 0.000 description 9
- 230000002107 myocardial effect Effects 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 206010003119 arrhythmia Diseases 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- JVIUIOWKTNJXAJ-UHFFFAOYSA-N acetic acid;2-ethoxy-2-oxoacetic acid Chemical compound CC(O)=O.CCOC(=O)C(O)=O JVIUIOWKTNJXAJ-UHFFFAOYSA-N 0.000 description 7
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical class C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 7
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- 238000002474 experimental method Methods 0.000 description 6
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- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 5
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- BUBNOQUZOCSBNU-UHFFFAOYSA-N benzene oxalic acid Chemical compound C1=CC=CC=C1.C(C(=O)O)(=O)O BUBNOQUZOCSBNU-UHFFFAOYSA-N 0.000 description 4
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
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- APDRKJYLOHFOPI-UHFFFAOYSA-N C(C(=O)O)(=O)O.C(C)C1=NC(=C2C=CC=CN12)C(=O)O Chemical compound C(C(=O)O)(=O)O.C(C)C1=NC(=C2C=CC=CN12)C(=O)O APDRKJYLOHFOPI-UHFFFAOYSA-N 0.000 description 1
- LHTPBAILYRLOPG-UHFFFAOYSA-N C(C(=O)O)(=O)O.C(C)C=1N=C2C=CC=CN2C1.C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.C(C)C=1N=C2C=CC=CN2C1 Chemical compound C(C(=O)O)(=O)O.C(C)C=1N=C2C=CC=CN2C1.C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.C(C)C=1N=C2C=CC=CN2C1 LHTPBAILYRLOPG-UHFFFAOYSA-N 0.000 description 1
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- VKZNBWBMHIAHCY-UHFFFAOYSA-N C1(=CC=CC=C1)C=1C=C2C=C(C=CN2C1C(C1=CC(=C(C=C1)OCCCN(CCC)CCC)Br)=O)C(=O)O Chemical compound C1(=CC=CC=C1)C=1C=C2C=C(C=CN2C1C(C1=CC(=C(C=C1)OCCCN(CCC)CCC)Br)=O)C(=O)O VKZNBWBMHIAHCY-UHFFFAOYSA-N 0.000 description 1
- ICRPELJIYRDIBA-UHFFFAOYSA-N C=1C=CN2C=CC=CC12.ClC1(CC=CC=C1)C(C)C(CCCC)C(C1=C(C(=C(C=C1)OCCCN(C)C)Cl)Cl)=O Chemical compound C=1C=CN2C=CC=CC12.ClC1(CC=CC=C1)C(C)C(CCCC)C(C1=C(C(=C(C=C1)OCCCN(C)C)Cl)Cl)=O ICRPELJIYRDIBA-UHFFFAOYSA-N 0.000 description 1
- CVMYSSYQYRGCCM-UHFFFAOYSA-N CC.C(C(=O)Cl)(=O)Cl Chemical compound CC.C(C(=O)Cl)(=O)Cl CVMYSSYQYRGCCM-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- LYMXYMZQRPBUAA-UHFFFAOYSA-N ClC=1C(=C(N2C=CC(=CC12)C(=O)O)C(C1=CC=C(C=C1)OCCCCCCN(CCCC)CCCC)=O)CCCC.C(C(=O)O)(=O)O.CO Chemical compound ClC=1C(=C(N2C=CC(=CC12)C(=O)O)C(C1=CC=C(C=C1)OCCCCCCN(CCCC)CCCC)=O)CCCC.C(C(=O)O)(=O)O.CO LYMXYMZQRPBUAA-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-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
- 240000008415 Lactuca sativa Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- RGTSQRQRVPHCGE-UHFFFAOYSA-N [1-bromo-2-(4-bromophenyl)indolizin-3-yl]-[4-[3-(dibutylamino)propoxy]phenyl]methanone Chemical compound BrC=1C(=C(N2C=CC=CC12)C(C1=CC=C(C=C1)OCCCN(CCCC)CCCC)=O)C1=CC=C(C=C1)Br RGTSQRQRVPHCGE-UHFFFAOYSA-N 0.000 description 1
- UCCZNXACIDLLOQ-UHFFFAOYSA-N [3,5-dichloro-4-[3-(dipropylamino)propoxy]phenyl]-(2-ethylindolizin-3-yl)methanone Chemical compound C(C)C=1C=C2C=CC=CN2C=1C(C1=CC(=C(C(=C1)Cl)OCCCN(CCC)CCC)Cl)=O UCCZNXACIDLLOQ-UHFFFAOYSA-N 0.000 description 1
- LWJYOZWLYKXKQL-UHFFFAOYSA-N [3-bromo-4-(3-bromopropoxy)phenyl]-(1-bromo-2-ethylindolizin-3-yl)methanone Chemical compound CCC=1C(Br)=C2C=CC=CN2C=1C(=O)C1=CC=C(OCCCBr)C(Br)=C1 LWJYOZWLYKXKQL-UHFFFAOYSA-N 0.000 description 1
- YDGOIPRSMDBUKX-UHFFFAOYSA-N [3-bromo-4-[3-(dibutylamino)propoxy]phenyl]-(1,2-dimethylindolizin-3-yl)methanone Chemical compound C1=C(Br)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(C)C(C)=C2N1C=CC=C2 YDGOIPRSMDBUKX-UHFFFAOYSA-N 0.000 description 1
- BLFSHHZREVWESO-UHFFFAOYSA-N [3-bromo-4-[3-(dibutylamino)propoxy]phenyl]-(1-bromo-2-methylindolizin-3-yl)methanone Chemical compound C1=C(Br)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(C)C(Br)=C2N1C=CC=C2 BLFSHHZREVWESO-UHFFFAOYSA-N 0.000 description 1
- NRTGWAAGLRTUJZ-UHFFFAOYSA-N [4-[3-(dibutylamino)propoxy]phenyl]-(2-ethylindolizin-3-yl)methanone Chemical compound C1=CC(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CC)C=C2N1C=CC=C2 NRTGWAAGLRTUJZ-UHFFFAOYSA-N 0.000 description 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
- CVOKPUSIMWYQQA-UHFFFAOYSA-N acetic acid;chloroethane Chemical compound CCCl.CC(O)=O CVOKPUSIMWYQQA-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229950007869 butoprozine Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000002089 crippling effect Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000000950 dibromo group Chemical group Br* 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 229960005215 dichloroacetic acid Drugs 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 150000002012 dioxanes Chemical class 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- NQYKOGPMIBDYAS-UHFFFAOYSA-N heptane;oxalic acid Chemical compound OC(=O)C(O)=O.CCCCCCC NQYKOGPMIBDYAS-UHFFFAOYSA-N 0.000 description 1
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- MZGOUPQENOEKHJ-UHFFFAOYSA-N indolizine-7-carboxylic acid Chemical compound C1=C(C(=O)O)C=CN2C=CC=C21 MZGOUPQENOEKHJ-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000006198 methoxylation reaction Methods 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- NEIFFYIKZKMFII-UHFFFAOYSA-N n-(3-chloropropyl)butan-1-amine Chemical compound CCCCNCCCCl NEIFFYIKZKMFII-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 1
- 150000002913 oxalic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000012045 salad Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- UMFCIIBZHQXRCJ-NSCUHMNNSA-N trans-anol Chemical compound C\C=C\C1=CC=C(O)C=C1 UMFCIIBZHQXRCJ-NSCUHMNNSA-N 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
- 230000002792 vascular Effects 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7942146 | 1979-12-06 | ||
| GB7942146 | 1979-12-06 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI803792L FI803792L (fi) | 1981-06-07 |
| FI67846B FI67846B (fi) | 1985-02-28 |
| FI67846C true FI67846C (fi) | 1985-06-10 |
Family
ID=10509659
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI803792A FI67846C (fi) | 1979-12-06 | 1980-12-05 | Foerfarande foer framstaellning av nya terapeutiskt aktiva 3-(4-(dialkylaminoalkyl)-oxi-bensoyl)-indolizinderivat |
Country Status (40)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2970233C (en) * | 2014-12-10 | 2023-01-03 | Ono Pharmaceutical Co., Ltd. | Dihydroindolizinone derivative |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1518443A (en) | 1976-02-19 | 1978-07-19 | Labaz | Indolizine derivatives and process for preparing the same |
-
1980
- 1980-10-31 IL IL61385A patent/IL61385A/xx unknown
- 1980-11-04 GR GR63275A patent/GR70224B/el unknown
- 1980-11-05 ZA ZA00806831A patent/ZA806831B/xx unknown
- 1980-11-05 IS IS2594A patent/IS1209B6/is unknown
- 1980-11-07 CH CH8289/80A patent/CH651041A5/fr not_active IP Right Cessation
- 1980-11-12 AU AU64292/80A patent/AU536320B2/en not_active Ceased
- 1980-11-13 PH PH24853A patent/PH17028A/en unknown
- 1980-11-19 NL NLAANVRAGE8006310,A patent/NL184683C/xx not_active IP Right Cessation
- 1980-11-25 BR BR8007691A patent/BR8007691A/pt unknown
- 1980-11-26 ZW ZW285/80A patent/ZW28580A1/xx unknown
- 1980-12-01 CA CA000365859A patent/CA1152077A/en not_active Expired
- 1980-12-01 BG BG049830A patent/BG35598A3/xx unknown
- 1980-12-01 BG BG062985A patent/BG37379A3/xx unknown
- 1980-12-02 YU YU3041/80A patent/YU42366B/xx unknown
- 1980-12-02 SE SE8008444A patent/SE441926B/sv not_active IP Right Cessation
- 1980-12-03 IE IE2520/80A patent/IE50519B1/en unknown
- 1980-12-03 MA MA19209A patent/MA19007A1/fr unknown
- 1980-12-04 PL PL1980231828A patent/PL129365B1/pl unknown
- 1980-12-04 PL PL1980231829A patent/PL127865B1/pl unknown
- 1980-12-04 PT PT72151A patent/PT72151B/pt unknown
- 1980-12-04 CS CS814016A patent/CS222698B2/cs unknown
- 1980-12-04 NZ NZ195754A patent/NZ195754A/en unknown
- 1980-12-04 CS CS808517A patent/CS222692B2/cs unknown
- 1980-12-04 PL PL1980228265A patent/PL127999B1/pl unknown
- 1980-12-04 CS CS808517A patent/CS222697B2/cs unknown
- 1980-12-04 IN IN1344/CAL/80A patent/IN151241B/en unknown
- 1980-12-05 IT IT26463/80A patent/IT1218424B/it active
- 1980-12-05 HU HU802915A patent/HU185019B/hu not_active IP Right Cessation
- 1980-12-05 RO RO108949A patent/RO85271B/ro unknown
- 1980-12-05 SU SU803213301A patent/SU1058505A3/ru active
- 1980-12-05 ES ES497504A patent/ES497504A0/es active Granted
- 1980-12-05 BE BE0/203053A patent/BE886511A/fr not_active IP Right Cessation
- 1980-12-05 RO RO108948A patent/RO84707B/ro unknown
- 1980-12-05 JP JP17252180A patent/JPS56103181A/ja active Granted
- 1980-12-05 DK DK521980A patent/DK146977C/da not_active IP Right Cessation
- 1980-12-05 AT AT0596780A patent/AT376438B/de not_active IP Right Cessation
- 1980-12-05 NO NO803681A patent/NO157019C/no unknown
- 1980-12-05 RO RO102781A patent/RO81452B/ro unknown
- 1980-12-05 FI FI803792A patent/FI67846C/fi not_active IP Right Cessation
- 1980-12-05 DE DE3046017A patent/DE3046017C2/de not_active Expired
- 1980-12-05 LU LU82983A patent/LU82983A1/fr unknown
- 1980-12-06 AR AR283495A patent/AR227036A1/es active
- 1980-12-06 OA OA57269A patent/OA06711A/xx unknown
- 1980-12-06 DD DD80225817A patent/DD155069A5/de unknown
-
1981
- 1981-12-16 ES ES508051A patent/ES508051A0/es active Granted
- 1981-12-16 ES ES508052A patent/ES8300109A1/es not_active Expired
- 1981-12-16 ES ES508053A patent/ES508053A0/es active Granted
- 1981-12-22 SU SU813367150A patent/SU1109051A3/ru active
-
1982
- 1982-02-24 AR AR288535A patent/AR229692A1/es active
- 1982-02-24 AR AR288533A patent/AR227093A1/es active
- 1982-02-24 AR AR227094A patent/AR227094A1/es active
-
1983
- 1983-02-24 YU YU443/83A patent/YU42840B/xx unknown
- 1983-02-24 YU YU444/83A patent/YU42127B/xx unknown
-
1984
- 1984-04-25 SG SG33384A patent/SG33384G/en unknown
- 1984-08-13 KE KE3438A patent/KE3438A/xx unknown
- 1984-08-23 HK HK658/84A patent/HK65884A/xx unknown
- 1984-10-12 SU SU843801012A patent/SU1287751A3/ru active
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: S.A. LABAZ-SANOKI N.V. |