CS222692B2 - Method of preparation of the new indolizine derivatives - Google Patents
Method of preparation of the new indolizine derivatives Download PDFInfo
- Publication number
- CS222692B2 CS222692B2 CS808517A CS851780A CS222692B2 CS 222692 B2 CS222692 B2 CS 222692B2 CS 808517 A CS808517 A CS 808517A CS 851780 A CS851780 A CS 851780A CS 222692 B2 CS222692 B2 CS 222692B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- oxy
- indolizine
- acid
- butylaminopropyl
- bromo
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 33
- 238000002360 preparation method Methods 0.000 title claims description 13
- 125000003406 indolizinyl group Chemical class C=1(C=CN2C=CC=CC12)* 0.000 title 1
- 239000002253 acid Substances 0.000 claims description 115
- -1 chloro, bromo, iodo Chemical group 0.000 claims description 68
- 239000000460 chlorine Substances 0.000 claims description 64
- 230000008569 process Effects 0.000 claims description 25
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- OWOMPJLGAFWXAP-UHFFFAOYSA-N [3,5-dichloro-4-[3-(dibutylamino)propoxy]phenyl]-(2-propan-2-ylindolizin-3-yl)methanone Chemical compound C1=C(Cl)C(OCCCN(CCCC)CCCC)=C(Cl)C=C1C(=O)C1=C(C(C)C)C=C2N1C=CC=C2 OWOMPJLGAFWXAP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 claims 12
- 125000001207 fluorophenyl group Chemical group 0.000 claims 7
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- 150000002431 hydrogen Chemical class 0.000 claims 4
- UHZANVOZGSZWJP-UHFFFAOYSA-N (2-butylindolizin-3-yl)-[3-chloro-4-[3-(dibutylamino)propoxy]phenyl]methanone Chemical compound C1=C(Cl)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CCCC)C=C2N1C=CC=C2 UHZANVOZGSZWJP-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- LTWWHSMUVBPPQC-UHFFFAOYSA-N [1-bromo-2-(4-chlorophenyl)indolizin-3-yl]-[3-chloro-4-[3-(dibutylamino)propoxy]phenyl]methanone Chemical compound C1=C(Cl)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(C=2C=CC(Cl)=CC=2)C(Br)=C2N1C=CC=C2 LTWWHSMUVBPPQC-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
- JRNFPZAAZKPQFK-UHFFFAOYSA-N [3-chloro-4-[3-(dibutylamino)propoxy]phenyl]-(2-ethylindolizin-3-yl)methanone Chemical compound C1=C(Cl)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CC)C=C2N1C=CC=C2 JRNFPZAAZKPQFK-UHFFFAOYSA-N 0.000 claims 1
- DVTWAVJCDNJCLR-UHFFFAOYSA-N [4-(3-bromopropoxy)-3-chlorophenyl]-(2-ethylindolizin-3-yl)methanone Chemical compound CCC1=C(N2C=CC=CC2=C1)C(=O)C1=CC(Cl)=C(OCCCBr)C=C1 DVTWAVJCDNJCLR-UHFFFAOYSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- GEOVEUCEIQCBKH-UHFFFAOYSA-N hypoiodous acid Chemical compound IO GEOVEUCEIQCBKH-UHFFFAOYSA-N 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 150000003335 secondary amines Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 112
- 150000001875 compounds Chemical class 0.000 description 49
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- 230000000694 effects Effects 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 230000002378 acidificating effect Effects 0.000 description 14
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical group CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 8
- 229930182837 (R)-adrenaline Natural products 0.000 description 8
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 206010003119 arrhythmia Diseases 0.000 description 8
- 230000017531 blood circulation Effects 0.000 description 8
- 229960005139 epinephrine Drugs 0.000 description 8
- 230000002107 myocardial effect Effects 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 229950007869 butoprozine Drugs 0.000 description 7
- 150000002478 indolizines Chemical class 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000036284 oxygen consumption Effects 0.000 description 6
- 206010002383 Angina Pectoris Diseases 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000006793 arrhythmia Effects 0.000 description 5
- 230000002526 effect on cardiovascular system Effects 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 101710094396 Hexon protein Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000004872 arterial blood pressure Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- KBHFIKGSWAQZEJ-UHFFFAOYSA-N 1H-indole zinc Chemical compound [Zn].C1=CC=C2NC=CC2=C1 KBHFIKGSWAQZEJ-UHFFFAOYSA-N 0.000 description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 3
- ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 229960005260 amiodarone Drugs 0.000 description 3
- 230000003257 anti-anginal effect Effects 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 229960002768 dipyridamole Drugs 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- MWQVQEFJAIFHFZ-UHFFFAOYSA-N 2,3-dichloro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(Cl)=C1Cl MWQVQEFJAIFHFZ-UHFFFAOYSA-N 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- FMAWAVRGYAKOGW-UHFFFAOYSA-N 4h-indolizin-4-ium;chloride Chemical compound Cl.C1=CC=CN2C=CC=C21 FMAWAVRGYAKOGW-UHFFFAOYSA-N 0.000 description 2
- 101100462138 Brassica napus OlnB1 gene Proteins 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FFOPEPMHKILNIT-UHFFFAOYSA-N Isopropyl butyrate Chemical compound CCCC(=O)OC(C)C FFOPEPMHKILNIT-UHFFFAOYSA-N 0.000 description 2
- 208000021908 Myocardial disease Diseases 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 208000006218 bradycardia Diseases 0.000 description 2
- 230000036471 bradycardia Effects 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 210000003161 choroid Anatomy 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 239000003415 peat Substances 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- HBQPMLUGRVEWPU-UHFFFAOYSA-N (1-bromo-2-phenylindolizin-3-yl)-[3,5-dichloro-4-[3-(dibutylamino)propoxy]phenyl]methanone Chemical compound CCCCN(CCCC)CCCOC1=C(C=C(C=C1Cl)C(=O)C2=C(C(=C3N2C=CC=C3)Br)C4=CC=CC=C4)Cl HBQPMLUGRVEWPU-UHFFFAOYSA-N 0.000 description 1
- VOVOFYMZGRLDMD-UHFFFAOYSA-N (1-bromo-2-propylindolizin-3-yl)-[3,5-dibromo-4-[3-(dipropylamino)propoxy]phenyl]methanone Chemical compound BrC=1C(=C(N2C=CC=CC=12)C(C1=CC(=C(C(=C1)Br)OCCCN(CCC)CCC)Br)=O)CCC VOVOFYMZGRLDMD-UHFFFAOYSA-N 0.000 description 1
- LGAKWJSUPPVZKW-UHFFFAOYSA-N (2-butylindolizin-3-yl)-[3-chloro-4-[3-(dibutylamino)propoxy]phenyl]methanone;hydrochloride Chemical compound Cl.C1=C(Cl)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CCCC)C=C2N1C=CC=C2 LGAKWJSUPPVZKW-UHFFFAOYSA-N 0.000 description 1
- QITNVELBDZPOOT-UHFFFAOYSA-N (2-butylindolizin-3-yl)-[4-[3-(dibutylamino)propoxy]-3-methylphenyl]methanone Chemical compound CCCCC1=C(N2C=CC=CC2=C1)C(=O)C3=CC(=C(C=C3)OCCCN(CCCC)CCCC)C QITNVELBDZPOOT-UHFFFAOYSA-N 0.000 description 1
- NUWXFGOWVXYMPS-UHFFFAOYSA-N (4-carbonochloridoylphenyl) 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=CC=C(C(Cl)=O)C=C1 NUWXFGOWVXYMPS-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- USKLUPUZMZMEOL-UHFFFAOYSA-N 1h-indole;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC=C2NC=CC2=C1 USKLUPUZMZMEOL-UHFFFAOYSA-N 0.000 description 1
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 description 1
- SOQWSEWRMYFXRL-UHFFFAOYSA-N 4-(4-methylphenyl)sulfonyloxybenzoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=CC=C(C(O)=O)C=C1 SOQWSEWRMYFXRL-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- VDQAETCUODSQQV-UHFFFAOYSA-N 5,6-dichloro-5-methoxycyclohexa-1,3-diene Chemical compound COC1(Cl)C=CC=CC1Cl VDQAETCUODSQQV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LAINEAZHXZVANE-UHFFFAOYSA-N CCCC1=C(N2C=CC=CC2=C1)C(=O)C3=CC(=C(C(=C3)Cl)OCCCN(CCC)CCC)Cl Chemical compound CCCC1=C(N2C=CC=CC2=C1)C(=O)C3=CC(=C(C(=C3)Cl)OCCCN(CCC)CCC)Cl LAINEAZHXZVANE-UHFFFAOYSA-N 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- 241000024080 Hiera Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- XTOCVSZSMHTDAJ-UHFFFAOYSA-N [1-bromo-2-(3-chloro-4-methylphenyl)indolizin-3-yl]-[3,5-dibromo-4-[3-(dibutylamino)propoxy]phenyl]methanone Chemical compound CCCCN(CCCC)CCCOC1=C(C=C(C=C1Br)C(=O)C2=C(C(=C3N2C=CC=C3)Br)C4=CC(=C(C=C4)C)Cl)Br XTOCVSZSMHTDAJ-UHFFFAOYSA-N 0.000 description 1
- TUDINPQHTRFSQM-UHFFFAOYSA-N [1-bromo-2-(4-methylphenyl)indolizin-3-yl]-[3,5-dibromo-4-[3-(dibutylamino)propoxy]phenyl]methanone Chemical compound CCCCN(CCCC)CCCOC1=C(C=C(C=C1Br)C(=O)C2=C(C(=C3N2C=CC=C3)Br)C4=CC=C(C=C4)C)Br TUDINPQHTRFSQM-UHFFFAOYSA-N 0.000 description 1
- XOHBIKMJDLXOKF-UHFFFAOYSA-N [1-chloro-2-(4-chlorophenyl)indolizin-3-yl]-[4-[3-(dipropylamino)propoxy]phenyl]methanone Chemical compound ClC=1C(=C(N2C=CC=CC=12)C(C1=CC=C(C=C1)OCCCN(CCC)CCC)=O)C1=CC=C(C=C1)Cl XOHBIKMJDLXOKF-UHFFFAOYSA-N 0.000 description 1
- MZYKCIIDMZKVSQ-UHFFFAOYSA-N [2,3-dichloro-4-[3-(dibutylamino)propoxy]phenyl]-(2-phenylindolizin-3-yl)methanone Chemical compound ClC1=C(Cl)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(C=2C=CC=CC=2)C=C2N1C=CC=C2 MZYKCIIDMZKVSQ-UHFFFAOYSA-N 0.000 description 1
- ZBSCKGSZIYTUAW-UHFFFAOYSA-N [3-chloro-4-[3-(dibutylamino)propoxy]phenyl]-(2-ethylindolizin-3-yl)methanone;hydrochloride Chemical compound Cl.C1=C(Cl)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CC)C=C2N1C=CC=C2 ZBSCKGSZIYTUAW-UHFFFAOYSA-N 0.000 description 1
- RMUKXITWZNPTRV-UHFFFAOYSA-N [4-[3-(dibutylamino)propoxy]-3-methoxyphenyl]-(2-ethylindolizin-3-yl)methanone Chemical compound CCCCN(CCCC)CCCOC1=C(C=C(C=C1)C(=O)C2=C(C=C3N2C=CC=C3)CC)OC RMUKXITWZNPTRV-UHFFFAOYSA-N 0.000 description 1
- YJOLEQFKGSBIBO-UHFFFAOYSA-N [4-[3-(dibutylamino)propoxy]-3-methylphenyl]-(2-methylindolizin-3-yl)methanone Chemical compound C1=C(C)C(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(C)C=C2N1C=CC=C2 YJOLEQFKGSBIBO-UHFFFAOYSA-N 0.000 description 1
- UXWYSOYZJWKETC-UHFFFAOYSA-N [4-[3-(dipropylamino)propoxy]-3-methoxyphenyl]-(1-methoxy-2-phenylindolizin-3-yl)methanone Chemical compound COC=1C(=C(N2C=CC=CC12)C(C1=CC(=C(C=C1)OCCCN(CCC)CCC)OC)=O)C1=CC=CC=C1 UXWYSOYZJWKETC-UHFFFAOYSA-N 0.000 description 1
- IIKQILIXUHMUKX-UHFFFAOYSA-N [4-[3-(dipropylamino)propoxy]-3-methoxyphenyl]-[2-(4-fluorophenyl)-1-methoxyindolizin-3-yl]methanone Chemical compound CCCN(CCC)CCCOC1=C(C=C(C=C1)C(=O)C2=C(C(=C3N2C=CC=C3)OC)C4=CC=C(C=C4)F)OC IIKQILIXUHMUKX-UHFFFAOYSA-N 0.000 description 1
- RLZXLUWKZCMNNZ-UHFFFAOYSA-N [4-[3-(dipropylamino)propoxy]phenyl]-(1-methoxy-2-phenylindolizin-3-yl)methanone Chemical compound COC=1C(=C(N2C=CC=CC=12)C(C1=CC=C(C=C1)OCCCN(CCC)CCC)=O)C1=CC=CC=C1 RLZXLUWKZCMNNZ-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 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
- 230000000397 acetylating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 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
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000001466 anti-adreneric effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 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
- 239000004305 biphenyl Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- PASOAYSIZAJOCT-UHFFFAOYSA-N butanoic acid Chemical compound CCCC(O)=O.CCCC(O)=O PASOAYSIZAJOCT-UHFFFAOYSA-N 0.000 description 1
- WDUJWTHGXVUWSJ-UHFFFAOYSA-N butanoic acid Chemical compound CCCC(O)=O.CCCC(O)=O.CCCC(O)=O WDUJWTHGXVUWSJ-UHFFFAOYSA-N 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 230000007681 cardiovascular toxicity Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 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
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001335 demethylating effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- ZEFLLXXLELNTJL-UHFFFAOYSA-N heptane Chemical compound CCCCCCC.CCCCCCC.CCCCCCC ZEFLLXXLELNTJL-UHFFFAOYSA-N 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 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
- ATADHKWKHYVBTJ-UHFFFAOYSA-N hydron;4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol;chloride Chemical compound Cl.CNCC(O)C1=CC=C(O)C(O)=C1 ATADHKWKHYVBTJ-UHFFFAOYSA-N 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 230000005370 isotopic spin Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000012057 packaged powder Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 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
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 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
- 239000001294 propane Substances 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (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 (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7942146 | 1979-12-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS222692B2 true CS222692B2 (en) | 1983-07-29 |
Family
ID=10509659
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS808517A CS222692B2 (en) | 1979-12-06 | 1980-12-04 | Method of preparation of the new indolizine derivatives |
| CS808517A CS222697B2 (en) | 1979-12-06 | 1980-12-04 | Method of preparation of the new indoline derivatives |
| CS814016A CS222698B2 (en) | 1979-12-06 | 1980-12-04 | Method of preparation of the new indolizine derivatives |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS808517A CS222697B2 (en) | 1979-12-06 | 1980-12-04 | Method of preparation of the new indoline derivatives |
| CS814016A CS222698B2 (en) | 1979-12-06 | 1980-12-04 | Method of preparation of the new indolizine derivatives |
Country Status (40)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107001363B (zh) * | 2014-12-10 | 2019-06-21 | 小野药品工业株式会社 | 二氢吲嗪酮衍生物 |
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 IS IS2594A patent/IS1209B6/is unknown
- 1980-11-05 ZA ZA00806831A patent/ZA806831B/xx 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 BG062985A patent/BG37379A3/xx unknown
- 1980-12-01 BG BG049830A patent/BG35598A3/xx unknown
- 1980-12-02 SE SE8008444A patent/SE441926B/sv not_active IP Right Cessation
- 1980-12-02 YU YU3041/80A patent/YU42366B/xx unknown
- 1980-12-03 MA MA19209A patent/MA19007A1/fr unknown
- 1980-12-03 IE IE2520/80A patent/IE50519B1/en unknown
- 1980-12-04 PL PL1980231829A patent/PL127865B1/pl unknown
- 1980-12-04 PL PL1980231828A patent/PL129365B1/pl unknown
- 1980-12-04 CS CS808517A patent/CS222692B2/cs unknown
- 1980-12-04 NZ NZ195754A patent/NZ195754A/en unknown
- 1980-12-04 IN IN1344/CAL/80A patent/IN151241B/en unknown
- 1980-12-04 PL PL1980228265A patent/PL127999B1/pl unknown
- 1980-12-04 CS CS808517A patent/CS222697B2/cs unknown
- 1980-12-04 CS CS814016A patent/CS222698B2/cs unknown
- 1980-12-04 PT PT72151A patent/PT72151B/pt unknown
- 1980-12-05 RO RO108948A patent/RO84707B/ro unknown
- 1980-12-05 AT AT0596780A patent/AT376438B/de not_active IP Right Cessation
- 1980-12-05 ES ES497504A patent/ES8205798A1/es not_active Expired
- 1980-12-05 FI FI803792A patent/FI67846C/fi not_active IP Right Cessation
- 1980-12-05 LU LU82983A patent/LU82983A1/fr unknown
- 1980-12-05 DE DE3046017A patent/DE3046017C2/de not_active Expired
- 1980-12-05 RO RO108949A patent/RO85271B/ro unknown
- 1980-12-05 SU SU803213301A patent/SU1058505A3/ru active
- 1980-12-05 NO NO803681A patent/NO157019C/no unknown
- 1980-12-05 RO RO102781A patent/RO81452B/ro unknown
- 1980-12-05 DK DK521980A patent/DK146977C/da not_active IP Right Cessation
- 1980-12-05 BE BE0/203053A patent/BE886511A/fr not_active IP Right Cessation
- 1980-12-05 JP JP17252180A patent/JPS56103181A/ja active Granted
- 1980-12-05 IT IT26463/80A patent/IT1218424B/it active
- 1980-12-05 HU HU802915A patent/HU185019B/hu not_active IP Right Cessation
- 1980-12-06 OA OA57269A patent/OA06711A/xx unknown
- 1980-12-06 AR AR283495A patent/AR227036A1/es active
- 1980-12-06 DD DD80225817A patent/DD155069A5/de unknown
-
1981
- 1981-12-16 ES ES508052A patent/ES508052A0/es active Granted
- 1981-12-16 ES ES508051A patent/ES8300108A1/es not_active Expired
- 1981-12-16 ES ES508053A patent/ES8300110A1/es not_active Expired
- 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
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3883540A (en) | Unsymmetrical esters of N-substituted 1,4-dihydropyridine 3,5-dicarboxylic acid | |
| JP5897566B2 (ja) | 環式ｎ，ｎ’−ジアリールチオ尿素及びｎ，ｎ’−ジアリール尿素−アンドロゲン受容体アンタゴニスト、抗癌剤、その調製のための方法及び使用 | |
| EP0025111B1 (en) | 3-aminopropoxyaryl derivatives, their preparation and pharmaceutical compositions containing them | |
| WO1993022298A1 (fr) | Derive d'oxazolidine et son sel pharmaceutiquement acceptable | |
| SK282661B6 (sk) | Trisubstituované fenylové deriváty a farmaceutické prostriedky s ich obsahom | |
| HU179745B (en) | Process for preparing new phthalazine derivatives and pharmaceutical compositions containing these compounds | |
| CS223842B2 (en) | Method of making the pyridoxin derivatives | |
| HU189166B (en) | Process for producing pyridazin-amine derivatives | |
| EP3564242B1 (en) | Compound for selectively inhibiting kinase and use thereof | |
| JPH06184139A (ja) | ４−置換１，２，４−トリアゾール誘導体 | |
| US3558652A (en) | N-monosubstituted pyrrylaminoethanols | |
| Miyano et al. | New antiarrhythmic agents. N-aryl-8-pyrrolizidinealkanamides | |
| GB2299581A (en) | 3-(Tetrahydropyridin-1-yl-methyl)pyrrolo[2,3-b]pyridine derivatives as ligands for dopamine receptor subtypes | |
| CZ121393A3 (en) | The use of dihydropyridine derivatives with annellated carbon or heterocyclic rings for the preparation of pharmaceutical preparations and heterocyclic annellated dihydropyridines | |
| HUE031676T2 (en) | An effective medicine for neuropathic pain | |
| JPH05507072A (ja) | Ｅｇｆレセプタチロシンキナーゼを阻害する複素環式エテンジイル化合物 | |
| CS222692B2 (en) | Method of preparation of the new indolizine derivatives | |
| US4520026A (en) | Indolizine derivatives and use as cardiovascular agents | |
| US4499095A (en) | Indolizine derivatives and their use in treating heart ailments | |
| CN108341816A (zh) | 一种选择性抑制激酶化合物 | |
| CN118434746A (zh) | 一种哒嗪类化合物、其药物组合物及应用 | |
| GB2086885A (en) | Imidazoles | |
| US4378362A (en) | Indolizine derivatives and process for preparing the same | |
| US4206217A (en) | 3-[4-(1,3-Diazacycloalken-2-yl)-phenyl]-1,2-benzisothiazoles, their manufacture, and drugs containing these compounds | |
| US3954754A (en) | 3-Hydrazino-cycloalkyl[c]pyridazines |