CA2129301A1 - Benzo-fused heterocyclic compounds with a 5-membered ring, process for their preparation, their use as medicaments, their use as diagnostic agents, and medicaments containing them - Google Patents
Benzo-fused heterocyclic compounds with a 5-membered ring, process for their preparation, their use as medicaments, their use as diagnostic agents, and medicaments containing themInfo
- Publication number
- CA2129301A1 CA2129301A1 CA002129301A CA2129301A CA2129301A1 CA 2129301 A1 CA2129301 A1 CA 2129301A1 CA 002129301 A CA002129301 A CA 002129301A CA 2129301 A CA2129301 A CA 2129301A CA 2129301 A1 CA2129301 A1 CA 2129301A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- compound
- substituents
- group
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims abstract description 15
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 5
- 230000008569 process Effects 0.000 title claims abstract description 5
- 239000000032 diagnostic agent Substances 0.000 title abstract 2
- 229940039227 diagnostic agent Drugs 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 239000001301 oxygen Substances 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 21
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims abstract description 20
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims abstract description 10
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
- 229960000789 guanidine hydrochloride Drugs 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- 229960004198 guanidine Drugs 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000004434 sulfur atom Chemical group 0.000 claims description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 206010061216 Infarction Diseases 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 230000007574 infarction Effects 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
- XWLANNQRZFUAPV-UHFFFAOYSA-N n-(n-chloro-n'-methylcarbamimidoyl)-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)NC(NCl)=NC)=CC2=C1 XWLANNQRZFUAPV-UHFFFAOYSA-N 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- FWZUBSMPPRSUSD-UHFFFAOYSA-N 2-chloro-1-phenylindole-3-carboxylic acid Chemical compound C12=CC=CC=C2C(C(=O)O)=C(Cl)N1C1=CC=CC=C1 FWZUBSMPPRSUSD-UHFFFAOYSA-N 0.000 claims description 2
- SOIPLEFTUKIQPU-UHFFFAOYSA-N 2-phenoxy-1-phenylindole-3-carboxylic acid Chemical compound C=1C=CC=CC=1N1C2=CC=CC=C2C(C(=O)O)=C1OC1=CC=CC=C1 SOIPLEFTUKIQPU-UHFFFAOYSA-N 0.000 claims description 2
- SZEHIGJDYBQXQB-UHFFFAOYSA-N 5-chloro-n-(n'-ethylcarbamimidoyl)-1h-indole-2-carboxamide Chemical compound ClC1=CC=C2NC(C(=O)NC(N)=NCC)=CC2=C1 SZEHIGJDYBQXQB-UHFFFAOYSA-N 0.000 claims description 2
- CPYRAYIXLOAFNW-UHFFFAOYSA-N 5-chloro-n-(n'-methylcarbamimidoyl)-1h-indole-2-carboxamide Chemical compound ClC1=CC=C2NC(C(=O)N=C(N)NC)=CC2=C1 CPYRAYIXLOAFNW-UHFFFAOYSA-N 0.000 claims description 2
- PWFRXYGVBFGWEC-UHFFFAOYSA-N 5-fluoro-1-methyl-2,3-dihydroindole-2-carboxylic acid Chemical compound FC1=CC=C2N(C)C(C(O)=O)CC2=C1 PWFRXYGVBFGWEC-UHFFFAOYSA-N 0.000 claims description 2
- MQGGPFGQQPTFER-UHFFFAOYSA-N 5-fluoro-n-(n'-methylcarbamimidoyl)-1h-indole-2-carboxamide Chemical compound FC1=CC=C2NC(C(=O)NC(N)=NC)=CC2=C1 MQGGPFGQQPTFER-UHFFFAOYSA-N 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000002249 Diabetes Complications Diseases 0.000 claims description 2
- 206010012655 Diabetic complications Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 230000003111 delayed effect Effects 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 3
- 230000000302 ischemic effect Effects 0.000 claims 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 229910020587 CmF2m+1 Inorganic materials 0.000 claims 2
- 230000006793 arrhythmia Effects 0.000 claims 2
- 230000002093 peripheral effect Effects 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
- AACXATMOEQTZJH-UHFFFAOYSA-N 1-methyl-2,3-dihydroindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)CC2=C1 AACXATMOEQTZJH-UHFFFAOYSA-N 0.000 claims 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
- PPJSRJUPJJEHLL-UHFFFAOYSA-N 5-chloro-n-(n-chloro-n'-methylcarbamimidoyl)-1h-indole-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=C2NC(C(=O)N=C(NCl)NC)=CC2=C1 PPJSRJUPJJEHLL-UHFFFAOYSA-N 0.000 claims 1
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 206010008190 Cerebrovascular accident Diseases 0.000 claims 1
- 206010019668 Hepatic fibrosis Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 230000003176 fibrotic effect Effects 0.000 claims 1
- 206010020718 hyperplasia Diseases 0.000 claims 1
- 210000001428 peripheral nervous system Anatomy 0.000 claims 1
- 238000004321 preservation Methods 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 208000005069 pulmonary fibrosis Diseases 0.000 claims 1
- 201000002793 renal fibrosis Diseases 0.000 claims 1
- 206010040560 shock Diseases 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 107
- 230000008018 melting Effects 0.000 description 107
- 239000002253 acid Substances 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- -1 alkyl radicals Chemical class 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000002168 alkylating agent Substances 0.000 description 13
- 229940100198 alkylating agent Drugs 0.000 description 13
- 239000011734 sodium Substances 0.000 description 12
- 239000007795 chemical reaction product Substances 0.000 description 11
- TZMFJUDUGYTVRY-UHFFFAOYSA-N pentane-2,3-dione Chemical compound CCC(=O)C(C)=O TZMFJUDUGYTVRY-UHFFFAOYSA-N 0.000 description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- ZTVIKZXZYLEVOL-DGKWVBSXSA-N 2-hydroxy-2-phenylacetic acid [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] ester Chemical group C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-DGKWVBSXSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- 230000003288 anthiarrhythmic effect Effects 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- QXJMCSBBTMVSJS-UHFFFAOYSA-N 1-(1h-indol-2-yl)ethanone Chemical class C1=CC=C2NC(C(=O)C)=CC2=C1 QXJMCSBBTMVSJS-UHFFFAOYSA-N 0.000 description 3
- HCUARRIEZVDMPT-UHFFFAOYSA-M 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)[O-])=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229960002576 amiloride Drugs 0.000 description 3
- 239000003416 antiarrhythmic agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000004941 influx Effects 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 2
- KOTZNHLNBDTYMS-UHFFFAOYSA-N 3-bromo-1h-indole-2-carboxylic acid Chemical class C1=CC=C2C(Br)=C(C(=O)O)NC2=C1 KOTZNHLNBDTYMS-UHFFFAOYSA-N 0.000 description 2
- TXBNNSAGWGTPAP-UHFFFAOYSA-N 5-chloro-n-(n-chloro-n'-methylcarbamimidoyl)-1h-indole-2-carboxamide Chemical compound ClC1=CC=C2NC(C(=O)NC(NCl)=NC)=CC2=C1 TXBNNSAGWGTPAP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 2
- 244000166550 Strophanthus gratus Species 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- OKANYBNORCUPKZ-UHFFFAOYSA-N ethyl 2-ethyl-3-oxobutanoate Chemical compound CCOC(=O)C(CC)C(C)=O OKANYBNORCUPKZ-UHFFFAOYSA-N 0.000 description 2
- UCCIFVNIAMAXLD-UHFFFAOYSA-N ethyl 3-bromo-5-chloro-1h-indole-2-carboxylate Chemical compound C1=C(Cl)C=C2C(Br)=C(C(=O)OCC)NC2=C1 UCCIFVNIAMAXLD-UHFFFAOYSA-N 0.000 description 2
- 238000005048 flame photometry Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 2
- 229960003343 ouabain Drugs 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- QNRXNRGSOJZINA-QMMMGPOBSA-N (2s)-2,3-dihydro-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2N[C@H](C(=O)O)CC2=C1 QNRXNRGSOJZINA-QMMMGPOBSA-N 0.000 description 1
- RBKHNGHPZZZJCI-UHFFFAOYSA-N (4-aminophenyl)-phenylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)C1=CC=CC=C1 RBKHNGHPZZZJCI-UHFFFAOYSA-N 0.000 description 1
- SKBNVXRFQDOXRP-UHFFFAOYSA-N 1,3,4,6-tetramethylindole-2-carboxylic acid Chemical compound CC1=CC(C)=C2C(C)=C(C(O)=O)N(C)C2=C1 SKBNVXRFQDOXRP-UHFFFAOYSA-N 0.000 description 1
- KNMCRHYTVLCQPZ-UHFFFAOYSA-N 1-(3,4,6-trimethyl-1h-indol-2-yl)ethanone Chemical compound CC1=CC(C)=C2C(C)=C(C(=O)C)NC2=C1 KNMCRHYTVLCQPZ-UHFFFAOYSA-N 0.000 description 1
- ACYAOODLPIBZNI-UHFFFAOYSA-N 1-(3-methyl-5-propan-2-yl-1h-indol-2-yl)ethanone Chemical compound CC(C)C1=CC=C2NC(C(C)=O)=C(C)C2=C1 ACYAOODLPIBZNI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
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- C07D235/32—Benzimidazole-2-carbamic acids, unsubstituted or substituted; Esters thereof; Thio-analogues thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/86—Benzo [b] furans; Hydrogenated benzo [b] furans with an oxygen atom directly attached in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4326005.5 | 1993-08-03 | ||
| DE4326005A DE4326005A1 (de) | 1993-08-03 | 1993-08-03 | Benzokondensierte 5-Ringheterocyclen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, ihre Verwendung als Diagnostikum, sowie sie enthaltendes Medikament |
| DEP4414316.8 | 1994-04-25 | ||
| DE19944414316 DE4414316A1 (de) | 1994-04-25 | 1994-04-25 | Benzokondensierte 5-Ringheterocyclen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, ihre Verwendung als Diagnostikum, sowie sie enthaltendes Medikament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2129301A1 true CA2129301A1 (en) | 1995-02-04 |
Family
ID=25928286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002129301A Abandoned CA2129301A1 (en) | 1993-08-03 | 1994-08-02 | Benzo-fused heterocyclic compounds with a 5-membered ring, process for their preparation, their use as medicaments, their use as diagnostic agents, and medicaments containing them |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0639573A1 (enExample) |
| JP (1) | JPH07145149A (enExample) |
| KR (2) | KR100343292B1 (enExample) |
| CN (1) | CN1118347A (enExample) |
| AU (1) | AU682371B2 (enExample) |
| CA (1) | CA2129301A1 (enExample) |
| FI (1) | FI943579A7 (enExample) |
| HU (1) | HU218790B (enExample) |
| IL (1) | IL110503A (enExample) |
| NO (1) | NO301584B1 (enExample) |
| NZ (1) | NZ264130A (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| US9394285B2 (en) | 2013-03-15 | 2016-07-19 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
Families Citing this family (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2121391A1 (en) * | 1993-04-28 | 1994-10-29 | Atsuyuki Kojima | Indoloylguanidine derivatives |
| US6169107B1 (en) | 1993-04-28 | 2001-01-02 | Sumitomo Pharmaceutical Co., Ltd. | Indoloylguanidine derivatives |
| DE69525763T2 (de) * | 1994-04-11 | 2002-10-02 | Chugai Seiyaku K.K., Tokio/Tokyo | 4,6-DI-t-BUTYL-2,3-DIHYDROBENZOTHIOPHENE, DIE LDL OXIDATION HEMMEN |
| DE4412334A1 (de) * | 1994-04-11 | 1995-10-19 | Hoechst Ag | Substituierte N-Heteroaroylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| CA2160600A1 (en) * | 1994-10-18 | 1996-04-19 | Masahumi Kitano | Indoloylguanidine derivatives |
| US5834466A (en) * | 1994-12-22 | 1998-11-10 | The Regents Of The University Of California | Method for protecting of heart by limiting metabolic and ionic abnormalities developed during ischemia, following ischemia or resulting from ischemia |
| DE69603771T2 (de) * | 1995-04-18 | 2000-09-07 | Hoechst Ag | Substituierte Indenoylguanidines mit antiarrhythmischer und cardioprotektiver Wirkung |
| DE19540995A1 (de) * | 1995-11-03 | 1997-05-07 | Hoechst Ag | Substituierte Sulfonimidamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE19542306A1 (de) * | 1995-11-14 | 1997-05-15 | Hoechst Ag | Sulfonylamino-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| PL316439A1 (en) * | 1995-11-20 | 1997-05-26 | Hoechst Ag | Novel substituted derivatives of benzoyloguanidine, method of obtaining them, their application in production of pharmaceutic and diagnostic agents and pharmaceutic agent as such |
| DE19546736A1 (de) * | 1995-12-14 | 1997-06-19 | Hoechst Ag | Substituierte Chromanylsulfonyl(thio)harnstoffe, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung pharmazeutischer Präparate |
| DE19548708A1 (de) * | 1995-12-23 | 1997-06-26 | Merck Patent Gmbh | Cyclische Sulfone |
| DE19548812A1 (de) * | 1995-12-27 | 1997-07-03 | Hoechst Ag | Verwendung von Inhibitoren des zellulären Na·+·/H·+·-Exchangers (NHE) zur Herstellung eines Medikaments zur Atemstimulation |
| NZ314105A (en) * | 1996-02-02 | 1997-12-19 | Sumitomo Pharma | Guanidine derivative substituted with a substituted indole which is peri condensed with a heterocyclic ring |
| WO1997031611A2 (en) * | 1996-03-01 | 1997-09-04 | Chiron Corporation | Treatment of begnin prostatic hyperplasia |
| WO1998055475A1 (en) * | 1997-06-02 | 1998-12-10 | Fujisawa Pharmaceutical Co., Ltd. | Guanidine deriviatives as inhibitors of na+/h+ exchange in cells |
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| DE60330227D1 (de) | 2002-03-13 | 2010-01-07 | Array Biopharma Inc | N3-alkylierte benzimidazol-derivate als mek-hemmer |
| FR2842525B1 (fr) * | 2002-07-16 | 2005-05-13 | Aventis Pharma Sa | Derives de 3-guanidinocarbonyl-1-heteroaryl-indole, procede de preparation a titre de medicaments et compositions pharmaceutiques les renfermant |
| FR2842526B1 (fr) * | 2002-07-16 | 2007-07-13 | Aventis Pharma Sa | Compositions pharmaceutiques contenant un derive de 3-guanidinocarbonyl-1-heteroaryl-indole, procede de preparation a titre de medicaments |
| US7141600B2 (en) | 2003-04-15 | 2006-11-28 | The Regents Of The University Of California | Small molecule inhibition of a PDZ-domain interaction |
| FR2856062B1 (fr) * | 2003-06-12 | 2005-11-11 | Aventis Pharma Sa | Derives 3-guanidinocarbonyl-heterocycle, procede de preparation et intermediaires de ce procede a titre de medicaments et compositions pharmaceutiques les renfermant |
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| US7795295B2 (en) | 2004-07-01 | 2010-09-14 | The Regents Of The University Of California | Small molecule inhibition of PDZ-domain interaction |
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| KR102767180B1 (ko) | 2024-10-17 | 2025-02-14 | 효림이엔아이 주식회사 | 슬러지 수집 안정성이 향상된 원형 슬러지 수집기 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4544670A (en) * | 1982-08-24 | 1985-10-01 | William H. Rorer, Inc. | Method of treating coccidiosis with acyl guanidines |
| DE3304019A1 (de) * | 1983-02-07 | 1984-08-09 | Kali-Chemie Pharma Gmbh, 3000 Hannover | 3-acyloxy-1-phenyl-2-aminocarbonylindol-verbindungen sowie verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3929582A1 (de) * | 1989-09-06 | 1991-03-07 | Hoechst Ag | Benzoylguanidine, verfahren zu ihrer herstellung, ihre verwendung als medikament sowie sie enthaltendes medikament |
| DE4127026A1 (de) * | 1991-08-16 | 1993-02-18 | Boehringer Ingelheim Kg | Neue pyrazinderivate, ihre herstellung und verwendung |
-
1994
- 1994-07-28 EP EP94111765A patent/EP0639573A1/de not_active Withdrawn
- 1994-07-29 IL IL11050394A patent/IL110503A/xx not_active IP Right Cessation
- 1994-07-29 NZ NZ264130A patent/NZ264130A/en unknown
- 1994-08-01 FI FI943579A patent/FI943579A7/fi unknown
- 1994-08-01 AU AU68844/94A patent/AU682371B2/en not_active Ceased
- 1994-08-02 KR KR1019940019259A patent/KR100343292B1/ko not_active Expired - Fee Related
- 1994-08-02 NO NO942864A patent/NO301584B1/no not_active IP Right Cessation
- 1994-08-02 KR KR1019940019071A patent/KR950005817A/ko not_active Ceased
- 1994-08-02 JP JP6198940A patent/JPH07145149A/ja active Pending
- 1994-08-02 CN CN94109516A patent/CN1118347A/zh active Pending
- 1994-08-02 CA CA002129301A patent/CA2129301A1/en not_active Abandoned
- 1994-08-03 HU HU9402271A patent/HU218790B/hu not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| US9394285B2 (en) | 2013-03-15 | 2016-07-19 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
Also Published As
| Publication number | Publication date |
|---|---|
| HU218790B (hu) | 2000-12-28 |
| KR950005512A (ko) | 1995-03-20 |
| KR100343292B1 (ko) | 2002-12-26 |
| NZ264130A (en) | 1995-12-21 |
| HUT70547A (en) | 1995-10-30 |
| NO942864L (no) | 1995-02-06 |
| AU682371B2 (en) | 1997-10-02 |
| FI943579L (fi) | 1995-02-04 |
| AU6884494A (en) | 1995-02-16 |
| NO942864D0 (enExample) | 1994-08-02 |
| FI943579A0 (fi) | 1994-08-01 |
| FI943579A7 (fi) | 1995-02-04 |
| IL110503A0 (en) | 1994-10-21 |
| IL110503A (en) | 2000-06-29 |
| EP0639573A1 (de) | 1995-02-22 |
| CN1118347A (zh) | 1996-03-13 |
| JPH07145149A (ja) | 1995-06-06 |
| NO301584B1 (no) | 1997-11-17 |
| KR950005817A (ko) | 1995-03-20 |
| HU9402271D0 (en) | 1994-09-28 |
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| Date | Code | Title | Description |
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