DE3445691C2 - - Google Patents
Info
- Publication number
- DE3445691C2 DE3445691C2 DE3445691A DE3445691A DE3445691C2 DE 3445691 C2 DE3445691 C2 DE 3445691C2 DE 3445691 A DE3445691 A DE 3445691A DE 3445691 A DE3445691 A DE 3445691A DE 3445691 C2 DE3445691 C2 DE 3445691C2
- Authority
- DE
- Germany
- Prior art keywords
- ethyl
- benzamidine
- mixture
- methoxy
- dec
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 68
- -1 Amidine compounds Chemical class 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052801 chlorine Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000002462 imidazolines Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- HYHIGVWALQFMOP-UHFFFAOYSA-N 4-[2-[4-(aminomethyl)phenyl]ethyl]-n'-methoxybenzenecarboximidamide Chemical compound C1=CC(C(/N)=N/OC)=CC=C1CCC1=CC=C(CN)C=C1 HYHIGVWALQFMOP-UHFFFAOYSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
- 239000000203 mixture Substances 0.000 description 85
- 239000000243 solution Substances 0.000 description 69
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
- 239000002904 solvent Substances 0.000 description 60
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000013078 crystal Substances 0.000 description 27
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000010992 reflux Methods 0.000 description 24
- 235000019441 ethanol Nutrition 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- 229960004756 ethanol Drugs 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 235000019445 benzyl alcohol Nutrition 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000003937 benzamidines Chemical class 0.000 description 8
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000000470 constituent Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 238000010531 catalytic reduction reaction Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 238000006959 Williamson synthesis reaction Methods 0.000 description 5
- 150000003973 alkyl amines Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 210000003540 papillary muscle Anatomy 0.000 description 5
- HPEBQBPULRUAAV-UHFFFAOYSA-N (4-methoxyphenyl)methyl N-[amino-(3-benzoyl-4-hydroxyphenyl)methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)NC(=N)C1=CC=C(O)C(C(=O)C=2C=CC=CC=2)=C1 HPEBQBPULRUAAV-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 239000004342 Benzoyl peroxide Substances 0.000 description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 150000001409 amidines Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 235000019400 benzoyl peroxide Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 4
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- GYPANLYCVNJHLL-UHFFFAOYSA-N 1,4-xylene;dihydrobromide Chemical compound Br.Br.CC1=CC=C(C)C=C1 GYPANLYCVNJHLL-UHFFFAOYSA-N 0.000 description 3
- BPKCSDHUTRRAQN-UHFFFAOYSA-N 4-[2-[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]ethenyl]benzonitrile Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC(C=C1)=CC=C1C=CC1=CC=C(C#N)C=C1 BPKCSDHUTRRAQN-UHFFFAOYSA-N 0.000 description 3
- POEDKNIMHLXOEX-UHFFFAOYSA-N 4-[2-[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]ethyl]benzonitrile Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC(C=C1)=CC=C1CCC1=CC=C(C#N)C=C1 POEDKNIMHLXOEX-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 3
- FKCBLVCOSCZFHV-UHFFFAOYSA-N acetonitrile;ethanol Chemical compound CCO.CC#N FKCBLVCOSCZFHV-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 229960001412 pentobarbital Drugs 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 210000005245 right atrium Anatomy 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 230000002861 ventricular Effects 0.000 description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
- DQJUAUGPNCLTNF-UHFFFAOYSA-N (3-chloro-4-methylphenyl)methanamine;hydrochloride Chemical compound Cl.CC1=CC=C(CN)C=C1Cl DQJUAUGPNCLTNF-UHFFFAOYSA-N 0.000 description 2
- SHVDSQSUDVJXEY-UHFFFAOYSA-N (3-methoxy-4-methylphenyl)methanol Chemical compound COC1=CC(CO)=CC=C1C SHVDSQSUDVJXEY-UHFFFAOYSA-N 0.000 description 2
- CZOIJCXSCMYTRJ-UHFFFAOYSA-N (4-methoxyphenyl)methyl (nz)-n-[amino-[3-benzoyl-4-[[2-chloro-4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]methoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)\N=C(/N)C(C=C1C(=O)C=2C=CC=CC=2)=CC=C1OCC(C(=C1)Cl)=CC=C1CN1C(=O)C2=CC=CC=C2C1=O CZOIJCXSCMYTRJ-UHFFFAOYSA-N 0.000 description 2
- KBWKSSNYHWHRSO-UHFFFAOYSA-N (4-methoxyphenyl)methyl (nz)-n-[amino-[4-[[3-(aminomethyl)phenyl]methoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)NC(=N)C(C=C1)=CC=C1OCC1=CC=CC(CN)=C1 KBWKSSNYHWHRSO-UHFFFAOYSA-N 0.000 description 2
- HVVLBBMXUJOGGT-UHFFFAOYSA-N (4-methoxyphenyl)methyl (nz)-n-[amino-[4-[[3-(bromomethyl)phenyl]methoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)NC(=N)C(C=C1)=CC=C1OCC1=CC=CC(CBr)=C1 HVVLBBMXUJOGGT-UHFFFAOYSA-N 0.000 description 2
- OIGKFRMEJJZKHI-UHFFFAOYSA-N (4-methoxyphenyl)methyl (nz)-n-[amino-[4-[[4-(bromomethyl)phenyl]methoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)NC(=N)C(C=C1)=CC=C1OCC1=CC=C(CBr)C=C1 OIGKFRMEJJZKHI-UHFFFAOYSA-N 0.000 description 2
- ASXWPKHEKJAWDR-UHFFFAOYSA-N (4-methoxyphenyl)methyl (nz)-n-[amino-[4-[[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]methoxy]-3-methoxyphenyl]methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)\N=C(/N)C(C=C1OC)=CC=C1OCC(C=C1)=CC=C1CN1C(=O)C2=CC=CC=C2C1=O ASXWPKHEKJAWDR-UHFFFAOYSA-N 0.000 description 2
- SGOVTHFSNDRBRH-UHFFFAOYSA-N (4-methoxyphenyl)methyl n-[3-[4-(chloromethyl)phenyl]prop-2-enyl]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)NCC=CC1=CC=C(CCl)C=C1 SGOVTHFSNDRBRH-UHFFFAOYSA-N 0.000 description 2
- SYBRLAFMXHYIPF-UHFFFAOYSA-N (4-methoxyphenyl)methyl n-[amino-[3-benzoyl-4-[[4-[3-[(4-methoxyphenyl)methoxycarbonylamino]prop-1-enyl]phenyl]methoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)NCC=CC(C=C1)=CC=C1COC1=CC=C(C(=N)NC(=O)OCC=2C=CC(OC)=CC=2)C=C1C(=O)C1=CC=CC=C1 SYBRLAFMXHYIPF-UHFFFAOYSA-N 0.000 description 2
- UZDDXUMOXKDXNE-UHFFFAOYSA-N 1-(4-methylphenyl)ethanamine Chemical compound CC(N)C1=CC=C(C)C=C1 UZDDXUMOXKDXNE-UHFFFAOYSA-N 0.000 description 2
- KGYUBBFNBRAXAV-UHFFFAOYSA-N 2-[(4-methylphenyl)methyl]isoindole-1,3-dione Chemical compound C1=CC(C)=CC=C1CN1C(=O)C2=CC=CC=C2C1=O KGYUBBFNBRAXAV-UHFFFAOYSA-N 0.000 description 2
- FMGIAMOOHWQISI-UHFFFAOYSA-N 3-(bromomethyl)-4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1CBr FMGIAMOOHWQISI-UHFFFAOYSA-N 0.000 description 2
- VMCCYZSBZYUNTN-UHFFFAOYSA-N 3-[2-[3-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]ethyl]-n'-methylbenzenecarboximidamide;hydrochloride Chemical compound Cl.CNC(=N)C1=CC=CC(CCC=2C=C(CN3C(C4=CC=CC=C4C3=O)=O)C=CC=2)=C1 VMCCYZSBZYUNTN-UHFFFAOYSA-N 0.000 description 2
- XPDAKEOBPKFUAH-UHFFFAOYSA-N 3-azaniumyl-3-(4-methylphenyl)propanoate Chemical compound CC1=CC=C(C(N)CC(O)=O)C=C1 XPDAKEOBPKFUAH-UHFFFAOYSA-N 0.000 description 2
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 description 2
- VKUZKODMGPGAHT-UHFFFAOYSA-N 4-[2-[4-(aminomethyl)phenyl]ethyl]benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.C1=CC(CN)=CC=C1CCC1=CC=C(C(N)=N)C=C1 VKUZKODMGPGAHT-UHFFFAOYSA-N 0.000 description 2
- RACHKMQTWAAUFC-UHFFFAOYSA-N 4-[2-[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]ethyl]-n'-methylbenzenecarboximidamide;hydrochloride Chemical compound Cl.C1=CC(C(=N)NC)=CC=C1CCC(C=C1)=CC=C1CN1C(=O)C2=CC=CC=C2C1=O RACHKMQTWAAUFC-UHFFFAOYSA-N 0.000 description 2
- WWRAPNKULQNXOC-UHFFFAOYSA-N 4-[[4-(bromomethyl)phenyl]methoxy]benzonitrile Chemical compound C1=CC(CBr)=CC=C1COC1=CC=C(C#N)C=C1 WWRAPNKULQNXOC-UHFFFAOYSA-N 0.000 description 2
- BSGWALCXPZDPTE-UHFFFAOYSA-N 4-[[4-[(dimethylamino)methyl]phenyl]methoxy]benzonitrile Chemical compound C1=CC(CN(C)C)=CC=C1COC1=CC=C(C#N)C=C1 BSGWALCXPZDPTE-UHFFFAOYSA-N 0.000 description 2
- QJRWLNLUIAJTAD-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC=C1O QJRWLNLUIAJTAD-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 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 2
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- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 239000004312 hexamethylene tetramine Substances 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- CEAJFNBWKBTRQE-UHFFFAOYSA-N methanamine;methanol Chemical compound NC.OC CEAJFNBWKBTRQE-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- LRCOSGGIMSNVAA-UHFFFAOYSA-N methyl 3-[4-[2-(4-carbamimidoylphenyl)ethyl]phenyl]-3-(1,3-dioxoisoindol-2-yl)propanoate;hydrochloride Chemical compound Cl.O=C1C2=CC=CC=C2C(=O)N1C(CC(=O)OC)C(C=C1)=CC=C1CCC1=CC=C(C(N)=N)C=C1 LRCOSGGIMSNVAA-UHFFFAOYSA-N 0.000 description 1
- YOSDLDDROGPMOG-UHFFFAOYSA-N methyl 3-[4-[2-(4-cyanophenyl)ethyl]phenyl]-3-(1,3-dioxoisoindol-2-yl)propanoate Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(CC(=O)OC)C(C=C1)=CC=C1CCC1=CC=C(C#N)C=C1 YOSDLDDROGPMOG-UHFFFAOYSA-N 0.000 description 1
- USCUVTTXCFXGNA-UHFFFAOYSA-N methyl 3-amino-3-[4-[2-(4-carbamimidoylphenyl)ethyl]phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C(N)CC(=O)OC)=CC=C1CCC1=CC=C(C(N)=N)C=C1 USCUVTTXCFXGNA-UHFFFAOYSA-N 0.000 description 1
- XGBXOGQDEAGJKO-UHFFFAOYSA-N methyl 4-(2-aminoethyl)benzoate Chemical compound COC(=O)C1=CC=C(CCN)C=C1 XGBXOGQDEAGJKO-UHFFFAOYSA-N 0.000 description 1
- LPWSIMUBBCJMKV-UHFFFAOYSA-N methyl 4-[2-[4-[1-(1,3-dioxoisoindol-2-yl)ethyl]phenyl]ethyl]benzenecarboximidate;hydrochloride Chemical compound Cl.C1=CC(C(=N)OC)=CC=C1CCC1=CC=C(C(C)N2C(C3=CC=CC=C3C2=O)=O)C=C1 LPWSIMUBBCJMKV-UHFFFAOYSA-N 0.000 description 1
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- LNSOSGIMOFFUBV-UHFFFAOYSA-N n'-(2-aminoethyl)-3-[2-[4-(aminomethyl)phenyl]ethyl]-4-methoxybenzenecarboximidamide;trihydrochloride Chemical compound Cl.Cl.Cl.COC1=CC=C(C(=N)NCCN)C=C1CCC1=CC=C(CN)C=C1 LNSOSGIMOFFUBV-UHFFFAOYSA-N 0.000 description 1
- HXRUXINYBQUOQU-UHFFFAOYSA-N n'-[2-(3,4-dimethoxyphenyl)ethyl]-4-[2-[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]ethyl]benzenecarboximidamide;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCNC(=N)C(C=C1)=CC=C1CCC(C=C1)=CC=C1CN1C(=O)C2=CC=CC=C2C1=O HXRUXINYBQUOQU-UHFFFAOYSA-N 0.000 description 1
- HVJPBHYDCJWIEZ-UHFFFAOYSA-N n'-amino-4-[[4-(aminomethyl)phenyl]methoxy]-3-methoxybenzenecarboximidamide Chemical compound COC1=CC(C(=N)NN)=CC=C1OCC1=CC=C(CN)C=C1 HVJPBHYDCJWIEZ-UHFFFAOYSA-N 0.000 description 1
- NREWNGCDJYEERL-UHFFFAOYSA-N n'-amino-4-[[4-(aminomethyl)phenyl]methoxy]-3-methoxybenzenecarboximidamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.COC1=CC(C(=N)NN)=CC=C1OCC1=CC=C(CN)C=C1 NREWNGCDJYEERL-UHFFFAOYSA-N 0.000 description 1
- WLMLFPIFGHNZFU-UHFFFAOYSA-N n'-cyclohexyl-4-[2-[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]ethyl]benzenecarboximidamide;hydrochloride Chemical compound Cl.C=1C=C(CCC=2C=CC(CN3C(C4=CC=CC=C4C3=O)=O)=CC=2)C=CC=1C(=N)NC1CCCCC1 WLMLFPIFGHNZFU-UHFFFAOYSA-N 0.000 description 1
- QXVYNBRIVMKNKH-UHFFFAOYSA-N n'-methyl-4-[2-[4-(methylaminomethyl)phenyl]ethyl]benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.C1=CC(CNC)=CC=C1CCC1=CC=C(C(=N)NC)C=C1 QXVYNBRIVMKNKH-UHFFFAOYSA-N 0.000 description 1
- BZCLSQZPKHAJON-UHFFFAOYSA-N n'-methyl-4-[[3-(methylaminomethyl)phenyl]methoxy]benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.CNCC1=CC=CC(COC=2C=CC(=CC=2)C(=N)NC)=C1 BZCLSQZPKHAJON-UHFFFAOYSA-N 0.000 description 1
- WWECJGLXBSQKRF-UHFFFAOYSA-N n,n-dimethylformamide;methanol Chemical compound OC.CN(C)C=O WWECJGLXBSQKRF-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
- LPNBBFKOUUSUDB-UHFFFAOYSA-M p-toluate Chemical compound CC1=CC=C(C([O-])=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-M 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000001013 sinoatrial node Anatomy 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/22—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/24—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58237715A JPS60130561A (ja) | 1983-12-16 | 1983-12-16 | アミジン誘導体およびそれを含む強心剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
DE3445691A1 DE3445691A1 (de) | 1985-07-04 |
DE3445691C2 true DE3445691C2 (en, 2012) | 1988-07-14 |
Family
ID=17019421
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19843445691 Granted DE3445691A1 (de) | 1983-12-16 | 1984-12-14 | Amidinderivate, verfahren zu ihrer herstellung und pharmazeutische mittel |
Country Status (5)
Country | Link |
---|---|
US (1) | US4598077A (en, 2012) |
JP (1) | JPS60130561A (en, 2012) |
DE (1) | DE3445691A1 (en, 2012) |
FR (1) | FR2556720B1 (en, 2012) |
GB (1) | GB2152501B (en, 2012) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6133173A (ja) * | 1984-07-25 | 1986-02-17 | Torii Yakuhin Kk | アミジン化合物 |
GB8520774D0 (en) * | 1985-08-20 | 1985-09-25 | Shell Int Research | Diphenyl ether herbicides |
JP2531218Y2 (ja) * | 1991-09-04 | 1997-04-02 | 株式会社丸山製作所 | 噴頭の折曲装置 |
DE4309285A1 (de) * | 1993-03-23 | 1994-09-29 | Boehringer Ingelheim Kg | Heterocyclen enthaltende Amidinderivate, ihre Herstellung und Verwendung |
RU2130017C1 (ru) * | 1993-08-12 | 1999-05-10 | Астра Актиенболаг | Производные амидина, способ их получения и лекарственное средство на их основе, обладающее свойством ингибировать активность синтетазы оксида азота (у) |
DE69508875T2 (de) * | 1994-09-20 | 1999-09-16 | Ono Pharmaceutical Co. Ltd., Osaka | Amidinophenol-Derivate als Protease-hemmende Verbindungen |
AU707215B2 (en) * | 1995-01-05 | 1999-07-08 | Torii Pharmaceutical Co., Ltd. | Thrombolytic agents |
WO1998007421A1 (fr) * | 1996-08-16 | 1998-02-26 | Ishihara Sangyo Kaisha, Ltd. | Composition medicinale |
US7375125B2 (en) * | 1999-08-04 | 2008-05-20 | Ore Pharmaceuticals, Inc. | Melanocortin-4 receptor binding compounds and methods of use thereof |
WO2009058216A1 (en) * | 2007-11-01 | 2009-05-07 | Acucela, Inc. | Amine derivative compounds for treating ophthalmic diseases and disorders |
CN103012200B (zh) * | 2011-09-20 | 2014-12-17 | 北京大学 | 具有β-分泌酶抑制功能的化合物及其制备方法与应用 |
DK3247699T3 (da) | 2015-01-22 | 2019-08-12 | Sanofi Aventis Deutschland | Proces til produktion of 2-[4-(cyclopropancarbonyl)phenyl]-2-methyl-propannitril |
CA3086099C (en) | 2017-11-16 | 2023-05-09 | Montdorex Inc. | Mono- and di-amidine endo-exonuclease inhibitors and methods for inhibiting endo-exonuclease activity |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1241832B (de) * | 1963-02-23 | 1967-06-08 | Hoechst Ag | Verfahren zur Herstellung von Pyrimidiniumverbindungen |
US4025555A (en) * | 1976-07-23 | 1977-05-24 | Pfizer Inc. | Aromatic amidines as antiviral agents in animals |
-
1983
- 1983-12-16 JP JP58237715A patent/JPS60130561A/ja active Granted
-
1984
- 1984-12-14 DE DE19843445691 patent/DE3445691A1/de active Granted
- 1984-12-14 FR FR8419150A patent/FR2556720B1/fr not_active Expired
- 1984-12-14 US US06/681,476 patent/US4598077A/en not_active Expired - Lifetime
- 1984-12-14 GB GB08431598A patent/GB2152501B/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
JPS60130561A (ja) | 1985-07-12 |
GB8431598D0 (en) | 1985-01-30 |
GB2152501B (en) | 1987-08-26 |
FR2556720B1 (fr) | 1988-01-08 |
US4598077A (en) | 1986-07-01 |
GB2152501A (en) | 1985-08-07 |
FR2556720A1 (fr) | 1985-06-21 |
DE3445691A1 (de) | 1985-07-04 |
JPH0310616B2 (en, 2012) | 1991-02-14 |
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