JP4039588B2 - 置換された２−ナフトイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 - Google Patents
置換された２−ナフトイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 Download PDFInfo
- Publication number
- JP4039588B2 JP4039588B2 JP13822797A JP13822797A JP4039588B2 JP 4039588 B2 JP4039588 B2 JP 4039588B2 JP 13822797 A JP13822797 A JP 13822797A JP 13822797 A JP13822797 A JP 13822797A JP 4039588 B2 JP4039588 B2 JP 4039588B2
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- alkyl
- formula
- substituted
- methyl
- 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 - Fee Related
Links
- OECMIBNCPUMKFU-UHFFFAOYSA-N n-(diaminomethylidene)naphthalene-2-carboxamide Chemical class C1=CC=CC2=CC(C(=O)N=C(N)N)=CC=C21 OECMIBNCPUMKFU-UHFFFAOYSA-N 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- 239000000032 diagnostic agent Substances 0.000 title 1
- 229940039227 diagnostic agent Drugs 0.000 title 1
- 239000008177 pharmaceutical agent Substances 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 37
- 239000000203 mixture Substances 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 21
- 238000011282 treatment Methods 0.000 description 21
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 19
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 19
- 229910052717 sulfur Inorganic materials 0.000 description 19
- 239000003814 drug Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 125000000753 cycloalkyl group Chemical group 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- 230000002265 prevention Effects 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 11
- -1 indazoyl Chemical group 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 229960002576 amiloride Drugs 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
- APOPAXUENTVHHC-UHFFFAOYSA-N n-(diaminomethylidene)naphthalene-1-carboxamide Chemical group C1=CC=C2C(C(=O)NC(=N)N)=CC=CC2=C1 APOPAXUENTVHHC-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 201000001320 Atherosclerosis Diseases 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 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 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- LTPOSIZJPSDSIL-UHFFFAOYSA-N 5,6-diphenylmorpholin-2-one Chemical compound O1C(=O)CNC(C=2C=CC=CC=2)C1C1=CC=CC=C1 LTPOSIZJPSDSIL-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 206010048554 Endothelial dysfunction Diseases 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000008694 endothelial dysfunction Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 208000028867 ischemia Diseases 0.000 description 5
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 description 4
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 description 4
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- 206010061216 Infarction Diseases 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000007574 infarction Effects 0.000 description 4
- 230000004941 influx Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 206010040560 shock Diseases 0.000 description 4
- 230000035939 shock Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- SKTKMAWOMQFTNS-UHFFFAOYSA-N 6-methoxycarbonylnaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(C(=O)OC)=CC=C21 SKTKMAWOMQFTNS-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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000003288 anthiarrhythmic effect Effects 0.000 description 3
- 239000003416 antiarrhythmic agent Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- QDERNBXNXJCIQK-UHFFFAOYSA-N ethylisopropylamiloride Chemical compound CCN(C(C)C)C1=NC(N)=C(C(=O)N=C(N)N)N=C1Cl QDERNBXNXJCIQK-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 150000005209 naphthoic acids Chemical class 0.000 description 3
- 229960003343 ouabain Drugs 0.000 description 3
- KZRRSHWRUTVRPI-UHFFFAOYSA-N 2-(6-methoxycarbonylnaphthalen-2-yl)oxyacetic acid Chemical compound C1=C(OCC(O)=O)C=CC2=CC(C(=O)OC)=CC=C21 KZRRSHWRUTVRPI-UHFFFAOYSA-N 0.000 description 2
- KOYNSYQEKPNAOB-UHFFFAOYSA-N 2-[[6-(diaminomethylidenecarbamoyl)naphthalene-2-carbonyl]amino]ethyl n-(diaminomethylidene)carbamate Chemical compound C1=C(C(=O)NC(N)=N)C=CC2=CC(C(=O)NCCOC(=O)NC(=N)N)=CC=C21 KOYNSYQEKPNAOB-UHFFFAOYSA-N 0.000 description 2
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 2
- YAFGMPAIRCFEQR-UHFFFAOYSA-N 2-n-(diaminomethylidene)-6-n-(pyridin-3-ylmethyl)naphthalene-2,6-dicarboxamide;dihydrochloride Chemical compound Cl.Cl.C1=CC2=CC(C(=O)NC(=N)N)=CC=C2C=C1C(=O)NCC1=CC=CN=C1 YAFGMPAIRCFEQR-UHFFFAOYSA-N 0.000 description 2
- RXMUPNVSYKGKMY-UHFFFAOYSA-N 3-amino-6-chloro-n-(diaminomethylidene)-5-(dimethylamino)pyrazine-2-carboxamide Chemical compound CN(C)C1=NC(N)=C(C(=O)N=C(N)N)N=C1Cl RXMUPNVSYKGKMY-UHFFFAOYSA-N 0.000 description 2
- PFIGQADVUSMBQQ-UHFFFAOYSA-N 4-(diethylamino)-3-ethoxy-6-methoxy-1-methylnaphthalene-2-carboxylic acid Chemical compound C1=CC(OC)=CC2=C(N(CC)CC)C(OCC)=C(C(O)=O)C(C)=C21 PFIGQADVUSMBQQ-UHFFFAOYSA-N 0.000 description 2
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 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
- KHUXJKKWPCFOSI-UHFFFAOYSA-N 6-(2-hydroxyethylcarbamoyl)naphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(C(=O)NCCO)=CC=C21 KHUXJKKWPCFOSI-UHFFFAOYSA-N 0.000 description 2
- LHLYNTKDQFORTN-UHFFFAOYSA-N 6-[2-(diethylamino)ethoxy]naphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(OCCN(CC)CC)=CC=C21 LHLYNTKDQFORTN-UHFFFAOYSA-N 0.000 description 2
- YRQOSWNFDJDLGH-UHFFFAOYSA-N 6-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethoxy]-n-(diaminomethylidene)naphthalene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=CC2=CC(C(=O)NC(=N)N)=CC=C2C=C1OCCN(CC1)CCN1C1=CC=C(Cl)C=C1 YRQOSWNFDJDLGH-UHFFFAOYSA-N 0.000 description 2
- ZYAGRZVREIPJJD-UHFFFAOYSA-N 6-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethoxy]naphthalene-2-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CC=C2C=C1OCCN(CC1)CCN1C1=CC=C(Cl)C=C1 ZYAGRZVREIPJJD-UHFFFAOYSA-N 0.000 description 2
- XSEQMTQGIZKJSR-UHFFFAOYSA-N 6-[2-[di(propan-2-yl)amino]ethoxy]naphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(OCCN(C(C)C)C(C)C)=CC=C21 XSEQMTQGIZKJSR-UHFFFAOYSA-N 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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010003225 Arteriospasm coronary Diseases 0.000 description 2
- 208000003890 Coronary Vasospasm Diseases 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 208000007530 Essential hypertension Diseases 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
- 206010021143 Hypoxia Diseases 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-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
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 244000166550 Strophanthus gratus Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000000923 atherogenic effect Effects 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 201000011634 coronary artery vasospasm Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005048 flame photometry Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000000055 hyoplipidemic effect Effects 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NTDOJQGLOAUCFX-UHFFFAOYSA-N methyl 4-acetyloxy-6-methoxy-1-methylnaphthalene-2-carboxylate Chemical compound C1=C(OC)C=CC2=C(C)C(C(=O)OC)=CC(OC(C)=O)=C21 NTDOJQGLOAUCFX-UHFFFAOYSA-N 0.000 description 2
- HMNABSBBBWHDPT-UHFFFAOYSA-N methyl 4-hydroxy-6-methoxy-1-methylnaphthalene-2-carboxylate Chemical compound C1=C(OC)C=CC2=C(C)C(C(=O)OC)=CC(O)=C21 HMNABSBBBWHDPT-UHFFFAOYSA-N 0.000 description 2
- SSXLJDRGQULNMK-UHFFFAOYSA-N methyl 6-(2-morpholin-4-ylethoxy)naphthalene-2-carboxylate Chemical compound C1=CC2=CC(C(=O)OC)=CC=C2C=C1OCCN1CCOCC1 SSXLJDRGQULNMK-UHFFFAOYSA-N 0.000 description 2
- QYOYVDZQNIKVNM-UHFFFAOYSA-N methyl 6-[2-(diethylamino)ethoxy]naphthalene-2-carboxylate Chemical compound C1=C(C(=O)OC)C=CC2=CC(OCCN(CC)CC)=CC=C21 QYOYVDZQNIKVNM-UHFFFAOYSA-N 0.000 description 2
- IDOBIEPGMHYDNM-UHFFFAOYSA-N methyl 6-[2-[di(propan-2-yl)amino]ethoxy]naphthalene-2-carboxylate Chemical compound C1=C(OCCN(C(C)C)C(C)C)C=CC2=CC(C(=O)OC)=CC=C21 IDOBIEPGMHYDNM-UHFFFAOYSA-N 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- VSEORRJPSJBKEH-UHFFFAOYSA-N n-(diaminomethylidene)-6-(2-morpholin-4-ylethoxy)naphthalene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=CC2=CC(C(=O)NC(=N)N)=CC=C2C=C1OCCN1CCOCC1 VSEORRJPSJBKEH-UHFFFAOYSA-N 0.000 description 2
- GJIWTFORHYKXNU-UHFFFAOYSA-N n-(diaminomethylidene)-6-[2-(diaminomethylideneamino)-2-oxoethoxy]naphthalene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=C(C(=O)NC(N)=N)C=CC2=CC(OCC(=O)NC(=N)N)=CC=C21 GJIWTFORHYKXNU-UHFFFAOYSA-N 0.000 description 2
- CDUWSNIRQRYTKE-UHFFFAOYSA-N n-(diaminomethylidene)-6-[2-(diethylamino)ethoxy]naphthalene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=C(C(=O)NC(N)=N)C=CC2=CC(OCCN(CC)CC)=CC=C21 CDUWSNIRQRYTKE-UHFFFAOYSA-N 0.000 description 2
- IAVRBROZFZNFKF-UHFFFAOYSA-N n-(diaminomethylidene)-6-[2-[di(propan-2-yl)amino]ethoxy]naphthalene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=C(C(=O)NC(N)=N)C=CC2=CC(OCCN(C(C)C)C(C)C)=CC=C21 IAVRBROZFZNFKF-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 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
- 230000001575 pathological effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000011477 surgical intervention Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- MFLYTCSVJYYAOR-UHFFFAOYSA-N (carbamimidoylazaniumyl)formate Chemical compound NC(=N)NC(O)=O MFLYTCSVJYYAOR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- JWGQVEQXLLXHRY-UHFFFAOYSA-N 1-(2-chloroethyl)-4-(4-chlorophenyl)piperazine Chemical compound C1CN(CCCl)CCN1C1=CC=C(Cl)C=C1 JWGQVEQXLLXHRY-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- GLYNMRBRWBSXQP-UHFFFAOYSA-N 2-[[6-(diaminomethylidenecarbamoyl)naphthalene-2-carbonyl]amino]ethyl n-(diaminomethylidene)carbamate;dihydrochloride Chemical compound Cl.Cl.C1=C(C(=O)NC(N)=N)C=CC2=CC(C(=O)NCCOC(=O)NC(=N)N)=CC=C21 GLYNMRBRWBSXQP-UHFFFAOYSA-N 0.000 description 1
- ZAPMTSHEXFEPSD-UHFFFAOYSA-N 4-(2-chloroethyl)morpholine Chemical compound ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- KAUQJMHLAFIZDU-UHFFFAOYSA-N 6-Hydroxy-2-naphthoic acid Chemical compound C1=C(O)C=CC2=CC(C(=O)O)=CC=C21 KAUQJMHLAFIZDU-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 0 CC(C)N(CCOc(cc1)cc(cc2)c1cc2C(N=C(N)N)=O)C(C)* Chemical compound CC(C)N(CCOc(cc1)cc(cc2)c1cc2C(N=C(N)N)=O)C(C)* 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 208000018152 Cerebral disease Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- MUXOBHXGJLMRAB-UHFFFAOYSA-N Dimethyl succinate Chemical compound COC(=O)CCC(=O)OC MUXOBHXGJLMRAB-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 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
- 229920000084 Gum arabic Polymers 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 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
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000009692 acute damage Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000009693 chronic damage Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- GYUVMLBYMPKZAZ-UHFFFAOYSA-N dimethyl naphthalene-2,6-dicarboxylate Chemical compound C1=C(C(=O)OC)C=CC2=CC(C(=O)OC)=CC=C21 GYUVMLBYMPKZAZ-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000004066 metabolic change Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- ZBTRJRYKQWTQDX-UHFFFAOYSA-N methyl 4-[2-(diethylamino)ethoxy]-6-methoxy-1-methylnaphthalene-2-carboxylate Chemical compound C1=C(OC)C=C2C(OCCN(CC)CC)=CC(C(=O)OC)=C(C)C2=C1 ZBTRJRYKQWTQDX-UHFFFAOYSA-N 0.000 description 1
- QUCCTADIFZDGTL-UHFFFAOYSA-N methyl 6-(2-methoxy-2-oxoethoxy)naphthalene-2-carboxylate Chemical compound C1=C(C(=O)OC)C=CC2=CC(OCC(=O)OC)=CC=C21 QUCCTADIFZDGTL-UHFFFAOYSA-N 0.000 description 1
- HMRROBKAACRWBP-UHFFFAOYSA-N methyl naphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CC=CC2=C1 HMRROBKAACRWBP-UHFFFAOYSA-N 0.000 description 1
- IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- DBVADBHSJCWFKI-UHFFFAOYSA-N n-(2-chloroethyl)-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C(C)C)CCCl DBVADBHSJCWFKI-UHFFFAOYSA-N 0.000 description 1
- ODKBEPYUHMPDHY-UHFFFAOYSA-N n-(diaminomethylidene)-4-[2-(diethylamino)ethoxy]-6-methoxy-1-methylnaphthalene-2-carboxamide Chemical compound C1=C(OC)C=C2C(OCCN(CC)CC)=CC(C(=O)NC(N)=N)=C(C)C2=C1 ODKBEPYUHMPDHY-UHFFFAOYSA-N 0.000 description 1
- DOQAQGZSMGRTDJ-UHFFFAOYSA-N n-(diaminomethylidene)-4-[2-(diethylamino)ethoxy]-6-methoxy-1-methylnaphthalene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=C(OC)C=C2C(OCCN(CC)CC)=CC(C(=O)NC(N)=N)=C(C)C2=C1 DOQAQGZSMGRTDJ-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000009993 protective function Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000054 salidiuretic effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- 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
- C07D213/40—Acylated substituent nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- A61P9/10—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/22—Y being a hydrogen or a carbon atom, e.g. benzoylguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19621483:1 | 1996-05-29 | ||
| DE19621483A DE19621483A1 (de) | 1996-05-29 | 1996-05-29 | Substituierte 2-Naphthoylguanidine, Verfahren zur ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JPH1081664A JPH1081664A (ja) | 1998-03-31 |
| JPH1081664A5 JPH1081664A5 (enExample) | 2005-04-07 |
| JP4039588B2 true JP4039588B2 (ja) | 2008-01-30 |
Family
ID=7795549
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13822797A Expired - Fee Related JP4039588B2 (ja) | 1996-05-29 | 1997-05-28 | 置換された２−ナフトイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US6087304A (enExample) |
| EP (1) | EP0810206B1 (enExample) |
| JP (1) | JP4039588B2 (enExample) |
| KR (1) | KR970074776A (enExample) |
| CN (1) | CN1167759A (enExample) |
| AR (1) | AR008373A1 (enExample) |
| AT (1) | ATE198320T1 (enExample) |
| AU (1) | AU710065B2 (enExample) |
| BR (1) | BR9703338A (enExample) |
| CA (1) | CA2206366C (enExample) |
| CZ (1) | CZ163097A3 (enExample) |
| DE (2) | DE19621483A1 (enExample) |
| DK (1) | DK0810206T3 (enExample) |
| ES (1) | ES2154002T3 (enExample) |
| GR (1) | GR3035126T3 (enExample) |
| HR (1) | HRP970292B1 (enExample) |
| HU (1) | HUP9700955A3 (enExample) |
| ID (1) | ID16989A (enExample) |
| IL (1) | IL120924A (enExample) |
| NO (1) | NO308527B1 (enExample) |
| NZ (1) | NZ314915A (enExample) |
| PL (1) | PL185754B1 (enExample) |
| PT (1) | PT810206E (enExample) |
| RU (1) | RU2190600C2 (enExample) |
| SI (1) | SI0810206T1 (enExample) |
| SK (1) | SK282020B6 (enExample) |
| TR (1) | TR199700428A2 (enExample) |
| TW (1) | TW416944B (enExample) |
| ZA (1) | ZA974665B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8853242B2 (en) | 2009-08-06 | 2014-10-07 | Astellas Pharma Inc. | Nitrogenous-ring acylguanidine derivative |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19621482A1 (de) | 1996-05-29 | 1997-12-04 | Hoechst Ag | Substituierte 1-Naphthoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| JP2002538151A (ja) | 1999-03-02 | 2002-11-12 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | カテプシンの可逆的インヒビターとして有用な化合物 |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| AR039156A1 (es) * | 2002-03-28 | 2005-02-09 | Novartis Ag | Amidas del acido piperidinilamino sulfamico o piperazinil sulfamico y su uso para la manufactura de un medicamento en enfermedades mediadas por la accion de la sulfatasa esteroide |
| DK1755593T3 (da) * | 2004-06-02 | 2008-05-19 | Hoffmann La Roche | Naphtalenderivater der er nyttige som histamin-3-receptorligander |
| TW200614995A (en) * | 2004-11-10 | 2006-05-16 | Nicholas Piramal India Ltd | Tricyclic guanidine derivatives as sodium-proton exchange inhibitors |
| AU2013205388B2 (en) * | 2005-06-24 | 2016-05-05 | Biotron Limited | Antiviral compounds and methods |
| DK2826770T3 (en) * | 2005-06-24 | 2019-01-07 | Biotron Ltd | Acylguanidine compounds with antiviral activity |
| ATE478847T1 (de) * | 2006-09-15 | 2010-09-15 | Pfizer | Substituierte pyridylmethylbicyclocarboxyamidverbindungen |
| WO2010090305A1 (ja) * | 2009-02-09 | 2010-08-12 | アステラス製薬株式会社 | 置換アシルグアニジン誘導体 |
| EP2394987A4 (en) * | 2009-02-09 | 2012-09-05 | Astellas Pharma Inc | ACYLGUANIDINDERIVAT |
| CN103339109B (zh) | 2011-02-02 | 2015-04-29 | 安斯泰来制药有限公司 | 四氢异喹啉衍生物 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4251545A (en) * | 1979-09-19 | 1981-02-17 | Gaf Corporation | Fungicidal process using 1-(alkoxyaroyl)guanidines |
| IT1238227B (it) * | 1989-12-01 | 1993-07-12 | Modulo di smistamento per impianti di convogliamento a nastro e simili | |
| DE4035961A1 (de) * | 1990-11-02 | 1992-05-07 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| IL109570A0 (en) * | 1993-05-17 | 1994-08-26 | Fujisawa Pharmaceutical Co | Guanidine derivatives, pharmaceutical compositions containing the same and processes for the preparation thereof |
| DE4318658A1 (de) * | 1993-06-04 | 1994-12-08 | Hoechst Ag | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE4415873A1 (de) * | 1994-05-05 | 1995-11-09 | Hoechst Ag | Substituierte bizyklische Heteroaroylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| JPH08225513A (ja) * | 1994-12-21 | 1996-09-03 | Kanebo Ltd | ナフトイルグアニジン誘導体 |
| DE19621482A1 (de) * | 1996-05-29 | 1997-12-04 | Hoechst Ag | Substituierte 1-Naphthoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
-
1996
- 1996-05-29 DE DE19621483A patent/DE19621483A1/de not_active Withdrawn
-
1997
- 1997-02-28 PL PL97318723A patent/PL185754B1/pl not_active IP Right Cessation
- 1997-05-16 SI SI9730102T patent/SI0810206T1/xx unknown
- 1997-05-16 DE DE59702802T patent/DE59702802D1/de not_active Expired - Lifetime
- 1997-05-16 EP EP97108013A patent/EP0810206B1/de not_active Expired - Lifetime
- 1997-05-16 DK DK97108013T patent/DK0810206T3/da active
- 1997-05-16 PT PT97108013T patent/PT810206E/pt unknown
- 1997-05-16 AT AT97108013T patent/ATE198320T1/de not_active IP Right Cessation
- 1997-05-16 US US08/857,631 patent/US6087304A/en not_active Expired - Lifetime
- 1997-05-16 ES ES97108013T patent/ES2154002T3/es not_active Expired - Lifetime
- 1997-05-27 SK SK670-97A patent/SK282020B6/sk unknown
- 1997-05-27 HR HR970292A patent/HRP970292B1/xx not_active IP Right Cessation
- 1997-05-27 TR TR97/00428A patent/TR199700428A2/xx unknown
- 1997-05-27 AR ARP970102253A patent/AR008373A1/es unknown
- 1997-05-27 HU HU9700955A patent/HUP9700955A3/hu unknown
- 1997-05-27 TW TW086107120A patent/TW416944B/zh not_active IP Right Cessation
- 1997-05-27 IL IL12092497A patent/IL120924A/en not_active IP Right Cessation
- 1997-05-27 AU AU23645/97A patent/AU710065B2/en not_active Ceased
- 1997-05-27 NZ NZ314915A patent/NZ314915A/en unknown
- 1997-05-27 CN CN97113187A patent/CN1167759A/zh active Pending
- 1997-05-27 CZ CZ971630A patent/CZ163097A3/cs unknown
- 1997-05-28 CA CA002206366A patent/CA2206366C/en not_active Expired - Fee Related
- 1997-05-28 RU RU97109003/04A patent/RU2190600C2/ru not_active IP Right Cessation
- 1997-05-28 NO NO972433A patent/NO308527B1/no not_active IP Right Cessation
- 1997-05-28 ID IDP971814A patent/ID16989A/id unknown
- 1997-05-28 JP JP13822797A patent/JP4039588B2/ja not_active Expired - Fee Related
- 1997-05-28 ZA ZA9704665A patent/ZA974665B/xx unknown
- 1997-05-28 KR KR1019970021107A patent/KR970074776A/ko not_active Ceased
- 1997-05-30 BR BR9703338A patent/BR9703338A/pt not_active IP Right Cessation
-
2000
- 2000-12-28 GR GR20000402772T patent/GR3035126T3/el not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8853242B2 (en) | 2009-08-06 | 2014-10-07 | Astellas Pharma Inc. | Nitrogenous-ring acylguanidine derivative |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4081159B2 (ja) | フェニル−置換されたアルケニルカルボン酸グアニジド、それらの製法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 | |
| JP3780004B2 (ja) | 置換されたベンゾイルグアニジン、それらの製法、医薬または診断薬としてのそれらの使用およびそれらを含有する医薬 | |
| JP3718240B2 (ja) | 置換ベンゾイルグアニジン、その製造方法およびそれを含有する医薬 | |
| JP4039588B2 (ja) | 置換された２−ナフトイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 | |
| JP3718257B2 (ja) | パーフルオロアルキル基を有するフェニル−置換されたアルケニルカルボグアニジドおよびそれらの製造法 | |
| JPH06234730A (ja) | ２，４−置換された５−（ｎ−置換スルファモイル）ベンゾイルグアニジン、それらの製法、薬剤または診断剤としてのそれらの使用およびそれらを含有する薬剤 | |
| JP4177466B2 (ja) | 置換された桂皮酸グアニジド、それらの製法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 | |
| JP3962110B2 (ja) | 置換されたベンジルオキシカルボニルグアニジン、それらの製造法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 | |
| JPH06234727A (ja) | 置換されたベンゾイルグアニジン、それらの製法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 | |
| JP3790557B2 (ja) | ジアシル−置換されたグアニジン、それらの製法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 | |
| RU2176638C2 (ru) | Замещенные инданилидинацетилгуанидины, способ их получения, применение в качестве лекарственных или диагностических средств и лекарственные средства, содержащие эти соединения | |
| JP4039587B2 (ja) | 置換された１−ナフトイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 | |
| JPH1067731A (ja) | オルト−置換されたベンゾイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 | |
| JPH1081662A (ja) | ビス−オルト−置換されたベンゾイルグアニジン、その製法、医薬または診断剤としてのその使用およびそれを含有する医薬 | |
| JPH09221465A (ja) | 置換ジアリールジカルボン酸ジグアニジド、それらの製造法、薬剤または診断剤としてのそれらの使用およびそれらを含有する薬剤 | |
| JPH107644A (ja) | オルト−置換されたベンゾイルグアニジン、それらの製造方法、医薬または診断薬としてのそれらの使用およびそれらを含有する医薬 | |
| MXPA97003922A (en) | 2-naftoilguanidinas substituted, procedure for preparation, its employment as a diagnostic occasive drug, as well as a medicinal product chelas conti | |
| JPH09169719A (ja) | 置換されたベンゼンジカルボン酸ジグアニジド、それらの製法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 | |
| MXPA97003921A (en) | 1-naftoilguanidinas substitute, procedure for its preparation, its employment as a medicine or diagnostic agent, as well as a medication that the | |
| JPH09169718A (ja) | 置換されたベンゼンジカルボン酸ジグアニジド、それらの製法、医薬または診断剤としてのそれらの使用およびそれらを含有する医薬 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040527 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040527 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070612 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070912 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20071023 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20071102 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101116 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111116 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111116 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121116 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121116 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131116 Year of fee payment: 6 |
|
| LAPS | Cancellation because of no payment of annual fees |