JP4081159B2 - 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 - Google Patents
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 Download PDFInfo
- Publication number
- JP4081159B2 JP4081159B2 JP22461397A JP22461397A JP4081159B2 JP 4081159 B2 JP4081159 B2 JP 4081159B2 JP 22461397 A JP22461397 A JP 22461397A JP 22461397 A JP22461397 A JP 22461397A JP 4081159 B2 JP4081159 B2 JP 4081159B2
- Authority
- JP
- Japan
- Prior art keywords
- bis
- acid guanidide
- benzenedihydrochloride
- methylpropenoic
- guanidide
- 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
- 239000003814 drug Substances 0.000 title claims description 24
- 239000002253 acid Substances 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 33
- -1 —O k C m H 2m + 1 Inorganic materials 0.000 claims description 32
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 9
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 9
- 229940117389 dichlorobenzene Drugs 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 6
- 230000000241 respiratory effect Effects 0.000 claims description 5
- 208000031225 myocardial ischemia Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- WMDWNYHVFMGYNB-UHFFFAOYSA-N naphthalene;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC2=CC=CC=C21 WMDWNYHVFMGYNB-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
- 208000033626 Renal failure acute Diseases 0.000 claims description 2
- 201000011040 acute kidney failure Diseases 0.000 claims description 2
- 208000012998 acute renal failure Diseases 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 230000001413 cellular effect Effects 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 238000003860 storage Methods 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- 230000002093 peripheral effect Effects 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 230000006793 arrhythmia Effects 0.000 claims 1
- 201000002818 limb ischemia Diseases 0.000 claims 1
- 230000037356 lipid metabolism Effects 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 210000001428 peripheral nervous system Anatomy 0.000 claims 1
- 238000004321 preservation Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 55
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
- 239000007787 solid Substances 0.000 description 46
- 238000002844 melting Methods 0.000 description 39
- 230000008018 melting Effects 0.000 description 39
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 37
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 30
- 150000005690 diesters Chemical class 0.000 description 30
- 239000003921 oil Substances 0.000 description 29
- 235000019198 oils Nutrition 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 238000010561 standard procedure Methods 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 239000011734 sodium Substances 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 22
- 239000003480 eluent Substances 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 21
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 19
- 239000012043 crude product Substances 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 238000001035 drying Methods 0.000 description 17
- BVSRWCMAJISCTD-UHFFFAOYSA-N ethyl 2-diethoxyphosphorylpropanoate Chemical compound CCOC(=O)C(C)P(=O)(OCC)OCC BVSRWCMAJISCTD-UHFFFAOYSA-N 0.000 description 17
- 102100022897 Sodium/hydrogen exchanger 10 Human genes 0.000 description 16
- 230000009467 reduction Effects 0.000 description 16
- 239000012230 colorless oil Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 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
- 238000004519 manufacturing process Methods 0.000 description 12
- 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 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- 201000001320 Atherosclerosis Diseases 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 229960002576 amiloride Drugs 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 9
- 238000006859 Swern oxidation reaction Methods 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 229960004198 guanidine Drugs 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 6
- 206010048554 Endothelial dysfunction Diseases 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 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 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000008694 endothelial dysfunction Effects 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- NINOYJQVULROET-UHFFFAOYSA-N n,n-dimethylethenamine Chemical group CN(C)C=C NINOYJQVULROET-UHFFFAOYSA-N 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000011272 standard treatment Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- 206010061216 Infarction Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- XWBDWELWBUWSNI-UHFFFAOYSA-N dimethyl 4-nitrobenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C=C1C(=O)OC XWBDWELWBUWSNI-UHFFFAOYSA-N 0.000 description 4
- 230000007574 infarction Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000007530 Essential hypertension Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 101710097665 Leucine aminopeptidase 1 Proteins 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 101710082688 Probable leucine aminopeptidase 1 Proteins 0.000 description 3
- 108091006647 SLC9A1 Proteins 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 102100022147 Torsin-1A-interacting protein 1 Human genes 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 230000006378 damage 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
- 108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 229960003343 ouabain Drugs 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 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 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-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
- SYOJXEJTEHERCF-UHFFFAOYSA-N 3-bromo-2-chloro-5-(dibromomethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(Br)Br)=CC(Br)=C1Cl SYOJXEJTEHERCF-UHFFFAOYSA-N 0.000 description 2
- OCKAQFGSQYTPFP-UHFFFAOYSA-N 3-bromo-2-chloro-5-formylbenzoic acid Chemical compound OC(=O)C1=CC(C=O)=CC(Br)=C1Cl OCKAQFGSQYTPFP-UHFFFAOYSA-N 0.000 description 2
- WWBCWHSPJLLRAB-UHFFFAOYSA-N 3-bromo-2-chloro-5-methylbenzoic acid Chemical compound CC1=CC(Br)=C(Cl)C(C(O)=O)=C1 WWBCWHSPJLLRAB-UHFFFAOYSA-N 0.000 description 2
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-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
- 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
- 206010003225 Arteriospasm coronary Diseases 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 208000003890 Coronary Vasospasm Diseases 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-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
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 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
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 108091006650 SLC9A2 Proteins 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 102100030382 Sodium/hydrogen exchanger 2 Human genes 0.000 description 2
- 244000166550 Strophanthus gratus Species 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- 239000003416 antiarrhythmic agent Substances 0.000 description 2
- 230000036523 atherogenesis Effects 0.000 description 2
- 230000000923 atherogenic effect Effects 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 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
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 201000011634 coronary artery vasospasm Diseases 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- WXNPBMRWMNCHBT-UHFFFAOYSA-N diethyl 4-ethoxybenzene-1,2-dicarboxylate Chemical compound CCOC(=O)C1=CC=C(OCC)C=C1C(=O)OCC WXNPBMRWMNCHBT-UHFFFAOYSA-N 0.000 description 2
- JJXVDRYFBGDXOU-UHFFFAOYSA-N dimethyl 4-hydroxybenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=CC=C(O)C=C1C(=O)OC JJXVDRYFBGDXOU-UHFFFAOYSA-N 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- VGOFCWDZRLXTRQ-UHFFFAOYSA-N ethyl 3-bromo-2-chloro-5-formylbenzoate Chemical compound CCOC(=O)C1=CC(C=O)=CC(Br)=C1Cl VGOFCWDZRLXTRQ-UHFFFAOYSA-N 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 238000005048 flame photometry Methods 0.000 description 2
- 230000000055 hyoplipidemic effect Effects 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002715 modification method Methods 0.000 description 2
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical group [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 2
- UPIDXCYJXHFCOZ-UHFFFAOYSA-N n,n-dimethylformamide;sodium Chemical compound [Na].CN(C)C=O UPIDXCYJXHFCOZ-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000006772 olefination reaction Methods 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
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 2
- QIWKUEJZZCOPFV-UHFFFAOYSA-N phenyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC1=CC=CC=C1 QIWKUEJZZCOPFV-UHFFFAOYSA-N 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- MGAXYKDBRBNWKT-UHFFFAOYSA-N (5-oxooxolan-2-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC(=O)CC1 MGAXYKDBRBNWKT-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- LCMZECCEEOQWLQ-UHFFFAOYSA-N 2-amino-3-bromo-5-methylbenzoic acid Chemical compound CC1=CC(Br)=C(N)C(C(O)=O)=C1 LCMZECCEEOQWLQ-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- CEEJSCAKNYSVHF-UHFFFAOYSA-N 2-methoxycarbonyl-5-nitrobenzoic acid Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C=C1C(O)=O CEEJSCAKNYSVHF-UHFFFAOYSA-N 0.000 description 1
- KKMZQOIASVGJQE-UHFFFAOYSA-N 3-thiophen-2-ylprop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=CS1 KKMZQOIASVGJQE-UHFFFAOYSA-N 0.000 description 1
- MWRVRCAFWBBXTL-UHFFFAOYSA-N 4-hydroxyphthalic acid Chemical compound OC(=O)C1=CC=C(O)C=C1C(O)=O MWRVRCAFWBBXTL-UHFFFAOYSA-N 0.000 description 1
- SLBQXWXKPNIVSQ-UHFFFAOYSA-L 4-nitrophthalate Chemical class [O-]C(=O)C1=CC=C([N+]([O-])=O)C=C1C([O-])=O SLBQXWXKPNIVSQ-UHFFFAOYSA-L 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000010444 Acidosis Diseases 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
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- CMILDHVJDAYIOU-FIFLTTCUSA-N C/C(/C(N=C(N)N)=O)=C\c1ccccc1/C=C(\C)/C(N=C(N)N)=O Chemical compound C/C(/C(N=C(N)N)=O)=C\c1ccccc1/C=C(\C)/C(N=C(N)N)=O CMILDHVJDAYIOU-FIFLTTCUSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 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
- 208000003417 Central Sleep Apnea Diseases 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 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
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-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
- 101000702479 Homo sapiens Sodium/hydrogen exchanger 1 Proteins 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 206010020591 Hypercapnia Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 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
- MYBQDWMPQOVDMS-OZDSWYPASA-N NC(N)=NC(/C(/F)=C/c1cc(/C=C(/C(N=C(N)N)=O)\F)ccc1)=O Chemical compound NC(N)=NC(/C(/F)=C/c1cc(/C=C(/C(N=C(N)N)=O)\F)ccc1)=O MYBQDWMPQOVDMS-OZDSWYPASA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 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
- 101100421625 Rattus norvegicus Slc9a3 gene Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 108091006649 SLC9A3 Proteins 0.000 description 1
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102100030375 Sodium/hydrogen exchanger 3 Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108091081024 Start codon Proteins 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
- 208000034972 Sudden Infant Death Diseases 0.000 description 1
- 206010042440 Sudden infant death syndrome Diseases 0.000 description 1
- 235000019486 Sunflower oil 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
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- NTECHUXHORNEGZ-UHFFFAOYSA-N acetyloxymethyl 3',6'-bis(acetyloxymethoxy)-2',7'-bis[3-(acetyloxymethoxy)-3-oxopropyl]-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-carboxylate Chemical compound O1C(=O)C2=CC(C(=O)OCOC(C)=O)=CC=C2C21C1=CC(CCC(=O)OCOC(C)=O)=C(OCOC(C)=O)C=C1OC1=C2C=C(CCC(=O)OCOC(=O)C)C(OCOC(C)=O)=C1 NTECHUXHORNEGZ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant 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
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229940127282 angiotensin receptor antagonist 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
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- IZALUMVGBVKPJD-UHFFFAOYSA-N benzene-1,3-dicarbaldehyde Chemical compound O=CC1=CC=CC(C=O)=C1 IZALUMVGBVKPJD-UHFFFAOYSA-N 0.000 description 1
- XILYOLONIFWGMT-UHFFFAOYSA-N benzene;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC=C1 XILYOLONIFWGMT-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- DNOSZYUZVCJLMM-UHFFFAOYSA-N carbamimidoylazanium;benzoate Chemical compound NC(N)=[NH2+].[O-]C(=O)C1=CC=CC=C1 DNOSZYUZVCJLMM-UHFFFAOYSA-N 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000012659 cardioprotective agent Substances 0.000 description 1
- 229940045200 cardioprotective agent Drugs 0.000 description 1
- IWXNYAIICFKCTM-UHFFFAOYSA-N cariporide Chemical compound CC(C)C1=CC=C(C(=O)N=C(N)N)C=C1S(C)(=O)=O IWXNYAIICFKCTM-UHFFFAOYSA-N 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 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
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- LYSAITVMFHMYMK-UHFFFAOYSA-N diethyl 4,5-dichlorobenzene-1,2-dicarboxylate Chemical compound CCOC(=O)C1=CC(Cl)=C(Cl)C=C1C(=O)OCC LYSAITVMFHMYMK-UHFFFAOYSA-N 0.000 description 1
- FTCRSVIWWRAXJH-UHFFFAOYSA-N dimethyl 4-(4-methoxyphenoxy)benzene-1,2-dicarboxylate Chemical compound C1=C(C(=O)OC)C(C(=O)OC)=CC=C1OC1=CC=C(OC)C=C1 FTCRSVIWWRAXJH-UHFFFAOYSA-N 0.000 description 1
- CZFDZJOQZVOGBF-UHFFFAOYSA-N dimethyl 4-(4-methylphenoxy)benzene-1,2-dicarboxylate Chemical compound C1=C(C(=O)OC)C(C(=O)OC)=CC=C1OC1=CC=C(C)C=C1 CZFDZJOQZVOGBF-UHFFFAOYSA-N 0.000 description 1
- OYPFPVHARQFUER-UHFFFAOYSA-N dimethyl 4-[(4-methoxyphenyl)methoxy]benzene-1,2-dicarboxylate Chemical compound C1=C(C(=O)OC)C(C(=O)OC)=CC=C1OCC1=CC=C(OC)C=C1 OYPFPVHARQFUER-UHFFFAOYSA-N 0.000 description 1
- AMNIKUDFXYWYSY-UHFFFAOYSA-N dimethyl 4-bromobenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=CC=C(Br)C=C1C(=O)OC AMNIKUDFXYWYSY-UHFFFAOYSA-N 0.000 description 1
- YGLCCNKVFPSADI-UHFFFAOYSA-N dimethyl 4-phenoxybenzene-1,2-dicarboxylate Chemical compound C1=C(C(=O)OC)C(C(=O)OC)=CC=C1OC1=CC=CC=C1 YGLCCNKVFPSADI-UHFFFAOYSA-N 0.000 description 1
- LCZTYKOGGGXTRP-UHFFFAOYSA-N dimethyl 4-pyridin-3-yloxybenzene-1,2-dicarboxylate Chemical compound C1=C(C(=O)OC)C(C(=O)OC)=CC=C1OC1=CC=CN=C1 LCZTYKOGGGXTRP-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 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
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013613 expression plasmid Substances 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
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 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
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 102000052674 human SLC9A1 Human genes 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 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
- 230000007954 hypoxia Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000012105 intracellular pH reduction Effects 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000002530 ischemic preconditioning effect Effects 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
- 210000003734 kidney Anatomy 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
- 125000005647 linker group Chemical group 0.000 description 1
- 210000004185 liver Anatomy 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
- 239000000395 magnesium oxide Substances 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 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
- RDOXTESZEPMUJZ-UHFFFAOYSA-N methyl phenyl ether Natural products COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- XARNMUQDYQFLNA-UHFFFAOYSA-N n-(diaminomethylidene)-3-methylsulfonyl-4-piperidin-1-ylbenzamide;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC(C(=O)N=C(N)N)=CC=C1N1CCCCC1 XARNMUQDYQFLNA-UHFFFAOYSA-N 0.000 description 1
- FNDLQABGYJQJPH-UHFFFAOYSA-N n-(diaminomethylidene)-3-methylsulfonyl-4-propan-2-ylbenzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC(C)C1=CC=C(C(=O)N=C(N)N)C=C1S(C)(=O)=O FNDLQABGYJQJPH-UHFFFAOYSA-N 0.000 description 1
- ZIPLKLQPLOWLTM-UHFFFAOYSA-N naphthalene-2,3-dicarbaldehyde Chemical compound C1=CC=C2C=C(C=O)C(C=O)=CC2=C1 ZIPLKLQPLOWLTM-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 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
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 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
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 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
- 230000002035 prolonged effect 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
- 230000009993 protective function Effects 0.000 description 1
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical class OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000054 salidiuretic effect Effects 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 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
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction 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
- 238000011477 surgical intervention Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 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
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 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
- 230000035899 viability Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003752 zinc compounds Chemical class 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19633966A DE19633966A1 (de) | 1996-08-22 | 1996-08-22 | Phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE19633966:9 | 1996-08-22 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JPH10109970A JPH10109970A (ja) | 1998-04-28 |
| JPH10109970A5 JPH10109970A5 (enExample) | 2005-06-02 |
| JP4081159B2 true JP4081159B2 (ja) | 2008-04-23 |
Family
ID=7803413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP22461397A Expired - Fee Related JP4081159B2 (ja) | 1996-08-22 | 1997-08-21 | 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 |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US6005010A (enExample) |
| EP (1) | EP0825178B1 (enExample) |
| JP (1) | JP4081159B2 (enExample) |
| KR (1) | KR19980018898A (enExample) |
| CN (1) | CN1065861C (enExample) |
| AR (1) | AR008305A1 (enExample) |
| AT (1) | ATE202338T1 (enExample) |
| AU (1) | AU713664B2 (enExample) |
| BR (1) | BR9704483A (enExample) |
| CA (1) | CA2213714C (enExample) |
| CZ (1) | CZ265997A3 (enExample) |
| DE (2) | DE19633966A1 (enExample) |
| DK (1) | DK0825178T3 (enExample) |
| ES (1) | ES2158413T3 (enExample) |
| GR (1) | GR3036123T3 (enExample) |
| HR (1) | HRP970450B1 (enExample) |
| HU (1) | HUP9701416A3 (enExample) |
| ID (1) | ID18066A (enExample) |
| IL (1) | IL121590A (enExample) |
| MX (1) | MX9706380A (enExample) |
| NO (1) | NO309468B1 (enExample) |
| NZ (1) | NZ328639A (enExample) |
| PL (1) | PL321748A1 (enExample) |
| PT (1) | PT825178E (enExample) |
| RU (1) | RU2193026C2 (enExample) |
| SI (1) | SI0825178T1 (enExample) |
| SK (1) | SK282632B6 (enExample) |
| TR (1) | TR199700827A2 (enExample) |
| ZA (1) | ZA977494B (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19633966A1 (de) * | 1996-08-22 | 1998-02-26 | Hoechst Ag | Phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE19849722A1 (de) * | 1998-10-28 | 2000-05-04 | Aventis Pharma Gmbh | Substituierte Phenyl-alkenoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| AU4707900A (en) * | 1999-05-07 | 2000-11-21 | Trustees Of The University Of Pennsylvania, The | Methods for controlling intraocular pressure |
| DE19960204A1 (de) * | 1999-12-14 | 2001-06-28 | Aventis Pharma Gmbh | Substituierte Norlbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE10015248A1 (de) * | 2000-03-28 | 2001-10-04 | Merck Patent Gmbh | Bisamidino-Verbindungen als NHE-3 Inhibitoren |
| DE10046993A1 (de) | 2000-09-22 | 2002-04-11 | Aventis Pharma Gmbh | Substituierte Zimtsäureguanidide, Verfahren zur ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltendes Medikament |
| DE10063294A1 (de) | 2000-12-19 | 2002-07-04 | Aventis Pharma Gmbh | Substituierte Heterocyclo-Norbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE10161767A1 (de) * | 2001-12-15 | 2003-06-26 | Merck Patent Gmbh | 2-Guanidino-4-heterocyclyl-chinazoline |
| DE10163239A1 (de) * | 2001-12-21 | 2003-07-10 | Aventis Pharma Gmbh | Substituierte Imidazolidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie enthaltendes Medikament |
| US20030187045A1 (en) * | 2001-12-21 | 2003-10-02 | Uwe Heinelt | Substituted imidazolidines, process for their preparation, and their use as a medicament or diagnostic |
| US7049333B2 (en) | 2002-06-04 | 2006-05-23 | Sanofi-Aventis Deutschland Gmbh | Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis |
| US20050054705A1 (en) * | 2003-02-04 | 2005-03-10 | Aventis Pharma Deutschland Gmbh | N-substituted (benzoimidazol-2-yl) phenylamines, process for their preparation, their use as medicament or diagnostic aid, and medicament comprising them |
| DE10304374A1 (de) * | 2003-02-04 | 2004-08-05 | Aventis Pharma Deutschland Gmbh | Neue substituierte 2-Aminoimidazole, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE10341240A1 (de) | 2003-09-08 | 2005-04-07 | Aventis Pharma Deutschland Gmbh | Substituierte Thienoimidazole, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE102005001411A1 (de) | 2005-01-12 | 2006-07-27 | Sanofi-Aventis Deutschland Gmbh | Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament |
| ATE479679T1 (de) | 2007-06-28 | 2010-09-15 | Sanofi Aventis Us Llc | Verfahren zur herstellung von n-(2-chlor-4-methyl-3-thienyl)-1h-benzimidazol- 2-amin hydrochlorid und zwischenprodukte dafür |
| WO2009054545A1 (ja) * | 2007-10-26 | 2009-04-30 | Jsr Corporation | 液晶配向剤、液晶配向膜の形成方法及び液晶表示素子 |
| EP2342178B1 (en) | 2008-09-02 | 2016-09-28 | Sanofi | Substituted aminoindanes and analogs thereof, and the pharmaceutical use thereof |
| CN103819403B (zh) | 2008-12-31 | 2017-01-04 | 阿德利克斯公司 | 用于治疗与体液潴留或盐超负荷有关的病症和胃肠道病症的化合物和方法 |
| WO2018129556A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| US20120088737A2 (en) * | 2009-10-02 | 2012-04-12 | Ajinomoto Co., Inc | Novel acyl guanidine derivatives |
| RU2015107019A (ru) | 2012-08-21 | 2016-10-10 | Эрделикс Инк. | Соединения и способы для ингибирования nhe-опосредованного антипорта в лечении расстройств, ассоциированных с задержкой жидкости или солевой перегрузкой и заболеваний желудочно-кишечного тракта |
| US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| CN105392483B (zh) | 2013-04-12 | 2019-03-15 | 阿德利克斯公司 | 用于抑制磷酸盐转运的nhe3结合化合物和方法 |
| EA201991676A1 (ru) | 2017-01-09 | 2020-01-30 | Арделикс, Инк. | Ингибиторы nhe-опосредованного антипорта |
| KR20240090875A (ko) | 2017-01-09 | 2024-06-21 | 알데릭스, 인코포레이티드 | 위장관 장애를 치료하는 데 유용한 화합물 |
| CN111386279A (zh) | 2017-08-04 | 2020-07-07 | 阿德利克斯股份有限公司 | 用于治疗高钾血症的甘草次酸衍生物 |
| JP7735185B2 (ja) | 2019-02-07 | 2025-09-08 | アルデリックス， インコーポレイテッド | 高カリウム血症の治療で使用するためのグリチルレチン酸誘導体 |
| JP2022533251A (ja) | 2019-05-21 | 2022-07-21 | アルデリックス， インコーポレイテッド | 患者において血清リン酸塩を低下させるための組み合わせ |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4544670A (en) * | 1982-08-24 | 1985-10-01 | William H. Rorer, Inc. | Method of treating coccidiosis with acyl guanidines |
| DE4328352A1 (de) * | 1993-08-24 | 1995-03-02 | Hoechst Ag | Substituierte N,N'-Di-benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE4421536A1 (de) * | 1994-06-20 | 1995-12-21 | Hoechst Ag | Perfluoralkylgruppen tragende phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE19633966A1 (de) * | 1996-08-22 | 1998-02-26 | Hoechst Ag | Phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
-
1996
- 1996-08-22 DE DE19633966A patent/DE19633966A1/de not_active Withdrawn
-
1997
- 1997-08-18 SI SI9730153T patent/SI0825178T1/xx unknown
- 1997-08-18 DE DE59703851T patent/DE59703851D1/de not_active Expired - Lifetime
- 1997-08-18 ES ES97114244T patent/ES2158413T3/es not_active Expired - Lifetime
- 1997-08-18 EP EP97114244A patent/EP0825178B1/de not_active Expired - Lifetime
- 1997-08-18 PT PT97114244T patent/PT825178E/pt unknown
- 1997-08-18 AT AT97114244T patent/ATE202338T1/de not_active IP Right Cessation
- 1997-08-18 DK DK97114244T patent/DK0825178T3/da active
- 1997-08-19 HU HU9701416A patent/HUP9701416A3/hu unknown
- 1997-08-20 NZ NZ328639A patent/NZ328639A/xx unknown
- 1997-08-20 SK SK1138-97A patent/SK282632B6/sk unknown
- 1997-08-20 TR TR97/00827A patent/TR199700827A2/xx unknown
- 1997-08-20 CN CN97117484A patent/CN1065861C/zh not_active Expired - Fee Related
- 1997-08-20 US US08/915,329 patent/US6005010A/en not_active Expired - Lifetime
- 1997-08-20 AR ARP970103787A patent/AR008305A1/es unknown
- 1997-08-20 CZ CZ972659A patent/CZ265997A3/cs unknown
- 1997-08-21 RU RU97114306/04A patent/RU2193026C2/ru not_active IP Right Cessation
- 1997-08-21 ID IDP972923A patent/ID18066A/id unknown
- 1997-08-21 ZA ZA9707494A patent/ZA977494B/xx unknown
- 1997-08-21 HR HR970450A patent/HRP970450B1/xx not_active IP Right Cessation
- 1997-08-21 JP JP22461397A patent/JP4081159B2/ja not_active Expired - Fee Related
- 1997-08-21 NO NO973850A patent/NO309468B1/no not_active IP Right Cessation
- 1997-08-21 MX MX9706380A patent/MX9706380A/es not_active IP Right Cessation
- 1997-08-21 IL IL12159097A patent/IL121590A/en not_active IP Right Cessation
- 1997-08-21 AU AU35192/97A patent/AU713664B2/en not_active Ceased
- 1997-08-22 PL PL97321748A patent/PL321748A1/xx unknown
- 1997-08-22 KR KR1019970040115A patent/KR19980018898A/ko not_active Ceased
- 1997-08-22 BR BR9704483A patent/BR9704483A/pt active Search and Examination
- 1997-08-22 CA CA002213714A patent/CA2213714C/en not_active Expired - Fee Related
-
2001
- 2001-06-27 GR GR20010400976T patent/GR3036123T3/el not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6005010A (en) | Phenyl-substituted alkenylcarboxylic acid guanidides, process for their preparation, their use as a medicament or diagnostic, and medicament containing them | |
| JP3655650B2 (ja) | オルト置換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 | |
| US6399824B1 (en) | Substituted cinnamic, acid guanidides, process for their preparation, their use as a medicament, and medicament comprising them | |
| MXPA97006380A (en) | Guarides of alkenil-carboxylic acids replaced with phenyl, procedures for preparation, use as a medicine or diagnostic agent, as well as a medication that contains them | |
| AU677337B2 (en) | Substituted benzoylguanidines, process for their preparation, their use as a medicament or diagnostic, and medicament containing them | |
| 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 | |
| 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 | |
| JP3545793B2 (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 | |
| JP3647901B2 (ja) | 尿素置換ベンゾイルグアニジン、その製造方法、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 | |
| US6087304A (en) | Substituted 2-naphthoylguanidines, process for their preparation, their use as a medicament or diagnostic, and medicament containing them | |
| 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 | |
| JPH07224022A (ja) | パーフルオロアルキル基を有するフェニル置換アルキルカルボグアニジドおよびその調製方法 | |
| US5665739A (en) | Substituted benzoylguanidines, process and their preparation, their use as pharmaceutical or diagnostic, and pharmaceutical containing them | |
| JP4101904B2 (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 | |
| 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 | |
| JP3977897B2 (ja) | オルト−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 | |
| SK282440B6 (sk) | Substituované guanididy kyseliny tiofenylalkenylkarboxylovej, spôsob ich prípravy, ich použitie ako liečiva alebo diagnostika, ako aj liečivo, ktoré ich obsahuje |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040820 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040820 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070612 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070912 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20070918 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071206 |
|
| 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: 20080115 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080208 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110215 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: 20120215 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120215 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130215 Year of fee payment: 5 |
|
| LAPS | Cancellation because of no payment of annual fees |