HRP20060084A2 - Nitrooksi derivati losartana, valsartana, kandesartana, telmisartana, eprosartana i olmesartana kao blokatori angiotenzin ii receptora za tretiranje kardiovaskularnih bolesti - Google Patents
Nitrooksi derivati losartana, valsartana, kandesartana, telmisartana, eprosartana i olmesartana kao blokatori angiotenzin ii receptora za tretiranje kardiovaskularnih bolesti Download PDFInfo
- Publication number
- HRP20060084A2 HRP20060084A2 HR20060084A HRP20060084A HRP20060084A2 HR P20060084 A2 HRP20060084 A2 HR P20060084A2 HR 20060084 A HR20060084 A HR 20060084A HR P20060084 A HRP20060084 A HR P20060084A HR P20060084 A2 HRP20060084 A2 HR P20060084A2
- Authority
- HR
- Croatia
- Prior art keywords
- image
- compound
- group
- defined above
- formula
- Prior art date
Links
- 108050000824 Angiotensin II receptor Proteins 0.000 title claims abstract description 11
- 102000008873 Angiotensin II receptor Human genes 0.000 title claims abstract description 11
- 238000011282 treatment Methods 0.000 title claims description 11
- 208000024172 Cardiovascular disease Diseases 0.000 title claims description 10
- 239000002083 C09CA01 - Losartan Substances 0.000 title abstract description 12
- 229960004773 losartan Drugs 0.000 title abstract description 11
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 title abstract description 6
- 239000002080 C09CA02 - Eprosartan Substances 0.000 title abstract description 3
- 239000002053 C09CA06 - Candesartan Substances 0.000 title abstract description 3
- 239000005537 C09CA07 - Telmisartan Substances 0.000 title abstract description 3
- 239000005480 Olmesartan Substances 0.000 title abstract description 3
- 229960000932 candesartan Drugs 0.000 title abstract description 3
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 title abstract description 3
- 229960004563 eprosartan Drugs 0.000 title abstract description 3
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 title abstract description 3
- 229960005117 olmesartan Drugs 0.000 title abstract description 3
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 title abstract description 3
- 229960005187 telmisartan Drugs 0.000 title abstract description 3
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 title abstract 2
- -1 valsatan Substances 0.000 title description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
- 229910004679 ONO2 Inorganic materials 0.000 claims abstract description 16
- 239000000243 solution Substances 0.000 claims description 33
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
- 239000005541 ACE inhibitor Substances 0.000 claims description 7
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 7
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 7
- 239000002876 beta blocker Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000002934 diuretic Substances 0.000 claims description 7
- 229940030606 diuretics Drugs 0.000 claims description 7
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 7
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 6
- 230000002785 anti-thrombosis Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 229960004676 antithrombotic agent Drugs 0.000 claims description 4
- 239000000480 calcium channel blocker Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 239000003087 receptor blocking agent Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
- 208000010496 Heart Arrest Diseases 0.000 claims description 2
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 2
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims description 2
- 206010030043 Ocular hypertension Diseases 0.000 claims description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000002702 enteric coating Substances 0.000 claims description 2
- 238000009505 enteric coating Methods 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 208000007232 portal hypertension Diseases 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims 2
- 230000000699 topical effect Effects 0.000 claims 2
- 230000002744 anti-aggregatory effect Effects 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 239000002502 liposome Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 abstract description 2
- 229960004699 valsartan Drugs 0.000 abstract description 2
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 abstract 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 20
- 238000000034 method Methods 0.000 description 20
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- ZKJNVODQIYQUNQ-UHFFFAOYSA-N [2-butyl-5-chloro-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 ZKJNVODQIYQUNQ-UHFFFAOYSA-N 0.000 description 16
- 239000013058 crude material Substances 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- PSIFNNKUMBGKDQ-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 PSIFNNKUMBGKDQ-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 150000002828 nitro derivatives Chemical class 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 150000007530 organic bases Chemical class 0.000 description 10
- ZETOHPSSBWBMED-UHFFFAOYSA-N 4-nitrooxybutanoic acid Chemical compound OC(=O)CCCO[N+]([O-])=O ZETOHPSSBWBMED-UHFFFAOYSA-N 0.000 description 9
- 150000007529 inorganic bases Chemical class 0.000 description 9
- 238000005903 acid hydrolysis reaction Methods 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 8
- 150000003536 tetrazoles Chemical group 0.000 description 8
- 101710134784 Agnoprotein Proteins 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000002798 polar solvent Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 6
- NXYIECYJINSHGC-UHFFFAOYSA-N 4-(nitrooxymethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CO[N+]([O-])=O)C=C1 NXYIECYJINSHGC-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 239000012454 non-polar solvent Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- GHGCYSSKZWCSNC-UHFFFAOYSA-N 11-nitrooxyundecanoic acid Chemical compound OC(=O)CCCCCCCCCCO[N+]([O-])=O GHGCYSSKZWCSNC-UHFFFAOYSA-N 0.000 description 4
- GRHQDJDRGZFIPO-UHFFFAOYSA-N 4-bromobutanoic acid Chemical compound OC(=O)CCCBr GRHQDJDRGZFIPO-UHFFFAOYSA-N 0.000 description 4
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
- 229960004373 acetylcholine Drugs 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 230000032050 esterification Effects 0.000 description 4
- 238000005886 esterification reaction Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- 230000001196 vasorelaxation Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- SPZQKUARGGNELK-UHFFFAOYSA-N 3-(nitrooxymethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(CO[N+]([O-])=O)=C1 SPZQKUARGGNELK-UHFFFAOYSA-N 0.000 description 3
- OITNBJHJJGMFBN-UHFFFAOYSA-N 4-(chloromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CCl)C=C1 OITNBJHJJGMFBN-UHFFFAOYSA-N 0.000 description 3
- NVRVNSHHLPQGCU-UHFFFAOYSA-N 6-bromohexanoic acid Chemical compound OC(=O)CCCCCBr NVRVNSHHLPQGCU-UHFFFAOYSA-N 0.000 description 3
- CBSFPBTYVIYRQZ-UHFFFAOYSA-N 6-nitrooxyhexanoic acid Chemical compound OC(=O)CCCCCO[N+]([O-])=O CBSFPBTYVIYRQZ-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000005227 gel permeation chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- 230000001131 transforming effect Effects 0.000 description 3
- WBMIQBCBWZHXQZ-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 4-bromobutanoate Chemical compound FC1=C(F)C(F)=C(OC(=O)CCCBr)C(F)=C1F WBMIQBCBWZHXQZ-UHFFFAOYSA-N 0.000 description 2
- PNERJLFIGBYJAE-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 4-nitrooxybutanoate Chemical compound [O-][N+](=O)OCCCC(=O)OC1=C(F)C(F)=C(F)C(F)=C1F PNERJLFIGBYJAE-UHFFFAOYSA-N 0.000 description 2
- YAQLSKVCTLCIIE-UHFFFAOYSA-N 2-bromobutyric acid Chemical compound CCC(Br)C(O)=O YAQLSKVCTLCIIE-UHFFFAOYSA-N 0.000 description 2
- FETCESOEGZHHTR-UHFFFAOYSA-N 2-butyl-5-chloro-1h-imidazole-4-carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1 FETCESOEGZHHTR-UHFFFAOYSA-N 0.000 description 2
- PBSUMBYSVFTMNG-UHFFFAOYSA-N 3-(chloromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(CCl)=C1 PBSUMBYSVFTMNG-UHFFFAOYSA-N 0.000 description 2
- RTNKEDXGWMZBRN-UHFFFAOYSA-N 3-bromopropyl 2-butyl-5-chloro-1h-imidazole-4-carboxylate Chemical compound CCCCC1=NC(Cl)=C(C(=O)OCCCBr)N1 RTNKEDXGWMZBRN-UHFFFAOYSA-N 0.000 description 2
- KOKZAWRRJZLZRJ-UHFFFAOYSA-N 3-nitrooxypropyl 2-butyl-5-chloro-1h-imidazole-4-carboxylate Chemical compound CCCCC1=NC(Cl)=C(C(=O)OCCCO[N+]([O-])=O)N1 KOKZAWRRJZLZRJ-UHFFFAOYSA-N 0.000 description 2
- 102000005862 Angiotensin II Human genes 0.000 description 2
- 101800000733 Angiotensin-2 Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 230000004931 aggregating effect Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 229950006323 angiotensin ii Drugs 0.000 description 2
- 230000006502 antiplatelets effects Effects 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ACAUJAGLAAHLIR-UHFFFAOYSA-N 2-benzyl-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1CC1=CC=CC=C1 ACAUJAGLAAHLIR-UHFFFAOYSA-N 0.000 description 1
- AHDSLQVVTUMWQS-UHFFFAOYSA-N 2-butyl-5-chloro-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 AHDSLQVVTUMWQS-UHFFFAOYSA-N 0.000 description 1
- JEDGAPUZBUOYQF-UHFFFAOYSA-N 2-nitrooxyhexanoic acid Chemical compound CCCCC(C(O)=O)O[N+]([O-])=O JEDGAPUZBUOYQF-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- YCAIYRWHKSJKEB-UHFFFAOYSA-N 3-(chloromethyl)benzoyl chloride Chemical compound ClCC1=CC=CC(C(Cl)=O)=C1 YCAIYRWHKSJKEB-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 1
- LRTRXDSAJLSRTG-UHFFFAOYSA-N 4-bromobutanoyl chloride Chemical compound ClC(=O)CCCBr LRTRXDSAJLSRTG-UHFFFAOYSA-N 0.000 description 1
- ZTFVTXDWDFIQEU-UHFFFAOYSA-N 5-[2-[4-(bromomethyl)phenyl]phenyl]-1-trityltetrazole Chemical compound C1=CC(CBr)=CC=C1C1=CC=CC=C1C1=NN=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZTFVTXDWDFIQEU-UHFFFAOYSA-N 0.000 description 1
- QUIJTMPWWMXUEY-UHFFFAOYSA-N 5-[2-[4-[(2-butyl-4-chloroimidazol-1-yl)methyl]phenyl]phenyl]-2h-tetrazole Chemical compound CCCCC1=NC(Cl)=CN1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 QUIJTMPWWMXUEY-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 101150059573 AGTR1 gene Proteins 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 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
- 239000004475 Arginine Substances 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 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 1
- 238000006595 Griess deamination reaction Methods 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 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 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229940087373 calcium oxide Drugs 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000011970 concomitant therapy Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000003126 guanylate cyclase inhibitor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical class CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 description 1
- 150000004106 losartan derivatives Chemical class 0.000 description 1
- 229960000519 losartan potassium Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 238000004094 preconcentration Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 230000002883 vasorelaxation effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/20—Two benzimidazolyl-2 radicals linked together directly or via a hydrocarbon or substituted hydrocarbon radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03102379 | 2003-07-31 | ||
PCT/EP2004/051550 WO2005011646A2 (en) | 2003-07-31 | 2004-07-20 | Nitrooxy derivatives of losartan, valsatan, candesartan, telmisartan, eprosartan and olmesartan as angiotensin-ii receptor blockers for the treatment of cardiovascular diseases |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20060084A2 true HRP20060084A2 (hr) | 2006-04-30 |
Family
ID=34112476
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20060084A HRP20060084A2 (hr) | 2003-07-31 | 2006-02-24 | Nitrooksi derivati losartana, valsartana, kandesartana, telmisartana, eprosartana i olmesartana kao blokatori angiotenzin ii receptora za tretiranje kardiovaskularnih bolesti |
Country Status (30)
Country | Link |
---|---|
US (1) | US20060276523A1 (ru) |
EP (1) | EP1653950B1 (ru) |
JP (1) | JP2007500684A (ru) |
KR (1) | KR20060056352A (ru) |
CN (1) | CN100496490C (ru) |
AR (1) | AR045145A1 (ru) |
AT (1) | ATE383155T1 (ru) |
AU (1) | AU2004260830B2 (ru) |
BR (1) | BRPI0413028A (ru) |
CA (1) | CA2534451A1 (ru) |
CY (1) | CY1110447T1 (ru) |
DE (1) | DE602004011230T2 (ru) |
DK (1) | DK1653950T3 (ru) |
EC (1) | ECSP066334A (ru) |
ES (1) | ES2299861T3 (ru) |
HK (1) | HK1095093A1 (ru) |
HR (1) | HRP20060084A2 (ru) |
IL (1) | IL172703A0 (ru) |
IS (1) | IS2534B (ru) |
MA (1) | MA27987A1 (ru) |
MX (1) | MXPA06001263A (ru) |
NO (1) | NO20060900L (ru) |
NZ (1) | NZ544463A (ru) |
PL (2) | PL1653950T3 (ru) |
PT (1) | PT1653950E (ru) |
RU (1) | RU2374240C2 (ru) |
SI (1) | SI1653950T1 (ru) |
UA (1) | UA87983C2 (ru) |
WO (1) | WO2005011646A2 (ru) |
ZA (1) | ZA200600856B (ru) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2005263655A1 (en) | 2004-07-20 | 2006-01-26 | Nicox S.A. | Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof |
WO2006079610A1 (en) * | 2005-01-31 | 2006-08-03 | Nicox S.A. | Nitrooxy sartan derivatives as angiotensin ii receptor blockers for the treatment of cardiovascular and inflammatory diseases |
CN101024643A (zh) | 2006-02-20 | 2007-08-29 | 上海艾力斯医药科技有限公司 | 咪唑-5-羧酸类衍生物、制备方法及其应用 |
TW200821303A (en) * | 2006-08-08 | 2008-05-16 | Speedel Experimenta Ag | Organic compounds |
CA2668744C (en) | 2006-11-17 | 2015-09-15 | Queen's University At Kingston | Compounds and methods for treating protein folding disorders |
AU2006351517B8 (en) * | 2006-12-06 | 2012-01-19 | Shenzhen Salubris Pharmaceuticals Co., Ltd. | The salts of imidazol-5-carboxylic acid derivatives, preparation methods and use thereof |
TW200831079A (en) * | 2006-12-13 | 2008-08-01 | Merck & Co Inc | Angiotensin II receptor antagonists |
JP2010513273A (ja) * | 2006-12-13 | 2010-04-30 | メルク アンド カンパニー インク. | アンジオテンシンii受容体拮抗薬 |
CN101214242A (zh) | 2007-01-05 | 2008-07-09 | 上海艾力斯医药科技有限公司 | 新的药用组合物 |
EP1980559A1 (en) * | 2007-04-10 | 2008-10-15 | CTG Pharma S.r.l. | Cardiovascular agents |
CN101317842A (zh) | 2007-06-07 | 2008-12-10 | 上海艾力斯医药科技有限公司 | 一种咪唑-5-羧酸衍生物的治疗用途 |
CN101407511B (zh) * | 2007-10-11 | 2013-01-09 | 上海艾力斯生物医药有限公司 | 一种结晶型的咪唑-5-羧酸衍生物 |
AR069340A1 (es) | 2007-11-26 | 2010-01-13 | Merck & Co Inc | Antagonistas del receptor de angiotensina ii |
CA2709071C (en) | 2007-12-14 | 2016-11-15 | Labogroup S.A.S. | Delivering aerosolizable food products |
JP2011510082A (ja) * | 2008-01-24 | 2011-03-31 | メルク・シャープ・エンド・ドーム・コーポレイション | アンジオテンシンii受容体拮抗薬 |
EP2250168B1 (en) * | 2008-02-08 | 2014-11-19 | Merck Sharp & Dohme Corp. | Angiotensin ii receptor antagonists |
US20100311800A1 (en) * | 2008-02-26 | 2010-12-09 | Nicoletta Almirante | Angiotensin ii receptor antagonists |
CA2712695A1 (en) * | 2008-02-26 | 2009-09-03 | Nicoletta Almirante | New angiotensin ii receptor blocker derivatives |
AU2009246670A1 (en) * | 2008-05-15 | 2009-11-19 | Merck Sharp & Dohme Corp. | Angiotensin II receptor antagonists |
CN101596189A (zh) * | 2008-06-05 | 2009-12-09 | 上海艾力斯生物医药有限公司 | 含有咪唑-5-羧酸类衍生物的药用组合物 |
WO2009150007A1 (en) * | 2008-06-09 | 2009-12-17 | Nicox S.A. | Angiotensin ii receptor antagonists |
AR073259A1 (es) * | 2008-07-29 | 2010-10-28 | Merck & Co Inc | Derivados de furosemida utiles como diureticos |
WO2010015447A1 (en) * | 2008-08-08 | 2010-02-11 | Nicox S.A. | Angiotensin ii receptor antagonists |
EP2194048A1 (en) | 2008-12-02 | 2010-06-09 | Dirk Sartor | Nitrate esters for the treatment of vascular and metabolic diseases |
EP2373630A1 (en) * | 2008-12-05 | 2011-10-12 | Merck Sharp & Dohme Corp. | Nitrooxy derivatives as angiotensin ii receptor antagonists |
NZ594738A (en) | 2009-01-23 | 2013-11-29 | Hanmi Science Co Ltd | Solid pharmaceutical composition comprising amlodipine and losartan and process for producing same |
JP2013525323A (ja) | 2010-04-19 | 2013-06-20 | カーディオリンクス・アーゲー | 血管性及び代謝性疾患の処置のための酸化窒素ドナー担持バルサルタン誘導体 |
CA2796963A1 (en) * | 2010-04-23 | 2011-10-27 | Piramal Enterprises Limited | Nitric oxide releasing prodrugs of therapeutic agents |
WO2011160974A2 (en) | 2010-06-21 | 2011-12-29 | Nicox S.A. | Statin derivatives |
JO3350B1 (ar) | 2011-03-07 | 2019-03-13 | Merck Sharp & Dohme | مشتقات حلقية غير متجانسة محتوية على مجموعات أمينو أولية ومركبات داي أزينيومديولات |
US9844599B2 (en) | 2013-01-21 | 2017-12-19 | Apparao Satyam | Nitric oxide releasing produgs of therapeutic agents |
CN103275074B (zh) * | 2013-06-21 | 2016-08-10 | 黄冈鲁班药业股份有限公司 | 一种奥美沙坦衍生物及其制备方法 |
CN105820125B (zh) * | 2015-01-09 | 2018-12-07 | 北京中医药大学 | 一种用于治疗高血压的化合物及其制备方法和用途 |
EP3348548A4 (en) | 2015-09-07 | 2019-04-03 | Zhejiang Huahai Pharmaceutical Co., Ltd | DRUG MOLECULE RELEASING NITRIC OXIDE |
CN106800537B (zh) * | 2017-01-18 | 2019-02-01 | 广东隆赋药业股份有限公司 | 丁苯酞-替米沙坦杂合物及其制备方法和用途 |
CN108892624B (zh) * | 2018-06-20 | 2020-12-15 | 重庆威鹏药业有限公司 | 沙库巴曲硝基氧衍生物及其制备方法和应用 |
CN114105881B (zh) * | 2020-08-31 | 2024-01-26 | 沈阳海诺威医药科技有限公司 | 血小板聚集抑制剂及其制备方法和用途 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69034103T2 (de) * | 1989-06-14 | 2004-07-15 | Smithkline Beecham Corp. | Imidazoalkensäure |
IT1311924B1 (it) * | 1999-04-13 | 2002-03-20 | Nicox Sa | Composti farmaceutici. |
EP1312379A4 (en) * | 2000-08-25 | 2004-08-25 | Takeda Chemical Industries Ltd | FIBRINOGENIC REDUCTION AGENTS |
ITMI20011744A1 (it) * | 2001-08-09 | 2003-02-09 | Nicox Sa | Farmaci per le vasculopatie |
-
2004
- 2004-07-20 CA CA002534451A patent/CA2534451A1/en not_active Abandoned
- 2004-07-20 EP EP04766269A patent/EP1653950B1/en active Active
- 2004-07-20 DK DK04766269T patent/DK1653950T3/da active
- 2004-07-20 DE DE602004011230T patent/DE602004011230T2/de active Active
- 2004-07-20 PT PT04766269T patent/PT1653950E/pt unknown
- 2004-07-20 AT AT04766269T patent/ATE383155T1/de not_active IP Right Cessation
- 2004-07-20 US US10/566,292 patent/US20060276523A1/en not_active Abandoned
- 2004-07-20 UA UAA200600273A patent/UA87983C2/ru unknown
- 2004-07-20 ES ES04766269T patent/ES2299861T3/es active Active
- 2004-07-20 PL PL04766269T patent/PL1653950T3/pl unknown
- 2004-07-20 SI SI200430655T patent/SI1653950T1/sl unknown
- 2004-07-20 JP JP2006521571A patent/JP2007500684A/ja active Pending
- 2004-07-20 WO PCT/EP2004/051550 patent/WO2005011646A2/en active IP Right Grant
- 2004-07-20 MX MXPA06001263A patent/MXPA06001263A/es active IP Right Grant
- 2004-07-20 CN CNB200480022483XA patent/CN100496490C/zh not_active Expired - Fee Related
- 2004-07-20 AU AU2004260830A patent/AU2004260830B2/en not_active Ceased
- 2004-07-20 NZ NZ544463A patent/NZ544463A/en unknown
- 2004-07-20 PL PL379420A patent/PL379420A1/pl not_active Application Discontinuation
- 2004-07-20 KR KR1020067001893A patent/KR20060056352A/ko not_active Application Discontinuation
- 2004-07-20 BR BRPI0413028-6A patent/BRPI0413028A/pt not_active IP Right Cessation
- 2004-07-20 RU RU2006105804/04A patent/RU2374240C2/ru not_active IP Right Cessation
- 2004-07-28 AR ARP040102685A patent/AR045145A1/es unknown
-
2005
- 2005-12-20 IL IL172703A patent/IL172703A0/en not_active IP Right Cessation
-
2006
- 2006-01-30 EC EC2006006334A patent/ECSP066334A/es unknown
- 2006-01-30 ZA ZA200600856A patent/ZA200600856B/en unknown
- 2006-02-13 MA MA28789A patent/MA27987A1/fr unknown
- 2006-02-24 NO NO20060900A patent/NO20060900L/no not_active Application Discontinuation
- 2006-02-24 HR HR20060084A patent/HRP20060084A2/hr not_active Application Discontinuation
- 2006-02-27 IS IS8332A patent/IS2534B/is unknown
-
2007
- 2007-03-05 HK HK07102421.8A patent/HK1095093A1/xx not_active IP Right Cessation
-
2008
- 2008-04-07 CY CY20081100385T patent/CY1110447T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20060084A2 (hr) | Nitrooksi derivati losartana, valsartana, kandesartana, telmisartana, eprosartana i olmesartana kao blokatori angiotenzin ii receptora za tretiranje kardiovaskularnih bolesti | |
AU2004243443B2 (en) | Nitrooxyderivatives of fluvastatin, pravastatin, cerivastatin, atorvastatin and rosuvastatin as cholesterol-reducing agents with improved anti-inflammatory, antithrombotic and antiplatelet activity | |
EP0941218A1 (en) | Antithrombotic organic nitrates | |
PT96399A (pt) | Processo de preparacao de derivados de imidazol e de composicoes farmaceuticas que os contem | |
RU2078764C1 (ru) | Производные тетразола, способ их получения и фармацевтическая композиция, обладающая свойствами антагониста рецептора ангиотензина п | |
JP2011513269A (ja) | 新規アンジオテンシンiiレセプターブロッカー誘導体 | |
WO2010015447A1 (en) | Angiotensin ii receptor antagonists | |
RU2125990C1 (ru) | Производные замещенной гетероциклом фенил-циклогексан-карбоновой кислоты, смесь их изомеров или отдельные изомеры и их соли | |
EP1635816B1 (en) | Enalapril-nitroxyderivatives derivatives and related compounds as ace inhibitors for the treatment of cardiovascular diseases | |
JP2009514809A (ja) | レニン阻害剤のニトロ誘導体 | |
JPH0649034A (ja) | プロペノイル−イミダゾール誘導体 | |
JP3116256B2 (ja) | (チオ)ウレア誘導体 | |
JP4649410B2 (ja) | カプトプリル誘導体 | |
EP0864568B1 (en) | Agents for treatment of cardiac diseases | |
JP2011513268A (ja) | アンジオテンシンii受容体アンタゴニスト | |
KR0178086B1 (ko) | 히스티딘 유도체, 이의 제조방법 | |
Okazaki et al. | Studies on nonpeptide angiotensin II receptor antagonists. IV. Synthesis and biological evaluation of 4-acrylamide-1H-imidazole derivatives | |
EP0145304B1 (en) | Tetrahydro-beta-carboline derivatives and process for the preparation thereof | |
EP1403252A1 (en) | Novel butadiene derivatives, process for preparation of the same and intermediates for the synthesis thereof | |
JPH06287182A (ja) | アルキルグリシン誘導体 | |
JPH09301956A (ja) | 5位にオルトメトキシフェニルピペラジニルアルキル基を有する新規イミダゾール誘導体及びその製造法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
ARAI | Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application | ||
PNAN | Change of the applicant name, address/residence |
Owner name: NICOX S.A., FR |
|
ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20100708 Year of fee payment: 7 |
|
OBST | Application withdrawn |