SK14032003A3 - Dipeptidové deriváty s N-terminálnou 2-tioacylovou skupinou a farmaceutické prostriedky s ich obsahom - Google Patents

Info

Publication number

SK14032003A3

SK14032003A3 SK1403-2003A SK14032003A SK14032003A3 SK 14032003 A3 SK14032003 A3 SK 14032003A3 SK 14032003 A SK14032003 A SK 14032003A SK 14032003 A3 SK14032003 A3 SK 14032003A3

Authority

SK

Slovakia

Prior art keywords

group

lower alkyl

carbocyclic

alkyl group

compound

Prior art date

2001-05-15

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003112 inhibitor Substances 0.000 title abstract description 13
• 108010016626 Dipeptides Proteins 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 125
• 102000003729 Neprilysin Human genes 0.000 claims abstract description 21
• 108090000028 Neprilysin Proteins 0.000 claims abstract description 21
• 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 claims abstract description 16
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims abstract description 16
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims abstract 2
• 125000000217 alkyl group Chemical group 0.000 claims description 128
• -1 pyrrolidinocarbonyl Chemical group 0.000 claims description 72
• 125000002837 carbocyclic group Chemical group 0.000 claims description 41
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 37
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
• 125000002252 acyl group Chemical group 0.000 claims description 32
• 125000004432 carbon atom Chemical group C* 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 29
• 238000000034 method Methods 0.000 claims description 26
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 20
• 150000002148 esters Chemical class 0.000 claims description 19
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 241000124008 Mammalia Species 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 12
• 125000004423 acyloxy group Chemical group 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 206010020772 Hypertension Diseases 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
• 150000002019 disulfides Chemical class 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 125000002947 alkylene group Chemical group 0.000 claims description 6
• 229920006395 saturated elastomer Polymers 0.000 claims description 6
• 206010019280 Heart failures Diseases 0.000 claims description 5
• 125000005841 biaryl group Chemical group 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 4
• 208000029422 Hypernatremia Diseases 0.000 claims description 3
• 206010030113 Oedema Diseases 0.000 claims description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
• 125000004175 fluorobenzyl group Chemical group 0.000 claims description 3
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
• JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims 2
• 150000002431 hydrogen Chemical class 0.000 claims 1
• 235000015250 liver sausages Nutrition 0.000 claims 1
• XYSQXZCMOLNHOI-UHFFFAOYSA-N s-[2-[[4-(acetylsulfamoyl)phenyl]carbamoyl]phenyl] 5-pyridin-1-ium-1-ylpentanethioate;bromide Chemical compound [Br-].C1=CC(S(=O)(=O)NC(=O)C)=CC=C1NC(=O)C1=CC=CC=C1SC(=O)CCCC[N+]1=CC=CC=C1 XYSQXZCMOLNHOI-UHFFFAOYSA-N 0.000 claims 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
• 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 abstract description 14
• 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 abstract description 13
• 230000009977 dual effect Effects 0.000 abstract description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
• 239000000203 mixture Substances 0.000 description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
• 239000000243 solution Substances 0.000 description 36
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 235000019439 ethyl acetate Nutrition 0.000 description 30
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
• 230000005764 inhibitory process Effects 0.000 description 24
• 241000700159 Rattus Species 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• 239000003921 oil Substances 0.000 description 19
• 235000019198 oils Nutrition 0.000 description 19
• 238000012360 testing method Methods 0.000 description 19
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• 102400000686 Endothelin-1 Human genes 0.000 description 18
• 101800004490 Endothelin-1 Proteins 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000012267 brine Substances 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
• 239000007858 starting material Substances 0.000 description 16
• 230000000694 effects Effects 0.000 description 15
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 14
• 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 14
• 239000002253 acid Substances 0.000 description 14
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 239000003981 vehicle Substances 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 239000011541 reaction mixture Substances 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• 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 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 150000001721 carbon Chemical group 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 125000005843 halogen group Chemical group 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 235000015424 sodium Nutrition 0.000 description 9
• 125000003396 thiol group Chemical group [H]S* 0.000 description 9
• 241001465754 Metazoa Species 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 210000001105 femoral artery Anatomy 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 7
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
• 230000004872 arterial blood pressure Effects 0.000 description 7
• 239000003814 drug Substances 0.000 description 7
• 210000003191 femoral vein Anatomy 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 239000007789 gas Substances 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 230000036772 blood pressure Effects 0.000 description 6
• 238000009833 condensation Methods 0.000 description 6
• 230000005494 condensation Effects 0.000 description 6
• 239000006260 foam Substances 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 230000036584 pressor response Effects 0.000 description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
• 230000004044 response Effects 0.000 description 6
• 102400000344 Angiotensin-1 Human genes 0.000 description 5
• 101800000734 Angiotensin-1 Proteins 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 229940024606 amino acid Drugs 0.000 description 5
• 235000001014 amino acid Nutrition 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound 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)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 239000002934 diuretic Substances 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• 238000003127 radioimmunoassay Methods 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• 210000002700 urine Anatomy 0.000 description 5
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 108050009340 Endothelin Proteins 0.000 description 4
• 102000002045 Endothelin Human genes 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
• 101500027366 Rattus norvegicus Atrial natriuretic peptide Proteins 0.000 description 4
• 125000005907 alkyl ester group Chemical group 0.000 description 4
• 230000003276 anti-hypertensive effect Effects 0.000 description 4
• 125000003435 aroyl group Chemical group 0.000 description 4
• 150000005347 biaryls Chemical group 0.000 description 4
• 150000001735 carboxylic acids Chemical class 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 4
• 229910052736 halogen Inorganic materials 0.000 description 4
• 150000002367 halogens Chemical class 0.000 description 4
• 230000001631 hypertensive effect Effects 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 239000000376 reactant Substances 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 238000013222 sprague-dawley male rat Methods 0.000 description 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 description 3
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 150000001733 carboxylic acid esters Chemical class 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 125000004093 cyano group Chemical group *C#N 0.000 description 3
• 229960004486 desoxycorticosterone acetate Drugs 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
• 238000006073 displacement reaction Methods 0.000 description 3
• 230000001882 diuretic effect Effects 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• UVPOIPYHTOFDIB-MERQFXBCSA-N ethyl (2s)-2-amino-3-phenylmethoxypropanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)COCC1=CC=CC=C1 UVPOIPYHTOFDIB-MERQFXBCSA-N 0.000 description 3
• 125000004494 ethyl ester group Chemical group 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 150000004820 halides Chemical class 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 230000005291 magnetic effect Effects 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 235000018102 proteins Nutrition 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• CEBYCSRFKCEUSW-NAYZPBBASA-N (2S)-1-[[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxyphenyl)sulfonyl-3-hydroxy-2H-indol-2-yl]-oxomethyl]-2-pyrrolidinecarboxamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC=C(Cl)C=C2[C@](O)(C=2C(=CC=CC=2)Cl)[C@@H]1C(=O)N1[C@H](C(N)=O)CCC1 CEBYCSRFKCEUSW-NAYZPBBASA-N 0.000 description 2
• SVSFQTBYDQAZSF-FZSMXKCYSA-N (2r)-2-bromo-3-methylbutanoic acid;n-propan-2-ylpropan-2-amine Chemical compound CC(C)NC(C)C.CC(C)[C@@H](Br)C(O)=O SVSFQTBYDQAZSF-FZSMXKCYSA-N 0.000 description 2
• CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound 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](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 2
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
• XOTALBWPHRSWRG-MRVPVSSYSA-N 1-[[(2r)-2-bromo-3-methylbutanoyl]amino]cyclopentane-1-carboxylic acid Chemical compound CC(C)[C@@H](Br)C(=O)NC1(C(O)=O)CCCC1 XOTALBWPHRSWRG-MRVPVSSYSA-N 0.000 description 2
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
• JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 2
• MFNXWZGIFWJHMI-UHFFFAOYSA-N 2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(O)=O MFNXWZGIFWJHMI-UHFFFAOYSA-N 0.000 description 2
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
• JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
• 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 102400000345 Angiotensin-2 Human genes 0.000 description 2
• 101800000733 Angiotensin-2 Proteins 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• 208000010412 Glaucoma Diseases 0.000 description 2
• 101000841259 Homo sapiens Endothelin-converting enzyme 1 Proteins 0.000 description 2
• 206010020880 Hypertrophy Diseases 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• IDGQXGPQOGUGIX-VIFPVBQESA-N O-BENZYL-l-SERINE Chemical compound OC(=O)[C@@H](N)COCC1=CC=CC=C1 IDGQXGPQOGUGIX-VIFPVBQESA-N 0.000 description 2
• 208000004880 Polyuria Diseases 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
• 208000012322 Raynaud phenomenon Diseases 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• 229910004298 SiO 2 Inorganic materials 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 239000002250 absorbent Substances 0.000 description 2
• 230000002745 absorbent Effects 0.000 description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 125000005236 alkanoylamino group Chemical group 0.000 description 2
• 125000003282 alkyl amino group Chemical group 0.000 description 2
• 229950006323 angiotensin ii Drugs 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 239000003529 anticholesteremic agent Substances 0.000 description 2
• 229940127226 anticholesterol agent Drugs 0.000 description 2
• 239000003472 antidiabetic agent Substances 0.000 description 2
• 239000002220 antihypertensive agent Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 239000011324 bead Substances 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 159000000007 calcium salts Chemical class 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• DXXUGBPKQDTBQW-UHFFFAOYSA-L chlorisondamine Chemical compound [Cl-].[Cl-].ClC1=C(Cl)C(Cl)=C(Cl)C2=C1C[N+](CC[N+](C)(C)C)(C)C2 DXXUGBPKQDTBQW-UHFFFAOYSA-L 0.000 description 2
• 229950002565 chlorisondamine Drugs 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 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 2
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 230000035619 diuresis Effects 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• PGEVGMOTJUZUKY-MERQFXBCSA-N ethyl (2r)-2-amino-3-benzylsulfanylpropanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)CSCC1=CC=CC=C1 PGEVGMOTJUZUKY-MERQFXBCSA-N 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000002223 garnet Substances 0.000 description 2
• 210000002216 heart Anatomy 0.000 description 2
• 102000045616 human ECE1 Human genes 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 238000000099 in vitro assay Methods 0.000 description 2
• 208000001286 intracranial vasospasm Diseases 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 201000006370 kidney failure Diseases 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• 230000001452 natriuretic effect Effects 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 238000010647 peptide synthesis reaction Methods 0.000 description 2
• 150000002989 phenols Chemical class 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
• 230000004962 physiological condition Effects 0.000 description 2
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 239000001103 potassium chloride Substances 0.000 description 2
• 235000011164 potassium chloride Nutrition 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 229960001153 serine Drugs 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• SLZHLQUFNFXTHB-UHFFFAOYSA-M sodium;5-butan-2-yl-5-ethyl-2-sulfanylidenepyrimidin-3-ide-4,6-dione Chemical compound [Na+].CCC(C)C1(CC)C([O-])=NC(=S)NC1=O SLZHLQUFNFXTHB-UHFFFAOYSA-M 0.000 description 2
• 238000003797 solvolysis reaction Methods 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 125000001425 triazolyl group Chemical group 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
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• IFVORPLRHYROAA-LBPRGKRZSA-N (2r)-3-benzylsulfanyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CSCC1=CC=CC=C1 IFVORPLRHYROAA-LBPRGKRZSA-N 0.000 description 1
• DMBKPDOAQVGTST-LBPRGKRZSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylmethoxypropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)COCC1=CC=CC=C1 DMBKPDOAQVGTST-LBPRGKRZSA-N 0.000 description 1
• AAXWBCKQYLBQKY-IRXDYDNUSA-N (2s)-2-[[(2s)-2-[(2-benzamidoacetyl)amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-4-methylpentanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)C=1C=CC=CC=1)C1=CN=CN1 AAXWBCKQYLBQKY-IRXDYDNUSA-N 0.000 description 1
• XUHRVZXFBWDCFB-QRTDKPMLSA-N (3R)-4-[[(3S,6S,9S,12R,15S,18R,21R,24R,27R,28R)-12-(3-amino-3-oxopropyl)-6-[(2S)-butan-2-yl]-3-(2-carboxyethyl)-18-(hydroxymethyl)-28-methyl-9,15,21,24-tetrakis(2-methylpropyl)-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octazacyclooctacos-27-yl]amino]-3-[[(2R)-2-[[(3S)-3-hydroxydecanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid Chemical compound CCCCCCC[C@H](O)CC(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H]1[C@@H](C)OC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CO)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC1=O)[C@@H](C)CC XUHRVZXFBWDCFB-QRTDKPMLSA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• XGASTRVQNVVYIZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCl)=C1 XGASTRVQNVVYIZ-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• CDDDRVNOHLVEED-UHFFFAOYSA-N 1-cyclohexyl-3-[1-[[1-(cyclohexylcarbamoylamino)cyclohexyl]diazenyl]cyclohexyl]urea Chemical compound C1CCCCC1(N=NC1(CCCCC1)NC(=O)NC1CCCCC1)NC(=O)NC1CCCCC1 CDDDRVNOHLVEED-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• YMQRPXBBBOXHNZ-UHFFFAOYSA-N 2-chloro-1-morpholin-4-ylethanone Chemical compound ClCC(=O)N1CCOCC1 YMQRPXBBBOXHNZ-UHFFFAOYSA-N 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• QKVCSJBBYNYZNM-UHFFFAOYSA-N 2-methyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound OC(=O)C(C)(C)NC(=O)OCC1=CC=CC=C1 QKVCSJBBYNYZNM-UHFFFAOYSA-N 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical compound C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-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
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
• CLPFFLWZZBQMAO-CQSZACIVSA-N 4-[(5r)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1[C@@H]1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-CQSZACIVSA-N 0.000 description 1
• RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
• 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 description 1
• WMWOMMJQVXRFAP-UHFFFAOYSA-N 5-chloro-4,6-dimethoxytriazine Chemical compound COC1=NN=NC(OC)=C1Cl WMWOMMJQVXRFAP-UHFFFAOYSA-N 0.000 description 1
• VNACOBVZDCLAEV-UHFFFAOYSA-N 6-[2-[[2-(2-cyanopyrrolidin-1-yl)-2-oxoethyl]amino]ethylamino]pyridine-3-carbonitrile;dihydrochloride Chemical compound Cl.Cl.C1CCC(C#N)N1C(=O)CNCCNC1=CC=C(C#N)C=N1 VNACOBVZDCLAEV-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
• 229940123338 Aldosterone synthase inhibitor Drugs 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
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 235000001258 Cinchona calisaya Nutrition 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 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
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 102100029112 Endothelin-converting enzyme 1 Human genes 0.000 description 1
• 208000010228 Erectile Dysfunction Diseases 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 208000003098 Ganglion Cysts Diseases 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 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
• 239000004471 Glycine Substances 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 206010020571 Hyperaldosteronism Diseases 0.000 description 1
• 206010020590 Hypercalciuria Diseases 0.000 description 1
• 206010020601 Hyperchlorhydria Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
• UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
• 108010004098 Leucyl aminopeptidase Proteins 0.000 description 1
• 102000002704 Leucyl aminopeptidase Human genes 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000027530 Meniere disease Diseases 0.000 description 1
• IMWZZHHPURKASS-UHFFFAOYSA-N Metaxalone Chemical compound CC1=CC(C)=CC(OCC2OC(=O)NC2)=C1 IMWZZHHPURKASS-UHFFFAOYSA-N 0.000 description 1
• NZXKDOXHBHYTKP-UHFFFAOYSA-N Metohexital Chemical compound CCC#CC(C)C1(CC=C)C(=O)NC(=O)N(C)C1=O NZXKDOXHBHYTKP-UHFFFAOYSA-N 0.000 description 1
• 208000019695 Migraine disease Diseases 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
• 241001529936 Murinae Species 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 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
• 206010036618 Premenstrual syndrome Diseases 0.000 description 1
• 208000028017 Psychotic disease Diseases 0.000 description 1
• 206010037423 Pulmonary oedema Diseases 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 208000032851 Subarachnoid Hemorrhage Diseases 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
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 208000005400 Synovial Cyst Diseases 0.000 description 1
• 206010042957 Systolic hypertension Diseases 0.000 description 1
• 102100024547 Tensin-1 Human genes 0.000 description 1
• 108010088950 Tensins Proteins 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• FNYLWPVRPXGIIP-UHFFFAOYSA-N Triamterene Chemical compound NC1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC=C1 FNYLWPVRPXGIIP-UHFFFAOYSA-N 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 206010060953 Ventricular failure Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
• NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
• 229960005054 acepromazine Drugs 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
• 150000008041 alkali metal carbonates Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
• 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000005530 alkylenedioxy group Chemical group 0.000 description 1
• 150000001371 alpha-amino acids Chemical class 0.000 description 1
• 235000008206 alpha-amino acids Nutrition 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229960000528 amlodipine Drugs 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 238000005349 anion exchange Methods 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000003178 anti-diabetic effect Effects 0.000 description 1
• 229940125708 antidiabetic agent Drugs 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 229940127088 antihypertensive drug Drugs 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 230000001746 atrial effect Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
• 239000012964 benzotriazole Substances 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• UIEATEWHFDRYRU-UHFFFAOYSA-N bepridil Chemical compound C1CCCN1C(COCC(C)C)CN(C=1C=CC=CC=1)CC1=CC=CC=C1 UIEATEWHFDRYRU-UHFFFAOYSA-N 0.000 description 1
• 229960003665 bepridil Drugs 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• 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 1
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 229960002781 bisoprolol Drugs 0.000 description 1
• VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
• 238000009530 blood pressure measurement Methods 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
• 229960003065 bosentan Drugs 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
• RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• 229960005057 canrenone Drugs 0.000 description 1
• UJVLDDZCTMKXJK-WNHSNXHDSA-N canrenone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CCC(=O)C=C3C=C2)C)CC[C@@]11C)C[C@@]11CCC(=O)O1 UJVLDDZCTMKXJK-WNHSNXHDSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 239000002371 cardiac agent Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 239000000496 cardiotonic agent Substances 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000001627 cerebral artery Anatomy 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• CDSBFDCCJJDFCV-CKZSCMLPSA-N chembl2107777 Chemical compound C([C@H]1CC[C@@]2(C(=O)N(C3=CC=C(C=C32)OCC)S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)C)OC)CC1)CN1CCOCC1 CDSBFDCCJJDFCV-CKZSCMLPSA-N 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
• 229960002604 colestipol Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000002301 combined effect Effects 0.000 description 1
• 238000002485 combustion reaction Methods 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 238000005947 deacylation reaction Methods 0.000 description 1
• 238000006264 debenzylation reaction Methods 0.000 description 1
• 230000000593 degrading effect Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
• 229960004166 diltiazem Drugs 0.000 description 1
• 239000012470 diluted sample Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003651 drinking water Substances 0.000 description 1
• 235000020188 drinking water Nutrition 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• ZJKNESGOIKRXQY-UHFFFAOYSA-N enoximone Chemical compound C1=CC(SC)=CC=C1C(=O)C1=C(C)NC(=O)N1 ZJKNESGOIKRXQY-UHFFFAOYSA-N 0.000 description 1
• 229960000972 enoximone Drugs 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 238000009585 enzyme analysis Methods 0.000 description 1
• 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 description 1
• 229960004563 eprosartan Drugs 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• AWXFMJRGSMGYRX-MOPGFXCFSA-N ethyl (2s)-2-[[2-[[(2s)-2-acetylsulfanyl-3-methylbutanoyl]amino]-2-methylpropanoyl]amino]-3-benzylsulfonylpropanoate Chemical compound CC(=O)S[C@@H](C(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](C(=O)OCC)CS(=O)(=O)CC1=CC=CC=C1 AWXFMJRGSMGYRX-MOPGFXCFSA-N 0.000 description 1
• AEGBKEZIIKIIGQ-INIZCTEOSA-N ethyl (2s)-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-3-phenylmethoxypropanoate Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(=O)N[C@H](C(=O)OCC)COCC1=CC=CC=C1 AEGBKEZIIKIIGQ-INIZCTEOSA-N 0.000 description 1
• QYOQPNCFBOMIBQ-MRXNPFEDSA-N ethyl (2s)-3-benzylsulfonyl-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]propanoate Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(=O)N[C@@H](C(=O)OCC)CS(=O)(=O)CC1=CC=CC=C1 QYOQPNCFBOMIBQ-MRXNPFEDSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
• 229960000815 ezetimibe Drugs 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 229940125753 fibrate Drugs 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 229960003883 furosemide Drugs 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960003627 gemfibrozil Drugs 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• 229960001381 glipizide Drugs 0.000 description 1
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 108010016268 hippuryl-histidyl-leucine Proteins 0.000 description 1
• 229960002003 hydrochlorothiazide Drugs 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 230000003308 immunostimulating effect Effects 0.000 description 1
• 201000001881 impotence Diseases 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
• 229960004569 indapamide Drugs 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 208000002551 irritable bowel syndrome Diseases 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 239000000644 isotonic solution Substances 0.000 description 1
• 229960004427 isradipine Drugs 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 210000000231 kidney cortex Anatomy 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• WHXMKTBCFHIYNQ-SECBINFHSA-N levosimendan Chemical compound C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1 WHXMKTBCFHIYNQ-SECBINFHSA-N 0.000 description 1
• 229960000692 levosimendan Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
• PPHTXRNHTVLQED-UHFFFAOYSA-N lixivaptan Chemical compound CC1=CC=C(F)C=C1C(=O)NC(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 PPHTXRNHTVLQED-UHFFFAOYSA-N 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• 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 description 1
• 229960004844 lovastatin Drugs 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
• 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
• 239000000314 lubricant Substances 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• 229960000509 metaxalone Drugs 0.000 description 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
• 229960003105 metformin Drugs 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 1
• 229960002455 methoxyflurane Drugs 0.000 description 1
• MXDSPOYNAHOHEU-KKSFZXQISA-N methyl (2s)-4-[[(2s)-2-acetylsulfanyl-3-methylbutanoyl]amino]-2-amino-2-(benzenesulfonamidomethyl)-4-methyl-3-oxopentanoate Chemical compound CC(=O)S[C@@H](C(C)C)C(=O)NC(C)(C)C(=O)[C@](N)(C(=O)OC)CNS(=O)(=O)C1=CC=CC=C1 MXDSPOYNAHOHEU-KKSFZXQISA-N 0.000 description 1
• OPUJUITUYWGUEP-UHFFFAOYSA-N methyl 1-aminocyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1(N)CCCC1 OPUJUITUYWGUEP-UHFFFAOYSA-N 0.000 description 1
• VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 229960002237 metoprolol Drugs 0.000 description 1
• IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• WRNXUQJJCIZICJ-UHFFFAOYSA-N mozavaptan Chemical compound C12=CC=CC=C2C(N(C)C)CCCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C WRNXUQJJCIZICJ-UHFFFAOYSA-N 0.000 description 1
• 229950000546 mozavaptan Drugs 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• 239000002833 natriuretic agent Substances 0.000 description 1
• 238000013059 nephrectomy Methods 0.000 description 1
• 229960001783 nicardipine Drugs 0.000 description 1
• HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
• 229960001597 nifedipine Drugs 0.000 description 1
• 229960000715 nimodipine Drugs 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 238000005375 photometry Methods 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
• 229960002797 pitavastatin Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 230000012495 positive regulation of renal sodium excretion Effects 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229960002965 pravastatin Drugs 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
• 201000011461 pre-eclampsia Diseases 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 208000005333 pulmonary edema Diseases 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 229960001404 quinidine Drugs 0.000 description 1
• 229960000948 quinine Drugs 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000006894 reductive elimination reaction Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 239000002461 renin inhibitor Substances 0.000 description 1
• 229940086526 renin-inhibitors Drugs 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 230000000894 saliuretic effect Effects 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 229920000260 silastic Polymers 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000008279 sol Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
• 229960002256 spironolactone Drugs 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 238000012453 sprague-dawley rat model Methods 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical class O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 229960002898 threonine Drugs 0.000 description 1
• 239000003749 thyromimetic agent Substances 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 210000003437 trachea Anatomy 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 229960001288 triamterene Drugs 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 230000036325 urinary excretion Effects 0.000 description 1
• 229960004295 valine Drugs 0.000 description 1
• 229960004699 valsartan Drugs 0.000 description 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 description 1
• 239000002536 vasopressin receptor antagonist Substances 0.000 description 1
• 229960001722 verapamil Drugs 0.000 description 1
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
• 230000002618 waking effect Effects 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1