NZ529438A - Dipeptide derivatives - Google Patents

Info

Publication number

NZ529438A

NZ529438A NZ529438A NZ52943802A NZ529438A NZ 529438 A NZ529438 A NZ 529438A NZ 529438 A NZ529438 A NZ 529438A NZ 52943802 A NZ52943802 A NZ 52943802A NZ 529438 A NZ529438 A NZ 529438A

Authority

NZ

New Zealand

Prior art keywords

lower alkyl

carbocyclic

hydrogen

represent

aryl

Prior art date

2001-05-15

Links

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• 108010016626 Dipeptides Proteins 0.000 title abstract description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 117
• -1 methoxyacetyl Chemical group 0.000 claims abstract description 71
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 56
• 239000001257 hydrogen Substances 0.000 claims abstract description 55
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 38
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 18
• 102000003729 Neprilysin Human genes 0.000 claims abstract description 18
• 108090000028 Neprilysin Proteins 0.000 claims abstract description 18
• 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 14
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims abstract description 14
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims abstract description 14
• 150000002431 hydrogen Chemical group 0.000 claims abstract description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims abstract description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 118
• 125000002837 carbocyclic group Chemical group 0.000 claims description 37
• 150000003839 salts Chemical class 0.000 claims description 29
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 23
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
• 125000003545 alkoxy group Chemical group 0.000 claims description 19
• 150000002148 esters Chemical class 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 241000124008 Mammalia Species 0.000 claims description 13
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• 125000004432 carbon atom Chemical group C* 0.000 claims description 12
• 125000002252 acyl group Chemical group 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 125000004423 acyloxy group Chemical group 0.000 claims description 10
• 206010020772 Hypertension Diseases 0.000 claims description 9
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 9
• 150000002019 disulfides Chemical class 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 208000024172 Cardiovascular disease Diseases 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
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 230000002401 inhibitory effect Effects 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
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
• 239000005977 Ethylene Substances 0.000 claims description 3
• 208000029422 Hypernatremia Diseases 0.000 claims description 3
• 206010030113 Oedema Diseases 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
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000000623 heterocyclic group Chemical group 0.000 claims description 2
• 125000005841 biaryl group Chemical group 0.000 claims 4
• JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 claims 2
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
• 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 abstract description 14
• 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 abstract description 13
• 239000003112 inhibitor Substances 0.000 abstract description 11
• 230000009977 dual effect Effects 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 86
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
• 239000000203 mixture Substances 0.000 description 48
• 239000000243 solution Substances 0.000 description 38
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
• 235000019439 ethyl acetate Nutrition 0.000 description 29
• 229940093499 ethyl acetate Drugs 0.000 description 28
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
• 230000005764 inhibitory process Effects 0.000 description 26
• 238000000034 method Methods 0.000 description 26
• 241000700159 Rattus Species 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 20
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
• 239000003921 oil Substances 0.000 description 19
• 235000019198 oils Nutrition 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000012267 brine Substances 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
• 239000007858 starting material Substances 0.000 description 17
• 239000002253 acid Substances 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• HZZGDPLAJHVHSP-GKHTVLBPSA-N big endothelin 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)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)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=CN=CN1 HZZGDPLAJHVHSP-GKHTVLBPSA-N 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 239000000741 silica gel Substances 0.000 description 11
• 229910002027 silica gel Inorganic materials 0.000 description 11
• 239000003981 vehicle Substances 0.000 description 11
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 230000008569 process Effects 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 239000011541 reaction mixture Substances 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 238000009833 condensation Methods 0.000 description 9
• 230000005494 condensation Effects 0.000 description 9
• 229910052736 halogen Inorganic materials 0.000 description 9
• 150000002367 halogens Chemical class 0.000 description 9
• 230000036584 pressor response Effects 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 8
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 235000015424 sodium Nutrition 0.000 description 8
• 102400000344 Angiotensin-1 Human genes 0.000 description 7
• 101800000734 Angiotensin-1 Proteins 0.000 description 7
• 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 7
• 230000004872 arterial blood pressure Effects 0.000 description 7
• 150000001721 carbon Chemical group 0.000 description 7
• 210000001105 femoral artery Anatomy 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 125000003396 thiol group Chemical group [H]S* 0.000 description 7
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
• 102400000686 Endothelin-1 Human genes 0.000 description 6
• 101800004490 Endothelin-1 Proteins 0.000 description 6
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• 229940024606 amino acid Drugs 0.000 description 6
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 239000002934 diuretic Substances 0.000 description 6
• 210000003191 femoral vein Anatomy 0.000 description 6
• 239000006260 foam Substances 0.000 description 6
• 239000007789 gas Substances 0.000 description 6
• 229910052740 iodine Inorganic materials 0.000 description 6
• 229910052938 sodium sulfate Inorganic materials 0.000 description 6
• 235000011152 sodium sulphate Nutrition 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 235000001014 amino acid Nutrition 0.000 description 5
• 150000005347 biaryls Chemical group 0.000 description 5
• 230000036772 blood pressure Effects 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 125000005843 halogen group Chemical group 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• 229940002612 prodrug Drugs 0.000 description 5
• 239000000651 prodrug Substances 0.000 description 5
• 238000003127 radioimmunoassay Methods 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 238000011699 spontaneously hypertensive rat Methods 0.000 description 5
• 210000002700 urine Anatomy 0.000 description 5
• 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 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• 101500027366 Rattus norvegicus Atrial natriuretic peptide Proteins 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 239000007983 Tris buffer Substances 0.000 description 4
• 125000005907 alkyl ester group Chemical group 0.000 description 4
• 230000003276 anti-hypertensive effect Effects 0.000 description 4
• 125000003118 aryl group Chemical group 0.000 description 4
• 150000001735 carboxylic acids Chemical class 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 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 4
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 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
• 239000012442 inert solvent Substances 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 239000008188 pellet Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 238000013222 sprague-dawley male rat Methods 0.000 description 4
• 125000001424 substituent group Chemical group 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 239000000725 suspension Substances 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
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 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
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-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
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 125000005236 alkanoylamino group Chemical group 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 239000012300 argon atmosphere Substances 0.000 description 3
• 125000003435 aroyl group Chemical group 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 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 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
• 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
• 230000029142 excretion Effects 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
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 230000001631 hypertensive effect Effects 0.000 description 3
• 230000005291 magnetic effect Effects 0.000 description 3
• 238000005259 measurement Methods 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
• 230000004044 response Effects 0.000 description 3
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