JPH057384B2 - - Google Patents

Info

Publication number

JPH057384B2

JPH057384B2 JP13967382A JP13967382A JPH057384B2 JP H057384 B2 JPH057384 B2 JP H057384B2 JP 13967382 A JP13967382 A JP 13967382A JP 13967382 A JP13967382 A JP 13967382A JP H057384 B2 JPH057384 B2 JP H057384B2

Authority

JP

Japan

Prior art keywords

group

hydrogen

formula

general formula

tetrahydro

Prior art date

1981-08-11

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 claims description 259
• -1 lower-alkoxy Chemical class 0.000 claims description 124
• 239000001257 hydrogen Substances 0.000 claims description 115
• 229910052739 hydrogen Inorganic materials 0.000 claims description 115
• 239000000203 mixture Substances 0.000 claims description 104
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 88
• 125000000217 alkyl group Chemical group 0.000 claims description 87
• 150000003839 salts Chemical class 0.000 claims description 79
• 239000002904 solvent Substances 0.000 claims description 77
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 73
• 239000002253 acid Substances 0.000 claims description 72
• 125000003545 alkoxy group Chemical group 0.000 claims description 67
• 238000000034 method Methods 0.000 claims description 58
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
• 238000002844 melting Methods 0.000 claims description 47
• 230000008018 melting Effects 0.000 claims description 47
• 125000004043 oxo group Chemical group O=* 0.000 claims description 44
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 43
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 39
• 125000003118 aryl group Chemical group 0.000 claims description 38
• 230000001747 exhibiting effect Effects 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 33
• 230000003287 optical effect Effects 0.000 claims description 31
• 150000002367 halogens Chemical class 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
• AYQMNFRCBKOMIA-UHFFFAOYSA-N 1-benzazepin-2-one Chemical compound O=C1C=CC=C2C=CC=CC2=N1 AYQMNFRCBKOMIA-UHFFFAOYSA-N 0.000 claims description 29
• GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 claims description 28
• 150000002148 esters Chemical class 0.000 claims description 25
• 230000008569 process Effects 0.000 claims description 22
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 125000002837 carbocyclic group Chemical group 0.000 claims description 15
• 239000003638 chemical reducing agent Substances 0.000 claims description 15
• 238000004587 chromatography analysis Methods 0.000 claims description 15
• 125000004423 acyloxy group Chemical group 0.000 claims description 14
• 150000001412 amines Chemical class 0.000 claims description 12
• HRVRAYIYXRVAPR-UHFFFAOYSA-N 1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound N1C(=O)CCCC2=CC=CC=C21 HRVRAYIYXRVAPR-UHFFFAOYSA-N 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 125000005843 halogen group Chemical group 0.000 claims description 9
• FJZLANUAMGHEGO-UHFFFAOYSA-N 1,3-dihydro-1-benzazepin-2-one Chemical compound N1C(=O)CC=CC2=CC=CC=C21 FJZLANUAMGHEGO-UHFFFAOYSA-N 0.000 claims description 8
• 238000001640 fractional crystallisation Methods 0.000 claims description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 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 description 6
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 6
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 230000003276 anti-hypertensive effect Effects 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
• 239000005977 Ethylene Substances 0.000 claims description 4
• 229960005190 phenylalanine Drugs 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• 238000002425 crystallisation Methods 0.000 claims description 2
• 238000002156 mixing Methods 0.000 claims description 2
• 125000001424 substituent group Chemical group 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 34
• 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims 8
• 239000003937 drug carrier Substances 0.000 claims 2
• NHKRQDYGVIMAAT-UHFFFAOYSA-N 1,3,4,5,5a,6,7,8,9,9a-decahydrobenzo[b]azepin-2-one Chemical compound N1C(=O)CCCC2CCCCC21 NHKRQDYGVIMAAT-UHFFFAOYSA-N 0.000 claims 1
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
• 125000002877 alkyl aryl group Chemical group 0.000 claims 1
• 230000003177 cardiotonic effect Effects 0.000 claims 1
• 239000000243 solution Substances 0.000 description 179
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 176
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 158
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 157
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 132
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 116
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 115
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 108
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 103
• 230000002829 reductive effect Effects 0.000 description 91
• 235000019441 ethanol Nutrition 0.000 description 72
• 238000003756 stirring Methods 0.000 description 66
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 61
• 239000003054 catalyst Substances 0.000 description 53
• 239000011541 reaction mixture Substances 0.000 description 49
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 43
• 239000007858 starting material Substances 0.000 description 43
• 239000000126 substance Substances 0.000 description 43
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 40
• 229960000583 acetic acid Drugs 0.000 description 40
• 239000000284 extract Substances 0.000 description 37
• 235000011054 acetic acid Nutrition 0.000 description 36
• 238000006243 chemical reaction Methods 0.000 description 34
• 239000000047 product Substances 0.000 description 32
• 239000000725 suspension Substances 0.000 description 32
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
• 235000019341 magnesium sulphate Nutrition 0.000 description 30
• 229910052757 nitrogen Inorganic materials 0.000 description 28
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 230000009467 reduction Effects 0.000 description 24
• 238000006722 reduction reaction Methods 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 23
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 22
• 239000012299 nitrogen atmosphere Substances 0.000 description 22
• 239000002585 base Substances 0.000 description 21
• 125000003277 amino group Chemical group 0.000 description 20
• 239000000706 filtrate Substances 0.000 description 20
• 239000010410 layer Substances 0.000 description 20
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• 238000005804 alkylation reaction Methods 0.000 description 19
• 239000007789 gas Substances 0.000 description 19
• 239000011734 sodium Substances 0.000 description 19
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
• 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 18
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
• 238000007792 addition Methods 0.000 description 18
• 230000036772 blood pressure Effects 0.000 description 18
• 238000000746 purification Methods 0.000 description 18
• 235000015424 sodium Nutrition 0.000 description 18
• 229910052708 sodium Inorganic materials 0.000 description 18
• 230000029936 alkylation Effects 0.000 description 17
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
• 229910052938 sodium sulfate Inorganic materials 0.000 description 16
• 235000011152 sodium sulphate Nutrition 0.000 description 16
• 238000000354 decomposition reaction Methods 0.000 description 15
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 14
• 230000007062 hydrolysis Effects 0.000 description 14
• 238000006460 hydrolysis reaction Methods 0.000 description 14
• 238000010521 absorption reaction Methods 0.000 description 13
• 239000007864 aqueous solution Substances 0.000 description 13
• 239000011343 solid material Substances 0.000 description 13
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
• 150000007513 acids Chemical class 0.000 description 12
• 238000006482 condensation reaction Methods 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 11
• 238000005984 hydrogenation reaction Methods 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• 125000006239 protecting group Chemical group 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• 108010064733 Angiotensins Proteins 0.000 description 10
• 102000015427 Angiotensins Human genes 0.000 description 10
• 241000700159 Rattus Species 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
• 125000003282 alkyl amino group Chemical group 0.000 description 10
• 238000007796 conventional method Methods 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
• 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 125000004185 ester group Chemical group 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• 238000011282 treatment Methods 0.000 description 9
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• 102400000344 Angiotensin-1 Human genes 0.000 description 8
• 101800000734 Angiotensin-1 Proteins 0.000 description 8
• 241000124008 Mammalia Species 0.000 description 8
• 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 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 8
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
• 239000003960 organic solvent Substances 0.000 description 8
• 229910052763 palladium Inorganic materials 0.000 description 8
• 239000003208 petroleum Substances 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 239000000376 reactant Substances 0.000 description 8
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
• 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 7
• 239000013543 active substance Substances 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 239000008101 lactose Substances 0.000 description 7
• 229910052751 metal Inorganic materials 0.000 description 7
• 239000002184 metal Substances 0.000 description 7
• 239000002480 mineral oil Substances 0.000 description 7
• 235000010446 mineral oil Nutrition 0.000 description 7
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 229920002472 Starch Polymers 0.000 description 6
• 239000000908 ammonium hydroxide Substances 0.000 description 6
• 239000008346 aqueous phase Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 238000009835 boiling Methods 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000012467 final product Substances 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 150000007522 mineralic acids Chemical class 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 150000002825 nitriles Chemical class 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 239000008107 starch Substances 0.000 description 6
• 235000019698 starch Nutrition 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 125000004442 acylamino group Chemical group 0.000 description 5
• 229910052783 alkali metal Inorganic materials 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 5
• 125000004494 ethyl ester group Chemical group 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 239000012046 mixed solvent Substances 0.000 description 5
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
• 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 5
• 238000005932 reductive alkylation reaction Methods 0.000 description 5
• 239000000052 vinegar Substances 0.000 description 5
• 235000021419 vinegar Nutrition 0.000 description 5
• IBMWLBPQYWLTJM-UHFFFAOYSA-N 1-benzazepin-2-one;hydrochloride Chemical compound Cl.O=C1C=CC=C2C=CC=CC2=N1 IBMWLBPQYWLTJM-UHFFFAOYSA-N 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
• 206010020772 Hypertension Diseases 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
• 238000007126 N-alkylation reaction Methods 0.000 description 4
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
• 125000002252 acyl group Chemical group 0.000 description 4
• 125000001931 aliphatic group Chemical group 0.000 description 4
• 229910000102 alkali metal hydride Inorganic materials 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 239000012141 concentrate Substances 0.000 description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
• FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 150000004678 hydrides Chemical class 0.000 description 4
• 238000007327 hydrogenolysis reaction Methods 0.000 description 4
• 150000001261 hydroxy acids Chemical class 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• 239000013067 intermediate product Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 238000004811 liquid chromatography Methods 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 4
• FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 159000000000 sodium salts Chemical class 0.000 description 4
• 230000001629 suppression Effects 0.000 description 4
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
• MADRIHWFJGRSBP-UHFFFAOYSA-N 2-[[1-(carboxymethyl)-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2CCC1NC(C(O)=O)CCC1=CC=CC=C1 MADRIHWFJGRSBP-UHFFFAOYSA-N 0.000 description 3
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
• 241000282472 Canis lupus familiaris Species 0.000 description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
• 241000790917 Dioxys <bee> Species 0.000 description 3
• 206010019280 Heart failures Diseases 0.000 description 3
• MMFKFJORZBJVNF-UWVGGRQHSA-N His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MMFKFJORZBJVNF-UWVGGRQHSA-N 0.000 description 3
• YGPSJZOEDVAXAB-QMMMGPOBSA-N L-kynurenine Chemical compound OC(=O)[C@@H](N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-QMMMGPOBSA-N 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 241001024304 Mino Species 0.000 description 3
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical group CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
• 241000287462 Phalacrocorax carbo Species 0.000 description 3
• GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 3
• 238000005903 acid hydrolysis reaction Methods 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 150000008046 alkali metal hydrides Chemical class 0.000 description 3
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 150000001540 azides Chemical class 0.000 description 3
• CNNBRFOPQDCGFV-UHFFFAOYSA-N benzyl 2-oxopropanoate Chemical compound CC(=O)C(=O)OCC1=CC=CC=C1 CNNBRFOPQDCGFV-UHFFFAOYSA-N 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 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 3
• 229940079593 drug Drugs 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000012362 glacial acetic acid Substances 0.000 description 3
• 108010025306 histidylleucine Proteins 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 150000002466 imines Chemical class 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 229910052987 metal hydride Inorganic materials 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 150000007530 organic bases Chemical class 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 150000002923 oximes Chemical class 0.000 description 3
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
• 238000010647 peptide synthesis reaction Methods 0.000 description 3
• 239000008363 phosphate buffer Substances 0.000 description 3
• 229910052697 platinum Inorganic materials 0.000 description 3
• 229910003446 platinum oxide Inorganic materials 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000007363 ring formation reaction Methods 0.000 description 3
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
• 238000007614 solvation Methods 0.000 description 3
• 238000001228 spectrum Methods 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000000454 talc Substances 0.000 description 3
• 229910052623 talc Inorganic materials 0.000 description 3
• 235000012222 talc Nutrition 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• YGPSJZOEDVAXAB-UHFFFAOYSA-N (R)-Kynurenine Natural products OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 description 2
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
• DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 2
• VUQMOERHEHTWPE-UHFFFAOYSA-N 1-ethylpiperidin-2-one Chemical compound CCN1CCCCC1=O VUQMOERHEHTWPE-UHFFFAOYSA-N 0.000 description 2
• JTCTZPXAQOMDEI-UHFFFAOYSA-N 2-(3-amino-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetic acid Chemical compound OC(=O)CN1C(=O)C(N)CCC2=CC=CC=C21 JTCTZPXAQOMDEI-UHFFFAOYSA-N 0.000 description 2
• QKFWIYJJJMRHSJ-UHFFFAOYSA-N 2-[(2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl)amino]-4-phenylbutanoic acid Chemical compound C1CC2=CC=CC=C2NC(=O)C1NC(C(=O)O)CCC1=CC=CC=C1 QKFWIYJJJMRHSJ-UHFFFAOYSA-N 0.000 description 2
• XPCFTKFZXHTYIP-UHFFFAOYSA-N 2-[3-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid Chemical compound C1CC2=CC=CC=C2N(CC(O)=O)C(=O)C1NC(C(=O)OCC)CCC1=CC=CC=C1 XPCFTKFZXHTYIP-UHFFFAOYSA-N 0.000 description 2
• FWMRQZJBZPWMLY-UHFFFAOYSA-N 3-amino-7-chloro-1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound N1C(=O)C(N)CCC2=CC(Cl)=CC=C21 FWMRQZJBZPWMLY-UHFFFAOYSA-N 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
• VOEMRDMQXDUFDU-UHFFFAOYSA-N 3-chloro-1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound N1C(=O)C(Cl)CCC2=CC=CC=C21 VOEMRDMQXDUFDU-UHFFFAOYSA-N 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
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• LNHPAGLFHADFGG-UHFFFAOYSA-N Cl[I][Cu] Chemical compound Cl[I][Cu] LNHPAGLFHADFGG-UHFFFAOYSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229930006000 Sucrose Natural products 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• UCFPXKPBCDPVFG-UHFFFAOYSA-N [Na].N=1C(C=CC=C2C1C=CC=C2)=O Chemical compound [Na].N=1C(C=CC=C2C1C=CC=C2)=O UCFPXKPBCDPVFG-UHFFFAOYSA-N 0.000 description 2
• 238000000862 absorption spectrum Methods 0.000 description 2
• KBVKNVAEPUWIKK-UHFFFAOYSA-M acetonitrile;tetrabutylazanium;bromide Chemical compound [Br-].CC#N.CCCC[N+](CCCC)(CCCC)CCCC KBVKNVAEPUWIKK-UHFFFAOYSA-M 0.000 description 2
• FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 150000003973 alkyl amines Chemical class 0.000 description 2
• 125000005907 alkyl ester group Chemical group 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 125000005530 alkylenedioxy group Chemical group 0.000 description 2
• QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 150000003863 ammonium salts Chemical class 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 230000003796 beauty Effects 0.000 description 2
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical group CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 238000009530 blood pressure measurement Methods 0.000 description 2
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 235000001465 calcium Nutrition 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 150000004292 cyclic ethers Chemical class 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• 230000018044 dehydration Effects 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• 150000005690 diesters Chemical class 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 229910001873 dinitrogen Inorganic materials 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 230000006806 disease prevention Effects 0.000 description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 238000005886 esterification reaction Methods 0.000 description 2
• 239000012259 ether extract Substances 0.000 description 2
• ATTDHWNIZZYGGX-UHFFFAOYSA-N ethyl 2-(3-chloro-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetate Chemical compound C1CC(Cl)C(=O)N(CC(=O)OCC)C2=CC=CC=C21 ATTDHWNIZZYGGX-UHFFFAOYSA-N 0.000 description 2
• YVOYFSPQMQKWBP-IBLUKRHDSA-N ethyl 2-[(3s)-5-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxo-4,5,5a,6,7,8,9,9a-octahydro-3h-benzo[b]azepin-1-yl]acetate Chemical compound OC1C[C@H](NC(=O)OC(C)(C)C)C(=O)N(CC(=O)OCC)C2CCCCC21 YVOYFSPQMQKWBP-IBLUKRHDSA-N 0.000 description 2
• GWBJXBUPIPXINZ-UHFFFAOYSA-N ethyl 2-amino-4-(2-nitrophenyl)butanoate Chemical compound CCOC(=O)C(N)CCC1=CC=CC=C1[N+]([O-])=O GWBJXBUPIPXINZ-UHFFFAOYSA-N 0.000 description 2
• NPYOFNZCULOOTR-UHFFFAOYSA-N ethyl 2-amino-4-[2-[(2-ethoxy-2-oxoethyl)amino]phenyl]butanoate Chemical compound CCOC(=O)CNC1=CC=CC=C1CCC(N)C(=O)OCC NPYOFNZCULOOTR-UHFFFAOYSA-N 0.000 description 2
• 210000001105 femoral artery Anatomy 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 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 2
• 239000000499 gel Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 208000019622 heart disease Diseases 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 229940071870 hydroiodic acid Drugs 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 235000001055 magnesium Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000011976 maleic acid Substances 0.000 description 2
• 239000001630 malic acid Substances 0.000 description 2
• 235000011090 malic acid Nutrition 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 150000004681 metal hydrides Chemical class 0.000 description 2
• 150000002739 metals Chemical class 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• 230000000704 physical effect Effects 0.000 description 2
• 229960005235 piperonyl butoxide Drugs 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
• 229910000105 potassium hydride Inorganic materials 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 230000009257 reactivity Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 238000011699 spontaneously hypertensive rat Methods 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• 235000002906 tartaric acid Nutrition 0.000 description 2
• QQWYQAQQADNEIC-UHFFFAOYSA-N tert-butyl [[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON=C(C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000008215 water for injection Substances 0.000 description 2
• 239000008096 xylene Substances 0.000 description 2
• 229910052725 zinc Inorganic materials 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
• GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• PPKPKFIWDXDAGC-IHWYPQMZSA-N (z)-1,2-dichloroprop-1-ene Chemical group C\C(Cl)=C\Cl PPKPKFIWDXDAGC-IHWYPQMZSA-N 0.000 description 1
• BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
• VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 1
• ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
• BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-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
• WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
• VUVOWLHLMZMHHK-UHFFFAOYSA-N 1-methyl-3,4-dihydro-1-benzazepine-2,5-dione Chemical compound CN1C(CCC(C2=C1C=CC=C2)=O)=O VUVOWLHLMZMHHK-UHFFFAOYSA-N 0.000 description 1
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
• SPXOTSHWBDUUMT-UHFFFAOYSA-N 138-42-1 Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-N 0.000 description 1
• XPFSMDZLNJRDNP-UHFFFAOYSA-N 1h-azepine-2,5-dione Chemical compound O=C1C=CNC(=O)C=C1 XPFSMDZLNJRDNP-UHFFFAOYSA-N 0.000 description 1
• KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 1
• 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
• LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 1
• KCEFVIWAXZRGPZ-UHFFFAOYSA-N 2-(3-azido-8-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetic acid Chemical compound C1CC(N=[N+]=[N-])C(=O)N(CC(O)=O)C2=CC(OC)=CC=C21 KCEFVIWAXZRGPZ-UHFFFAOYSA-N 0.000 description 1
• NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• VPSRQEHTHIMDQM-UHFFFAOYSA-N 2-[3-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid;hydron;chloride Chemical compound Cl.C1CC2=CC=CC=C2N(CC(O)=O)C(=O)C1NC(C(=O)OCC)CCC1=CC=CC=C1 VPSRQEHTHIMDQM-UHFFFAOYSA-N 0.000 description 1
• YRVNVTXYGNAFSA-UHFFFAOYSA-N 2-[3-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]-8-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid Chemical compound C1CC2=CC=C(OC)C=C2N(CC(O)=O)C(=O)C1NC(C(=O)OCC)CCC1=CC=CC=C1 YRVNVTXYGNAFSA-UHFFFAOYSA-N 0.000 description 1
• WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
• QQOAIELYHQFRCD-UHFFFAOYSA-N 2-[7-chloro-3-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid Chemical compound C1CC2=CC(Cl)=CC=C2N(CC(O)=O)C(=O)C1NC(C(=O)OCC)CCC1=CC=CC=C1 QQOAIELYHQFRCD-UHFFFAOYSA-N 0.000 description 1
• VXOCJPIUNZCBOX-UHFFFAOYSA-N 2-[7-chloro-3-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid;hydrochloride Chemical compound Cl.C1CC2=CC(Cl)=CC=C2N(CC(O)=O)C(=O)C1NC(C(=O)OCC)CCC1=CC=CC=C1 VXOCJPIUNZCBOX-UHFFFAOYSA-N 0.000 description 1
• GQSSPXVAHKNXTB-UHFFFAOYSA-N 2-[[1-(2-ethoxy-2-oxoethyl)-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2CCC1NC(C(O)=O)CCC1=CC=CC=C1 GQSSPXVAHKNXTB-UHFFFAOYSA-N 0.000 description 1
• RHJSFBMZKANYIW-UHFFFAOYSA-N 2-[[1-(cyanomethyl)-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid Chemical compound C1CC2=CC=CC=C2N(CC#N)C(=O)C1NC(C(=O)O)CCC1=CC=CC=C1 RHJSFBMZKANYIW-UHFFFAOYSA-N 0.000 description 1
• HUVMWNQIWCGVIC-UHFFFAOYSA-N 2-amino-4-(2-aminophenyl)butanoic acid Chemical compound OC(=O)C(N)CCC1=CC=CC=C1N HUVMWNQIWCGVIC-UHFFFAOYSA-N 0.000 description 1
• IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
• RZPFVRFSYMUDJO-UHFFFAOYSA-N 2h-naphthalen-1-one Chemical class C1=CC=C2C(=O)CC=CC2=C1 RZPFVRFSYMUDJO-UHFFFAOYSA-N 0.000 description 1
• AUAKXRGQXZRTQC-UHFFFAOYSA-N 3-amino-1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound N1C(=O)C(N)CCC2=CC=CC=C21 AUAKXRGQXZRTQC-UHFFFAOYSA-N 0.000 description 1
• KMFHLURLRXQOAG-UHFFFAOYSA-N 3-amino-1-benzazepin-2-one Chemical class O=C1C(N)=CC=C2C=CC=CC2=N1 KMFHLURLRXQOAG-UHFFFAOYSA-N 0.000 description 1
• PDFYKDYEFKYENU-UHFFFAOYSA-N 3-azido-1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound N1C(=O)C(N=[N+]=[N-])CCC2=CC=CC=C21 PDFYKDYEFKYENU-UHFFFAOYSA-N 0.000 description 1
• VLRGXXKFHVJQOL-UHFFFAOYSA-N 3-chloropentane-2,4-dione Chemical compound CC(=O)C(Cl)C(C)=O VLRGXXKFHVJQOL-UHFFFAOYSA-N 0.000 description 1
• ITSMDHXJQRRVKG-UHFFFAOYSA-N 3-methoxy-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)C(OC)=CC(=O)C2=CC=CC=C21 ITSMDHXJQRRVKG-UHFFFAOYSA-N 0.000 description 1
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• AZRRZGIBBLWSSQ-UHFFFAOYSA-N 4-ethyl-7-phenyl-3,5-diazabicyclo[2.2.2]octane-2,6-dione Chemical compound N1C(=O)C2C(=O)NC1(CC)CC2C1=CC=CC=C1 AZRRZGIBBLWSSQ-UHFFFAOYSA-N 0.000 description 1
• 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
• BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
• RBMXJQAHEYFBEP-UHFFFAOYSA-N 7,8-dimethoxy-1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound C1CCC(=O)NC2=C1C=C(OC)C(OC)=C2 RBMXJQAHEYFBEP-UHFFFAOYSA-N 0.000 description 1
• RCEGKZNHKLTDFI-UHFFFAOYSA-N 7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one Chemical compound C1=CC=C2C(=O)NC2=C1 RCEGKZNHKLTDFI-UHFFFAOYSA-N 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 229910000497 Amalgam Inorganic materials 0.000 description 1
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• 229910015900 BF3 Inorganic materials 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 101800004538 Bradykinin Proteins 0.000 description 1
• 102400000967 Bradykinin Human genes 0.000 description 1
• RCYJKGIYWFZGTP-UHFFFAOYSA-N C1=CC=C2C(O)=[N+]([O-])N=NC2=C1 Chemical compound C1=CC=C2C(O)=[N+]([O-])N=NC2=C1 RCYJKGIYWFZGTP-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 229940093817 Convertase inhibitor Drugs 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-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
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
• 241000255925 Diptera Species 0.000 description 1
• 241000257465 Echinoidea Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
• 241000521257 Hydrops Species 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• JTTHKOPSMAVJFE-VIFPVBQESA-N L-homophenylalanine Chemical compound OC(=O)[C@@H](N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-VIFPVBQESA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 241001072332 Monia Species 0.000 description 1
• 206010028347 Muscle twitching Diseases 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
• 230000006181 N-acylation Effects 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 241000237502 Ostreidae Species 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229920000388 Polyphosphate Polymers 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical class [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 235000009233 Stachytarpheta cayennensis Nutrition 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229910000831 Steel Inorganic materials 0.000 description 1
• 241000272534 Struthio camelus Species 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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 group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 229920002807 Thiomer Polymers 0.000 description 1
• 229910052776 Thorium Inorganic materials 0.000 description 1
• 241000384512 Trachichthyidae Species 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 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
• JETSKDPKURDVNI-UHFFFAOYSA-N [C].[Ca] Chemical compound [C].[Ca] JETSKDPKURDVNI-UHFFFAOYSA-N 0.000 description 1
• CIAXFBVXQWOYPA-UHFFFAOYSA-N [C].[K] Chemical compound [C].[K] CIAXFBVXQWOYPA-UHFFFAOYSA-N 0.000 description 1
• ZYBXCIBWFOILPE-UHFFFAOYSA-N [Na].N#CC#N Chemical compound [Na].N#CC#N ZYBXCIBWFOILPE-UHFFFAOYSA-N 0.000 description 1
• OEQKBSRIASECCM-UHFFFAOYSA-N [bromo(phenyl)methyl] acetate Chemical compound CC(=O)OC(Br)C1=CC=CC=C1 OEQKBSRIASECCM-UHFFFAOYSA-N 0.000 description 1
• SUHUQLOULPAPRO-UHFFFAOYSA-N [bromo-[bromo(phenyl)methoxy]methyl]benzene Chemical compound C=1C=CC=CC=1C(Br)OC(Br)C1=CC=CC=C1 SUHUQLOULPAPRO-UHFFFAOYSA-N 0.000 description 1
• CVOKPUSIMWYQQA-UHFFFAOYSA-N acetic acid;chloroethane Chemical compound CCCl.CC(O)=O CVOKPUSIMWYQQA-UHFFFAOYSA-N 0.000 description 1
• LASSZCILJSRSJH-UHFFFAOYSA-N acetonitrile;hydrobromide Chemical compound Br.CC#N LASSZCILJSRSJH-UHFFFAOYSA-N 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012190 activator Substances 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
• 235000004279 alanine Nutrition 0.000 description 1
• 238000006136 alcoholysis reaction Methods 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 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
• 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 125000005210 alkyl ammonium group Chemical group 0.000 description 1
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical group 0.000 description 1
• 125000005263 alkylenediamine group Chemical group 0.000 description 1
• 150000004716 alpha keto acids Chemical class 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 229940093740 amino acid and derivative Drugs 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
• 238000005349 anion exchange Methods 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940124572 antihypotensive agent Drugs 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 230000004872 arterial blood pressure Effects 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
• 238000005815 base catalysis Methods 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• FXZOZBDSJDUFOV-UHFFFAOYSA-N benzyl 2-(3-azido-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetate Chemical compound O=C1C(N=[N+]=[N-])CCC2=CC=CC=C2N1CC(=O)OCC1=CC=CC=C1 FXZOZBDSJDUFOV-UHFFFAOYSA-N 0.000 description 1
• HODIZADPXPKWNS-UHFFFAOYSA-N benzyl 2-[[1-(2-ethoxy-2-oxoethyl)-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2CCC1NC(C(=O)OCC=1C=CC=CC=1)CCC1=CC=CC=C1 HODIZADPXPKWNS-UHFFFAOYSA-N 0.000 description 1
• RWCSKKNSVKJXAY-UHFFFAOYSA-N benzyl 2-[[1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoate Chemical compound O=C1N(CC(=O)OC(C)(C)C)C2=CC=CC=C2CCC1NC(C(=O)OCC=1C=CC=CC=1)CCC1=CC=CC=C1 RWCSKKNSVKJXAY-UHFFFAOYSA-N 0.000 description 1
• PWCONBNHBCCZHP-UHFFFAOYSA-N benzyl acetate hydrobromide Chemical compound Br.CC(=O)OCC1=CC=CC=C1 PWCONBNHBCCZHP-UHFFFAOYSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
• 238000010876 biochemical test Methods 0.000 description 1
• 230000004531 blood pressure lowering effect Effects 0.000 description 1
• QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 229910000011 cadmium carbonate Inorganic materials 0.000 description 1
• GKDXQAKPHKQZSC-UHFFFAOYSA-L cadmium(2+);carbonate Chemical compound [Cd+2].[O-]C([O-])=O GKDXQAKPHKQZSC-UHFFFAOYSA-L 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000004653 carbonic acids Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 239000013043 chemical agent Substances 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
• 229940106681 chloroacetic acid Drugs 0.000 description 1
• 125000004965 chloroalkyl group Chemical group 0.000 description 1
• HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
• KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
• JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical class [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229940000425 combination drug Drugs 0.000 description 1
• 239000013068 control sample Substances 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 229940045803 cuprous chloride Drugs 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• WVIIMZNLDWSIRH-UHFFFAOYSA-N cyclohexylcyclohexane Chemical compound C1CCCCC1C1CCCCC1 WVIIMZNLDWSIRH-UHFFFAOYSA-N 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000006477 desulfuration reaction Methods 0.000 description 1
• 230000023556 desulfurization Effects 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 229910000071 diazene Inorganic materials 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
• SVTSUGNXHXMMFU-UHFFFAOYSA-N diethyl 2-acetamido-2-[2-(2-nitrophenyl)ethyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)(NC(C)=O)CCC1=CC=CC=C1[N+]([O-])=O SVTSUGNXHXMMFU-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Natural products CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• HBFXVTVOSLPOEY-UHFFFAOYSA-N ethoxyethane;2-propan-2-yloxypropane Chemical compound CCOCC.CC(C)OC(C)C HBFXVTVOSLPOEY-UHFFFAOYSA-N 0.000 description 1
• GXLKWQMQMGFUMV-UHFFFAOYSA-N ethyl 2-(2,3-dioxo-4,5-dihydro-1-benzazepin-1-yl)acetate Chemical compound C1CC(=O)C(=O)N(CC(=O)OCC)C2=CC=CC=C21 GXLKWQMQMGFUMV-UHFFFAOYSA-N 0.000 description 1
• AMZFVTSKKHPVBV-UHFFFAOYSA-N ethyl 2-(2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetate Chemical compound C1CCC(=O)N(CC(=O)OCC)C2=CC=CC=C21 AMZFVTSKKHPVBV-UHFFFAOYSA-N 0.000 description 1
• FGLBHTZRGOXAOR-UHFFFAOYSA-N ethyl 2-(3-azido-8-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetate Chemical compound C1CC(N=[N+]=[N-])C(=O)N(CC(=O)OCC)C2=CC(OC)=CC=C21 FGLBHTZRGOXAOR-UHFFFAOYSA-N 0.000 description 1
• UPSHGHPDMZMLNM-SLTAFYQDSA-N ethyl 2-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxo-4,5,5a,6,7,8,9,9a-octahydro-3h-benzo[b]azepin-1-yl]acetate Chemical compound C1C[C@H](NC(=O)OC(C)(C)C)C(=O)N(CC(=O)OCC)C2CCCCC21 UPSHGHPDMZMLNM-SLTAFYQDSA-N 0.000 description 1
• NKPNCAYTOLXSEG-UHFFFAOYSA-N ethyl 2-[[1-(2-ethoxy-2-oxoethyl)-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoate Chemical compound O=C1N(CC(=O)OCC)C2=CC=CC=C2CCC1NC(C(=O)OCC)CCC1=CC=CC=C1 NKPNCAYTOLXSEG-UHFFFAOYSA-N 0.000 description 1
• YCVAJRLVYHWCPM-UHFFFAOYSA-N ethyl 2-amino-4-(2-aminophenyl)butanoate Chemical compound CCOC(=O)C(N)CCC1=CC=CC=C1N YCVAJRLVYHWCPM-UHFFFAOYSA-N 0.000 description 1
• WFLQXECQLHZKMV-UHFFFAOYSA-N ethyl 2-amino-4-phenylbutanoate Chemical compound CCOC(=O)C(N)CCC1=CC=CC=C1 WFLQXECQLHZKMV-UHFFFAOYSA-N 0.000 description 1
• ZLZXSWNRZFMSSS-UHFFFAOYSA-N ethyl 2-bromo-4-phenylbutanoate Chemical compound CCOC(=O)C(Br)CCC1=CC=CC=C1 ZLZXSWNRZFMSSS-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• 229960003750 ethyl chloride Drugs 0.000 description 1
• CKTNHGVJKUQEBM-UHFFFAOYSA-N ethylazanide Chemical compound CC[NH-] CKTNHGVJKUQEBM-UHFFFAOYSA-N 0.000 description 1
• LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 238000005187 foaming Methods 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 125000001475 halogen functional group Chemical group 0.000 description 1
• VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 230000001631 hypertensive effect Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 229910017053 inorganic salt Inorganic materials 0.000 description 1
• PELJISAVHGXLAL-UHFFFAOYSA-N iodomethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCI PELJISAVHGXLAL-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000002960 lipid emulsion Substances 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 150000004701 malic acid derivatives Chemical class 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000010907 mechanical stirring Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 150000002736 metal compounds Chemical class 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
• 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
• 150000002763 monocarboxylic acids Chemical class 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 230000005311 nuclear magnetism Effects 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
• 239000012044 organic layer Substances 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• UWBHMRBRLOJJAA-UHFFFAOYSA-N oxaluric acid Chemical compound NC(=O)NC(=O)C(O)=O UWBHMRBRLOJJAA-UHFFFAOYSA-N 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
• 235000020636 oyster Nutrition 0.000 description 1
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 235000015927 pasta Nutrition 0.000 description 1
• IZUPBVBPLAPZRR-UHFFFAOYSA-M pentachlorophenolate Chemical compound [O-]C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-M 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 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
• 125000005633 phthalidyl group Chemical group 0.000 description 1
• 230000037074 physically active Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 239000001205 polyphosphate Substances 0.000 description 1
• 235000011176 polyphosphates Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 description 1
• 229910001950 potassium oxide Inorganic materials 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• NXXCYNZMBSPHGI-UHFFFAOYSA-N potassium sodium 2-methylpropan-2-olate Chemical compound [Na+].[K+].CC(C)(C)[O-].CC(C)(C)[O-] NXXCYNZMBSPHGI-UHFFFAOYSA-N 0.000 description 1
• AKEKKCGPLHMFCI-UHFFFAOYSA-L potassium sodium hydrogen carbonate Chemical group [Na+].[K+].OC([O-])=O.OC([O-])=O AKEKKCGPLHMFCI-UHFFFAOYSA-L 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000010970 precious metal Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000005588 protonation Effects 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 239000012048 reactive intermediate Substances 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 238000007711 solidification Methods 0.000 description 1
• 230000008023 solidification Effects 0.000 description 1
• 238000002798 spectrophotometry method Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000010959 steel Substances 0.000 description 1
• 239000000021 stimulant Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 150000003463 sulfur Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000035488 systolic blood pressure Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• NOILBTUWXJCEER-UHFFFAOYSA-N tert-butyl 2-(3-amino-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)propanoate Chemical compound C1CC(N)C(=O)N(C(C)C(=O)OC(C)(C)C)C2=CC=CC=C21 NOILBTUWXJCEER-UHFFFAOYSA-N 0.000 description 1
• MCGKTYXEGJUDFD-UHFFFAOYSA-N tert-butyl 2-(3-azido-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)propanoate Chemical compound C1CC(N=[N+]=[N-])C(=O)N(C(C)C(=O)OC(C)(C)C)C2=CC=CC=C21 MCGKTYXEGJUDFD-UHFFFAOYSA-N 0.000 description 1
• JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical class CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
• QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 230000007306 turnover Effects 0.000 description 1
• 210000000689 upper leg Anatomy 0.000 description 1
• 239000005526 vasoconstrictor agent Substances 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 239000002023 wood Substances 0.000 description 1